Targeting RNA G-quadruplex with repurposed drugs blocks SARS-CoV-2 entry.

The rapid emergence of SARS-CoV-2 variants of concern, the complexity of infection, and the functional redundancy of host factors, underscore an urgent need for broad-spectrum antivirals against the continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report the potential of RNA G-quadruplex (RG4)-targeting therapeutic strategy for SARS-CoV-2 entry. Combining bioinformatics, biochemical and biophysical approaches, we characterize the existence of RG4s in several SARS-CoV-2 host factors. In silico screening followed by experimental validation identify Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, as RG4-stabilizing agents with repurposing potential for COVID-19. Both TPT and BBM can reduce the protein level of RG4-containing host factors, including ACE2, AXL, FURIN, and TMPRSS2. Intriguingly, TPT and BBM block SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo. These findings emphasize the significance of RG4 in SARS-CoV-2 pathogenesis and provide a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment.

Time-Dependent and Excitation-Dependent Afterglow Color Evolution from the Assembly of Dual Carbon Dots in Zeolite.

Afterglow materials with time-dependent color output emerge as huge prospects in advanced optical information encryption but remain a formidable challenge due to the limited exciton transfer from a single emission center. Here, multiple time-dependent afterglow color evolutions are achieved by the strategy of controllable assembly of dual carbon dots (CDs) with an individual afterglow color and decay rate into an RHO zeolite. The strategy possesses high controllability such that B-CDs and G-CDs can be independently generated and in situ embedded into a matrix; in particular, the doped amount of two kinds of CDs can be adjusted conveniently to produce interesting variable afterglow colors. Triggered by different excitations, the prepared B&G-CDs@RHO composites exhibit the conversion of TADF and RTP behaviors, as well as time-dependent afterglow color output from deep-blue to green (365 nm excitation) and static cyan (254 nm excitation). The unique luminescence and excellent stability allow the composite applied in information encryption with high-security levels.

MicrobeTCM: A comprehensive platform for the interactions of microbiota and traditional Chinese medicine.

Thanks to the advancements in bioinformatics, drugs, and other interventions that modulate microbes to treat diseases have been emerging continuously. In recent years, an increasing number of databases related to traditional Chinese medicine (TCM) or gut microbes have been established. However, a database combining the two has not yet been developed. To accelerate TCM research and address the traditional medicine and micro ecological system connection between short board, we have developed the most comprehensive micro-ecological database of TCM. This initiative includes the standardization of the following advantages: (1) A repeatable process achieved through the standardization of a retrieval strategy to identify literature. This involved identifying 419 experiment articles from PubMed and six authoritative databases; (2) High-quality data integration achieved through double-entry extraction of literature, mitigating uncertainties associated with natural language extraction; (3) Implementation of a similar strategy aiding in the prediction of mechanisms of action. Leveraging drug similarity, target entity similarity, and known drug-target entity association, our platform enables the prediction of the effects of a new herb or acupoint formulas using the existing data. In total, MicrobeTCM includes 171 diseases, 725 microbes, 1468 herb-formulas, 1032 herbs, 15780 chemical compositions, 35 acupoint-formulas, and 77 acupoints. For further exploration, please visit https://www.microbetcm.com.

Impact of capitation on physicians' behavior among patients with hypertension: an interrupted time series study in rural China.

OBJECTIVE: The purpose of this study is to explore the change in physicians' hypertension treatment behavior before and after the reform of the capitation in county medical community. METHODS: Spanning from January 2014 to December 2019, monthly data of outpatient and inpatient were gathered before and after the implementation of the reform in April 2015. We employed interrupted time series analysis method to scrutinize the instantaneous level and slope changes in the indicators associated with physicians' behavior. RESULTS: Several indicators related to physicians' behavior demonstrated enhancement. After the reform, medical cost per visit for inpatient exhibited a reverse trajectory (-53.545, 95%CI: -78.620 to -28.470, p < 0.01). The rate of change in outpatient drug combination decelerated (0.320, 95%CI: 0.149 to 0.491, p < 0.01). The ratio of infusion declined for both outpatient and inpatient cases (-0.107, 95%CI: -0.209 to -0.004, p < 0.1; -0.843, 95%CI: -1.154 to -0.532, p < 0.01). However, the results revealed that overall medical cost per visit and drug proportion for outpatient care continued their initial upward trend. After the reform, the decline of drug proportion for outpatient care was less pronounced compared to the period prior to the reform, and length of stay also had a similar trend. CONCLUSION: To some extent, capitation under the county medical community encourages physicians to control the cost and adopt a more standardized diagnosis and treatment behavior. This study provides evidence to consider the impact of policy changes on physicians' behavior when designing payment methods and healthcare systems aimed at promoting PHC.

