Extracellular vesicle biomarkers for complement dysfunction in schizophrenia.

Schizophrenia, a complex neuropsychiatric disorder, frequently experiences a high rate of misdiagnosis due to subjective symptom assessment. Consequently, there is an urgent need for innovative and objective diagnostic tools. In this study, we used cutting-edge extracellular vesicles' (EVs) proteome profiling and XGBoost-based machine learning to develop new markers and personalized discrimination scores for schizophrenia diagnosis and prediction of treatment response. We analysed plasma and plasma-derived EVs from 343 participants, including 100 individuals with chronic schizophrenia, 34 first-episode and drug-naïve patients, 35 individuals with bipolar disorder, 25 individuals with major depressive disorder and 149 age- and sex-matched healthy controls. Our innovative approach uncovered EVs-based complement changes in patients, specific to their disease-type and status. The EV-based biomarkers outperformed their plasma counterparts, accurately distinguishing schizophrenia individuals from healthy controls with an area under curve (AUC) of 0.895, 83.5% accuracy, 85.3% sensitivity and 82.0% specificity. Moreover, they effectively differentiated schizophrenia from bipolar disorder and major depressive disorder, with AUCs of 0.966 and 0.893, respectively. The personalized discrimination scores provided a personalized diagnostic index for schizophrenia and exhibited a significant association with patients' antipsychotic treatment response in the follow-up cohort. Overall, our study represents a significant advancement in the field of neuropsychiatric disorders, demonstrating the potential of EV-based biomarkers in guiding personalized diagnosis and treatment of schizophrenia.

10-hydroxy-2-decenoic acid alleviates lipopolysaccharide-induced intestinal mucosal injury through anti-inflammatory, antioxidant, and gut microbiota modulation activities in chickens.

Introduction: This study aimed to investigated the effects of 10-hydroxy-2-decenoic acid (10-HDA) on the growth performance, intestinal barrier, inflammatory response, oxidative stress, and gut microbiota of chickens challenged with lipopolysaccharide (LPS). Methods: A total of 240 one-day-old chickens were randomly assigned to five treatment groups: (1) control group (basal diet + saline); (2) LPS group (basal diet + LPS); (3) Chlortetracycline (CTC) group (basal diet containing 75 mg/kg CTC + LPS); (4) 0.1% 10-HDA group (basal diet containing 1 g/kg 10-HDA + LPS); and (5) 0.5% 10-HDA group (basal diet containing 5 g/kg 10-HDA + LPS). All chickens were injected intraperitoneally with 0.5 mg/kg body weight of either LPS or saline at 17, 19, and 21 days of age. Results: The results showed that dietary 10-HDA supplementation attenuated the loss in growth performance caused by the LPS challenge (p < 0.05). 10-HDA effectively alleviated LPS-induced intestinal mucosal injury, as evidenced by reduced bleeding, decreased serum diamine oxidase levels (p < 0.05), and increased villus/crypt ratios of the jejunum and ileum (p < 0.05). Dietary treatment with 0.1% 10-HDA reduced the concentrations of inflammatory cytokines (TNF-α, IL-1ß, IL-6; p < 0.05), and increased immunoglobulin (IgA, IgG) and antioxidant enzyme levels (CAT, GSH-px, T-SOD) in the serum of LPS-challenged chickens (p < 0.05). These effects were similar to those observed in the CTC group. Moreover, 0.1% 10-HDA treatment reversed the LPS-induced variations in the mRNA expression of genes related to inflammation, antioxidant capacity, and intestinal tight junctions (p < 0.05). 16S rRNA analysis revealed that 10-HDA supplementation increased the relative abundance of Faecalibacterium and Clostridia_UCG-014 (p < 0.05). Additionally, it decreased the abundance of Clostridia_vadinBB60_group, Eubacterium_nodatum_group, and UC5-1-2E3 (p < 0.05). These changes were correlated with reduced inflammation and improved antioxidant capacity in the LPS-challenged chickens. Conclusion: Collectively, dietary 10-HDA supplementation alleviated LPS-induced intestinal mucosal injury and the loss of growth performance through anti-inflammatory, antioxidant, and gut microbiota modulation activities in chickens. Moreover, 0.1% 10-HDA supplementation had comparable or even better protection for LPS-challenged chickens than supplementation with antibiotics or 0.5% 10-HDA. 10-HDA has the potential to be used as an alternative to antibiotics in protecting the intestinal health and improving the performance of poultry.

