A single cell atlas of the mouse seminal vesicle.

During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling to the female reproductive tract and in nourishing sperm for their onwards journey. Along with minor contributions from the prostate and the epididymis, the majority of seminal fluid is produced by a somewhat understudied organ known as the seminal vesicle. Here, we report the first single-cell RNA-seq atlas of the mouse seminal vesicle, generated using tissues obtained from 23 mice of varying ages, exposed to a range of dietary challenges. We define the transcriptome of the secretory cells in this tissue, identifying a relatively homogeneous population of the epithelial cells which are responsible for producing the majority of seminal fluid. We also define the immune cell populations - including large populations of macrophages, dendritic cells, T cells, and NKT cells - which have the potential to play roles in producing various immune mediators present in seminal plasma. Together, our data provide a resource for understanding the composition of an understudied reproductive tissue with potential implications for paternal control of offspring development and metabolism.

Gender disparities in summer outdoor heat risk across China: Findings from a national county-level assessment during 1991-2020.

Increasing anthropogenic global warming has emerged as a significant challenge to human health in China, as extreme heat hazards increasingly threaten outdoor-exposed populations. Differences in thermal comfort, outdoor activity duration, and social vulnerability between females and males may exacerbate gender inequalities in heat-related health risks, which have been overlooked by previous studies. Here, we combine three heat hazards and outdoor activity duration to identify the spatiotemporal variation in gender-specific heat risk in China during 1991-2020. We found that females' heat risk tends to be higher than that of males. Gender disparities in heat risk decrease in southern regions, while those in northern regions remain severe. Males are prone to overheating in highly urbanized areas, while females in low urbanized areas. Males' overheating risk is mainly attributed to population clustering associated with prolonged outdoor activity time and skewed social resource allocation. In contrast, females' overheating risk is primarily affected by social inequalities. Our findings suggest that China needs to further diminish gender disparities and accelerate climate adaptation planning.

New allele of mouse DNA/RNA helicase senataxin causes meiotic arrest and infertility.

In brief: A new allele of the senataxin gene Setxspcar3 causes meiotic arrest of spermatocytes with aberrant DNA damage and accumulation of R-loops. Abstract: An unbiased screen for discovering novel mouse genes for fertility identified the spcar3, spermatocyte arrest 3, mutant phenotype. The spcar3 mutation identified a new allele of the Setx gene, encoding senataxin, a DNA/RNA helicase that regulates transcription termination by resolving DNA/RNA hybrid R-loop structures. The Setxspcar3 mutant mice exhibit male infertility and female subfertility. Histology of the Setxspcar3 mutant testes revealed the absence of spermatids and mature spermatozoa in the seminiferous tubules. Cytological analysis of chromosome preparations of the Setxspcar3 mutant spermatocytes revealed normal synapsis, but aberrant DNA damage in the autosomes, defective formation of the sex body, and arrest of meiosis in mid-prophase. Additionally, Setxspcar3 testicular cells exhibit abnormal accumulation of R-loops. Transient expression assays identified regions of the senataxin protein required for sub-nuclear localization. Together, these results not only confirm that senataxin is required for normal meiosis and spermatogenesis but also provide a new resource for the determination of its role in maintaining R-loop formation and genome integrity.

Parameter calibration of the discrete element simulation model for soaking paddy loam soil based on the slump test.

The discrete element computer simulation method is an effective tool that enables the study of the interaction mechanism between the pulping components and the paddy soil during the paddy field pulping process. The findings are valuable in optimizing the parameters of the paddy beating device to improve its working quality and efficiency. However, the lack of accurate soil models for paddy soil has limited the application and development of the discrete element method in paddy pulping research. This study selected the Hertz-Mindlin with Johnson-Kendall-Roberts discrete element model for the pre-pulping paddy loam soil and used the slump error as the test index to select nine parameters, including soil Poisson's ratio and surface energy, as test factors to calibrate the model parameters. The Plackett-Burman test identified soil shear modulus, surface energy, and soil-iron plate static friction coefficient as significant factors affecting the test index. The steepest ascent test results determined the test range of the above parameters. The Box-Behnken test obtained the regression model between the significant factors and the test index, and the regression model was optimized using the slump error as the target. The optimal combination of parameters was surface energy of 3.257 J/m2, soil shear modulus of 0.709 MPa, and static friction coefficient between soil and iron plate of 0.701. The slump simulation test using this combination of parameters yielded an average slump error of 2.04%. The collective results indicate the accuracy of the calibrated discrete element simulation parameters for paddy loam soil. These parameters can be used for discrete element simulation analysis of the paddy pulping process after paddy field soaking.