AntDAS-DDA: A New Platform for Data-Dependent Acquisition Mode-Based Untargeted Metabolomic Profiling Analysis with Advantage of Recognizing Insource Fragment Ions to Improve Compound Identification.

Data-dependent acquisition (DDA) mode in ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) can provide massive amounts of MS1 and MS/MS information of compounds in untargeted metabolomics and can thus facilitate compound identification greatly. In this work, we developed a new platform called AntDAS-DDA for the automatic processing of UHPLC-HRMS data sets acquired under the DDA mode. Several algorithms, including extracted ion chromatogram extraction, feature extraction, MS/MS spectrum construction, fragment ion identification, and MS1 spectrum construction, were developed within the platform. The performance of AntDAS-DDA was investigated comprehensively with a mixture of standard and complex plant data sets. Results suggested that features in complex sample matrices can be extracted effectively, and the constructed MS1 and MS/MS spectra can benefit in compound identification greatly. The efficiency of compound identification can be improved by about 20%. AntDAS-DDA can take full advantage of MS/MS information in multiple sample analyses and provide more MS/MS spectra than single sample analysis. A comparison with advanced data analysis tools indicated that AntDAS-DDA may be used as an alternative for routine UHPLC-HRMS-based untargeted metabolomics. AntDAS-DDA is freely available at http://www.pmdb.org.cn/antdasdda.

A fully human connective tissue growth factor blocking monoclonal antibody ameliorates experimental rheumatoid arthritis through inhibiting angiogenesis.

BACKGROUND: Connective tissue growth factor (CTGF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) by facilitating angiogenesis and is a promising therapeutic target for RA treatment. Herein, we generated a fully human CTGF blocking monoclonal antibody (mAb) through phage display technology. RESULTS: A single-chain fragment variable (scFv) with a high affinity to human CTGF was isolated through screening a fully human phage display library. We carried out affinity maturation to elevate its affinity for CTGF and reconstructed it into a full-length IgG1 format for further optimization. Surface plasmon resonance (SPR) data showed that full-length antibody IgG mut-B2 bound to CTGF with a dissociation constant (KD) as low as 0.782 nM. In the collagen-induced arthritis (CIA) mice, IgG mut-B2 alleviated arthritis and decreased the level of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, we confirmed that the TSP-1 domain of CTGF is essential for the interaction. Additionally, the results of Transwell assays, tube formation experiments, and chorioallantoic membrane (CAM) assays showed that IgG mut-B2 could effectively inhibit angiogenesis. CONCLUSION: The fully human mAb that antagonizes CTGF could effectively alleviate arthritis in CIA mice, and its mechanism is tightly associated with the TSP-1 domain of CTGF.

Impact of capitation prepayment on the medical expenses and health service utilization of patients with coronary heart disease: a community policy intervention program in a county in China.

BACKGROUND: Medical costs have been rising rapidly in recent years, and China is controlling medical costs from the perspective of health insurance payments. OBJECTIVES: To explore the impact of the capitation prepayment method on medical expenses and health service utilization of coronary heart disease (CHD) patients, which provides a scientific basis for further improvement of the payment approach. METHODS: The diagnosis records of visits for CHD in the database from 2014 to 2016 (April to December each year) were selected, and two townships were randomly selected as the pilot and control groups. Propensity score matching (PSM) and difference-in-difference (DID) model were used to assess changes in outpatient and inpatient expenses and health service utilization among CHD patients after the implementation of the capitation prepayment policy. RESULTS: There were eventually 3,900 outpatients and 664 inpatients enrolled in this study after PSM. The DID model showed that in the first year of implementing the reform, total outpatient expenses decreased by CNY 13.953, drug expenses decreased by CNY 11.289, as well as Medicare payments decreased by CNY 8.707 in the pilot group compared to the control group. In the second year of implementing the reform, compared with the control group, the pilot group had a reduction of CNY 3.123 in other expenses, and a reduction of CNY 6.841 in Medicare payments. There was no significant change in inpatient expenses in the pilot group compared to the control group, but there was an increase of 0.829 visits to rural medical institutions, and an increase of 0.750 visits within the county for inpatients. CONCLUSIONS: The capitation prepayment method has been effective in controlling the outpatient expenses of CHD patients, as well as improving the medical service capacity of medical institutions within the Medical Community, and increasing the rate of inside county visits for inpatients.