Cancer-associated fibroblasts undergoing neoadjuvant chemotherapy suppress rectal cancer revealed by single-cell and spatial transcriptomics.

Neoadjuvant chemotherapy (NAC) for rectal cancer (RC) shows promising clinical response. The modulation of the tumor microenvironment (TME) by NAC and its association with therapeutic response remain unclear. Here, we use single-cell RNA sequencing and spatial transcriptome sequencing to examine the cell dynamics in 29 patients with RC, who are sampled pairwise before and after treatment. We construct a high-resolution cellular dynamic landscape remodeled by NAC and their associations with therapeutic response. NAC markedly reshapes the populations of cancer-associated fibroblasts (CAFs), which is strongly associated with therapeutic response. The remodeled CAF subsets regulate the TME through spatial recruitment and crosstalk to activate immunity and suppress tumor progression through multiple cytokines, including CXCL12, SLIT2, and DCN. In contrast, the epithelial-mesenchymal transition of malignant cells is upregulated by CAF_FAP through MIR4435-2HG induction, resulting in worse outcomes. Our study demonstrates that NAC inhibits tumor progression and modulates the TME by remodeling CAFs.

Antibiotic resistance and drug modification: Synthesis, characterization and bioactivity of newly modified potent pleuromutilin derivatives with a substituted piperazine moiety.

Antibiotic-resistant bacteria pose a major global public health concern, owing to the lack of effective antibacterial drugs. Consequently, the discovery and development of innovative antibacterial drug classes with unique mechanisms of action are urgently needed. In this study, we designed, synthesised, and tested a series of novel pleuromutilin derivatives with piperazine linker substituted by amino acids moieties to determine their antibacterial properties. Most synthesized compounds exhibited potent activities against Staphylococcus aureus (S. aureus), methicillin-resistant S. aureus (MRSA), and methicillin-resistant Staphylococcus epidermidis. Compound 6l, the most potent antibacterial agent created in this study, displayed a rapid bactericidal activity against MRSA, Klebsiella pneumoniae and S. aureus cfr N12. Moreover, pharmacokinetics study of compound 6l exhibited good PK performance with a low in vivo clearance (CL = 1965 mL/h/kg) and a suitable half-life (T1/2 = 11.614 ± 5.123 h). Molecular docking experiments revealed the binding model of compound 6l to the unmethylated A2503 of peptidyl transferase centre of 23S rRNA. Interaction pattern of 6l with cfr-mediated ribosomes revealed by molecular dynamics. Moreover in vivo mouse systemic infection experiments with compound 6l revealed its effectiveness against MRSA and S. aureus cfr N12 with the ED50 of 11.08 mg/kg and 14.63 mg/kg body weight, respectively.

Single-Cell RNA Sequencing Reveals Heterogeneity in the Tumor Microenvironment between Young-Onset and Old-Onset Colorectal Cancer.

BACKGROUND: The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. Compared with old-onset colorectal cancer (oCRC), yCRC has different clinical and molecular characteristics. However, the difference in the tumor microenvironment (TME) between yCRC and oCRC remains unclear. METHODS: Fourteen untreated CRC tumor samples were subjected to single-cell RNA sequencing analysis. RESULTS: B cells and naïve T cells are enriched in yCRC, while effector T cells and plasma cells are enriched in oCRC. Effector T cells of yCRC show decreased interferon-gamma response and proliferative activity; meanwhile, Treg cells in yCRC show stronger oxidative phosphorylation and TGF-ß signaling than that in oCRC. The down-regulated immune response of T cells in yCRC may be regulated by immune and malignant cells, as we observed a downregulation of antigen presentation and immune activations in B cells, dendritic cells, and macrophages. Finally, we identified malignant cells in yCRC and oCRC with high heterogeneity and revealed their interactions with immune cells in the TME. CONCLUSIONS: Our data reveal significant differences of TME between yCRC and oCRC, of which the TME of yCRC is more immunosuppressive than oCRC. Malignant cells play an essential role in the formation of the suppressive tumor immune microenvironment.

