Ethylene-mediated stomatal responses to dehydration and rehydration in seed plants.

Ethylene, a plant hormone that significantly influences both plant growth and response to stress, plays a well-established role in stress signaling. However, its impact on stomatal opening and closure during dehydration and rehydration remains relatively unexplored and is still debated. Exogenous ethylene has been proven to induce stomatal closure through a series of signaling pathways, including the accumulation of reactive oxygen species (ROS), subsequent synthesis of nitric oxide (NO) and hydrogen sulfide (H2S), and SLOW ANION CHANNEL-ASSOCIATED 1 (SLAC1) activation. Thus, it has been suggested that ethylene might function to induce stomatal closure synergistically with abscisic acid (ABA). Furthermore, it has also been shown that increased ethylene can inhibit ABA- and jasmonic acid (JA)-induced stomatal closure, thus hindering drought-induced closure during dehydration. Simultaneously, other stresses, such as chilling, ozone pollution and K+ deficiency, inhibit drought and ABA-induced stomatal closure through an ethylene synthesis dependent way. However, ethylene has been shown to take on an opposing role during rehydration, preventing stomatal opening in the absence of ABA through its own signaling pathway. These findings offer novel insights into the function of ethylene in stomatal regulation during dehydration and rehydration, gaining a better understanding of the mechanisms underlying ethylene-induced stomatal movement in seed plants.

Synthesis and anti-parasites efficacy of coumarin derivatives against Dactylogyrus intermedius.

Dactylogyrus is one of the most common parasitic diseases in fish and causes huge losses to the aquaculture industry. With the advantages of safety, low toxicity and easy degradation, plant-derived drugs are ideal for the creation of green aquatic ingredients. The use of plant-derived drugs in aquaculture is limited by their low content and high processing costs, which is a challenge that can be solved by the chemical synthesis of plant-derived drugs. Eleven new coumarin derivatives were synthesized and assessed for their anthelmintic activity in this study. Among them, the derivative 7-((1-tosyl-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (N11) has good anthelmintic activity and its mean anthelmintic efficacy against D. intermedius at a concentration of 10 µM reached 99.84%, which is even better than the anthelmintic activity of the positive control mebendazole. Further studies showed that N11 had concentration values of 3.31 and 1.94 µM for 50% maximal effect (EC50 ) against D. intermedius at 24 and 48 h, respectively. Furthermore, scanning electron microscopy revealed that N11 caused damage to D. intermedius. What is more noteworthy is that a substantial reduction in the ATP content of the parasite was observed following in vitro and in vivo administration of N11. Moreover, it was also found that N11 was able to inhibit the horizontal transmission of D. intermedius. Furthermore, real-time quantitative PCR analysis was utilized to determine the expression profile of genes associated with anti-inflammatory cytokines (IL-10, TGF-ß and IL-4) in goldfish. In all examined organs, it was observed that the expression of anti-inflammatory cytokines increased subsequent to treatment with N11, according to the results. Thus, these results all suggest that N11 possesses good anthelmintic activity and is a potentially effective agent for the control of D. intermedius.

Polyamines inhibit abscisic acid-induced stomatal closure by scavenging hydrogen peroxide.

Stomatal closure is regulated by plant hormones and some small molecules to reduce water loss under stress conditions. Both abscisic acid (ABA) and polyamines alone induce stomatal closure; however, whether the physiological functions of ABA and polyamines are synergistic or antagonistic with respect to inducing stomatal closure is still unknown. Here, stomatal movement in response to ABA and/or polyamines was tested in Vicia faba and Arabidopsis thaliana, and the change in the signaling components under stomatal closure was analyzed. We found that both polyamines and ABA could induce stomatal closure through similar signaling components, including the synthesis of hydrogen peroxide (H2 O2 ) and nitric oxide (NO) and the accumulation of Ca2+ . However, polyamines partially inhibited ABA-induced stomatal closure both in epidermal peels and in planta by activating antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), to eliminate the ABA-induced increase in H2 O2 . These results strongly indicate that polyamines inhibit abscisic acid-induced stomatal closure, suggesting that polyamines could be used as potential plant growth regulators to increase photosynthesis under mild drought stress.

Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study.

Background: Autism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long been recognized. Altered immune function and gut microbiota have been found in ASD populations. Immune dysfunction has been hypothesized to involve in the pathophysiology of a subtype of ASD. Methods: A cohort of 105 ASD children were recruited and grouped based on IFN-γ levels derived from ex vivo stimulated γδT cells. Fecal samples were collected and analyzed with a metagenomic approach. Comparison of autistic symptoms and gut microbiota composition was made between subgroups. Enriched KEGG orthologues markers and pathogen-host interactions based on metagenome were also analyzed to reveal the differences in functional features. Results: The autistic behavioral symptoms were more severe for children in the IFN-γ-high group, especially in the body and object use, social and self-help, and expressive language performance domains. LEfSe analysis of gut microbiota revealed an overrepresentation of Selenomonadales, Negatiyicutes, Veillonellaceae and Verrucomicrobiaceae and underrepresentation of Bacteroides xylanisolvens and Bifidobacterium longum in children with higher IFN-γ level. Decreased metabolism function of carbohydrate, amino acid and lipid in gut microbiota were found in the IFN-γ-high group. Additional functional profiles analyses revealed significant differences in the abundances of genes encoding carbohydrate-active enzymes between the two groups. And enriched phenotypes related to infection and gastroenteritis and underrepresentation of one gut-brain module associated with histamine degradation were also found in the IFN-γ-High group. Results of multivariate analyses revealed relatively good separation between the two groups. Conclusions: Levels of IFN-γ derived from γδT cell could serve as one of the potential candidate biomarkers to subtype ASD individuals to reduce the heterogeneity associated with ASD and produce subgroups which are more likely to share a more similar phenotype and etiology. A better understanding of the associations among immune function, gut microbiota composition and metabolism abnormalities in ASD would facilitate the development of individualized biomedical treatment for this complex neurodevelopmental disorder.

Nesting the SIRV model with NAR, LSTM and statistical methods to fit and predict COVID-19 epidemic trend in Africa.

OBJECTIVE: Compared with other regions in the world, the transmission characteristics of the COVID-19 epidemic in Africa are more obvious, has a unique transmission mode in this region; At the same time, the data related to the COVID-19 epidemic in Africa is characterized by low data quality and incomplete data coverage, which makes the prediction method of COVID-19 epidemic suitable for other regions unable to achieve good results in Africa. In order to solve the above problems, this paper proposes a prediction method that nests the in-depth learning method in the mechanism model. From the experimental results, it can better solve the above problems and better adapt to the transmission characteristics of the COVID-19 epidemic in African countries. METHODS: Based on the SIRV model, the COVID-19 transmission rate and trend from September 2021 to January 2022 of the top 15 African countries (South Africa, Morocco, Tunisia, Libya, Egypt, Ethiopia, Kenya, Zambia, Algeria, Botswana, Nigeria, Zimbabwe, Mozambique, Uganda, and Ghana) in the accumulative number of COVID-19 confirmed cases was fitted by using the data from Worldometer. Non-autoregressive (NAR), Long-short term memory (LSTM), Autoregressive integrated moving average (ARIMA) models, Gaussian and polynomial functions were used to predict the transmission rate ß in the next 7, 14, and 21 days. Then, the predicted transmission rate ßs were substituted into the SIRV model to predict the number of the COVID-19 active cases. The error analysis was conducted using root-mean-square error (RMSE) and mean absolute percentage error (MAPE). RESULTS: The fitting curves of the 7, 14, and 21 days were consistent with and higher than the original curves of daily active cases (DAC). The MAPE between the fitted and original 7-day DAC was only 1.15% and increased with the longer of predict days. Both the predicted ß and DAC of the next 7, 14, and 21 days by NAR and LSTM nested models were closer to the real ones than other three ones. The minimum RMSEs for the predicted number of COVID-19 active cases in the next 7, 14, and 21 days were 12,974, 14,152, and 12,211 people, respectively when the order of magnitude for was 106, with the minimum MAPE being 1.79%, 1.97%, and 1.64%, respectively. CONCLUSION: Nesting the SIRV model with NAR, LSTM, ARIMA methods etc. through functionalizing ß respectively could obtain more accurate fitting and predicting results than these models/methods alone for the number of confirmed COVID-19 cases in Africa in which nesting with NAR had the highest accuracy for the 14-day and 21-day predictions. The nested model was of high significance for early understanding of the COVID-19 disease burden and preparedness for the response.

