Association between red cell distribution width and hypertension: Results from NHANES 1999-2018.

The relationship between red cell distribution width (RDW) and hypertension remains a contentious topic, with a lack of large-scale studies focusing on the adults in the United States. This study aimed to investigate the association between RDW and hypertension among US adults from 1999 to 2018. METHODS: Data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. RDW values were obtained from the Laboratory Data's Complete Blood Count with 5-part Differential-Whole Blood module. Hypertension data were obtained through hypertension questionnaires and blood pressure measurements. Multivariable weighted logistic regression analyses were conducted to assess the association between RDW and hypertension, followed by subgroup and smooth curve analyses. RESULTS: Compared to the non-hypertensive group, the hypertensive group exhibited higher RDW values (13.33±1.38 vs. 12.95±1.27, P <0.001). After adjusting for covariates, weighted multivariable logistic regression analysis revealed a positive correlation between RDW and hypertension prevalence (OR: 1.17, 95% CI 1.13, 1.21, P <0.001). When RDW was included as a categorical variable, participants in the fourth quartile had the highest risk of hypertension (OR: 1.86, 95% CI 1.70, 2.03, P <0.001). Subgroup analysis showed that, except for age, BMI and weak/failing kidneys, gender, race, education level, smoking, alcohol use, congestive heart failure, and stroke did not significantly influence this correlation (all P-values for interaction >0.05).Smooth curve fitting analysis revealed a reverse J-shaped relationship between RDW and hypertension prevalence, with an inflection point at 12.93%. CONCLUSION: We first explored the relationship between RDW and hypertension among US adults and discovered a reverse J-shaped association, providing further insights into the relationship between blood cell counts and hypertension and offering a new foundation for hypertension prevention and control.

Bariatric surgery and COVID-19 outcomes: a systematic review and meta-analysis.

BACKGROUND: Obesity and its associated complications have a negative impact on human health. Metabolic and bariatric surgery (MBS) ameliorates a series of clinical manifestations associated with obesity. However, the overall efficacy of MBS on COVID-19 outcomes remains unclear. OBJECTIVES: The objective of this article is to analyze the relationship between MBS and COVID-19 outcomes. SETTING: A meta-analysis. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched to retrieve the related articles from inception to December 2022. All original articles reporting MBS-confirmed SARS-CoV-2 infection were included. Outcomes including hospital admission, mortality, intensive care unit (ICU) admission, mechanical ventilation utilization, hemodialysis during admission, and hospital stay were selected. Meta-analysis with fixed or random-effect models was used and reported in terms of odds ratios (ORs) or weighted mean differences (WMDs) along with their 95% confidence intervals (CIs). Heterogeneity was assessed with the I2 test. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: A total of 10 clinical trials involving the investigation of 150,848 patients undergoing MBS interventions were included. Patients who underwent MBS had a lower risk of hospital admission (OR: .47, 95% CI: .34-.66, I2 = 0%), mortality (OR: .43, 95% CI: .28-.65, I2 = 63.6%), ICU admission (OR: .41, 95% CI: .21-.77, I2 = 0%), and mechanical ventilation (OR: .51, 95% CI: .35-.75, I2 = 56.2%) than those who did not undergo surgery, but MBS did not affect hemodialysis risk or COVID-19 infection rate. In addition, the length of hospital stay for patients with COVID-19 after MBS was significantly reduced (WMD: -1.81, 95% CI: -3.11-.52, I2 = 82.7%). CONCLUSIONS: Our findings indicate that MBS is shown to improve COVID-19 outcomes, including hospital admission, mortality, ICU admission, mechanical ventilation, and hospital stay. Patients with obesity who have undergone MBS infected with COVID-19 will have better clinical outcomes than those without MBS.

Effects of anti-inflammatory therapies on glycemic control in type 2 diabetes mellitus.

