CG9920 is necessary for mitochondrial morphogenesis and individualization during spermatogenesis in Drosophila melanogaster.

Drosophila melanogaster is an ideal model organism for investigating spermatogenesis due to its powerful genetics, conserved genes and visible morphology of germ cells during sperm production. Our previous work revealed that ocnus (ocn) knockdown resulted in male sterility, and CG9920 was identified as a significantly downregulated protein in fly abdomen after ocn knockdown, suggesting a role of CG9920 in male reproduction. In this study, we found that CG9920 was highly expressed in fly testes. CG9920 knockdown in fly testes caused male infertility with no mature sperms in seminal vesicles. Immunofluorescence staining showed that depletion of CG9920 resulted in scattered spermatid nuclear bundles, fewer elongation cones that did not migrate to the anterior region of the testis, and almost no individualization complexes. Transmission electron microscopy revealed that CG9920 knockdown severely disrupted mitochondrial morphogenesis during spermatogenesis. Notably, we found that CG9920 might not directly interact with Ocn, but rather was inhibited by STAT92E, which itself was indirectly affected by Ocn. We propose a possible novel pathway essential for spermatogenesis in D. melanogaster, whereby Ocn indirectly induces CG9920 expression, potentially counteracting its inhibition by the JAK-STAT signaling pathway.

Association of Thyroid Autoantibodies with Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients.

Background: Diabetic nephropathy (DN) is one of the most common and severe complications in patients with type 2 diabetes mellitus (T2DM). Thyroid dysfunction has been associated with diabetes and its complications but the relationship between thyroid autoantibodies and T2DM-DN remains unclear. Objective: The study aims to investigate the association between thyroid autoantibodies and diabetic nephropathy in patients with T2DM and analyze the expression of serum thyroid hormone levels in T2DM-DN patients and its prognostic value. Methods: 117 patients with T2DM who visited our hospital from December 2020 to December 2022 were recruited and assigned to group A (65 patients with T2DM-DN) and group B (52 patients with T2DM without DN). Serum TH levels of patients with DN and normal diabetic patients were analyzed, and the prognosis of patients was evaluated. Results: The results demonstrated that compared to group B, group A had higher serum cystatin C (cysC), serum creatinine (SCr), thyroglobulin antibody (TgAb), and urinary microalbumin/creatinine (UACR) levels, while the levels of free triiodothyronine (FT3), albumin (ALB), and estimated glomerular filtration rate (eGFR) were lower (P < .05). FT3 in group A2 was inferior to that in group A0 and group A1 (P < .05). After correction, the results demonstrated that the level of thyroid peroxidase antibody (TPOAb) in group A1 was superior to that in group A0 (P < .05). The positive rates of TPOAb (20%) and TgAb (23.08%) in patients with T2DM-DN were drastically superior to those in patients with T2DM without DN. Among the independent risk factors for DN, the OR of positive TPOAb was 8.125. Conclusion: The level and positive rate of thyroid autoantibodies in patients with T2DM-DN were high and TPOAb positivity might be a risk factor for the occurrence of T2DM-DN.

Quantitative proteomics and phosphoproteomics reveal insights into mechanisms of ocnus function in Drosophila testis development.