Evidence for RNA or protein transport from somatic tissues to the male reproductive tract in mouse.

The development of tools to manipulate the mouse genome, including knockout and transgenic technology, has revolutionized our ability to explore gene function in mammals. Moreover, for genes that are expressed in multiple tissues or at multiple stages of development, the use of tissue-specific expression of the Cre recombinase allows gene function to be perturbed in specific cell types and/or at specific times. However, it is well known that putative tissue-specific promoters often drive unanticipated 'off-target' expression. In our efforts to explore the biology of the male reproductive tract, we unexpectedly found that expression of Cre in the central nervous system resulted in recombination in the epididymis, a tissue where sperm mature for ~1-2 weeks following the completion of testicular development. Remarkably, we not only observed reporter expression in the epididymis when Cre expression was driven from neuron-specific transgenes, but also when Cre expression in the brain was induced from an AAV vector carrying a Cre expression construct. A surprisingly wide range of Cre drivers - including six different neuronal promoters as well as the adipose-specific Adipoq Cre promoter - exhibited off-target recombination in the epididymis, with a subset of drivers also exhibiting unexpected activity in other tissues such as the reproductive accessory glands. Using a combination of parabiosis and serum transfer experiments, we find evidence supporting the hypothesis that Cre may be trafficked from its cell of origin to the epididymis through the circulatory system. Together, our findings should motivate caution when interpreting conditional alleles, and suggest the exciting possibility of inter-tissue RNA or protein trafficking in modulation of reproductive biology.

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Vertical expansion makes the structure and pattern of the city more complicated. Traditional two-dimensional landscape pattern cannot completely reflect the ecological structure and functional characteristics of urban landscape. In this study, we used the three-dimensional landscape pattern metrics to quantify the regional three-dimensional landscape pattern, and used boosted regression tree (BRT) machine learning algorithms to comprehensively analyze the interaction between social-environmental factors and urban landscape patterns in the central part of Shanghai. Results showed that high building ratio, mean architecture height, and architecture height standard deviation had higher values in the surrounding area of the inner ring. The number of buildings and landscape shape index were higher in the outer ring than those in other area. Building coverage ratio, floor area ratio and Shannon's diversity index had higher values in the central part, with the metrics of Puxi being generally higher than those of Pudong. Population density and normalized vegetation index (NDVI) interacted most significantly with the three-dimensional landscape pattern, with GDP as the least influential factor. Within a certain range, the three-dimensional landscape pattern metrics increased with larger population density in the social factors, and decreased with lower rate of NDVI and water surface ratio in the environmental factors. Our results demonstrated that the BRT method was effective in quantifying the interaction between landscape pattern and social-environmental factors. Our results help improve the understanding of the relationship between ecological environment and human well-being in the central part of Shanghai and provide a scientific basis for the urban three-dimensional expansion planning.

Linking hydraulic geometry, land use, and stream water quality in the Taihu Basin, China.

Understanding the complexity of catchment-scale human activities, natural factors, and stream water quality is particularly important for basin water resources management. Thorough investigations on how multiple environmental factors quantitatively and simultaneously affect water quality are limited. This study employed Spearman's correlation and ridge regression analysis (RRA) to disentangle the hydraulic geometry and land use contributions to water quality variables (WQVs). Nine and six indicators were used to describe the hydraulic geometry and land use characteristics, respectively, in the Taihu Basin. The results revealed significant correlations between the land use, hydraulic geometry, and stream water quality. Built-up land and cropland negatively impacted the stream water quality, while woodland had the opposite trend. The structure and morphological connectivity of the river network were associated with most WQVs. The hydrologic connectivity characteristics strongly influenced ammonia-nitrogen (NH3-N), permanganate index (CODMn), and dissolved oxygen (DO). Six equations that estimated the stream water quality were established through RRA. Human factors impose a greater impact on the stream water quality than natural factors in the Taihu Basin. Our findings provide quantitative insights to mitigate water pollution via reasonable management and control of the river structure and connectivity and land-use patterns.

Mapping multiple water pollutants across China using the grey water footprint.

