Genomic and Expression Analysis of Cassava (Manihot esculenta Crantz) Chalcone Synthase Genes in Defense against Tetranychus cinnabarinus Infestation.

Cassava is susceptible to mites, especially Tetranychus cinnabarinus. Secondary metabolism products such as flavonoids play an important role as antimicrobial metabolites protecting plants against biotic stressors including fungal, pathogen, bacterial, and pest defense. The chalcone synthase (CHS) is the initial step of the phenylpropanoid pathway for producing flavonoids and is the gatekeeper of the pathway. Until recently, the CHS genes family has not been systematically studied in cassava. Thirty-nine CHS genes were identified from the cassava genome database. Based on phylogenetic and sequence composition analysis, these CHSs were divided into 3 subfamilies. Within the same subfamily, the gene structure and motif compositions of these CHS genes were found to be quite conserved. Duplication events, particularly segmental duplication of the cassava CHS genes, were identified as one of the main driving force of its expansion. Various cis-elements contained in the promoter might regulate the gene expression patterns of MeCHS. Protein-protein interaction (PPI) network analysis showed that MeCHS1 and MeCHS10 protein are more closely related to other family members. The expression of MeCHS genes in young leaves was higher than that in other tissues, and their expression varies even within the same tissue. Coincidentally, these CHS genes of most LAP subclasses were highly expressed in young leaves. The verified MeCHS genes showed consistent with the real-time reverse transcription quantitative PCR (RT-qPCR) and proteomic expression in protected and affected leaves respectively, indicating that these MeCHS genes play crucial roles in the response to T. cinnabarinus. This study is the first to comprehensively expatiate the information on MeCHS family members. These data will further enhance our understanding both the molecular mechanisms and the effects of CHS genes. In addition, the results will help to further clarify the effects on T. cinnabarinus and provide a theoretical basis for the potential functions of the specific CHS gene in resistance to mites and other biotic stress.

Exploring the impact of pericentric inversion of chromosome 9 on fertility in sperm donors.

ABSTRACT: Pericentric inversion of chromosome 9 (inv[9]) is a common chromosomal structural variant, but its impact on clinical outcomes remains debated. The screening criteria of sperm banks are rarely mentioned to individuals with inv(9). In this study, we evaluated the fertility of sperm donors with inv(9) who met eligibility criteria for sperm banks (inv[9]-eligible donors). From March 2004 to May 2022, chromosomal analysis of 16 124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province (Changsha, China) found that 251 (1.6%) had chromosome variations, with inv(9) being the most prevalent at 1.1%. All 169 inv(9)-eligible donors were contacted to collect fertility outcome data, along with 206 eligible donors without inv(9) as controls. In addition, semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization (FISH), mitochondrial membrane potential, DNA fragmentation index, acrosome integrity, reactive oxygen species (ROS), and sperm morphology. Results showed that inv(9) did not significantly increase reproductive risks overall. Despite detecting ROS level differences, the clinical impact may be insignificant. This study provides new data on the inv(9) population that can serve as a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individuals carrying inv(9) variant.

Long-term storage modifies the microRNA expression profile of cryopreserved human semen.

The global practice of cryopreservation of human semen is commonplace in Assisted Reproductive Technology (ART) labs and sperm banks. However, information on the effects of long-term cryopreservation on semen is limited to clinical data summaries and descriptions. For this study, we prepared 4 semen specimens of fresh semen, 4 specimens cryostored for at least 1 year, 3 specimens cryostored for at least 5 years, 4 specimens cryostored for at least 10 years, and 3 specimens cryostored for at least 15 years. Total RNA was extracted from each sample, amplified, labeled, and mapped to the known primary microRNA (miRNA) in the miRBase database, enabling the prediction of novel miRNAs. We found that cryopreservation can lead to changes in miRNA expression, and with the increase in storage time, these changes became more pronounced. Meanwhile, the expression of let-7d-3p, let-7c-5p and let-7i-3p miRNAs changed dynamically over cryostorage time in frozen-thawed human sperm. Furthermore, we analyzed the time-dependent dynamics of cryostorage-expressed miRNAs and their target mRNAs and found that half of the target genes were expressed in oocytes. These intersection genes were mainly enriched in cancer and cytoskeletal signaling pathways. Our findings showed that the miRNA expression profile of cryopreserved human semen is modified by long-term storage. Furthermore, as the storage time increases, the impact on human sperm becomes more pronounced in terms of miRNAs, which may have an effect on subsequent fertilization and embryonic development.