Association between gestational weight gain and preterm birth and post-term birth: a longitudinal study from the National Vital Statistics System database.

BACKGROUND: To evaluate the association between gestational weight gain (GWG) and preterm birth and post-term birth. METHODS: This longitudinal-based research studied singleton pregnant women from the National Vital Statistics System (NVSS) (2019). Total GWG (kg) was converted to gestational age-standardized z scores. The z-scores of GWG were divided into four categories according to the quartile of GWG, and the quantile 2 interval was used as the reference for the analysis. Univariate and multivariate logistic regression analyses were performed to investigate the association between GWG and preterm birth, post-term birth, and total adverse outcome (preterm birth + post-term birth). Subgroup analysis stratified by pre-pregnancy body mass index (BMI) was used to estimate associations between z-scores and outcomes. RESULTS: Of the 3,100,122 women, preterm birth occurred in 9.45% (292,857) population, with post-term birth accounting for 4.54% (140,851). The results demonstrated that low GWG z-score [odds ratio (OR): 1.04, 95% confidence interval (CI): 1.03 to 1.05, P < 0.001], and higher GWG z-scores (quantile 3: OR: 1.42, 95% CI: 1.41 to 1.44, P < 0.001; quantile 4: OR: 2.79, 95% CI: 2.76 to 2.82, P < 0.001) were positively associated with preterm birth. Low GWG z-score (OR: 1.18, 95% CI: 1.16 to 1.19, P < 0.001) was positively associated with an increased risk of post-term birth. However, higher GWG z-scores (quantile 3: OR: 0.84, 95% CI: 0.83 to 0.85, P < 0.001; quantile 4: 0.59, 95% CI: 0.58 to 0.60, P < 0.001) was associated with a decreased risk of post-term birth. In addition, low GWG z-score and higher GWG z-scores were related to total adverse outcome. A subgroup analysis demonstrated that pre-pregnancy BMI, low GWG z-score was associated with a decreased risk of preterm birth among BMI-obesity women (OR: 0.96, 95% CI: 0.94 to 0.98, P < 0.001). CONCLUSION: Our result suggests that the management of GWG may be an important strategy to reduce the number of preterm birth and post-term birth.

Effect of CD38 on B-cell function and its role in the diagnosis and treatment of B-cell-related diseases.

CD38 is a multifunctional receptor and enzyme present on the surface of B lymphocytes, which can induce B lymphocytes proliferation and apoptosis by crosslinking related cytokines to affect the function of B cells, thus affecting immune regulation in humans and promoting tumorigenesis. The level of CD38 expression in B cells has become an important factor in the clinical diagnosis, treatment, and prognosis of malignant tumors and other related diseases. Therefore, studying the relationship between CD38 expression on the surface of B cells and the occurrence of the disease is of great significance for elucidating its association with disease pathogenesis and the clinical targeted therapy. In this paper, we review the effects of CD38 on B-cell activation, proliferation, and differentiation, and elaborate the functional role and mechanism of CD38 expression on B cells. We also summarize the relationship between the level of CD38 expression on the surface of B cells and the diagnosis, treatment, and prognosis of various diseases, as well as the potential use of targeted CD38 treatment for related diseases. This will provide an important theoretical basis for the scientific research and clinical diagnosis and treatment of B-cell-related diseases.

A conversion-type lithium artificial synapse with dispersed nano-silica fabricated by UV-curing method.

The rapid growth of information puts forward new requirements for computer including denser memory capacity and faster response beyond the traditional von Neumann architecture. One promising strategy is to employ novel computing devices such as artificial synapses (AS). Here, an Au/LPSE-SiO2/Si AS (LPSE-SiO2AS) with a simple sandwich structure was fabricated by UV curing. LPSE-SiO2AS emulated synaptic plasticity including excitatory postsynaptic current, paired-pulse facilitation, and spike-dependent plasticity. It also simulated the memory strengthening and forgetting analogue to biological system. The realization of synaptic plasticity is due to the homogeneously dispersed nano-silica in LPSE, which acts as lithium ions trapping center and conducts a reversible electrochemical conversion reaction with Li ions with pulse stimulation. These results indicate the potential for LPSE-SiO2AS in future large-scale integrated neuromorphic networks.