Overexpression of a ceramide synthase gene,GhCS1, inhibits fiber cell initiation and elongation by promoting the synthesis of ceramides containing dihydroxy LCB and VLCFA.

Cotton is an important natural fiber crop worldwide. Cotton fiber cell is regarded as an ideal material for studying the growth and development of plant cells. Sphingolipids are important components of biomembrane and bioactive molecules which participate in many processes such as plant growth, development regulation, stimulus sensing, and stress response. However, the functions of sphingolipids in the cotton fiber development are still unclear. In the present study, we identified a cotton ceramide synthase gene, GhCS1, which is predominantly expressed in fiber cell. The GhCS1 is located in the endoplasmic reticulum and has the conserved domains of ceramide synthase. Overexpression of GhCS1 gene inhibited both vegetative and reproductive growth in cotton. Importantly, the fiber cell initiation and elongation were severely inhibited when compared with control. Comparison of the sphingolipid profile in the 0-DPA (days past anthesis) ovule (with fiber cell) between control and transgenic cotton plants showed that the content of sphingosines (Sph) decreased significantly in transgenic ovules, whereas the content of phyto-sphingosines (Phyto-Sph) had no change. Meanwhile, the content of ceramide containing Sph and very-long-chain fatty acid (VLCFA) increased significantly in transgenic ovules, while ceramide containing Phyto-Sph and long-chain fatty acids (LCFA)/VLCFA significantly decreased. These results indicated that GhCS1 was a functional ceramide synthase, which preferentially used Sph and VLCFA as substrates and was different from the Arabidopsis ceramide synthase AtLOH1/AtLOH3, which preferentially used Phyto-Sph and VLCFA as substrates, and also different from AtLOH2, which preferentially used Sph and LCFA as substrates. It is suggested that GhCS1 might be a new ceramide synthase gene in the plant, play some roles in the development of fiber cells and cotton plants.

GhCYP710A1 Participates in Cotton Resistance to Verticillium Wilt by Regulating Stigmasterol Synthesis and Plasma Membrane Stability.

Cotton is an important economic crop. Cotton Verticillium wilt caused by Verticillium dahliae seriously damages production. Phytosterols play roles in plant-pathogen interaction. To explore the function and related mechanism of phytosterols in the interaction between Verticillium dahliae and cotton plants, and the resistance to Verticillium wilt, in this study, we analyzed the changes of sterol composition and content in cotton roots infected by Verticillium dahliae, and identified the sterol C22-desaturase gene GhCYP710A1 from upland cotton. Through overexpressing and silencing the gene in cotton plant, and ectopically expressing the gene in Arabidopsis, we characterized the changes of sterol composition and the resistance to Verticillium wilt in transgenic plants. The infection of Verticillium dahliae resulted in the content of total sterol and each sterol category decreasing in cotton root. The ratio of stigmasterol to sitosterol (St/Si) increased, indicating that the conversion of sitosterol to stigmasterol was activated. Consistently, the expression level of GhCYP710A1 was upregulated after infection. The GhCYP710A1 has the conservative domain that is essential for sterol C22-desaturase in plant and is highly expressed in root and stem, and its subcellular location is in the endoplasmic reticulum. The ectopic expression of GhCYP710A1 gene promoted the synthesis of stigmasterol in Arabidopsis. The St/Si value is dose-dependent with the expression level of GhCYP710A1 gene. Meanwhile, the resistance to Verticillium wilt of transgenic Arabidopsis increased and the permeability of cell membrane decreased, and the content of ROS decreased after V991 (a strain of Verticillium dahliae) infection. Consistently, the resistance to Verticillium wilt significantly increased in the transgenic cotton plants overexpressing GhCYP710A1. The membrane permeability and the colonization of V991 strain in transgenic roots were decreased. On the contrary, silencing GhCYP710A1 resulted in the resistance to Verticillium wilt being decreased. The membrane permeability and the colonization of V991 were increased in cotton roots. The expression change of GhCYP710A1 and the content alteration of stigmasterol lead to changes in JA signal transduction, hypersensitivity and ROS metabolism in cotton, which might be a cause for regulating the Verticillium wilt resistance of cotton plant. These results indicated that GhCYP710A1 might be a target gene in cotton resistance breeding.