BACKGROUND: Testis is the only organ supporting sperm production and with the largest number of proteins and tissue-specific proteins in animals. In our previous studies, we have found that knockdown of ocnus (ocn), a testis-specific gene, resulted in much smaller testis with no germ cells in Drosophila melanogaster. However, the molecular consequences of ocn knockdown in fly testes are unknown. RESULTS: In this study, through iTRAQ quantitative proteomics sequencing, 606 proteins were identified from fly abdomens as having a significant and at least a 1.5-fold change in expression after ocn knockdown in fly testes, of which 85 were up-regulated and 521 were down-regulated. Among the differential expressed proteins (DEPs), apart from those proteins involved in spermatogenesis, the others extensively affected biological processes of generation of precursor metabolites and energy, metabolic process, and mitochondrial transport. Protein-protein interaction (PPI) analyses of DEPs showed that several kinases and/or phosphatases interacted with Ocn. Re-analyses of the transcriptome revealed 150 differential expressed genes (DEGs) appeared in the DEPs, and their changing trends in expressions after ocn knockdown were consistent. Many common down-regulated DEGs and DEPs were testis-specific or highly expressed in the testis of D. melanogaster. Quantitative RT-PCR (qRT-PCR) confirmed 12 genes appeared in both DEGs and DEPs were significantly down-regulated after ocn knockdown in fly testes. Furthermore, 153 differentially expressed phosphoproteins (DEPPs), including 72 up-regulated and 94 down-regulated phosphorylated proteins were also identified (13 phosphoproteins appeared in both up- and down-regulated groups due to having multiple phosphorylation sites). In addition to those DEPPs associated with spermatogenesis, the other DEPPs were enriched in actin filament-based process, protein folding, and mesoderm development. Some DEPs and DEPPs were involved in Notch, JAK/STAT, and cell death pathways. CONCLUSIONS: Given the drastic effect of the ocn knockdown on tissue development and testis cells composition, the differences in protein abundance in the ocn knockdown flies might not necessarily be the direct result of differential gene regulation due to the inactivation of ocn. Nevertheless, our results suggest that the expression of ocn is essential for Drosophila testis development and that its down-regulation disturbs key signaling pathways related to cell survival and differentiation. These DEPs and DEPPs identified may provide significant candidate set for future studies on the mechanism of male reproduction of animals, including humans.

Cytochrome c1-like is required for mitochondrial morphogenesis and individualization during spermatogenesis in Drosophila melanogaster.

The Drosophila testis is an excellent system for studying the process from germ stem cells to motile sperm, including the proliferation of male germ cells, meiosis of primary spermatocytes, mitochondrial morphogenesis, and spermatid individualization. We previously demonstrated that ocnus (ocn) plays an essential role in male germ cell development. Among those genes and proteins whose expression levels were changed as a result of ocn knockdown, cytochrome c1-like (cyt-c1L) was downregulated significantly. Here, we show that cyt-c1L is highly expressed in the testis of D. melanogaster. Knockdown or mutation of cyt-c1L in early germ cells of flies resulted in male sterility. Immunofluorescence staining showed that cyt-c1L knockdown testes had no defects in early spermatogenesis; however, in late stages, in contrast to many individualization complexes (ICs) composed of F-actin cones that appeared at different positions in control testes, no actin cones or ICs were observed in cyt-c1L knockdown testes. Furthermore, no mature sperm were found in the seminal vesicle of cyt-c1L knockdown testes whereas the control seminal vesicle was full of mature sperm with needle-like nuclei. cyt-c1L knockdown also caused abnormal mitochondrial morphogenesis during spermatid elongation. Excessive apoptotic signals accumulated in the base of cyt-c1L knockdown fly testes. These results suggest that cyt-c1L may play an important role in spermatogenesis by affecting the mitochondrial morphogenesis and individualization of sperm in D. melanogaster.

Manganese overexposure induces Parkinson-like symptoms, altered lipid signature and oxidative stress in C57BL/6 J mouse.

Although adequate intake of manganese (Mn) is essential to humans, Mn in excess is neurotoxic. Exposure to extremely high doses of Mn results in "manganism", a condition that exhibits Parkinson-like symptoms. However, the mechanisms underlying its neurotoxic effects in Mn-induced parkinsonism pathogenesis are unclear. In this study, 8-week-old male C57BL/6 J mice were injected intraperitoneally with saline and 50 mg/kg MnCl2 respectively once daily for 14 days to produce an acute Mn neurotoxicity model. Accumulation of Mn in the midbrain, motor dysfunction and loss of dopaminergic neurons in the substantia nigra evidenced Mn neurotoxicity. Untargeted lipidomic analysis demonstrated that Mn overexposure altered lipidome profiles. A significant modulation of 12 lipid subclasses belonging to 5 different categories were found in the midbrain and among the most abundant lipids were sphingolipids, glycerophospholipids, and glycerides. The levels of sphingomyelin (SM) were significantly decreased after Mn treatment. The expression of SM biosynthesis genes was decreased dramatically while sphingomyelinase was up-regulated. In addition, we observed oxidative stress in both the midbrain of mice and MN9D cells, indicated by the increase of MDA level, the decrease of reduced GSH level and the inhibition of SOD and GPx enzyme activities. There was a correlation between these changes and motor dysfunctions. Overall, our study is the first to use lipidomics techniques to explore the pathogenesis of Mn-induced parkinsonism in C57BL/6 J mice. Mn induced molecular events in the midbrain, such as lipid metabolism disorders, oxidative stress and dopaminergic neurons injury, may mechanistically play important roles in the pathogenesis of Parkinson-like symptoms. Moreover, these findings emphasize the necessity for reducing the health risk of environmental neurotoxic pollutants in relation to parkinsonism.

