Utilizing transcriptomics and metabolomics to unravel key genes and metabolites of maize seedlings in response to drought stress.

BACKGROUND: Drought stress can substantially restrict maize growth and productivity, and global warming and an increasing frequency of extreme weather events are likely to result in more yield losses in the future. Therefore, unraveling the molecular mechanism underlying the response to drought stress is essential for breeding drought-resilient crops. RESULTS: In this study, we subjected the 3-leaf-period plants of two maize inbred lines, a drought-tolerant line (si287) and a drought-sensitive line (X178), to drought stress for seven days while growing in a chamber. Subsequently, we measured physiological traits and analyzed transcriptomic and metabolic profiles of two inbred lines. Our KEGG analysis of genes and metabolites revealed significant differences in pathways related to glycolysis/gluconeogenesis, flavonoid biosynthesis, starch and sucrose metabolism, and biosynthesis of amino acids. Additionally, our joint analysis identified proline, tryptophan and phenylalanine are crucial amino acids for maize response to drought stress. Furthermore, we concentrated on tryptophan (Trp), which was found to enhance tolerance via IAA-ABA signaling, as well as SA and nicotinamide adenine dinucleotide (NAD) consequent reactive oxygen species (ROS) scavenging. We identified three hub genes in tryptophan biosynthesis, indole-3-acetaldehyde oxidase (ZmAO1, 542,228), catalase 1 (ZmCAT1, 542,369), and flavin-containing monooxygenase 6 (ZmYUC6, 103,629,142), High expression of these genes plays a significant role in regulating drought tolerance. Two metabolites related to tryptophan biosynthesis, quinolinic acid, and kynurenine improved maize tolerance to drought stress by scavenging reactive oxygen species. CONCLUSIONS: This study illuminates the mechanisms underlying the response of maize seedlings to drought stress. Especially, it identifies novel candidate genes and metabolites, enriching our understanding of the role of tryptophan in drought stress. The identification of distinct resistance mechanisms in maize inbred lines will facilitate the exploration of maize germplasm and the breeding of drought-resilient hybrids.

Decreased frequency of a novel T-lymphocyte subset, CD3+ CD4- CD7+ CD57- T cells, in hepatitis B virus-related end-stage liver disease might contribute to disease progression.

CD7 and CD57 are related to the differentiation and functional stages of CD8+ T cells. However, the role of their combined presence in CD8+ T cells in patients with chronic hepatitis B virus (HBV) infection, especially those with end-stage liver disease, remains unclear. Blood samples from healthy volunteers and patients with chronic hepatitis B were analyzed via Luminex assay and ELISA to measure plasma cytokine levels. Further, recombinant IL-22 was used to stimulate peripheral blood mononuclear cells from healthy volunteers, and the frequency of CD3+ CD4- CD7+ CD57- T cells and apoptosis rates were investigated via flow cytometry. Patients with end-stage liver disease, particularly those with acute to chronic liver failure, showed decreased CD3+ CD4- CD7+ CD57- T cell frequency. Furthermore, the prevalence of CD3+ CD4- CD7+ CD57- T cells was negatively correlated with disease severity, prognosis, and complications (ascites). We also observed that IL-22 promoted apoptosis and brought about a decrease in the number of CD3+ CD4- CD7+ CD57- T cells in a dose-dependent manner. CD3+ CD4- CD7+ CD57- T cells displayed a B and T lymphocyte attenuator (BTLA)high CD25high CD127high immunosuppressive phenotype and showed low interferon-γ, tumor necrosis factor-α, granzyme A, and perforin expression levels. The present findings will elucidate the pathogenesis of HBV-related end-stage liver disease and aid the identification of novel drug targets.

3-Methyladenine-enhanced susceptibility to sorafenib in hepatocellular carcinoma cells by inhibiting autophagy.

