Metabonomics analysis of the flavor characteristics of Wuyi Rock Tea (Rougui) with "rock flavor" and microbial contributions to the flavor.

Wuyi Rock Tea (WRT) has different characteristics of "rock flavor" due to different production areas. In this study, we investigated the flavor characteristics and key components of "rock flavor" and the influence of microorganisms on the substances by combining metabolomics and microbiomics with the Rougui WRTs from the Zhengyan, Banyan, and Waishan production areas. The results showed that Rougui has a strong floral and fruity aroma, which is mainly brought by hotrienol, and the sweet, smooth, and fresh taste is composed of epicatechin gallate, epigallocatechin, epigallocatechin gallate, caffeine, theanine, soluble sugar, and sweet and bitter amino acids. Bacteria Chryseobacterium, Pedobacter, Bosea, Agrobacterium, Stenotrophomonas, and Actinoplanes mainly influence the production of hotrienol, epicatechin gallate, and theanine. Fungi Pestalotiopsis, Fusarium, Elsinoe, Teichospora and Tetracladium mainly influence the production of non-volatile compounds. This study provides a reference for the biological formation mechanism of the characteristic aroma of WRT's "rock falvor".

Lacto-ovo-vegetarian diet is inversely associated with the osteosarcopenia in older adults.

OBJECTIVE: Osteosarcopenia adversely affects the quality of life and physical health of older adults. We sought to explore the association between dietary patterns and osteosarcopenia in community-dwelling older adults. METHODS: This is a cross-sectional study from Northeast China, in which, we included older community adults aged 60 and above. Through face-to-face interviews, we collected dietary information from participants using a food frequency questionnaire. Subsequently, principal component analysis (PCA) was used to obtain the dietary patterns of the participants. Through physical examination, we obtained the participants' information on osteosarcopenia, which was defined by the coexist of osteopenia and sarcopenia. We analysed the association between dietary patterns and dietary compositions with ostesarcopenia. RESULTS: In this study, a total of 9429 participants were included, and the prevalence of osteosarcopenia in community-dwelling older adults was 6.2%. PCA identified three main dietary patterns, and the lacto-ovo-vegetarian dietary pattern was inversely associated with osteosarcopenia. Compared to the lowest lacto-ovo-vegetarian quartile (Q1), the Q4 group (OR = 0.64, 95% CI:0.49-0.83) was inversely associated with osteosarcopenia. Through the weighted quantile sum regression model, we also found that the overall effect of the lacto-ovo-vegetarian dietary components was inversely associated with osteosarcopenia (OR = 0.58, 95% CI: 0.37-0.92); the largest contributors were vegetables, fresh milk, eggs, and dairy products. CONCLUSION: Overall, we found that a lacto-ovo-vegetarian dietary pattern, particularly the consumption of vegetables, fresh milk, eggs, and dairy products, was inversely associated with osteosarcopenia in older adults. And this might provide new insights for the prevention and treatment of osteosarcopenia.

Genome-wide QTL mapping for agronomic traits in the winter wheat cultivar Pindong 34 based on 90K SNP array.

