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Background Cardiovascular disease (CVD) is a major cause of human mortality worldwide, characterized by its insidious onset, intricate and variable course, and poor prognosis. Early identification and active intervention of potentially critically ill patients is essential to improve their prognosis. Objective To conduct a scoping review of the research on early warning assessment tools for cardiovascular disease risk at home and abroad, summarize and analyze their assessment content and application, ultimately providing reference for the selection of appropriate early warning tools for cardiovascular disease patients in China. Methods CNKI, Wanfang Data, VIP, CBM, PubMed, Web of Science, Cochrane Library, Embase, CINAHL, and Scopus were systematically searched from inception to May 2023. Two investigators independently screened literature and extracted data, analyzed in terms of assessment content, study subjects, validation method, reliability and validity, and predictive efficacy. Results A total of 16 papers were included, comprising 7 papers on the development and validation of assessment tools and 9 papers on the localized application of these tools, involving 20 early warning assessment tools for cardiovascular disease risk. The results of the analysis showed that each assessment tool contained 3 to 17 assessment items, with the most frequently mentioned items of age, systolic blood pressure, respiratory rate, oxygen saturation, heart rate, comorbidities, level of consciousness, and gender. The results of the reliability and validity tests for 2 papers indicated robust reliability and validity, while all other studies lacked reliability and validity evaluations. Ten papers reported the area under the curve (AUC), with values ranging from 0.550 to 0.926 9. Conclusion Diverse early warning assessment tools for cardiovascular disease risk are available, however, their overall quality remains to be improved and there is a lack of specific assessment tools. In the future, it is imperative to conduct further validations of the reliability and validity of the existing tools, and develop localized early warning assessment tools specialized for cardiovascular diseases considering the unique characteristics of the disease, which exhibit robust reliability and validity.

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responding to immunotherapy. The relationships between tumor DNA damage response, patient immune system and immunotherapy have recently attracted attention. Accumulating evidence suggests that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsive to immunotherapies, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of the DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of patients with gastric adenocarcinoma, using publicly available datasets. The results demonstrated that DRGS high score patients showed significantly better therapeutic outcomes for ICB compared to DRGS low score patients (p < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocyte infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival, as compared to the low-score patients. Results obtained from HPA and IHC supported significant dysregulation of the genes in DRGS in gastric cancer tissues, and a positive correlation in protein expression between DRGS and PD-L1. Therefore, the DRGS scoring system may have implications in tailoring immunotherapy in gastric cancers. A preprint has previously been published (Yuan et al., 2021).

Gastric cancer (GC) is one of the main causes of cancer-associated morbidity and mortality worldwide. The present study aimed to investigate the role of the gene encoding formin homology 2 domain containing 1 (FHOD1) protein in GC development. Data from The Cancer Genome Atlas were firstly analyzed, and immunohistochemistry was conducted on GC tissues. The results demonstrated that FHOD1 expression in GC tissues was significantly increased compared with adjacent non-tumor tissues. Furthermore, the expression level of FHOD1 was negatively associated with the overall survival of patients with GC. For the functional studies, lentivirus-mediated short hairpin RNA against FHOD1 and FHOD1-overexpression vectors were constructed to knockdown and overexpress the expression level of FHOD1 in human GC cell lines, respectively. The results indicated that FHOD1 knockdown inhibited the proliferation, colony formation and migratory and invasive abilities of GC cells. Conversely, overexpression of FHOD1 in GC cells promoted soft-agar colony formation and migratory and invasive abilities. In addition, it was demonstrated that genes of which expression levels were correlated with FHOD1 were enriched in the Gene Ontology term of 'extracellular matrix (ECM) structural constituent', suggesting that FHOD1 may serve an important role in the regulation of ECM. In conclusion, the present study demonstrated that FHOD1 may exert an oncogenic role in cultured GC cells and be inversely associated with the overall survival of patients with GC.