Effects of nisin on bacterial community and fermentation profiles, in vitro rumen fermentation, microbiota, and methane emission of alfalfa silage.

BACKGROUND: Alfalfa (Medicago sativa L.) has been used widely in preparing silage. However, forage legumes are prone to contamination by spoilage bacteria during fermentation. Nisin has broad-spectrum antibacterial properties and has been applied as an inhibitor of rumen methane emissions. However, little research has been carried out on the application of nisin in silage. This study therefore aimed to investigate the impacts of different nisin concentrations on the bacterial community and fermentation dynamics, in vitro ruminal fermentation characteristics, microbiota, and methane emissions of alfalfa silage. RESULTS: The detection limits of organic acid in nisin-treated silages were not reached in 0.09 g kg-1 nisin (0.09 level) from days 1 to 7 of ensiling. With increasing nisin concentrations, the silage dry matter increased linearly (P < 0.05), and dry matter loss decreased linearly (P < 0.05). Moreover, both the 0.06 g kg-1 nisin (0.06 level) and 0.09 level treatments increased the relative abundance of Pediococcus acidilactici during ensiling. Concurrently, as the nisin concentrations increased, ruminal methane production decreased linearly (P < 0.05), while the relative abundances of ruminal Succinivibrio, Fibrobacter succinogenes and Ruminobacter amylophilus increased linearly (P < 0.05). The populations of ruminal total bacteria, methanogens, protozoa, and fungi decreased linearly with increasing nisin concentrations (P < 0.05). CONCLUSION: The addition of nisin delayed the fermentation process, preserved more nutrients in alfalfa silage, and promoted fermentation dominated by P. acidilactici in the late phase of ensiling. Moreover, nisin reduced in vitro rumen methane emissions without adverse effects on dry matter digestibility. © 2023 Society of Chemical Industry.

Comprehensive profiling of the metabolome in corn silage inoculated with or without Lactiplantibacillus plantarum using different untargeted metabolomics analyses.

Silage fermentation is a complicated biochemical process involving interactions between microbes and metabolites. However, the overall metabolome feature of ensiled forage and its response to lactic acid bacteria inoculation is poorly understood. Hence, in this study metabolome profiles of whole-plant corn silage inoculated with or without Lactiplantibacillus plantarum were characterised via solid-phase microextraction/gas chromatography/mass spectrometry (SPME-GC-MS), gas chromatography/time-of-flight mass spectrometry (GC-TOF-MS), and Liquid chromatography/Q Exactive HFX mass spectrometry (LC-QE-MS/MS) analysis. There were 2087 identified metabolites including 1143 reliably identified metabolites in fresh and ensiled whole-plant corn. After ensiling, the increased metabolites in whole-plant corn were mainly composed of organic acids, volatile organic compounds (VOC), benzene and substituted derivatives, carboxylic acids and derivatives, fatty acyls, flavonoids, indoles and derivatives, organooxygen compounds (including amines and amides), phenols, pyridines and derivatives, and steroids and steroid derivatives, which includes neurotransmitters and metabolites with aromatic, antioxidant, anti-inflammatory, and antimicrobial activities. Phenylacetaldehyde was the most abundant aromatic metabolite after ensiling. L-isoleucine and oxoproline were the major free amino acids in silage. Ensiling markedly increased the relative abundances of 3-phenyllactic acid, chrysoeriol, 6-O-acetylaustroinulin, acetylcholine, γ-aminobutyric acid, pyridoxine, and alpha-linoleic acid. Inoculation with L. plantarum remarkably changed silage VOC composition, and essential amino acids, 3-phenyllactic acid, and cinnamaldehyde compared with untreated silage. The present study does not only provide a deeper insight into metabolites of the ensiled whole-plant corn but also reveals metabolites with specific biological functions that could be much helpful in screening novel lactic acid bacteria to well ensile forages. Inoculation with L. plantarum significantly affects the metabolome in ensiled whole-plant corn.

