Incontinence-associated dermatitis (IAD) is a common nursing challenge in clinical practice, imposing a significant burden on both patients and healthcare providers. Studies have reported that nurses' Show more
Incontinence-associated dermatitis (IAD) is a common nursing challenge in clinical practice, imposing a significant burden on both patients and healthcare providers. Studies have reported that nurses' preventive attitudes toward IAD significantly influence its prevalence, and there may be a potential association between achievement motivation and these attitudes. Previous research on nurses' preventive attitudes toward IAD has primarily focused on overall levels, overlooking potential heterogeneity within the population. This study aimed to investigate the heterogeneity in clinical nurses' preventive attitudes toward IAD using a person-centered approach and to identify the influencing factors for different subgroups. A secondary aim was to utilize Self-Determination Theory (SDT) to elucidate the relationship between the identified attitude profiles and nurses' achievement motivation, thereby providing targeted strategies to enhance their preventive attitudes. This study selected 1058 clinical nurses from a tertiary hospital in Fujian, China, as research participants from September to October 2024. The study utilized the following instruments: a general information questionnaire, the Attitude Toward the Prevention of Incontinence-Associated Dermatitis Instrument, and the Achievement Motivation Scale. Latent profile analysis (LPA) was employed to identify the latent profiles of nurses' attitudes toward IAD prevention. At the same time, Two subgroups of nurses' attitudes toward IAD prevention were identified: the low-level group (63.42%) and the high-level, low-personal-responsibility group (36.57%). A significant correlation was found between nurses' attitudes toward IAD prevention and achievement motivation. Nurses with a more positive preventive attitude scored higher on the motivation for success dimension, while those with a less positive attitude scored higher on the motivation to avoid failure dimension. Factors influencing nurses' attitudes toward IAD prevention included position, department, number of participants in wound/ostomy/incontinence care training, satisfaction with the work atmosphere, and achievement motivation scores. This study revealed heterogeneity in nurses' attitudes toward IAD prevention. Nurses with positive attitudes tended to adopt a success-driven approach, while those with relatively negative attitudes leaned toward a failure-avoidance strategy, reflecting two fundamentally distinct coping mechanisms. Nursing managers should address these individual differences by targeting achievement motivation as an intervention point. Management strategies should be tailored to the distinct profiles; for instance, interventions for the "low-level group" should prioritize building competence through structured training, while strategies for the "high-level, low-personal-responsibility group" should focus on enhancing autonomy and personal accountability. By adopting such targeted approaches, managers can more effectively enhance nurses' preventive attitudes, thereby improving care quality and reducing IAD incidence. Show less
With the advancement of genomic technologies, precision lifestyle interventions tailored to individual genetic backgrounds have emerged as a novel approach for preventing and managing chronic diseases Show more
With the advancement of genomic technologies, precision lifestyle interventions tailored to individual genetic backgrounds have emerged as a novel approach for preventing and managing chronic diseases such as obesity. Several randomized controlled trials (RCTs) targeting obese or overweight populations have found that individuals with different genotypes exhibit varying responses to the same lifestyle intervention (gene-lifestyle intervention interactions). To date, more than 20 genes, including Show less
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of Show more
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of chlorogenic acid (CHA), a multifunctional natural active compound, in AD therapy by developing a trifunctional nanocarrier (MC-H/R/si). CHA was effectively conjugated with iron-based metal-organic frameworks (MIL/Fe-100) through chelation interaction. The resulting nanocomplex (MC) not only enhances the bioavailability of CHA but also facilitates a synergistic antioxidant effect between CHA and MIL/Fe-100. Importantly, CHA can chelate Zn Show less
Meng Xiong, Renjie Luo, Zhijiao Zhang+4 more · 2025 · Inflammation research : official journal of the European Histamine Research Society ... [et al.] · Springer · added 2026-04-24
Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulate Show more
Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulated by macrophages. This study aimed to elucidate the effect of Recombinant Mouse IL-27 Protein on macrophage ferroptosis and polarization, as well as its impact on sepsis-induced ARDS. A cecal ligation and puncture (CLP)-induced sepsis model was established using wild-type (WT) or IL27R In vitro, IL-27 alone did not alter the expression of proteins linked to the ferroptosis pathway or macrophage polarization. Contrastingly, the combination of IL-27 with LPS further amplified LPS-induced alterations in the ferroptosis pathway, thereby promoting macrophage M1 polarization and inhibiting M2 polarization. Additionally, IL-27 + LPS increased ROS levels in macrophages. A sepsis-induced ARDS mouse model was then established via CLP. In vivo, IL-27 exacerbated CLP-induced lung injury in WT mice. Additionally, it decreased the expression levels of ferroptosis-related proteins (Nrf2, HO-1, GPX4) and increased those of Ptgs2 in the lung tissue of septic mice. Besides, GSH and SOD levels in lung tissue were also reduced. Moreover, IL-27 also promoted M1 polarization and inhibited M2 polarization in macrophages. In IL27R Oltipraz may alleviate ARDS-related lung injury by up-regulating Nrf2 expression and concurrently inhibiting macrophage ferroptosis. Show less