Introduction: Agronomic traits are key components of wheat yield. Exploitation of the major underlying quantitative trait loci (QTLs) can improve the yield potential in wheat breeding. Methods: In this study, we constructed a recombinant inbred line (RIL) population from Mingxian 169 (MX169) and Pindong 34 (PD34) to determine the QTLs for grain length (GL), grain width (GW), grain length-to-width ratio (LWR), plant height (PH), spike length (SL), grain number per spike (GNS), and the thousand grain weight (TGW) across four environments using wheat 90K SNP array. Results: A QTL associated with TGW, i.e., QTGWpd.swust-6BS, was identified on chromosome 6B, which explained approximately 14.1%-16.2% of the phenotypic variation. In addition, eight QTLs associated with GL were detected across six chromosomes in four different test environments. These were QGLpd.swust-1BL, QGLpd.swust-2BL, QGLpd.swust-3BL.1, QGLpd.swust-3BL.2, QGLpd.swust-5DL, QGLpd.swust-6AL, QGLpd.swust-6DL.1, and QGLpd.swust-6DL.2. They accounted for 9.0%-21.3% of the phenotypic variation. Two QTLs, namely, QGWpd.swust-3BS and QGWpd.swust-6DL, were detected for GW on chromosomes 3B and 6D, respectively. These QTLs explained 12.8%-14.6% and 10.8%-15.2% of the phenotypic variation, respectively. In addition, two QTLs, i.e., QLWRpd.swust-7AS.1 and QLWRpd.swust-7AS.2, were detected on chromosome 7A for the grain LWR, which explained 10.9%-11.6% and 11.6%-11.2% of the phenotypic variation, respectively. Another QTL, named QGNSpd-swust-6DS, was discovered on chromosome 6D, which determines the GNS and which accounted for 11.4%-13.8% of the phenotypic variation. Furthermore, five QTLs associated with PH were mapped on chromosomes 2D, 3A, 5A, 6B, and 7B. These QTLs were QPHpd.swust-2DL, QPHpd.swust-3AL, QPHpd.swust-5AL, QPHpd.swust-6BL, and QPHpd.swust-7BS, which accounted for 11.3%-19.3% of the phenotypic variation. Lastly, a QTL named QSLpd.swust-3AL, conferring SL, was detected on chromosome 3A and explained 16.1%-17.6% of the phenotypic variation. All of these QTLs were defined within the physical interval of the Chinese spring reference genome. Discussion: The findings of this study have significant implications for the development of fine genetic maps, for genomic breeding, and for marker-assisted selection to enhance wheat grain yield.

The mediating effect of uncertainty in illness between heart failure symptoms and health-related quality of life among rural patients with heart failure: A multi-center cross-sectional study.

BACKGROUND: The health-related quality of life (HRQoL) of patients with heart failure (HF) in rural settings in China remains unclear. Limited studies explored the mediating effect of uncertainty in illness between heart failure symptoms and HRQoL in this population. OBJECTIVES: To explore the status of HRQoL in rural patients with HF; assess the impact of HF symptoms and uncertainty in illness on HRQoL; and examine the mediating effect of uncertainty in illness on the relationship between symptoms and HRQoL in rural patients with HF. METHODS: Overall, 298 rural patients with HF were recruited from five township hospitals of Taishan and Jinzhong City in China between November 2021 and August 2022. Three variables, namely HF symptoms, uncertainty in illness, and HRQoL were measured using three validated scales. RESULTS: The average score of HRQoL in rural patients with HF was 43.19. Of the participants, 60.4 %, 35.23 %, and 4.37 % exhibited poor, moderate, and good HRQoL, respectively. The HF symptoms (ß = -0.47) and uncertainty in illness (ß = -0.34) directly influenced HRQoL. Moreover, the HF symptoms also indirectly affected HRQoL through uncertainty in illness (ß = -0.07). The indirect effect accounted for 12.96 % of the total effect of HF symptoms on HRQoL. CONCLUSION: Rural patients with HF exhibited poor HRQoL. In this population, HF symptoms and uncertainty in illness were negatively associated with HRQoL. Uncertainty in illness mediated the relationship between HF symptoms and HRQoL. Tailored healthcare services should be developed for the rural population to alleviate HF symptoms, reduce uncertainty in illness, and enhance their HRQoL.

Adverse childhood experiences, sarcopenia, and social participation in older adults: a cohort study.