The primary pollutants and pollution levels of surface water present spatial and temporal changes. This study quantified the grey water footprint (GWF) and surface water pollution level (WPL) in China from 2003 to 2018 based on four pollutants: chemical oxygen demand (COD), ammonia nitrogen (NH3-N), total nitrogen (TN) and total phosphorus (TP). Additionally, the spatiotemporal distribution of the primary water pollutant (PWP) and driving forces of the GWF were analyzed based on the WPLs and the logarithmic mean Divisia index (LMDI) decomposition method. The results showed that the GWF in China decreased by 13% from 2003 to 2018 and the WPL decreased from 1.11 in 2003 to 0.94 in 2018. An analysis of regional GWFs with multiple pollutants could prevent the underestimation of GWFs and WPLs caused by changes in the PWPs. The GWF spatial distribution was high in the southeast and low in the northwest, while the provinces with larger WPLs were mainly concentrated in northern China. The PWP changed from COD to TN in 2007 because of the increase in nitrogen application in China, the low TN reduction capacity of wastewater treatment plants and the improved comprehensive utilization rate of livestock and poultry manure. The driving force analysis results showed that water efficiency and technological and industrial structural effects promoted the reduced GWF. Our research conclusions and policy suggestions could provide references for reducing the GWF and improving the water quality in China.

Vegetation coverage change of the demonstration area of ecologically friendly development in the Yangtze River Delta, China based on GEE and BRT during 1984-2019.

The demonstration area of ecologically friendly development in the Yangtze River Delta is a major national strategy area, and thus eco-environmental protection should be a priority for the sustainable development. Exploring the spatial-temporal variations of franctional vegetation coverage (FVC) is conducive to accurate assessing the ecological quality of environment, which is of great significance to regional sustainable development. In this study, the characteristics and trends of spatial-temporal variation of vegetation cover during 1984-2019 in the demonstration area were analyzed based on Google Earth Engine (GEE). The effects of different ecological factors on FVC were quantified by the boosted regression tree (BRT). Results showed that,the changing trend of FVC in the study area shifted from decreasing to increasing trend from 1984 to 2019. The spatial distribution of FVC in the study area varied with both stages and regions. FVC was mainly degraded. Compared with the year 1984, the area of vegetation degradation and improvement in 2019 accounted for 49.8% and 12.8%, respectively. The vegetation degradation mainly occurred in the north of Wujiang, south of Jiashan, and northeast of Qingpu. Human activities severely weakened the influence of natural factors on FVC. Our findings suggested that the GEE is an effective tool for monitoring the dynamics of vegetation coverage.

Stability of the cytosine methylome during post-testicular sperm maturation in mouse.

Beyond the haploid genome, mammalian sperm carry a payload of epigenetic information with the potential to modulate offspring phenotypes. Recent studies show that the small RNA repertoire of sperm is remodeled during post-testicular maturation in the epididymis. Epididymal maturation has also been linked to changes in the sperm methylome, suggesting that the epididymis might play a broader role in shaping the sperm epigenome. Here, we characterize the genome-wide methylation landscape in seven germ cell populations from throughout the male reproductive tract. We find very few changes in the cytosine methylation landscape between testicular germ cell populations and cauda epididymal sperm, demonstrating that the sperm methylome is stable throughout post-testicular maturation. Although our sequencing data suggested that caput epididymal sperm exhibit a highly unusual methylome, follow-up studies revealed that this resulted from contamination of caput sperm by extracellular DNA. Extracellular DNA formed web-like structures that ensnared sperm, and was present only in sperm samples obtained from the caput epididymis and vas deferens of virgin males. Curiously, contaminating extracellular DNA was associated with citrullinated histone H3, potentially resulting from a PAD-driven genome decondensation process. Taken together, our data emphasize the stability of cytosine methylation in mammalian sperm, and identify a surprising, albeit transient, period during which sperm are associated with extracellular DNA.

Deficient spermiogenesis in mice lacking Rlim.

The X-linked gene Rlim plays major roles in female mouse development and reproduction, where it is crucial for the maintenance of imprinted X chromosome inactivation in extraembryonic tissues of embryos. However, while females carrying a systemic Rlim knockout (KO) die around implantation, male Rlim KO mice appear healthy and are fertile. Here, we report an important role for Rlim in testis where it is highly expressed in post-meiotic round spermatids as well as in Sertoli cells. Systemic deletion of the Rlim gene results in lower numbers of mature sperm that contains excess cytoplasm, leading to decreased sperm motility and in vitro fertilization rates. Targeting the conditional Rlim cKO specifically to the spermatogenic cell lineage largely recapitulates this phenotype. These results reveal functions of Rlim in male reproduction specifically in round spermatids during spermiogenesis.

Future river basin health assessment through reliability-resilience-vulnerability: Thresholds of multiple dryness conditions.

