Hypoxia induces alterations in tRNA modifications involved in translational control.

BACKGROUND: Adaptation to high-altitude hypobaric hypoxia has been shown to require a set of physiological traits enabled by an associated set of genetic modifications, as well as transcriptome regulation. These lead to both lifetime adaptation of individuals to hypoxia at high altitudes and generational evolution of populations as seen for instance in those of Tibet. Additionally, RNA modifications, which are sensitive to environmental exposure, have been shown to play pivotal biological roles in maintaining the physiological functions of organs. However, the dynamic RNA modification landscape and related molecular mechanisms in mouse tissues under hypobaric hypoxia exposure remain to be fully understood. Here, we explore the tissue-specific distribution pattern of multiple RNA modifications across mouse tissues. RESULTS: By applying an LC-MS/MS-dependent RNA modification detection platform, we identified the distribution of multiple RNA modifications in total RNA, tRNA-enriched fragments, and 17-50-nt sncRNAs across mouse tissues; these patterns were associated with the expression levels of RNA modification modifiers in different tissues. Moreover, the tissue-specific abundance of RNA modifications was sensitively altered across different RNA groups in a simulated high-altitude (over 5500 m) hypobaric hypoxia mouse model with the activation of the hypoxia response in mouse peripheral blood and multiple tissues. RNase digestion experiments revealed that the alteration of RNA modification abundance under hypoxia exposure impacted the molecular stability of tissue total tRNA-enriched fragments and isolated individual tRNAs, such as tRNAAla, tRNAval, tRNAGlu, and tRNALeu. In vitro transfection experiments showed that the transfection of testis total tRNA-enriched fragments from the hypoxia group into GC-2spd cells attenuated the cell proliferation rate and led to a reduction in overall nascent protein synthesis in cells. CONCLUSIONS: Our results reveal that the abundance of RNA modifications for different classes of RNAs under physiological conditions is tissue-specific and responds to hypobaric hypoxia exposure in a tissue-specific manner. Mechanistically, the dysregulation of tRNA modifications under hypobaric hypoxia attenuated the cell proliferation rate, facilitated the sensitivity of tRNA to RNases, and led to a reduction in overall nascent protein synthesis, suggesting an active role of tRNA epitranscriptome alteration in the adaptive response to environmental hypoxia exposure.

Full-Section Deformation Monitoring of High-Altitude Fault Tunnels Based on Three-Dimensional Laser Scanning Technology.

In traditional tunnel monitoring, the characteristic points of an object within a tunnel are measured to obtain information about the object. Considering the limitations of the traditional method in measuring the complex surface structure of tunnels, such as limited monitoring points, a long measurement period, and low precision, this study introduces an approach that uses three-dimensional (3D) laser scanning for monitoring tunnel cross-section deformation. Using this approach, the soft surrounding rock of a high-altitude ultralong tunnel was taken as the monitoring object. The test tunnel was first scanned using a 3D laser scanner, and the collected data were processed. The internal structural data of the tunnel were subsequently compared with its actual contour lines and the data of its primary branch and secondary lining on different dates. The results indicate that the arch roof of the tunnel tended to be stable within a certain time range when the positions of the primary branch and secondary lining were at different measuring points with different pile numbers. The deformation of the pile number on the left and right sides did not generally exceed 0.02 m, except at a few measuring points. A comparison between the actual cross section of the initial branch and that of the designed section showed that the actual elevation of the arch of the initial branch of the tunnel was greater than its designed elevation by no more than 0.3 m. Hence, through this study, a convenient and practical method is presented for monitoring deformation in complex curved tunnel structures.

Dynamic Threshold Cable-Stayed Bridge Health Monitoring System Based on Temperature Effect Correction.

