Identification and function analysis of BCL2 in immune response of Pteria penguin.

B-cell lymphoma/leukemia-2 (BCL2), an anti-apoptotic factor in the mitochondrial regulatory pathway of apoptosis, is critically important in immune defenses. In this study, a novel BCL2 gene was characterized from Pteria penguin (P. penguin). The PpBCL2 was 1482 bp long, containing an open reading frame (ORF) of 588 bp encoding 195 amino acids. Four highly conserved BCL-2 homology (BH) domains were found in PpBCL2. Amino acid alignment and phylogenetic tree showed that PpBCL2 had the highest similarity with BCL2 of Crassostrea gigas at 65.24 %. Tissue expression analysis showed that PpBCL2 had high constitutive expression in gill, digestive diverticulum and mantle, and was significantly increased 72 h of Vibrio parahaemolyticus (V. parahaemolyticus) challenge in these immune tissues. Furthermore, PpBCL2 silencing significantly inhibited antimicrobial activity of hemolymph supernatant by 1.4-fold, and significantly reduced the survival rate by 51.7 % at 72 h post infection in P. penguin. These data indicated that PpBCL2 played an important role in immune response of P. penguin against V. parahaemolyticus infection.

A deep-learning-based genomic status estimating framework for homologous recombination deficiency detection from low-pass whole genome sequencing.

Genome-wide sequencing allows for prediction of clinical treatment responses and outcomes by estimating genomic status. Here, we developed Genomic Status scan (GSscan), a long short-term memory (LSTM)-based deep-learning framework, which utilizes low-pass whole genome sequencing (WGS) data to capture genomic instability-related features. In this study, GSscan directly surveys homologous recombination deficiency (HRD) status independent of other existing biomarkers. In breast cancer, GSscan achieved an AUC of 0.980 in simulated low-pass WGS data, and obtained a higher HRD risk score in clinical BRCA-deficient breast cancer samples (p = 1.3 × 10-4, compared with BRCA-intact samples). In ovarian cancer, GSscan obtained higher HRD risk scores in BRCA-deficient samples in both simulated data and clinical samples (p = 2.3 × 10-5 and p = 0.039, respectively, compared with BRCA-intact samples). Moreover, HRD-positive patients predicted by GSscan showed longer progression-free intervals in TCGA datasets (p = 0.0011) treated with platinum-based adjuvant chemotherapy, outperforming existing low-pass WGS-based methods. Furthermore, GSscan can accurately predict HRD status using only 1 ng of input DNA and a minimum sequencing coverage of 0.02 × , providing a reliable, accessible, and cost-effective approach. In summary, GSscan effectively and accurately detected HRD status, and provide a broadly applicable framework for disease diagnosis and selecting appropriate disease treatment.

Coupling coefficient calculation and optimization of positive rectangular series coils in wireless power transfer systems.

In wireless power transfer (WPT) systems using magnetic coupling resonance, when there is a registration deviation between the transmitting and receiving coils, there will be significant fluctuations in the coupling coefficient, output power, and transmission efficiency, which will seriously affect the stability of the WPT system. The coupling coefficient is related to the length and width of the rectangular coil, number of turns, mutual geometric position, and space magnetic medium, making it difficult to maintain a constant value when the coil is offset. A single-emitter two-receiver positive-series rectangular coils structure and a method of calculating the structure are proposed. Then an optimization method for mutual inductance was proposed, and the structural parameters that met the design requirements were obtained using the proposed optimization method. The calculation formula for coupling coefficient was verified through simulation and experiments. The results showed that when the offset distance of the receiving coil along the Y-axis (driving direction) and X-axis reaches half of the length of the transmitting coil and 10 cm, the coupling coefficient, transmission efficiency, and output power remain almost unchanged.

Cadmium facilitates the formation of large lipid droplets via PLCß2-DAG-DGKε-PA signal pathway in Leydig cells.