Several protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) levels in statin-intolerant patients, but none Show more
Several protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) levels in statin-intolerant patients, but none have been verified in Chinese patients. This study aimed to evaluate the efficacy and safety of ongericimab, a novel PCSK9 monoclonal antibody, in Chinese statin-intolerant patients with primary hypercholesterolemia or mixed dyslipidemia. This was a randomized, multicenter, double-blind, placebo-controlled phase 3 study designed to enroll 120 statin-intolerant adult patients. Eligible patients were randomly assigned in a 2:1 ratio to receive ongericimab 150 mg or placebo subcutaneously every 2 weeks for 12 weeks in the double-blind treatment period, followed by 40 weeks of ongericimab treatment during the open-label period. The primary endpoint was a percentage change in LDL-C from baseline to week 12. The key secondary endpoints included percentage change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC), and lipoprotein(a) [Lp(a)]. From February 6, 2023, to September 23, 2024, a total of 139 patients were enrolled. The least-squares (LS) mean difference between ongericimab and placebo groups in LDL-C from baseline to week 12 was -66.2 % (95 % CI: 74.2 %, -58.2 %; p < 0.0001), with reductions sustained up to week 52. Ongericimab also significantly reduced levels of non-HDL-C, ApoB, TC, and Lp(a). The overall incidence of treatment-emergent adverse events was comparable between the ongericimab and placebo groups. Ongericimab significantly reduced LDL-C as well as other atherogenic lipid levels and was well tolerated in Chinese statin-intolerant patients with primary hypercholesterolemia or mixed dyslipidemia. http://www. gov; Unique Identifier: NCT05621070. Show less
Post traumatic stress disorder (PTSD) is a serious and persistent mental diseases. Nowadays, Treatment of PTSD patients in clinical practice is mainly based on drug therapy accompanied by psychologica Show more
Post traumatic stress disorder (PTSD) is a serious and persistent mental diseases. Nowadays, Treatment of PTSD patients in clinical practice is mainly based on drug therapy accompanied by psychological therapy. However, the therapeutic effect is unsatisfactory. It is urgent to detect how to treat PTSD patients. Here, we found that ginsenoside can significantly relieve PTSD symptoms in mice model. Rg3, one of the main pharmacological components of ginsenoside, prevents PTSD by promoting alternatively activated M2 phenotype microglia while inhibiting classically activated inflammatory M1 phenotype microglia. Mechanistically, Rg3 up-regulates fibroblast growth factor receptor 1 (FGFR1) expression in microglia to suppress excessive activation of microglia and reduce neuronal apoptosis. Importantly, knocking down FGFR1 expression in BV2 cells promoted a pro-inflammatory phenotype of BV2 cells, while over-expressing FGFR1 reversed this effect. In vivo PTSD mice model results showed that knockdown FGFR1 prevents the therapeutic effect of Rg3, which indicates that FGFR1 is an essential target of PTSD. Our results reveal that Rg3 may be a potential drug to treat PTSD patients. Show less
Previous studies have investigated the role of metabolic factors in risk of hematological malignancies with contradicting findings. Existing studies are generally limited by potential concern of rever Show more
Previous studies have investigated the role of metabolic factors in risk of hematological malignancies with contradicting findings. Existing studies are generally limited by potential concern of reverse causality and confounding by inflammation. Therefore, we aimed to investigate the associations of glucose, lipid, and apolipoprotein biomarkers with the risk of hematological malignancy. We performed a study of over 560,000 individuals of the Swedish AMORIS cohort, with measurements of biomarkers for carbohydrate, lipid, and apolipoprotein metabolism during 1985-1996 and follow-up until 2020. We conducted a prospective cohort study and used Cox models to investigate the association of nine different metabolic biomarkers (glucose, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), LDL-C/HDL-C, triglyceride (TG), apolipoprotein B (ApoB), apolipoprotein A-I (ApoA I), and ApoB/ApoA-I) with risk of hematological malignancy, after excluding the first five years of follow-up and adjustment for inflammatory biomarkers. We observed a decreased risk of hematological malignancy associated with one SD increase of TC (HR 0.93; 95% CI 0.91-0.96), LDL-C (HR 0.94; 95% CI 0.91-0.97), HDL-C (HR 0.92; 95% CI 0.86-0.99), and ApoA-I (HR 0.96; 95% CI 0.93-0.996). Our study highlights a decreased risk of hematological malignancy associated with a higher level of TC, LDL-C, HDL-C, and ApoA-I. Show less
The lack of standardized objective approaches hinders the accurate diagnosis and treatment of depression. Herein, a novel electrochemical platform was created utilizing cost-effective and rapid 3D pri Show more