OBJECTIVES: To examine the relationships between adverse childhood experiences (ACEs) and developing sarcopenia in older adults and the modifying effects of active social participation. METHODS: This prospective cohort study used survey data from the China Health and Retirement Longitudinal Study, including baseline surveys from 2011, follow-up data from 2013, follow-up data from 2015, and information on ACEs from the 2014 Life History Survey. Information concerning 10 ACEs, including five threat-related ACEs and five deprivation-related ACEs before 17 years of age was obtained by questionnaires through face-to-face interviews. Sarcopenia status was assessed according to the Asian Working Group for Sarcopenia 2019 algorithm, consisted of low muscle mass, and low muscle strength, or poor physical performance. The relationship between ACEs, social participation, and sarcopenia was evaluated using Cox proportional hazard regression models. RESULTS: The study population comprised 6859 older adults in main analyses. Having experienced ≥ 3 ACEs led to an increased 31% risk of developing sarcopenia (hazard ratio [HR]:1.31, 95% confidence interval [CI]:1.10-1.56). Participants having experienced ≥ 2 threat-related ACEs (HR:1.22, 95%CI:1.04-1.43) or deprivation-related ACEs (HR:1.22, 95%CI:1.02-1.46) had a 22% higher risk of developing sarcopenia. Active social participation significantly modified the association between ACEs (p < 0.05), especially threat-related ACEs (p < 0.05), and sarcopenia. CONCLUSIONS: ACEs were associated with the development of sarcopenia; however, social participation had a modifying effect. These findings provide insights for early identification of vulnerable groups, advance intervention timing, and highlight the benefits of promoting active social participation among individuals with sarcopenia who have experienced ACEs.

Direct C-H Alkylation of Benzothiadiazoles via Organic Photoredox Catalysis.

2,1,3-Benzothiadiazole is widely used as a privileged scaffold in pharmaceuticals and organic functional materials. Nonetheless, many current methods for the functionalization of 2,1,3-benzothiadiazole rely on preactivation, transition metal catalysts/promoters, or an elevated reaction temperature. Herein we disclose a transition-metal-free visible-light-induced photocatalytic method for the direct C-H alkylation of 2,1,3-benzothiadiazole using readily accessible carboxylic acid derivatives, i.e., N-hydroxyphthalimide esters (NHPEs), as alkylating reagents under room temperature. This mild and scalable method is highlighted by the late-stage installation of the benzothiadiazole scaffold in drugs and natural products.

Metabolomics analysis of flavor differences in Shuixian (Camellia sinensis) tea from different production regions and their microbial associations.

Shuixian is renowned for its "rock flavor". However, the variations in Shuixian flavor are unclear, as the discussion mainly considers regional factors and overlooks the role of microorganisms. Sensory evaluation of Shuixian from three different regions (Zhengyan, Banyan, and Waishan) revealed that each had unique flavor characteristics: a woody aroma with slight acidity, a strong floral and fruity aroma with good freshness, and a distinct sweet aroma and sourness. Metabolomic analyses have revealed that 2-methylpyrazine was a crucial component of the woody aroma, whereas other metabolites contributed to sweet aroma, freshness, and acidity. Moreover, examinations of the relationship between flavor metabolites and microorganisms revealed that fungi had a more pronounced influence on the metabolite content of Shuixian. The study evaluated the role of fermentation microorganisms in shaping the flavor based on Shuixian flavor analyses, contributing to further research into the "rock flavor", as well as potential microbial interventions.

Exosomes miRNA-499a-5p targeted CD38 to alleviate anthraquinone induced cardiotoxicity: experimental research.