As an effective targeted therapy for advanced hepatocellular carcinoma (HCC), sorafenib resistance has been frequently reported in recent years, with the activation of autophagy by cancer cells under drug stress being one of the crucial reasons. Sorafenib treatment could enhance autophagy in HCC cells and autophagy is also considered as an important mechanisms of drug resistance. Therefore, the inhibition of autophagy is a potential way to improve the sensitivity and eliminate drug resistance to restore their efficacy. To determine whether autophagy is involved in sorafenib resistance and investigate its role in the regulation of HepG2 cells' (an HCC cell line) chemosensitivity to sorafenib, we simultaneously treated HepG2 with sorafenib and 3-Methyladenine (3-MA) (a common autophagy inhibitor). First, by performing cell counting kit 8 cell viability assay, Hoechst 33342 apoptosis staining, and Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis kit detection, we found that both sorafenib and 3-MA effectively inhibitted the proliferative activity of HepG2 cells and induced their apoptosis to a certain extent. This effect was significantly enhanced after these two drugs were combined, which was also confirmed by the increased expression of apoptosis-related proteins. Subsequently, by using AAV-GFP-LC3 transfection methods and transmission electron microscopy, we found that both the number and activity of autophagosomes in HepG2 cells in sorafenib and 3-MA group were significantly reduced, suggesting that autophagy activity was inhibited, and this result was consistent with the expression results of autophagy-related proteins. Therefore, we conclude that 3-MA may attenuate the acquired drug resistance of sorafenib by counteracting its induction of autophagy activity, thus enhancing its sensitivity to advanced HCC therapy.

Ratios of regulatory T cells/T-helper 17 cells and transforming growth factor-ß1/interleukin-17 to be associated with the development of hepatitis B virus-associated liver cirrhosis.

BACKGROUND AND AIM: The aim of this study is to evaluate the association of the regulatory T cells (Treg)/T-helper (Th) 17 cells and transforming growth factor-ß1 (TGF-ß1)/interleukin-17 (IL-17) ratios with the survival and disease progression in patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC). METHODS: The frequencies of Treg and Th17 cells were analyzed in 28 patients with HBV-LC, 70 patients with chronic hepatitis B (CHB) and 20 normal controls (NC) by flow cytometry. The levels of cytokines related to Treg/Th17 differentiation, including IL-10, TGF-ß1, IL-17, and IL-23, were measured by ELISA. RESULTS: Compared with NC, Treg cells were significantly increased in CHB patients and slightly increased in HBV-LC patients, whereas Th17 cells were markedly increased both in patients with CHB and HBV-LC. HBV-LC patients, especially the nonsurvival ones, manifested a profound decrease in the Treg/Th17 ratio, which was negatively correlated with Child-Pugh and model of end-stage liver disease scores. Serum IL-10, TGF-ß1, IL-17, and IL-23 levels were all significantly higher in HBV-LC patients than in NC. In addition, the TGF-ß1/IL-17 ratio was also markedly increased in patients with HBV-LC, especially in nonsurvival and decompensated liver cirrhosis patients, and positively correlated with total bilirubin, Child-Pugh, and model of end-stage liver disease scores. CONCLUSIONS: The decreased Treg/Th17 ratio and increased TGF-ß1/IL-17 ratio may be associated with the survival and disease progression in HBV-LC patients, and both of the two ratios can be used independently to predict the prognosis and disease progression of HBV-LC patients.

Impacts of conventional and biodegradable microplastics in maize-soil ecosystems: Above and below ground.

The increasing accumulation of microplastics (MPs) in agroecosystems has raised significant environmental and public health concerns, facilitating the application of biodegradable plastics. However, the comparative effects of conventional and biodegradable MPs in agroecosystem are still far from fully understood. Here we developed microcosm experiments to reveal the ecological effects of conventional (polyethylene [PE] and polypropylene [PP]) and biodegradable (polyadipate/butylene terephthalate [PBAT] and polycaprolactone [PCL]) MPs (0, 1%, 5%; w/w) in the maize-soil ecosystem. We found that PCL MPs reduced plant production by 73.6-75.2%, while PE, PP and PBAT MPs elicited almost negligible change. The addition of PCL MPs decreased specific enzyme activities critical for soil nutrients cycling by 71.5-95.3%. Biodegradable MPs tended to reduce bacterial α-diversity. The 1% treatments of PE and PBAT, and PCL enhanced bacterial networks complexity, whereas 5% of PE and PBAT, and PP had adverse effect. Moreover, biodegradable MPs appeared to reduce the α-diversity and networks complexity of fungal community. Overall, PCL reduced the ecosystem multifunctionality, mainly by inhibiting the microbial metabolic activity. This study offers evidence that biodegradable MPs can impair agroecosystem multifunctionality, and highlights the potential risks to replace the conventional plastics by biodegradable ones in agricultural practices.

