To evaluate the current status and latent profiles of caregiver self-care contributions for patients with chronic obstructive pulmonary disease (COPD) and examine the associations between demographic Show more
To evaluate the current status and latent profiles of caregiver self-care contributions for patients with chronic obstructive pulmonary disease (COPD) and examine the associations between demographic characteristics, health literacy, confidence in self-care contributions, family intimacy, and profile membership. We recruited 275 dyads of patients with COPD and their family caregivers from five tertiary hospitals between May and November 2022 using convenience sampling. Latent profile analysis (LPA) was used to identify distinct profiles of caregiver self-care contributions. Univariate analysis and multinomial logistic regression were subsequently conducted to examine associations between participant characteristics and profile membership. LPA identified four distinct profiles of caregiver self-care contributions: low-contributing, under-monitored, maintenance-prioritized, and high-contributing. Significant differences were observed across these profiles in terms of patients' symptom severity, exacerbation frequency, number of hospitalizations, caregivers' education levels, caregiving duration, health literacy, confidence in self-management contributions, and family intimacy using univariate analysis. Multinomial logistic regression analysis revealed that caregivers' education levels, caregiving duration, confidence in self-management contributions, and health literacy were significant predictors of profile membership. Caregiver self-care contributions for patients with COPD can be characterized by four distinct profiles, with caregivers' educational level, health literacy, and confidence in self-management identified as key factors associated with profile membership. Show less
Premature ejaculation (PE) accompanied by anxiety or depression is a complex clinical condition at the intersection of male reproductive dysfunction and emotional disorders. Increasing evidence sugges Show more
Premature ejaculation (PE) accompanied by anxiety or depression is a complex clinical condition at the intersection of male reproductive dysfunction and emotional disorders. Increasing evidence suggests that serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) play central and interrelated roles in its pathogenesis. In this review we examine the bidirectional functions of 5-HT and BDNF in both the reproductive and nervous systems, highlighting their importance in regulating ejaculation, emotional stability, and synaptic plasticity. A comprehensive literature search (2010-2025) was conducted across multiple databases using relevant Medical Subject Headings (MeSH) terms, including pertinent original research and review articles, to synthesize the roles and regulatory pathways of 5-HT and BDNF in PE with comorbid anxiety or depression. We summarize the shared and distinct roles of 5-HT and BDNF in maintaining physiological balance across these systems and focus on their involvement in the major pathological processes underlying PE with anxiety or depression, including neurotransmitter imbalance, neuroendocrine dysregulation, inflammation, and oxidative stress. Furthermore, we outline the related signaling pathways through which 5-HT and BDNF exert their effects and interact. We also evaluate current pharmacological and non-pharmacological interventions targeting these molecules, demonstrating their potential to improve both ejaculatory control and emotional symptoms, and critically appraise selective serotonin reuptake inhibitor (SSRI)-related risks and highlighted the need for individualized dosing and monitoring. Emerging evidence suggests that Traditional Chinese Medicine formulations can extend intravaginal ejaculatory latency and mitigate mood symptoms and may serve as stand-alone or adjunctive options to reduce reliance on selective serotonin reuptake inhibitors (SSRIs). Overall, 5-HT and BDNF are not only deeply involved in the biological mechanisms of PE with comorbid psychological disorders, but also represent promising biomarkers and therapeutic targets, and their integrative neuro-reproductive regulatory functions provide new insights into the diagnosis and treatment of this multifaceted condition. Show less
Maintaining nerve integrity and rescuing/regenerating injured neurons are pivotal for spinal cord injury (SCI) repair. Herein, an immuno-neuroprotectant (INPT) is developed to mitigate secondary SCI a Show more
Maintaining nerve integrity and rescuing/regenerating injured neurons are pivotal for spinal cord injury (SCI) repair. Herein, an immuno-neuroprotectant (INPT) is developed to mitigate secondary SCI and promote neuroregeneration via sequestration of neutrophil extracellular traps (NETs) and targeted delivery of brain-derived neurotrophic factor (BDNF). To construct the INPT, positively charged BDNF is engineered into negatively charged A-BDNF nanoparticles (A-BDNF NPs) via reversible modification with adenosine triphosphate, and A-BDNF NPs are further coated with polySia-overexpressing microglia membrane (PBM). In SCI mice, intravenously injected INPT effectively accumulates in the injured spinal cord and then binds to NETs through the over-expressed polySia on PBM. This binding triggers PBM shedding from the NPs, and thereby, phosphatidylserine localized at the cytoplasmic leaflet of PBM is exposed and displayed on the NETs surface. Consequently, the PBM-bound NETs are cleared by phagocytes via efferocytosis, which provokes neuroprotective immune responses. Meanwhile, the mildly acidic environment triggers traceless restoration of A-BDNF NPs to the native BDNF to foster neuroregeneration. Thus, PBM-mediated NETs sequestration cooperates with BDNF-mediated neuroregeneration to restore neurological recovery. This study provides an enlightened approach for remedying NET-associated pathophysiological aberrations and also renders a facile yet effective platform for biomacromolecule delivery to the central nervous system. Show less
The Lipoprotein(a) (LPA) rs3798220 and rs10455872 polymorphisms have been indicated to be involved with the coronary heart disease (CHD) susceptibility. However, there are still differences between th Show more
The Lipoprotein(a) (LPA) rs3798220 and rs10455872 polymorphisms have been indicated to be involved with the coronary heart disease (CHD) susceptibility. However, there are still differences between the individual studies. To explore the correlation of LPA gene rs3798220 and rs10455872 polymorphisms and CHD, the current meta-analysis was performed. The random or fixed effect genetic models were used to calculate the pooled odds ratios (ORs) and their corresponding 95 % confidence intervals (CI). A significant association was found between LPA rs3798220 polymorphism and CHD under allelic (OR: 1.488), recessive (OR: 1.543), dominant (OR: 1.534), homozygous (OR: 1.544), heterozygous (OR: 1.498) and additive genetic models (OR: 1.531). There was also a significant association between LPA rs10455872 polymorphism and CHD under allelic (OR: 1.607), dominant (OR: 1.751), heterozygous (OR: 1.723) and additive genetic models (OR: 1.686). LPA rs3798220 and rs10455872 polymorphisms were significantly associated with increased CAD risk. The persons carrying C allele of LPA rs3798220 and G allele of LPA rs10455872 polymorphisms might have higher CHD risk than the T allele of rs3798220 or A allele of rs10455872 carriers. Show less