Skeletal molecular editing gained considerable recent momentum and emerged as a uniquely powerful tool for late‐stage diversifications. Thus far, superstoichiometric amounts of costly hypervalent iodine(III) reagents were largely required for skeletal indole editing. In contrast, we herein show that electricity enables sustainable nitrogen atom insertion reactions to give bio‐relevant quinazoline scaffolds without stoichiometric chemical redox‐waste product. The transition metal‐free electro‐editing was enabled by the oxygen reduction reaction (ORR) and proved robust on scale, while tolerating a variety of valuable functional groups. [ABSTRACT FROM AUTHOR]

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To describe the pharmacokinetics/pharmacodynamics (PK/PD) of a 2 h infusion of ceftazidime‐avibactam (CAZ‐AVI) in critically ill patients with augmented renal clearance (ARC). A retrospective review of all critically ill patients with ARC who were treated with CAZ‐AVI between August 2020 and May 2023 was conducted. Patients whose 12‐h creatinine clearance prior to CAZ‐AVI treatment and steady‐state concentration (Css) of CAZ‐AVI were both monitored were enrolled. The free fraction (fCss) of CAZ‐AVI was calculated from Css. The joint PK/PD targets of CAZ‐AVI were considered optimal when a Css/minimum inhibitory concentration (MIC) ratio for CAZ ≥4 (equivalent to 100% fT > 4 MIC) and a Css/CT ratio of AVI >1 (equivalent to 100% fT > CT 4.0 mg/L) were reached simultaneously, quasioptimal when only one of the two targets was reached, and suboptimal when neither target was reached. The relationship between PK/PD goal achievement, microbial eradication and the clinical efficacy of CAZ‐AVI was evaluated. Four patients were included. Only one patient achieved optimal joint PK/PD targets, while the other three reached suboptimal targets. The patient with optimal PK/PD targets achieved microbiological eradication, while the other three patients did not, but all four patients achieved good clinical efficacy. Standard dosages may not enable most critically ill patients with ARC to reach the optimal joint PK/PD targets of CAZ‐AVI. Optimal drug dose adjustment of CAZ‐AVI in ARC patients requires dynamic drug concentration monitoring. [ABSTRACT FROM AUTHOR]

Indole derivatives are fundamental structural units in many bioactive compounds and molecular materials. The site‐selective C7‐functionalization of these moieties has been proven to be extremely challenging due to the inherent reactivity of the C2‐ and C3‐positions. Herein, we report the first electro‐C7‐alkenylation of indoles. This novel and sustainable methodology provides highly exclusive access to the C7‐position devoid of often toxic and expensive chemical oxidants. Moreover, an array of substrates was successfully alkenylated at the C7‐position, and versatile product diversification was achieved. [ABSTRACT FROM AUTHOR]

In recent years, waterborne photo-curable technology have been used in biomedical applications, such as dental materials, 3D biological printing, in vitro polymerization, cell encapsulation, etc. Water-soluble photoinitiators exhibiting good water solubility, low cytotoxicity, and high initiation efficiency have become key substances for the widespread development and application of photo-curable technology in biomedical applications. Therefore, researchers designed and synthesized a serious of water-soluble photoinitiators, and explored the application of this photoinitiators in drug delivery, bio-inspired detoxification, cell sensor, cartilage repair, volumetric bioprinting, biological tissue adhesive and photodynamic tumor therapy, and so on. In this review, the recent state of art of water-soluble photoinitiator including types, photoinitiation mechanisms, and application examples in biomedicine of water-based photoinitiators is provided. Moreover, the perspective on the future development of water-soluble photoinitiators is also discussed, hoping to provide some inspiration for the development and application of water-based photoinitiating systems. [ABSTRACT FROM AUTHOR]

Twofold distal C−H functionalization was accomplished by difunctionalization of nonactivated alkenes to provide rapid access to multifunctionalized molecules. The multicomponent ruthenium‐catalyzed remote 1,n‐difunctionalization (n=6,7) of nonactivated alkenes with fluoroalkyl halides and heteroarenes in a modular manner is reported. The meta‐C(sp2)−H/C‐6(sp3)−H distal functionalization featured mild conditions, unique selectivity, and broad substrate scope with a domino process for twofold remote C(sp2)−H/C(sp3)−H activation of the sequential formation of three different carbon‐centered radicals. A plausible mechanism was proposed based on detailed experimental and computational studies. [ABSTRACT FROM AUTHOR]

Transition-metal-catalyzed C–H activation has emerged as a powerful strategy for molecular synthesis with unique levels of resource economy. Weak secondary dispersion interactions were found to play an essential role in these transformations in terms of kinetic efficacy and selectivity. This Account summarizes our group's recent progress in the rationalization and quantification of London dispersion effects within the transition-metal-catalyzed C–H activation. 1 Introduction 2 Annulation Reactions 3 Alkylation Reactions 4 Arylation Reactions 5 Olefination Reactions 6 Oxygenation Reactions 7 Conclusion [ABSTRACT FROM AUTHOR]