The lack of standardized objective approaches hinders the accurate diagnosis and treatment of depression. Herein, a novel electrochemical platform was created utilizing cost-effective and rapid 3D printing technology to overcome the constraints of conventional diagnostic methods. This method allows for highly sensitive detection of Apolipoprotein A4 (Apo-A4), an important biomarker for depression, using dual-signal outputs. The electrode material utilized in this setup consisted of a combination of carbon black/polylactic acid (CB/PLA) and ferrocene-chitosan-gold nanoparticles (Fc-CS-AuNPs). On the other hand, the signal label was composed of gold nanoparticles-thionine-secondary antibody (AuNPs-Thi-Ab Show less
Diabetic cardiomyopathy (DCM) in type 2 diabetes (T2D) may lead to heart failure and patient death. Fibroblast growth factor 21 (FGF21) is a therapeutic candidate for treating this disease. However, o Show more
Diabetic cardiomyopathy (DCM) in type 2 diabetes (T2D) may lead to heart failure and patient death. Fibroblast growth factor 21 (FGF21) is a therapeutic candidate for treating this disease. However, one impediment to its clinical use is its weak ability to activate downstream signaling pathways. In this study, based on our in-depth understanding of the binding properties of fibroblast growth factor receptor 1c (FGFR1c) with paracrine FGF1 and endocrine FGF21, we engineered a novel FGF21 analog named FGF21 Show less
Accelerated population aging and rising incidence of bone defects have intensified the need for advanced bone regeneration strategies. While tissue-engineered scaffolds fabricated via 3D printing offe Show more
Accelerated population aging and rising incidence of bone defects have intensified the need for advanced bone regeneration strategies. While tissue-engineered scaffolds fabricated via 3D printing offer promising alternatives to conventional grafts, most techniques fail to replicate the multi-scale fibrous architecture of native bone extracellular matrix, limiting their biofunctionality. To address this, we developed a hybrid manufacturing strategy integrating low-temperature thermally induced phase separation with extrusion-based 3D printing of polylactic acid (PLA) scaffolds. By optimizing solvent ratios (THF: DMF = 3:1) and freezing temperatures (-196 °C-4 °C), we produced scaffolds with tunable micro-nano fibrous surfaces and macroporous structures. Key findings revealed that scaffolds processed at -196 °C (PLA-196) exhibited the highest porosity (pore size: 6.01 ± 2.06 μm), superior hydrophilicity, and enhanced compressive modulus. These scaffolds significantly promoted BMSC adhesion, proliferation, and osteogenic differentiation via activation of Show less
Biomarker profiling from biofluids such as blood are widely measured in clinical research, using for example Olink proteomics panels. One such research focus area is cardiovascular disease (CVD), for Show more
Biomarker profiling from biofluids such as blood are widely measured in clinical research, using for example Olink proteomics panels. One such research focus area is cardiovascular disease (CVD), for which chronic sleep restriction (SR) is a risk factor. However, it remains unclear whether blood levels of commonly measured CVD biomarkers are sensitive to acute dynamic factors such as SR, physical exercise (PEx), and time of day. In this crossover design, 16 normal-weight, healthy men underwent three highly standardized in-lab nights of SR (4.25 h/night) and normal sleep (NS, 8.5 h/night) in randomized order, with 88 CVD blood protein biomarkers quantified using the Olink technology (and selected validation using ELISA) in the morning, evening, and immediately before and repeatedly after 30 min of high-intensity exercise. We found significant time-of-day-dependent changes in several CVD biomarkers. Whereas several proteins were exercise-induced across sleep conditions (such as the canonical exerkines IL- 6 and BDNF), exercise-induced proteomic dynamics differed in response to recurrent SR, compared with following NS. Moreover, SR compared with NS resulted in a biomarker profile previously associated with increased prospective risk of several CVDs across large-scale cohorts (such as higher circulating levels of IL-27 and LGALS9). Our findings highlight how dynamic physiology can modulate CVD biomarker levels. These results also underscore the need to consider sleep duration as a key determinant of cardiovascular health-an emphasis reflected in recent American Heart Association guidelines. Further studies in women, older individuals, and patients with prior CVD, and across different chronotypes and dietary schedules are warranted. Show less
Interleukin-27 receptor alpha (IL27RA), a key subunit of the interleukin-27 receptor, plays an essential role in T cell-mediated immunity. However, its relevance in breast cancer and response to immun Show more
Interleukin-27 receptor alpha (IL27RA), a key subunit of the interleukin-27 receptor, plays an essential role in T cell-mediated immunity. However, its relevance in breast cancer and response to immunotherapy remains unexplored. We integrated bulk and single-cell RNA sequencing data from TCGA, GEO, and scRNA-seq datasets to analyze IL27RA expression, prognosis, immune infiltration, and treatment response. TIDE and immune checkpoint-treated clinical cohorts were used to assess immunotherapy responsiveness. Chemotherapy sensitivity was predicted using GDSC data, and IL27RA protein expression was validated by Western blot. IL27RA was downregulated in breast cancer but high expression correlated with favorable survival. It was primarily expressed in T cells, particularly CD8⁺ subsets, and associated with enriched immune infiltration and elevated checkpoint gene expression. IL27RA high-expression patients showed lower TIDE scores, better outcomes in ICI-treated cohorts, and higher sensitivity to multiple chemotherapeutic agents. IL27RA is a potential immune biomarker that reflects an inflamed tumor microenvironment and predicts benefit from immunotherapy and chemotherapy in breast cancer. These findings provide novel insights into immune-based stratification using single-cell transcriptomic data. Show less
