Electrophotocatalytic oxygenation of multiple adjacent C-H bonds.

Oxygen-containing functional groups are nearly ubiquitous in complex small molecules. The installation of multiple C-O bonds by the concurrent oxygenation of contiguous C-H bonds in a selective fashion would be highly desirable but has largely been the purview of biosynthesis. Multiple, concurrent C-H bond oxygenation reactions by synthetic means presents a challenge1-6, particularly because of the risk of overoxidation. Here we report the selective oxygenation of two or three contiguous C-H bonds by dehydrogenation and oxygenation, enabling the conversion of simple alkylarenes or trifluoroacetamides to their corresponding di- or triacetoxylates. The method achieves such transformations by the repeated operation of a potent oxidative catalyst, but under conditions that are sufficiently selective to avoid destructive overoxidation. These reactions are achieved using electrophotocatalysis7, a process that harnesses the energy of both light and electricity to promote chemical reactions. Notably, the judicious choice of acid allows for the selective synthesis of either di- or trioxygenated products.

The Impact of high-performance work system perceived by medical staff on job satisfaction: the mediating role of self-efficacy.

As the mainstay of healthcare, the job satisfaction of medical staff deserves attention. This study aimed to explore the correlation between the perception of the high-performance work system (P-HPWS) and job satisfaction of medical staff in public hospitals and to further investigate the mediating effect of self-efficacy. From November 2019 to January 2020, a cross-sectional survey on working doctors and nurses was conducted in five tertiary public hospitals in China. A total of 520 participants were surveyed. The P-HPWS, job satisfaction, and self-efficacy were assessed using the 25-item self-administered scale, six-item job satisfaction questionnaire, and the General Self-Efficacy Scale, respectively. Linear regression and mediation effects models were used to identify the associations between primary variables. The results showed a significant positive correlation between P-HPWS and job satisfaction (P < 0.01), while self-efficacy played a mediating role between P-HPWS and job satisfaction. This finding reveals the benefits of improving employees' P-HPWS and self-efficacy on their job satisfaction, and that hospitals can improve their management systems by implementing and refining HPWS.

Non-Pharmacological Interventions in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: To determine the effectiveness of non-pharmacologic interventions and the additional benefits of their combination in patients with heart failure with reduced ejection fraction (HFrEF). DATA SOURCES: We searched PubMed, Embase, and the Cochrane Clinical Trials Register from the date of database inception to April 22, 2023. STUDY SELECTION: Randomized controlled trials involving non-pharmacologic interventions conducted in patients with HFrEF were included. DATA EXTRACTION: Data were extracted by 2 independent reviewers based on a pre-tested data extraction form. The quality of evidence was assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation method. DATA SYNTHESIS: A total of 82 eligible studies (4574 participants) were included. We performed a random-effects model within a Bayesian framework to calculate weighted mean differences (WMDs) and 95% credibility intervals. High or moderate certainty evidence indicated that high-intensity aerobic interval training (HIAIT) was best on improving 6-minute walk distance (6MWD; 68.55 m [36.41, 100.47]) and left ventricular ejection fraction (6.28% [3.88, 8.77]), while high-intensity aerobic continuous training (HIACT) is best on improving peak oxygen consumption (Peak VO2; 3.48 mL/kg•min [2.84, 4.12]), quality of life (QOL; -17.26 [-29.99, -7.80]), resting heart rate (-8.20 bpm [-13.32, -3.05]), and N-terminal pro-B-type natriuretic peptide (-600.96 pg/mL [-902.93, -404.52]). Moderate certainty evidence supported the effectiveness of inspiratory muscle training to improve peak oxygen consumption and functional electrical stimulation to improve QOL. Moderate-intensity aerobic continuous training (MIACT) plus moderate-intensity resistance training (MIRT) had additional benefits in Peak VO2, 6MWD, and QOL. This review did not provide a comprehensive evaluation of adverse events. CONCLUSIONS: Both HIAIT and HIACT are the most effective single non-pharmacologic interventions for HFrEF. MIACT plus MIRT had additional benefits in improving peak oxygen consumption, 6MWD, and QOL.

Non-pharmacological interventions for older patients with hypertension: A systematic review and network meta-analysis.