Genetic testing of sperm donors in China: a survey of current practices.

Background: The National Health and Family Planning Commission of China (NHFPCC) issued the "Measures for the Management of Human Sperm Banks," which was revised in 2003 and is still in effect today. One of the standard guidelines is that potential donors undergo laboratory testing to exclude infectious and genetic diseases and karyotype analysis. However, patient demands for donor genetic testing have also increased, and only karyotype analysis to exclude genetic diseases is not sufficient to meet these demands. Objective: To examine donor genetic screening practices at sperm banks in China and to evaluate the qualifications and skills of genetic counselors at the banks. Materials and methods: An electronic survey was distributed to twenty-seven sperm banks to examine donor genetic screening practices at sperm banks in China and to evaluate the qualifications and skills of genetic counselors at the banks. Twenty-six human sperm banks responded to a 32-question survey about their current practices related to genetic testing of sperm donors. Results: The 26 sperm banks reported that all qualified sperm donors undergo karyotype analysis; 22 banks (84.6%) collected three generations of family history from each qualified sperm donor; 10 (38.5%) reported that they attempted to accommodate special requests from donor semen recipients for particular genetic tests. Only 2 of the 26 (7.7%) sperm banks reported that they performed whole-exome sequencing. At all the sperm banks, consent for genetic testing was obtained as part of the overall contract for sperm donors. Nineteen (73.1%) sperm banks had genetic counselors on their staff, while six (23.1%) had no genetic counselors on their staff but had access to genetic counselors at the hospital. Only one (3.8%) sperm bank had no genetic counselors on their staff or at the hospital. Conclusions: The need for larger scale genetic testing of donors and recipients and an extensive panel of genetic tests specific to the Chinese population. Additionally, professionally trained geneticists must be employed as genetic counsellors so that the results of genetic tests and their implications can be explained to donors.

MAGEB2-Mediated Degradation of EGR1 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cell Lines.

Spermatogonial stem cells are committed to initiating and maintaining male spermatogenesis, which is the foundation of male fertility. Understanding the mechanisms underlying SSC fate decisions is critical for controlling spermatogenesis and male fertility. However, the key molecules and mechanisms responsible for regulating human SSC development are not clearly understood. Here, we analyzed normal human testis single-cell sequencing data from the GEO dataset (GSE149512 and GSE112013). Melanoma antigen gene B2 (MAGEB2) was found to be predominantly expressed in human SSCs and further validated by immunohistology. Overexpression of MAGEB2 in SSC lines severely weakened cell proliferation and promoted apoptosis. Further, using protein interaction prediction, molecular docking, and immunoprecipitation, we found that MAGEB2 interacted with early growth response protein 1 (EGR1) in SSC lines. Reexpression of EGR1 in MAGEB2 overexpression cells partially rescued decreased cell proliferation. Furthermore, MAGEB2 was shown to be downregulated in specific NOA patients, implying that abnormal expression of MAGEB2 may impair spermatogenesis and male fertility. Our results offer new insights into the functional and regulatory mechanisms in MAGEB2-mediated human SSC line proliferation and apoptosis.

Effects of ambient air pollution on cause-specific hospitalizations in Wuhan during 2017-2019.

BACKGROUND: Few studies have focused on the associations between air pollutants and multiple organ system diseases in the entire hospitalized population. The present study aims to explore the short-term effects of six routinely monitored air pollutants on the broad causes of hospital admissions and estimate the resulting hospital admission burdens. METHODS: Daily hospital admission records from 2017 to 2019 were obtained from the Wuhan Information center of Health and Family Planning. Generalized additive models (GAMs) were employed to evaluate the effects of air pollutants on the percent increase in the cause-specific daily number of hospital admissions. Increased hospital admission numbers, days, and expenses were also estimated. RESULTS: A total of 2636,026 hospital admissions were identified. We found that both PM2.5 and PM10 increased the risk of hospital admissions for most disease categories. Short-term exposure to PM2.5 was positively associated with hospitalizations of several rarely studied disease categories, such as diseases of the eye and adnexa (2.83%, 95%CI: 0.96-4.73%, P < 0.01) and diseases of the musculoskeletal system and connective tissue (2.17%, 95% CI: 0.88-3.47%, P < 0.001). NO2 was observed to have a robust effect on diseases of the respiratory system (1.36%, 95%CI: 0.74-1.98%, P < 0.001). CO was significantly associated with hospital admissions for six disease categories. Furthermore, each 10-µg/m3 increase in PM2.5 was associated with an annual increase of 13,444 hospital admissions (95% CI: 6239-20,649), 124,344 admission days (95% CI: 57,705-190,983), and 166-million-yuan admission expenses (95% CI: 77-255). CONCLUSION: Our study suggested that particulate matter (PM) had a short-term effect on hospital admissions of most major disease categories and resulted in a considerable hospital admission burden. In addition, the health effects of NO2 and CO emissions require more attention in megacities.