Associations between interleukin-1-B gene -511G/A polymorphism and sepsis risk: A meta-analysis.

The role of the cytokine (IL) gene has been indicated in the progression of sepsis. Nevertheless, the outcomes remain controversial. This meta-analysis aimed to examine the relationship of IL-1B gene -511G/A polymorphism and the risk of sepsis. To perform a retrospective database analysis, the CNKI PubMed,EMBASE and Cochrane Library databases were searched for related articles. Then, the combined odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated using a fixed- or a random-effects model. A total of six related articles were discovered. The result of the meta-analysis showed that IL-1B -511G/A polymorphism was not significantly correlated with sepsis risk in the total population, but in the subgroup analysis we found that IL-1B -511G/A polymorphism was associated with sepsis risk in Caucasian populations (A vs. G: OR = 1.22, 95 %CI = 1.01-1.48; AA vs. GG: OR = 2.14, 95 %CI = 1.33-3.43; Recessive model: OR = 2.59, 95 %CI = 1.68-4.01). This meta-analysis showed that the IL-1B -511A allele might be a low-penetrant risk factor for sepsis in Caucasians.

Fluoride exposure induces lysosomal dysfunction unveiled by an integrated transcriptomic and metabolomic study in bone marrow mesenchymal stem cells.

Fluoride has received much attention for its predominant bone toxicity in the human body. However, the toxic mechanism of bone injury caused by fluoride exposure remains largely unclear. Bone marrow mesenchymal stem cells (BMSCs) are widely used as model cells for evaluating bone toxicity after environmental toxicant exposure. In this study, BMSCs were exposed to fluoride at 1, 2, and 4 mM for 24 h, and fluoride significantly inhibited cell viability at 2 and 4 mM. A multiomics analysis combining transcriptomics with metabolomics was employed to detect alterations in genes and metabolites in BMSCs treated with 2 mM fluoride. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of transcriptomics profiles identified "lysosomes" as the top enriched pathway, which was severely damaged by fluoride exposure. Lysosomal damage was indicated by decreases in the expression of lysosomal associated membrane protein 2 (LAMP 2) and cathepsin B (CTSB) as well as an increase in pH. Upregulation of the lysosome-related genes Atp6v0b and Gla was observed, which may be attributed to a compensatory lysosomal biogenesis transcriptional response. Interestingly, inhibition of glutathione metabolism was observed in fluoride-treated BMSCs at the metabolomic level. Moreover, an integrative analysis between altered genes, metabolites and lysosome signaling pathways was conducted. Palmitic acid, prostaglandin C2, and prostaglandin B2 metabolites were positively associated with Atp6v0b, a lysosome-related gene. Overall, our results provide novel insights into the mechanism responsible for fluoride-induced bone toxicity.

miR-3614-5p downregulation promotes cadmium-induced breast cancer cell proliferation and metastasis by targeting TXNRD1.