BACKGROUND: The purpose of this study was to investigate the effects of cardiac homing peptide (CHP) engineered bone marrow mesenchymal stem cells (BMMSc) derived exosomes (B-exo) loaded miRNA-499a-5p on doxorubicin (DOX) induced cardiotoxicity. METHODS: miRNA chip analysis was used to analyze the differences between DOX induced H9c2 cells and control group. CHP engineering was performed on BMMSc derived exosomes to obtain C-B-exo. miRNA-499a-5p mimic was introduced into C-B-exo by electroporation technology to obtain C-B-exo-miRNA-499a-5p. DOX was used to establish a model of cardiotoxicity to evaluate the effects of C-B-exo- miRNA-499a-5p in vivo and in vitro . Western blot, immunohistochemistry, immunofluorescence, and other molecular biology methods were used to evaluate the role and mechanism of C-B-exo-miRNA-499a-5p on DOX induced cardiotoxicity. RESULTS: miRNA chip analysis revealed that miRNA-499a-5p was one of the most differentially expressed miRNAs and significantly decreased in DOX induced H9c2 cells as compared to the control group. Exo-and B-exo have a double-layer membrane structure in the shape of a saucer. After engineering the CHP of B-exo, the results showed that the delivery of miRNA-499a-5p significantly increased and significantly reached the target organ (heart). The experimental results showed that C-B-exo-miRNA-499a-5p significantly improved electrocardiogram, decreased myocardial enzyme, serum and cardiac cytokines, improved cardiac pathological changes, inhibited CD38/MAPK/NF-κB signal pathway. CONCLUSIONS: In this study, C-B-exo-miRNA-499a-5p significantly improved DOX-induced cardiotoxicity via CD38/MAPK/NF-κB signal pathway, providing a new idea and method for the treatment of DOX induced cardiotoxicity.

Enrichment of grape berries and tomato fruit with health-promoting tartaric acid by expression of the Vitis vinifera transketolase VvTK2 gene.

Tartaric acid (TA) is a major non-fermentable plant soluble acid that abundantly occur in grapes and wines, imparting low pH and tart flavour to berries thereby regulating numerous quality attributes of wine, such as flavour, microbial stability, and aging potential. Evaluation of acidity in mature fruits of 21 wine grape (Vitis vinifera) varieties revealed significant variation between 'Beichun' and 'Gewürztraminer', which was correlated with TA content. RNA-seq analysis of fruits from the two cultivars at different developmental stages revealed that a transketolase gene, VvTK2, was significantly dominantly expressed in the high TA phenotype 'Beichun' variety. Subcellular localization assay showed that VvTK2 protein was located in the chloroplast. Virus-induced VvTK2 gene silencing significantly decreased the expression of 2-keto-L-gulonic acid reductase (Vv2-KGR) as well as L-idonate dehydrogenase (VvL-IdnDH3) and inhibited TA accumulation, while its transient over-expression in grape showed the opposite results. Heterologous VvTK2 over-expression in tomato demonstrated its obvious capacity to induce TA synthesis. Overall, these results highlights a novel role of VvTK2 in modulating TA biosynthesis, which could be an excellent strategy for future genetic improvement of grape flavour.

Bullying Victimization and Internalizing Problems among Adolescents: A Moderated Mediation Model of Peer Autonomy Support and Self-Esteem.

The present study employed the social-ecological diathesis-stress model as a theoretical framework to extend previous research by examining the underlying mechanism and conditional process that contribute to the positive association between bullying victimization and internalizing problems among adolescents. A moderated mediation model involving peer autonomy support and self-esteem was tested using a sample of 1723 adolescents (50.7% girls; M age = 12.79, SD = 1.58), who completed questionnaires assessing internalizing problems, bullying victimization, peer autonomy support, and self-esteem. The findings revealed that self-esteem partially mediated the positive association between bullying victimization and adolescents' internalizing problems. Specifically, bullying victimization was inversely related to self-esteem, which, in turn, was negatively associated with internalizing problems. Further moderation analyses demonstrated that these direct and indirect associations varied based on levels of peer autonomy support. Simple slope analyses specifically indicated that (a) peer autonomy support buffered against the negative association of bullying victimization with self-esteem and internalizing problems, and (b) peer autonomy support mitigated the negative association of self-esteem with internalizing problems. The elucidation of this mechanism and conditional process holds important implications for early interventions and prevention efforts aimed at mitigating the detrimental association of bullying victimization with adolescents' healthy emotional functions.

Neutrophil membrane-engineered Panax ginseng root-derived exosomes loaded miRNA 182-5p targets NOX4/Drp-1/NLRP3 signal pathway to alleviate acute lung injury in sepsis: experimental studies.