Haojie Ni, Yiyi Xiong, Min Liu+14 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
The pathological mechanism of Alzheimer's disease (AD) is complex. The binding of Aβ to α7 nicotinic acetylcholine receptor (α7nAChR) contributes to neuronal damage. Sinomenine (SIN) is an alkaloid ex Show more
The pathological mechanism of Alzheimer's disease (AD) is complex. The binding of Aβ to α7 nicotinic acetylcholine receptor (α7nAChR) contributes to neuronal damage. Sinomenine (SIN) is an alkaloid extracted from the traditional Chinese medicine Qingfengteng (Sinomenium acutum). The anti-inflammatory, antioxidant, and immunomodulatory effects of SIN were confirmed to be closely associated with the α7nAChR. This study aimed to investigate whether α7nAChR serves as a pharmacological target of SIN against AD, and to evaluate the neuroprotective effects of SIN both in vivo and in vitro, focusing on the α7nAChR/Nrf2/Keap1 signaling pathway. In this study, the effects of SIN in both APP/PS1 transgenic mice and SH-SY5Y cells subjected to Aβ1-42-induced injury were assessed. The selective antagonist α-bungarotoxin (α-BTX), the agonist nicotine (Nic) of α7nAChR, and α7nAChR siRNA were employed. The cognitive function, Aβ deposition, synaptic plasticity markers, the tau protein phosphorylation, mitochondrial membrane potential, oxidative stress and the α7nAChR/Nrf2/Keap1 signaling pathway were analyzed in vivo and/or in vitro. SIN significantly enhanced learning and memory abilities in APP/PS1 mice, reduced Aβ plaque deposition and synaptic dysfunction, and inhibited hyperphosphorylation of tau protein and oxidative stress in the brain. In Aβ1-42-induced neuronal injury model, SIN alleviated apoptosis, increased BDNF and ACh levels, inhibited mitochondrial damage, stabilized calcium homeostasis, and suppressed oxidative stress. Meanwhile, SIN disrupted Nrf2-Keap1 binding to promote the Nrf2/HO-1 signaling pathway. Nevertheless, SIN effects above were inhibited by α-BTX. The knockdown of α7nAChR in vitro significantly promoted Nrf2/HO-1 pathway and BDNF expression. SIN exerts neuroprotective effect in APP/PS1 transgenic mice and Aβ1-42-induced neuronal injury by inhibiting oxidative stress via α7nAChR/Nrf2/Keap1 pathway. This study provides evidence for α7nAChR as a new target and the clinical application potential of SIN in AD treatment. Show less
Acute alcohol consumption is known to exert widespread physiological effects, yet the immediate impacts on metabolic biomarkers remain incompletely understood. The present randomized controlled trial Show more
Acute alcohol consumption is known to exert widespread physiological effects, yet the immediate impacts on metabolic biomarkers remain incompletely understood. The present randomized controlled trial was conducted to investigate the acute effects of a single episode of alcohol ingestion on various biomarkers in healthy individuals. A total of 45 male participants were recruited and randomized into an alcohol group (n = 40) and a control group (n = 5) at an 8:1 ratio. Volunteers in the alcohol group ingested 40% Absolut vodka within 15 min. Blood pressure, heart rate, and blood oxygen saturation were measured at 0 h, 1 h, 3 h, 5 h, 12 h, and 24 h. Venous blood samples were drawn at 0 h, 1 h, 5 h, 12 h, and 24 h after alcohol intake. Our results showed that levels of liver function markers, including α-fucosidase (AFU), albumin (ALB), and alkaline phosphatase (ALP), were significantly increased in the alcohol group compared to the control group. The 24-h area under curve (AUC) of AFU, ALB, and ALP were significantly higher in the alcohol group. The liver fibrosis maker collagen type Ⅳ (Ⅳ-C) tended to be higher at 1 h and 12 h in the alcohol group compared to the control group. Lipid levels, including triglycerides (TG), apolipoprotein A1 (APOA1), and the APOA1/APOB, were significantly elevated after alcohol ingestion, particularly at 5 h and 12 h. The 24 h-AUC of TG, APOA1, and APOA1/APOB were higher in the alcohol group than in the control group. Additionally, cardiac function indicators, including heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were significantly elevated in the alcohol group. SBP and DBP remained higher 24 h after alcohol ingestion compared to the control group. This study demonstrated that even a single episode of binge drinking could induce significant alterations of biomarkers related to liver function, cardiac function, and lipid profiles. These findings provided valuable insights into the short-term impact of alcohol on health and highlighted the importance of further research to explore the long-term implications of repeated acute alcohol exposure. Given the very small control group, these results should be interpreted as preliminary and confirmed in larger, more balanced randomized trials. The online version contains supplementary material available at 10.1038/s41598-026-40028-1. Show less
Atherosclerosis is a chronic inflammatory disease marked by lipid accumulation and immune cell infiltration in arterial walls. Macrophages contribute by internalizing oxidized low-density lipoprotein, Show more
Atherosclerosis is a chronic inflammatory disease marked by lipid accumulation and immune cell infiltration in arterial walls. Macrophages contribute by internalizing oxidized low-density lipoprotein, forming foam cells, and driving inflammation. The ubiquitin-proteasome system regulates immune and inflammatory responses in atherosclerosis. This study investigated the protective role of TRIM31 (tripartite motif-containing 31), an E3 ubiquitin ligase, in macrophage lipid metabolism and inflammation through selective regulation of LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1). Transcriptomic profiling, macrophage-specific TRIM31 was selectively upregulated in macrophages under oxidized low-density lipoprotein stimulation and in atherosclerosis plaques. Trim31 deficiency exacerbated plaque burden, foam cell formation, and inflammatory signaling (n=8 per group). Single-cell analysis revealed enrichment of lipid transport and inflammatory pathways in Trim31-deficient plaques. LOX-1 was identified as a key TRIM31 substrate. TRIM31 promoted K48-linked ubiquitination of LOX-1 at lysine 12, facilitating its degradation. The atheroprotective effects of Trim31 were abolished in TRIM31, an inducible, macrophage-enriched protective factor in atherosclerosis, restricts foam cell formation and inflammation by targeting LOX-1 for proteasomal degradation. These findings position TRIM31 as a promising therapeutic target for macrophage-driven atherogenesis. Show less
