FgPfn participates in vegetative growth, sexual reproduction, pathogenicity, and fungicides sensitivity via affecting both microtubules and actin in the filamentous fungus Fusarium graminearum.

Fusarium head blight (FHB), caused by Fusarium graminearum species complexes (FGSG), is an epidemic disease in wheat and poses a serious threat to wheat production and security worldwide. Profilins are a class of actin-binding proteins that participate in actin depolymerization. However, the roles of profilins in plant fungal pathogens remain largely unexplored. Here, we identified FgPfn, a homolog to profilins in F. graminearum, and the deletion of FgPfn resulted in severe defects in mycelial growth, conidia production, and pathogenicity, accompanied by marked disruptions in toxisomes formation and deoxynivalenol (DON) transport, while sexual development was aborted. Additionally, FgPfn interacted with Fgα1 and Fgß2, the significant components of microtubules. The organization of microtubules in the ΔFgPfn was strongly inhibited under the treatment of 0.4 µg/mL carbendazim, a well-known group of tubulin interferers, resulting in increased sensitivity to carbendazim. Moreover, FgPfn interacted with both myosin-5 (FgMyo5) and actin (FgAct), the targets of the fungicide phenamacril, and these interactions were reduced after phenamacril treatment. The deletion of FgPfn disrupted the normal organization of FgMyo5 and FgAct cytoskeleton, weakened the interaction between FgMyo5 and FgAct, and resulting in increased sensitivity to phenamacril. The core region of the interaction between FgPfn and FgAct was investigated, revealing that the integrity of both proteins was necessary for their interaction. Furthermore, mutations in R72, R77, R86, G91, I101, A112, G113, and D124 caused the non-interaction between FgPfn and FgAct. The R86K, I101E, and D124E mutants in FgPfn resulted in severe defects in actin organization, development, and pathogenicity. Taken together, this study revealed the role of FgPfn-dependent cytoskeleton in development, DON production and transport, fungicides sensitivity in F. graminearum.

Pathways for macrophage uptake of cell-free circular RNAs.

Circular RNAs (circRNAs) are stable RNAs present in cell-free RNA, which may comprise cellular debris and pathogen genomes. Here, we investigate the phenomenon and mechanism of cellular uptake and intracellular fate of exogenous circRNAs. Human myeloid cells and B cells selectively internalize extracellular circRNAs. Macrophage uptake of circRNA is rapid, energy dependent, and saturable. CircRNA uptake can lead to translation of encoded sequences and antigen presentation. The route of internalization influences immune activation after circRNA uptake, with distinct gene expression programs depending on the route of RNA delivery. Genome-scale CRISPR screens and chemical inhibitor studies nominate macrophage scavenger receptor MSR1, Toll-like receptors, and mTOR signaling as key regulators of receptor-mediated phagocytosis of circRNAs, a dominant pathway to internalize circRNAs in parallel to macropinocytosis. These results suggest that cell-free circRNA serves as an "eat me" signal and danger-associated molecular pattern, indicating orderly pathways of recognition and disposal.

Unraveling the genetic basis of the causal association between inflammatory cytokines and osteonecrosis.