BACKGROUND: The purpose of this study was to prepare neutrophil membrane-engineered Panax ginseng root-derived exosomes (N-exo) and investigate the effects of N-exo microRNA (miRNA) 182-5p (N-exo-miRNA 182-5p) on acute lung injury (ALI) in sepsis. METHODS: Panax ginseng root-derived exosomes were separated by differential centrifugation. Neutrophil membrane engineering was performed on exo to obtain N-exo. miRNA182-5p was transmitted into N-exo by electroporation technology to obtain N-exo-miRNA 182-5p. LPS was used to establish an in-vivo and in-vitro model of ALI of sepsis to evaluate the anti-inflammatory effect of N-exo-miRNA 182-5p. RESULTS: The results of transmission electron microscope showed that exo was a double-layer membrane structure like a saucer. Nanoparticle size analysis showed that the average particle size of exo was 129.7 nm. Further, compared with exo, the level of miRNA182-5p was significantly increased in N-exo. The experimental results showed that N-exo-miRNA 182-5p significantly improved ALI via target regulation of NOX4/Drp-1/NLRP3 signal pathway in vivo and in vitro . CONCLUSION: In conclusion, this study prepared a novel engineered exosome (N-exo and N-exo-miRNA 182-5p significantly improved ALI in sepsis via target regulation of NOX4/Drp-1/NLRP3 signal pathway, providing new ideas and methods for treatment of ALI in sepsis.

Economic burden attributable to healthcare-associated infections at western China hospitals: 6 Year, prospective cohort study.

OBJECTIVES: Healthcare-associated infections (HAIs) represent a major threat to patient safety and are associated with significant economic burden. Calculating the costs attributable to HAIs is challenging given the various sources of bias. Although HAIs as a reasonably preventable medical harm should have been closely linked to medical insurance incentives, there was little linkage between HAIs and medicare in western China owing to the lack of economic evaluation data. The present study aimed to generate estimates of the attributable costs associated with HAIs and the magnitude of costs growth. METHODS: In this cohort study designed horizontally and vertically from 2016 to 2022, we compared outcomes of randomly sampling patients with HAIs and individually matched patients without HAIs in two cohorts at a 6-year interval at 34 hospitals in western China. The primary outcome was the direct medical cost for the entire hospital stay, converted to US dollars ($ for the benchmark year), discounted at 3% annually, and estimated separately in the full analysis set (FAS) and the per protocol set (PPS). We used multiple linear regression to adjust the discounted costs and to assess subgroups effects within each cohort. We nested a dynamic vertical comparison of costs attributable to HAIs between the front and rear cohorts. RESULTS: A total of 230 patients with HAIs in 2016 and 204 patients with HAIs in 2022 were enrolled. After a 1:1 match, all 431 pairs were recruited as FAS, of which 332 pairs as PPS met all matching restrictions. Compared to the 2016 cohort in FAS, the patients with HAIs in 2022 had a significantly older age (64.40 ± 16.45 years), higher repeat hospitalization rate (65 [32.02%] of 203), and lower immune function (69 [33.99%] of 203). The discounted costs and adjusted-discounted costs for patients with HAIs in the 2022 cohort were found to be significantly higher than those of patients without HAIs (discounted costs: $5484.60 [IQR 8426.03] vs $2554.04(4530.82), P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3040.21(1823.36), P < 0.001, respectively), and also higher than those of patients with HAIs in the 2016 cohort (discounted costs: $5484.60 [8426.03] vs $3553.00 [6127.79], P < 0.001; adjusted-discounted costs: $5235.90 [3772.12] vs $3703.82 [3159.14], P < 0.001, respectively). In vertical comparison of PPS, the incremental costs of the 2022 cohort are 1.48 times higher than those of the 2016 cohort ($964.63(4076.15) vs $652.43 [2533.44], P = 0.084). CONCLUSIONS: This meticulously designed study in western China has successfully and accurately examined the economic burden attributable to HAIs. Their rapidly increasing tendency poses a serious challenge to patients, hospitals, and the medical insurance. A closer linkage between HAIs and ongoing motivating system changes is urgently needed in western China.

