Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing.

Nonobstructive azoospermia (NOA) is a severe condition in infertile men, and increasing numbers of causative genes have been identified during the last few decades. Although certain causative genes can explain the presence of NOA in some patients, a proportion of NOA patients remain to be addressed. This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing. Whole-exome sequencing was performed in 46 male patients diagnosed with NOA. First, screening was performed for 119 genes known to be related to male infertility. Next, further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls. Finally, risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed. The frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls. Potential risk genes that may be causes of NOA were identified, including seven genes that were highly/specifically expressed in the testes. Four risk genes previously reported to be involved in spermatogenesis (MutS homolog 5 [MSH5], cilia- and flagella-associated protein 54 [CFAP54], MAP7 domain containing 3 [MAP7D3], and coiled-coil domain containing 33 [CCDC33]) and three novel risk genes (coiled-coil domain containing 168 [CCDC168], chromosome 16 open reading frame 96 [C16orf96], and serine protease 48 [PRSS48]) were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls. This study on clinical NOA patients provides further evidence for the four previously reported risk genes. The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of NOA.

Characteristics of Families with Members Going Out for Work and Associated Factors among Persons with Schizophrenia in Rural China.

BACKGROUND: The characteristics associated with having family members going out for work among persons with schizophrenia in rural China are unknown. This study aimed to explore the characteristics of families with members going out for work and the risk factors among persons with schizophrenia in a rural area of China. METHODS: This study employed a cross-sectional dataset from a mental health survey, using the International Classification of Disease, Tenth Revision (ICD-10), conducted among 152,776 people aged 15 years and older in Xinjin District, Chengdu, China, in 2015. RESULTS: A total of 598 persons with schizophrenia were included in this study, and 20.4% (n = 122) of them had at least one family member who went out for work. Compared with those without family going out for work, participants with family going out for work had significantly larger numbers of family members, higher monthly incomes and lower percentages of social low-income insurance. Participants with family going out for work were more likely to be females, married and with higher levels of subjective and instrumental support. The statuses of families with members going out for work were significantly associated with larger numbers of family members and higher levels of instrumental support. CONCLUSIONS: Our findings indicate specific characteristics of families with members going out for work and factors associated with having family going out for work among persons with schizophrenia (number of family members and instrumental support). Culture-specific mental health policies and community-based services should be developed for persons with schizophrenia who have family going out for work in rural China.

Observing a topological phase transition with deep neural networks from experimental images of ultracold atoms.

Although classifying topological quantum phases have attracted great interests, the absence of local order parameter generically makes it challenging to detect a topological phase transition from experimental data. Recent advances in machine learning algorithms enable physicists to analyze experimental data with unprecedented high sensitivities, and identify quantum phases even in the presence of unavoidable noises. Here, we report a successful identification of topological phase transitions using a deep convolutional neural network trained with low signal-to-noise-ratio (SNR) experimental data obtained in a symmetry-protected topological system of spin-orbit-coupled fermions. We apply the trained network to unseen data to map out a whole phase diagram, which predicts the positions of the two topological phase transitions that are consistent with the results obtained by using the conventional method on higher SNR data. By visualizing the filters and post-convolutional results of the convolutional layer, we further find that the CNN uses the same information to make the classification in the system as the conventional analysis, namely spin imbalance, but with an advantage concerning SNR. Our work highlights the potential of machine learning techniques to be used in various quantum systems.

A near-infrared fluorescent probe based on the hemicyanine skeleton for the detection of hydrogen peroxide in vivo.

As a member of the reactive oxygen species, hydrogen peroxide (H2O2) plays critical roles in oxidative stress and cell signaling. Intracellular abnormal levels of H2O2 production are closely related to many diseases. Therefore, the real-time monitoring of H2O2 in the cells is important. In this work, we designed a novel fluorescent probe (Mito-H2O2) for the specific detection of H2O2 based on the hemicyanine skeleton, with bright near-infrared fluorescence emission. Mito-H2O2 displayed fast response, excellent water-solubility and great fluorescence intensity enhancement after the addition of H2O2. Furthermore, Mito-H2O2 has been successfully applied to image both of the exogenous and endogenous H2O2 in cells and mice with negligible cytotoxity.

Pollen micromorphology of eastern Chinese Polygonatum and its role in taxonomy by using scanning electron microscopy.