Background: Previous studies have reported that the occurrence and development of osteonecrosis is closely associated with immune-inflammatory responses. Mendelian randomization was performed to further assess the causal correlation between 41 inflammatory cytokines and osteonecrosis. Methods: Two-sample Mendelian randomization utilized genetic variants for osteonecrosis from a large genome-wide association study (GWAS) with 606 cases and 209,575 controls of European ancestry. Another analysis included drug-induced osteonecrosis with 101 cases and 218,691 controls of European ancestry. Inflammatory cytokines were sourced from a GWAS abstract involving 8,293 healthy participants. The causal relationship between exposure and outcome was primarily explored using an inverse variance weighting approach. Multiple sensitivity analyses, including MR-Egger, weighted median, simple model, weighted model, and MR-PRESSO, were concurrently applied to bolster the final results. Results: The results showed that bFGF, IL-2 and IL2-RA were clinically causally associated with the risk of osteonecrosis (OR=1.942, 95% CI=1.13-3.35, p=0.017; OR=0.688, 95% CI=0.50-0.94, p=0.021; OR=1.386, 95% CI=1.04-1.85, p = 0.026). there was a causal relationship between SCF and drug-related osteonecrosis (OR=3.356, 95% CI=1.09-10.30, p=0.034). Conclusion: This pioneering Mendelian randomization study is the first to explore the causal link between osteonecrosis and 41 inflammatory cytokines. It conclusively establishes a causal association between osteonecrosis and bFGF, IL-2, and IL-2RA. These findings offer valuable insights into osteonecrosis pathogenesis, paving the way for effective clinical management. The study suggests bFGF, IL-2, and IL-2RA as potential therapeutic targets for osteonecrosis treatment.

The synergistic antibacterial activity and mechanism of colistin-oxethazaine combination against gram-negative pathogens.

Background: The rapid spread of bacteria with plasmid-mediated resistance to antibiotics poses a serious threat to public health. The search for potential compounds that can increase the antibacterial activity of existing antibiotics is a promising strategy for addressing this issue. Methods: Synergistic activity of the FDA-approved agent oxethazine combined with colistin was investigated in vitro using checkerboard assays and time-kill curves. The synergistic mechanisms of their combination of oxethazine and colistin was explored by fluorescent dye, scanning electron microscopy (SEM) and LC-MS/MS. The synergistic efficacy was evaluated in vivo by the Galleria mellonella and mouse sepsis models. Results: In this study, we found that oxethazine could effectively enhance the antibacterial activity of colistin against both mcr-positive and -negative pathogens, and mechanistic assays revealed that oxethazine could improve the ability of colistin to destruct bacterial outer membrane and cytoplasmic membrane permeability. In addition, their combination triggered the accumulation of reactive oxygen species causing additional damage to the membrane structure resulting in cell death. Furthermore, oxethazine significantly enhanced the therapeutic efficacy of colistin in two animal models. Conclusion: These results suggested that oxethazine, as a promising antibiotic adjuvant, can effectively enhance colistin activity, providing a potential strategy for treating multidrug-resistant bacteria.

Effects of vaginal dilation therapy on vaginal length, vaginal stenosis, vaginal elasticity and sexual function of cervical cancer survivors.

BACKGROUND: Cervical cancer survivors can experience vaginal length shortening, vaginal stenosis, vaginal elasticity deterioration, sexual frequency reduction and sexual dysfunction. This prospective, uncontrolled, monocentric clinical interventional study aimed to evaluate the effect of vaginal dilation therapy on vaginal condition and sexual function of cervical cancer survivors who had not received timely vaginal dilation. METHODS: A total of 139 patients completed the study. They received 6 months of vaginal dilation therapy. We evaluated their vaginal elasticity, vaginal diameter, vaginal length and sexual function before and after vaginal dilation therapy. Their vaginal conditions were evaluated by customised vaginal moulds, and the sexual function was assessed by female sexual function index. The SPSS 25 software was used to analyse all the data. RESULTS: Age, vaginal diameter and sexual intercourse frequency before diagnosis were significantly associated with female sexual dysfunction of the patients after cancer treatment. Vaginal dilation therapy improved vaginal stenosis, vaginal length and sexual function in all the patients; however, the vaginal elasticity and incidence of sexual dysfunction did not improve significantly. Sexual intercourse frequency before diagnosis, vaginal elasticity, time interval from last treatment and treatment modalities were significantly associated with the change in female sexual function index score before and after vaginal dilation therapy. Patients with a time interval from the last treatment less than 24 months or those who had moderate or good vaginal elasticity, benefitted more from vaginal dilatation therapy. CONCLUSIONS: Cervical cancer survivors who had not received timely vaginal dilation still benefitted from vaginal dilation therapy, irrespective of the treatment methods they received. Moreover, vaginal dilation therapy should be performed as early as possible after cervical cancer treatment.