Background: The overall evidence base of anti-inflammatory therapies in patients with type 2 diabetes mellitus (T2DM) has not been systematically evaluated. The purpose of this study was to assess the effects of anti-inflammatory therapies on glycemic control in patients with T2DM. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched up to 21 September 2022 for randomized controlled trials (RCTs) with anti-inflammatory therapies targeting the proinflammatory cytokines, cytokine receptors, and inflammation-associated nuclear transcription factors in the pathogenic processes of diabetes, such as interleukin-1ß (IL-1ß), interleukin-1ß receptor (IL-1ßR), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB). We synthesized data using mean difference (MD) and 95% confidence interval (CI). Heterogeneity between studies was assessed by I2 tests. Sensitivity and subgroup analyses were also conducted. Results: We included 16 RCTs comprising 3729 subjects in the meta-analyses. Anti-inflammatory therapies can significantly reduce the level of fasting plasma glucose (FPG) (MD = - 10.04; 95% CI: -17.69, - 2.40; P = 0.01), glycated haemoglobin (HbA1c) (MD = - 0.37; 95% CI: - 0.51, - 0.23; P < 0.00001), and C-reactive protein (CRP) (MD = - 1.05; 95% CI: - 1.50, - 0.60; P < 0.00001) compared with control, and therapies targeting IL-1ß in combination with TNF-α have better effects on T2DM than targeting IL-1ß or TNF-α alone. Subgroup analyses suggested that patients with short duration of T2DM may benefit more from anti-inflammatory therapies. Conclusion: Our meta-analyses indicate that anti-inflammatory therapies targeting the pathogenic processes of diabetes can significantly reduce the level of FPG, HbA1c, and CRP in patients with T2DM.

Associations between COVID-19 infection and sex steroid hormones.

Aims: Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and within a few months of the first outbreak, it was declared a global pandemic by the WHO. The lethal virus SARS-CoV-2 is transmitted through respiratory droplets and enters host cells through angiotensin-converting enzyme 2 (ACE-2) receptors. ACE-2 receptors are highly expressed in many tissues, including testes. Therefore, the objective of this study was to summarize the available literature regarding the correlation between sex hormone levels and COVID-19. Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were reviewed systematically through August 2022 for studies comparing sex hormone levels between different patient groups: COVID-19 versus no COVID-19, more severe versus less severe COVID-19, and non-survivors versus survivors. Various types of clinical research reporting sex hormone levels, including free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17ß-oestradiol (E2), the oestradiol-to-testosterone ratio (E2/T), prolactin (PRL), and sex hormone-binding globulin (SHBG), were included. Random- or fixed-effects models were used to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Heterogeneity among the studies was assessed by the I2 index, and data analyses were performed using meta-analysis with Stata version 12.0. Results: Twenty-two articles that included 3369 patients were ultimately included in the meta-analysis. According to analysis of the included studies, patients with COVID-19 had significantly low T/LH, FSH/LH, and SHBG levels and high levels of LH, and E2/T, but their levels of FT, FSH, PRL, E2, and progesterone were not affected. Publication bias was not found according to funnel plots and Egger's regression and Begg's rank correlation tests. Conclusion: Low T/LH, FSH/LH, and SHBG serum levels and high LH, and E2/T levels may increase the risk of COVID-19. Additionally, the greater is the clinical severity of COVID-19, the higher is the probability of increases in LH, and E2/T serum levels and decreases in T/LH, FSH/LH, and SHBG levels. COVID-19 may have unfavourable effects on gonadal functions, which should be taken seriously by clinicians. Routine monitoring of sex hormone levels might help clinicians to evaluate disease severity in patients with COVID-19.

Functional Characterization of a Cucumber (Cucumis sativus L.) Vacuolar Invertase, CsVI1, Involved in Hexose Accumulation and Response to Low Temperature Stress.