Atherosclerosis (AS) is closely associated with gut microbiota that plays an important role in regulating intestinal mucosal barrier function, chronic inflammation, and immune homeostasis. Thus, targe Show more
Atherosclerosis (AS) is closely associated with gut microbiota that plays an important role in regulating intestinal mucosal barrier function, chronic inflammation, and immune homeostasis. Thus, targeting the modulation of gut microbitoa repesents a promising strategy for the control of AS. Clostridium butyricum (C. butyricum) serving as a kind of probiotics has shown a variety of biological benefits, but it's impact on atherosclerosis remains poorly understood. Sixty male ApoE C. butyricum ameliorated dyslipidemia and attenuated atherosclerotic plaque formation in ApoE C. butyricum intervention may exert anti-AS effects by reshaping gut homeostasis via the regulation of immune cells, providing a potential strategy for clinical treatment. Show less
Si-Jia Jin, En-Guang Dou, Lei Wang+3 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder characterized by progressive aortic wall degeneration, inflammation, and vascular smooth muscle cells (VSMCs) loss. Despite exte Show more
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder characterized by progressive aortic wall degeneration, inflammation, and vascular smooth muscle cells (VSMCs) loss. Despite extensive research, no effective pharmacological treatment is currently available to prevent or halt AAA progression. This study aimed to discover effective therapeutic agents for AAA and identify potential natural compounds with pharmacological efficacy against the disease by targeting matrix metalloproteinase-2 (MMP2), a key enzyme involved in extracellular matrix degradation and aneurysm progression. An integrated screening strategy combining cytotoxicity evaluation, high-content immunofluorescence imaging, and molecular docking was applied to an angiotensin II (Ang II)-stimulated rat aortic smooth muscle cells (RASMCs) model. A total of 138 natural products were systematically assessed. The anti-aneurysmal efficacy of the identified compound was further validated in both CaCl₂-induced and Ang II-infused ApoE Salvianolic acid B (Sal B), a major polyphenol from Salvia miltiorrhiza, was identified as a potent anti‑AAA candidate. It suppressed aneurysm formation, reduced elastin degradation, and attenuated inflammatory infiltration in vivo, while preserving the contractile phenotype, lowering ROS, and inhibiting MMP activity in Ang II‑stimulated RASMCs in vitro. Mechanistically, Ang II suppresses NRF2, leading to downregulation of the System Xc⁻-GPX4 axis and promoting lipid peroxidation and VSMC ferroptosis. This ferroptosis then activates the AGE-RAGE pathway, amplifying inflammation and MMP‑driven matrix degradation. Sal B counteracts this cascade by restoring NRF2 activity, improving lipid metabolism, and inhibiting MMPs, thereby blocking ferroptosis‑initiated inflammation and preserving aortic integrity. Salvianolic acid B exerts protective effects against AAA by attenuating oxidative stress, ferroptosis, and inflammation. These findings highlight Sal B as a promising natural therapeutic candidate for the prevention and treatment of abdominal aortic aneurysm. Show less
Post-cardiac surgery anxiety or depression (PCPAD) is a common neuropsychiatric complication following cardiovascular interventional procedures, which significantly increases the risk of adverse cardi Show more
Post-cardiac surgery anxiety or depression (PCPAD) is a common neuropsychiatric complication following cardiovascular interventional procedures, which significantly increases the risk of adverse cardiovascular events and long-term mortality. Existing treatment strategies have limitations, and clinical needs remain unmet. The gut-brain axis (GBA) serves as a core network regulating neuroimmune and endocrine responses, and its imbalance involves key links such as intestinal flora dysbiosis and neuroimmune crosstalk disorders. It is closely related to the pathogenesis of this complication, providing a novel perspective for targeted interventions. This review aims to systematically clarify the mechanism of GBA in PCPAD, comprehensively explore therapeutic strategies targeting this axis, and focus on the intervention value and application potential of natural products. The study was designed and conducted in strict accordance with the PRISMA 2020 guidelines. Relevant literatures were searched from PubMed, Web of Science Core Collection, ScienceDirect, Embase, Cochrane Library, and CNKI databases from their inception to December 2025. Literatures focusing on GBA-related mechanisms of PCPAD or investigating the mechanisms and clinical applications of natural products targeting GBA for PCPAD treatment were included. Conference abstracts, case reports, duplicate publications, and other ineligible literatures were excluded. Through quality control strategies including double independent screening and verification, priority inclusion of high-credibility evidence, and data cross-validation, 168 eligible literatures were finally included. The composition and functions of GBA, its imbalance mechanisms, and the basic and clinical evidence of natural product-based interventions were systematically analyzed. Studies have shown that GBA imbalance is the core pathogenesis of PCPAD, among which the inflammatory cascade initiated by intestinal flora dysbiosis, abnormal activation of the neuroendocrine axis, disorder of immune-nerve crosstalk, and abnormal gene and epigenetic regulation are key pathological links. In summary, GBA imbalance, especially gut microbiota dysbiosis and neuroimmune interactions, plays a critical role in the pathogenesis of PCPAD. Natural products (including traditional Chinese medicine (TCM) monomers, TCM compound prescriptions, patented TCM drugs, and natural products from other plant sources worldwide) can exert therapeutic effects by synergistically regulating GBA homeostasis through multiple targets. Specifically, they include increasing the abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus, promoting the production of anti-inflammatory metabolites such as short-chain fatty acids, repairing intestinal barrier function, inhibiting pro-inflammatory pathways such as NF-κB and NLRP3 inflammasome, and regulating the levels of neurotransmitters and neurotrophic factors such as 5-HT and BDNF. Basic and clinical studies have confirmed that these natural products have high biocompatibility and low toxic side effects, and are compatible with the safe medication needs of patients during the organ function recovery period after cardiac surgery. Several natural products have been proven to modulate GBA dysfunction, with potential for clinical therapeutic application. This review systematically elucidates a new paradigm of precise intervention for PCPAD via natural products that regulate GBA through multiple targets, addressing the limitation of traditional single-target therapies and providing a low-cost, easily promotable solution for clinical translation. Additionally, natural product-based interventions offer a novel approach for treating post-cardiac surgery complications. In the future, it is necessary to further conduct large-sample, multicenter clinical trials to clarify their mechanisms of action and standardized dosage regimens, strengthen toxicological research, facilitate the translation from basic research to clinical practice, and provide more precise therapeutic strategies for patients. Show less