Cadmium (Cd), which is considered an endocrine disruptor, has been linked to the onset of breast cancer (BC). Our recent study demonstrated that Cd-induced BC progression has a strong correlation with miR-374c-5p dysregulation. The aim of our work was to investigate other potential miRNAs involved in Cd-induced BC cell proliferation and metastasis. In our study, the miRNA profiles of Cd-treated T-47D cells (10 µM, 72 h) were analyzed by miRNA-seq, and our results confirmed that miR-3614-5p was the top downregulated miRNA. Moreover, miR-3614-5p mimic transfection significantly decreased the proliferative ability, migration and invasive ability of BC cell lines (T-47D and MCF-7). Furthermore, we analyzed the overlapping genes from our RNA-seq data and predicted targets from the mirDIP database, and twelve genes (ALDH1A3, FBN1, GRIA3, NOS1, PLD5, PTGER4, RASGRF2, RELN, RNF150, SLC17A4, TG, and TXNRD1) were identified as potential binding targets of miR-3614-5p in the current model. Nonetheless, only miR-3614-5p inhibition caused an increase in TXNRD1 expression upon Cd exposure in T-47D and MCF-7 cell lines. Importantly, luciferase reporter assays further verified that miR-3614-5p suppressed the expression of TXNRD1 by directly binding to the 3'-untranslated region (UTR), and TXNRD1 inhibition significantly repressed the proliferation and metastasis capacity of BC cells upon Cd exposure. Together, our findings demonstrated that Cd exposure repressed the expression of miR-3614-5p, thus activating TXNRD1 expression, which promoted the abnormal proliferation and metastasis of BC cells.

N6-methyladenosine-mediated downregulation of miR-374c-5p promotes cadmium-induced cell proliferation and metastasis by targeting GRM3 in breast cancer cells.

Cadmium (Cd) is a toxic heavy metal that can facilitate the development and progression of breast cancer (BC). Emerging evidence has indicated that the progression of Cd-exposed BC is related to the dysregulation of microRNAs (miRNAs). The purpose of our study was to investigate the expression pattern and underlying mechanisms of miR-374c-5p in Cd-mediated BC progression. In this study, T-47D cells and MCF-7 cells were treated with different concentrations of Cd (0.1, 1 and 10 µM) for 72 h. MiR-374c-5p expression was downregulated, and transfection of miR-374c-5p mimics significantly decreased BC cell proliferation, migration and invasion induced by 10 µM Cd. Importantly, we used the Cytoscape software plugin cytoHubba to analyse the intersected genes between our RNA-Seq results and the mirDIP database, and six hub genes (CNR1, CXCR4, GRM3, RTN1, SLC1A6 and ZEB1) were identified as potential direct targets of miR-374c-5p in our model; however, luciferase reporter assays indicated that miR-374c-5p only repressed GRM3 by directly binding to its 3'-untranslated region (UTR). Of note, we verified that suppression of N6-methyladenosine (m6A) modification led to miR-374c-5p downregulation by decreasing its RNA transcript stability. Together, these findings demonstrated that m6A modification of pri-miRNA-374c blocks miRNA-374c-5p maturation and then activates GRM3 expression, which drives BC cell metastasis after Cd exposure.

shrub is required for spermatogenesis of Drosophila melanogaster.

Shrub (CG8055) encodes the vps32/snf7 protein, a filament-forming subunit of the ESCRT (endosomal sorting complexes required for transport)-III complex involved in inward membrane budding. It was reported that shrub was required for abscission in female germline stem cells. In this study, we showed that the expression level of shrub in the testis was significantly higher than that in the ovary of 1-day-old Drosophila melanogaster, suggesting a role in male reproduction. Then we used nosGal4 driver to knockdown shrub specifically in the fly testis and found that this resulted in a significantly lower paternal effect egg hatch rate relative to the control group. Immunofluorescence staining showed that shrub knockdown in fly testes caused an accumulation of early-stage germ cells and lack of spectrin caps. In the late stages (spermiogenesis), the control testis contained multiple compacted spermatid bundles and individualization complexes (ICs) consisting of actin cones, whereas there were scattered spermatid nuclei and only a few ICs with disorganized actin cones in the shrub knockdown testis. Finally, the control seminal vesicle was full of mature sperms with needle-like heads, but in shrub knockdown testis 75% of seminal vesicles had no mature sperms. We also found that knockdown of shrub in fly testes led to upregulated expression of several cytoskeleton-associated genes, and an accumulation of ubiquitylated proteins. These results suggest that knockdown of shrub in fly testes might damage spermatogenesis by affecting transportability.