The early health warning of a cable-stayed bridge is of great significance for discovering the abnormal condition of the structure, eliminating the risk factors, and ensuring the normal operation of the bridge in order to set a reasonable safety monitoring threshold to ensure the safety warning and condition assessment of the bridge structure. A method of dynamic early warning by considering the temperature effect is adopted in this paper on the basis of the benchmark threshold. Based on the long-term deflection monitoring data of a bridge in Wuhan, the generalized Pareto distribution (GPD) extreme value analysis theory is used to set the benchmark threshold. Then, by constructing the seasonal autoregressive integrated moving average (SARIMA) long-span bridge temperature effect prediction model, the reference threshold is dynamically adjusted. Finally, it is compared with the traditional fixed threshold monitoring system. The results show that the dynamic threshold has stronger adaptability to the monitoring of cable-stayed bridges and can also achieve effective monitoring of local mutations in other periods. Dynamic threshold early warning can reduce the shortcomings of traditional early warning methods such as underreporting and misreporting. At the same time, the GPD extreme value analysis theory overcomes the disadvantage that the extreme value information is not fully utilized. It has an important application value for bridge health monitoring.

New Variant of Vibrio parahaemolyticus, Sequence Type 3, Serotype O10:K4, China, 2020.

In 2020, a new serotype of Vibrio parahaemolyticus O10:K4 emerged and caused several outbreaks and sporadic cases in Guangxi, China. Phylogenetic analysis indicated that those strains are new variants of the sequence type 3 pandemic clone. The new serotype may become dominant, warranting enhanced investigations and surveillance.

Alteration of RNA modification signature in human sperm correlates with sperm motility.

RNA modifications, which are introduced post-transcriptionally, have recently been assigned pivotal roles in the regulation of spermatogenesis and embryonic development. However, the RNA modification landscape in human sperm is poorly characterized, hampering our understanding about the potential role played by RNA modification in sperm. Through our recently developed high-throughput RNA modification detection platform based on liquid chromatography with tandem mass spectroscopy, we are the first to have characterized the RNA modification signature in human sperm. The RNA modification signature was generated on the basis of 49 samples from participants, including 13 healthy controls, 21 patients with asthenozoospermia (AZS) and 15 patients with teratozoospermia (TZS). In total, we identified 13 types of RNA modification marks on the total RNA in sperm, and 16 types of RNA modification marks on sperm RNA fragments of different sizes. The levels of these RNA modifications on the RNA of patients with AZS or TZS were altered, compared to controls, especially on sperm RNA fragments > 80 nt. A few types of RNA modifications, such as m1G, m5C, m2G and m1A, showed clear co-expression patterns as well as high linear correlations with clinical sperm motility. In conclusion, we characterized the RNA modification signature of human sperm and identified its correlation with sperm motility, providing promising candidates for use in clinical sperm quality assessment and new research insights for exploring the underlying pathological mechanisms in human male infertility syndromes.

Pan-Cancer Analysis Identifies CHD5 as a Potential Biomarker for Glioma.

The chromodomain helicase DNA binding domain 5 (CHD5) is required for neural development and plays an important role in the regulation of gene expression. Although CHD5 exerts a broad tumor suppressor effect in many tumor types, its specific functions regarding its expression levels, and impact on immune cell infiltration, proliferation and migration in glioma remain unclear. Here, we evaluated the role of CHD5 in tumor immunity in a pan-cancer multi-database using the R language. The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), and Cancer Cell Lines Encyclopedia (CCLE) datasets were utilized to determine the role of CHD5 in 33 types of cancers, including the expression level, prognosis, tumor progression, and immune microenvironment. Furthermore, we explored the effect of CHD5 on glioma proliferation and migration using the cell counting kit 8 (CCK-8) assay, transwell assays and western blot analysis. The findings from our pan-cancer analysis showed that CHD5 was differentially expressed in the tumor tissues as compared to the normal tissues. Survival analysis showed that CHD5 was generally associated with the prognosis of glioblastoma (GBM), low Grade Glioma (LGG) and neuroblastoma, where the low expression of CHD5 was associated with a worse prognosis in glioma patients. Then, we confirmed that the expression level of CHD5 was associated with tumor immune infiltration and tumor microenvironment, especially in glioma. Moreover, si-RNA mediated knockdown of CHD5 promoted the proliferation and migration of glioma cells in vitro. In conclusion, CHD5 was found to be differentially expressed in the pan-cancer analysis and might play an important role in antitumor immunity. CHD5 is expected to be a potential tumor prognostic marker, especially in glioma.

GDPD5 Related to Lipid Metabolism Is a Potential Prognostic Biomarker in Neuroblastoma.