The diagnostic value of glycosylated hemoglobin for gestational diabetes mellitus in Asian populations: A systematic review and meta-analysis.

AIMS: To investigate the role of glycosylated hemoglobin in assisting the oral glucose tolerance test for gestational diabetes mellitus (GDM) diagnosis in Asian populations. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to December 2020. Review Manager was applied to assess the quality of studies and risk of bias. MetaDiSc was used to measure diagnostic odds ratio, sensitivity, specificity, positive and negative likelihood ratios, area under receiving operating characteristic curve, and heterogeneity. RESULTS: A total of 19 original studies (32 669 women) were retrieved. The diagnostic efficiency of glycosylated hemoglobin was quantified from 4.5% to 6.0%. The pooled sensitivity (0.624, 0.609-0.638) and specificity and (0.624, 0.617-0.631) achieved optimal equilibrium at 5.0%. High sensitivity (0.911, 0.902-0.920) and low negative likelihood ratio (0.431, 0.365-0.508) at 4.6% as the rule-out cut-off, while with limited sensitivity, high specificity (0.990, 0.986-0.993) and positive likelihood ratio (8.309, 4.251-16.242) occurred at 5.8% as the rule-in cut-off. Heterogeneity was detected in parts of subgroup analyses (I2  > 50%). The diagnostic odds ratio and 95% confidence interval performance were better in the population with risk factors (6.314, 3.543-11.254) than those without (4.178, 2.332-7.488). CONCLUSIONS: Glycosylated hemoglobin is a potential tool in assisting GDM diagnosis in Asian populations, which has a better applicability based on the rule-out and rule-in algorithm (4.6%-5.8%), particularly for pregnant women with risk factors.

Chinese women's attitudes towards postpartum interventions to prevent type 2 diabetes after gestational diabetes: a semi-structured qualitative study.

BACKGROUND: Gestational diabetes (GDM) is a global problem affecting millions of pregnant women, including in mainland China. These women are at high risk of Type II diabetes (T2DM). Cost-effective and clinically effective interventions are needed. We aimed to explore Chinese women's perspectives, concerns and motivations towards participation in early postpartum interventions and/or research to prevent the development of T2DM after a GDM-affected pregnancy. METHODS: We conducted a qualitative study in two hospitals in Chengdu, Southwest China. Face-to-face semi-structured interviews were conducted with 20 women with recent experience of GDM: 16 postpartum women and 4 pregnant women. Women were asked about their attitudes towards postpartum screening for type 2 diabetes, lifestyle interventions, mHealth delivered interventions and pharmacologic interventions (specifically metformin). An inductive approach to analysis was used. Interviews were recorded, transcribed, and coded using NVivo 12 Pro. RESULTS: Most women held positive attitudes towards participating in T2DM screening, and were willing to participate in postpartum interventions to prevent T2DM through lifestyle change or mHealth interventions. Women were less likely to agree to pharmacological intervention, unless they had family members with diabetes or needed medication themselves during pregnancy. We identified seven domains influencing women's attitudes towards future interventions: (1) experiences with the health system during pregnancy; (2) living in an enabling environment; (3) the experience of T2DM in family members; (4) knowledge of diabetes and perception of risk; (5) concerns about personal and baby health; (6) feelings and emotions, and (7) lifestyle constraints. Those with more severe GDM, an enabling environment and health knowledge, and with experience of T2DM in family members expressed more favourable views of postpartum interventions and research participation to prevent T2DM after GDM. Those who perceived themselves as having mild GDM and those with time/lifestyle constraints were less likely to participate. CONCLUSIONS: Women with experiences of GDM in Chengdu are generally willing to participate in early postpartum interventions and/or research to reduce their risk of T2DM, with a preference for non-drug, mHealth based interventions, integrating lifestyle change strategies, blood glucose monitoring, postpartum recovery and mental health.