Effects of polystyrene nanoplastics on the physiological and biochemical characteristics of microalga Scenedesmusquadricauda.

The contamination of the aquatic environment with microplastics has become a global environmental concern. Microplastic particles can be shredded to form smaller nanoplastics, and knowledge on their impacts on phytoplankton, especially freshwater microalgae, is still limited. To investigate this issue, the microalga Scenedesmus quadricauda was exposed to polystyrene nanoplastics (PS-NPs) of five concentrations (10, 25, 50, 100, and 200 mg/L). The growth; the contents of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD); the chlorophyll content; and concentrations of soluble protein and soluble polysaccharide were accordingly measured. The results showed that the microalgal density increased with the increase of the polystyrene nanoplastic concentrations, and the physiological features of alga were enhanced after the stimulation of nanoplastics. Furthermore, a high concentration (200 mg/L) of nanoplastics increased the contents of chlorophyll, soluble protein, and polysaccharide (P < 0.05). The antioxidant enzyme activities of Scenedesmus quadricauda were significantly activated by nanoplastics. Lastly, we propose three possible algal recovery mechanisms in response to nanoplastics in which Scenedesmus quadricauda was tolerant with PS-NPs by cell wall thickening, internalization, and aggregation. The results of this study contribute to understanding of the ecological risks of nanoplastics on freshwater microalgae.

Phytocytokine SCREWs increase plant immunity through actively reopening stomata.

Plants secreted phytocytokine SMALL PHYTOCYTOKINES REGULATING DEFENSE AND WATER LOSS (SCREWs) and its receptor PLANT SCREW UNRESPONSIVE RECEPTOR (NUT) to counter abscisic acid (ABA)- and pathogen-induced stomatal closure (Liu et al.). This novel signaling process provides plants with a new strategy to increase immunity through disrupting an aqueous habitat for pathogen colonization.

The efficacy of Da Chaihu decoction combined with metformin tablets for type 2 diabetes mellitus: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy of Da Chaihu decoction combined with metformin tablets on patients with type 2 diabetes compared with metformin alone. METHODS: This systematic review and meta-analysis is written based on 2020 PRISMA Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020) reporting guidelines. We reviewed all the relevant studies from a search of the following databases from inception to February 2022 without any language restriction: Excerpta Medica Database (EMBASE), Google Scholar, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database(CBM). Data were extracted and the quality was independently evaluated by two reviewers, based on the inclusion and exclusion criteria. Data were analyzed using the Cochrane software RevMan 5.3. RESULTS: Six randomized controlled trials comprising 516 participants were included. The meta-analysis revealed the Da Chaihu decoction combined with metformin tablets group was significantly superior to the metformin tablets group in terms of fasting blood glucose(FPG) (-0.66 mmol/L; 95 % CI (confidence intervals) [- 1.28, - 0.04]), plasma glucose 2 h after meal (2-h PG) (-1.18 mmol/L; 95 % CI [-1.94, -0.42]) in six RCTs, body mass index (BMI) (-3.07 mmol/L; 95 % CI [-6.89, 0.75]) in three RCTs, glycosylated hemoglobin (HbAlc) (-0.36 mmol/L; 95 % CI [-1.04, 0.31]) in three RCTs, and triglycerides (TG) (-0.76 mmol/L; 95 % CI [-1.37, -0.15]) in two RCTs. In two RCTs, there were significant differences in terms of total cholesterol (TC) (-0.97 mmol/L; 95 % CI [-1.18, -0.76]). CONCLUSIONS: Very low-quality research shows that Da Chaihu decoction combined with metformin tablets exert a certain level of efficacy on patients with type 2 diabetes compared with metformin alone. However, random sequence generation methodology was reported in five studies leading to the low quality of the included studies. None of the six studies depicted the blinding method, allocation concealment, selective reporting, and assessed the purity and potency of the product. This observation requires verification through high-quality, multi-center, double-blinded randomized controlled trials, and assesses the purity and potency of the product.