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction that is closely associated with cholinergic system damage. Estrogen deficiency is a well-est Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction that is closely associated with cholinergic system damage. Estrogen deficiency is a well-established risk factor for AD in women. Osthole (OST), a phytoestrogen with mild, bidirectional regulatory properties, has been proposed as a potential estrogen replacement. This study aimed to investigate the mechanisms by which OST ameliorates cognitive impairment. Cognitive deficits were induced in female Sprague-Dawley rats by bilateral ovariectomy (OVX), and OST was subsequently administered by oral gavage. Behavioral tests revealed that OST significantly improved learning and memory and reduced anxiety-like and depression-like behaviors in OVX rats. H&E staining and Nissl staining demonstrated that OST reversed neuronal damage in the hippocampus and cortex. Western blotting, ELISA, and immunofluorescence staining indicated that OST treatment restored the estrogen-cholinergic-NGF axis: E Show less
Gene-environment interactions play a critical role in shaping phenotypic heterogeneity in complex psychiatric disorders. Brain-derived neurotrophic factor (BDNF) is a key genetic regulator of stress-s Show more
Gene-environment interactions play a critical role in shaping phenotypic heterogeneity in complex psychiatric disorders. Brain-derived neurotrophic factor (BDNF) is a key genetic regulator of stress-sensitive neuroplasticity. Yet, how We conducted a case-control study including 93 patients with first-episode schizophrenia (SZ) and 64 healthy controls. Childhood trauma exposure was assessed using the Childhood Trauma Questionnaire (CTQ), and symptom dimensions were evaluated with the Positive and Negative Syndrome Scale (PANSS). Three Patients with SZ exhibited significantly higher CTQ scores across all trauma subtypes compared with controls (all These findings demonstrate that Show less
MicroRNAs (miRNAs) are key regulators of myelination and cognitive functions, with miR-219 being particularly important for the differentiation and maturation of oligodendrocyte precursor cells (OPCs) Show more
MicroRNAs (miRNAs) are key regulators of myelination and cognitive functions, with miR-219 being particularly important for the differentiation and maturation of oligodendrocyte precursor cells (OPCs). However, its role in myelin damage and cognitive dysfunction during acute cerebral ischemia is not well understood. In this study, we used the MCAO/R rat model to investigate the mechanistic involvement of miR-219. Our results show that miR-219 alleviates cognitive dysfunction induced by MCAO/R. The agonist group showed a reduced time to locate the platform in the water maze, while the antagonist group showed an increased time compared to the solvent control. Additionally, miR-219 reduced myelin damage, as demonstrated by Luxol Fast Blue (LFB) staining, which indicated substantial hippocampal demyelination repair in the agonist group, whereas the antagonist group exhibited aggravated demyelination. Electron microscopy revealed enhanced myelin sheath regeneration and increased thickness in the agonist group, while the antagonist group displayed fewer and thinner myelin sheaths. Furthermore, miR-219 regulated OPC maturation, with more CNPase-positive cells in the agonist group and fewer in the antagonist group than the solvent control. In NG2 staining, the agonist group had fewer positive cells, while the antagonist group had more. miR-219 also decreased Lingo-1 expression, leading to reduced levels of AKT, RhoA, and mTOR in the downstream signaling pathway. These findings suggest that activating the miR-219-Lingo-1 signaling pathway during ischemia-reperfusion could offer a potential therapeutic approach for improving myelin damage and alleviating cognitive dysfunction in cerebral ischemia. Show less
Apolipoprotein B (apoB) is essential for lipoprotein assembly and secretion and plays a central role in the development of cardiovascular disease and metabolic dysfunction-associated steatotic liver d Show more
Apolipoprotein B (apoB) is essential for lipoprotein assembly and secretion and plays a central role in the development of cardiovascular disease and metabolic dysfunction-associated steatotic liver disease. Although apoB protein degradation during very-low-density lipoprotein maturation has been extensively studied, the regulation of A forward genetic screen in randomly mutagenized mice identified HELZ2 (helicase with zinc finger 2) as a critical regulator of lipid metabolism. The metabolic effects of HELZ2 mutations or deficiency were evaluated in mice maintained on a chow diet or a high-fat diet. We also used a doxycycline-inducible, liver-specific HELZ2 overexpression model to test the sufficiency of hepatocyte We discovered a unique gain-of-function mutation in HELZ2 (L1833P, called HELZ2 is a key regulator of Show less
Atherosclerosis serves as the fundamental pathological process underlying numerous cardiovascular disorders, and the change of macrophage polarisation is the key to regulate the inflammatory response Show more
Atherosclerosis serves as the fundamental pathological process underlying numerous cardiovascular disorders, and the change of macrophage polarisation is the key to regulate the inflammatory response of AS. SIRT6 plays a protective effect in AS, but whether it regulates macrophage polarisation in AS remains uncertain. We aimed to characterise the mechanistic role of SIRT6 in atherosclerosis development mediated by macrophage polarisation. ApoE Show less
High mobility group AT-hook 1 (HMGA1) is a chromatin regulator overexpressed in various cancers, often predicting poor outcomes. However, its role in head and neck squamous cell carcinoma (HNSCC) rema Show more
High mobility group AT-hook 1 (HMGA1) is a chromatin regulator overexpressed in various cancers, often predicting poor outcomes. However, its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. A hallmark of HNSCC is the rapid growth of its vasculature. Here, we identify an epigenetic mechanism whereby HMGA1 promotes tumor progression and angiogenesis via upregulation of fibroblast growth factor-binding protein 1 (FGFBP1). Show less