Cadmium (Cd) exposure damages the reproductive system. Lipid droplets (LDs) play an important role in steroid-producing cells to provide raw material for steroid hormone. We have found that the LDs of Leydig cells exposed to Cd are bigger than those of normal cells, but the effects on steroidogenesis and its underlying mechanism remains unclear. Using Isobaric tag for relative and absolute quantitation (iTARQ) proteomics, phosphodiesterase beta-2 (PLCß2) was identified as the most significantly up-regulated protein in immature Leydig cells (ILCs) and adult Leydig cells (ALCs) derived from male rats exposed to maternal Cd. Consistent with high expression of PLCß2, the size of LDs was increased in Leydig cells exposed to Cd, accompanied by reduction in cholesterol and progesterone (P4) levels. However, the high PLCß2 did not result in high diacylglycerol (DAG) level, because Cd exposure up-regulated diacylglycerol kinases ε (DGKε) to promote the conversion from DAG to phosphatidic acid (PA). Exogenous PA, which was consistent with the intracellular PA concentration induced by Cd, facilitated the formation of large LDs in R2C cells, followed by reduced P4 level in the culture medium. When PLCß2 expression was knocked down, the increased DGKε caused by Cd was reversed, and then the PA level was decreased to normal. As results, large LDs returned to normal size, and the level of total cholesterol was improved to restore steroidogenesis. The accumulation of PA regulated by PLCß2-DAG-DGKε signal pathway is responsible for the formation of large LDs and insufficient steroid hormone synthesis in Leydig cells exposed to Cd. These data highlight that LD is an important target organelle for Cd-induced steroid hormone deficiency in males.

An Integrated Multi-Functional Thermal Conductive and Flame Retardant Epoxy Composite with Functionalized Carbon Nitride Nanosheets.

In miniaturized and integrated electronic devices, thermal potential and fire hazards caused by heat diffusion require an efficient thermal management system with versatile electronic packaging equipment. The flame retardancy was endowed on the surface of carbon nitride after thermal etching (CNNS) containing piperazine pyrophosphate (PPAP) by hydrogen bonding, and the obtained nanosheet was defined as PPAP-CNNS. During solution blending and program-controlled curing, PPAP-CNNS was used as a multifunctional filler to fabricate highly thermoconductive and fire retardant epoxy resin (EP) composites. In line with expectations, the resultant EP composites containing 7 wt% PPAP-CNNS had an exceptional thermal conductivity (TC) of 1.1 W·m-1K-1, which was 4.8 times higher than pure EP. Simultaneously, there was a sharp drop in the heat release rate (HRR), total heat release (THR), smoke production rate (SPR), and total smoke production (TSP) compared to pure EP. These reductions were, respectively, 63.7%, 54.2%, 17.9%, and 57.2%. The addition of PPAP-CNNS increased the specific surface area, which increased the heat conduction routes, and also the shape of the compact and solid char layer during burning, protecting the underlying polymer. These improvements to dispersion and surface functionalization were made possible by the compound. These results indicate that the preparation of integrated multi-functional resin described in this study has a wide application.

Homologous recombination deficiency prediction using low-pass whole genome sequencing in breast cancer.

Homologous recombination repair deficiency (HRD) results in a defect in DNA repair and is a frequent driver of tumorigenesis. Poly(ADP-ribose) polymerase inhibitors (PARPi) or platinum-based therapies have increased theraputic effectiveness when treating HRD positive cancers. For breast cancer and ovairan cancer HRD companion diagnostic tests are commonly used. However, the currently used HRD tests are based on high-depth genome sequencing or hybridization-based capture sequencing, which are technically complex and costly. In this study, we modified an existing method named shallowHRD, which uses low-pass whole genome sequencing (WGS) for HRD detection, and estimated the performance of the modified shallowHRD pipeline. Our shallowHRD pipeline achieved an AUC of 0.997 in simulated low-pass WGS data, with a sensitivity of 0.981 and a specificity of 0.964; and achieved a higher HRD risk score in clinical BRCA-deficient breast cancer samples (p = 5.5 × 10-5, compared with BRCA-intact breast cancer samples). We also estimated the limit of detection the shallowHRD pipeline could accurately predict HRD status with a minimum sequencing depth of 0.1 ×, a tumor purity of > 20%, and an input DNA amount of 1 ng. Our study demostrates using low-pass sequencing, HRD status can be determined with high accuracy using a simple approach with greatly reduced cost.