Clinical characteristics and predictors of delayed discharge among children with SARS­CoV­2 Omicron variant infection.

The present study investigated the epidemiology and clinical characteristics of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant and determined the risk factors for delayed discharge or release from isolation for pediatric patients in Quanzhou, China in 2022. There were 145, 254 and 23 patients in the asymptomatic, mildly symptomatic and moderately symptomatic categories, respectively. The proportion of pediatric patients in the moderately symptomatic category increased with increasing age. No child aged <1 year and 9.02% of patients aged 13-18 years were in the moderately symptomatic category. The proportion of patients with asymptomatic infection did not differ significantly by vaccination status. The median days until the first negative conversion of viral RNA was 11 days, and the median hospitalization duration was 16 days. Most symptoms appeared in the upper respiratory tract. Notably, ~33.23% of patients showed elevated aspartate aminotransferase levels. C-reactive protein and interleukin-6 (IL-6) levels, and lymphocyte counts were consistently lower in asymptomatic patients than those in in symptomatic patients. Adjusted logistic regression analyses indicated that IL-6 levels and time to the first negative conversion of viral RNA were independent risk factors for delayed discharge. The area under the curve of the regression model for predicting delayed discharge was 0.760. In conclusion, these results could facilitate the formulation of global epidemic prevention policies for pediatric patients.

BTLA contributes to acute-on-chronic liver failure infection and mortality through CD4+ T-cell exhaustion.

B- and T-lymphocyte attenuator (BTLA) levels are increased in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This condition is characterized by susceptibility to infection and T-cell immune exhaustion. However, whether BTLA can induce T-cell immune exhaustion and increase the risk of infection remains unclear. Here, we report that BTLA levels are significantly increased in the circulating and intrahepatic CD4+ T cells from patients with HBV-ACLF, and are positively correlated with disease severity, prognosis, and infection complications. BTLA levels were upregulated by the IL-6 and TNF signaling pathways. Antibody crosslinking of BTLA activated the PI3K-Akt pathway to inhibit the activation, proliferation, and cytokine production of CD4+ T cells while promoting their apoptosis. In contrast, BTLA knockdown promoted their activation and proliferation. BTLA-/- ACLF mice exhibited increased cytokine secretion, and reduced mortality and bacterial burden. The administration of a neutralizing anti-BTLA antibody reduced Klebsiella pneumoniae load and mortality in mice with ACLF. These data may help elucidate HBV-ACLF pathogenesis and aid in identifying novel drug targets.

Botany, ethnopharmacology, phytochemistry and pharmacology of Erodii Herba Geranii Herba-An review.

ETHNOPHARMACOLOGICAL RELEVANCE: As a commonly used traditional Chinese herbal medicine, Erodii Herba Geranii Herba (Geranium wilfordii Maxim., Geranium carolinianum L. and Erodium stephanianum Willd.), which was known as Laoguancao (Chinese:), has high medicinal value. It has been used to dispel rheumatism, dredge the meridians, activate blood circulation, remove blood stasis, clear heat and detoxify, and stop diarrhea and dysentery. It's also used to treat eczema, sores, carbuncles, boils caused by accumulation of damp toxin. AIM OF THE REVIEW: This review aimed to provide a systematic and comprehensive analysis of the current research progress in terms of the botany, ethnopharmacology, phytochemistry and pharmacological activities of Erodii Herba Geranii Herba, and discuss expectations for prospective research and implementation about this herb. MATERIALS AND METHODS: Information on Erodii Herba Geranii Herba was gathered via the Internet (using Google Scholar, Baidu Scholar, Pubmed, Elsevier, ACS, Medline Plus, CNKI and Web of Science) and libraries. Additionally, information was also obtained from local books and brilliant scholars in ethnopharmacology. RESULTS: More than isolated 240 chemical compounds were recorded, and main compositions are tannins, flavones, organic acids and volatile oil. The pharmacoactives of Erodii Herba Geranii Herba and its active constituents are diverse, including antibacterial, antiviral, antioxidant, liver and kidney protection, anti-inflammatory and analgesic, other activities. Among them, the antibacterial, antiviral, anti-inflammatory, analgesic, antidiarrheal and other pharmacological activities of it are consistent with traditional applications. CONCLUSIONS: All kinds of research conducted on Erodii Herba Geranii Herba, especially in field of ethnopharmacological use, phytochemicals and pharmacology have been reviewed. There are plenty of active compounds with varied effects in Erodii Herba Geranii Herba. However, some traditional applications and pharmacological activities of Erodii Herba Geranii Herba have not been scientifically evaluated or convincing due to incomplete methods and ambiguous results, as well as the lack of clinical data. In order to verify the pharmacological activity, clinical efficacy and safety of it, a systematic and comprehensive research evaluation is also required. As an important traditional Chinese medicine, Erodii Herba Geranii Herba should be further explored to promote the development of new drugs and therapeutics for various diseases. How to make better use of it should be paid more attention to.