Interleukin-27 (IL-27) in the pleural fluid has gained significant attention as a diagnostic biomarker for tuberculous pleural effusion (TPE); however, considerable variability exists across available Show more
Interleukin-27 (IL-27) in the pleural fluid has gained significant attention as a diagnostic biomarker for tuberculous pleural effusion (TPE); however, considerable variability exists across available studies. This systematic review and meta-analysis aimed to determine the diagnostic accuracy of IL-27 in identifying TPE. In addition, we also compared the diagnostic accuracy of IL-27 and adenosine deaminase (ADA) with a head-to-head meta-analysis. We searched the PubMed and Web of Science databases to identify diagnostic test accuracy studies evaluating the accuracy of IL-27 for diagnosing TPE. The last search date was September 2025. We extracted data from the eligible studies and constructed a two-by-two table with true positives (TP), false positives (FP), true negatives (FN), and false negatives (FN). The QUADAS-2 tool was used to assess the quality of eligible studies. A bivariate model was applied to pool sensitivity and specificity, and a summary receiver operating characteristic (sROC) curve with the area under the curve (AUC) was generated to estimate the overall diagnostic accuracy of IL-27 and ADA. A Deeks funnel plot asymmetry test was used to evaluate publication bias. Nine studies encompassing ten cohorts were included, involving 1573 patients (429 with TPE and 1144 with non-TPE). The reported AUCs for IL-27 ranged from approximately 0.73 to 0.99 across eligible studies. The pooled sensitivity and specificity were 0.94 (95% CI, 0.83-0.98) and 0.96 (95% CI, 0.89-0.98), respectively. The AUC for sROC was 0.99 (95% CI, 0.97-0.99). The pooled positive likelihood ratio was 21.97 (95% CI, 7.95-60.69), the negative likelihood ratio was 0.07 (95% CI, 0.02-0.18), and the diagnostic odds ratio (DOR) was 329 (95% CI, 72-1506). Significant heterogeneity was observed in both sensitivity (I IL-27 is a promising diagnostic marker for TPE, and its diagnostic accuracy is comparable to that of ADA. IL-27 should be used as a complementary diagnostic marker to ADA for TPE. Show less
Pendimethalin (PMN) is a potent agrochemical that has shown severe neural alterations. Sanguinarine (SAN) is a naturally derived alkaloid that exhibits a wide range of biological properties. The curre Show more
Pendimethalin (PMN) is a potent agrochemical that has shown severe neural alterations. Sanguinarine (SAN) is a naturally derived alkaloid that exhibits a wide range of biological properties. The current research was conducted to explore the palliative potential of SAN against PMN-induced neurotoxicity. Thirty-two Sprague Dawley rats were divided into the control, PMN (125 mg/kg), PMN (125 mg/kg) + SAN (15 mg/kg), and SAN (15 mg/kg) alone treated group. PMN intoxication upregulated the mRNA expressions of Aif1 (iba1), cd68, TNF-α, IL-10, IL-6, IL-1β, Nos2, Arg1, and Trem2 while inhibiting the mRNA expression of Tmem119. Neural tissues showed altered redox state after PMN exposure as evidenced by escalated levels of ROS and MDA coupled with marked declined in the activities of HO-1, GPx, CAT, GSR, SOD, and GST. Additionally, PMN administration provoked a sharp decline in the levels of NGF, BDNF, GDNF, Synaptophysin, and PSD-95. Moreover, exposure of PMN elevated the levels of Caspase-9, Bax, and Caspase-3 coupled with a significant reduction in the levels of Bcl-2. Neural tissues showed severe morphological alterations including vacuolar degeneration, neuronal loss, microglial activation, apoptotic bodies, capillary congestion, perineuronal vacuolation, and neural edema after PMN intoxication. Importantly, SAN supplementation notably alleviated neural damage via suppressing the activation of microglial and inflammatory pathways along with regulating redox profile, apoptotic indices, and histopathological alterations. Our in-silico assessment showed excellent binding affinity of SAN with key regulatory proteins thereby suggesting its critical role in suppressing the activation of microglial cells. Show less
Hypothyroidism, the most prevalent endocrine disorder globally, is associated with increased cardiovascular risk. This study aims to evaluate cardiovascular risk factors-including serum oxidized low-d Show more
Hypothyroidism, the most prevalent endocrine disorder globally, is associated with increased cardiovascular risk. This study aims to evaluate cardiovascular risk factors-including serum oxidized low-density lipoprotein (ox-LDL), serum homocysteine (Hcy), and lipid profiles-and their correlations with thyroid-stimulating hormone (TSH) levels. Early identification of these risk predictors may reduce the incidence and mortality of cardiovascular disease in hypothyroid patients. This cross-sectional study included 676 participants. Subjects were stratified into four groups: three corresponding to TSH quartiles within the reference range and a fourth comprising subclinical hypothyroidism (SCH) patients with TSH levels above this range. All participants underwent physical examinations and provided fasting blood samples for measurement of TSH, free thyroxine (FT4), free triiodothyronine (FT3), blood glucose, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein(a) [Lp(a)], ox-LDL, and Hcy. Across the four subgroups, LDL-C, ApoB, ox-LDL, and Hcy levels exhibited significant increasing trends (all The observed correlations between ox-LDL, Hcy, and dyslipidemia in subclinical hypothyroidism may indicate a proatherogenic state. Elevated ox-LDL and Hcy emerge as independent factors associated with accelerated atherosclerosis in this condition. Show less
This study investigated the expression of brain-derived neurotrophic factor (BDNF) signaling components (BDNF-TrkB-AKT1) and apoptosis-related factors (Bcl-2 and Bax) in yak brain regions at different Show more