Although considerable progress has recently been made in the taxonomic study of Asparagaceae, but the Polygonatum remains one of the most poorly investigated genus. Therefore, the present study was designed with the aim, to document the pollen micromorphology of closely related Polygonatum taxa and its taxonomic significance. Pollen micro-morphological features were observed using scanning electron microscopy-SEM). The pollen grains are monad, navicular, monocolpate, and radially symmetrical. A significant variation was observed in the exine sculpturing. Moreover, most of the Polygonatum taxa have perforate pollen while some of them were mixed with psilate to perforate, perforate to microreticulate, sometimes scabrate, gemmate with baculate. Hence, this study documented the pollen morphology of Polygonatum taxa and strengthens the taxonomic identification of the genus Polygonatum based on pollen characters, which helps and can be used as an additional tool for the correct identification and discrimination of the species of Polygonatum at generic and species level.

Identification and Expression Profile of Olfactory Receptor Genes Based on Apriona germari (Hope) Antennal Transcriptome.

Insects' olfactory receptor plays a central role in detecting chemosensory information from the environment. Odorant receptors (ORs) and ionotropic receptors (IRs) are two types of olfactory receptors, and they are essential for the recognition of ligands at peripheral neurons. Apriona germari (Hope) (Coleoptera: Cerambycidae) is one of the most serious insect pests that cause damage to economic trees and landscaping trees, resulting in massive environmental damages and economic losses. Olfactory-based management strategy has been suggested as a promising strategy to control this wood-boring beetle. However, the olfactory perception mechanism in A. germari is now almost unknown. In the present study, RNA sequencing analysis was used to determine the transcriptomes of adult A. germari antennae. Among 36,834 unigenes derived from the antennal assembly, we identified 42 AgerORs and three AgerIRs. Based on the tissue expression pattern analysis, 27 AgerORs displayed a female-biased expression. Notably, AgerOR3, 5, 13, 33, and 40 showed a significant female-biased expression and were clustered with the pheromone receptors of Megacyllene caryae in the phylogenetic tree, suggesting that these AgerORs could be potential pheromone receptors for sensing male-produced sex pheromones in A. germari. The AgerIRs expression profile demonstrated that AgerIR2 had high expression levels in male labial palps, suggesting that this receptor may function to detect female-deposited trail-sex pheromone blend of A. germari. In addition, the phylogenetic tree showed that the Orco gene of five cerambycidae species was highly conservative. These results provide a foundation for further studies on the molecular mechanisms of olfactory chemoreception in A. germari apart from suggesting novel targets for the control of this pest in the future.

Treatment Status of Elderly Patients With Severe Mental Disorders in Rural China.

This study was performed to compare the treatment status between older (≥65 years) and younger adults (18-64 years) with severe mental illness (SMI) and explore factors associated with treatment status in rural China. Persons with SMI were identified in one mental health survey in 2015 in 6 townships of Xinjin County, Chengdu, China. Logistic regressions were conducted to explore factors associated with treatment status. Older adults with SMI, especially major depressive disorder, reported significantly lower rates of treatment than younger group. Older age, longer duration of illness, and poor mental status were risk factors for never-treated status in these patients. Never-treated status (46.3%) and poor treatment status in these older patients are serious issues. Different treatment statuses in these patients had various influencing factors. It is crucial to develop culture-specific, community-based mental health services to improve early identification, diagnosis, treatment, and recovery of older adults with SMI in rural China.

Changes in treatment status of patients with severe mental illness in rural China, 1994-2015.

BACKGROUND: Although it is crucial to improve the treatment status of people with severe mental illness (SMI), it is still unknown whether and how socioeconomic development influences their treatment status.AimsTo explore the change in treatment status in people with SMI from 1994 to 2015 in rural China and to examine the factors influencing treatment status in those with SMI. METHOD: Two mental health surveys using identical methods and ICD-10 were conducted in 1994 and 2015 (population ≥15 years old, n = 152 776) in the same six townships of Xinjin County, Chengdu, China. RESULTS: Compared with 1994, individuals with SMI in 2015 had significantly higher rates of poor family economic status, fewer family caregivers, longer duration of illness, later age at first onset and poor mental status. Participants in 2015 had significantly higher rates of never being treated, taking antipsychotic drugs and ever being admitted to hospital, and lower rates of using traditional Chinese medicine or being treated by traditional/spiritual healers. The factors strongly associated with never being treated included worse mental status (symptoms/social functioning), older age, having no family caregivers and poor family economic status. CONCLUSIONS: Socioeconomic development influences the treatment status of people with SMI in contemporary rural China. Relative poverty, having no family caregivers and older age are important factors associated with a worse treatment status. Culture-specific, community-based interventions and targeted poverty-alleviation programmes should be developed to improve the early identification, treatment and recovery of individuals with SMI in rural China.Declaration of interestNone.

A Plastid-Localized Pentatricopeptide Repeat Protein is Required for Both Pollen Development and Plant Growth in Rice.