Cucumber (Cucumis sativus L.), an important vegetable plant species, is susceptible to low temperature stress especially during the seedling stage. Vacuolar invertase (VI) plays important roles in plant responses to abiotic stress. However, the molecular and biochemical mechanisms of VI function in cucumber, have not yet been completely understood and VI responses to low temperature stress and it functions in cold tolerance in cucumber seedlings are also in need of exploration. The present study found that hexose accumulation in the roots of cucumber seedlings under low temperature stress is closely related to the observed enhancement of invertase activity. Our genome-wide search for the vacuolar invertase (VI) genes in cucumber identified the candidate VI-encoding gene CsVI1. Expression profiling of CsVI1 showed that it was mainly expressed in the young roots of cucumber seedlings. In addition, transcriptional analysis indicated that CsVI1 expression could respond to low temperature stress. Recombinant CsVI1 proteins purified from Pichia pastoris and Nicotiana benthamiana leaves could hydrolyze sucrose into hexoses. Further, overexpression of CsVI1 in cucumber plants could increase their hexose contents and improve their low temperature tolerance. Lastly, a putative cucumber invertase inhibitor was found could form a complex with CsVI1. In summary, these results confirmed that CsVI1 functions as an acid invertase involved in hexose accumulation and responds to low temperature stress in cucumber seedlings.

Genetic Determinants of Somatic Selection of Mutational Processes in 3,566 Human Cancers.

The somatic landscape of the cancer genome results from different mutational processes represented by distinct "mutational signatures." Although several mutagenic mechanisms are known to cause specific mutational signatures in cell lines, the variation of somatic mutational activities in patients, which is mostly attributed to somatic selection, is still poorly explained. Here, we introduce a quantitative trait, mutational propensity (MP), and describe an integrated method to infer genetic determinants of variations in the mutational processes in 3,566 cancers with specific underlying mechanisms. As a result, we report 2,314 candidate determinants with both significant germline and somatic effects on somatic selection of mutational processes, of which, 485 act via cancer gene expression and 1,427 act through the tumor-immune microenvironment. These data demonstrate that the genetic determinants of MPs provide complementary information to known cancer driver genes, clonal evolution, and clinical biomarkers. SIGNIFICANCE: The genetic determinants of the somatic mutational processes in cancer elucidate the biology underlying somatic selection and evolution of cancers and demonstrate complementary predictive power across cancer types.

Foxo1 controls gut homeostasis and commensalism by regulating mucus secretion.

Mucus produced by goblet cells in the gastrointestinal tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory network that controls mucus secretion and thereby changes gut microbiota has not been well studied. Here, we identify that Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in defects in goblet cell autophagy and mucus secretion, leading to an impaired gut microenvironment and dysbiosis. Subsequently, due to changes in microbiota and disruption in microbiome metabolites of short-chain fatty acids, Foxo1 deficiency results in altered organization of tight junction proteins and enhanced susceptibility to intestinal inflammation. Our study demonstrates that Foxo1 is crucial for IECs to establish commensalism and maintain intestinal barrier integrity by regulating goblet cell function.

A Fructan Exohydrolase from Maize Degrades Both Inulin and Levan and Co-Exists with 1-Kestotriose in Maize.

Enzymes with fructan exohydrolase (FEH) activity are present not only in fructan-synthesizing species but also in non-fructan plants. This has led to speculation about their functions in non-fructan species. Here, a cell wall invertase-related Zm-6&1-FEH2 with no "classical" invertase motif was identified in maize. Following heterologous expression in Pichia pastoris and in Nicotiana benthamiana leaves, the enzyme activity of recombinant Zm-6&1-FEH2 displays substrate specificity with respect to inulin and levan. Subcellular localization showed Zm-6&1-FEH2 exclusively localized in the apoplast, and its expression profile was strongly dependent on plant development and in response to drought and abscisic acid. Furthermore, formation of 1-kestotriose, an oligofructan, was detected in vivo and in vitro and could be hydrolyzed by Zm-6&1-FEH2. In summary, these results support that Zm-6&1-FEH2 enzyme from maize can degrade both inulin-type and levan-type fructans, and the implications of the co-existence of Zm-6&1-FEH2 and 1-kestotriose are discussed.