Mucocele: a rare complication following stapled haemorrhoidopexy.

BACKGROUND: Stapled haemorrhoidopexy (SH) has resulted in a unique collection of procedural complications with postoperative mucocele a particularly rare example. This study is designed to comprehensively describe the characteristics of rectal mucocele and discuss its pathogenesis following SH surgery. METHODS: A database of patients presenting with a rectal mucocele following an SH procedure was established and studied retrospectively. RESULTS: Seven patients (5 males; median age 32 years, range 20-75 years) were identified. All patients complained of variable anal discomfort with 5/7 presenting with inconstant anal pain, 2 with de novo evacuatory difficulty. These cases appeared at a median time of 6 months (range 2-84 months) after SH surgery. CONCLUSION: Rectal Mucocele develops when mucosal fragments become embedded and isolated under the mucosa. It is a preventable complication of SH surgery by ensuring correct purse string placement prior to stapled haemorrhoid excision.

ILDR1 promotes influenza A virus replication through binding to PLSCR1.

As a natural antiviral regulator, phospholipid scramblase 1 (PLSCR1) has been shown to inhibit influenza virus replication in infected cells through interacting with NP of influenza A virus (IAV). But its antiviral function as well as the underlying regulatory mechanism has not been examined in vivo. In the present work, we show that PLSCR1 expression is decreased in H1N1 SIV-infected mice, and Plscr1-/- mice are more susceptible to H1N1 SIV infection. By performing yeast two-hybrid screening, we identified immunoglobulin-like domain-containing receptor 1 (ILDR1) as a novel PLSCR1-binding partner. ILDR1 is highly expressed in the lungs, and its expression level is increased after virus infection. Interestingly, ILDR1 could not directly interact with virus NP protein, but could combine with PLSCR1 competitively. Our data indicates that there is a previously unidentified PLSCR1-ILDR1-NP regulatory pathway playing a vital role in limiting IAV infection, which provides novel insights into IAV-host interactions.

Ginsenoside Rg1 exerts anti­apoptotic effects on non­alcoholic fatty liver cells by downregulating the expression of SGPL1.

Non­alcoholic fatty liver disease (NAFLD) has a high incidence, and can lead to liver cirrhosis and even hepatocellular carcinoma in severe cases. To the best of our knowledge, there is currently no safe and effective treatment for the management of this disease. Ginsenoside Rg1 (Rg1) is an active monomer derived from ginseng and notoginseng. In the present study, HHL­5 hepatocytes were used to establish an in vitro cell model of NAFLD by medium­ and long­chain fat emulsion treatment, and the effects of Rg1 on adipose accumulation, apoptosis and the expression levels of apoptosis­related proteins in HHL­5 hepatocytes were examined. The results demonstrated that Rg1 inhibited the accumulation of fat in HHL­5 cells, while inhibiting apoptosis, and Rg1 downregulated the expression levels of the pro­apoptotic protein Bax and upregulated the expression levels of the anti­apoptotic protein Bcl­2, indicating that Rg1 could promote the stability or integrity of mitochondria and exert an anti­apoptotic effect by regulating Bcl­2 family proteins. In addition, Rg1 markedly downregulated the expression levels of sphingosine­1­phosphate lyase 1 (SGPL1), a key enzyme in the sphingosine signaling pathway, in HHL­5 cells with steatosis, and increased the expression levels of the downstream pro­survival signals phosphorylated (p­)Akt and p­Erk1/2. Furthermore, overexpression of SGPL1 abolished the anti­apoptotic effect of Rg1 on SGPL1­overexpressing HHL­5 cells with steatosis, and downregulated the expression levels of pro­survival proteins, such as Bcl­2, p­Akt and p­Erk1/2, whereas the expression levels of pro­apoptotic Bax were markedly increased. In conclusion, although there are some reports regarding the protective effect of Rg1 on fatty liver cells, to the best of our knowledge, the present study is the first to report that Rg1 may exert an anti­apoptotic effect on fatty liver cells by regulating SGPL1 in the sphingosine signaling pathway. Rg1 is the main component of the prescription drug Xuesaitong in China; therefore, the findings of the present study may provide a theoretical molecular basis for the use of Rg1 or Xuesaitong in the treatment of patients with NAFLD.