Narcissism Moderates the Association Between Autonomy-Supportive Parenting and Adolescents' Prosocial Behavior.

Prior research has separately investigated the associations of autonomy-supportive parenting and narcissism with adolescents' prosocial behavior, but their joint relationships with prosocial behavior have been rarely examined. The present research aimed to expand the existing literature by scrutinizing the main and interactive associations of autonomy-supportive parenting and narcissism with adolescents' prosocial behavior. In so doing, a series of four studies (collectively N = 2023), combining cross-sectional, longitudinal, and experimental designs, were conducted. The adolescents' mean age varied from 12.42 to 15.70 years, with a balanced representation of the sexes in those studies. Converging results across four studies showed that high narcissism magnified the positive association between autonomy-supportive parenting and adolescents' prosocial behavior. The interaction pattern presented also suggested adolescents with high narcissism scores were more affected than others-both for better and for worse-by autonomy-supportive parenting, although this interaction might be specific to particular facets of prosocial behavior. These results were robust after adjusting for a few key covariates and survived a set of additional analyses. The present findings provide a novel avenue to explain individual differences linking prosocial behavior with those two factors and further advance precise, individualized strategies to promote adolescents' prosocial behavior.

Unlocking mild-condition benzene ring contraction using nonheme diiron N-oxygenase.

Benzene ring contractions are useful yet rare reactions that offer a convenient synthetic route to various valuable chemicals. However, the traditional methods of benzene contraction rely on noble-metal catalysts under extreme conditions with poor efficiency and uncontrollable selectivity. Mild-condition contractions of the benzene ring are rarely reported. This study presents a one-step, one-pot benzene ring contraction reaction mediated by an engineered nonheme diiron N-oxygenase. Using various aniline substrates as amine sources, the enzyme causes the phloroglucinol-benzene-ring contraction to afford a series of 4-cyclopentene-1,3-dione structures. A reaction detail study reveals that the nonheme diiron N-oxygenase first oxidizes the aromatic amine to a nitroso intermediate, which then attacks the phloroglucinol anion and causes benzene ring contraction. Besides, we have identified two potent antitumor compounds from the ring-contracted products.

Photocatalytic Umpolung Strategy for the Synthesis of α-Amino Phosphine Oxides and Deuterated Derivatives.

Direct, economical, and green synthesis of deuterated α-amino phosphine oxides remains an elusive challenge in synthetic chemistry. Herein, we report a visible-light-driven umpolung strategy for synthesizing deuterated α-amino phosphine oxides from isocyanide using 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene as the photocatalyst and D2O as the deuterium source. Moreover, the streamlined and sustainable methodology can be applied in the modification of amino acids, natural products, and drugs. The strong antiproliferative activity of the desired products indicates that the method could provide a novel privileged scaffold for antitumor drug development.

Colonic expression of glutathione S-transferase alpha 4 and 4-hydroxynonenal adducts is correlated with the pathology of murine colitis-associated cancer.