The existing evidence regarding the impact of tamoxifen on lipoprotein(a) and apolipoproteins remains inconsistent. Therefore, this updated meta-analysis of randomized controlled trials (RCTs) aims to Show more
The existing evidence regarding the impact of tamoxifen on lipoprotein(a) and apolipoproteins remains inconsistent. Therefore, this updated meta-analysis of randomized controlled trials (RCTs) aims to enhance the quality of evidence concerning the effects of tamoxifen on these lipid parameters. Eligible RCTs published up to October 2024 were meticulously selected through a comprehensive search. A meta-analysis was then performed using a random-effects model, and results were presented as the weighted mean difference (WMD) with a 95% confidence interval (CI). Findings from the random-effects model revealed an increase in ApoA-I (WMD: 15.22 mg/dL, 95% CI: 6.43-24.01, P = 0.001), alongside decreases in ApoB (WMD: -9.33 mg/dL, 95% CI: -15.46 to -3.19, P = 0.003) and lipoprotein(a) (WMD: -3.35 mg/dL, 95% CI: -5.78 to -0.91, P = 0.007) levels following tamoxifen treatment in women. Subgroup analyses indicated a more significant reduction in lipoprotein(a) levels in RCTs with a duration of ≤24 weeks (WMD: -3.65 mg/dL) and in studies using tamoxifen doses of ≥20 mg/day (WMD: -4.53 mg/dL). This meta-analysis provides evidence that tamoxifen leads to a decrease in lipoprotein(a) levels, along with reductions in ApoB and increases in ApoA-I among women. Show less
The deer antler is a fully regenerable and the fastest-growing osseous organ. Circular RNA (circRNA), a novel member of the non-coding RNA family, has significant research potential and crucial roles Show more
The deer antler is a fully regenerable and the fastest-growing osseous organ. Circular RNA (circRNA), a novel member of the non-coding RNA family, has significant research potential and crucial roles in biological processes. This study aims to explore the impact and mechanisms of circRNA505 on antler chondrocytes. Functional experiments demonstrated that m5C-modified circRNA505 inhibits antler chondrocyte proliferation, enhances osteogenic differentiation, and facilitates cellular glycolysis. Mechanistically, dual luciferase and AGO2-RIP assays revealed a direct binding relationship between circRNA505, miR-127, and p53. Rescue assays further showed that circRNA505 affects cell proliferation and differentiation through the miR-127/p53 axis. Meanwhile, RNA Antisense Purification (RAP) screening and analysis of related proteins binding to circRNA505 demonstrated that circRNA505 binds to LDHA and increases the level of LDHA phosphorylation through FGFR1 to promote cellular glycolysis by FISH-IF, RIP, and Western blot experiments. Additionally, Me-RIP assays confirmed the m5C methylation modification of circRNA505. NSUN2 mediates the m5C modification of circRNA505, affecting its stability, while the m5C reader ALYREF promotes the nuclear export of circRNA505 in an ALYREF-dependent manner. This study provides new insights into the regulatory mechanisms underlying rapid antler development. Show less
The natural compound pterostilbene (PTE) has multiple cardiovascular protective effects. However, its effects on pulmonary arterial hypertension (PAH)-associated vascular remodeling remain to be eluci Show more
The natural compound pterostilbene (PTE) has multiple cardiovascular protective effects. However, its effects on pulmonary arterial hypertension (PAH)-associated vascular remodeling remain to be elucidated. This study investigated the effects of PTE on monocrotaline (MCT)-induced PAH in rats Experimental PAH was established by subcutaneous injection of MCT (50 mg/kg) in Sprague-Dawley rats, which were then randomly divided into vehicle or PTE (15 mg/kg via gavage) treatment groups. Endothelial-to-mesenchymal transition (EndMT) was modeled in hPAECs by treating with transforming growth factor-β, tumor necrosis factor-α, and interleukin-1β in combination. In rats with MCT-induced PAH, administration of PTE resulted in a reduction in right ventricular systolic pressure, thereby alleviating right ventricular hypertrophy. This was accompanied by mitigation of the remodeling of pulmonary arteries. PTE mitigates MCT-induced PAH and vascular remodeling in rats, at least in part, by inhibiting HMGA-mediated EndMT, suggesting that PTE may be a useful complementary medicine in the treatment of PAH. Show less
Graphical Abstract Lipoprotein lipase (LPL) mediates peripheral tissue triglyceride (TG) uptake. Hepatic ANGPTL3 (A3) and ANGPTL8 (A8) form a complex and inhibit LPL activity in the white adipose tiss Show more
Graphical Abstract Lipoprotein lipase (LPL) mediates peripheral tissue triglyceride (TG) uptake. Hepatic ANGPTL3 (A3) and ANGPTL8 (A8) form a complex and inhibit LPL activity in the white adipose tissue (WAT) via systematic circulation. ANGPTL4 (A4) is expressed in WAT and inhibits LPL activity locally. Feeding increases hepatic A8 expression and increases its inhibition for WAT LPL activity together with A3, while feeding suppresses WAT A4 expression and releases its inhibition on LPL. At room temperature, the feeding-suppressed A4 overrides the feeding-increased A3/A8, resulting in increased LPL activity in WAT by food intake. Browning improves hepatic insulin sensitivity and increases postprandial A8 expression. The feeding-increased A3/A8 overrides the feeding-suppressed A4, resulting in suppressed LPL activity in WAT by food intake. This reprogrammed LPL regulation plays an important role in reprogramming TG metabolism during adipose tissue browning. Show less