Cervical cancer survivors can experience vaginal condition deterioration and sexual dysfunction after treatment. Vaginal dilation can help improve vaginal stenosis, vaginal length and sexual function of these patients. However, some medical institutions in China do not provide timely vaginal dilation for this population. This study aimed to explore whether vaginal dilation was still effective for cervical cancer survivors who had not received timely vaginal dilation. The results showed that these patients still benefitted from vaginal dilation, irrespective of the treatment methods they received. Patients with a time interval from the last treatment less than 24 months or those who had moderate or good vaginal elasticity, benefitted more from vaginal dilation. The findings of the study is an indication to developing countries that more attention should be given to sexual issue of cervical cancer survivors in clinical practice, and vaginal dilation therapy should be performed promptly after treatment.

Bavachin Rejuvenates Sensitivity of Colistin against Colistin-Resistant Gram-Negative Bacteria.

The emergence of plasmid-mediated colistin resistance threatens the efficacy of colistin as a last-resort antibiotic used to treat infection caused by Gram-negative bacteria (GNB). Given the shortage of new antibiotics, the discovery of adjuvants to existing antibiotics is a promising strategy to combat infections caused by multidrug-resistant (MDR) GNB. This study was designed to investigate the potential synergistic antibacterial activity of bavachin, a bioactive compound extracted from the Psoralea Fructus, combined with colistin against MDR GNB. Herein, the synergistic efficacy in vitro and the therapeutic efficacy of colistin combined with bavachin in vivo were evaluated. The synergistic mechanism was detected by fluorescent probe and the transcript levels of mcr-1. Bavachin combined with colistin showed an excellent synergistic activity against GNB, as the FICI ≤ 0.5. In contrast to colistin alone, combination therapy dramatically increased the survival rate of Galleria mellonella and mice in vivo. Moreover, the combination of bavachin and colistin significantly reduced the amount of bacterial biofilm formation, improved the membrane disruption of colistin and inhibited mcr-1 transcription. These findings show that bavachin is a potential adjuvant of colistin, which may provide a new strategy to combat colistin-resistant bacteria infection with lower doses of colistin.

Emergence of brain-inspired small-world spiking neural network through neuroevolution.

Studies suggest that the brain's high efficiency and low energy consumption may be closely related to its small-world topology and critical dynamics. However, existing efforts on the performance-oriented structural evolution of spiking neural networks (SNNs) are time-consuming and ignore the core structural properties of the brain. Here, we introduce a multi-objective Evolutionary Liquid State Machine (ELSM), which blends the small-world coefficient and criticality to evolve models and guide the emergence of brain-inspired, efficient structures. Experiments reveal ELSM's consistent and comparable performance, achieving 97.23% on NMNIST and outperforming LSM models on MNIST and Fashion-MNIST with 98.12% and 88.81% accuracies, respectively. Further analysis shows its versatility and spontaneous evolution of topologies such as hub nodes, short paths, long-tailed degree distributions, and numerous communities. This study evolves recurrent spiking neural networks into brain-inspired energy-efficient structures, showcasing versatility in multiple tasks and potential for adaptive general artificial intelligence.

Mitochondria-Associated Protein FgNdk1 Regulates the Development, Pathogenicity, and SDHI Fungicide Sensitivity of Fusarium graminearum by Interacting with Succinate Dehydrogenase.