ABA activated SnRK2 kinases: an emerging role in plant growth and physiology.

Members of the SNF1-related protein kinase 2 (SnRK2) family are plant-specific serine or threonine kinases that play a pivotal role in the response of plants to abiotic stresses. Members of this plant-specific kinase family have included a critical regulator (SnRK2) of abscisic acid (ABA) response in plants. Plant organ development is governed substantially by the interaction of the SnRK2 and the phytohormone abscisic acid (ABA). Recent research has revealed a synergistic link between SnRK2 and ABA signaling in a plant's response to stress such as drought and shoot growth. SnRK2 kinases play a dual role in the control of SnRK1 and the development of a plant. The dual role of SnRK2 kinases promotes plant growth under optimal conditions and in the absence of ABA while inhibiting the growth of plants in response to ABA. In this review, we have uncovered the roles of ABA-activated SnRK2 kinases in plants, as well as their physiological mechanisms.

Interaction analysis of FADS2 gene variants with chronic hepatitis B infection in Chinese patients.

The risk of chronic hepatitis B (CHB) infection is often affected by polyunsaturated fatty acids (PUFAs) metabolism which is strongly influenced by single nucleotide polymorphisms (SNPs) within the PUFA metabolic pathway. Given this, we designed this study to determine the relationship between specific polymorphisms within fatty acid desaturase 2 (FADS2), a key enzyme in PUFA metabolism, and CHB infection. We completed this evaluation using a case-control study comprising 230 CHB patients and 234 unrelated healthy controls in which the genetic relationships between three previously identified SNPs, isolated via mass spectrometry, and CHB infection. Our data revealed that none of these three SNPs (rs174568, rs174601, and rs2727270) were significantly associated with susceptibility to CHB infection when compared to healthy controls. However, when we stratified our cohort by sex, male subjects with the TC genotype for FADS2 exhibited a decreased risk for CHB infection (OR = 0.62, 95%CI = 0.39-0.96; OR = 0.64, 95%CI = 0.41-1.00; OR = 0.57, 95%CI = 0.36-0.90). Furthermore, age stratification revealed that both the T allele and the TC genotypes for each of the three target SNPs were less common in Chinese CHB cases in people younger than 50 years old. Correlation analysis also revealed that there was no statistically significant relationship between these three SNPs and HBV-DNA replication or hepatitis B surface antigen (HBsAg) levels. Thus, our data suggests that rs174568, rs174601, and rs2727270 may affect the CHB outcomes in various age or sex subgroups, suggesting that they may be useful predictive or diagnostic biomarkers of CHB infection in some populations.

Additive Manufacturing of Two-Dimensional Conductive Metal-Organic Framework with Multidimensional Hybrid Architectures for High-Performance Energy Storage.