IL2-inducible T-cell Kinase is Required for HBV-induced Type T Interferon Expression and Antiviral Response.

Background and Aims: Hepatitis B is a vaccine-preventable liver infection caused by the hepatitis B virus (HBV), and is seen as a serious global health problem. HBV infection induces the expression of type I interferon (IFN), including IFN-α and IFN-ß, which have anti-HBV activities, and have been used for HBV treatment. IL2-inducible T-cell kinase (ITK) is a tyrosine kinase, which regulates T-cell differentiation and activation, while its precise effects on type I IFN production during HBV infection remain unknown. Methods: We monitored the ITK expression in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with acute and chronic HBV infection. We used ITK inhibitor ibrutinib to treat hepatocytes and evaluated the type I IFN expression after HBV infection. We also administrated ibrutinib to mice and evaluated its effect on HBV infection in vivo. We generated ITK, suppressor of cytokine signaling 1 (SOCS1) knockout and ITK/SOCS1 double knockout cells using CRISPR, and monitored the HBV-induced type I IFN production. Results: ITK and type I IFN were upregulated in patients with acute HBV infection. Inhibition of ITK by ibrutinib suppressed HBV-induced expression of type I IFN mRNA in mice. ITK knockout cells had decreased IRF3 activation but promoted the expression of SOCS1. ITK negatively regulated SOSC1 expression. The down regulation of type I IFN in ITK knockout cells after HBV stimulation was abolished in the absence of SOCS1. Conclusions: ITK regulated HBV-induced expression of type I IFN mRNA by modulating SOCS1.

Metabolic status indicators and influencing factors in non-obese, non-centrally obese nonalcoholic fatty liver disease.

Non-obese nonalcoholic fatty liver disease (NAFLD) is characterized by metabolic disorders and related complications. This study aimed to provide an integrated description of clinical, metabolic, and influencing factors for a specific category of patients with non-obese NAFLD. A total of 36 participants with body mass index (BMI) < 28 kg/m2 and visceral adipose tissue < 100 cm2 were classified into 2 groups: the non-obese, non-centrally obese control group (n = 17) and non-obese, non-centrally obese NAFLD group (n = 19). Hypertriglyceridemia, impaired fasting glucose, low high-density lipoprotein cholesterol levels, and hypertension were used to determine whether participants were metabolically abnormal. Based on a logistic regression model, odds ratios for the factors influencing NAFLD with 95% confidence intervals were calculated. Insulin resistance (IR) and fasting plasma glucose (FPG) levels were higher in the NAFLD group than in the control group (P < .05). The NAFLD group had a higher metabolic abnormality rate than the healthy control group (36.84% vs 5.88%, P = .044). Correlation analysis showed that IR was positively correlated with FPG and triglyceride (P < .05). BMI was the main influencing factor of NAFLD (regression coefficient ß = 0.631; odds ratio = 1.879; 95% confidence interval, 1.233-2.863). NAFLD patients with a BMI < 28 kg/m2 and visceral adipose tissue < 100 cm2 had more apparent IR, higher FPG, and a higher metabolic abnormality rate. IR may be affected by FPG and triglyceride. Even in non-obese and non-centrally obese individuals, BMI should be controlled to avoid NAFLD.

RAS-targeted cancer therapy: Advances in drugging specific mutations.