OBJECTIVE: To determine the most effective non-pharmacological interventions to control the blood pressure variation in older hypertensive patients. METHODS: Primary endpoints were office systolic blood pressure (SBP) and diastolic blood pressure (DBP). The quality of evidence was assessed using the "risk of bias 2″ tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. We performed a Bayesian network meta-analysis using R-4.0.2 software to compare the efficacy of interventions. RESULTS: 36 eligible studies (3,531 patients) with a median follow-up of 12 weeks, assessing 18 non-pharmacological interventions, were included. The percentages of high, moderate, low, and very low certainty evidence were 16.7%, 38.9%, 33.3%, and 11.1%, respectively. CONCLUSION: High certainty evidence suggests that self-management education is most effective in lowering SBP and DBP in older patients with hypertension, followed by moderate-intensity aerobic exercise. Moderate-intensity resistance training is the most effective exercise for lowering SBP. REGISTRATION: PROSPERO, #CRD42020209850.

Electrochemical vicinal oxyazidation of α-arylvinyl acetates.

α-Azidoketones are valuable and versatile building blocks in the synthesis of various bioactive small molecules. Herein, we describe an environmentally friendly and efficient electrochemical vicinal oxyazidation protocol of α-arylvinyl acetates to afford diverse α-azidoketones in good yields without the use of a stoichiometric amount of chemical oxidant. A range of functionality is shown to be compatible with this transformation, and further applications are demonstrated.

Nomograms predict survival of patients with lymph node-positive, luminal a breast cancer.

BACKGROUND: To develop nomograms for the prediction of the 1-, 3-, and 5-year overall survival (OS) and breast cancer-specific survival (BCSS) for patients with lymph node positive, luminal A breast cancer. METHODS: Thirty-nine thousand fifty-one patients from The Surveillance, Epidemiology, and End Results (SEER) database were included in our study and were set into a training group (n = 19,526) and a validation group (n = 19,525). Univariate analysis and Cox proportional hazards analysis were used to select variables and set up nomogram models on the basis of the training group. Kaplan-Meier curves and the log-rank test were adopted in the survival analysis and curves plotting. C-index, calibration plots and ROC curves were used to performed internal and external validation on the training group and validation group. RESULTS: Following independent factors were included in our nomograms: Age, marital status, grade, ethnic group, T stage, positive lymph nodes numbers, Metastasis, surgery, radiotherapy, chemotherapy. In both the training group and testing group, the calibration plots show that the actual and nomogram-predicted survival probabilities are consistent greatly. The C-index values of the nomograms in the training and validation cohorts were 0.782 and 0.806 for OS and 0.783 and 0.804 for BCSS, respectively. The ROC curves show that our nomograms have good discrimination. CONCLUSIONS: The nomograms may assist clinicians predict the 1-, 3-, and 5-year OS and BCSS of patients with lymph node positive, luminal A breast cancer.

Chirality-specific growth of single-walled carbon nanotubes on solid alloy catalysts.

Carbon nanotubes have many material properties that make them attractive for applications. In the context of nanoelectronics, interest has focused on single-walled carbon nanotubes (SWNTs) because slight changes in tube diameter and wrapping angle, defined by the chirality indices (n, m), will shift their electrical conductivity from one characteristic of a metallic state to one characteristic of a semiconducting state, and will also change the bandgap. However, this structure-function relationship can be fully exploited only with structurally pure SWNTs. Solution-based separation methods yield tubes within a narrow structure range, but the ultimate goal of producing just one type of SWNT by controlling its structure during growth has proved to be a considerable challenge over the last two decades. Such efforts aim to optimize the composition or shape of the catalyst particles that are used in the chemical vapour deposition synthesis process to decompose the carbon feedstock and influence SWNT nucleation and growth. This approach resulted in the highest reported proportion, 55 per cent, of single-chirality SWNTs in an as-grown sample. Here we show that SWNTs of a single chirality, (12, 6), can be produced directly with an abundance higher than 92 per cent when using tungsten-based bimetallic alloy nanocrystals as catalysts. These, unlike other catalysts used so far, have such high melting points that they maintain their crystalline structure during the chemical vapour deposition process. This feature seems crucial because experiment and simulation both suggest that the highly selective growth of (12, 6) SWNTs is the result of a good structural match between the carbon atom arrangement around the nanotube circumference and the arrangement of the catalytically active atoms in one of the planes of the nanocrystal catalyst. We anticipate that using high-melting-point alloy nanocrystals with optimized structures as catalysts paves the way for total chirality control in SWNT growth and will thus promote the development of SWNT applications.