Two-dimensional conductive metal-organic frameworks (2D CMOFs) can be regarded as high-performance electrode substances owing to their rich hierarchical porous architecture and excellent electrical conductivity. However, the sluggish kinetics behavior of electrodes within the bulk structure restricts their advances in energy storage fields. Herein, a series of graphene-based mixed-dimensional composite aerogels are achieved by incorporating the 2D M-tetrahydroxy-1,4-quinone (M-THQ) (M = Cu, Cu/Co, or Cu/Ni) into CNTs@rGO aerogel electrodes using a 3D-printing direct ink writing (DIW) technique. Benefiting from the high capacity of M-THQ and abundant porosity of the 3D-printed microlattice electrodes, an excellent capacitive performance of the M-THQ@CNTs@rGO cathodes is achieved based on the fast electron/ion transport. Furthermore, the 3D-printed lithium-ion hybrid supercapacitor (LIHCs) device assembled with Cu/Co-THQ@CNTs@rGO cathode and C60@VNNWs@rGO anode delivers a remarkable electrochemical performance. More importantly, this work manifests the practicability of printing 2D CMOFs electrodes, which provides a substantial research basis for 3D printing energy storage.

GABA: A Key Player in Drought Stress Resistance in Plants.

γ-aminobutyric acid (GABA) is a non-protein amino acid involved in various physiological processes; it aids in the protection of plants against abiotic stresses, such as drought, heavy metals, and salinity. GABA tends to have a protective effect against drought stress in plants by increasing osmolytes and leaf turgor and reducing oxidative damage via antioxidant regulation. Guard cell GABA production is essential, as it may provide the benefits of reducing stomatal opening and transpiration and controlling the release of tonoplast-localized anion transporter, thus resulting in increased water-use efficiency and drought tolerance. We summarized a number of scientific reports on the role and mechanism of GABA-induced drought tolerance in plants. We also discussed existing insights regarding GABA's metabolic and signaling functions used to increase plant tolerance to drought stress.

Pharmacological Activating Transcription Factor 6 Activation Is Beneficial for Liver Retrieval With ex vivo Normothermic Mechanical Perfusion From Cardiac Dead Donor Rats.

Background: Normothermic machine perfusion (NMP) could be beneficial for organ retrieval from donors after cardiac death (DCD). Activating transcription factor 6 (ATF6) was recently shown to mitigate liver ischemia/reperfusion injury and confer protection. The aims of this study were to assess the implication of ATF6 in liver retrieval from DCD rat livers with NMP and explore the effect of pharmacologic ATF-6 activation on liver retrieval. Methods: The livers from DCD rats were exposed to 30 min of warm ischemia and 8 h cold preservation followed by 2 h NMP with or without an ATF6 activator in the perfusate. Perfusates and livers were harvested to detect ATF6 expression, liver function, and inflammation. Results: DCD livers with NMP were associated with ATF6 overexpression and activation based on IHC and WB (P < 0.05). The ATF6 activator downregulated perfusate aminotransferases, decreased the Suzuki score, downregulated CD68 and MPO based on IHC, induced the expression of cytochrome c in mitochondria and inhibited the expression of cytochrome c in cytoplasm based on WB, reduced TNFα and IL-6 levels based on ELISA, decreased levels of MDA, GSSG and ATP, and increased SOD activity and GSH levels in the perfused livers (P < 0.05). Conclusion: ATF6 is important for liver retrieval, and an exogenous ATF6 activator accelerates liver retrieval from DCD rats in an ex vivo NMP model.

Post-infection cognitive impairments in a cohort of elderly patients with COVID-19.

BACKGROUND: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. METHODS: This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. RESULTS: Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p < 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p < 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p < 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p < 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p < 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.

Potassium mediated Co-Fe-based Prussian blue analogue architectures for aqueous potassium-ion storage.

Prussian blue analogs (PBAs) with unique structure show great potential for aqueous potassium-ion batteries (AKIBs). Herein, K2Co[Fe(CN)6] and KNi[Co(CN)6] architectures are developed as the cathode candidates for AKIBs. Moreover, the reaction kinetics detection and DFT calculations are employed to analyse the battery performances.