Comparison of Clinical Outcomes, Risks, and Costs for 20,910 Donor In Vitro Fertilization and 16,850 Donor Artificial Insemination Treatment Cycles: A Retrospective Analysis in China.

PURPOSE: To evaluate the effectiveness of donor in vitro fertilization (IVF-D) and donor artificial insemination (AI-D) in clinical outcomes, risks, and costs. METHODS: This study analyzed the cycle changes and clinical outcomes in 20,910 IVF-D and 16,850 AI-D cycles between 2013 and 2021 in the Reproductive and Genetic Hospital of CITIC-Xiangya. A cost-effectiveness analysis was performed to evaluate the costs per couple and per live birth cycle in the two treatment groups. RESULTS: IVF-D had higher pregnancy and live birth rates than AI-D (p < 0.001). The cumulative pregnancy and live birth rates for three AI-D cycles were 41.01% and 32.42%, respectively, higher than the rates for one or two AI-D cycles. The multiple birth and birth defect rate of AI-D was lower than that of IVF-D significantly. IVF-D mean cost per couple was higher than that of AI-D (CNY32,575 vs. CNY11,062, p < 0.001), with a mean cost difference of CNY21,513 (95% confidence interval, CNY20,517-22,508). The mean costs per live birth cycle for IVF-D and AI-D were CNY49,411 and CNY31,246, respectively. CONCLUSION: AI-D is more cost-effective and poses a lower risk for infertility couples than IVF-D, and patients should undergo three AI-D cycles to obtain the highest success rate.

Effects of green spaces on alleviating mortality attributable to PM2.5 in China.

Increasing research suggested that green spaces are associated with many health benefits, but evidence for the quantitative relationship between green spaces and mortality attributable to particulate matter with an aerodynamic diameter of 2.5 µm or less (PM2.5) is limited. We collected disease-specific mortality and PM2.5 data for a period of 4 years (2015-2018) along with green space data for an 8-year duration (2010-2017) in 31 provincial-level administrative regions of China. First, this study used the Integrated Exposure-Response model to estimate the mortality of four diseases attributable to PM2.5, including chronic obstructive pulmonary diseases (COPD), lung cancer (LC), ischemic heart disease (IHD), and cerebrovascular disease (CBVD). Then we performed linear regression and mixed-effects model to investigate the counteracting effect of green spaces on death caused by PM2.5 exposure. The differences in impacts among the Eastern, Central, and Western regions were explored using stratified analysis. The most significant results from linear regression analysis indicated that per 100 km2 of green spaces increase, there was a decreased total mortality (10-5) (COPD, LC, IHD, and CBVD) attributable to PM2.5 by - 4.012 [95% confidence interval (CI): - 5.535, - 2.488], while the reduction by mixed-linear regression analysis was - 2.702/105 (95% CI = - 3.645, - 1.759). Of all hysteresis analyses, the effect estimates (ß) at lag3 and lag4 were the largest. The effect of green spaces was more advantageous when targeting CBVD and the Eastern region. We found a negative correlation between green space exposure and mortality attributable to PM2.5, which can provide further support for city planners, government personnel, and others to build a healthier city and achieve national health goals.

Vacuolization in embryos on days 3 and 4 of in vitro development: Association with stimulation protocols, embryo development, chromosomal status, pregnancy and neonatal outcomes.

