Anterior disc displacement (ADD) is a common clinical issue and may cause osteoarthritis (OA). However, the research of protein changes in synovial fluid as disease development marker and potential tr Show more
Anterior disc displacement (ADD) is a common clinical issue and may cause osteoarthritis (OA). However, the research of protein changes in synovial fluid as disease development marker and potential treatment clue is still insufficient. We conducted the high-resolution mass spectrometry (MS) of synovial fluid collected from 60 patients with normal disk position to ADD and ADD with osteoarthritis (OA). The proteins with significant changes among the 3 groups were analyzed by biological information and further validated by in primary rat condyle chondrocytes and OA animal model. FGL2, THBS4, TNC, FN1, OMD etc. were significantly increased in ADD without OA (p < 0.05), which reflected the active extracellular matrix and collagen metabolism. FGFR1, FBLN2, GRB2 etc. were significantly increased in ADD with OA group (p < 0.05), which revealed an association with apoptosis and ferroptosis. Proteins such as P4HB, CBLN4, FHL1, VIM continuously increase in the whole disease progress (p < 0.05). Both the in vitro and in vivo results are consistent with protein changes detected in MS profile. This study firstly provides the expression changes of proteins from normal disc condyle relationship toward ADD with OA, which can be selected and studied further as disease progress marker and potential treatment targets. Show less
The Gualou-Xiebai-Banxia decoction (GXBD), a classical traditional Chinese medicine (TCM) formula, has beneficial effects in turbid phlegm obstruction syndrome, a type of coronary heart disease (CHD). Show more
The Gualou-Xiebai-Banxia decoction (GXBD), a classical traditional Chinese medicine (TCM) formula, has beneficial effects in turbid phlegm obstruction syndrome, a type of coronary heart disease (CHD). However, the underlying mechanism and effective constituents of GXBD remain elusive. Our previous studies have shown that the effective constituents of GXBD may be enriched in the n-butanol fraction (GXB-N) and water fraction (GXB-W), the targets of which remain unknown. To investigate whether GXB-N and GXB-W protect myocardial cells (MCs) via fibroblast growth factor 21 (FGF21) signaling and, if so, to elucidate the underlying mechanisms. Furthermore, to investigate the targets of GXB-N and GXB-W as potential therapeutic targets for cardiovascular disease (CVD). Cell viability and apoptosis were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, respectively. The content of FGF21 in the medium was measured using enzyme-linked immunosorbent assay (ELISA). Protein expression was detected using immunofluorescence and western blotting. Apoptosis increased markedly in MCs exposed to oxidized low density lipoprotein (ox-LDL) 100 μg/mL, with increased expression of FGF21, FGFR1 and βKlotho, phosphorylation of fibroblast receptor substrate 2α (FRS2α) was suppressed. Following incubation with GXB-N and GXB-W 200 μg/mL, the expression of FGF21, FGFR1, and βKlotho and the phosphorylation of FRS2α were increased. Ox-LDL may inhibit the phosphorylation of FRS2α, inducing considerable FGF21 resistance and resulting in MC apoptosis. GXB-N and GXB-W restored and enhanced FGF21 sensitivity in MCs, consequently rescuing cells from ox-LDL-induced apoptosis. The FGF21-FRS2α signal pathway may be part action targets of these two effective fractions of GXBD. Show less
As a global focus of animal husbandry, pigs provide essential meat resources for humans. Therefore, analyzing the genetic basis of adaptability, domestication, and artificial selection in pigs will co Show more
As a global focus of animal husbandry, pigs provide essential meat resources for humans. Therefore, analyzing the genetic basis of adaptability, domestication, and artificial selection in pigs will contribute to further breeding. This study performed a genome-wide selection sweep analysis to identify candidate genes related to domestication and adaptive selection via data from 2413 public genotypes. Two complementary statistical analyses, Show less
The metabolic reprogramming of macrophages is a potential therapeutic strategy for sepsis treatment, but the mechanism underlying this reprogramming remains unclear. Since glycolysis can drive macroph Show more