Nucleoside diphosphate kinase (NDK) plays an important role in many cellular processes in all organisms. In this study, we functionally characterized a nucleoside diphosphate kinase (FgNdk1) in Fusarium graminearum, a causal agent of Fusarium head blight (FHB). FgNdk1 was involved in the generation of energy in the electron-transfer chain by interacting with succinate dehydrogenase (FgSdhA, FgSdhC1, and FgSdhC2). Deletion of FgNdk1 not only resulted in abnormal mitochondrial morphology, decreased ATP content, defective fungal development, and impairment in the formation of the toxisome but also led to the suppressed expression level of DON biosynthesis enzymes, decreased DON biosynthesis, and declined pathogenicity as well. Furthermore, deletion of FgNdk1 caused increasing transcriptional levels of FgSdhC1 and FgdhC2, in the presence of pydiflumetofen, related to the decreased sensitivity to SDHI fungicides. Overall, this study identified a new regulatory mechanism of FgNdk1 in the pathogenicity and SDHI fungicide sensitivity of Fusarium graminearum.

Identification of therapeutic targets and prognostic biomarkers in the Siglec family of genes in tumor immune microenvironment of sarcoma.

Sarcomas (SARC) are a highly heterogeneous cancer type that is prone to recurrence and metastasis. Numerous studies have confirmed that Siglecs are involved in immune signaling and play a key role in regulating immune responses in inflammatory diseases and various cancers. However, studies that systematically explore the therapeutic and prognostic value of Siglecs in SARC patients are very limited. The online databases GEPIA, UALCAN, TIMER, The Kaplan-Meier Plotter, GeneMANIA, cBioPortal, and STING were used in this study. IHC staining was performed on the collected patient tissues, and clinical data were statistically analyzed. The transcript levels of most Siglec family members showed a high expression pattern in SARC. Compared with normal tissues, Siglec-5, Siglec-10, and Siglec-12 were abnormally highly expressed in tumor tissues. Importantly, Siglec-15 was significantly associated with poor prognosis. Functional enrichment analysis showed that the Siglec family was mainly enriched in hematopoietic cell lineages. The genes associated with molecular mutations in the Siglec family were mainly TP53 and MUC16, among which Siglec-2 and Siglec-15 were significantly associated with the survival of patients. The expression levels of all Siglec family members were significantly correlated with various types of immune cells (B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils and dendritic cells). Furthermore, a significant correlation was found between the somatic copy number changes of all Siglec molecules and the abundance of immune infiltrates. Our study paints a promising vision for the development of immunotherapy drugs and the construction of prognostic stratification models by investigating the therapeutic and prognostic potential of the Siglec family for SARC.

Bioactivity and Resistance Risk of Fluxapyroxad, a Novel SDHI Fungicide, in Didymella bryoniae.

Gummy stem blight, caused by Didymella bryoniae, is an important disease in watermelon in China. Fluxapyroxad, a new succinate dehydrogenase inhibitor fungicide, shows strong inhibition of the mycelia growth of D. bryoniae. However, its resistance risk in D. bryoniae is unclear. In this research, the sensitivities of 60 D. bryoniae strains to fluxapyroxad were investigated. The average EC50 value and MIC values of 60 D. bryoniae strains against fluxapyroxad were 0.022 ± 0.003 µg/ml and ≤0.1 µg/ml for mycelial growth, respectively. Eight fluxapyroxad-resistant mutants with medium resistance levels were acquired from three wild-type parental strains. The mycelial growth and dry weight of mycelia of most mutants were significantly lower than those of their parental strains. However, four resistant mutants showed a similar phenotype in pathogenicity compared with their parental strains. The above results demonstrated that there was a medium resistance risk for fluxapyroxad in D. bryoniae. The cross-resistance assay showed that there was positive cross-resistance between fluxapyroxad and pydiflumetofen, thifluzamide, and boscalid, but there was no cross-resistance between fluxapyroxad and tebuconazole and mepronil. These results will contribute to evaluating the resistance risk of fluxapyroxad for managing diseases caused by D. bryoniae and further increase our understanding about the mode of action of fluxapyroxad.

Admission Inflammation Markers Influence Long-term Mortality in Elderly Patients Undergoing Hip Fracture Surgery: A Retrospective Cohort Study.