Study question: Is vacuolization in embryos on Days 3 and 4 associated with parent-related factors, stimulation protocols, embryo development, embryo ploidy, pregnancy and neonatal outcomes? Study design size duration: This is a retrospective cohort study that comprised 5,703 embryos from 611 patients who underwent preimplantation genetic testing and time-lapse monitoring of their embryos from August 2017 to September 2021. Main results: Embryo vacuolization on Days 3 and 4 is associated with the LH level on the day of the hCG trigger and the number of retrieved oocytes. Compared to vacuole-negative embryos, the rates of blastocyst formation and good-blastocyst formation was significantly lower in vacuole-positive embryos. We observed no significant difference in the rates of euploidy, implantation, ongoing pregnancy, and live birth between vacuole-positive and vacuole-negative embryos. In vacuole-positive embryos, the embryos of which the vacuole-positive blastomeres were involved in embryo compaction exhibited significantly higher mosaicism rate compared with those of which the vacuole-positive blastomeres were not involved in embryo compaction. Conclusion: Vacuolization in embryos on Days 3 and 4 is associated with reduced blastocyst formation rate and high-quality blastocyst rate. Blastocysts had a low mosaicism rate if the vacuole-containing cells were rejected in compaction process, which supports the hypothesis that exclusion of abnormal blastomeres from compaction is a self-correction mechanism.

Genetic testing of sperm donors at a human sperm bank in China.

Background: In China, numerous human sperm banks only perform three-generation family history evaluation to exclude genetic diseases with clinical symptoms; therefore, many inherited risks cannot be detected before donor qualification even when a thorough genetic family history evaluation has been performed. Hence, the risk of recessive disease inheritance persists with the current eligibility guidelines in China regarding the donor selection process. Methods: Retrospective study that reviewed the genetic test analyses and clinical outcomes of young adult men who were qualified sperm donors at the Hunan Province Human Sperm Bank of China from January 1, 2018, to May 1, 2021. We included a total of 3231 qualified sperm donors: all donors underwent primary screening for thalassemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Whereafter, 278 of donors underwent genetic testing for specific genes, and 43 donors underwent whole exome sequencing. Results: 2.4% of 3231 qualified sperm donors might have thalassemia and 1.4% might have G6PD deficiency. Sperm donors with thalassemia and G6PD deficiency would be eliminated. Specific gene testing identified 7 of the 278 donors (2.5%) as carriers of at least one pathogenic or likely pathogenic variant in a gene, including 1.9% of 154 donors (3/154) as carrier variants in α-Like or ß-Like globin genes, 17.6% of 17 donors (3/17) as carrier variants in GJB2, 12.5% of 8 donors (1/8) as carrier variants in SMN1. In addition, among the 43 sperm donors carrying the 111 pathogenic/likely pathogenic variants, eight (18.6%) were carriers of pathogenic variants of the GJB2 gene. The frequency, therefore, was approximately 1 in 5. Conclusions: The data suggest that used blood routine and RDT can make a preliminary screening of sperm donors, and special gene testing should be performed for sperm donors according to the regional incidence of specific genetic diseases. Meanwhile, whole exome sequencing can be used as a supplementary application in sperm donor genetic testing, and aid a successful and healthy pregnancy. However, industry guidelines must be modified to incorporate its use.

An electrochemical aptasensor with N protein binding aptamer-complementary oligonucleotide as probe for ultra-sensitive detection of COVID-19.

The emergence of the COVID-19 epidemic has affected the lives of hundreds of millions of people globally. There is no doubt that the development of fast and sensitive detection methods is crucial while the worldwide effective vaccination programs are miles away from actualization. In this study, we have reported an electrochemical N protein aptamer sensor with complementary oligonucleotide as probe for the specific detection of COVID-19. The electrochemical aptasensor was prepared by fixing the double-stranded DNA hybrid obtained by the hybridization of N protein aptamer and its Fc-labeled complementary strand on the surface of a gold electrode. After incubation with the target, the aptamer dissociated from the labeled complementary DNA oligonucleotide hybrid to preferentially bind with N protein in the solution. The concentration of N protein was measured by detecting the changes in electrochemical current signals induced by the conformational transformation of the complementary DNA oligonucleotide left on the electrode surface. The sensor had a linear relationship between the logarithm of the N protein concentration from 10 fM to 100 nM (ΔIp = 0.098 log CN protein/fM - 0.08433, R2 = 0.99), and the detection limitation was 1 fM (S/N = 3). The electrochemical aptamer sensor was applied to test the spiked concentrations of throat swabs and blood samples from three volunteers, and the obtained results proved that the sensor has great potentials for the early detection of COVID-19 in patients.

Update on techniques for cryopreservation of human spermatozoa.