Efficacy of chemotherapy for lymph node-positive luminal A subtype breast cancer patients: an updated meta-analysis.

OBJECTIVE: To assess the association between chemotherapy and prognosis of patients with breast cancer of luminal A subtype and lymph node-positive, luminal A subtype breast cancer METHODS: Articles published between January 1, 2010, and May 1, 2020, were collected from PubMed, Embase, and Web of Science databases. On the basis of a test for heterogeneity, we selected the random effects model or fixed effects model for meta-analysis. Article quality was evaluated by sensitivity analysis, and Begg's and Egger's tests were used to measure publication bias. RESULTS: Six eligible articles were identified. The hazard ratio of overall survival of luminal A breast cancer patients who received both chemotherapy and endocrine therapy was 1.73 (95% CI 1.23, 2.43). The hazard ratio of overall survival for lymph node-positive, luminal A breast cancer patients who received chemotherapy and endocrine therapy was 1.86 and 95% CI 1.26, 2.81. The hazard ratio of relapse-free survival to disease-free survival was 1.30 (95% CI 0.85, 1.77). Tumor size, vascular invasion, and age did not show significant correlations with breast cancer prognosis. CONCLUSION: Compared with endocrine therapy alone, the addition of chemotherapy did not improve the prognosis of patients with luminal type A and lymph node positive cancer; instead, side effects of the additional chemotherapy may have negatively affected prognosis. Prospective studies are needed to determine whether the number of positive lymph nodes also correlates with efficacy of chemotherapy of luminal type A breast cancer.

Development of a High-Resolution All-Fiber Homodyne Laser Doppler Vibrometer.

Based on the homodyne detection, a compact and cost-effective all-fiber laser Doppler vibrometer (LDV) with high resolution is presented. For the signal processing, the discrimination algorithm combined with the nonorthogonal correction is applied. The algorithm corrects the quadrature imbalance and other nonlinearity. In the calibration experiment, with the glass pasted on a piezoceramic transducer (PZT), the velocity resolution of 62 nm/s at 4 kHz and displacement resolution of 2.468 pm are achieved. For the LDV-based acousto-optic communication, the minimum detectable sound pressure level (SPL) reached 0.12 Pa under the hydrostatic air-water surface. The results demonstrate that the designed homodyne LDV has a low system background noise and can offer high precision in the vibration measurement.

Melatonin protects oocytes from MEHP exposure-induced meiosis defects in porcine.

In 2011, DEHP (plasticizer) was reported to illegally be added in food and beverage products in Taiwan, which caused great concerns about food safety worldwide. DHEP has multiple toxic effects to human and animals such as endocrine disruption, cardiotoxicity, reproductive function, and development defects. However, the toxic effects of DEHP on mammalian oocyte quality are still unclear. Since MEHP is the active metabolite of DEHP in vivo, in this study we used porcine oocyte as model to explore the effects of MEHP on oocyte maturation and we also studied the effects of melatonin administration on MEHP exposure-induced meiosis defects. Our results showed that exposure to MEHP significantly decreased the polar body extrusion rate in porcine oocytes. Further study showed that cell cycle progression, meiotic spindle organization, and actin assembly were all disturbed after MEHP exposure. Moreover, the DNA and histone methylation levels were also affected, showing with altered 5mC and H3K4me2 levels. These results indicated that MEHP affected porcine oocyte maturation, while MEHP exposure-induced meiotic defects were all remarkably ameliorated by the administration of melatonin in porcine oocytes. We further tried to explore the causes of MEHP toxicity on oocytes, and we found that MEHP exposure resulted in significant elevations of oxidative stress and induced early apoptosis as well as elevated autophagy, while melatonin administration could reduce these. Taken together, our results indicated that MEHP exposure induced deterioration of oocyte quality, whereas melatonin supplement showed amelioration on oocyte maturation through its rescue effects on oocyte oxidative stress-mediated apoptosis and autophagy.

Manganese deception on graphene and implications in catalysis.