OBJECTIVES: Hip fractures in elderly patients are associated with a high mortality rate. Most deaths associated with hip fracture result from complications after surgery. Recent studies suggest that some inflammation biomarkers may be useful to estimate excess mortality. This study aimed to investigate the prognostic value of admission inflammation biomarkers in elderly patients with hip fracture. METHODS: We reports on a retrospective study of elderly hip fracture patients admitted to a hospital in China between January 2015 and December 2019. A total of 1085 patients were included in the study, and their demographic and pre-operative characteristics were analyzed. The inflammation biomarkers included monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP) to albumin ratio (CAR). The predictive performance of NLR, MLR and CAR was assessed by receiver operating characteristics (ROC) curve analysis and the association between admission inflammation markers and mortality was evaluated by Cox proportional regression. RESULTS: The 30-day, 1-year, 2-year, and 4-year mortality were 1.6%, 11.5%, 21.4% and 48.9%, respectively. The optimal cut-off values of admission NLR, MLR and CAR for 1-year mortality were 7.28, 0.76, and 1.36. After adjusting the covariates, preoperative NLR ≥ 7.28 (HR = 1.419, 95% CI: 1.080-1.864, p = 0.012) were found to be only independent risk factors with 4-year all-cause mortality, the preoperative CAR ≥ 1.36 was independently associated with 1-year (HR = 1.700, 95% CI: 1.173-2.465, p = 0.005), 2 year (HR = 1.464, 95% CI: 1.107-1.936, p = 0.008), and 4-year (HR = 1.341, 95% CI: 1.057-1.700, p = 0.016) all-cause mortality, While age, CCI score, and low hemoglobin at admission were also risk factors for postoperative all-cause mortality. CONCLUSION: Admission CAR and NLR may be useful indicators for predicting the long-term mortality of elderly patients undergoing hip fracture surgery, and that more research is needed to validate these findings.

Osteoclasts in Osteosarcoma: Mechanisms, Interactions, and Therapeutic Prospects.

Osteosarcoma is an extremely malignant tumor, and its pathogenesis is complex and remains incompletely understood. Most cases of osteosarcoma are accompanied by symptoms of bone loss or result in pathological fractures due to weakened bones. Enhancing the survival rate of osteosarcoma patients has proven to be a long-standing challenge. Numerous studies mentioned in this paper, including in-vitro, in-vivo, and in-situ studies have consistently indicated a close association between the symptoms of bone loss associated with osteosarcoma and the presence of osteoclasts. As the sole cells capable of bone resorption, osteoclasts participate in a malignant cycle within the osteosarcoma microenvironment. These cells interact with osteoblasts and osteosarcoma cells, secreting various factors that further influence these cells, disrupting bone homeostasis, and shifting the balance toward bone resorption, thereby promoting the onset and progression of osteosarcoma. Moreover, the interaction between osteoclasts and various other cells types, such as tumor-associated macrophages, myeloid-derived suppressor cells, DCs cells, T cells, and tumor-associated fibroblasts in the osteosarcoma microenvironment plays a crucial role in disease progression. Consequently, understanding the role of osteoclasts in osteosarcoma has sparked significant interest. This review primarily examines the physiological characteristics and functional mechanisms of osteoclasts in osteosarcoma, and briefly discusses potential therapies targeting osteoclasts for osteosarcoma treatment. These studies provide fresh ideas and directions for future research on the treatment of osteosarcoma.

Simplified Intrafemoral Injections Using Live Mice Allow for Continuous Bone Marrow Analysis.