This study aims to comprehensively analyze the intricate relationship between unsaturated fatty acids (UFAs, particularly omega-3 and omega-6 UFAs) and acne, from their clinical therapeutic effects to Show more
This study aims to comprehensively analyze the intricate relationship between unsaturated fatty acids (UFAs, particularly omega-3 and omega-6 UFAs) and acne, from their clinical therapeutic effects to their underlying genetic regulatory mechanisms, to elucidate the role of UFAs in acne pathogenesis. Clinical evidence synthesis: we systematically reviewed randomized controlled trials (RCTs) to evaluate the impact of UFA supplementation on acne treatment outcomes. Genetic analysis: two-sample Mendelian randomization (MR) analysis we used to investigate causal relationships between serum UFA metabolites and acne, identifying potential key regulatory enzymes. The synthesis of these RCT studies confirmed that UFA supplementation improved acne conditions. MR analysis revealed causal links between three serum UFA metabolites and acne, with dihomo-gamma-linolenic acid (DGLA) (OR = 8.457; 95% CI: 2.367-30.214; P-value = 0.001) as a risk factor and arachidonic acid (AA) (OR = 0.209; 95% CI: 0.071-0.618; P-value = 0.005) and eicosapentaenoic acid (EPA) (OR = 0.318; 95% CI: 0.102-0.991; P-value = 0.048) as protective factors. Functional annotation suggested enzymes such as Δ5 desaturase (FADS1) and Δ6 desaturase (FADS2) may play a role in acne regulation. This study offers evidence that supports a connection between UFAs and acne, examining this relationship from both clinical and genetic angles. These findings highlight the role of specific UFAs and their associated metabolic enzymes in the development of acne. Omega-3 UFAs seem to have a protective effect against acne, whereas certain types and ratios of omega-6 UFAs might contribute to acne formation. The varied impacts of UFAs on acne could be attributed to disease processes mediated by specific enzymes. However, the study's limitations include its genetic analysis being primarily based on European populations, which limits the applicability of the findings to other groups. Future research should aim to include a more diverse range of participants to improve the generalizability of the results. Show less
Despite the increasing approval and ongoing clinical trials of FGFR-targeted therapies, accurately detecting FGFR fusions remains a challenge due to limited research, low incidence rates, complex fusi Show more
Despite the increasing approval and ongoing clinical trials of FGFR-targeted therapies, accurately detecting FGFR fusions remains a challenge due to limited research, low incidence rates, complex fusion partner distribution, and unique kinase domain distribution. We conducted a multicenter study to comprehensively profile FGFR fusions in the largest Chinese pan-cancer cohort to date, comprising 118 FGFR fusions from 114 individuals. Both DNA- and RNA-based sequencing approaches were utilized to reveal novel and fundamental features of FGFR fusion. Our research reveals an incidence rate of 0.96% for FGFR rearrangements within this Chinese cohort, including a high incidence rate of FGFR fusions (40%) in parotid gland carcinoma. However, this is based on a small sample size of 5 tumors and should be interpreted cautiously pending validation in larger cohorts. We also uncovered distinct breakpoint distribution patterns across various FGFR rearrangements. For example, a primary breakpoint in intron17 of FGFR2 was predominant (21/22), while FGFR1/3 breakpoints displayed substantial diversity. For the first time, we identified "hot" breakpoints in FGFR1 intron17, exon18, and FGFR3's 3' untranslated region. These findings underline the importance of incorporating these regions in targeted sequencing to ensure comprehensive detection of FGFR1/3 fusions. Notably, we observed a predilection for intrachromosomal distribution in common FGFR1/2/3 fusions. In contrast, most novel fusions (12/15) exhibited an interchromosomal distribution pattern, indicating variations in the fusion formation mechanism. Importantly, our study demonstrates the substantial incremental value of RNA-NGS or other orthogonal methods in confirming the functionality of FGFR rearrangements initially identified by DNA sequencing. In our cohort, 46% (6/13) of rare FGFR1/2/3 fusions lacked detectable RNA transcripts; however, this does not definitively indicate non-functionality as factors such as low RNA quality, expression below detection limits, or nonsense-mediated decay may contribute. Therefore, RNA-based validation is critical for accurately identifying potentially targetable FGFR fusions and guiding therapy. Our findings offer critical novel insights into functional FGFR fusions and bear considerable clinical implications for identifying individuals whose tumors are most likely to respond favorably to FGFR-targeted therapies. Show less
Dual-specificity protein phosphatase 6 (DUSP6), also known as mitogenactivated protein kinase phosphatase 3 (MKP-3), was considered as a functional candidate gene for white fat accumulation in mice. H Show more