Anticancer Activity and Molecular Mechanism of Momordica cochinchinensis Seed Extract in Chronic Myeloid Leukemia Cells.

Targeting Bcr-Abl is the key to the treatment of chronic myeloid leukemia. Despite great progress in the treatment of patients with chronic CML, advanced CML patients are still unable to obtain effective and safe drugs. Momordica cochinchinensis seed is the dried ripe seed of Momordica cochinchinensis, which is a kind of fruit and consumed for dietary as well as medicinal uses. This study aimed to investigate the anticancer activity of Momordica cochinchinensis seed extract (MCSE) in CML cells. CML cells (KBM5 and KBM5-T315I) were treated with MCSE and analyzed for growth, apoptosis, and signal transduction. Nude mouse xenograft model was used to evaluate the antitumor activity of MCSE In Vivo. MCSE significantly reduced the cell viability of CML cells, triggered G0/G1 phase arrest in KBM5 cells and S phase arrest in KBM5-T315I cells. Concurrently, MCSE caused the activation of caspase-3, -8, -9, PARP and the degradation of Mcl-1, ultimately triggering endogenous and exogenous cell apoptosis. Meanwhile, MCSE downregulated Bcr-Abl levels and its downstream signaling pathways. Additionally, MCSE inhibited the growth of CML cells in nude mouse xenografts. Taken together, this study demonstrated the anticancer mechanism of MCSE, namely blocking Bcr-Abl and downregulating Mcl-1, and finally induced apoptosis of CML cells.

Effect of Mahuang Fuzi and Shenzhuo Decoction on Idiopathic Membranous Nephropathy: A Multicenter, Nonrandomized, Single-Arm Clinical Trial.

Objective: To explore the clinical effect of Mahuang Fuzi and Shenzhuo Decoction on idiopathic membranous nephropathy. Methods: This study is a multicenter, nonrandomized, single-arm clinical trial carried out as per the objective performance criteria, with the target being set at 35.0%. 184 cases of patients suffering from idiopathic membranous nephropathy with Shaoyin Taiyin syndrome were collected. These patients were treated with Mahuang Fuzi and Shenzhuo Decoction with a follow-up period of 3 years. The 24-hour urine protein and blood albumin were observed, and the remission rates of the patients were compared with the target. Results: The mean follow-up time was 18 (12.5, 30) months, and the remission rate was 61.4%, which is a statistically significant difference from the target group of 35%. The remission rates for patients who had and had not used immunosuppressive therapy were 59.6 and 65.5%, respectively, but the difference was not statistically significant (p = 0.254). However, the albumin before the treatment and the course of treatment of the patients was significantly correlated with the disease remission (p < 0.05). However, the albumin before the treatment and the course of treatment of the patients was significantly correlated with the disease remission (p < 0.05). There were no significant changes in renal function before and after treatment, and no severe adverse events occurred during treatment. Conclusion: Mahuang Fuzi and Shenzhuo Decoction have significant effects on idiopathic membranous nephropathy, and has the same effect on patients with membranous nephropathy who are newly treated as well as those who have been treated with immunosuppressive therapy without remission. In addition, the efficacy of this regimen is related to the albumin and the duration of the therapy, but not to 24-hour urine protein or other factors.

Comparative Metabolomics Analysis Reveals Sterols and Sphingolipids Play a Role in Cotton Fiber Cell Initiation.