Increasing dryness conditions under global warming are posing severe threats to water resources management in China. Projecting river basin responses to dryness conditions is beneficial to effectively managing water resources. However, existing studies have seldom considered the impact of multiple dryness conditions on future river basin health under global warming. Therefore, we combine the 3- and 12-month standard precipitation evapotranspiration index (SPEI) and reliability-resilience-vulnerability framework (RRV) to map future river basin health based on the responses of basins across China to different dryness conditions from 2021 to 2050. The calculation is based on downscaled outputs of 10 models from the Coupled Model Intercomparison Project Phase 5 (CMIP5) for three future emission scenarios (i.e., RCP2.6, RCP4.5 and RCP8.5). The results show that water deficits are projected to occur in most areas of China and significantly increase in the basins located in the northern part of China in the next 30 years due to global warming effects. The conditions in parts of the basins located in the northern part of China (especially in the Northwest River basins and Yellow River basin) are projected to be unhealthy and deteriorate significantly in the future, while the basins located in the southern part of China are projected to be moderate. The health status is anticipated to be worse under the RCP8.5 scenario than the RCP2.6 and RCP4.5 scenarios. Integrated results from the three thresholds indicated that normal dryness is applicable to most areas of northeastern, northern and southern China, while abnormal dryness is applicable to the remaining areas. Our findings could help reduce the impact of future dryness conditions on water resources and provide insights into risk planning and management for river basins in China under global warming.

Logic Gate Functions Built with Nonvolatile Resistive Switching and Thermoresponsive Memory Based on Biologic Proteins.

Logic gate functions built with nonvolatile resistive switching and thermoresponsive memory based on biologic proteins were investigated. The "NAND" and "NOR" functions of logic gates in soya protein devices have been built at room temperature by their nonvolatile ternary WORM resistive switching behaviors. Furthermore, heating the devices from room temperature to 358 K results in a switch from tristable state to bistable state WORM resistive switching behavior, indicating that the thermoresponsiveness can be efficiently memorized. The biologic transient nonvolatile memory device consisting of soya protein is illustrated. This device exhibits a long data retention time (104 s) and significant HRS/LRS ratio (∼105); the transient response of the current to voltage of an as-fabricated device is also explored. The soya protein based memory device on a gelatin film substrate is also assessed to validate the feasibility of degradation and biological compatibility for the implantable biological electronic device, that is, innoxious and avirulent to the human body. This can offer alternative avenues for exploring prospective bioelectronic devices.

The Association Between the rs2975760 and rs3792267 Single Nucleotide Polymorphisms of Calpain 10 (CAPN10) and Gestational Diabetes Mellitus.

BACKGROUND This study aimed to investigate the association between the rs2975760 and rs3792267 single nucleotide polymorphisms (SNPs) of the calpain 10 (CAPN10) gene and gestational diabetes mellitus. MATERIAL AND METHODS The study included 138 patients with gestational diabetes mellitus and 152 healthy pregnant women. Venous blood was separated, and the DNA was extracted. The rs2975760 and rs3792267SNP polymorphisms of CAPN10 were detected using polymerase chain reaction (PCR). The frequencies of different genotypes in patients with gestational diabetes mellitus and healthy pregnant women were determined, and the relationship between different SNP genotypes and the risk of gestational diabetes mellitus was analyzed. RESULTS There were no significant differences in the frequencies of the TT, CT and CC genotypes of rs2975760 and the frequencies of the GG, AG and AA genotypes of rs3792267 between the women with gestational diabetes and the controls. Expression of rs2975760 and rs3792267 were not associated with the risk of gestational diabetes in the dominant model, recessive model, and additive model. However, grade B and grade D diabetes in the CC and TC genotypes of rs2975760 were significantly different from those in the TT genotype (P<0.05). Grade B and grade D diabetes in the AA and AG genotypes of rs3792267 were significantly different compared with those in the GG genotype (P<0.05), and allele A was significantly increased compared with allele G (P<0.05). CONCLUSIONS The rs2975760 and rs3792267 SNP polymorphisms of CAPN10 showed no significant association with the incidence of gestational diabetes mellitus and only a mild association with the severity.

A factor analysis of residents' performance in municipal solid waste source-separated collection: A case study of pilot cities in China.