Rapamycin antagonizes cadmium-induced breast cancer cell proliferation and metastasis through directly modulating ACSS2.

Cadmium (Cd) is a carcinogen that stimulates breast cancer (BC) progression. Rapamycin is a macrolide antibiotic produced by Streptomyces hygroscopicus that possesses a wide array of pharmacological activities, including anti-BC activity. However, the effects of rapamycin on Cd-increased BC progression and the underlying mechanism have not been fully elucidated. Here, we hypothesize that rapamycin antagonizes Cd-induced BC cell proliferation and metastasis by directly modulating ACSS2. In this study, we found that rapamycin efficiently inhibited Cd-induced proliferation, invasion and migration in MCF-7 and T47-D cells. Moreover, a surface plasmon resonance (SPR) assay confirmed that rapamycin directly binds to the ACSS2 protein with a calculated equilibrium dissociation constant (KD) of 18.3 µM. Molecular docking showed that there are three binding sites in the ACSS2 protein and that rapamycin binds at the coenzyme A (COA) binding site with a docking score of - 12.26 and a binding free energy of - 26.34 kcal/mol. More importantly, rapamycin suppresses Cd-induced BC progression by activating ACSS2. After cells were cotreated with an ACSS2 inhibitor, the effects of rapamycin were abolished. In conclusion, our findings suggest that rapamycin suppresses Cd-augmented BC progression by upregulating ACSS2, and ACSS2 may serve as a direct target of rapamycin for inhibiting xenobiotic (e.g., Cd)-mediated BC progression.

Long-term exercise prevents hepatic steatosis: a novel role of FABP1 in regulation of autophagy-lysosomal machinery.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent diseases worldwide. Exercise is a first-line therapy and an important preventive measure for patients with NAFLD, but the underlying mechanisms are not clear. C57BL/6 mice were fed a high-fat diet (HFD) and subjected to 12 wk swimming exercise. Exercise protected against hepatic lipid accumulation and alleviated hepatocyte damage in HFD mice. Tandem mass tag-based quantitative proteomic analyses and ingenuity pathway analysis revealed that exercise down-regulated fatty acid-binding protein (FABP)1 signaling pathway, which was most closely associated with lipid metabolism. Moreover, exercise significantly decreased FABP1 expression, and liver-specific overexpression of FABP1 abolished the protective effect of exercise in NAFLD mice. Specifically, exercise significantly increased autophagic flux via restoring lysosomal function, including lysosomal proteolysis and lysosomal acidification maintenance, contributing to enhancement in autophagic clearance and subsequently alleviation of hepatic steatosis. Conversely, Fabp1 overexpression in the mouse liver blocked the protective effect of exercise via inhibiting autophagy flux. The present study identified FABP1 inhibition-mediated replenishment of the autophagy-lysosomal machinery as a novel endogenous mechanism whereby long-term exercise improves lipid homeostasis and ameliorates hepatic steatosis in NAFLD.-Pi, H., Liu, M., Xi, Y., Chen, M., Tian, L., Xie, J., Chen, M., Wang, Z., Yang, M., Yu, Z., Zhou, Z., Gao, F. Long-term exercise prevents hepatic steatosis: a novel role of FABP1 in regulation of autophagy-lysosomal machinery.

Inhibition of SERPINA3N-dependent neuroinflammation is essential for melatonin to ameliorate trimethyltin chloride-induced neurotoxicity.