Rat sarcoma (RAS), as a frequently mutated oncogene, has been studied as an attractive target for treating RAS-driven cancers for over four decades. However, it is until the recent success of kirsten-RAS (KRAS)G12C inhibitor that RAS gets rid of the title "undruggable". It is worth noting that the therapeutic effect of KRASG12C inhibitors on different RAS allelic mutations or even different cancers with KRASG12C varies significantly. Thus, deep understanding of the characteristics of each allelic RAS mutation will be a prerequisite for developing new RAS inhibitors. In this review, the structural and biochemical features of different RAS mutations are summarized and compared. Besides, the pathological characteristics and treatment responses of different cancers carrying RAS mutations are listed based on clinical reports. In addition, the development of RAS inhibitors, either direct or indirect, that target the downstream components in RAS pathway is summarized as well. Hopefully, this review will broaden our knowledge on RAS-targeting strategies and trigger more intensive studies on exploiting new RAS allele-specific inhibitors.

A simple-to-use score system for predicting HBsAg clearance to peginterferon alfa-2b in nucleoside analogs-experienced chronic hepatitis B patients.

Objective: Patients with chronic hepatitis B (CHB) often fail to achieve clearance of the hepatitis B surface antigen (HBsAg) with peginterferon treatment. Our study aimed to develop a simple-to-use scoring system to predict the likelihood of HBsAg clearance following treatment with peginterferon alfa-2b(PEG-IFN-α2b) in patients with CHB. Methods: A total of 231 patients were enrolled and divided into HBsAg clearance (n = 37) and non-HBsAg clearance (n = 194) groups. Multifactor logistic models were constructed using univariate and multiple logistic regression analyses. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis were used to evaluate the discrimination, calibration, and clinical applicability of the predictive scoring system. Results: Four clinical variables (age, baseline HBsAg level, HBsAg level decline at week 12, and alanine aminotransferase ratio at week 12) were independently associated with HBsAg clearance after PEG-IFN-α2b treatment and, therefore, were used to develop a predictive scoring system ranging from 0 to 13. The optimal cut-off value was >4, with a sensitivity of 86.49%, specificity of 72.16%, positive predictive value of 37.2%, negative predictive value of 96.6%, and an AUC of 0.872. This model exhibited good discrimination, calibration, and clinical applicability. Among patients with scores <4, 4, or > 4 HBsAg clearance was achieved in 0.85, 14.29, and 37.21% of the patients, respectively. Conclusion: The scoring system could effectively predict the predominance of HBsAg clearance after PEG-IFN-α2b treatment in the early stage. This may be helpful when making clinical decisions for the treatment of patients with CHB.

Clinical characteristics of patients infected with novel coronavirus wild strain, Delta variant strain and Omicron variant strain in Quanzhou: A real­world study.

This study aimed to investigate the clinical features of patients infected with novel coronavirus wild strains, Delta variant strains and Omicron variant strains to provide a reference for early clinical diagnosis and prognostic assessment. The demographic, clinical symptoms and ancillary examination data of 47 patients with novel coronavirus wild type strain infection, 18 with Delta variant infection and 20 with Omicron variant infection admitted to the First Hospital of Quanzhou affiliated with Fujian Medical University were collected and analyzed. The novel coronavirus wild strain and Delta strain were the predominant clinical types; patients infected with the Omicron strain were mainly asymptomatic. Fever and fatigue were the main clinical manifestations in the wild strain and Delta strain groups, whereas dry cough, nasal congestion, sore throat and fever were common clinical manifestations in the Omicron strain group. The Delta strain and Omicron variant groups had fewer comorbidities than the wild-type strain group, but no significant reduction was observed in the negative conversion time of nucleic acids. Significant differences were found in the neutrophil count/lymphocyte count ratio, lymphocyte count, eosinophil count, red blood cell count, hemoglobin level, erythrocyte sedimentation rate, C-reactive protein, prothrombin time, international normalized ratio and plasma D-dimer, PH, PaO2, lactic acid and albumin levels among the three groups. Patients infected with the Omicron strain in Quanzhou presented with mild symptoms of the upper respiratory tract as the primary clinical manifestation and had few comorbidities and a good prognosis; however, the negative conversion time of the new coronavirus nucleic acid was still considerably long.

Acid rain reduces plant-photosynthesized carbon sequestration and soil microbial network complexity.