The metabolic reprogramming of macrophages is a potential therapeutic strategy for sepsis treatment, but the mechanism underlying this reprogramming remains unclear. Since glycolysis can drive macrophage phenotype switching, the rate-limiting enzymes in glycolysis may be key to treating sepsis. Here, we found that, compared with other isoenzymes, the expression of 6-phosphofructokinase, muscle type (PFKM) was the most upregulated in monocytes from septic patients. Recombinant thrombomodulin (rTM) treatment downregulated the protein expression of PFKM in macrophages. Both rTM treatment and Pfkm knockout protected mice from sepsis and reduced the production of the proinflammatory cytokines IL-1β, IL-6, TNF-α, and IL-27, whereas PFKM overexpression increased the production of these cytokines. Mechanistically, rTM treatment inhibited glycolysis in macrophages by decreasing PFKM expression in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. HIF-1α overexpression increased methyltransferase-like 3 (METTL3) expression, elevated the m Show less
Inflammation significantly impacts Parkinson's disease (PD), yet the intricate relationship between inflammatory markers and PD remains elusive. To identify the peripheral biomarkers of PD and its cor Show more
Inflammation significantly impacts Parkinson's disease (PD), yet the intricate relationship between inflammatory markers and PD remains elusive. To identify the peripheral biomarkers of PD and its correlation with the motor and non-motor symptoms of PD. 79 PD patients and 65 controls were included in this study. Clinical information and the serum levels of IL-8, IL-27, IL-33, β-NGF, AgRP, and TRAILR2 in the participants were collected. Appropriate scales were used to assess the symptoms of PD. For the factors with significant differences in the two groups, multivariable logistic regression was used to determine its relationship with PD. Moreover, spearman correlation was conducted to explore the correlation between the factors and PD related symptoms. The IL-27 level was compared between the cognitively healthy PD group and the mild cognitive impairment in PD (PD-MCI). The serum level of TRAILR2 was positively correlated with age and was not associated with other clinical characteristics related to PD. Compared to controls, the serum levels of IL-27(P = 0.013) were increased whereas the levels of TRAILR2(P = 0.008) were decreased in PD patients. IL-8, IL-33, β-NGF, and AgRP showed no significant differences between the two groups. After controlling for the other variables, IL-27 was considered as an independent risk factor for PD in the multivariable logistic regression model. The receiver operating characteristic (ROC) curve for diagnosing PD with IL-27 yielded an area under the curve (AUC) of 0.621. Additionally, IL-27 level in PD patients was positively correlated with age, the disease duration, LEDD and negatively correlated with the MoCA scores. However, no significant difference was found in IL-27 levels between cognitively healthy PD and PD-MCI groups. Elevated serum IL-27 was a risk factor for PD and positively correlated with the cognitive decline in PD. Show less
Decidual regulatory T cells (Tregs) are essential for successful pregnancy outcome. A subset of Tregs, T cell immunoglobulin and mucin domain-containing protein 3-positive regulatory T cells (TregsTim Show more
Decidual regulatory T cells (Tregs) are essential for successful pregnancy outcome. A subset of Tregs, T cell immunoglobulin and mucin domain-containing protein 3-positive regulatory T cells (TregsTim-3+), plays a central role in the acceptance of the fetus during early stages of normal pregnancy. The molecular mechanism regulating the differentiation and function of TregsTim-3+ is unknown. Here, we investigated the role of the transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) on decidual TregTim-3+ differentiation. We demonstrated that Blimp-1 enhanced the coexpression of negative costimulatory molecules (Tim-3, T cell immunoreceptor with Ig and ITIM domains, and programmed cell death protein 1) on Tregs and improved their immunosuppressive functions, including increased IL-10 secretion, suppression of effector T cell proliferation, and promotion of macrophage polarization toward the M2 phenotype. Furthermore, we showed that IL-27 regulated the expression of Tim-3 and Blimp-1 through the STAT1 signaling pathway and that transfer of TregsBlimp-1+ into an abortion-prone mouse model effectively reduced embryo absorption rate. We postulated that abnormalities in the IL-27/Blimp-1 axis might be associated with recurrent pregnancy loss (RPL). These findings provided insights for developing more efficient immunotherapies for women with RPL. Show less