Despite the complexity of hematopoietic cell transplantation in humans, researchers commonly perform intravenous or intrafemoral (IF) injections in mice. In murine models, this technique has been adapted to enhance the seeding efficiency of transplanted hematopoietic stem and progenitor cells (HSPCs). This paper describes a detailed step-by-step technical procedure of IF injection and the following bone marrow (BM) aspiration in mice that allows for serial characterization of cells present in the BM. This method enables the transplantation of valuable samples with low cell numbers that are particularly difficult to engraft by intravenous injection. This procedure facilitates the creation of xenografts that are critical for pathological analysis. While it is easier to access peripheral blood (PB), the cellular composition of PB does not reflect the BM, which is the niche for HSPCs. Therefore, procedures providing access to the BM compartment are essential for studying hematopoiesis. IF injection and serial BM aspiration, as described here, allow for the prospective retrieval and characterization of cells enriched in the BM, such as HSPCs, without sacrificing the mice.

Adaptive structure evolution and biologically plausible synaptic plasticity for recurrent spiking neural networks.

The architecture design and multi-scale learning principles of the human brain that evolved over hundreds of millions of years are crucial to realizing human-like intelligence. Spiking neural network based Liquid State Machine (LSM) serves as a suitable architecture to study brain-inspired intelligence because of its brain-inspired structure and the potential for integrating multiple biological principles. Existing researches on LSM focus on different certain perspectives, including high-dimensional encoding or optimization of the liquid layer, network architecture search, and application to hardware devices. There is still a lack of in-depth inspiration from the learning and structural evolution mechanism of the brain. Considering these limitations, this paper presents a novel LSM learning model that integrates adaptive structural evolution and multi-scale biological learning rules. For structural evolution, an adaptive evolvable LSM model is developed to optimize the neural architecture design of liquid layer with separation property. For brain-inspired learning of LSM, we propose a dopamine-modulated Bienenstock-Cooper-Munros (DA-BCM) method that incorporates global long-term dopamine regulation and local trace-based BCM synaptic plasticity. Comparative experimental results on different decision-making tasks show that introducing structural evolution of the liquid layer, and the DA-BCM regulation of the liquid layer and the readout layer could improve the decision-making ability of LSM and flexibly adapt to rule reversal. This work is committed to exploring how evolution can help to design more appropriate network architectures and how multi-scale neuroplasticity principles coordinated to enable the optimization and learning of LSMs for relatively complex decision-making tasks.

Evaluating the Antibacterial and Antivirulence Activities of Floxuridine against Streptococcus suis.

Streptococcus suis is an emerging zoonotic pathogen that can cause fatal diseases such as meningitis and sepsis in pigs and human beings. The overuse of antibiotics is leading to an increased level of resistance in S. suis, and novel antimicrobial agents or anti-virulence agents for the treatment of infections caused by S. suis are urgently needed. In the present study, we investigated the antibacterial activity, mode of action and anti-virulence effects of floxuridine against S. suis. Floxuridine showed excessive antibacterial activity against S. suis both in vivo and in vitro; 4 × MIC of floxuridine could kill S. suis within 8 h in a time-kill assay. Meanwhile, floxuridine disrupted the membrane structure and permeability of the cytoplasmic membrane. Molecular docking revealed that floxuridine and SLY can be directly bind to each other. Moreover, floxuridine effectively inhibited the hemolytic capacity and expression levels of the virulence-related genes of S. suis. Collectively, these results indicate that the FDA-approved anticancer drug floxuridine is a promising agent and a potential virulence inhibitor against S. suis.

Using organoids to investigate human endometrial receptivity.

The human endometrium is only receptive to an implanting blastocyst in the mid-secretory phase of each menstrual cycle. Such time-dependent alterations in function require intricate interplay of various factors, largely coordinated by estrogen and progesterone. Abnormal endometrial receptivity is thought to contribute to two-thirds of the implantation failure in humans and therefore significantly hindering IVF success. Despite the incontrovertible importance of endometrial receptivity in implantation, the precise mechanisms involved in the regulation of endometrial receptivity remain poorly defined. This is mainly due to a lack of proper in vitro models that recapitulate the in vivo environment of the receptive human endometrium. Organoids were recently established from human endometrium with promising features to better mimic the receptive phase. Endometrial organoids show long-term expandability and the capability to preserve the structural and functional characteristics of the endometrial tissue of origin. This three-dimensional model maintains a good responsiveness to steroid hormones in vitro and replicates key morphological features of the receptive endometrium in vivo, including pinopodes and pseudostratified epithelium. Here, we review the current findings of endometrial organoid studies that have been focused on investigating endometrial receptivity and place an emphasis on methods to further refine and improve this model.