Dietary supplementation with selenium polysaccharide from selenium-enriched Phellinus linteus improves antioxidant capacity, immunity and production performance of laying hens.

BACKGROUND: Selenium (Se) plays a beneficial role in the physiological function of humans and animals. Selenium polysaccharide, improving enzyme activity and regulating immunity, is the extraction from selenium-rich plants or mushrooms. This study aimed to evaluate the effect of selenium polysaccharide from selenium-enriched Phellinus linteus on the antioxidative ability, immunity, serum biochemistry, and production performance of laying hens. METHODS: Three hundred sixty adult laying hens were randomly assigned to 4 groups. The four groups were divided as follows: CK (control group), PS group (4.2 g/kg polysaccharide), Se group (0.5 Se mg/kg), and PSSe group (4.2 g/kg with 0.5 Se mg/kg, Selenium polysaccharide). RESULTS: After the 8 weeks, the hens were sampled and the antioxidant ability(total antioxidant (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and Nitric Oxide (NO)), immunity(Interleukin-2(IL-2), Immunoglobulin M(IgM), Immunoglobulin A(IgA), Immunoglobulin G(IgG) and interferon-gamma (IFN-γ) and secretory Immunoglobulin A(sIgA)), serum biochemistry(total protein, triglycerides, total cholesterol, glucose, glutamic-pyruvictransaminase (ALT), and aspartate transaminase (AST)) and production performance were assessed. Compared with the control group, T-AOC, SOD, CAT, GSH, IL-2, IgM, IgA, sIgA, IgG, IFN-γ, total protein, average laying rate, average egg weight, and final body were significantly increased in the PS, Se, and PSSe groups, however, the MDA and NO, triglyceride, cholesterol, glucose, AST, ALT, average daily feed consumption, and feed conversion ratio were significantly decreased in the PS, Se, and PSSe groups. The PSSe group in the immune index, antioxidant ability and serum biochemistry was improved the highest. CONCLUSION: The result suggested that selenium polysaccharide from selenium-enriched Phellinus linteus can enhance the antioxidant ability and immunity, change serum biochemistry, providing a new method for improving the production performance of laying hens.

Presence of Viable, Clinically Relevant Legionella Bacteria in Environmental Water and Soil Sources of China.

The distribution of pathogenic Legionella in the environmental soil and water of China has not been documented yet. In this study, Legionella was detected in 129 of 575 water (22.43%) and 41 of 442 soil samples (9.28%) by culture. Twelve Legionella species were identified, of which 11 were disease-associated. Of the Legionella-positive samples, 109 of 129 (84.50%) water and 29 of 41 (70.73%) soil were positive for L. pneumophila, which accounted for about 75% of Legionella isolates in both water and soil, suggesting L. pneumophila was the most frequent species. Soil showed a higher diversity of Legionella spp. as compared with water (0.6279 versus 0.4493). In contrast, serogroup (sg) 1 was more prevalent among L. pneumophila isolates from water than from soil (26.66% versus 12.21%). Moreover, many disease-associated sequence types (STs) of L. pneumophila were found in China. Intragenic recombination was acting on L. pneumophila from both water and soil. Phylogeny, population structure, and molecular evolution analyses revealed a probable existence of L. pneumophila isolates with a special genetic background that is more adaptable to soil or water sources and a small proportion of genetic difference between water and soil isolates. The detection of viable, clinically relevant Legionella demonstrates soil as another source for harboring and dissemination of pathogenic Legionella bacteria in China. Future research should assess the implication in public health with the presence of Legionella in the soil and illustrate the genetic and pathogenicity difference of Legionella between water and soil, particularly the most prevalent L. pneumophila. IMPORTANCE Pathogenic Legionella spp. is the causative agent of Legionnaires' disease (LD), and L. pneumophila is the most common one. Most studies have focused on L. pneumophila from water and clinical samples. However, the soil is another important reservoir for this bacterium, and the distribution of Legionella spp. in water and soil sources has not been compared and documented in China yet. Discovering the distribution of Legionella spp. and L. pneumophila in the two environments may help a deep understanding of the pathogenesis and molecular evolution of the bacterium. Our research systematically uncovered the distributions of Legionella spp. in different regions and sources (e.g., water and soil) of China. Moreover, phylogeny, population structure, and molecular evolution study revealed the possible existence of L. pneumophila with a special genetic background that is more adaptable to soil or water sources, and genetic difference may exist.