Neuroblastoma (NB) is an extracranial solid tumor in children with poor prognosis in high-risk patients and its pathogenesis and prognostic markers urgently need to be explored. This study aimed to explore potential biomarkers related to NB from the aspect of lipid metabolism. Fifty-eight lipid metabolism-related differentially expressed genes between high-risk NB and non-high-risk NB in the GSE49710 dataset were analyzed using bioinformatics, including 45 down-regulated genes and 13 up-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified steroid hormone biosynthesis as an abnormal metabolic pathway in high-risk NB. Survival analysis established a three-gene prognostic model, including ACHE, GDPD5 and PIK3R1. In the test data, the AUCs of the established prognostic models used to predict patient survival at 1, 3 and 5 years were 0.84, 0.90 and 0.91, respectively. Finally, in the SH-SY5Y cell line, it was verified that overexpression of GDPD5 can inhibit cell proliferation and migration, as well as affect the lipid metabolism of SH-SY5Y, but not the sugar metabolism. hsa-miR-592 was predicted to be a potential target miRNA of GDPD5 by bioinformatics. In conclusion, this study develops a lipid-metabolism-related gene-based prognostic model for NB and demonstrates that GDPD5 inhibits SH-SY5Y proliferation and migration and may be targeted by hsa-miR-592 and inhibit SH-SY5Y fat synthesis.

BMP9-initiated osteogenic/odontogenic differentiation of mouse tooth germ mesenchymal cells (TGMCS) requires Wnt/ß-catenin signalling activity.

Teeth arise from the tooth germ through sequential and reciprocal interactions between immature epithelium and mesenchyme during development. However, the detailed mechanism underlying tooth development from tooth germ mesenchymal cells (TGMCs) remains to be fully understood. Here, we investigate the role of Wnt/ß-catenin signalling in BMP9-induced osteogenic/odontogenic differentiation of TGMCs. We first established the reversibly immortalized TGMCs (iTGMCs) derived from young mouse mandibular molar tooth germs using a retroviral vector expressing SV40 T antigen flanked with the FRT sites. We demonstrated that BMP9 effectively induced expression of osteogenic markers alkaline phosphatase, collagen A1 and osteocalcin in iTGMCs, as well as in vitro matrix mineralization, which could be remarkably blunted by knocking down ß-catenin expression. In vivo implantation assay revealed that while BMP9-stimulated iTGMCs induced robust formation of ectopic bone, knocking down ß-catenin expression in iTGMCs remarkably diminished BMP9-initiated osteogenic/odontogenic differentiation potential of these cells. Taken together, these discoveries strongly demonstrate that reversibly immortalized iTGMCs retained osteogenic/odontogenic ability upon BMP9 stimulation, but this process required the participation of canonical Wnt signalling both in vitro and in vivo. Therefore, BMP9 has a potential to be applied as an efficacious bio-factor in osteo/odontogenic regeneration and tooth engineering. Furthermore, the iTGMCs may serve as an important resource for translational studies in tooth tissue engineering.

Hypoxia-induced alteration of RNA modifications in the mouse testis and sperm†.

Hypobaric hypoxia as an extreme environment in a plateau may have deleterious effects on human health. Studies have indicated that rush entry into a plateau may reduce male fertility and manifest in decreased sperm counts and weakened sperm motility. RNA modifications are sensitive to environmental changes and have recently emerged as novel post-transcriptional regulators in male spermatogenesis and intergenerational epigenetic inheritance. In the present study, we generated a mouse hypoxia model simulating the environment of 5500 m in altitude for 35 days, which led to compromised spermatogenesis, decreased sperm counts, and an increased sperm deformation rate. Using this hypoxia model, we further applied our recently developed high-throughput RNA modification quantification platform based on liquid chromatography with tandem mass spectrometry, which exhibited the capacity to simultaneously examine 25 types of RNA modifications. Our results revealed an altered sperm RNA modifications signature in the testis (6 types) and mature sperm (11 types) under the hypoxia model, with 4 types showing overlap (Am, Gm, m7G, and m22G). Our data first drew the signature of RNA modification profiles and comprehensively analyzed the alteration of RNA modification levels in mouse testis and sperm under a mouse hypoxia model. These data may be highly related to human conditions under a similar hypoxia environment.