In the 1960s, sperm cryopreservation was developed as a method to preserve fertility. Currently, techniques for the cryopreservation of human spermatozoa have been widely used in assisted reproduction. However, although sperm cryobiology has made notable achievements, the optimal method for the recovery of viable spermatozoa after cryopreservation remains elusive. Postthawing sperm quality can be affected by cryoprotectants, ice formation, storage conditions, and osmotic stress during the freezing process. This review discusses recent advances in different cryopreservation techniques, cryoprotectants, and freezing and thawing methods during cryopreservation and new indications for the use of cryopreserved spermatozoa.

Short-term effects of air pollution on respiratory diseases among young children in Wuhan city, China.

BACKGROUND: The high risks for childhood respiratory diseases are associated with exposure to ambient air pollution. However, there are few studies that have explored the association between air pollution exposure and respiratory diseases among young children (particularly aged 0-2 years) based on the entire population in a megalopolis. METHODS: Daily hospital admission records were obtained from 54 municipal hospitals in Wuhan city, China. We included all children (aged 0-2 years) hospitalized with respiratory diseases between January 2017 and December 2018. Individual air pollution exposure assessment was used in Land Use Regression model and inverse distance weighted. Case-crossover design and conditional logistic regression models were adopted to estimate the hospitalization risk associated with air pollutants. RESULTS: We identified 62,425 hospitalizations due to respiratory diseases, of which 36,295 were pneumonia. Particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and nitrogen dioxide (NO2) were significantly associated with respiratory diseases and pneumonia. ORs of pneumonia were 1.0179 (95% CI 1.0097-1.0260) for PM2.5 and 1.0131 (95% CI 1.0042-1.0220) for NO2 at lag 0-7 days. Subgroup analysis suggested that NO2, Ozone (O3) and sulfur dioxide (SO2) only showed effects on pneumonia hospitalizations on male patients, but PM2.5 had effects on patients of both genders. Except O3, all pollutants were strongly associated with pneumonia in cold season. In addition, children who aged elder months and who were in central urban areas had a higher hospitalization risk. CONCLUSIONS: Air pollution is associated with higher hospitalization risk for respiratory diseases, especially pneumonia, among young children, and the risk is related to gender, month age, season and residential location.

Micro-straw: An efficient cryopreservation carrier for rare human spermatozoa.

BACKGROUND: Many cryopreservation carriers have been introduced to freeze rare human spermatozoa, however, these carriers relative attributes and comparative effectivenesses have not yet been systematically studied. OBJECTIVES: Is the micro-straw cryopreservation carrier more effective for cryopreserving rare human spermatozoa compared with the Cryoplus and a new micro-straw (LSL straw) carriers? MATERIALS AND METHODS: This study involves 93 samples from healthy sperm donors and 40 samples from patients diagnosed with oligospermia, asthenospermia, oligoasthenospermia, or obstructive azoospermia. We determined the optimal freeze-thaw protocol for the Micro-straw carrier. The post-thaw survival rate, normal sperm morphology, acrosome integrity, and DNA fragmentation for Micro-straw, Cryoplus, and LSL carriers were then determined. Finally, we verified the effects of freezing using these carriers by comparing the qualities of post-thaw spermatozoa from patients. RESULTS: The highest total motility (TM) and progressive motility (PR) survival rates were obtained by placing the Micro-straw at 1 cm above the LN2 surface for 70 s during freezing and in a 42°C water bath for 40 s during thawing. No differences were observed in the PR survival rate, acrosome integrity, and DNA fragmentation of the post-thaw spermatozoa from the three carriers. However, the normal morphology rate of spermatozoa frozen using the Micro-straw carrier was higher than for the Cryoplus carrier (p < 0.05), and the TM survival rate of spermatozoa frozen with the Micro-straw was higher than that for the LSL carrier (p < 0.01). In verification tests, there were no significant differences in the quality of post-thaw spermatozoa cryopreserved using these carriers for both rare spermatozoa or epididymal sperm. DISCUSSION AND CONCLUSION: Micro-straw, Cryoplus, and LSL carriers are all efficient means of freezing rare human spermatozoa. However, the Micro-straw carrier is more economical, safe, and user-friendly.

SPOC domain-containing protein 1 regulates the proliferation and apoptosis of human spermatogonial stem cells through adenylate kinase 4.