A γ-glutamylcysteine ligase AcGCL alleviates cadmium-inhibited fructooligosaccharides metabolism by modulating glutathione level in Allium cepa L.

Fructooligosaccharides (FOS) are important carbohydrates in plants. Cadmium (Cd) toxicity limits growth and development in several plant species. Whether FOS metabolism is affected by Cd and the molecular mechanisms of tolerance of the effects of Cd toxicity in plants remain enigmatic. In the present study, FOS metabolism was analyzed under Cd stress in onion (Allium cepa L.). Results showed that Cd stress can inhibit FOS accumulation in onion, followed by the upregulation of a putative onion γ-glutamylcysteine ligase gene AcGCL. Heterologous expression of the AcGCL protein in Escherichia coli revealed that this recombinant enzyme has GCL activity. Furthermore, overexpressing AcGCL significantly increased glutathione (GSH) accumulation in young onion roots under Cd treatment, accompanied by increased phytochelatin (PC) amount, and increased transcript expression of GSH synthetase (GS), and phytochelatin synthase (PCS) genes. Notably, compared with control, overexpressing AcGCL ameliorated Cd phytotoxicity on onion FOS metabolism, which correlated with increased FOS synthesis. Taken together, these results suggest that the function of AcGCL as a γ-glutamylcysteine ligase can alleviate Cd inhibited FOS metabolism by modulating GSH levels in onion.

The chemistry of Daphniphyllum alkaloids.

The triterpenoids Daphniphyllum alkaloids share the unique fused hexacyclic ring framework are isolated from the genus Daphniphyllum. These natural products possess comprehensive biological activities and exhibit excellent potential medicinal appliment. This review covers the reported isolation studies and biological activities of Daphniphyllum alkaloids spanning the period from 1966 to the beginning of 2020, In the meantime, the total synthesis of Daphniphyllum alkaloids will be emphatically summarized for supplement over this review series.

Integrative analysis reveals distinct subtypes with therapeutic implications in KRAS-mutant lung adenocarcinoma.

BACKGROUND: KRAS-mutant lung adenocarcinomas (LUADs) are heterogeneous and frequently occur in smokers. The heterogeneity of KRAS-mutant LUAD has been an obstacle for the drug discovery. METHODS: We integrated multiplatform datatypes and identified two corresponding subtypes in the patients and cell lines. We further characterized the features of these two subtypes and performed drug screening to identify subtype-specific drugs. Finally, we used the defining features of the KRAS subtypes for drug sensitivity prediction. FINDINGS: Patient-Subtype 1 (PS1) was characterized by increased smoking-related mutational signature activity, a low tumor-infiltrating lymphocyte (TIL)-associating score and STK11/KEAP1 co-mutations. Patient-Subtype 2 (PS2) was characterized by an increased smoking-related methylation signature activity, a high TIL-associating score and increased KRAS dependency. The cell line subtypes faithfully recapitulated all the patients' features. Drug screening of the two cell line subtypes yielded several potential candidates, such as cytarabine and enzastaurin for Cell-line-Subtype 1 (CS1) and a BTK inhibitor QL-XII-61 for Cell-line-Subtype 2 (CS2). The defining features, such as smoking-related methylation signature, were significantly associated with the sensitivity to several drugs. INTERPRETATION: The heterogeneity of KRAS-mutant LUAD is associated with smoking-related genomic and epigenomic aberration along with other features such as immunogenicity, KRAS dependency and STK11/KEAP1 co-mutations. These features might be used as biomarkers for drug sensitivity prediction. FUND: This research was funded by the Young Scientists Fund of the National Natural Science Foundation of China, the Natural Science Foundation of Fujian Province, China and the Education and Research Foundation for Young Scholars of Education Department of Fujian Province, China.