Heteroatom-doped metal-free graphene has been widely studied as the catalyst for the oxygen reduction reaction (ORR). Depending on the preparation method and the dopants, the ORR activity varies ranging from a two-electron to a four-electron pathway. The different literature reports are difficult to correlate due to the large variances. However, due to the potential metal contamination, the origin of the ORR activity from "metal-free" graphene remains confusing and inconclusive. Here we decipher the ORR catalytic activities of diverse architectures on graphene derived from reduced graphene oxide. High angle annular dark field scanning transmission electron microscopy, X-ray absorption near edge structure, extended X-ray absorption fine structure, and trace elemental analysis methods are employed. The mechanistic origin of ORR activity is associated with the trace manganese content and reaches its highest performance at an onset potential of 0.94 V when manganese exists as a mononuclear-centered structure within defective graphene. This study exposes the deceptive role of trace metal in formerly thought to be metal-free graphene materials. It also provides insight into the design of better-performing catalyst for ORR by underscoring the coordination chemistry possible for future single-atom catalyst materials.

Growth and Transfer of Seamless 3D Graphene-Nanotube Hybrids.

Seamlessly connected graphene and carbon nanotube hybrids (GCNTs) have great potential as carbon platform structures in electronics due to their high conductivity and high surface area. Here, we introduce a facile method for making patterned GCNTs and their intact transfer onto other substrates. The mechanism for selective growth of vertically aligned CNTs (VA-CNTs) on the patterned graphene is discussed. The complete transfer of the GCNT pattern onto other substrates is possible because of the mechanical strength of the GCNT hybrids. Electrical conductivity measurements of the transferred GCNT structures show Ohmic contact through the VA-CNTs to graphene--evidence of its integrity after the transfer process.

A statistical resolution measure of fluorescence microscopy with finite photons.

First discovered by Ernest Abbe in 1873, the resolution limit of a far-field microscope is considered determined by the numerical aperture and wavelength of light, approximately λ 2 N A . With the advent of modern fluorescence microscopy and nanoscopy methods over the last century, this definition is insufficient to fully describe a microscope's resolving power. To determine the practical resolution limit of a fluorescence microscope, photon noise remains one essential factor yet to be incorporated in a statistics-based theoretical framework. We proposed an information density measure quantifying the theoretical resolving power of a fluorescence microscope in the condition of finite photons. The developed approach not only allows us to quantify the practical resolution limit of various fluorescence and super-resolution microscopy modalities but also offers the potential to predict the achievable resolution of a microscopy design under different photon levels.

Comparative analysis of adverse event risks in breast cancer patients receiving pembrolizumab combined with paclitaxel versus paclitaxel monotherapy: insights from the FAERS database.

Objective: This study aimed to evaluate the risk of adverse events (AEs) in breast cancer patients treated with pembrolizumab combined with paclitaxel versus those receiving pembrolizumab or paclitaxel monotherapy, using the FDA Adverse Event Reporting System (FAERS) database. Methods: Data were extracted from the FAERS database for breast cancer patients treated with pembrolizumab combined with paclitaxel or with pembrolizumab or paclitaxel monotherapy from Q1 2016 to Q2 2023. Disproportionation analysis was performed by calculating the reporting odds ratio (ROR) with corresponding 95% confidence interval (95% CI), the information component (IC), and the lower bound of the information component 95% confidence interval (IC025) to identify potential safety signals. Results: No significant difference in AEs was observed between the combined treatment group and the pembrolizumab monotherapy group. However, the combined treatment group exhibited a substantial increase in AE risk compared to the paclitaxel monotherapy group. The most significant increases in AE risk were adrenal insufficiency (ROR = 189.94, 95% CI 25.41-1419.7, IC = 3.37, IC025 = 1.59), hypophysitis (ROR = 99.46, 95% CI 12.72-777.4, IC = 3.31, IC025 = 1.44), and myocarditis (ROR = 69.5, 95% CI 8.55-565.23, IC = 3.25, IC025 = 1.33). The time-to-event for combined treatment was 35 (34-70) days, for pembrolizumab was 43 (35-90) days, and for paclitaxel was 42 (37-76) days. The combination therapy group demonstrated significantly shorter intervals to the onset of adrenal insufficiency (p = 0.008), myocarditis (p < 0.001), and immune-related enterocolitis (p = 0.009). Conclusion: Analysis of the FAERS database indicates that combination therapy significantly elevates the risk of adrenal insufficiency, myocarditis, hypophysitis, and immune-related enterocolitis compared to paclitaxel monotherapy. These findings provide critical insights for clinicians in predicting and managing potential AEs associated with this treatment regimen.

