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.

SIRT5-Mediated Desuccinylation of RAB7A Protects Against Cadmium-Induced Alzheimer's Disease-Like Pathology by Restoring Autophagic Flux.

Cadmium (Cd) is a neurotoxic contaminant that induces cognitive decline similar to that observed in Alzheimer's disease (AD). Autophagic flux dysfunction is attributed to the pathogenesis of AD, and this study aimed to investigate the effect of autophagy on environmental Cd-induced AD progression and the underlying mechanism. Here, Cd exposure inhibited autophagosome-lysosome fusion and impaired lysosomal function, leading to defects in autophagic clearance and then to APP accumulation and nerve cell death. Proteomic analysis coupled with Ingenuity Pathway Analysis (IPA) identified SIRT5 as an essential molecular target in Cd-impaired autophagic flux. Mechanistically, Cd exposure hampered the expression of SIRT5, thus increasing the succinylation of RAB7A at lysine 31 and inhibiting RAB7A activity, which contributed to autophagic flux blockade. Importantly, SIRT5 overexpression led to the restoration of autophagic flux blockade, the alleviation of Aß deposition and memory deficits, and the desuccinylation of RAB7A in Cd-exposed FAD4T mice. Additionally, SIRT5 levels decrease mainly in neurons but not in other cell clusters in the brains of AD patients according to single-nucleus RNA sequencing data from the public dataset GSE188545. This study reveals that SIRT5-catalysed RAB7A desuccinylation is an essential adaptive mechanism for the amelioration of Cd-induced autophagic flux blockade and AD-like pathogenesis.

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.

Long-term cadmium exposure induces epithelial-mesenchymal transition in breast cancer cells by activating CYP1B1-mediated glutamine metabolic reprogramming in BT474 cells and MMTV-Erbb2 mice.

Cadmium (Cd) exposure is known to enhance breast cancer (BC) progression. Cd promotes epithelial-mesenchymal transition (EMT) in BC cells, facilitating BC cell aggressiveness and invasion, but the underlying molecular mechanisms are unclear. Hence, transgenic MMTV-Erbb2 mice (6 weeks) were orally administered Cd (3.6 mg/L, approximately equal to 19.64 µΜ) for 23 weeks, and BC cells (BT474 cells) were exposed to Cd (0, 0.1, 1 or 10 µΜ) for 72 h to investigate the effect of Cd exposure on EMT in BC cells. Chronic Cd exposure dramatically expedited tumor metastasis to multiple organs; decreased E-cadherin density; and increased Vimentin, N-cadherin, ZEB1, and Twist density in the tumor tissues of MMTV-Erbb2 mice. Notably, transcriptomic analysis of BC tumors revealed cytochrome P450 1B1 (CYP1B1) as a key factor that regulates EMT progression in Cd-treated MMTV-Erbb2 mice. Moreover, Cd increased CYP1B1 expression in MMTV-Erbb2 mouse BC tumors and in BT474 cells, and CYP1B1 inhibition decreased Cd-induced BC cell malignancy and EMT in BT474 cells. Importantly, the promotion of EMT by CYP1B1 in Cd-treated BC cells was presumably controlled by glutamine metabolism. This study offers novel perspectives into the effect of environmental Cd exposure on driving BC progression and metastasis, and this study provides important guidance for comprehensively assessing the ecological and health risks of Cd.

The antioxidant strain Lactiplantibacillus plantarum AS21 and Clostridium butyricum ameliorate DSS-induced colitis in mice by remodeling the assembly of intestinal microbiota and improving gut functions.