Chronic periodontitis (CP) and allergic rhinitis (AR) have attracted wide attention as global public health problems with high incidence. Recent studies have shown that circulating interleukin-27 (IL- Show more
Chronic periodontitis (CP) and allergic rhinitis (AR) have attracted wide attention as global public health problems with high incidence. Recent studies have shown that circulating interleukin-27 (IL-27) is associated with the risk of CP and AR. The aim of this study is to analyze the causal effect between them using Mendelian randomization (MR). Bidirectional MR analyses were performed with the use of publicly available genome-wide association study (GWAS) data. Summary data on circulating IL-27, CP, and AR published in genome-wide association studies were collected. Instrumental variables (IV) were extracted using assumptions of correlation, independence and exclusivity as criteria. Inverse variance weighting (IVW) was used as the main method, combined with weighted median method (WM) and MR-Egger and other MR Analysis methods for causal inference of exposure and outcome. Cochran's Q and MR-Egger intercept were used for sensitivity analysis. The IVW study showed a causal effect between increased circulating IL-27 levels and increased risk of CP (OR = 1.14, 95%CI = 1.02-1.26, There is a causal effect between circulating IL-27 level and CP, AR, which will help to find new ideas and methods for the diagnosis and treatment of CP and AR. Show less
Polycystic ovary syndrome (PCOS) is a diverse endocrine disorder widely recognized as the prevailing metabolic condition among women in their reproductive years. The precise pathophysiological mechani Show more
Polycystic ovary syndrome (PCOS) is a diverse endocrine disorder widely recognized as the prevailing metabolic condition among women in their reproductive years. The precise pathophysiological mechanisms underlying PCOS remain incompletely understood. However, existing evidence suggests that the development of PCOS may be linked to factors such as abdominal obesity, hyperandrogenism, and insulin resistance (IR). Excessive central adiposity in women with PCOS may lead to the development of a chronic, low-grade inflammation characterized by the activation of proinflammatory cytokines. The cytokines that belong to the IL-12 family are a collection of distinct heterodimeric cytokines that include IL-12, IL-23, IL-27, and IL-35. Recent research has provided further evidence regarding the significance of IL-12 cytokines in influencing both innate and adaptive immune responses in different diseases. Additionally, these studies have discovered diverse roles for certain members of the IL-12 family, encompassing multiple immunological functions that can either act as effectors or regulators. In this discourse, we examine the distinctive and atypical structural and functional attributes of this particular cytokine family. This study aims to offer a comprehensive overview of the pathophysiological significance of the IL-12 family cytokines in PCOS patients. Additionally, the therapeutic potential of the cytokines as novel approaches for PCOS treatment will be proposed. Show less
Interleukin-27 (IL-27) is a member of the IL-12 family. The gene encoding IL-27 is located at chromosome 16p11. IL-27 is considered as a heterodimeric cytokine, which consists of Epstein-Barr virus (E Show more
Interleukin-27 (IL-27) is a member of the IL-12 family. The gene encoding IL-27 is located at chromosome 16p11. IL-27 is considered as a heterodimeric cytokine, which consists of Epstein-Barr virus (EBV)-induced gene 3 (Ebi3) and IL-27p28. Based on the function of IL-27, it binds to receptor IL-27rα or gp130 and then regulates downstream cascade. To date, findings show that the expression of IL-27 is abnormal in different inflammatory autoimmune diseases (including systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, Behcet's disease, inflammatory bowel disease, multiple sclerosis, systemic sclerosis, type 1 diabetes, Vogt-Koyanagi-Harada, and ankylosing spondylitis). Moreover, Show less
Coagulation system is currently known associated with the development of ischemic stroke (IS). Thus, the current study is designed to identify diagnostic value of coagulation genes (CGs) in IS and to Show more