The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening.

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple (Malus domestica). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1, an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2, encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3, encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1 This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1 Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2.

GABA consumption during early pregnancy impairs endometrial receptivity and embryo development in mice.

γ-Aminobutyrate (GABA) is commonly used as a food supplement and a health care product by young females, due to its positive roles in relieving stress, alleviating anxiety, and improving sleep. However, its recommended daily dose in different products varies widely. Besides, it is unknown whether, and how, GABA consumption during early pregnancy influences pregnancy establishment. In this study, we found that when pregnant mice were treated with a high (12.5 mg/g) dose of GABA (orally) during preimplantation, there was a reduction in the number of implantation sites on day 5 of pregnancy. Also, among these unimplanted embryos, most exhibited morphological degeneration and developmental retardation, and only a few of them developed into blastocysts but could not implant into the uterus. Moreover, the expression of uterine receptivity-related factors-LIF, E-cadherin, and HOXA10-were all downregulated, while the number of uterine glands was reduced in the high GABA dose group. Finally, in vitro results demonstrated that GABA (ranging from 10 to 50 µg/µL) markedly inhibited preimplantation embryo development in a dose-response manner. However, this inhibitory effect was not observed when the embryos were pretreated with 40 µΜ 2-hydroxysaclofen, a GABAB antagonist, indicating that GABA exerts its inhibitory effects via its B-type receptor. Our results suggest that exposure to certain GABA concentrations, during early pregnancy, can impair preimplantation embryo development via its B-type receptor, and endometrial receptivity, which greatly disturbs early embryo implantation in mice. These findings could raise concerns about GABA consumption during the early stages of pregnancy.

Apple (Malus domestica) MdERF2 negatively affects ethylene biosynthesis during fruit ripening by suppressing MdACS1 transcription.

Ripening in climacteric fruit requires the gaseous phytohormone ethylene. Although ethylene signaling has been well studied, knowledge of the transcriptional regulation of ethylene biosynthesis is still limited. Here we show that an apple (Malus domestica) ethylene response factor, MdERF2, negatively affects ethylene biosynthesis and fruit ripening by suppressing the transcription of MdACS1, a gene that is critical for biosynthesis of ripening-related ethylene. Expression of MdERF2 was suppressed by ethylene during ripening of apple fruit, and we observed that MdERF2 bound to the promoter of MdACS1 and directly suppressed its transcription. Moreover, MdERF2 suppressed the activity of the promoter of MdERF3, a transcription factor that we found to bind to the MdACS1 promoter, thereby increasing MdACS1 transcription. We determined that the MdERF2 and MdERF3 proteins directly interact, and this interaction suppresses the binding of MdERF3 to the MdACS1 promoter. Moreover, apple fruit with transiently downregulated MdERF2 expression showed higher ethylene production and faster ripening. Our results indicate that MdERF2 negatively affects ethylene biosynthesis and fruit ripening in apple by suppressing the transcription of MdACS1 via multiple mechanisms, thereby acting as an antagonist of positive ripening regulators. Our findings offer a deep understanding of the transcriptional regulation of ethylene biosynthesis during climacteric fruit ripening.

Apple MdACS6 Regulates Ethylene Biosynthesis During Fruit Development Involving Ethylene-Responsive Factor.