Ecological management model for the improvement of soil fertility through the regulation of rare microbial taxa in tea (Camellia sinensis L.) plantation soils.

Agricultural management is essential to enhance soil ecosystem service function through optimizing soil physical conditions and improving nutrient supply, which is predominantly regulated by soil microorganisms. Several studies have focused on soil biodiversity and function in tea plantation systems. However, the effects of different agriculture managements on soil fertility and microbes remain poorly characterized, especially for what concerns perennial agroecosystems. In this study, 40 soil samples were collected from 10 tea plantation sites in China to explore the effects of ecological and conventional managements on soil fertility, as well as on microbial diversity, community composition, and co-occurrence network. Compared with conventional management, ecological management was found to significantly enhance soil fertility, microbial diversity, and microbial network complexity. Additionally, a significant difference in community composition was clearly observed under the two agriculture managements, especially for rare microbial taxa, whose relative abundance significantly increased under ecological management. Random forest modeling revealed that rare taxa (e.g., Rokubacteria and Mortierellomycota), rather than dominant microbial taxa (e.g., Proteobacteria and Ascomycota), were key variables for predicting soil fertility. This indicates that rare taxa might play a fundamental role in biological processes. Overall, our results suggest that ecological management is more efficient than conventional management in regulating rare microbial taxa and maintaining a good soil fertility in tea plantation systems.

GDPLichi: a DNA Damage Repair-Related Gene Classifier for Predicting Lung Adenocarcinoma Immune Checkpoint Inhibitors Response.

Lung cancer is one of the most common and mortal malignancies, usually with a poor prognosis in its advanced or recurrent stages. Recently, immune checkpoint inhibitors (ICIs) immunotherapy has revolutionized the treatment of human cancers including lung adenocarcinoma (LUAD), and significantly improved patients' prognoses. However, the prognostic and predictive outcomes differ because of tumor heterogeneity. Here, we present an effective method, GDPLichi (Genes of DNA damage repair to predict LUAD immune checkpoint inhibitors response), as the signature to predict the LUAD patient's response to the ICIs. GDPLichi utilized only 7 maker genes from 8 DDR pathways to construct the predictive model and classified LUAD patients into two subgroups: low- and high-risk groups. The high-risk group was featured by worse prognosis and decreased B cells, CD8+ T cells, CD8+ central memory T cells, hematopoietic stem cells (HSC), myeloid dendritic cells (MDC), and immune scores as compared to the low-risk group. However, our research also suggests that the high-risk group was more sensitive to ICIs, which might be explained by increased TMB, neoantigen, immune checkpoint molecules, and immune suppression genes' expression, but lower TIDE score as compared to the low-risk group. This conclusion was verified in three other LUAD cohort datasets (GSE30219, GSE31210, GSE50081).

Virulence effector SidJ evolution in Legionella pneumophila is driven by positive selection and intragenic recombination.