Trimethyltin chloride (TMT) is a potent neurotoxin that causes neuroinflammation and neuronal cell death. Melatonin is a well-known anti-inflammatory agent with significant neuroprotective activity. Male C57BL/6J mice were intraperitoneally injected with a single dose of melatonin (10 mg/kg) before exposure to TMT (2.8 mg/kg, ip). Thereafter, the mice received melatonin (10 mg/kg, ip) once a day for another three consecutive days. Melatonin dramatically alleviated TMT-induced neurotoxicity in mice by attenuating hippocampal neuron loss, inhibiting epilepsy-like seizures, and ameliorating memory deficits. Moreover, melatonin markedly suppressed TMT-induced neuroinflammatory responses and astrocyte activation, as shown by a decrease in inflammatory cytokine production as well as the downregulation of neurotoxic reactive astrocyte phenotype markers. Mechanistically, serine peptidase inhibitor clade A member 3N (SERPINA3N) was identified as playing a central role in the protective effects of melatonin based on quantitative proteome and bioinformatics analysis. Most importantly, melatonin significantly suppressed TMT-induced SERPINA3N upregulation at both the mRNA and protein levels. The overexpression of Serpina3n in the mouse hippocampus abolished the protective effects of melatonin on TMT-induced neuroinflammation and neurotoxicity. Melatonin protected cells against TMT-induced neurotoxicity by inhibiting SERPINA3N-mediated neuroinflammation. Melatonin may be a promising and practical agent for reducing TMT-induced neurotoxicity in clinical practice.

A new function of immunity-related gene Zn72D in male fertility of Drosophila melanogaster.

Zn72D encodes the Drosophila zinc finger protein Zn72D. It was first identified to be involved in phagocytosis and indicated to have a role in immunity. Then it was demonstrated to have a function in RNA splicing and dosage compensation in Drosophila melanogaster. In this study, we discovered a new function of Zn72D in male fertility. We showed that knockdown of Zn72D in fly testes caused an extremely low egg hatch rate. Immunofluorescence staining of Zn72D knockdown testes exhibited scattered spermatid nuclei and no actin cones or individualization complexes (ICs) during spermiogenesis, whereas the early-stage germ cells and the spermatocytes were observed clearly. There were no mature sperms in the seminal vesicles of Zn72D knockdown fly testes, although a few sperms could be found close to the seminal vesicle. We further showed that many cytoskeleton-related genes were significantly downregulated in fly testes due to Zn72D knockdown. Taken together these findings suggest that Zn72D may have an important function in spermatogenesis by sustaining the cytoskeleton-based morphogenesis and individualization thus ensuring the proper formation of sperm in D. melanogaster.

Interleukin-1 Beta +3594 C/T Gene Polymorphism and Susceptibility to Sepsis: A Meta-Analysis.

Emerging evidence has indicated that the interleukin-1B (IL-1B) +3954 C > T polymorphism may affect individual susceptibility to sepsis. However, the results of published studies are inconclusive. The aim of this meta-analysis was to elucidate the association of this polymorphism with sepsis risk. Eligible studies were identified by a search of electronic databases. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were applied to assess the associations between the IL-1B +3954 C > T polymorphism and sepsis risk. Six case-control studies were included in this meta-analysis. The pooled analysis indicated that the IL-1B +3954 C > T polymorphism significantly decreased the risk of sepsis under the homozygote model (TT vs. CC: OR = 0.57, 95% CI:0.37-0.88). In stratified analysis, we found that the protective effect of the IL-1B +3954 C > T polymorphism on sepsis risk remained significant in the subgroup of Caucasians and for high-quality studies. In conclusion, the IL-1B +3954 C > T polymorphism is associated with decreased sepsis risk in Caucasians. Further well-designed studies with large sample sizes are required to confirm this conclusion.

Melatonin alleviates cadmium-induced liver injury by inhibiting the TXNIP-NLRP3 inflammasome.

Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in the liver and induces oxidative stress and inflammation. Melatonin possesses potent hepatoprotective properties against the development and progression of acute and chronic liver injury. Nevertheless, the molecular mechanism underlying the protective effects of melatonin against Cd-induced hepatotoxicity remains obscure. In this study, we aimed to investigate the effects of melatonin on Cd-induced liver inflammation and hepatocyte death. Male C57BL/6 mice were intraperitoneally injected with melatonin (10 mg/kg) once a day for 3 days before exposure to CdCl2 (2.0 mg/kg). We found that Cd induced hepatocellular damage and inflammatory infiltration as well as increased serum ALT/AST enzymes. In addition, we showed that Cd triggered an inflammatory cell death, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Moreover, melatonin treatment significantly alleviated Cd-induced liver injury by decreasing serum ALT/AST levels, suppressing pro-inflammatory cytokine production, inhibiting NLRP3 inflammasome activation, ameliorating oxidative stress, and attenuating hepatocyte death. Most importantly, melatonin markedly abrogated Cd-induced TXNIP overexpression and decreased the interaction between TXNIP and NLRP3 in vivo and in vitro. However, treatment with siRNA targeting TXNIP blocked the protective effects of melatonin in Cd-treated primary hepatocytes. Collectively, our results suggest that melatonin confers protection against Cd-induced liver inflammation and hepatocyte death via inhibition of the TXNIP-NLRP3 inflammasome pathway.

[Treatment of Chronic Endometritis by Penning Granule: a Clinical Randomized Controlled Trial].

Objective To observe the mechanism of Penning Granule ( PG) for treating chronic endometritis (CE). Methods Totally 38 CE patients in line with inclusive criteria were assigned to the PG group (23 cases) and the control group (15 cases) according to random digit table. PG (consisting of sargentgloryvine stem, Herba Patriniae, Hedyotis Diffusa, red peony root, Angelica Sinensis, prepared mastiche, prepared myrrh, common burreed tuber, zedoary root, Spina Gleditsiae, Danshen root, Radix Bupleuri, asarum , Astragalus, Pangolin) was administered to patients in the PG group, 105 g each time, twice per day for 4 successive weeks. Those in the control group took Levofloxacin (0.5 g, once per day) and Metronidazole Tablet (0. 5 g, twice daily for 1 successive week). They were followed-up for half a year after ending treatment. The morphological changes of uterine endometrium were observed by hyst- eroscopy before and after treatment, and endometrium biopsy performed at fixed position. The expres- sions of mucin-1 (MUC-1 ) and hypoxia induced facter-1 α (HIF-1α) in inflammatory endometrium were analyzed. The clinical effects were compared between PG and antibiotics from improvement of clinical symptoms, hysteroscopic manifestations, pathological analyses, and molecular levels. Results The markedly effective rate of clinical symptoms in the PG group was 91. 3% (21/23) , higher than that of the control group [60. 0% (9/15) ; P <-0. 05]. The plasma cell CD38 infiltration in endometrial stroma of the PG group were significantly decreased, showing better effect than antibiotics in the control group (P < 0.05). The positive expression of MUC-1 was increased and the expression of HIF-1 α was decreased in the PG group, showing better effect than antibiotics in the control group (P <0. 05). Conclusion PG showed obvious effects for treating chronic endometritis , and it was superior to that of antibiotics alone.

Crafting a Job among Chinese Employees: The Role of Empowering Leadership and the Links to Work-Related Outcomes.

The present study aims to examine the process through which empowering leadership shapes employees' work engagement and in-role performance by facilitating job-crafting behaviors, specifically seeking resources, seeking challenges, and reducing demands. Based on the extensive data from 733 Chinese employees across various organizations located predominantly in Chongqing and Xi'an, China, we carried out different types of statistical analysis such as confirmatory factor analysis (CFA) and structural equation modeling (SEM) to examine the relationships among empowering leadership, specific job-crafting behaviors, work engagement and in-role performance, test our hypothesis and our conceptual model. The results from structural equation modeling (SEM) suggested that empowering leadership was positively related to employees' work engagement and in-role performance; empowering leadership was positively related to employees' job crafting (seeking resources, seeking challenges and reducing demands); seeking resources, seeking challenges and reducing demands were positively related to in-role performance, and seeking challenges and reducing demands were positively related to work engagement. In the relationship between empowering leadership and in-role performance, seeking resources serves as a mediating factor. Similarly, seeking challenges mediates the association between empowering leadership and both work engagement and in-role performance. Furthermore, reducing demands mediates the links between empowering leadership and both work engagement and in-role performance. The implications of these findings are subsequently discussed.