Coagulation system is currently known associated with the development of ischemic stroke (IS). Thus, the current study is designed to identify diagnostic value of coagulation genes (CGs) in IS and to explore their role in the immune microenvironment of IS. Aberrant expressed CGs in IS were input into unsupervised consensus clustering to classify IS subtypes. Meanwhile, key CGs involved in IS were further selected by weighted gene co-expression network analysis (WGCNA) and machine learning methods, including random forest (RF), support vector machine (SVM), generalized linear model (GLM) and extreme-gradient boosting (XGB). The diagnostic performance of key CGs were evaluated by receiver operating characteristic (ROC) curves. At last, quantitative PCR (qPCR) was performed to validate the expressions of key CGs in IS. IS patients were classified into two subtypes with different immune microenvironments by aberrant expressed CGs. Further WGCNA, machine learning methods and ROC curves identified ACTN1, F5, TLN1, JMJD1C and WAS as potential diagnostic biomarkers of IS. In addition, their expressions were significantly correlated with macrophages, neutrophils and/or T cells. GSEA also revealed that those biomarkers may regulate IS via immune and inflammation. Moreover, qPCR verified the expressions of ACTN1, F5 and JMJD1C in IS. The current study identified ACTN1, F5 and JMJD1C as novel coagulation-related biomarkers associated with IS immune microenvironment, which enriches our knowledge of coagulation-mediated pathogenesis of IS and sheds light on next-step Show less
Gene fusion events result in chimeric proteins that are frequently found in human cancers. Specific targeted therapies are available for several types of cancer fusions including receptor tyrosine kin Show more
Gene fusion events result in chimeric proteins that are frequently found in human cancers. Specific targeted therapies are available for several types of cancer fusions including receptor tyrosine kinase gene moieties. RNA sequencing (RNAseq) can directly be used for detection of gene rearrangements in a single test, along with multiple additional biomarkers. However, tumor biosamples are usually formalin-fixed paraffin-embedded (FFPE) tissue blocks where RNA is heavily degraded, which in theory may result in decreased efficiency of fusion detection. Here, for the first time, we compared the efficacy of gene fusion detection by RNAseq for matched pairs of freshly frozen in RNA stabilizing solution (FF) and FFPE tumor tissue samples obtained from 29 human colorectal cancer patients. We detected no statistically significant difference in the number of chimeric transcripts in FFPE and FF RNAseq profiles. The known fusion Show less
The most prevalent hip disease in neonates is developmental dysplasia of the hip (DDH). A timely and accurate diagnosis is required to provide the most effective treatment for pediatric patients with Show more
The most prevalent hip disease in neonates is developmental dysplasia of the hip (DDH). A timely and accurate diagnosis is required to provide the most effective treatment for pediatric patients with DDH. Heredity and gene variation have been the subject of increased attention and research worldwide as one of the factors contributing to the pathogenesis of DDH. Genome-wide association studies (GWAS), genome-wide linkage analyses (GWLA), and exome sequencing (ES) have identified variants in numerous genes and single-nucleotide polymorphisms (SNPs) as being associated with susceptibility to DDH in sporadic and DDH family patients. Furthermore, the DDH phenotype can be observed in animal models that exhibit susceptibility genes or loci, including variants in Show less
Due to their low cost, good biocompatibility, and ease of structural modification, organic long-persistent luminescence (LPL) materials have garnered significant attention in organic light-emitting di Show more
Due to their low cost, good biocompatibility, and ease of structural modification, organic long-persistent luminescence (LPL) materials have garnered significant attention in organic light-emitting diodes, biological imaging, information encryption, and chemical sensing. Efficient charge separation and carrier migration by the host-guest structure or using polymers and crystal to build rigid environments are effective ways of preparing high-performance materials with long-lasting afterglow. In this study, four types of crystalline materials (MODPA: DDF-O, MODPA: DDF-CHO, MODPA: DDF-Br, and MODPA: DDF-TRC) were prepared by a convenient host-guest doping method at room temperature under ambient conditions, i.e., in the presence of oxygen. The first three types exhibited long-lived charge-separated (CS) states and achieved visible LPL emissions with durations over 7, 4, and 2 s, respectively. More surprisingly, for the DDF-O material prepared with PMMA as the polymer substrate, the afterglow time of DDF-O: PMMA was longer than 10 s. The persistent room-temperature phosphorescence effect caused by different CS state generation efficiencies and rigid environment were the main reason for the difference in LPL duration. The fourth crystalline material was without charge separation and exhibited no LPL because it was not a D-A system. The research results indicate that the CS state generation efficiency and a rigid environment are the key factors affecting the LPL properties. This work provides new understandings in designing organic LPL materials. Show less