Ethylene biosynthesis in plants involves different 1-aminocyclopropane-1-carboxylic acid synthase (ACS) genes. The regulation of each ACS gene during fruit development is unclear. Here, we characterized another apple (Malus×domestica) ACS gene, MdACS6. The transcript of MdACS6 was observed not only in fruits but also in other tissues. During fruit development, MdACS6 was initiated at a much earlier stage, whereas MdACS3a and MdACS1 began to be expressed at 35 d before harvest and immediateley after harvest, respectively. Moreover, the enzyme activity of MdACS6 was significantly lower than that of MdACS3a and MdACS1, accounting for the low ethylene biosynthesis in young fruits. Overexpression of MdACS6 (MdACS6-OE) by transient assay in apple showed enhanced ethylene production, and MdACS3a was induced in MdACS6-OE fruits but not in control fruits. In MdACS6 apple fruits silenced by the virus-induced gene silencing (VIGS) system (MdACS6-AN), neither ethylene production nor MdACS3a transcript was detectable. In order to explore the mechanism through which MdACS3a was induced in MdACS6-OE fruits, we investigated the expression of apple ethylene-responsive factor (ERF) genes. The results showed that the expression of MdERF2 was induced in MdACS6-OE fruits and inhibited in MdACS6-AN fruits. Yeast one-hybrid assay showed that MdERF2 protein could bind to the promoter of MdACS3a. Moreover, down-regulation of MdERF2 in apple flesh callus led to a decrease of MdACS3a expression, demonstrating the regulation of MdERF2 on MdACS3a. The mechanism through which MdACS6 regulates the action of MdACS3a was discussed.

High prevalence and genetic diversity of noroviruses among children with sporadic acute gastroenteritis in Nanning City, China, 2010-2011.

A molecular epidemiological study of Norovirus (NoV) infections in children aged <5 years was conducted in the outpatient department of a hospital between January 2010 and December 2011 in Nanning City, Guangxi Zhuang Autonomous Region of China. Fecal samples were collected from 354 pediatric patients with acute gastroenteritis, and were screened for the presence of NoV with one-step real-time reverse-transcription polymerase chain reaction (RT-PCR). NoV genogroup II (GII) was detected in 28.5% (101/342) of samples, but no NoV GI was found. Eighty-four of the NoV GII strains were successfully sequenced, and they were clustered into seven genotypes: GII.4 (77.4%), GII.2 (8.3%), GII.14 (4.8%), GII.7 (3.6%), GII.3 (2.4%), GII.6 (2.4%), and GII.12 (1.2%). The predominant GII.4 variant in circulation was variant 2006b (92.3%). Importantly, the emergence of variant GII.4 2010 was detected. NoV was detected throughout the year, but mainly during the cold months. The highest prevalence of NoV was detected in young children aged <2 years. The NoV detection rates did not differ significantly in males and females. This is the first report to demonstrate the high prevalence and genetic diversity of NoVs in children with sporadic acute gastroenteritis in Nanning. Our study findings indicate the need for continual surveillance to monitor epidemiological changes and potential new variants of these viruses.

Porcine reproductive and respiratory syndrome virus infection induces microRNA novel-216 production to facilitate viral-replication by targeting MAVS 3´UTR.

Porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic losses in the swine industry. In this study, the high-throughput sequencing, microRNAs (miRNAs) mimic, and lentivirus were used to screen for potential miRNAs that can promote PRRSV infection in porcine alveolar macrophages or Marc-145 cells. It was observed that novel-216, a previously unidentified miRNA, was upregulated through the p38 signaling pathway during PRRSV infection, and its overexpression significantly increased PRRSV replication. Further analysis revealed that novel-216 regulated PRRSV replication by directly targeting mitochondrial antiviral signaling protein (MAVS), an upstream molecule of type Ⅰ IFN that mediates the production and response of type Ⅰ IFN. The proviral function of novel-216 on PRRSV replication was abolished by MAVS overexpression, and this effect was reversed by the 3'UTR of MAVS, which served as the target site of novel-216. In conclusion, this study demonstrated that PRRSV-induced upregulation of novel-216 served to inhibit the production and response of typeⅠ IFN and facilitate viral replication, providing new insights into viral immune evasion and persistent infection.

Efficacy and safety of Zhishixiaopi decoction in functional dyspepsia: A meta-analysis of randomized controlled trials.