Gestational diabetes mellitus (GDM) is a common pregnancy complication affecting up to 1 in 6 pregnant women worldwide. Whilst the condition usually resolves soon after delivery, women are at high risk of developing type 2 diabetes mellitus (T2DM). In this study, we asked women living in Chengdu, a city in western China, about what they knew about their risk of diabetes and how they felt about participating in interventions after birth to prevent T2DM.After listening to the views of 20 women, we concluded that in this setting most women are happy to attend T2DM screening programs after birth, and would be willing to consider participating in interventions and research after birth to prevent T2DM.The interventions most preferred were those that aimed at lifestyle changes, and many women said would like to receive this information through their smartphone, for example through an app or social media channel. Women were reluctant to take medications to prevent T2DM.The main factors that influenced how women felt towards interventions to prevent T2DM were: (1) their experiences with the health system during pregnancy; (2) whether the home environment was supportive to make changes to diet and lifestyle; (3) any experiences of T2DM in family members; (4) their knowledge of diabetes and perception of risk; (5) concerns about personal and baby health; (6) feelings and emotions in the postnatal period, and (7) lifestyle constraints making it difficult to make dietary changes.

Gestational metformin administration in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized control studies.

AIMS: To evaluate metformin's effects on pregnancy outcomes in women with polycystic ovary syndrome. METHODS: A literature search was conducted using PubMed, EMBASE, Web of Science, MEDLINE, and the Cochrane Library. All randomized controlled trials comparing metformin administration during pregnancy versus placebo or blank in PCOS women were selected. The primary outcomes were the incidence of gestational diabetes mellitus (GDM), preterm delivery, and miscarriage. We combined data with the Review Manager. Bayesian meta-analysis was employed for further verification with the R software. RESULTS: Six randomized control trial studies involving 1229 participants were included. Metformin use was associated with reduced risk of preterm delivery (Risk ratios [RR], 0.45; 95% CI, 0.25-0.80; p, 0.007) and higher larger neonatal head circumference (Mean difference (MD), 0.47; 95% CI, 0.20-0.74; p, 0.0006] but had no effect on the incidence of GDM (RR 1.87; 95% CI, 0.58-1.87; p, 0.89), miscarriage (RR, 0.85; 95% CI, 0.45-1.60; p, 0.62), pre-eclampsia (RR, 1.18; 95% CI, 0.43-3.21; p, 0.75), neonatal length (MD, 0.33; 95% CI, -0.12-0.78; p, 0.15) and birthweight (MD, 73.78; 95% CI, -52.98-200.53; p, 0.17). CONCLUSIONS: Metformin administration in PCOS pregnancies was associated with reduced preterm delivery risk and larger neonatal head circumference.

Identification and Application of an Aptamer Targeting Papillary Thyroid Carcinoma Using Tissue-SELEX.

Aptamers, short DNA or RNA oligonucleotides, which evolved from systematic evolution of ligands by exponential enrichment (SELEX), can perform specific target recognition. Papillary thyroid carcinoma (PTC) is of high incidence worldwide, and the prognosis of advanced PTC is poor. Up to now, there is no specific biomarker that can identify PTC and defects still remain in existing diagnostic methods. Here we report an aptamer, termed TC-6, which is generated from tissue-SELEX by using sections of papillary thyroid carcinoma and a normal thyroid gland. TC-6 could specifically target intracellular components of papillary thyroid cells with high affinity ( Kd = 57.66 ± 5.93 nmol/L) and have performed excellent biocompatibility both in vivo and in vitro. Moreover, fluorescence imaging of PTC tumor-bearing mice revealed that TC-6 was able to accumulate in tumor sites and could distinguish thyroid carcinoma from other benign thyroid diseases efficiently. In addition, TC-6d, a truncated aptamer of TC-6, maintained its affinity toward PTC with Kd of 39.20 ± 8.20 nmol/L. Overall, these results indicate that TC-6 is a potential candidate for developing novel tools for diagnosis and targeted therapy of PTC.

FLA, which encodes a homolog of UBP, is required for chlorophyll accumulation and development of lemma and palea in rice.

KEY MESSAGE: FLA, the homolog of ubiquitin-specific protease does not have deubiquitination activity, but it is essential for flower and chloroplast development in rice. Ubiquitin-specific proteases (UBPs) are widely distributed and highly conserved proteins and are also members of the most important family of deubiquitination enzymes. Although the functions and phylogenies of UBPs from yeast, mammals and Arabidopsis have been widely reported, the functions and evolutionary relationships of UBPs in rice remain unclear. In this study, we characterized the rice flower and leaf color aberrant mutant (fla), which exhibited a variety of developmental defects, including abnormal floral organs and pollen development, and leaf bleaching. We isolated FLA by positional cloning and found that it encodes a homolog of ubiquitin-specific protease. FLA is a ubiquitously expressed gene with the highest expression in floral organs. Subcellular localization analysis indicated that FLA is a cell membrane protein. Through searches of the rice genome database ( http://rice.plantbiology.msu.edu ), we identified 35 UBP family members in the rice genome. These proteins were grouped into 16 subfamilies based on phylogenetic analysis, and FLA was found to belong to the G8 subfamily. In vitro activity assays revealed that FLA does not have deubiquitination activity. Our data suggest that FLA plays an important role in the development of floral organs and chloroplast in rice, but that this role probably does not involve deubiquitination activity, because FLA does not have an active site and deubiquitination activity.