This study investigated the expression of brain-derived neurotrophic factor (BDNF) signaling components (BDNF-TrkB-AKT1) and apoptosis-related factors (Bcl-2 and Bax) in yak brain regions at different altitudes. The cerebral cortex, cerebellum, hippocampus, thalamus, and medulla oblongata were collected from 3-year-old yaks living at low and high altitudes. The relative mRNA expression of BDNF, TrkB, AKT1, Bcl-2, and Bax was assessed by qRT-PCR. Protein abundance and cellular localization of BDNF, TrkB, AKT1, Bcl-2, and Bax were evaluated by Western blotting and immunohistochemistry, with immunoreactivity quantified by optical density analysis. Within each altitude group, BDNF, TrkB, AKT1, and Bcl-2 mRNA expression and the corresponding protein levels (BDNF, TrkB, AKT1, and Bcl-2) were significantly higher in the cerebral cortex and hippocampus than in the cerebellum, thalamus, and medulla oblongata (P < 0.05). In contrast, Bax mRNA and Bax protein levels did not differ significantly among the five regions. Compared with low-altitude yaks, high-altitude yaks showed significantly higher BDNF, TrkB, AKT1, and Bcl-2 mRNA expression and higher BDNF, TrkB, AKT1, and Bcl-2 protein levels in brain tissues (P < 0.05), whereas Bax protein expression did not differ between altitude groups. Immunohistochemistry revealed immunoreactivity for BDNF, TrkB, AKT1, Bcl-2, and Bax in both altitude groups, with prominent labeling in cortical pyramidal neurons and across the pyramidal cell layer in the hippocampal CA region. Immunoreactivity was also detected in large neurons of the thalamus and medulla oblongata. In the cerebellum, labeling was strongest in Purkinje cells, with weaker signals in the granule cell layer and molecular layer. BDNF-TrkB-AKT1 pathway components and Bcl-2 showed relatively higher expression in the cerebral cortex and hippocampus within each altitude group, whereas Bax expression did not vary across regions. These patterns are consistent with an association between BDNF-TrkB-AKT1 signaling and increased Bcl-2 expression without a corresponding increase in Bax, which may support neuronal adaptation in the cerebral cortex and hippocampus. Elevated expression of BDNF, TrkB, AKT1, and Bcl-2 at high altitude suggests enhanced adaptation to hypoxia in high-altitude yaks; the underlying mechanisms require further investigation. Show less
Given the globalization of the nursing workforce, psychological empowerment represents a critical intrinsic determinant of nurses' mobility intentions, specifically regarding cross-border work. To ide Show more
Given the globalization of the nursing workforce, psychological empowerment represents a critical intrinsic determinant of nurses' mobility intentions, specifically regarding cross-border work. To identify latent profiles of nurses' psychological empowerment, examine associated factors, and explore the relationship between these profiles and cross-border working intention. A cross-sectional multicenter study was conducted from March to September 2023. Using convenience sampling, clinical nurses were recruited through liaisons from nursing societies in nine cities of Guangdong Province. Data were collected through questionnaires covering sociodemographic questionnaire, psychological empowerment, and cross-border working intention, with analyses including chi-square tests, logistic regression, and latent profile analysis (LPA) performed using SPSS 23.0 and Mplus 8.3. A total of 3671 valid questionnaires were collected, and 39.5% of the respondents reported cross-border intentions. LPA identified three psychological empowerment profiles among nurses, ranked from high to low: the core-driven empowerment profile (16.94%), the adaptive empowerment profile (70.42%), and the constrained empowerment profile (12.64%). The nurses with lower salary, intermediate title, and without specialist nurse qualification were more likely to fall into the constrained empowerment profile. Psychological empowerment was positively correlated with nurses' cross-border work intention. The core-driven profile showed the highest cross-border work intention (50.6%), followed by the adaptive (38.2%) and constrained profiles (31.7%). For cross-border work, the constrained profile prioritized salary (87.1%) as the key concern, while the core-driven profile focused more on good promotion opportunities (70.3%). Psychological empowerment exerts a positive impact on clinical nurses' cross-border work intention, with the three identified empowerment profiles exhibiting divergent motivational priorities and decision logics. These findings highlight the need for subgroup-specific strategies to balance nursing workforce mobility and stability. The findings support a differentiated human resource strategy based on nurses' psychological empowerment profiles. For core-driven nurses, institutions should provide international career development channels to strengthen their domestic job embeddedness. For adaptive nurses, tailored skill training and decision-making autonomy should be offered to guide their mobility aspirations. For constrained nurses, competitive compensation and family support services should be prioritized to address their stability needs and rebuild professional confidence. These targeted measures balance talent mobility and domestic workforce stability. Show less
Severe peripheral nerve injury (PNI) remains a major clinical challenge, and functional recovery after conventional neurorrhaphy is often unsatisfactory due to fascicular mismatch, suture tension, and Show more
Severe peripheral nerve injury (PNI) remains a major clinical challenge, and functional recovery after conventional neurorrhaphy is often unsatisfactory due to fascicular mismatch, suture tension, and limited Schwann cell viability. To address these limitations, we previously developed a small-gap chitosan-based conduit that provides a controlled microenvironment for regenerative interventions. This study aimed to investigate whether SOX5 overexpression enhances Schwann cell regenerative potential and, when combined with this conduit, synergistically promotes peripheral nerve regeneration. Schwann cells were transduced with SOX5 lentivirus and assessed for proliferation, migration, and neurotrophic factor secretion in vitro. In a rat sciatic nerve transection model (2-mm gap), animals received a chitosan conduit with intraluminal injection of SOX5 lentivirus. Histological, electrophysiological, and behavioral assessments were conducted at 12 weeks post-surgery. SOX5 overexpression significantly enhanced Schwann cell proliferation, migration, and secretion of BDNF, NGF, CNTF, and VEGF, while maintaining the dedifferentiated repair phenotype. In vivo, the combination of SOX5 lentivirus and chitosan conduit improved axonal regeneration, reduced muscle atrophy, and increased conduction velocity and locomotor recovery relative to the empty conduit group. Lentivirus-mediated SOX5 overexpression drives Schwann cells toward a repair phenotype and, when integrated with a small-gap chitosan-based conduit, effectively promotes structural and functional nerve regeneration. Show less
Euphorbia Lathyris L. Seed (ELLS) is a Traditional Chinese Medicine (TCM), which has long been used in China. This study was designed to reveal the synergistic mechanism of ELLS in the treatment of co Show more