BACKGROUND: Spermatogonial stem cells (SSCs) are the origin of male spermatogenesis, which can reconstruct germ cell lineage in mice. However, the application of SSCs for male fertility restoration is hindered due to the unclear mechanisms of proliferation and self-renewal in humans. AIM: To investigate the role and mechanism of SPOC domain-containing protein 1 (SPOCD1) in human SSC proliferation. METHODS: We analyzed publicly available human testis single-cell RNA sequencing (RNA-seq) data and found that SPOCD1 is predominantly expressed in SSCs in the early developmental stages. Small interfering RNA was applied to suppress SPOCD1 expression to detect the impacts of SPOCD1 inhibition on SSC proliferation and apoptosis. Subsequently, we explored the target genes of SPOCD1 using RNA-seq and confirmed their role by restoring the expression of the target genes. In addition, we examined SPOCD1 expression in some non-obstructive azoospermia (NOA) patients to explore the correlation between SPOCD1 and NOA. RESULTS: The uniform manifold approximation and projection clustering and pseudotime analysis showed that SPOCD1 was highly expressed in the early stages of SSC, and immunohistological results showed that SPOCD1 was mainly localized in glial cell line-derived neurotrophic factor family receptor alpha-1 positive SSCs. SPOCD1 knockdown significantly inhibited cell proliferation and promoted apoptosis. RNA-seq results showed that SPOCD1 knockdown significantly downregulated genes such as adenylate kinase 4 (AK4). Overexpression of AK4 in SPOCD1 knockdown cells partially reversed the phenotypic changes, indicating that AK4 is a functional target gene of SPOCD1. In addition, we found a significant downregulation of SPOCD1 expression in some NOA patients, suggesting that the downregulation of SPOCD1 may be relevant for NOA. CONCLUSION: Our study broadens the understanding of human SSC fate determination and may offer new theories on the etiology of male infertility.

PM2.5-Associated Hospitalization Risk of Cardiovascular Diseases in Wuhan: Cases Alleviated by Residential Greenness.

PM2.5, a type of particulate matter with an aerodynamic diameter of less than 2.5 µm, is associated with the occurrence of cardiovascular diseases (CVDs), while greenness seems to be associated with better cardiovascular health. We identified 499,336 CVD cases in Wuhan's 74 municipal hospitals between 2017 and 2019. A high-resolution PM2.5 model and a normalized difference vegetation index (NDVI) map were established to estimate individual exposures. The time-stratified case-crossover design and conditional logistic regression models were applied to explore the associations between PM2.5 and CVDs under different levels of environmental factors. Greenness could alleviate PM2.5-induced hospitalization risks of cardiovascular diseases. Compared with patients in the low-greenness group (ER = 0.99%; 95% CI: 0.71%, 1.28%), patients in the high-greenness group (ER = 0.45%; 95% CI: 0.13%, 0.77%) showed a lower increase in total CVD hospitalizations. After dividing the greenness into quartiles and adding long-term PM2.5 exposure as a control factor, no significant PM2.5-associated hospitalization risks of CVD were identified in the greenest areas (quartile 4), whether the long-term PM2.5 exposure level was high or low. Intriguingly, in the least green areas (quartile 1), the PM2.5-induced excess risk of CVD hospitalization was 0.58% (95% CI: 0.04%, 1.11%) in the long-term high-level PM2.5 exposure group, and increased to 1.61% (95% CI: 0.95%, 2.27%) in the long-term low-level PM2.5 exposure group. In the subgroup analysis, males and participants aged 55-64 years showed more significant increases in the PM2.5-induced risk of contracting CVDs with a reduction in greenness and fine particle exposure conditions. High residential greenness can greatly alleviate the PM2.5-induced risk of cardiovascular admission. Living in the areas with long-term low-level PM2.5 may make people more sensitive to short-term increases in PM2.5, leading to CVD hospitalization.

MKK7-mediated phosphorylation of JNKs regulates the proliferation and apoptosis of human spermatogonial stem cells.

BACKGROUND: Human spermatogonial stem cells (SSCs) are the basis of spermatogenesis. However, little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences. AIM: To investigates the mechanisms involved in the proliferation of human SSC. METHODS: The expression of mitogen-activated protein kinase kinase 7 (MKK7) in human testis was identified using immunohistochemistry and western blotting (WB). MKK7 was knocked down using small interfering RNA, and cell proliferation and apoptosis were detected by WB, EdU, cell counting kit-8 and fluorescence-activated cell sorting. After bioinformatic analysis, the interaction of MKK7 with c-Jun N-terminal kinases ( JNKs ) was verified by protein co-immunoprecipitation and WB. The phosphorylation of JNKs was inhibited by SP600125, and the phenotypic changes were detected by WB, cell counting kit-8 and fluorescence-activated cell sorting. RESULTS: MKK7 is mainly expressed in human SSCs, and MKK7 knockdown inhibits SSC proliferation and promotes their apoptosis. MKK7 mediated the phosphorylation of JNKs, and after inhibiting the phosphorylation of JNKs, the phenotypic changes of the cells were similar to those after MKK7 downregulation. The expression of MKK7 was significantly downregulated in patients with abnormal spermatogenesis, suggesting that abnormal MKK7 may be associated with spermatogenesis impairment. CONCLUSION: MKK7 regulates the proliferation and apoptosis of human SSC by mediating the phosphorylation of JNKs.