Effects of production-living-ecological space changes on the ecosystem service value of the Yangtze River Delta urban agglomeration in China.

In the process of urbanization, exploring the relationship between production-living-ecological space (PLES) and ecosystem service value (ESV) is a major scientific issue in promoting regional sustainable development. The Yangtze River Delta (YRD) urban agglomeration is an ideal study area, which has the highest urbanization rate in China. Based on Landsat TM/ETM imaging data from 2005, 2010, 2015, and 2018, this study established a land use classification system of PLES. The spatial and temporal characteristics of PLES and ESV were analyzed, and the response of ESV to changes in PLES was investigated based on the elasticity formula. The results showed that from 2005 to 2018, production space and ecological space were the main types of PLES and exhibited an imbalance in transformation. Production space was the main transfer type, and living space significantly expanded. Moreover, from 2005 to 2018, the ESV of the YRD urban agglomeration showed an increasing and then decreasing trend. ESV presented a "high in the southwest and low in the northeast" spatial pattern. Furthermore, ESV was sensitive to changes in PLES, showing a trend of ecological space > production space > living space. However, the sensitivity of ESV to changes in PLES varied according to urbanization level.

The meta-analysis of sister chromatid exchange as a biomarker in healthcare workers with occupational exposure to antineoplastic drugs.

BACKGROUND: Sister chromatid exchange (SCE) can be used to identify early occupational health status in health care workers. Our aim is to comprehensively assess the relationship between long-term exposure to antineoplastic drugs (ADs) and SCE in health care workers via meta-analysis. METHODS: Five databases were systematically searched for relevant articles published from inception to November 30, 2022. Literature data are expressed as mean difference and 95% confidence intervals (CI) or relative risk and 95% CI. For I2 > 50% trials, random effect model is used for statistical analysis, otherwise fixed effect model is used. This review was registered in the International Prospective Register of Systematic Reviews (identifier CRD42023399914). RESULTS: Fourteen studies were included in this study. Results showed the level of SCE in healthcare workers exposed to ADs was significantly higher than in controls. The mean difference of the SCE trial was 0.53 (95% CI: 0.10-0.95, P = .01) under a random-effects model. CONCLUSIONS: The findings suggested a significant correlation between occupational exposure to ADs in health care workers and SCE, requiring the attention of health care workers in general.

Study on the changes of LHR, FSHR and AR with the development of testis cells in Hu sheep.

The process of testis development in mammals is accompanied by the proliferation and maturation of Sertoli, Leydig and germ cells. Spermatogenesis depends on hormone regulation, which must bind to a receptor to exert its biological effects. The changes in Hu sheep testis cell composition and FSHR, LHR and AR expression during different developmental stages are unclear (newborn, puberty and adulthood). To address this, using single-cell RNA sequencing, we analyzed testis cell composition and hormone receptor expression changes during three important developmental stages of Hu sheep. We observed significant changes in the composition of somatic and germ cells in different Hu sheep testis developmental stages. Furthermore, we analyzed the FSHR, LHR and AR distribution and expression changes at three important periods and verified them by qRT-PCR and immunofluorescence. Our results suggest that after birth, the proportion of germ cells increased gradually, peaking in adulthood; the proportion of Sertoli cells decreased gradually, reaching the lowest in adulthood; and the proportion of Leydig cells increased and then decreased, reaching the lowest in adulthood. In addition, FSHR, LHR and AR are mainly located in Sertoli, Leydig and germ cells. LHR and FSHR expression decreased with increasing age, while AR expression increased and then decreased with increasing age.