Effects of Modified Simultaneous Unipolar Saline-Irrigated Radiofrequency Ablation in Patients with Atrial Fibrillation Combined with Mitral Valve Disease.

OBJECTIVE: To investigate the therapeutic effects of a modified simultaneous unipolar saline-irrigated radiofrequency ablation by intracardiac operation under direct vision in patients with mitral valve diseases combined with atrial fibrillation (AF). METHODS: A total of 168 patients with mitral valve diseases combined with AF who underwent unipolar saline-irrigated radiofrequency ablation modified maze procedures were enrolled and divided into the mitral stenosis (MS) group (n = 87) and the mitral insufficiency (MI) group (n = 81). RESULTS: Those with a left atrium diameter (LAD) < 55 mm had a better cardioversion effect during the mid-term post-operation than those with a LAD ≥ 55 mm (P < 0.05). The cardioversion effect during the mid-term post-operation was better in those with a duration of AF < 2 years than those with AF ≥ 2 years (P < 0.05). The LAD reduced significantly during the early postoperative period in the MS group (P < 0.05). Compared with the early postoperative period, LAD further reduced, and the EF increased significantly during the mid-term post-operation (P<0.05). The LAD reduced significantly during the early postoperative period in the MI group (P < 0.05), together with relatively decreased EF (P < 0.05). Compared with the early postoperative period, LAD further reduced, and the EF increased significantly during the mid-term post-operation (P<0.05). The improvement of LAD in the MI group during the mid-term post-operation was better than that in the MS group (P < 0.05). CONCLUSION: The cardioversion effects and the improvement in cardiac function during the mid-term post-operation were good in the radiofrequency ablation by intracardiac operation under direct vision in patients with different mitral valve diseases combined with AF. The cardioversion effects during the early postoperative period and the mid-term post-operation were better in patients with MI than in those with MS.

Identification of Resectable N2 in NSCLC: A Single Center Experience and Review of the SEER Database.

BACKGROUND: Non-small cell lung carcinoma (NSCLC) with ipsilateral and/or subcarinal mediastinal lymphatic spread (N2) is a heterogeneous disease. The role of surgical resection in patients with N2 NSCLC remains controversial and no survival-based definition of "resectable N2" exists. The purpose of this study is to evaluate the factors that potentially affect the survival of N2 NSCLC patients who receive surgical resection and to define "resectable N2" based on the survival benefits. METHODS: Data from the open Surveillance, Epidemiology, and End Results (SEER) database from the National Cancer Institute in the United States were used to construct a nomogram. Patients who received surgery between 2010 and 2015 for N2 NSCLC were included. Independent prognostic factors for survival identified through Cox regression analysis were used to create the nomogram. The C-index, receiver operating characteristics (ROC) analyses, calibration curves, and risk stratification were used to evaluate the nomogram. The nomogram was also validated using data from 222 patients from Peking Union Medical College Hospital (PUMCH). Furthermore, lung cancer-related deaths were compared using competitive risk analysis. RESULTS: In total, 4267 patients were included in the SEER cohort. Male gender, old age, high T stage and grade, adenosquamous and squamous cell carcinoma, lower lobe and overlapping lesions, extended lobe or bilobectomy and pneumonectomy, no chemotherapy, radiation before and after surgery, positive number of lymph nodes, and lymph node ratio (LNR) were identified as independent risk factors for higher mortality. The nomogram was created using these parameters. The C-index was 0.665 (95% confidence interval (CI), 0.651-0.679) and 0.722 (95% CI, 0.620-0.824) in the SEER and PUMCH cohorts, respectively. The calibration curves showed satisfactory consistency between the predicted and actual survival status in both the SEER and PUMCH cohorts. Competitive risk analysis confirmed that the variables in the nomogram, except radiation, are risk factors for prognosis. CONCLUSIONS: "Resectable N2" should be assessed by a multidisciplinary team. The novel nomogram developed in this study may help with clinical decision-making for this patient population.