Cotton fiber is a seed trichome that protrudes from the outer epidermis of cotton ovule on the day of anthesis (0 day past anthesis, 0 DPA). The initial number and timing of fiber cells are closely related to fiber yield and quality. However, the mechanism underlying fiber initiation is still unclear. Here, we detected and compared the contents and compositions of sphingolipids and sterols in 0 DPA ovules of Xuzhou142 lintless-fuzzless mutants (Xufl) and Xinxiangxiaoji lintless-fuzzless mutants (Xinfl) and upland cotton wild-type Xuzhou142 (XuFL). Nine classes of sphingolipids and sixty-six sphingolipid molecular species were detected in wild-type and mutants. Compared with the wild type, the contents of Sphingosine-1-phosphate (S1P), Sphingosine (Sph), Glucosylceramide (GluCer), and Glycosyl-inositol-phospho-ceramides (GIPC) were decreased in the mutants, while the contents of Ceramide (Cer) were increased. Detail, the contents of two Cer molecular species, d18:1/22:0 and d18:1/24:0, and two Phyto-Cer molecular species, t18:0/22:0 and t18:0/h22:1 were significantly increased, while the contents of all GluCer and GIPC molecular species were decreased. Consistent with this result, the expression levels of seven genes involved in GluCer and GIPC synthesis were decreased in the mutants. Furthermore, exogenous application of a specific inhibitor of GluCer synthase, PDMP (1-phenyl-2-decanoylamino-3-morpholino-1-propanol), in ovule culture system, significantly inhibited the initiation of cotton fiber cells. In addition, five sterols and four sterol esters were detected in wild-type and mutant ovules. Compared with the wild type, the contents of total sterol were not significantly changed. While the contents of stigmasterol and campesterol were significantly increased, the contents of cholesterol were significantly decreased, and the contents of total sterol esters were significantly increased. In particular, the contents of campesterol esters and stigmasterol esters increased significantly in the two mutants. Consistently, the expression levels of some sterol synthase genes and sterol ester synthase genes were also changed in the two mutants. These results suggested that sphingolipids and sterols might have some roles in the initiation of fiber cells. Our results provided a novel insight into the regulatory mechanism of fiber cell initiation.

Sphingolipid Profile during Cotton Fiber Growth Revealed That a Phytoceramide Containing Hydroxylated and Saturated VLCFA Is Important for Fiber Cell Elongation.

Cotton fiber is a single-celled seed trichrome that arises from the epidermis of the ovule's outer integument. The fiber cell displays high polar expansion and thickens but not is disrupted by cell division. Therefore, it is an ideal model for studying the growth and development of plant cells. Sphingolipids are important components of membranes and are also active molecules in cells. However, the sphingolipid profile during fiber growth and the differences in sphingolipid metabolism at different developmental stages are still unclear. In this study, we detected that there were 6 classes and 95 molecular species of sphingolipids in cotton fibers by ultrahigh performance liquid chromatography-MS/MS (UHPLC-MS/MS). Among these, the phytoceramides (PhytoCer) contained the most molecular species, and the PhytoCer content was highest, while that of sphingosine-1-phosphate (S1P) was the lowest. The content of PhytoCer, phytoceramides with hydroxylated fatty acyls (PhytoCer-OHFA), phyto-glucosylceramides (Phyto-GluCer), and glycosyl-inositol-phospho-ceramides (GIPC) was higher than that of other classes in fiber cells. With the development of fiber cells, phytosphingosine-1-phosphate (t-S1P) and PhytoCer changed greatly. The sphingolipid molecular species Ceramide (Cer) d18:1/26:1, PhytoCer t18:1/26:0, PhytoCer t18:0/26:0, PhytoCer t18:1/h20:0, PhytoCer t18:1/h26:0, PhytoCer t18:0/h26:0, and GIPC t18:0/h16:0 were significantly enriched in 10-DPA fiber cells while Cer d18:1/20:0, Cer d18:1/22:0, and GIPC t18:0/h18:0 were significantly enriched in 20-DPA fiber cells, indicating that unsaturated PhytoCer containing hydroxylated and saturated very long chain fatty acids (VLCFA) play some role in fiber cell elongation. Consistent with the content analysis results, the related genes involved in long chain base (LCB) hydroxylation and unsaturation as well as VLCFA synthesis and hydroxylation were highly expressed in rapidly elongating fiber cells. Furthermore, the exogenous application of a potent inhibitor of serine palmitoyltransferase, myriocin, severely blocked fiber cell elongation, and the exogenous application of sphingosine antagonized the inhibition of myriocin for fiber elongation. Taking these points together, we concluded that sphingolipids play crucial roles in fiber cell elongation and SCW deposition. This provides a new perspective for further studies on the regulatory mechanism of the growth and development of cotton fiber cells.