Euphorbia Lathyris L. Seed (ELLS) is a Traditional Chinese Medicine (TCM), which has long been used in China. This study was designed to reveal the synergistic mechanism of ELLS in the treatment of colorectal cancer (CRC) by using network pharmacology method and molecular docking. In addition, related in vitro experiments will be conducted to verify the efficacy of ELLS. ELLS related compounds were obtained from TCMSP database. Then active compounds were screened by ADME (absorption, distribution, metabolism, and excretion). Additionally, TCMSP, BATMAN-TCM, STITCH, Swiss Target Prediction and literatures were used to capture the relationships between drugs and targets. A compound-target (C-T) network was established by Cytoscape. Target genes related to CRC were acquired from GeneCards, TTD and OMIM databases. Correlations about compound-target-pathway (C-T-P) were visualized by Cytoscape. The protein-protein interaction (PPI) network was constructed by STRING. Gene survival analysis came from the GEPIA2. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via metascape. Molecular docking analysis was constructed by the AutoDock Vina. And the efficacy of ELLS in combating CRC was verified using HCT116 and SW620 cells. A total of 12 active compounds and 173 associated targets of ELLS compounds were identified. Sixty-three common genes were obtained by matching 173 potential genes of ELLS with 1554 CRC related genes and PPI network screened out key targets, including AKT1, CASP3, ESR1, TNF, HSP90AA1. Five core compounds were beta-sitosterol, stigmasterol, euphol, Artemetin and lathyrol. Eight core targets were PRKACA, PRKCA, AR, BAX, GSK3B, NFKB1, RXRA and NCOA2 in the C-T-P network. KEGG pathway analysis indicated that ELLS effectively treated CRC through regulation of pathways in cancer, Epstein-Barr virus infection, thyroid hormone signaling pathway, bile secretion, and transcriptional misregulation in cancer. Gene survival analysis showed that 7 genes (APAF1, APOE, CASP3, HDAC2, NFKB1, PGR, and SNAI1) were significantly related in CRC patients’ survival and prognosis. Molecular docking results suggested that almost all of the core compound-targets had an excellent binding activity (affinity < − 5 kcal/mol). CCK8 results indicated that ELLS (20 µg/mL, 24-hour treatment) significantly inhibited the proliferation of HCT116 cells, while it had minimal impact on the viability of normal NCM460 cells under the same conditions (survival rate ≥ 80%). Key targets of ELLS could regulate multiple signaling pathways and biological process in treating CRC which provided a scientific basis for further elucidating the mechanism of molecules and screening drug targets. Show less
Aging worsens Alzheimer's disease (AD) peripheral metabolism and central pathology, yet few interventions are effective when started late. Methionine restriction (MR) induces the hepatokine FGF21 and Show more
Aging worsens Alzheimer's disease (AD) peripheral metabolism and central pathology, yet few interventions are effective when started late. Methionine restriction (MR) induces the hepatokine FGF21 and may protect brain function, but its efficacy and mechanisms when started late are unclear. Fourteen-month-old male APP/PS1 mice received 17 weeks of MR (0.17% methionine); behavioral, histological, and molecular assays were performed and hippocampal FGFR1 was knocked down by adeno-associated virus. Late-life MR improved peripheral glucose/lipid profiles, reduced Aβ deposition, preserved synaptic markers, and suppressed neuroinflammation. MR-induced hepatic FGF21 and brain FGFR1-AMPKα signaling to inhibit NFκB; hippocampal FGFR1 knockdown abolished MR's neuroprotective effects while leaving peripheral metabolic changes intact. Even when initiated in late life, MR robustly reduces AD pathology via the hepatic FGF21-brain FGFR1 axis, independent of peripheral metabolic changes. These preclinical findings position MR and FGF21-FGFR1 axis as actionable late-life intervention targets with potential for clinical translation. Show less
Patient safety competency (PSC) is a core element of nursing practice, essential for ensuring high-quality and safe patient care. Newly recruited nurses often face challenges such as transition shock, Show more
Patient safety competency (PSC) is a core element of nursing practice, essential for ensuring high-quality and safe patient care. Newly recruited nurses often face challenges such as transition shock, limited clinical experience, and fragmented safety education, which may hinder their ability to maintain patient safety. Most studies have assessed PSC using total scale scores, overlooking internal heterogeneity within this group. This study aimed to identify latent profiles of PSC among newly recruited nurses and explore the influencing factors to provide evidence for targeted competency development and management strategies. From July to August 2023, a convenience sample of newly recruited nurses was obtained from seven tertiary grade-A hospitals in Shandong Province, China. Data were collected using the General Information Questionnaire, the Transition Shock Scale of Newly Graduated Nurses, the Nurses' Perception of Organizational Support Scale, and the Patient Safety Nurse Competency Evaluation Scale. Latent Profile Analysis (LPA) was conducted to identify the potential subgroups of patient safety competency among newly recruited nurses. Univariate analysis and multivariate logistic regression were performed to examine the influencing factors associated with different latent profile categories. The patient safety competency of newly recruited nurses was categorized into 3 potential profiles: "high safety competency group" (36.9%), "medium safety competency group" (49.4%), and "low safety competency group" (13.7%). The results of the logistic regression analysis revealed that education level, average number of night shifts per week, participation in safety training, involvement in patient safety-related projects, transition shock, and perceived organizational support were significant predictors of patient safety competency among newly recruited nurses (P < 0.05). This study identified three distinct latent profiles of patient safety competency among newly recruited nurses, revealing a moderate overall competency level with notable heterogeneity. Nursing managers should pay particular attention to nurses with moderate and low competency levels and implement targeted, evidence-based interventions to strengthen their patient safety competency and promote safer clinical practice. Not applicable. Show less
High-dose methotrexate for pediatric cancer treatment is frequently associated with mucositis, which can lead to delayed or discontinued treatment and impact survival. While individual genetic variant Show more