Effector proteins translocated by the Dot/Icm type IV secretion system determine the virulence of Legionella pneumophila (L. pneumophila). Among these effectors, members of the SidE family (SidEs) regulate several cellular processes through a unique phosphoribosyl ubiquitination mechanism mediated by another effector, SidJ. Host-cell calmodulin (CaM) activates SidJ to glutamylate the SidEs of ubiquitin (Ub) ligases and to make a balanced Ub ligase activity. Given the central role of SidJ in this regulatory process, studying the nature of evolution of sidJ is important to understand the virulence of L. pneumophila and the interaction between the bacteria and its hosts. By studying sidJ from a large number of L. pneumophila strains and using various molecular evolution algorithms, we demonstrated that intragenic recombination drove the evolution of sidJ and contributed to sidJ diversification. Additionally, we showed that four codons of sidJ which are located in the N-terminal (NTD) (codons 58 and 200) and C-terminal (CTD) (codons 868 and 869) domains, but not in the kinase domain (KD) had been subjected to strong positive selection pressure, and variable mutation profiles of these codons were identified. Protein structural modeling of SidJ provided possible explanations for these mutations. Codons 868 and 869 mutations might engage in regulating the interactions of SidJ with CaM through hydrogen bonds and affect the CaM docking to SidJ. Mutation in codon 58 of SidJ might affect the distribution of main-chain atoms that are associated with the interaction with CaM. In contrast, mutations in codon 200 might influence the α-helix stability in the NTD. These mutations might be important to balance Ub ligase activity for different L. pneumophila hosts. This study first reported that intragenic recombination and positive Darwinian selection both shaped the genetic plasticity of sidJ, contributing to a deeper understanding of the adaptive mechanisms of this intracellular bacterium to different hosts.

[Effects of Roxithromycin on Reproduction,Growth, and Anti-oxidation System of Daphnia magna].

Roxithromycin (ROX) is widespread in the water environment and has been reported to have ecotoxicological effects on aquatic organisms. To improve our understanding of these effects, we selected Daphnia magna as a test organism to study acute and chronic ROX toxicity on reproduction, growth, and antioxidant systems. The acute ROX toxicity was low, with 48 h-LC50 and 96h-LC50ROX values of 60.26 mg·L-1 and 39.81 mg·L-1, respectively. Furthermore, ROX concentrations of 0.5 µg·L-1 and 50 µg·L-1 significantly increased the frequency of egg laying, total number of eggs, and number of eggs per fetus. In the early exposure stages, ROX altered the sexual maturation time of Daphnia magna, affecting the frequency of egg laying and the number of eggs per fetus to cope with environmental stress. The intrinsic growth rate was also significantly increased by 50 µg·L-1 ROX. In both treatment groups, Daphnia magna had a shorter body length, abnormal heart rate, and inhibited swimming activity. Moreover, 50 µg·L-1 ROX inhibited the activities of POD, CAT, and GSH-Px by approximately 50% and induced MDA by more than 100%, resulting in the accumulation of reactive oxygen species in the body, which could potentially damage the cell membrane. In the 50 µg·L-1 ROX treatment, per 06 was up-regulated, enhancing the immune response of Daphnia magna. In contrast. gst and gst-theta were down-regulated, suggesting that ROX could weaken the detoxification effect of Daphnia magna. jhe, ecra, ecrb, rxr, vg1, vg2, and vit-2 were also down-regulated. ROX affected the secretion of juvenile and thyroid hormones, inhibiting the synthesis of vitellogenin. Finally, ROX also affected the growth and disturbed the population stability of Daphnia magna. This study provides a reference for the effects of ROX on the reproduction and growth of aquatic organisms and their responses at protein and gene levels.

Dynamic behaviors of hyperbolic-type memristor-based Hopfield neural network considering synaptic crosstalk.