Probiotics are known for their beneficial effects on improving intestinal function by alleviating the gut microbial diversity. However, the influences of antioxidant lactic acid bacteria (LAB) and anti-inflammatory Clostridium butyricum (CB) on ameliorating enteritis remain unclear. In this study, we investigated the effects of the antioxidant strain Lactiplantibacillus plantarum AS21 and CB alone, or in combination on intestinal microbiota, barrier function, oxidative stress and inflammation in mice with DSS-induced colitis. All probiotic treatments relieved the pathological development of colitis by improving the integrity of the intestinal mucosal barrier and the length of the colon. The probiotics also suppressed inflammation and oxidative stress by improving gut short-chain fatty acids and inhibiting the p38-MAPK/NF-κB pathway in colon tissues. According to the meta-network analysis, three distinct modules containing sensitive OTUs of the gut bacterial community specific to the control, DSS and DSS + probiotics groups were observed, and unlike the other two modules, Lachnospiraceae and Clostridia dominated the sensitive OTUs in the DSS + probiotics group. In addition, administration of the present probiotics particularly increased antioxidant and anti-inflammatory microbes Muribaculaceae, Bifidobacterium, Prevotellaceae and Alloprevotella. Furthermore, combined probiotic strain treatment showed a more stable anti-colitis effect than a single probiotic strain. Collectively, the present probiotics exhibited protective effects against colitis by suppressing the inflammation and oxidative damage in the colon, improving the gut microbiota and their functions, and consequently preventing the gut leak. The results indicate that the combination of the antioxidant properties of LAB and the anti-inflammatory properties of CB as nutritional intervention and adjuvant therapy could be an effective strategy to prevent and alleviate colitis.

Responses of microbial community dynamics, co-occurrences, functional shifts, and natural fermentation profiles of Elymus nutans silage to altitudinal gradients.

IMPORTANCE: On the Qinghai-Tibet Plateau (QTP), feed shortages are common due to cold environmental conditions and the short growing season of crops. Therefore, effective preservation, such as the ensiling of local forage, is becoming increasingly important to balance the seasonal imbalance between the forage supply and the nutritional needs of domestic animals in this area. However, the structure of the microbial community of the forage, which is influenced by climatic conditions such as altitude differences, has a major impact on the fermentation quality and microbial succession of the ensiled forage. Therefore, we investigated microbial community dynamics, co-occurrence, functional shifts, and natural fermentation profiles of Elymus nutans silage as a function of altitudinal gradients. Results show that silage from Chenduo at higher elevations has better fermentation quality and higher abundance of Lacticaseibacillus and Levilactobacillus than ensiled forage from other regions. This work may contribute to guiding for silage production in QTP.

Chronic cadmium exposure triggered ferroptosis by perturbing the STEAP3-mediated glutathione redox balance linked to altered metabolomic signatures in humans.

Cadmium (Cd), a predominant environmental pollutant, is a canonical toxicant that acts on the kidneys. However, the nephrotoxic effect and underlying mechanism activated by chronic exposure to Cd remain unclear. In the present study, male mice (C57BL/6J, 8 weeks) were treated with 0.6 mg/L cadmium chloride (CdCl2) administered orally for 6 months, and tubular epithelial cells (TCMK-1 cells) were treated with low-dose (1, 2, and 3 µM) CdCl2 for 72 h (h). Our study results revealed that environmental Cd exposure triggered ferroptosis and renal dysfunction. Spatially resolved metabolomics enabled delineation of metabolic profiles and visualization of the disruption to glutathione homeostasis related to ferroptosis in mouse kidneys. Multiomics analysis revealed that chronic Cd exposure induced glutathione redox imbalance that depended on STEAP3-driven lysosomal iron overload. In particular, glutathione metabolic reprogramming linked to ferroptosis emerged as a metabolic hallmark in the blood of Cd-exposed workers. In conclusion, this study provides the first evidence indicating that chronic Cd exposure triggers ferroptosis and renal dysfunction that depend on STEAP3-mediated glutathione redox imbalance, greatly increasing our understanding of the metabolic reprogramming induced by Cd exposure in the kidneys and providing novel clues linking chronic Cd exposure to nephrotoxicity.

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.

The role of mindfulness and dysexecutive functioning in the association between depression and COVID-19-related stress: cross-sectional and longitudinal analyses.