High-dose methotrexate for pediatric cancer treatment is frequently associated with mucositis, which can lead to delayed or discontinued treatment and impact survival. While individual genetic variants have been implicated, the cumulative impact of genetic variation within relevant biological pathways remains unexplored. We evaluated single nucleotide polymorphisms across 18 pathways previously identified as relevant to mucositis in 278 pediatric patients with acute lymphoblastic leukemia from six academic health centers across Canada. Pathway enrichment was assessed using the Joint Association of Genetic variants tool, and a predictive model was developed using XGBoost, a supervised machine learning algorithm based on gradient-boosted decision trees. Pathway enrichment identified significant associations in IL6 (P = 0.04) and WNT/β-catenin (P = 0.048) signaling pathways. The predictive model (area under the curve [AUC] = 0.76) highlighted single nucleotide polymorphisms associated with inflammation- and mucosa-related genes, including PRKCD, IL17B, MAST3, and CAPN9, with both risk and protective effects. Model performance dropped by 0.15 in AUC (from 0.76 to 0.61) after removing single nucleotide polymorphism features, underscoring their predictive value. This pathway-informed approach identifies genetic contributors to methotrexate-induced mucositis and supports polygenic risk prediction. Our findings provide a foundation for individualized toxicity risk profiling and suggest potential therapeutic targets to mitigate treatment-limiting mucositis in pediatric oncology. Show less
Irritable bowel syndrome (IBS) associated with early-life stress (ELS) commonly manifests as anxiety and visceral hypersensitivity. However, the pathogenic mechanisms underlying these effects are not Show more
Irritable bowel syndrome (IBS) associated with early-life stress (ELS) commonly manifests as anxiety and visceral hypersensitivity. However, the pathogenic mechanisms underlying these effects are not fully understood. This study aims to investigate the role of brain-derived neurotrophic factor (BDNF) as a key mediator of ELS-induced changes through the brain-gut axis. A Sprague-Dawley male maternal separation (MS) rat model was used to induce anxiety and visceral hypersensitivity associated with ELS. BDNF levels were measured in the limbic system (cingulate gyrus, amygdala, and hippocampus) and serum. The correlation between BDNF levels, anxiety, and visceral hypersensitivity was analyzed. Corticotropin-releasing factor (CRF) expression in the hippocampus and the extent of visceral hyper-sensitivity were assessed in control, MS, and MS+K252a (a BDNF receptor antagonist) groups. MS rats exhibited higher levels of anxiety and visceral hypersensitivity compared to controls. BDNF production in the hippocampus was elevated in MS rats and positively correlated with anxiety (r = -0.78, p < 0.05) and visceral hypersensitivity (r = 0.93, p < 0.01). CRF expression, a key mediator of stress and visceral hypersensitivity, was also increased in the hippocampus of MS rats. Inhibition of BDNF signaling using K252a reduced CRF expression and alleviated visceral hypersensitivity. This study demonstrates that BDNF may mediate ELS-induced anxiety and visceral hypersensitivity through hippocampal TrkB-CRF signaling, providing a mechanistic basis for targeting BDNF in stress-related IBS. Show less
Xinjiang Province possesses several local sheep breeds which are well known for their tender meat, delicious taste, and lack of odor. At present, the microbial composition in the gastrointestinal trac Show more
Fujian Tablets (FJT), a traditional Chinese medicinal (TCM) preparation, has been clinically used in the rehabilitation of neurological disorders related to ischemic brain injury in the context of TCM Show more
Fujian Tablets (FJT), a traditional Chinese medicinal (TCM) preparation, has been clinically used in the rehabilitation of neurological disorders related to ischemic brain injury in the context of TCM theory. However, its molecular mechanism underlying the promotion of post-ischemic stroke motor function recovery, especially via regulating corticospinal tract (CST) remodeling-a key structure for motor control-remains unelucidated. This study aimed to investigate the effect of FJT on CST remodeling in the denervated hemisphere and motor function recovery in middle cerebral artery occlusion (MCAO) rats, and to explore its potential mechanism by focusing on the balance between precursor brain-derived neurotrophic factor (proBDNF) and mature BDNF (mBDNF), which is tightly regulated by BDNF-cleaving enzymes (Pcsk1 and Furin). The MCAO rat model was established using the intraluminal filament method. Model rats were randomly divided into four groups: MCAO model group, FJT low-dose group, FJT medium-dose group, and FJT high-dose group. Motor function was evaluated by Catwalk gait analysis (assessing average speed, step length, and standing time). CST remodeling and conduction efficiency were determined via biotinylated dextran amine (BDA) neural tracing and motor evoked potential (MEP) detection, respectively. The mRNA and protein expressions of BDNF, cleaving enzymes (Pcsk1, Furin), and related receptors (TrkB, p75NTR, Sortilin) in brain tissues were measured using quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. BDNF silencing experiment was performed to verify the role of BDNF in FJT-induced effects. Additionally, in vitro neuronal culture was used to observe the effects of FJT, exogenous mBDNF, and Pcsk1/Furin inhibitors on neuronal growth. Compared with the MCAO model group, medium-dose FJT exhibited the most significant therapeutic effects. Specifically, FJT notably improved gait parameters increasing average speed from 20.77 mm/s (MCAO) to 25.71 mm/s (FJT) and step length by approximately 21.14 %. Furthermore, FJT enhanced MEP conduction efficiency and promoted CST remodeling, characterized by a 5.26 % increase in BDA-positive nerve fibers and elevated growth-associated protein 43 (GAP43) expression in the denervated hemisphere. At the molecular level, FJT upregulated the mRNA and protein expressions of Pcsk1 and Furin, increased the levels of BDNF and its functional receptor TrkB, and downregulated the expressions of proBDNF-preferring receptors p75NTR and Sortilin, ultimately shifting the proBDNF/mBDNF ratio toward mBDNF dominance. BDNF silencing significantly attenuated these improvements, reversing FJT-induced motor recovery and CST remodeling. In vitro, FJT-promoted neuronal growth was mimicked by exogenous mBDNF but reversed by Pcsk1/Furin inhibitors. Compared with the MCAO model group, medium-dose FJT exhibited the most significant therapeutic effects. Specifically, FJT notably improved gait parameters, increasing the average speed from 20.77 mm/s (MCAO) to 25.71 mm/s (FJT) and step length by approximately 21.14 %. Furthermore, FJT enhanced MEP conduction efficiency and promoted CST remodeling, characterized by a 5.26% increase in BDA-positive nerve fibers and elevated Growth-Associated Protein 43 (GAP43) expression in the denervated hemisphere. At the molecular level, FJT upregulated the mRNA and protein expressions of Pcsk1 and Furin, increased the levels of BDNF and its functional receptor TrkB, and downregulated the expressions of proBDNF-preferring receptors p75NTR and Sortilin, ultimately shifting the proBDNF/mBDNF ratio toward mBDNF dominance. BDNF silencing significantly attenuated these improvements, reversing FJT-induced motor recovery and CST remodeling. In vitro, FJT-promoted neuronal growth was mimicked by exogenous mBDNF but reversed by Pcsk1/Furin inhibitors. Show less