Chronic inflammation-induced oxidative stress is an important driving force for developing colitis-associated cancer (CAC). 4-hydroxynonenal (4-HNE) is a highly reactive aldehyde derived from lipid peroxidation of ω-6 polyunsaturated fatty acids that contributes to colorectal carcinogenesis. Glutathione S-transferase alpha 4 (Gsta4) specifically conjugates glutathione to 4-HNE and thereby detoxifies 4-HNE. The correlation of these oxidative biomarkers with the pathological changes in CAC is, however, unclear. In this study, we investigated the expression of Gsta4 and 4-HNE adducts in azoxymethane/dextran sulfate sodium (AOM/DSS)-induced murine CAC, and analyzed the correlations of 4-HNE and Gsta4 with inflammatory cytokines and the pathological scores in the colon biopsies. Real-time quantitative PCR showed that expression of IL6, TNFα, and Gsta4 sequentially increased in colon tissues for mice treated with DSS for 1, 2, and 3 cycles, respectively. Moreover, immunohistochemical staining showed remarkably increased expression of 4-HNE adducts, Gsta4, TNFα, and IL6 in the colon biopsies after 3 cycles of DSS treatment. Correlation analysis demonstrated that 4-HNE adducts in the colon biopsies were positively correlated with Gsta4 expression. Additionally, the expression of Gsta4 and 4-HNE adducts were strongly correlated with the pathological changes of colon, as well as the expression of TNFα and IL6 in colon tissues. These results provide evidence for the association of oxidative biomarkers Gsta4 and 4-HNE with the pathological changes of CAC and may help developing novel histopathological biomarkers and prevention targets for CAC.

L-Arginine, as an essential amino acid, is a potential substitute for treating COPD via regulation of ROS/NLRP3/NF-κB signaling pathway.

BACKGROUNDS: Chronic obstructive pulmonary disease (COPD) is a frequent and common disease in clinical respiratory medicine and its mechanism is unclear. The purpose of this study was to find the new biomarkers of COPD and elucidate its role in the pathogenesis of COPD. Analysis of metabolites in plasma of COPD patients were performed by ultra-high performance liquid chromatography (UPLC) and quadrupole time-of-flight mass spectrometry (TOF-MS). The differential metabolites were analyzed and identified by multivariate analysis between COPD patients and healthy people. The role and mechanisms of the differential biomarkers in COPD were verified with COPD rats, arginosuccinate synthetase 1 (ASS-l) KO mice and bronchial epithelial cells (BECs). Meanwhile, whether the differential biomarkers can be the potential treatment targets for COPD was also investigated. 85 differentials metabolites were identified between COPD patients and healthy people by metabonomic. RESULTS: L-Arginine (LA) was the most obvious differential metabolite among the 85 metabolites. Compare with healthy people, the level of LA was markedly decreased in serum of COPD patients. It was found that LA had protective effects on COPD with in vivo and in vitro experiments. Silencing Ass-1, which regulates LA metabolism, and α-methy-DL-aspartic (NHLA), an Ass-1 inhibitor, canceled the protective effect of LA on COPD. The mechanism of LA in COPD was related to the inhibition of ROS/NLRP3/NF-κB signaling pathway. It was also found that exogenous LA significantly improved COPD via regulation of ROS/NLRP3/NF-κB signaling pathway. L-Arginine (LA) as a key metabolic marker is identified in COPD patients and has a protective effect on COPD via regulation of ROS/NLRP3/NF-κB signaling pathway. CONCLUSION: LA may be a novel target for the treatment of COPD and also a potential substitute for treating COPD.

Analysis of somatic mutations and key driving factors of cervical cancer progression.

We investigated the somatic mutations and key driving factors of cervical cancer by whole exome sequencing . We found 22,183 somatic single nucleotide variations (SNVs) in 52 paired samples. Somatic SNVs in cervical cancer were significantly higher than those in high-grade intraepithelial lesion and low-grade squamous intraepithelial lesion groups (P < 0.05). C → T/G accounted for 44.12% of base substitution. Copy number variation (false discovery rate < 0.05) was found in 57 chromosome regions. The three regions with significant differences between cervical cancer and non-cervical cancer groups were 1q21.1, 3q26.33, and 13q33.1, covering genes related to tumor proliferation, differentiation, and apoptosis. The frequency of human papillomavirus (HPV) insertion/integration and the number of "tCw" mutations in the cervical cancer group were significantly higher than those in the non-cervical cancer group (P < 0.05). The total number of mutations was positively correlated with the number of "tCw" mutations (R 2 = 0.7967). HPV insertion/integration (OR = 2.302, CI = 1.523-3.589, P = 0.0005), APOBEC enrichment (OR = 17.875, CI = 2.117-150.937, P = 0.001), and HLA-B*39 in HLA-I (OR = 6.435, CI = 0.823-48.919, P = 0.0042) were risk factors for cervical cancer, while HLA-DQB1*05 in HLA-II was a protective factor (OR = 0.426, CI = 0.197-0.910, P = 0.032). Conclusively, HPV insertion/integration, APOBEC mutagenesis, and HLA polymorphisms are high-risk factors for cervical cancer and may be causes of genome instability and somatic mutations. This study provides experimental data for revealing the molecular mechanism of cervical cancer.