Several mitochondrial-targeted pentatricopeptide repeat (PPR) proteins involved in pollen development have been reported to be fertility restorer (Rf) proteins. However, the roles of plastid-localized PPR proteins in plant male reproduction are poorly defined. Here, we described a plastid-localized PPR-SMR protein, OsPPR676, which is required for plant growth and pollen development in rice. In this study, OsPPR676 was confirmed to be an interacted protein with Osj10gBTF3, ß-subunit of nascent polypeptide-associated complex (ß-NAC), by bimolecular fluorescence complementation assays, indicating that both proteins are probably involved in the same regulatory pathway of pollen development. Compared with other chloroplast-rich tissues, OsPPR676 was only weakly expressed in anther, but in the Mei and YM stages of pollen development, its expression was relatively strong in the tapetum. Disruption of OsPPR676 resulted in growth retardation of plants and partial sterility of pollens. Phenotypic analysis of different osppr676 mutant lines implied that the SMR domain was not essential for the function of OsPPR676. We further demonstrated that OsPPR676 is essential for production of plastid atpB subunit, and then plays crucial roles in biosynthesis of fatty acids, carbohydrates, and other organic matters via affecting activity of ATP synthase.

The family economic status and outcome of people with schizophrenia in Xinjin, Chengdu, China: 14-year follow-up study.

BACKGROUND: Little is known about whether family economic status might influence the long-term (e.g. over 10 years) outcome of persons with schizophrenia in the community. AIM: To examine the differences in outcome at 14-year follow-up of persons with schizophrenia from high versus low family economic status backgrounds in a Chinese rural area. METHOD: A prospective 14-year follow-up study was conducted in six townships in Xinjin County, Chengdu, China. All participants with schizophrenia ( n = 510) were identified in an epidemiological investigation of 123,572 people aged 15 years and older and followed up from 1994 to 2008. RESULTS: Individuals from low family economic status (

Astragaloside IV prevents high glucose-induced podocyte apoptosis via downregulation of TRPC6.

Diabetic nephropathy (DN) is one of the most important causes of end­stage renal disease. Astragaloside IV (AS-IV) is a saponin isolated from Astragalus membranaceus, which possesses various pharmacological activities. AS­IV prevents podocyte apoptosis and ameliorates renal injury in DN; however, few studies have focused on its effects on ion channels. The transient receptor potential channel 6 (TRPC6) is an important Ca2+­permeable ion channel in podocytes, which is involved in high glucose (HG)-induced podocyte apoptosis. The aim of the present study was to investigate whether AS­IV prevented HG­induced podocyte apoptosis via TRPC6. Cultured podocytes were pre­treated with 10, 20 or 40 µM AS­IV for 1 h prior to HG exposure for 24 h. Apoptosis, cell viability, expression of TRPC6, nuclear factor of activated T cells (NFAT2) and B­cell lymphoma 2­associated X protein (Bax), as well as the intracellular Ca2+ concentration were subsequently analyzed. The results indicated that HG induced podocyte apoptosis and upregulation of TRPC6, and increased intracellular Ca2+. Furthermore, enhanced NFAT2 and Bax expression was detected. Conversely, AS­IV protected HG­induced podocyte apoptosis, downregulated TRPC6 expression and suppressed intracellular Ca2+ in HG-stimulated podocytes. AS­IV also suppressed NFAT2 and Bax expression. These results suggest that AS­IV may prevent HG-induced podocyte apoptosis via downregulation of TRPC6, which is possibly mediated via the calcineurin/NFAT signaling pathway.

Overexpression of HOXC11 homeobox gene in clear cell renal cell carcinoma induces cellular proliferation and is associated with poor prognosis.

Novel evidence has confirmed the involvement of dysregulated expression of HOX genes in cancer. HOX genes are a family of 39 transcription factors, divided in four clusters (HOXA to HOXD), that during normal development regulate cell proliferation and specific cell fate. The aim of this study was to investigate whether genes of the HOXC cluster might play a role in renal cancer. The expression of HOXC11 was detected through polymerase chain reaction and immunohistochemical staining, and we demonstrated that HOXC11 was significantly higher in renal cell carcinoma (RCC) compared to normal kidney tissue. We further demonstrated that HOXC11 overexpression in HK-2 human epithelial cell line promoted proliferation, whereas downregulation of HOXC11 endogenous levels in human RCC cells (Caki-2 cells) decreased proliferation. In RCC, expression of HOXC11 and Ki67, a marker of proliferation, correlates strongly with each other (r s = 0.47, p < 0.003). High immunohistochemical expression of HOXC11 was correlated with T stage (p = 0.06), N stage (p = 0.07), disease stage (p = 0.08), and Ki67 expression (p = 0.07), and patients with tumors showing high number of HOXC11-positive cells had shorter overall survival (p = 0.08) and shorter progression-free survival after treatment (p = 0.08) compared with patients with tumors exhibiting low amount of HOXC11-positive cells. Our data suggest that HOXC11 may contribute to RCC carcinogenesis by increasing tumor cell proliferation and imply that HOXC11 may be an important determinant of RCC patient prognosis.