BACKGROUND: Functional dyspepsia (FD) refers to a group of clinical symptoms caused by gastric and duodenal dysfunction. Which is a chronic functional disorder of the gastrointestinal tract with no cure. Zhishixiaopi decoction (ZSXP) is a type of Chinese herbal prescription that for treating FD. Although some randomized controlled trials (RCTs) report that ZSXP can significantly improve FD clinical symptoms and/or laboratory results, the trial design varies greatly among studies, making it challenging to draw a conclusion of the efficacy of ZSXP in treating FD. DESIGN: A systematic review and a meta-analysis. SETTING: Mianyang Central Hospital. OBJECTIVE: We conducted a systematic review and a meta-analysis to evaluate the efficacy and safety of ZSXP for treating FD. METHODS: We developed inclusion and exclusion criteria based on FD diagnosed criteria, interventions to treat FD, and outcomes of these interventions. Search strategies combined disease terms, symptom terms, anatomy terms and intervention terms. Literature search was conducted on eight online databases in English or Chinese, including Medline (via PubMed), Embase (via Ovid), The Cochrane Library, Web of Science, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database. INTERVENTION: The experimental group received oral administration of ZSXP and had a complete treatment process. ZSXP needs to fully contain the key herbal ingredients, regardless of whether the dosage of each herb is consistent with the original prescription. The Control group received monotherapy or combination therapy of other Western medicine and had a complete treatment process. OUTCOMES: The primary outcomes appraised were Total effective rate (TER), serum levels of Motilin(MOT), Gastrin(GAS) and Somatostatin (SS), Gastric emptying rate (GER) using a Barium meal method (GER(B)) and Gastric half emptying time using an Ultrasonic method (GHET(T1/2)). The Cochrane Bias Risk Tool was used for quality critical appraisal, Review Manager (RevMan) version 5.3 was used for statistical analysis. RESULTS: A total of 21 medium-quality RCTs were included in the meta-analysis. All 21 included studies were conducted and completed in Mainland China from 1998 to 2020. The treatment duration was between two weeks to two months. The meta-analysis suggests that, compared with the Western medicine treatment group, ZSXP treatment was more effective to improving the TER in FD [Odds ratio, OR = 3.54, 95%CI:(2.49, 5.05), Z = 6.99, P<0.00001] without significant increase in adverse events. However, no statistical significance was found between the groups in serum MOT levels [Standard mean difference, SMD = 1.05, 95%CI:(-0.42, 2.53), Z = 1.04, P = 0.16], serum GAS levels [SMD = -0.16, 95%CI:(-1.20, 0.88), Z = 0.31, P = 0.76], serum SS levels [SMD = -0.04, 95%CI:(-1.97, 1.89), Z = 0.04, P = 0.97], GER(B) [SMD = 1.09, 95%CI:(-0.81, 3.00), Z = 1.12, P = 0.26]or GHET(T1/2) [Mean difference, MD = -2.18, 95%CI:(-5.55, 1.19), Z = 1.27, P = 0.20]. CONCLUSIONS: The meta-analysis suggests that Zhishixiaopi treatment is a relatively effective and safe traditional Chinese medicine prescription and could be used for functional dyspepsia treatment. Considering the limitations of this study, the conclusion needs to be further confirmed by high-quality, multi-center, and large-sample randomized controlled trials.

Gamma-amino butyric acid and the A-type receptor suppress decidualization of mouse uterine stromal cells by down-regulating cyclin D3.

Uterine decidualization, characterized by stromal cell proliferation and differentiation into polyploid decidual cells, is critical to the establishment of pregnancy in mice, although the mechanism underlying this process remains poorly understood. This study is the first to investigate the expression of gamma-amino butyric acid (GABA) and the GABA A-type receptor π subunit (GABPR) in the early-pregnancy mouse uterus and their roles in decidualization. The expression of GABRP was detected from Day 4 to 8 of pregnancy. The effects of GABA and GABA A-type receptor on cell proliferation and apoptosis were investigated using the Cell Titer 96® AQueous One Solution Cell Proliferation Assay and flow cytometry. The levels of cyclin D3 protein were measured in cultured stromal cells artificially induced to undergo decidualization, and treated with GABA and a GABA A-type receptor agonist or antagonist, respectively, at the same time. mRNA expression of gabrp in implantation sites was lower than that in inter-implanted sites. GABA and GABRP protein were localized in the luminal and glandular epithelium, stromal cells, and decidual cells. In vitro, GABPR protein level was decreased in cultured stromal cells during the decidualization process. The addition of GABA and the GABA A-type receptor agonist Muscimol inhibited stromal cell proliferation, promoted apoptosis, and arrested cells in S-phase, followed by decreased expression of cyclin D3. These results show that in mice, GABA was actively involved in inhibiting stromal cell proliferation and suppresses decidualization progress through GABA A-type receptors by down-regulating cyclin D3 level.