Background: Since the COVID-19 outbreak, the severity of college student's mental health has increased, with depression being the most prominent. This study's primary purpose was to explore (1) whether the perceived stress of COVID-19 was associated with depression through sequential mediation of mindfulness and dysexecutive function and also (2) the temporal association among mindfulness, dysexecutive function and depression.Methods: We performed two studies to evaluate dysexecutive function as a mechanism through which mindfulness impacts depression under the stress of the COVID-19 pandemic. Study 1 used a sequential mediation model to test the mediating role of mindfulness and dysexecutive function between the perceived stress of COVID-19 and depression based on 1,665 emerging adults. Study 2 used a random-effect, cross-lagged panel model (RE-CLPM) to test the directionality among mindfulness, dysexecutive function, and depression based on 370 emerging adults.Results: The cross-sectional study showed that perceived stress of COVID-19 was positively associated with depression through the sequential mediation of mindfulness and dysexecutive function (effect: 0.08, 95%CI = [0.07, 0.10]), also through the mediation of mindfulness (effect: 0.05, 95%CI = [0.03, 0.06]) and dysexecutive function (effect: 0.08, 95%CI = [0.06, 0.10]) separately. The RE-CLPM study indicated that dysexecutive function mediates the reciprocal relation between mindfulness and depression at the within-person level.Conclusion: These results suggest that dysexecutive function is an intermediate psychological mechanism that exacerbates depression under pandemic-related stress. Mindfulness can predict dysexecutive function and subsequently improve depression. As depression under pandemic-related stress can weaken the mindful state, long-term mindfulness practices are needed to maintain mental health during COVID-19.

Dysexecutive function is a potential cognitive risk factor of depression under pandemic stress using cross-sectional data.The random effect cross-lagged panel model (RE-CLPM) demonstrated temporal association among mindfulness, dysexecutive functions, and depression.Long-term mindfulness practices are needed to maintain mental health under COVID-19 stress.

Environmental cadmium exposure facilitates mammary tumorigenesis via reprogramming gut microbiota-mediated glutamine metabolism in MMTV-Erbb2 mice.

Cadmium (Cd) is a heavy metal that has been widely reported to be linked to the onset and progression of breast cancer (BC). However, the mechanism of Cd-induced mammary tumorigenesis remains elusive. In our study, a transgenic mouse model that spontaneously develops tumors through overexpression of wild-type Erbb2 (MMTV-Erbb2) was constructed to investigate the effects of Cd exposure on BC tumorigenesis. The results showed that oral exposure to 3.6 mg/L Cd for 23 weeks dramatically accelerated tumor appearance and growth, increased Ki67 density and enhanced focal necrosis and neovascularization in the tumor tissue of MMTV-Erbb2 mice. Notably, Cd exposure enhanced glutamine (Gln) metabolism in tumor tissue, and 6-diazo-5-oxo-l-norleucine (DON), a Gln metabolism antagonist, inhibited Cd-induced breast carcinogenesis. Then our metagenomic sequencing and mass spectrometry-based metabolomics confirmed that Cd exposure disturbed gut microbiota homeostasis, especially Helicobacter and Campylobacter abundance remodeling, which altered the gut metabolic homeostasis of Gln. Moreover, intratumoral Gln metabolism profoundly increased under Cd-elevated gut permeability. Importantly, depletion of microbiota with an antibiotic cocktail (AbX) treatment led to a significant delay in the appearance of palpable tumors, inhibition of tumor growth, decrease in tumor weight, reduction in Ki67 expression and low-grade pathology in Cd-exposed MMTV-Erbb2 mice. Also, transplantation of Cd-modulated microbiota decreased tumor latency, accelerated tumor growth, increased tumor weight, upregulated Ki67 expression and exacerbated neovascularization as well as focal necrosis in MMTV-Erbb2 mice. In summary, Cd exposure induced gut microbiota dysbiosis, elevated gut permeability and increased intratumoral Gln metabolism, leading to the promotion of mammary tumorigenesis. This study provides novel insights into environmental Cd exposure-mediated carcinogenesis.

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.

Transcriptomics integrated with metabolomics unravels the interweaving of inflammatory response and 1-stearoyl-2-arachidonoyl-sn-glycerol metabolic disorder in chronic cadmium exposure-induced hepatotoxicity.

Chronic Cd exposure induces an inflammatory response that contributes to liver damage. In the present study, C57BL/6 J mice (8 weeks) were administered CdCl2 (0.6 mg/L) orally for 6 months, and the underlying mechanism of chronic Cd-induced hepatotoxicity was explored through the application of transcriptomics and metabolomics. Chronic Cd exposure induced focal necrosis and inflammatory cell infiltration in the livers of mice. Importantly, hepatic IL-1ß, IL-6, IL-9, IL-10, IL-17 and GM-CSF levels were significantly increased following chronic Cd exposure. Ingenuity Pathway Analysis of the transcriptomics profiles combined with RTqPCR was used to identify and optimize a crucial inflammatory response network in chronic Cd hepatotoxicity. Furthermore, an integrative analysis combining inflammatory response genes with differential metabolites revealed that 1-stearoyl-2-arachidonoyl-sn-glycerol and 4-hydroxybutanoic acid lactone levels were significantly correlated with all inflammatory response genes. Overall, our findings in this study help decipher the underlying mechanisms and key molecular events of chronic Cd hepatotoxicity.