Dual-specificity protein phosphatase 6 (DUSP6), also known as mitogenactivated protein kinase phosphatase 3 (MKP-3), was considered as a functional candidate gene for white fat accumulation in mice. However, the physiological function of the DUSP6 gene on white adipocyte adipogenesis in farm animals remains unknown. In this study, we aimed to clarify the effect of DUSP6 on porcine subcutaneous preadipocyte proliferation and differentiation. We first make clear that the patterns of DUSP6 expression is associated with fat contents in porcine fat deposition related tissues. Porcine subcutaneous preadipocytes were isolated and induced to differentiation. Small interfering RNAs were applied to deplete DUSP6. MTT assay, CCK-8 analysis, Oil Red O staining, triglyceride determination and reverse transcription quantitative polymerase chain reaction were applied to study the regulatory role of DUSP6 during adipocyte adipogenesis in pigs. We found that the expression levels of DUSP6 were significantly higher in backfat and longissimus dorsi tissues from fat-type pigs than in those from lean-type pigs. Consistently, the significantly induced expression of DUSP6 was also observed in differentiated adipocytes. In addition, knockdown of DUSP6 greatly inhibited preadipocytes proliferation, through the decreased cell viability and downregulated mRNA expressions of cell proliferation-associated genes, including PCNA, CDK1, CDK2. Furthermore, knockdown of DUSP6 significantly inhibited preadipocytes differentiation, as evidenced by markedly reduced lipid droplet formation, attenuated triglyceride accumulation and downregulated expression levels of adipogenic transcription masters (PPARγ, C/EBPβ, FASN and FABP4) in DUSP6 knockdown cells. Our results demonstrate that DUSP6 is required for white adipocyte adipogenesis in pigs. Show less
Abdominal aortic aneurysm (AAA) is a severe aortic disease for which no pharmacological interventions have yet been developed. This investigation focused on identifying protein-based therapeutic targe Show more
Abdominal aortic aneurysm (AAA) is a severe aortic disease for which no pharmacological interventions have yet been developed. This investigation focused on identifying protein-based therapeutic targets and assessing how proteins mediate the interplay between modifiable risk factors and AAA development. Causal inferences between plasma proteins and AAA were drawn using 2-sample Mendelian randomization, followed by comprehensive sensitivity testing, colocalization, and replication efforts. Further analyses included database interrogation, single-cell RNA data analysis, enrichment analysis, protein-protein interaction networks, and immunohistochemistry to map the tissue-specific expression of these proteins, their expression within AAA tissues, and their biological roles. Mediation Mendelian randomization was employed to evaluate the mediating effects of AAA-related proteins on the associations between AAA and 3 risk factors: hypertension, smoking, and obesity. A total of 43 proteins were identified as having causal links to AAA. Colocalization analysis pinpointed 13 proteins with strong evidence of colocalization with AAA. Of these, the causal involvement of 10 proteins was substantiated by external validation data. Consistent evidence for PCSK9 (proprotein convertase subtilisin/kexin type 9), IL6R (interleukin-6R), ECM1 (extracellular matrix protein 1), and ANGPTL4 (angiopoietin-related protein 4) was further validated through tissue immunohistochemistry and blood data. Moreover, Mendelian randomization analysis identified 10 proteins as mediators of the influence of hypertension, smoking, and obesity on AAA development. This analysis identifies 4 proteins (PCSK9, IL6R, ECM1, and ANGPTL4) as high-priority therapeutic targets for AAA and emphasizes the intermediary role of plasma proteins in linking hypertension, smoking, obesity, and AAA. Further investigations are needed to clarify the specific roles of these proteins in AAA pathology. Show less
Lung squamous cell carcinoma (LUSC) is a highly aggressive malignancy with limited targeted therapies and poor clinical outcomes. Ferroptosis, an iron-dependent form of regulated cell death, plays a c Show more
Lung squamous cell carcinoma (LUSC) is a highly aggressive malignancy with limited targeted therapies and poor clinical outcomes. Ferroptosis, an iron-dependent form of regulated cell death, plays a crucial role in tumor progression, metabolic reprogramming, and immune modulation. Increasing evidence suggests that dysregulation of ferroptosis contributes to therapeutic resistance and immune escape in various cancers. MYO19, a mitochondrial trafficking protein, has recently been implicated in oxidative stress and metabolic control, but its role in ferroptosis and tumor immunity remains unclear. Meanwhile, microRNAs (miRNAs) are recognized as key post-transcriptional regulators in cancer biology. Among them, hsa-miR-520a-3p has been reported to exhibit tumor-suppressive functions in several malignancies. However, the interplay between hsa-miR-520a-3p and MYO19, and their potential involvement in ferroptosis regulation and immune modulation in LUSC, has not been systematically investigated. Data were collected from TCGA, UCSC XENA, ENCORI, HPA, and UALCAN public database. Differential expression, prognostic, correlation analyses and miRNA analyses were performed using bioinformatics tools including TIMER, TISIDB, Kaplan-Meier Plotter, and ENCORI. Ferroptosis-related analysis utilized Ze-Xian Liu's dataset. Functional assays, including CCK-8 viability, Transwell migration, and MDA/GSH measurements, were performed in NCI-H226 and NCI-H2170 cells after transfection with miR-520a-3p mimics/inhibitors or MYO19 knockdown/overexpression constructs. Ferroptosis sensitivity was further tested under RSL3 treatment, and ferroptosis protein markers as well as rescue experiments were analyzed by Western blotting. The result revealed that MYO19 was significantly upregulated in multiple tumor types and correlated with unfavorable prognosis. Especially in LUSC, elevated MYO19 expression was associated with advanced stage, reduced immune infiltration, and enrichment of ferroptosis-resistant transcriptional programs, whereas hsa-miR-520a-3p showed opposite patterns. Overexpression of hsa-miR-520a-3p in NCI-H226 and NCI-H2170 cells increased lipid peroxidation (MDA increased), reduced intracellular GSH, and enhanced RSL3-induced cytotoxicity, indicative of ferroptosis activation. Conversely, MYO19 knockdown elevated ACSL4 and reduced SLC7A11, changes that were partially reversed by MYO19 re-expression. These findings suggest that the hsa-miR-520a-3p/MYO19 axis is associated with ferroptosis susceptibility and may influence the immunosuppressive tumor microenvironment. Show less