Acid rain threatens the structure and function of terrestrial ecosystems; however, the mechanisms by which acid rain affects the photosynthesized carbon (C) fluxes and soil microbial communities are far less understood, thus impeding accurate projections of regional C flux in the plant-soil-atmosphere system. In this study, we performed an isotopic 13C labeling experiment to trace C footprints in a maize-soil system under acid rain pollution (pH 4.5 and 3.0; SO42-/NO3-= 2:1). Our results showed that acid rain exerted a negligible effect on total plant biomass as well as shoot biomass. Acid rain of pH 3.0 inhibited plant 13C assimilation and the flow of fixed 13C to the soil. Acid rain decreased soil total C and organic nitrogen (N) but increased inorganic N (i.e., nitrate-N) content. The acid rain of pH 3.0 enhanced soil bulk density, led to soil acidification, and promoted soil microbial diversity. However, acid rain reduced the connectivity and complexity of soil microbial network. Soil 13C content was mainly regulated by soil pH, ammonium-N, and root biomass. Our findings demonstrated that acid rain reduces photosynthesized C sequestration of maize-soil system and soil microbial taxa interactions.

Distinguishing COVID-19 from seasonal influenza in patients under age 65 years-a retrospective observational cohort study comparing the 2009 influenza A (H1N1) and 2022 SARS-CoV-2 pandemics.

Introduction: This study explored the differences in clinical characteristics between the 2009 pandemic influenza A (H1N1) and SARS-CoV-2 BA.2 variant (Omicron) infections in patients younger than age 65 years, to improve identification of these diseases and better respond to the current epidemic. Methods: Data from 127 patients with the 2009 pandemic influenza A (H1N1) diagnosed between May and July of 2009 and 3,265 patients with Omicron diagnosed between March and May of 2022 were collected. Using a 1:2 match based on age (difference <2 years), sex, and underlying diseases, data from 115 patients with the 2009 pandemic influenza A (H1N1) infection (H1N1 group) and 230 patients with SARS-CoV-2 Omicron BA.2 infection (Omicron group) were analyzed. The clinical manifestations were compared between the groups, logistic regression was performed to identify possible independent risk factors for each group, and multiple linear regression was used to analyze the factors predicting time for nucleic acid negativization (NAN). Results: The median [interquartile range] age of the two groups was 21 [11, 26] years. Compared with the H1N1 group, the Omicron group had: lower white blood cell counts and C-reactive protein levels; less fever, nasal congestion, sore throat, cough, sputum, and headache; and more olfactory loss, muscle soreness, and lactate dehydrogenase (LDH) abnormalities. Patients in the Omicron group used fewer antibiotics and antiviral drugs, and the time for NAN was longer (17 [14,20] VS 4 [3,5] days, P<0.001). Logistic regression showed that fever, cough, headache, and increased white blood cell count were more strongly correlated with the H1N1 group, while muscle soreness and LDH abnormalities were more strongly correlated with the Omicron group. Fever (B 1.529, 95% confidence interval [0.149,2.909], P=0.030) significantly predicted a longer time for NAN in patients with Omicron. Discussion: There are significant differences in clinical characteristics between SARS-CoV-2 Omicron infection and the 2009 pandemic influenza A (H1N1) infection. Recognition of these differences has important implications for clinical practice.

Synthesis, anti-aging and mechanism of magnolol derivatives.

Magnolol (M), a hydroquinone containing an allyl side chain, is one of the major active components of Houpoea officinalis for antioxidation and anti-aging. To enhance the antioxidant activity of magnolol, the different sites of magnolol were structurally modified in this experiment, and a total of 12 magnolol derivatives were obtained. Based on the preliminary exploration of the anti-aging effect of magnolol derivatives in a Caenorhabditis elegans (C. elegans) model. Our results indicate that the active groups of magnolol exerting anti-aging effects were allyl groups and hydroxyl on the phenyl. Meanwhile, the anti-aging effect of the novel magnolol derivative M27 was found to be significantly superior to that of magnolol. To investigate the effect of M27 on senescence and the potential mechanism of action, we investigated the effect of M27 on senescence in C. elegans. In this study, we investigated the effect of M27 on C. elegans physiology by examining body length, body curvature and pharyngeal pumping frequency. The effect of M27 on stress resistance in C. elegans was explored by acute stress experiments. The mechanism of M27 anti-aging was investigated by measuring ROS content, DAF-16 nuclear translocation, sod-3 expression, and lifespan of transgenic nematodes. Our results indicate that M27 prolonged the lifespan of C. elegans. Meanwhile, M27 improved the healthy lifespan of C. elegans by improving pharyngeal pumping ability and reducing lipofuscin accumulation in C. elegans. M27 increased resistance to high temperature and oxidative stress in C. elegans by reducing ROS. M27 induced DAF-16 translocation from cytoplasm to nucleus in transgenic TJ356 nematodes and upregulated the expression of sod-3 (a gene downstream of DAF-16) in CF1553 nematodes. Furthermore, M27 did not extend the lifespan of daf-16, age-1, daf-2, and hsp-16.2 mutants. This work suggests that M27 may ameliorate aging and extend lifespan in C. elegans through the IIS pathway.