Breast cancer is the most commonly diagnosed cancer worldwide. Although major treatments represented by chemotherapy have shown effectiveness at the initial period, recurrence and metastasis still occ Show more
Breast cancer is the most commonly diagnosed cancer worldwide. Although major treatments represented by chemotherapy have shown effectiveness at the initial period, recurrence and metastasis still occur later after treatments. The alternation of the tumor microenvironment by chemotherapy is confirmed as a trigger of the elevated proliferation and migration of the remaining tumor cells. Using bioinformatic methods, differential gene expression analysis was used to determine DEGs between post-chemotherapy and pre-chemotherapy samples of breast cancer patients, followed by survival analysis and ELISA analysis of the potential key genes. An in vitro model of 2 breast cancer cells lines was used to demonstrate the role of VWF in the evasion and migration of breast cancer cells, using cell migration, evasion and wound healing assays, PCR and molecular docking analysis. 19 hub genes were further identified using GO and KEGG pathway analyses and WGCNA. The 5 secreted protein-coding genes with reported carcinogenesis effects (VWF, SVEP1, DPT, ADIPOQ, and LPL) were further analyzed in breast cancer patients and VWF was identified as a potential key regulator in the anthracycline-based chemotherapy-exacerbated metastasis. It was further confirmed that anthracycline-based chemotherapeutics doxorubicin exacerbated VWF upregulation and the evasion and migration of breast cancer cells. Based on molecular docking analysis and previous study, berberine was used as an inhibitor of VWF, and showed an effective inhibition of the doxorubicin-exacerbated VWF upregulation, migration and evasion in breast cancer. Doxorubicin-exacerbated evasion and migration through VWF upregulation. Berberine as an inhibitor of VWF was able to reversed the doxorubicin-exacerbated VWF upregulation and evasion and migration in breast cancer cells. Show less
The differences in muscle development potential between male and female ducks lead to variations in body weight, significantly affecting the growth of the Muscovy duck meat industry. The aim of this s Show more
The differences in muscle development potential between male and female ducks lead to variations in body weight, significantly affecting the growth of the Muscovy duck meat industry. The aim of this study is to explore the regulatory mechanisms for the muscle development differences between genders. Muscovy ducks of both sexes were selected for measurements of body weight, growth traits, hormone levels, and muscle gene expression. The results show that male ducks compared to females had greater weight and growth traits ( Show less
Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a Show more
Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation. Show less
Optical signals with distinctive properties, such as contactless, fast response, and high identification, are harnessed to realize advanced anti-counterfeiting. However, the simultaneous attainment of Show more
Optical signals with distinctive properties, such as contactless, fast response, and high identification, are harnessed to realize advanced anti-counterfeiting. However, the simultaneous attainment of multi-color, -temporal, and -modal luminescence performance remains a compelling and imperative pursuit. In our work, a temperature/photon-responded dynamic self-activated luminescence originating from nonstoichiometric Zn Show less
Laser-based additive manufacturing has garnered significant attention in recent years as a promising 3D-printing method for fabricating metallic components. However, the surface roughness of additive Show more