Altered levels of human plasma metabolites have been implicated in the etiology of bipolar disorder (BD). However, the causality between metabolites and the disease was not well described. We performe Show more
Altered levels of human plasma metabolites have been implicated in the etiology of bipolar disorder (BD). However, the causality between metabolites and the disease was not well described. We performed a bidirectional metabolome-wide Mendelian randomization (MR) analysis to evaluate the potential causal relationships between 871 plasma metabolites and BD. We used DrugBank and ChEMBL to evaluate whether related metabolites are potential therapeutic targets. Finally, Bayesian colocalization analysis was performed to identify shared genomic loci BD and identified metabolites. Our MR results showed that six metabolites were significantly associated with a reduced risk of BD, including arachidonate (20:4n6) (OR: 0.90, 95% CI: 0.84-0.95) and sphingomyelin (d18:2/24:1, d18:1/24:2) (OR: 0.92, 95% CI: 0.87-0.96), while five metabolites were significantly associated with an increased risk of BD, including 1-palmitoyl-2-linoleoyl-GPE (16:0/18:2) (OR: 1.09, 95% CI: 1.05-1.13). However, our reverse MR analysis showed that BD was not associated with the levels of any metabolite. Additionally, the leave-one-out analysis revealed SNPs within chromosome 11 loci harboring MYRF, FADS1, and FADS2 as ones with the potential to influence partial causal effects. Druggability evaluation showed that 10 of the BD-related metabolites, such as sphingomyelin and cytidine, have been targeted by pharmacologic intervention. Colocalization analysis highlighted one colocalized region (chromosome 11q12) shared by 11 metabolites and BD and pointed to some genes as possible players, including FADS1, FADS2, FADS3, and SYT7. Our study supported a causal role of plasma metabolites in the susceptibility to BD, and the identified metabolites may provide a new avenue for the prevention and treatment of BD. Show less
While most patients with stage I non-small cell lung cancer (NSCLC) remain recurrence-free after resection, some still develop recurrent disease. The surgical curative time window concept, defined as Show more
While most patients with stage I non-small cell lung cancer (NSCLC) remain recurrence-free after resection, some still develop recurrent disease. The surgical curative time window concept, defined as no recurrence through 5-year follow-up, helps identify potentially cured patients, yet predictive clinicopathologic features in stage I invasive NSCLC need clarification. This study sought to identify such features to enable risk-adapted surveillance. We analyzed a prospectively collected dataset of patients with stage I invasive NSCLC who underwent R0 resection between 2008 and 2015. Cox regression analysis was used to evaluate the association between clinicopathologic features and disease recurrence, aiming to identify independent prognostic factors. A total of 1,817 patients met the inclusion criteria. The 5-year cumulative incidence of recurrence was 14.6%. Female sex, tumor size ≤2 cm, lepidic-predominant adenocarcinoma (LPA) histologic type, presence of a ground-glass opacity (GGO) component, and solid component size ≤10 mm were identified as independent prognostic factors. A risk stratification system was subsequently developed, classifying patients into two groups: a low-risk group (with ≥4 factors; n=341) and an elevated-risk group (with <4 factors; n=1,476). Kaplan-Meier analysis revealed statistically significant differences in recurrence-free survival (RFS), overall survival (OS), and lung cancer-specific survival (LCSS) between the two groups (P<0.001). The low-risk group is considered to represent the population within the surgical curative time window. Patients with stage I invasive NSCLC who meet at least four of the following five criteria-female sex, tumor size ≤2 cm, solid component ≤10 mm, presence of a GGO component, and LPA histologic type-may be considered within the "surgical curative time window" and may therefore qualify for reduced surveillance intensity. Show less
This study aimed to explore the effects of chili meal (CM), a by-product of chili pepper oil extraction, on the productive performance, intestinal health, and lipid metabolism of laying hens fed low-p Show more