Detection rates of norovirus gastroenteritis and factors associated with the infection before and during COVID-19 pandemic: a secondary analysis of surveillance data in Guangxi Zhuang Autonomous Region, Southern China.

Background: Changes in oral and hand hygiene behaviors have been reported during the COVID-19 pandemic in 2020 which may be associated with the incidence of the norovirus infection, a common cause of gastroenteritis. Objective: To estimate the trends of detection rates of norovirus gastroenteritis and associated factors before COVID-19 in 2015-2019 and during the COVID-19 in 2020 in Guangxi, China. Methods: A secondary analysis of Guangxi surveillance data of gastroenteritis patients was conducted. The detection rate in 2020 was predicted using an autoregressive integrated moving average modeland associated factors were analyzed using multiple logistic regression adjusted for interaction effects. Results: Of 7,903 gastroenteritis patients, the overall detection rate of norovirus gastroenteritis was 12.8%, (14.3% before and 6.1% during COVID-19). Detection rates gradually decreased from 2015 to 2020, of which the slope of predicted line was slightly flatter than the actual line. The odds ratios of detection were double to triple increase during COVID-19 in the younger age group and having food intake outside their homes. Tourist city, season, and types of food were independent associated factors. Conclusion: The detection rates were higher during the COVID-19 year among the population aged 45 years or less and those who consumed food outside their home.

Iron deficiency and overload in men and woman of reproductive age, and pregnant women.

Iron is an essential micronutrient for human biology and health, but high iron levels can be dangerous. Both iron deficiency and iron overload have been linked to reproductive health. This review summarizes the effects of iron deficiency and overload on omen of reproductive age (including pregnant women) and adult men. In addition, appropriate iron levels and the need for iron and nutritional supplements at different stages of life and pregnancy are discussed. In general, men should be aware of the risk of iron overload at any stage of life; women should take appropriate iron supplements before menopause; postmenopausal women should pay attention to the risk of iron overload; and pregnant women should receive reasonable iron supplementation in middle and late pregnancy. By summarizing evidence on the relationship between iron and reproductive health, this review aims to promote the development of strategies to optimize reproductive capacity from the perspective of nutrition. However, additional detailed experimental investigations and clinical studies are needed to assess the underlying causes and mechanisms of the observed associations between iron and reproductive health.

Efficacy of intravenous immunoglobulin in the treatment of recurrent spontaneous abortion: A systematic review and meta-analysis.

OBJECTIVE: We aimed to evaluate the efficacy of IVIG in the treatment with patients with recurrent spontaneous abortion (RSA). METHODS: PubMed, Embase, Web of science, Cochrane library were searched for randomized controlled (RCTs) about effect of IVIG on RSA from inception to August 20, 2021. Values of standardized mean differences (SMD) were determined for continuous outcomes. RESULTS: A total of 15 articles involving 902 patients were included in meta-analysis. Compared with the control group, IVIG can increase the live birth rate of recurrent spontaneous abortion patients [OR = 3.06, 95%CI (1.23, 7.64, P = .02]. However, recurrent abortion was divided into primary and secondary abortion for subgroup analysis, and there was no statistical difference. Besides, IVIG can also increase the expression in peripheral blood CD3+[OR = .4, 95%CI(-2.47, 3.15, P = .81],CD4+[OR = 1.16, 95%CI(-4.60, 6.93, P = .69], and a decrease in the expression of CD8+[OR = -1.78, 95%CI(-5.30, 1.75, P = .32], but there is no statistical significance. CONCLUSIONS: IVIG can significantly increase the live birth rate of recurrent spontaneous abortion. However, the evidence needs further verification and the curative effect is uncertain. It is necessary to further explore the pathogenesis of recurrent abortion and the mechanism of IVIG in the treatment of recurrent spontaneous abortion. Besides, more high-quality randomized controlled trials suitable for population, race, dosage and timing of IVIG in the treatment of recurrent abortion are needed to confirm its effectiveness, and effective systematic evaluation is also needed to evaluate its use benefit.