Laser-based additive manufacturing has garnered significant attention in recent years as a promising 3D-printing method for fabricating metallic components. However, the surface roughness of additive manufactured components has been considered a challenge to achieving high performance. At present, the average surface roughness (Sa) of AM parts can reach high levels, greater than 50 μm, and a maximum distance between the high peaks and the low valleys of more than 300 μm, which requires post machining. Therefore, laser polishing is increasingly being utilized as a method of surface treatment for metal alloys, wherein the rapid remelting and resolidification during the process significantly alter both the surface quality and subsurface material properties. In this paper, the surface roughness, microstructures, microhardness, and wear resistance of the as-received, continuous wave laser polishing (CWLP), and pulsed laser polishing (PLP) processed samples were investigated systematically. The results revealed that the surface roughness (Sa) of the as-received sample was 6.29 μm, which was reduced to 0.94 μm and 0.84 μm by CWLP and PLP processing, respectively. It was also found that a hardened layer, about 200 μm, was produced on the Ti Show less
Yuan-Zheng Zhu, Jian-Kun Liu, Xue-Er Li+7 more · 2024 · The journals of gerontology. Series A, Biological sciences and medical sciences · Oxford University Press · added 2026-04-24
Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associat Show more
Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associated secretory phenotype (SASP). How SASP contributes to atherosclerosis and CAD, however, remains unclear. Here, we integrated RNA-array datasets of senescent human coronary arterial endothelial cells (HCAECs) and aortic smooth muscle cells (HASMCs) as well as genome-wide association data for CAD. We identified 26 genes from HCAECs and 6 genes from HASMCs related to SASP and CAD in both in-house and published datasets. Of which, Cystatin C (CST3), a CAD susceptibility gene, was found to be expressed in both HCAECs and HASMCs, thus, it was prioritized for further investigation. We demonstrated it was significantly elevated in senescent vascular cells, aged arteries, and early atherosclerosis. In vitro experiments showed that CST3 enhances the monocyte-endothelial cell adhesion. Additionally, ligand-receptor pairing analyses revealed two important pathways, COL4A1-ITGA1 and LPL-LRP1 pathways, linked to the critical processes in the development of atherosclerosis, including cell adhesion, inflammation response, extracellular matrix organization, and lipid metabolism. We further demonstrated a reduced monocyte-endothelial cell adhesion following the knockdown of COL4A1 or ITGA1 and a significantly increased expression of COL4A1, ITGA1, and LPL in arterial intima of aged mice and ApoE-/- mice. Our findings demonstrate that vascular cell-derived SASP proteins increase the CAD susceptibility and identify CST3 functionally contributing to atherosclerosis. Show less
As the drawbacks of antibiotics in treating bacterial infections emerged, physical methods such as near-infrared-activated (NIR-activated) bacterial killing, have attracted great interests for their a Show more
As the drawbacks of antibiotics in treating bacterial infections emerged, physical methods such as near-infrared-activated (NIR-activated) bacterial killing, have attracted great interests for their advantages of no resistance, short action time and few side effects. In this manuscript, NIR-activated bacteria-killing performance of chiral copper sulphide nanoparticles (L-/d-CuS NPs) was investigated using linearly polarized light (LPL) and circularly polarized light (CPL) as illumination sources, respectively. Chiral CuS NPs showed enhanced NIR-activated bacteria-killing effect compared with achiral CuS NPs under the same conditions. Moreover, these chiral CuS NPs showed obvious chirality-related antibacterial effect: the bacterial killing was more efficient under CPL activation, and L- and d-CuS NPs had higher antibacterial efficiency under left circularly polarized light (LCPL) and right circularly polarized light (RCPL), respectively. The possible mechanism of bacteria-killing performance for chiral CuS NPs was discussed in detailed. Photothermal bacteria-killing tests of chiral CuS NPs "sealed" in polydimethylsiloxane (PDMS) demonstrated the individual influence of photothermal effect. These observations in this paper could provide ideas for the potential applications of chiral nanostructures with enhanced photothermal effect in efficient bacterial killing. Show less
Fish physiological health is often negatively impacted by high-temperature environments and there are few studies on how dietary lipids affect fish growth and physiology when exposed to heat stress. T Show more