Function and inhibition of DYRK1A: Emerging roles of treating multiple human diseases.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is an evolutionarily conserved protein kinase and the most studied member of the Dual-specificity tyrosine-regulated kinase (DYRK) family. It has been shown that it participates in the development of plenty of diseases, and both the low or high expression of DYRK1A protein could lead to disorder. Thus, DYRK1A is recognized as a key target for the therapy for these diseases, and the studies on natural or synthetic DYRK1A inhibitors have become more and more popular. Here, we provide a comprehensive review for DYRK1A from the structure and function of DYRK1A, the roles of DYRK1A in various types of diseases, including diabetes mellitus, neurodegenerative diseases, and kinds of cancers, and the studies of its natural and synthetic inhibitors.

Epidemiological and clinical features of SARS-CoV-2 Omicron variant infection in Quanzhou, Fujian province: a retrospective study.

Epidemiological and clinical data of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2) admitted to three designated hospitals in Quanzhou City, Fujian Province, China, were collected and analyzed. Overall, 2,541 patients infected with BA.2, comprising 1,060 asymptomatic, 1,287 mild, and 194 moderate infections, were enrolled. The percentage of moderate infections was higher in patients aged ≥ 60 years than in those aged < 18 years and 18-59 years. The median hospitalization duration was 17 days. Among the 2,541 patients, 43.52% had a clear history of close contact. The vaccination rate was 87.92%, and the percentage of asymptomatic infections was higher in vaccinated than in unvaccinated patients. Moreover, patients with underlying diseases, including hypertension and diabetes mellitus, had more moderate infections than those without underlying diseases. The three most common clinical manifestations were fever, dry cough, and sore throat. The albumin-to-globulin (A/G) ratio and lymphocyte count decreased in cases with mild and moderate infections, while procalcitonin, erythrocyte sedimentation rate, interleukin-6, D-dimer, and C4 levels increased. Advanced age, non-vaccination, and underlying comorbid diseases were high-risk factors for disease progression in patients. However, dynamic monitoring of blood routine parameters, A/G ratio, and inflammatory indicators facilitated the prediction of disease progression.

Prevalence, clinical characteristics, and outcomes of spontaneous portosystemic shunt in patients with hepatitis B-related cirrhosis: A multicenter study from China.

BACKGROUND: The impact of spontaneous portosystemic shunt (SPSS) on decompensated events and mortality for patients with hepatitis B-related cirrhosis remains poorly investigated. AIMS: To evaluate the prevalence, clinical characteristics, and outcomes of SPSS among patients with hepatitis B-related cirrhosis. METHODS: Patients who were diagnosed with hepatitis B-related cirrhosis were retrospectively recruited. All eligible patients were classified into SPSS and non-SPSS groups and their clinical characteristics and outcomes were compared and analyzed. RESULTS: Of the 1282 patients included in this study, SPSS was identified in 488 patients (38.1%). SPSS group had more severe liver function impairment, higher prevalence and severity of esophageal and gastric varices (EGV), and a higher prevalence of EGV bleeding (EGVB), portal vein thrombosis (PVT), hepatic encephalopathy (HE), ascites, and hepatocellular carcinoma (HCC, all P<0.05). During the follow-up period, SPSS group experienced a significantly higher incidence of EGVB, PVT, and HE (all P<0.05); however, there was no significant difference in the incidence of ascites, HCC, and mortality between the two groups (all P>0.05). CONCLUSION: With hepatitis B-related cirrhosis, SPSS was common and characterized by severe liver damage and a high prevalence of decompensated events. Moreover, patients with SPSS had higher risks of EGVB, PVT, and HE.