Crosstalk phenomena taking place between synapses can influence signal transmission and, in some cases, brain functions. It is thus important to discover the dynamic behaviors of the neural network infected by synaptic crosstalk. To achieve this, in this paper, a new circuit is structured to emulate the Coupled Hyperbolic Memristors, which is then utilized to simulate the synaptic crosstalk of a Hopfield Neural Network (HNN). Thereafter, the HNN's multi-stability, asymmetry attractors, and anti-monotonicity are observed with various crosstalk strengths. The dynamic behaviors of the HNN are presented using bifurcation diagrams, dynamic maps, and Lyapunov exponent spectrums, considering different levels of crosstalk strengths. Simulation results also reveal that different crosstalk strengths can lead to wide-ranging nonlinear behaviors in the HNN systems.

Micro/nano-structured TiO2 surface with dual-functional antibacterial effects for biomedical applications.

Implant-associated infections are generally difficult to cure owing to the bacterial antibiotic resistance which is attributed to the widespread usage of antibiotics. Given the global threat and increasing influence of antibiotic resistance, there is an urgent demand to explore novel antibacterial strategies other than using antibiotics. Recently, using a certain surface topography to provide a more persistent antibacterial solution attracts more and more attention. However, the clinical application of biomimetic nano-pillar array is not satisfactory, mainly because its antibacterial ability against Gram-positive strain is not good enough. Thus, the pillar array should be equipped with other antibacterial agents to fulfill the bacteriostatic and bactericidal requirements of clinical application. Here, we designed a novel model substrate which was a combination of periodic micro/nano-pillar array and TiO2 for basically understanding the topographical bacteriostatic effects of periodic micro/nano-pillar array and the photocatalytic bactericidal activity of TiO2. Such innovation may potentially exert the synergistic effects by integrating the persistent topographical antibacterial activity and the non-invasive X-ray induced photocatalytic antibacterial property of TiO2 to combat against antibiotic-resistant implant-associated infections. First, to separately verify the topographical antibacterial activity of TiO2 periodic micro/nano-pillar array, we systematically investigated its effects on bacterial adhesion, growth, proliferation, and viability in the dark without involving the photocatalysis of TiO2. The pillar array with sub-micron motif size can significantly inhibit the adhesion, growth, and proliferation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Such antibacterial ability is mainly attributed to a spatial confinement size-effect and limited contact area availability generated by the special topography of pillar array. Moreover, the pillar array is not lethal to S. aureus and E. coli in 24 h. Then, the X-ray induced photocatalytic antibacterial property of TiO2 periodic micro/nano-pillar array in vitro and in vivo will be systematically studied in a future work. This study could shed light on the direction of surface topography design for future medical implants to combat against antibiotic-resistant implant-associated infections without using antibiotics.

Exosomal transfer of obesity adipose tissue for decreased miR-141-3p mediate insulin resistance of hepatocytes.

Exosomes, the nano-vesicles released from living cells, were the important mediator for cell-to-cell communication. In order to clarify whether the exosomes derived from obesity adipose tissue mediate insulin resistance of hepatocytes, we extract the exosomes from the adipose tissue of different mice models. Exosomes derived from ob/ob mice (Ob-exosomes), B6 mice fed with a high-fat diet (HFD-exosomes) and normal B6 mice (WT-exosomes) displayed similar size and molecular makers, but their effect on the insulin sensitivity of hepatocytes were obviously different or opposite. Abundant exosomal miRNAs in Ob-, HFD- and WT-exosomes were detected by the Next Generation Sequencing. The levels of miR-141-3p in Ob- and HFD-exosomes were significantly lower than WT-exosomes. MiR-141-3p can be effectively delivered into AML12 cells accompanied by the absorption of exosomes, but the absorption of miR-141-3p into AML12 cells could be blocked by GW4869, an inhibitor of exosome biogenesis and release. Importantly, the Ob-exosomes or miR-141-3p knockdown in WT--exosomes obviously inhibited the insulin response and glucose uptake of AML12 cells, however, the inhibitory effects on insulin function disappeared after the overexpression of miR-141-3p in Ob-exosomes or AML12 cells. The effects of miR-141-3p on insulin function could be achieved by improving the level of phosphorylation of AKT and enhancing insulin signal transduction. Therefore, the absorption of hepatocytes for exosomes released from obesity adipose tissue containing less miR-141-3p than healthy adipose tissue can significantly inhibit the insulin sensitivity and glucose uptake. Our study may certify a novel mechanism that the secretion of "harmful" exosomes from obesity adipose tissues cause insulin resistance.