Fish physiological health is often negatively impacted by high-temperature environments and there are few studies on how dietary lipids affect fish growth and physiology when exposed to heat stress. The main objective of this research was to examine the impact of dietary lipid levels on growth and physiological status of juvenile turbot (Scophthalmus maximus L.) and determine if dietary lipid concentration could alleviate the possible adverse effects of heat stress. Five diets containing 6.81%, 9.35%, 12.03%, 14.74%, and 17.08% lipid, respectively, were formulated and fed to turbot (initial weight 5.13 ± 0.02 g) under high-temperature conditions (24.0-25.0 °C). Meanwhile, the diet with 12.03% lipid (considered by prior work to be an optimal dietary lipid level) was fed to turbot of the same size at normal temperature. Results suggested that, among the different dietary lipid levels under high-temperature conditions, fish fed the optimal lipid (12.03%) exhibited better growth compared to non-optimal lipid groups, as evidenced by higher weight gain and specific growth rate. Simultaneously, the optimal lipid diet may better maintain lipid homeostasis, as attested by lower liver and serum lipid, along with higher liver mRNA levels of lipolysis-related genes (pgc1α, lipin1, pparα, lpl and hl) and lower levels of synthesis-related genes (lxr, fas, scd1, pparγ, dgat1 and dgat2). Also, the optimal lipid diet might mitigate oxidative damage by improving antioxidant enzyme activity, decreasing malondialdehyde levels, and up-regulating oxidation-related genes (sod1, sod2, cat, gpx and ho-1). Furthermore, the optimal lipid may enhance fish immunity, as suggested by the decrease in serum glutamic-oxalacetic/pyruvic transaminase activities, down-regulation of pro-inflammatory genes and up-regulation of anti-inflammation genes. Correspondingly, the optimal lipid level suppressed MAPK signaling pathway via decreased phosphorylation levels of p38, JNK and ERK proteins in liver. In summary, the optimal dietary lipid level facilitated better growth and physiological status in turbot under thermal stress. Show less
The introduction of single-cell RNA sequencing (scRNA-seq) technology has spurred additional advancements in analyzing the cellular composition of tissues. The
The purpose of this paper was to construct a prognostic model, miRNA-mRNA regulatory network and protein-protein interaction (PPI) network for lung squamous cell carcinoma (LUSC) used data from the ca Show more
The purpose of this paper was to construct a prognostic model, miRNA-mRNA regulatory network and protein-protein interaction (PPI) network for lung squamous cell carcinoma (LUSC) used data from the cancer genome atlas (TCGA) database. In this study, we first downloaded and sorted out the expression matrix containing 19962 mRNA transcripts (including 502 LUSC and 51 normal control (NC) samples) and the expression matrix containing 2205 miRNA transcripts (including 478 LUSC and 45 NC samples) from the TCGA database. We obtained 389 differentially expressed miRNAs (DE-miRNAs), of which 305 were upregulated and 84 down-regulated DE-miRNAs. Next, a total of 7 prognosis-related DE-miRNAs (PDE-miRNAs) were identified by Cox regression analysis, and the prognosis model consisting of three PDE-miRNAs (hsa-miR-4746-5p, hsa-miR-556-3p and hsa-miR-489-3p) was optimized. Then, we drew the survival curves and found that the survival rates of the three PDE-miRNA high and low expression groups and the survival rates of the high-risk and low-risk patients in the prognosis model had significant statistical differences. In addition, the receiver operating characteristics (ROC) curve analysis and independent prognostic analysis confirmed that the prognostic model we built has a relatively accurate ability to predict the grouping and prognosis of LUSC patients. Finally, Cox regression analysis were used to construct the miRNA-mRNA regulatory network, which showed the regulatory relationship between PDE-miRNAs and targeted mRNAs. Moreover, we constructed the PPI network composed of 145 targeted mRNAs and the subnetwork composed of 10 hub-targeted mRNAs (FCGR3A, IL13, CCR2, PPARGC1A, FCGR3B, ACSL1, PLXNA4, LPL, KAT2B and AOC3), which showed the interaction between targeted mRNAs. The above results indicated that the prognosis model we built can predict LUSC patients relatively accurately. The miRNA-mRNA regulatory network and the PPI network of targeted mRNAs illustrated the regulatory mechanisms and interactions between RNAs, which were of certain reference significance for us to further understand the molecular pathogenesis of LUSC and for clinical early diagnosis and treatment. Show less