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.

Metagenomics insights into the effects of lactic acid bacteria inoculation on the biological reduction of antibiotic resistance genes in alfalfa silage.

Antibiotic resistance genes (ARGs) are a new type of pollutant and pose major threats to public health. However, the distribution and transmission risk of ARGs in alfalfa silage as the main forage for ruminants have not been studied. This study first deciphered the effects of Lactobacillus plantarum MTD/1 or Lactobacillus buchneri 40788 inoculations on distribution and transmission mechanism of ARGs in alfalfa silage by metagenomics. Results showed that multidrug and bacitracin resistance genes were the dominant ARGs in ensiled alfalfa. The natural ensiling process increased the abundances of bacitracin, beta_lactam, and aminoglycoside in alfalfa silage with 30% DM, and vancomycin in alfalfa silage with 40% DM. Meanwhile, prolonged wilting increased ARG enrichment in fresh alfalfa. Interestingly, alfalfa silage inoculated with L. plantarum MTD/1 or L. buchneri 40788 reduced the abundances of total ARG, and multidrug, MLS, vancomycin, aminoglycoside, tetracycline, and fosmidomycin resistance genes by reductions of the host bacteria and the enrichment of ARGs located in the plasmid. The hosts of ARG in alfalfa silage were mainly derived from harmful bacteria or pathogens, and some of the clinical ARGs were observed in alfalfa silage. Basically, the combined effect of microbes, MGEs, and fermentation quality was the major driver of ARG transfer and dissemination in microecosystem of ensiling, where the microbes appeared to be the crucial factor. In summary, inoculation with the present lactic acid bacteria could reduce ARG abundance in ensiled alfalfa, and a better effect was observed in L. plantarum-treated silage than in L. buchneri treated silage.

Long-term cadmium exposure impairs cognitive function by activating lnc-Gm10532/m6A/FIS1 axis-mediated mitochondrial fission and dysfunction.

Cadmium (Cd), a ubiquitous environmental contaminant, is deemed a possible aetiological cause of cognitive disorders in humans. Nevertheless, the exact mechanism by which chronic exposure to Cd causes neurotoxicity is not fully understood. In this study, mouse neuroblastoma cells (Neuro-2a cells) and primary hippocampal neurons were exposed to low-dose (1, 2, and 4 µM for Neuro-2a cells or 0.5, 1, and 1.5 µM for hippocampal neurons) cadmium chloride (CdCl2) for 72 h (h), and male mice (C57BL/6J, 8 weeks) were orally administered CdCl2 (0.6 mg/L, approximately equal to 2.58 µg/kg·bw/d) for 6 months to investigate the effects and mechanism of chronic Cd-induced neurotoxicity. Here, chronic exposure to Cd impaired mitochondrial function by promoting excess reactive oxygen species (ROS) production, altering mitochondrial membrane potential (Δψm) and reducing adenosine triphosphate (ATP) content, contributing to neuronal cell death. Specifically, microarray analysis revealed that the long noncoding RNA Gm10532 (lnc-Gm10532) was most highly expressed in Neuro-2a cells exposed to 4 µM CdCl2 for 72 h compared with controls, and inhibition of lnc-Gm10532 significantly antagonized CdCl2-induced mitochondrial dysfunction and neurotoxicity. Mechanistically, lnc-Gm10532 increased Fission 1 (FIS1) expression and mitochondrial fission by recruiting the m6A writer methyltransferase-like 14 (METTL14) and enhancing m6A modification of Fis1 mRNA. Moreover, lnc-Gm10532 was also required for chronic Cd-induced mitochondrial dysfunction and memory deficits in a rodent model. Therefore, data of this study reveal a new epigenetic mechanism of chronic Cd neurotoxicity.

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.

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.