To explore the potential effectiveness of a localized waste recycling system in Chinese cities, several rounds of a municipal solid waste source-separated collection (MSWSC) program were implemented throughout China from 2000 to 2017. In our study, to evaluate the achievements of the MSWSC program, a structured questionnaire survey and face-to-face interviews were conducted in eight representative cities from the MSWSC pilot cities. Influencing factors were examined via a Hierarchical Linear Model (HLM) on both the individual level and the city level. The differences in MSWSC performance among the eight research cities were investigated through a comparative analysis. The results suggested that gender, age, knowledge of MSWSC, satisfaction with sanitation and satisfaction with publicity had significant impacts on MSWSC, and we further found that the city-level factors influenced the relationship between MSWSC performance and the individual-level variables. Differences among the eight research sites indicated that Nanjing and Hangzhou exhibited relatively high achievements in the implementation of MSWSC program, while Yichun and Guiyang showed poor performance. The experiences of these advanced pilot cities suggest that specific containers for designated waste types, widespread public education, and sufficient MSWSC incentives must be provided and publicized to promote municipal solid waste recycling behaviors. Given the unique status of municipal solid waste management in China and its regional heterogeneity, the MSWSC system should be further discussed with regard to local conditions in a wider range of city settings. Implications: This study attempts to discuss the factors affecting performance on municipal solid waste source-separated collection (MSWSC) by considering the nested data of two levels of individual and city from a structured questionnaire survey. Therefore, a Hierarchical Linear Model is established which can analyze the intra-group and inter-group effects of two-level variables. The proposed method can be expanded to other cities to determine the main factors affecting MSWSC or to evaluate the residents' performance on MSWSC.

Blockade of CTLA-4 and Tim-3 pathways induces fetal loss with altered cytokine profiles by decidual CD4+T cells.

The single and/or combination use of immune checkpoint blockade therapies in human infectious diseases and cancer are rapidly expanding. Despite early efforts, substantial uncertainty remains about the safety and efficacy of immune checkpoint blockade in some populations. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T-cell immunoglobulin mucin-3 (Tim-3) are the major targetable co-inhibitory receptors on T cells. Here we showed that in animal studies, treatment with either CTLA-4- or Tim-3-blocking antibody caused greater susceptibility to fetal loss with altered cytokine profiles by decidual CD4+T (dCD4+T) cells. CTLA-4 and Tim-3 pathways appeared to play key roles in maintaining maternal-fetal tolerance by regulating the function of dCD4+T cells. In addition, the abnormality in number and functionality of dCTLA-4+Tim-3+CD4+T cells was associated with miscarriage. These findings underscored the important roles of the CTLA-4 and Tim-3 pathways in regulating dCD4+T cells function and maintaining normal pregnancy. Our study also emphasized the importance of careful consideration of reproductive safety when choosing immune checkpoint blockade therapies in real world clinical care.

Small RNAs Are Trafficked from the Epididymis to Developing Mammalian Sperm.

The biogenesis of the RNA payload of mature sperm is of great interest, because RNAs delivered to the zygote at fertilization can affect early development. Here, we tested the hypothesis that small RNAs are trafficked to mammalian sperm during the process of post-testicular maturation in the epididymis. By characterizing small RNA dynamics during germ cell maturation in mice, we confirm and extend prior observations that sperm undergo a dramatic switch in the RNA payload from piRNAs to tRNA fragments (tRFs) upon exiting the testis and entering the epididymis. Small RNA delivery to sperm could be recapitulated in vitro by incubating testicular spermatozoa with caput epididymosomes. Finally, tissue-specific metabolic labeling of RNAs in intact mice definitively shows that mature sperm carry RNAs that were originally synthesized in the epididymal epithelium. These data demonstrate that soma-germline RNA transfer occurs in male mammals, most likely via vesicular transport from the epididymis to maturing sperm.

Small RNAs Gained during Epididymal Transit of Sperm Are Essential for Embryonic Development in Mice.

The small RNA payload of mammalian sperm undergoes dramatic remodeling during development, as several waves of microRNAs and tRNA fragments are shipped to sperm during post-testicular maturation in the epididymis. Here, we take advantage of this developmental process to probe the function of the sperm RNA payload in preimplantation development. We generated zygotes via intracytoplasmic sperm injection (ICSI) using sperm obtained from the proximal (caput) versus distal (cauda) epididymis and then characterized the development of the resulting embryos. Embryos generated using caput sperm significantly overexpress multiple regulatory factors throughout preimplantation development, subsequently implant inefficiently, and fail soon after implantation. Remarkably, microinjection of purified cauda-specific small RNAs into caput-derived embryos not only completely rescued preimplantation molecular defects but also suppressed the post-implantation embryonic lethality phenotype. These findings reveal an essential role for small RNA remodeling during post-testicular maturation of mammalian sperm and identify a specific preimplantation gene expression program responsive to sperm-delivered microRNAs.