Interaction analysis of gene variants related to one-carbon metabolism with chronic hepatitis B infection in Chinese patients.

BACKGROUND: The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one-carbon metabolism genes. In the present study, we investigated the relationship between polymorphisms belonging to the one-carbon metabolic pathway and CHB infection. METHODS: A case-control study using 230 CHB patients and 234 unrelated healthy controls was carried out to assess the genetic association of 24 single nucleotide polymorphisins (SNPs) determined by mass spectrometry. RESULTS: Three SNPs, comprising rs10717122 and rs2229717 in serine hydroxymethyltransferase1/2 (SHMT2) and rs585800 in betaine-homocysteine S-methyltransferase (BHMT), were associated with the risk of CHB. Patients with DEL allele, DEL.DEL and DEL.T genotypes of rs10717122 had a 1.40-, 2.00- and 1.83-fold increased risk for CHB, respectively. Cases inheriting TA genotype of rs585800 had a 2.19-fold risk for CHB infection. The T allele of rs2229717 was less represented in the CHB cases (odds ratio = 0.66, 95% confidence interval = 0.48-0.92). The T allele of rs2229717 was less in patients with a low hepatitis B virus-DNA level compared to the control group (odds ratio = 0.49, 95% confidence interval = 0.25-0.97) and TT genotype of rs2229717 had a significant correlation with hepatitis B surface antigen level (p = 0.0195). Further gene-gene interaction analysis showed that subjects carrying the rs10717122 DEL.DEL/DEL.T and rs585800 TT/TA genotypes had a 2.74-fold increased risk of CHB. CONCLUSIONS: The results of the present study suggest that rs10717122, rs585800 and rs2229717 and gene-gene interactions of rs10717122 and rs585800 affect the outcome of CHB infection, at the same time as indicating their usefulness as a predictive and diagnostic biomarker of CHB infection.

[Astragaloside â £'s Therapeutic Effect on Myocardial Infarction via Affecting Autophagy and the Mechanism Study].

OBJECTIVE: The purpose of this study was to investigate the protective effect of astragaloside Ⅳ (AS-Ⅳ) on neonatal rats' hypoxic/reoxygenated (H/R) injured myocardial cells and to explore its underlying mechanism. METHODS: Cardiac cells were extracted from newborn rats and divided into control, H/R, H/R-low AS-Ⅳ (0.1 µmol/L AS-Ⅳ), H/R-medium AS-Ⅳ (1 µmol/L AS-Ⅳ), H/R-high AS-Ⅳ (10 µmol/L AS-Ⅳ) and H/R-high AS-Ⅳ-AKT (10 µmol/L AS-Ⅳ+5 µmol/L AKT) groups. After 48 h of treatment, the contents of LC3-Ⅱ, p62, AKT, pAKT, rapamycin (mTOR) mammalian targets and uncoordinated 51-like kinase 1 (ULK1) in cardiac myocytes were compared. Immunofluorescence staining was used to detect the expression of P62 in myocardium autophagosome. RESTULTS: AS-Ⅳ improved the proliferative activity of cardio AS-Ⅳ improved the proliferative activity of cardiomyocytes in H/R injury in a dose-dependent manner and inhibited the level of cell autophagy. However, when AKT inhibitors were added, the effect of AS-Ⅳ was partially inhibited ( P<0.05). Gene and protein expression showed that AS-Ⅳ had no significant effect on the expression of AKT and mTOR genes ( P>0.05), but could significantly promote the phosphorylation of AKT and mTOR ( P<0.05). Immunofluorescence staining results showed that high concentrations of the AS - Ⅳ can reverse H/R injury induced the expression of autophagy body P62. CONCLUSION: AS-Ⅳ showed protection effect on H/R injured myocardial cells. The possible mechanism is by reducing the autophagy level via activating the mTOR signal in the PI3K/AKT pathway, thereby preventing H/R damage in neonatal rat cardiomyocytes.