[1.5 T Nuclear Magnetic Resonance Imaging System Failure Treatment and Rectification Summary].

Quench of magnetic resonance imaging system refers to the process that the superconducting condition inside the magnet is destroyed due to some reason. The large current stored in the coil is quickly converted into heat at the place where the resistance is formed, and a large amount of liquid helium in the magnet is evaporated. If it happens, it will cause huge loss to the user. We introduce the real cases of 1.5 T magnetic resonance imaging system's quench fault, maintenance treatment and management improvement, which can be used for reference by various medical institutions, so as to better strengthen the operation and maintenance management of magnetic resonance imaging system, so as to avoid the occurrence of out of tolerance fault, and do a good job in the guarantee work after the out of tolerance fault.

Tea Polyphenols Enhanced the Antioxidant Capacity and Induced Hsps to Relieve Heat Stress Injury.

Keap1-Nrf2-ARE and heat shock proteins (Hsps) are important endogenous protection mechanisms initiated by heat stress to play a double protective role for cell adaptation and survival. H9C2 cells and 80 300-day-old specific pathogen-free chickens were randomly divided into the control and tea polyphenol groups and used to establish a heat stress model in vitro and in vivo. This task was conducted to explore the protection and mechanism of tea polyphenols in relieving thermal injury. A supplement with 10 µg/mL tea polyphenols could effectively relieve the heat damage of H9C2 cells at 42°C. Accordingly, weaker granular degeneration, vacuolar degeneration, and nucleus deep staining were shown. A strong antioxidant capacity was manifested in the upregulation of the total antioxidant capacity (T-AOC) (at 5 h, P < 0.05), Hemeoxygenase-1 mRNA (at 2 h, P < 0.01), superoxide dismutase (SOD) (at 2, 3, and 5 h, P < 0.05), and Nrf2 (at 0 and 5 h, P < 0.01). A high expression of Hsps was reflected in CRYAB at 3 h; Hsp27 at 0, 2, and 3 h (P < 0.01); and Hsp70 at 3 and 5 h (P < 0.01). The supplement with 0.2 g/L tea polyphenols in the drinking water also had a good effect in alleviating the heat stress damage of the myocardial cells of hens at 38°C. Accordingly, light pathological lesions and downregulation of the myocardial injury-related indicators (LDH, CK, CK-MB, and TNF-α) were shown. The mechanism was related to the upregulation of T-AOC (at 0 h, P < 0.05), GSH-PX (at 0.5 d, P < 0.01), SOD (at 0.5 d), and Nrf2 (at 0 d with P < 0.01 and 2 d with P < 0.05) and the induced expression of CRYAB (at 0.5 and 2 d), Hsp27 (at 0, 0.5, and 5 d), and Hsp70 (at 0 and 0.5 d). In conclusion, the tea polyphenols enhanced the antioxidant capacity and induced Hsps to relieve heat stress injury.

iTRAQ-based quantitative proteomic analysis reveals the toxic mechanism of diclofenac sodium on the kidney of broiler chicken.

Diclofenac sodium (DS) is one of the nonsteroidal anti-inflammatory drugs (NSAIDs), which exhibits potent toxicity to birds. To search the molecular mechanism of DS induced nephrotoxicity in broiler chicken, 20 apparently healthy 30-day old broiler chickens were separated randomly into two groups (n = 10): Group A was kept as control while DS was administered at the dose rate of 10 mg/kg body weight in group B through oral gavage. Kidney samples were collected, and the proteins were identified and quantified by iTRAQ. 434 differentially expressed proteins (DEPs) were screened, including 277 up-regulated DEPs and 157 down-regulated DEPs. The functional annotation and classification results indicated that DEPs were significantly enriched in apoptosis and metabolism-related pathways via GO and KEGG analysis. Compared with the control group, the most significant enrichment pathways are "ribosome", "metabolic pathways" and "protein processing in endoplasmic reticulum". Based on the proteomic results and relevant literature, some DEPs that potentially related to the toxicity of DS were screened. The mRNA transcript levels of these DEPs were characterized by qRT-PCR, and the results showed that Slc22a7, Gatm, Glud1, Agxt2 and Gldc were significantly down-regulated, while Gsl, Gpt2 and Asns were significantly up-regulated. We speculate that the toxic mechanism of DS to chicken might be that it induces kidney cell apoptosis, interferes with purine metabolism and inhibits the expression of OAT2. The current study provides a reference for elucidating the nephrotoxic mechanism of diclofenac sodium to broiler chicken from the molecular perspective.