VDAC2 malonylation participates in sepsis-induced myocardial dysfunction via mitochondrial-related ferroptosis.

Sepsis-induced myocardial dysfunction (SIMD) is a prevalent and severe form of organ dysfunction with elusive underlying mechanisms and limited treatment options. In this study, the cecal ligation and puncture and lipopolysaccharide (LPS) were used to reproduce sepsis model in vitro and vivo. The level of voltage-dependent anion channel 2 (VDAC2) malonylation and myocardial malonyl-CoA were detected by mass spectrometry and LC-MS-based metabolomics. Role of VDAC2 malonylation on cardiomyocytes ferroptosis and treatment effect of mitochondrial targeting nano material TPP-AAV were observed. The results showed that VDAC2 lysine malonylation was significantly elevated after sepsis. In addition, the regulation of VDAC2 lysine 46 (K46) malonylation by K46E and K46Q mutation affected mitochondrial-related ferroptosis and myocardial injury. The molecular dynamic simulation and circular dichroism further demonstrated that VDAC2 malonylation altered the N-terminus structure of the VDAC2 channel, causing mitochondrial dysfunction, increasing mitochondrial ROS levels, and leading to ferroptosis. Malonyl-CoA was identified as the primary inducer of VDAC2 malonylation. Furthermore, the inhibition of malonyl-CoA using ND-630 or ACC2 knock-down significantly reduced the malonylation of VDAC2, decreased the occurrence of ferroptosis in cardiomyocytes, and alleviated SIMD. The study also found that the inhibition of VDAC2 malonylation by synthesizing mitochondria targeting nano material TPP-AAV could further alleviate ferroptosis and myocardial dysfunction following sepsis. In summary, our findings indicated that VDAC2 malonylation plays a crucial role in SIMD and that targeting VDAC2 malonylation could be a potential treatment strategy for SIMD.

Transfer of the high-temperature adult-plant stripe rust resistance gene Yr62 in four Chinese wheat cultivars.

Wheat stripe rust is one of the diseases that seriously affect wheat production worldwide. Breeding resistant cultivars is an effective way to control this disease. The wheat stripe rust resistance gene Yr62 has high-temperature adult-plant resistance (HTAP). In this study, PI 660,060, a single Yr62 gene line, was crossed with four Chinese wheat cultivars, LunXuan987 (LX987), Bainongaikang58 (AK58), ZhengMai9023 (ZM9023), and HanMai6172 (H6172). F1 seeds of four cross combinations were planted and self-crossed to develop the advance generations in the field. The seeds of each cross were mixed harvested and about 2400 to 3000 seeds were sown in each generation for F1 to F4 to maintain the maximum possible genotypes. Forty-five lines were selected and evaluated for resistance to stripe rust and agronomic traits, including plant height, number of grains per spike, and tiller number, in F5 and F6. Then, 33 lines with good agronomic traits and high disease resistance were developed to F9 generation. SSR markers Xgwm251 and Xgwm192 flank linked with the Yr62 were used to detect the presence of Yr62 in these 33 F9 lines. Of these, 22 lines were confirmed with the resistance gene Yr62. Finally, nine lines with good agronomic traits and disease resistance were successfully selected. The selected wheat lines in this study provide material support for the future breeding of wheat for stripe rust resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01393-1.