Synthesis of CF3-Isoquinolinones and Imidazole-Fused CF3-Isoquinolinones Based on C-H Activation-Initiated Cascade Reactions of 2-Aryloxazolines.

Presented herein are novel syntheses of CF3-isoquinolinones and imidazole fused CF3-isoquinolinones based on the cascade reactions of 2-aryloxazolines with trifluoromethyl imidoyl sulfoxonium ylides. The formation of CF3-isoquinolinone involves an intriguing cascade process including oxazolinyl group-assisted aryl alkylation through C(sp2)-H bond metalation, carbene formation, migratory insertion, and proto-demetalation followed by intramolecular condensation and water-promoted oxazolinyl ring-scission. With this method, the isoquinolinone scaffold tethered with valuable functional groups was effectively constructed. By taking advantage of the functional groups embedded therein, the products thus obtained could be readily transformed into imidazole-fused CF3-isoquinolinones or coupled with some clinical drugs to furnish hybrid compounds with potential applications in drug development. In general, the developed protocols feature expeditious and convenient formation of valuable CF3-heterocyclic skeletons, broad substrate scope, and ready scalability. In addition, studies on the activity of selected products against some human cancer cell lines demonstrated their potential as lead compounds for the development of novel anticancer drugs.

Interleukin-1ß stimulated macrophage derived exosomes improve myocardial injury in sepsis via regulation of mitochondrial homeostasis: Experimental research.

BACKGROUND: The purpose of this study was to investigate the effects of interleukin-1ß (IL-1ß) stimulation on the protection of macrophage derived exosomes miR-146a (M-IL-exo-146a) on sepsis induced myocardial injury (SMI) in vitro and in vivo. METHODS: Macrophage derived exosomes (M-exo) and IL-1ß stimulated macrophage exosomes (M-IL-exo) were isolated from macrophages of sepsis with or without IL-1ß. The expressions of miR-146a in M-exo and M- IL-exo were detected by fluorescence quantitative PCR. Related molecular biology technologies were used to evaluate the role and mechanism of M-exo-146a and M-IL-exo-146a on SMI and the enhancing effect of IL-1ß. RESULTS: Compared with M-exo, the expression of miR-146a in M-IL-exo was significantly increased. M-IL-exo-146a significantly alleviated SMI by decreasing the level of serum myocardial enzymes, serum and myocardial oxidative stress and cytokines, and improved myocardial mitochondrial imbalance. The mechanism responsible for IL-1ß enhancing the production of IL-M-exo miR-146a was via JNK-1/2 signal pathway. The mechanism responsible for M-exo-IL-miR-146a protecting SMI was related to miR-146a inhibiting inflammatory response and mitochondrial function via MAPK4/Drp1 signal pathway. CONCLUSIONS: This study provides a new strategy for the treatment of SMI by delivering IL-1ß stimulated macrophage derived exosomes.

Associations between parental autonomy support and depressive symptoms among Chinese college students: the chain-mediating effects of mindfulness and self-esteem.

Introduction: Despite extensive research on contextual factors will relieve college students' depressive symptoms, significant gaps remain in understanding the underlying mechanisms of this relationship, particularly through individual strength factors such as mindfulness and self-esteem. Based on self-determination theory, we explore the association between parental autonomy support and depressive symptoms among Chinese college students and whether mindfulness and self-esteem serve as mediators. Methods: A total of 1,182 Chinese college students aged 16 to 27 years (Mage = 20.33, SD = 1.63; female = 55.7%) participated in this research. Questionnaires pertaining to parental autonomy support, mindfulness, self-esteem, and depressive symptoms were administered. Results: The results revealed that depressive symptoms were negatively correlated with both paternal and maternal autonomy support, with mindfulness and self-esteem acting as chain-mediators. Specifically, mindfulness and self-esteem were positively impacted by parental autonomy support, whereas depressive symptoms were negatively impacted by mindfulness and self-esteem. Furthermore, paternal and maternal autonomy support significantly impacted depressive symptoms via both direct and indirect pathways. Indirect effects included three paths: mediation through mindfulness, mediation through self-esteem, and mediation through the mindfulness and self-esteem chain. Discussion: The study highlights the fundamental mechanisms that account for the association between Chinese college students' parental autonomy support and depressive symptoms, these insights can be used to prevent and manage mental health problems among Chinese college students. For example, parents' autonomy support can directly reduce depressive symptoms, but we can also indirectly promote college students' mental health by emphasizing the mediation role of students' mindfulness and self-esteem.

Synthesis of CF3-Substituted N-Heterocyclic Compounds Based on C-H Activation-Initiated Formal [2 + 3] Annulation Featuring with a Latent Nucleophilic Site.

Presented herein is a novel synthesis of CF3-substituted pyrrolo[1,2-a]indole derivatives based on the cascade reactions of N-alkoxycarbamoyl indoles with CF3-ynones. Mechanistically, the formation of a product involves a tandem process initiated by Rh(III)-catalyzed and N-alkoxycarbamoyl group-directed regioselective C2-H alkenylation of the indole scaffold followed by in situ removal of the directing group and intramolecular N-nucleophilic addition/annulation under one set of reaction conditions. To our knowledge, this is the first example in which a N-alkoxycarbamoyl unit initially acts as a directing group for C2-H functionalization of the indole scaffold and is then removed to provide the required reactive NH-moiety for subsequent intramolecular condensation. Moreover, the products thus obtained could be conveniently transformed into structurally and biologically attractive cycloheptenone fused indole derivatives through an acid-promoted cascade transformation. In addition, studies on the activity of selected products against human cancer cell lines demonstrated their potential as lead compounds for the development of novel anticancer drugs.

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.

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.

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.

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".

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.

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.

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.

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.

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.

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.