This study aimed to explore the effects of chili meal (CM), a by-product of chili pepper oil extraction, on the productive performance, intestinal health, and lipid metabolism of laying hens fed low-protein (LP) diets. A total of 384 Hy-Line brown laying hens (32 weeks old) were divided into six groups: control (CON) diet with 16.5 % crude protein (CP), LP diet with 15 % CP, and LP diets supplemented with 3 %, 5 %, 7 %, and 9 % CM. Results showed that dietary CM supplementation of up to 5 % did not negatively affect the productive performance of laying hens fed LP diets. However, the groups receiving 7 % and 9 % CM exhibited a significant increase in the feed-to-egg ratio (P < 0.05). Additionally, dietary CM supplementation effectively enhanced egg yolk color in a dose-dependent manner (P < 0.05). Intestinal morphology analysis indicated that the 5 % CM group had a higher villus height-to-crypt depth ratio than the LP and 9 % CM groups (P < 0.05), with no significant differences among the other groups. Dietary supplementation with 3 %-7 % CM did not significantly affect serum and jejunal antioxidant capacity, and the 9 % CM group exhibited the highest levels of serum and jejunal malondialdehyde among the groups (P < 0.05). Dietary CM supplementation significantly increased anti-inflammatory cytokines (IL-4 and IL-10) and decreased pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the serum and jejunal tissue of laying hens (P < 0.05). Moreover, CM supplementation significantly altered the cecal microbiota composition in laying hens, increasing the abundance of beneficial bacteria, such as Desulfovibrio and Megamonas. Furthermore, dietary CM supplementation significantly decreased serum triglyceride levels; downregulated liver mRNA levels of ACC, FAS, and SREBP-1C/2; and upregulated the mRNA levels of ACOX1, PPAR-α, Apob, and CPT in laying hens fed LP diets. In conclusion, CM supplementation should not exceed 5 % to avoid negative impacts on performance while supporting intestinal health and lipid metabolism. Show less
Mitochondria play an essential role in regulating various physiological functions including bioenergetics, calcium homeostasis, redox signaling, and lipid metabolism and also are involved in the patho Show more
Mitochondria play an essential role in regulating various physiological functions including bioenergetics, calcium homeostasis, redox signaling, and lipid metabolism and also are involved in the pathogenesis of cardiovascular diseases. However, the relationship between mitochondrial calcium homeostasis in vascular smooth muscle cells (VSMCs) and atherosclerosis remains poorly understood. Here, we demonstrate that cholesterol induces mitochondrial calcium overload and lipid accumulation in VSMCs, which is resulted from dysregulation of mitochondrial calcium uniporter (MCU), as evidenced by genetic and pharmacologic inhibition of MCU. Furthermore, MCU inhibitors alleviate Western diet-induced atherosclerosis in ApoE-/- mice. Mechanistically, high-fat and high-cholesterol diets induce the contact between mitochondria and the endoplasmic reticulum (ER) in VSMCs as indicated by transmission electron microscopy, proximity ligation assay and immunofluorescence staining, which increases the formation of mitochondria-associated membranes (MAMs), leading to Ca2 + release from the ER into the mitochondria and thus elevating Ca2 + in the mitochondria. Using mitochondrial calcium uptake 1 (MICU1) mutant and Ca2 + detection assay, we confirmed that this increased Ca2 + binds to MICU1, a blocker of MCU, to impair its ability to block MCU, thus enabling the MCU to remain open and resulting in mitochondrial calcium overload. Further, mitochondrial calcium overload dysregulates fatty acid β-oxidation by modulating medium-chain acyl-CoA dehydrogenase (ACADM), thereby leading to lipid deposition. The inhibition of MCU alleviates the pathological changes elecited by cholesterol. Our findings unveil the previously unrecognized role of MAM-MICU1-MCU axis in cholesterol-induced mitochondrial calcium overload and atherosclerosis, indicating that MCU represents a promising therapeutic target for the treatment of atherosclerosis. Show less
Glucose homeostasis, essential for metabolic health, requires coordinated insulin and glucagon activity to maintain blood glucose balance. Dysregulation of glucose homeostasis causes hyperglycaemia an Show more
Glucose homeostasis, essential for metabolic health, requires coordinated insulin and glucagon activity to maintain blood glucose balance. Dysregulation of glucose homeostasis causes hyperglycaemia and glucose intolerance, hallmark features of type 2 diabetes. While SEC16 homologue B (SEC16B), an endoplasmic reticulum export factor, has been linked to obesity, type 2 diabetes and lipid metabolism, its role in glucose regulation remains poorly defined. This study aims to investigate SEC16B's contribution to glucose homeostasis by systematically dissecting its conserved physiological mechanisms across species. To interrogate SEC16B's role, we combined Drosophila genetics (RNA interference-mediated dSec16 knockdown) with murine models (Sec16b deletion) under standard or high-fat diet conditions. Glucose and insulin tolerance tests assessed glucose homeostasis. Mechanistic insights into beta cell dysfunction were derived from immunostaining, glucose-stimulated insulin secretion assays and RNA-seq profiling of murine pancreatic islets. Both disruption of dSec16 in Drosophila and Sec16b deletion in mice triggered glucose intolerance under standard diet conditions, recapitulating conserved metabolic dysfunction. In addition, Sec16b loss impaired glycaemic control in mice fed a high-fat diet. Mechanistically, Sec16b deficiency impairs insulin secretion by downregulating cholinergic signalling and compromising intracellular Ca Our study reveals SEC16B, a genome-wide association study-identified obesity risk gene, as an evolutionarily conserved regulator of glucose homeostasis. By linking SEC16B to cholinergic-driven insulin secretion and calcium dynamics, we resolve a mechanistic gap in beta cell dysfunction and metabolic disease. This finding provides novel insights into the mechanisms underlying glucose homeostasis and may enhance our understanding of potential treatments for metabolic diseases. Show less