Hormonal changes and folliculogenesis in female offspring of rats exposed to cadmium during gestation and lactation.

It has been suggested that the toxic effects of cadmium (Cd) may disrupt ovarian and uterine functions in adults. However, Cd exposure during gestation and lactation and its effects on the reproductive development in female offspring is still not clear, and the mechanisms underlying exposure toxicology remain mostly unexplored. To investigate how Cd exposure of female rats (F0) during gestation and lactation affects the reproductive development of their female offspring, we studied the steroidogenesis, folliculogenesis, puberty onset, and litter size of the first (F1) and second (F2) filial generations following F0 female rats which had been exposed to CdCl2. The mechanisms related to the early onset of puberty induced by such exposure in female offspring were explored. Maternal exposure to Cd dramatically increased the biosynthesis of steroid hormones in F1 female offspring by the activation of cAMP/PKA pathway and up-regulated expression of steroidogenesis related proteins such as StAR, CYP11A1, 3ß-HSD and CYP19A1. The high levels of steroid hormones contributed to an early puberty onset, promoted the differentiation and maturation of follicles, and led to the proliferation of endometrium that resulted in a uterus weight gain. The increased number of antral follicles eventually caused a big litter size. Despite of being free from additional Cd exposure, the levels of CYP11A1 and CYP19A1 in the ovaries of F2 female rats were also high, which resulted in a high concentration of serum progesterone. These results suggested that hormonal changes induced by exposure to Cd in utero might have a lasting effect beyond the first generation. These findings may help to better understand the origin of female sexual dysfunction in the developmental stages in general.

Exposure to cadmium during gestation and lactation affects development and function of Leydig cells in male offspring.

Toxic effects of maternal exposure to Cadmium (Cd) on Leydig cells of male offspring arises much concern recently, but its toxic effects on the development of Leydig cells and androgen synthesis have not been elucidated. In this study, female rats were exposed to Cd during gestation and lactation, and the development of Leydig cells in the first filial-generation (F1) male rats was investigated. The steroidogenic signaling pathway and biomarkers related to the development of Leydig cells were detected to disclose how maternal Cd-exposure caused reproductive damage. F1 male rats with maternal Cd-exposure gained a low relative weight of testis and declined levels of steroid hormones. Maternal Cd-exposure interrupted the development of Leydig cells with high expression of SRD5α and cell morphology of immature Leydig cells in adulthood, inhibited the activation of cyclic adenosine monophosphate/ protein kinase A signaling pathway and down-regulated the steroidogenic enzymes. These results would help to disclose the origin of male sexual dysfunction in the developmental stages of Leydig cells.

Assessment of balance and vestibular functions in patients with idiopathic sudden sensorineural hearing loss.

This study investigated the relationship among the severity of hearing impairment, vestibular function and balance function in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). A total of 35 ISSNHL patients (including 21 patients with vertigo) were enrolled. All of the patients underwent audiometry, sensory organization test (SOT), caloric test, cervical vestibular-evoked myogenic potential (cVEMP) test and ocular vestibular-evoked myogenic potential (oVEMP) test. Significant relationship was found between vertigo and hearing loss grade (P=0.009), and between SOT VEST grade and hearing loss grade (P=0.001). The abnormal rate of oVEMP test was the highest, followed by the abnormal rates of caloric and cVEMP tests, not only in patients with vertigo but also in those without vertigo. The vestibular end organs were more susceptible to damage in patients with vertigo (compared with patients without vertigo). Significant relationship was found between presence of vertigo and SOT VEST grade (P=0.010). We demonstrated that vestibular end organs may be impaired not only in patients with vertigo but also in patients without vertigo. The cochlear and vestibular impairment could be more serious in patients with vertigo than in those without vertigo. Vertigo does not necessarily bear a causal relationship with the impairment of the vestibular end organs. SOT VEST grade could be used to reflect the presence of vertigo state in the ISSNHL patients. Apart from audiometry, the function of peripheral vestibular end organs and balance function should be evaluated to comprehensively understand ISSNHL. Better assessment of the condition will help us in clinical diagnosis, treatment and prognosis evaluation of ISSNHL.