Allowance and allocation of industrial volatile organic compounds emission in China for year 2020 and 2030.

As an effective pollution control method, emission allowance and allocation just implemented in volatile organic compounds (VOCs) control strategy of China in 2016. This article presents a possible way to set the emission allowance targets and establishes an allowance allocation model for the object year, 2020 and 2030, using 2010 as the reference year. On the basis of regression and scenario analysis method, the emission allowance targets were designed, which were 17.902Tg and 18.224Tg for 2020 and 2030, with an increasing rate of 28.75% and 31.06% compared to 2010. From the perspective of industries, processes using VOCs-containing products, like machinery and equipment manufacturing, would continue to be the most significant industrial VOCs emission sources in the future of China. Four allocation indicators were selected, which are per capita GDP of each province, per capita industrial VOCs emission of each province, the economic contribution of industrial sector to regional economy of each province, and the emission intensity per land area of each province, respectively. Based on information entropy, the weights of the indicators were calculated and an emission allocation model was established, and the results showed that provinces like Shandong, Jiangsu, Guangdong, Zhejiang and Fujian were calculated to obtain more emission allowance while burden more reduction responsibility. Meanwhile, provinces like Guizhou, Ningxia, Hainan, Qinghai and Xizang were on the contrary. This paper suggests governments to enhance or ease to industrial VOCs reduction burden of each province in order to stimulate its economy or change its way of economy development.

Image and Clinical Characteristics of the Right Coronary Artery Originating From the Left Coronary Sinus: A Database Review.

This article systematically explores the imaging and clinical characteristics of a relatively rare cardiac anomaly: the right coronary artery originating from the left coronary sinus. Through a comprehensive analysis of existing literature, this study aims to provide a comprehensive understanding of the prevalence, diagnostic methods, and potential clinical implications of this anatomical variation. Anatomical classification is introduced, along with clinical imaging diagnostic methods, including coronary angiography, computed tomography, and magnetic resonance imaging. Additionally, the review delves into the clinical significance of this anomaly, including its potential associations with myocardial ischemia, arrhythmias, and acute cardiac events, outlining clinical approaches to diagnosing myocardial ischemia. The study results consolidate current knowledge about this cardiac variation, emphasizing the importance of recognizing and appropriately managing it in clinical practice.

Upregulated LncRNA-LINC00659 expression by H. pylori infection promoted the progression of gastritis to cancer by regulating PTBP1 expression.

CONTEXT: Helicobacter pylori ( H. pylori ), a spiral-shaped bacterium, is closely associated with chronic, progressive gastric mucosal damage, gastric atrophy, and even gastric cancer (GC). An increasing number of studies have addressed the correlation between long noncoding RNAs (lncRNAs) and H. pylori pathogenicity in GC. OBJECTIVE: In this study, we found that the expression level of LINC00659 gradually increased in the progression from atrophic gastritis, intestinal metaplasia, and dysplasia to GC in H. pylori -infected patients. Thus, we aimed to further explore the function of LINC00659 in the progression of gastritis to cancer under H. pylori infection. MATERIALS AND METHODS: StarBase predictions, ribonucleic acid (RNA)-binding protein immunoprecipitation assays, and gene ontology functional annotation (GO)/Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to identify the RNA-binding proteins of LINC00659; moreover, qRT‒PCR, western blotting, RNA interference, and immunofluorescence assays were used to investigate the function of LINC00659. RESULTS: LINC00659 bound directly to the RNA-binding protein polypyrimidine tract-binding protein (PTBP1). Importantly, qRT‒PCR and western blot assays demonstrated that PTBP1 expression increased in the progression from inflammation to cancer in the stomach of H. pylori -infected patients and H. pylori -infected GES-1 cells. However, LINC00659 knockdown downregulated PTBP1 expression and inhibited PTBP1 binding under H. pylori infection. Finally, LINC00659 knockdown significantly reduced H. pylori -induced human gastric epithelial cell senescence and suppressed interleukin (IL)-6 and IL-8 secretion by reducing the phosphorylation level of NF-κB p65. CONCLUSIONS: This study indicated that LINC00659 may have the potential to be a novel promising prognostic and therapeutic marker for H. pylori -associated gastric diseases.