Effects of stomatal development on stomatal conductance and on stomatal limitation of photosynthesis in Syringa oblata and Euonymus japonicus Thunb.

During leaf development, the increase in stomatal conductance cannot meet photosynthetic demand for CO2, thus leading to stomatal limitation of photosynthesis (Ls). Considering the crucial influences of stomatal development on stomatal conductance, we speculated whether stomatal development limits photosynthesis to some extent. To test this hypothesis, stomatal development, stomatal conductance and photosynthesis were carefully studied in both Syringa oblata (normal greening species) and Euonymus japonicus Thunb (delayed greening species). Our results show that the size of stomata increased gradually with leaf expansion, resulting in increased stomatal conductance up to the time of full leaf expansion. During this process, photosynthesis also increased steadily. Compared to that in S. oblata, the development of chloroplasts in E. japonicus Thunb was obviously delayed, leading to a delay in the improvement of photosynthetic capacity. Further analysis revealed that before full leaf expansion, stomatal limitation increased rapidly in both S. oblata and E. japonicus Thunb; after full leaf expansion, stomatal limitation continually increased in E. japonicus Thunb. Accordingly, we suggested that the enhancement of photosynthetic capacity is the main factor leading to stomatal limitation during leaf development but that stomatal development can alleviate stomatal limitation with the increase of photosynthesis by controlling gas exchange.

Elevated microRNA-185 is associated with high vascular endothelial growth factor receptor 2 expression levels and high microvessel density in clear cell renal cell carcinoma.

MicroRNAs (miRNAs) are involved in a number of biological processes, including tumor biology. Previous studies have demonstrated that miRNA-185 regulates signaling downstream of vascular endothelial growth factor receptor 2 (VEGFR-2) and, consequently, angiogenesis. The aim of this study was to analyze the potential relationship between miRNA-185, VEGFR-2, and angiogenesis in samples from renal cell carcinoma (RCC) patients. Tumor tissue was obtained from 82 patients. The miRNA-185 and VEGFR-2 gene expression levels were analyzed by PCR, and the protein concentrations of VEGFR-2 were detected by ELISA. Angiogenesis, visualized by the endothelial cell marker CD34 combined with caldesmon, was assessed by immunohistochemistry and the microvessel density (MVD) technique. In situ hybridization was performed for miRNA-185. Tumors were classified as low or high miRNA-185-expressing using the median as the cutoff. The median gene expression levels of VEGFR-2 were significantly lower in the tumors expressing low levels of miRNA-185, 0.31 (95 % CI, 0.25-0.37), compared to those expressing high levels of miRNA-185, 0.47 (95 % CI, 0.27-0.59), p = 0.02. A positive association was certified with VEGFR-2 protein levels, p = 0.06. The median MVD was significantly lower in the tumors expressing low levels of miRNA-185, 6.8 (95 % CI, 6.33-7.67), compared to those expressing high levels, 8.0 (95 % CI, 6.33-9.00), p < 0.01. miRNA-185 was detected in endothelial cells by in situ hybridization detection. The results suggest that high levels of miRNA-185 in RCC are associated with high VEGFR-2 mRNA and protein levels and a higher density of microvessels. However, further investigation should be performed to analyze the prognostic value of miRNA-185 in RCC.

Structural characterisation and antioxidant activity evaluation of phenolic compounds from cold-pressed Perilla frutescens var. arguta seed flour.

A total of 11 phenolic compounds, as well as sucrose (12) and tryptophan (13), were isolated from cold-pressed Perilla frutescens var. arguta seed flour using column chromatography, and their chemical structures were identified as 3'-dehydroxyl-rosmarinic acid-3-o-glucoside (1), rosmarinic acid-3-o-glucoside (2), rosmarinic acid (3), rosmarinic acid methyl ester (4), luteolin (5), luteolin-5-o-glucoside (6), apigenin (7), caffeic acid (8), caffeic acid-3-o-glucoside (9), vanillic acid (10) and cimidahurinine (11) using NMR and time-of-flight mass spectrometry. Of these components, compound 1 is novel, and this is the first report of compounds 10 and 11 in perilla seeds. HPLC quantification combined with antioxidant activity evaluation revealed that rosmarinic acid and rosmarinic acid-3-o-glucoside were the dominant phenolic antioxidants with strong antioxidant activities.