Antiviral activity of portulaca oleracea L. extracts against porcine epidemic diarrhea virus by partial suppression on myd88/NF-κb activation in vitro.

Porcine epidemic diarrhea virus (PEDV), especially variants, causes a highly contagious enteric disease which could give rise to huge economic losses in the swine industry worldwide. Portulaca oleracea L. has been reported to regulate intestine disease and involved in viral infections. However, the underlying mechanisms of Portulaca oleracea L. extracts against PEDV have not been fully elucidated. In this study, the antiviral effects and potential mechanisms of Portulaca oleracea L. extracts against PEDV were investigated in vitro. We first examined the inhibitory effects of different Portulaca oleracea L. extracts on the PEDV(JX-16 strain) in vitro and found that the water extract of Portulaca oleracea L.(PO)could significantly inhibit PEDV replication by 92.73% on VH cells and 63.07% on Vero cells. Furthermore, time-course analysis showed PO inhibited PEDV replication during the adsorption period of infectious cycle. Western blot and indirect immunofluorescence assay indicated that PO down-regulated the S protein expression in a dose-dependent manner. In addition, our results demonstrated the ability of PO to inhibit PEDV replication in VH cells by down-regulating the cytokine levels (TNF-α,IL-22 and IFN-α) and inhibiting the NF-κB signaling pathway activated by PEDV. Thus, Portulaca oleracea L extracts have potential utility in the preventive and therapeutic strategies for PEDV infection.

Passive mode locking in fiber lasers due to the polarization-dependent losses.

Weak polarization dependence exists in most fiber components. We numerically demonstrated passive mode locking in fiber lasers based on weak polarization dependence down to polarization-dependent loss of 1.76 dB. Different polarization dependences are investigated to unveil its role for achieving passive mode locking. The anomalous dispersion region and the normal dispersion regime are both tested. It is found that, independent of operating dispersion regime, stronger gain is required for achieving mode locking with lower polarization dependence. Our numerical demonstration confirms previous experimental results and broadens the knowledge on additive-pulse mode locking.

Heat stress decreases egg production of laying hens by inducing apoptosis of follicular cells via activating the FasL/Fas and TNF-α systems.

Heat stress (HS) causes significant economic losses in the poultry industry every year. However, the mechanisms for the adverse effects of HS on avian follicular development are largely unknown. The aim of this study was to test whether HS induces apoptosis of follicular cells and impairs egg production by activating the FasL/Fas and tumor necrosis factor (TNF)-α systems. To this end, Hy-Line Brown laying hens, at 32 wk of age, were either exposed to HS of 35°C to 37°C or maintained at 24°C to 26°C (control) for 5 D. At the end of the HS period, follicle numbers, apoptosis, FasL/Fas and TNF-α activation, oxidative stress, and hormone secretion were examined in ovarian follicles. Egg production was observed daily during both the stressed (day S1-S5) and the poststress recovery (day R1-R15) periods. The results demonstrated that HS on hens significantly 1) decreased laying rates from day S3 to R6; 2) reduced numbers of large yellow and hierarchical follicles; 3) triggered apoptosis while increasing the expression of FasL, Fas, TNF-α, and TNF-receptor 1 in small and large yellow follicles; and 4) increased levels of oxidative stress, corticotrophin-releasing hormone, and corticosterone while decreasing the estradiol/progesterone ratio in follicular fluid in small and large yellow follicles. Taken together, the results suggested that hen HS impaired egg production by reducing the number of follicles through inducing apoptosis and that it triggered apoptosis in follicular cells by activating the FasL/Fas and TNF-α systems.