Influencing factors of glycemic control in singleton pregnancies complicated by gestational diabetes mellitus in western China: A retrospective study.

To investigate the factors influencing glycemic control in gestational diabetes mellitus (GDM) patients and their impacts on pregnancy outcomes, providing insights for GDM management. Pregnant women diagnosed with GDM at a tertiary hospital in western China in 2019. Participants were categorized based on varying levels of glycemic control during pregnancy. A retrospective analysis was conducted, utilizing univariate and multivariate regression analyses, to identify factors influencing glycemic control in GDM patients. Based on various approaches to manage glucose, subjects were categorized into A1 (diet and exercise guidance alone) and A2 (insulin usage) groups. Based on whether glucose levels met the glycemic target in women with GDM, subjects were further divided into satisfactory and unsatisfactory groups. A total of 2621 women meeting the inclusion criteria were enrolled in the study. Independent factors associated with GDM A2 included higher prepregnancy body mass index (odds ratio [OR] = 1.070, 95% confidence interval [CI]: 1.019-1.122, P = .006), a history of GDM (OR = 1.888, 95% CI: 1.052-3.389, P = .033), elevated fasting plasma glucose (FPG) in early pregnancy (OR = 1.828, 95% CI: 1.320-2.532, P < .001), elevated 1-hour postprandial glucose (1-h PG) (OR = 1.126, 95% CI: 1.0091.256, P = .034), and 2-h PG by oral glucose tolerance test (OGTT) (OR = 1.181, 95% CI: 1.046-1.333, P = .007). Higher FPG by OGTT was an independent risk factor for unsatisfactory glycemic control (OR = 1.590, 95% CI: 1.273-1.985, P < .001). Compared with the A1 group, the A2 group has longer hospitalization, higher rates of cesarean section, placenta previa, and neonatal pneumonia (P < .05). Compared with the satisfactory group, the unsatisfactory group has lower gestational age, lower rates of cesarean section and placenta previa, and higher rates of postpartum hemorrhage for mothers; lower length and weight, and higher rates of premature birth, jaundice, hypoglycemia, pneumonia, respiratory distress syndrome, anemia, hospitalization, and hospitalization for more than 15 days in both pediatric unit and neonatal intensive care unit for newborns (P < .05). Elevated prepregnancy body mass index, FPG in early pregnancy, 1-h and 2-h PG during OGTT, and with a history with GDM are independent factors influencing insulin utilization, while elevated 0-h PG is an independent influencing factor of unsatisfactory glycemic control. Poor glycemic control has negative impacts on both maternal and fetal outcomes under 2 classifications.

Comparative transcriptomic and metabolomic analyses reveal key regulatory gene for methyl jasmonate-induced steroidal saponins synthesis in Dioscorea composita.

Dioscorea composita (D. composita) is a perennial herb with abundant steroidal saponins that have gained worldwide attention for their remarkable efficacy in cardiovascular diseases. However, few studies have been worked on the regulatory network of steroidal saponins biosynthesis under phytohormone induced. In this study, we combined the transcriptome and metabolome analysis to reveal the variation of diosgenin and steroidal saponins in transcriptional and metabolism levels under methyl-jasmonate (MeJA) treatment. Although the application of MeJA indeed significantly increased the accumulation of diosgenin of D. composita, different types of steroidal saponins exhibited different accumulation patterns. Consistently, the expression levels of UDP-glycosyltransferases and Cytochrome P450 monooxygenases genes that highly related to the accumulation of steroidal saponins were either up- or down-regulated. Correlation analyses of transcription factors (TFs)-steroidal saponins and structural genes-TFs were further to identified the TFs potentially involved in the regulation of steroidal saponins biosynthesis. Silencing of DcWRKY11 in Dioscorea composita decreases the accumulation of steroidal saponins by regulating the expression steroidal saponins synthesis genes, suggesting that DcWRKY11 is a positive regulator in the regulation of steroidal saponins biosynthesis. Our findings take a deeper understanding of the regulatory network of MeJA-mediated steroidal saponins biosynthesis in D. composita.