Assessment of Balance and Vestibular Functions in Patients with Idiopathic Sudden Sensorineural Hearing Loss / 华中科技大学学报（医学）（英德文版）

This study investigated the relationship among the severity of hearing impairment,vestibular function and balance function in patients with idiopathic sudden sensorineural hearing loss (ISSNHL).A total of 35 ISSNHL patients (including 21 patients with vertigo) were enrolled.All of the patients underwent audiometry,sensory organization test (SOT),caloric test,cervical vestibular-evoked myogenic potential (cVEMP) test and ocular vestibular-evoked myogenic potential (oVEMP) test.Significant relationship was found between vertigo and hearing loss grade (P=0.009),and between SOT VEST grade and hearing loss grade (P=0.001).The abnormal rate of oVEMP test was the highest,followed by the abnormal rates of caloric and cVEMP tests,not only in patients with vertigo but also in those without vertigo.The vestibular end organs were more susceptible to damage in patients with vertigo (compared with patients without vertigo).Significant relationship was found between presence of vertigo and SOT VEST grade (P=0.010).We demonstrated that vestibular end organs may be impaired not only in patients with vertigo but also in patients without vertigo.The cochlear and vestibular impairment could be more serious in patients with vertigo than in those without vertigo.Vertigo does not necessarily bear a causal relationship with the impairment of the vestibular end organs.SOT VEST grade could be used to reflect the presence of vertigo state in the ISSNHL patients.Apart from audiometry,the function of peripheral vestibular end organs and balance function should be evaluated to comprehensively understand ISSNHL.Better assessment of the condition will help us in clinical diagnosis,treatment and prognosis evaluation of ISSNHL.

Expression of glycine receptors and gephyrin in rat medial vestibular nuclei and flocculi following unilateral labyrinthectomy.

The medial vestibular nucleus (MVN) and the cerebellar flocculus have been known to be the key areas involved in vestibular compensation (VC) following unilateral labyrinthectomy (UL). In this study, we examined the role of gephyrin and glycine receptor (GlyR) in VC using Sprague-Dawley rats, in an aim to gain deeper insight into the mechanisms responsible for VC. The expression of the α1 and ß subunits of GlyR and gephyrin was immunohistochemically localized in rat MVN and flocculi. The mRNA and protein expression of GlyR (α1 and ß subunits) and gephyrin was quantitatively determined by RT-qPCR and western blot analysis at 8 h, and at 1, 3 and 7 days following UL. It was found that in the ipsilateral MVN, the mRNA and protein expression of the ß subunit of GlyR was significantly increased in comparison to the sham-operated (P<0.01) rats, and in comparison to the contralateral side (P<0.01) at 8 h following UL. In the ipsilateral flocculi, GlyR ß protein expression was significantly elevated (P<0.01 for all), as compared to the sham-operated rats at 8 h, and at 1 and 3 days and to the contralateral side 8 h, 1 and 3 days following UL. No significant differences were observed in the mRNA and protein expression of GlyR α1 and gephyrin in the MVN or flocculi between the two sides (ipsilateral and contralateral) in the UL group, and between the sham-operated group and the UL group at any time point. The findings of our study thus suggest that GlyR plays a major role in the recovery of the resting discharge of the deafferented MVN neurons in the central vestibular system.