Effects of mutual shading on the regulation of photosynthesis in field-grown sorghum.

In the field, close planting inevitably causes mutual shading and depression of leaf photosynthesis. To clarify the regulative mechanisms of photosynthesis under these conditions, the effects of planting density on leaf structure, gas exchange and proteomics were carefully studied in field-grown sorghum. In the absence of mineral deficiency, (1) close planting induced a significant decrease in light intensity within populations, which further resulted in much lower stomatal density and other anatomical characteristics associated with shaded leaves; (2) sorghum grown at high planting density had a lower net photosynthetic rate and stomatal conductance than those grown at low planting density; (3) approximately 62 protein spots changed their expression levels under the high planting density conditions, and 22 proteins associated with photosynthesis were identified by mass spectrometry. Further analysis revealed the depression of photosynthesis caused by mutual shading involves the regulation of leaf structure, absorption and transportation of CO2, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. Additionally, heat shock protein and oxygen-evolving enhancer protein play important roles in photoprotection in field-grown sorghum. A model for the regulation of photosynthesis under mutual shading was suggested based on our results.

Comparative transcriptomic analysis of the heat stress response in the filamentous fungus Metarhizium anisopliae using RNA-Seq.

The entomopathogenic fungus Metarhizium anisopliae is widely used for biological control of a variety of insect pests. The effectiveness of the microbial pest control agent, however, is limited by poor thermotolerance. The molecular mechanism underlying the response to heat stress in the conidia of entomopathogenic fungi remains unclear. Here, we conducted high-throughput RNA-Seq to analyze the differential gene expression between control and heat treated conidia of M. anisopliae at the transcriptome level. RNA-Seq analysis generated 6,284,262 and 5,826,934 clean reads in the control and heat treated groups, respectively. A total of 2,722 up-regulated and 788 down-regulated genes, with a cutoff of twofold change, were identified by expression analysis. Among these differentially expressed genes, many were related to metabolic processes, biological regulation, cellular processes and response to stimuli. The majority of genes involved in endocytic pathways, proteosome pathways and regulation of autophagy were up-regulated, while most genes involved in the ribosome pathway were down-regulated. These results suggest that these differentially expressed genes may be involved in the heat stress response in conidia. As expected, significant changes in expression levels of genes encoding heat shock proteins and proteins involved in trehalose accumulation were observed in conditions of heat stress. These results expand our understanding of the molecular mechanisms of the heat stress response of conidia and provide a foundation for future investigations.

Reduced mir-29b-3p expression up-regulate CDK6 and contributes to IgA nephropathy.

IgA nephropathy (IgAN) is the most common glomerulonephritis and the etiology of which is complex and multiple, and the pathological damage of IgAN is diversified. MicroRNA is a kind of gene expression suppressor and recently, researchers have found that microRNAs may play an important role in the pathogenesis of IgAN. Herein, we found that miR-29b-3p not miR-29a or miR-29c was significantly down regulated in IgAN patients' renal tissues. Predicted by bioinformatics tools and confirmed by dual luciferase assay and western blot, we found that the expression of CDK6 was repressed by miR-29b-3p directly. Subsequently, we found that miR-29b-3p down-regulation caused CDK6 overexpression can promote NF-κB signal by phosphorylating p65 which may enhance inflammation during IgAN pathogenesis.

[Species diversity and temporal niche of entomopathogenic fungi in the extensively managed tea plantation soil].

The species diversity and temporal niche of entomopathogenic fungi community in the rhizosphere soil collected from the extensively managed Huangshan fuzz tip tea plantation were investigated. A total of 140 soil samples were collected at the location of Tangkou Town, Huangshan of Anhui Province during August, 2012 to June, 2013, and totally 1041 fungal isolates were obtained on selective medium with soil dilution plating. The results showed that the entomopathogenic fungi community in the tea plantation soil was diverse with 13 species in 6 genera. Purpureocillium lilacinum (309 strains), Beauveria bassiana (255 strains), and Metarhizium anisopliae (101 strains) were the dominant species accounting for 29.7%, 24.5% and 9.7% of the relative frequency, respectively. P. lilacinum had the widest temporal niche breadth among these dominant entomopathogenic fungi from the tea plantation soil, while B. bassiana had the narrowest. Among the entomopathogenic fungi, B. bassiana and B. brongniartii had the biggest temporal niche overlap of 1.965, while Isaria javanicus and B. bassiana had the smallest of 0.374.