Acute Effects of Air Pollution on Ischemic Heart Disease Hospitalizations: A Population-Based Time-Series Study in Wuhan, China, 2017-2018.

Evidence of the acute effects of air pollutants on ischemic heart disease (IHD) hospitalizations based on the entire population of a megacity in central China is lacking. All IHD hospitalization records from 2017 to 2018 were obtained from the Wuhan Information Center of Health and Family Planning. Daily air pollutant concentrations and meteorological data were synchronously collected from the Wuhan Environmental Protection Bureau. A time-series study using generalized additive models was conducted to systematically examine the associations between air pollutants and IHD hospitalizations. Stratified analyses by gender, age, season, hypertension, diabetes, and hyperlipidemia were performed. In total, 139,616 IHD hospitalizations were included. Short-term exposure to air pollutants was positively associated with IHD hospitalizations. The age group ≥76 was at higher exposure risk, and the associations appeared to be more evident in cold seasons. PM2.5 and PM10 appeared to have greater effects on males and those without hypertension or diabetes, whereas NO2 and SO2 had greater effects on females and those with hypertension or diabetes. The risk of IHD hospitalization due to air pollutants was greater in people without hyperlipidemia. Our study provides new evidence of the effects of air pollution on the increased incidence of IHD in central China.

The Role of METTL3-Mediated N6-Methyladenosine (m6A) of JPH2 mRNA in Cyclophosphamide-Induced Cardiotoxicity.

Cyclophosphamide (CYP)-induced cardiotoxicity is a common side effect of cancer treatment. Although it has received significant attention, the related mechanisms of CYP-induced cardiotoxicity remain largely unknown. In this study, we used cell and animal models to investigate the effect of CYP on cardiomyocytes. Our data demonstrated that CYP-induced a prolonged cardiac QT interval and electromechanical coupling time courses accompanied by JPH2 downregulation. Moreover, N6-methyladenosine (m6A) methylation sequencing and RNA sequencing suggested that CYP induced cardiotoxicity by dysregulating calcium signaling. Importantly, our results demonstrated that CYP induced an increase in the m6A level of JPH2 mRNA by upregulating methyltransferases METTL3, leading to the reduction of JPH2 expression levels, as well as increased field potential duration and action potential duration in cardiomyocytes. Our results revealed a novel mechanism for m6A methylation-dependent regulation of JPH2, which provides new strategies for the treatment and prevention of CYP-induced cardiotoxicity.

Sperm donor lifestyle survey: modifiable risk factors for potential sperm donors.

OBJECTIVES: To examine the association between modifiable lifestyle factors and the main semen parameter values, the number of qualified sperm donors, and to provide some sensible guidance for sperm donors. METHODS: Healthy men screened as potential sperm donors were recruited in the Hunan Province Human Sperm Bank of China from March 2019 to December 2019. Participants were invited to complete interviewer-assisted questionnaires on eleven items of information. Univariate and multivariate analyses were conducted to analyze which lifestyle factors collected by the questionnaire had an impact on the eligibility and main semen parameters of sperm donors. RESULTS: The eligibility of men as sperm donors was strongly influenced by the duration of abstinence (P = 0.002). The rate of eligibility sperm donors increased significantly with the number of days of abstinence. In addition, semen volume increased with abstinence time (P = 0.000). Exercise frequency (P = 0.025) and abstinence time (P = 0.000) were positively correlated with sperm concentration, and masturbation frequency was negatively correlated with sperm concentration (P = 0.013). Progressive sperm motility was significantly affected by abstinence time (P = 0.000) and bedtime (P = 0.047). CONCLUSIONS: Abstinence time was highly associated with semen parameters and donor qualification. Increase the abstinence time before donation may be meaningful in improving the proportion of eligible sperm donors.