Correlation between S100A7 and immune characteristics, methylation, tumor stemness and tumor heterogeneity in pan-cancer and its role in chemotherapy resistance in breast cancer.

OBJECTIVE: To explore the relationships between S100A7 and the immune characteristics, tumor heterogeneity, and tumor stemness pan-cancer as well as the effect of S100A7 on chemotherapy sensitivity in breast cancer. METHODS: TCGA-BRCA and TCGA-PANCANCER RNA-seq data and clinical follow-up survival data were collected from the University of California Santa Cruz database. Survival analyses were performed to explore the relationship between S100A7 expression and pan-cancer prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and Gene Set Enrichment Analysis (GSEA) were used to identify the potential pathways related to the differentially expressed genes in breast cancer. Spearman's and Wilcoxon's tests were used to investigate the relationships between S100A7 expression and immune characteristics, methylation, tumor heterogeneity, and tumor stemness. The potential functions of S100A7 and its influence on chemotherapy sensitivity in breast cancer were elucidated using reverse transcription-quantitative PCR, Cell Counting Kit-8 (CCK-8) assay, Transwell assay, and wound healing assay. RESULTS: S100A7 was highly expressed in most types of tumors and was associated with poor prognosis. S100A7 was closely associated with immunomodulators, immune checkpoint and immune cell infiltration. Further, S100A7 was related to tumor mutational burden, tumor heterogeneity, methylation and tumor stemness in breast cancer. High S100A7 expression was associated with the invasiveness, migration, proliferation and chemotherapy resistance of breast cancer cells in vitro experiments. CONCLUSION: High S100A7 expression was related with poor prognosis and chemotherapy resistance in breast cancer, making it a potential immune and chemotherapy resistance biomarker.

Identification of molecular subtypes based on chromatin regulator-related genes and experimental verification of the role of ASCL1 in conferring chemotherapy resistance to breast cancer.

Objective: The aim of this study was to identify the molecular subtypes of breast cancer based on chromatin regulator-related genes. Methods: The RNA sequencing data of The Cancer Genome Atlas-Breast Cancer cohort were obtained from the official website, while the single-cell data were downloaded from the Gene Expression Omnibus database (GSE176078). Validation was performed using the Molecular Taxonomy of Breast Cancer International Consortium dataset. Furthermore, the immune characteristics, tumor stemness, heterogeneity, and clinical characteristics of these molecular subtypes were analyzed. The correlation between chromatin regulators and chemotherapy resistance was examined in vitro using the quantitative real-time polymerase chain reaction (qRT-PCR) and Cell Counting Kit-8 (CCK8) assays. Results: This study identified three stable molecular subtypes with different prognostic and pathological features. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction analyses revealed that the differentially expressed genes were associated with disease processes, such as mitotic nuclear division, chromosome segregation, condensed chromosome, and specific chromosome region. The T stage and subtypes were correlated with the clinical features. Tumor heterogeneity (mutant-allele tumor heterogeneity, tumor mutational burden, purity, and homologous recombination deficiency) and tumor stemness (RNA expression-based stemness score, epigenetically regulated RNA expression-based stemness score, DNA methylation-based stemness score, and epigenetically regulated DNA methylation-based stemness score) significantly varied between the three subtypes. Furthermore, Western blotting, qRT-PCR, and CCK8 assays demonstrated that the expression of ASCL1 was positively correlated with chemotherapy resistance in breast cancer. Conclusion: This study identified the subtypes of breast cancer based on chromatin regulators and analyzed their clinical features, gene mutation status, immunophenotype, and drug sensitivity. The results of this study provide effective strategies for assessing clinical prognosis and developing personalized treatment strategies.

Mendelian randomization with incomplete measurements on the exposure in the Hispanic Community Health Study/Study of Latinos.

Mendelian randomization has been widely used to assess the causal effect of a heritable exposure variable on an outcome of interest, using genetic variants as instrumental variables. In practice, data on the exposure variable can be incomplete due to high cost of measurement and technical limits of detection. In this paper, we propose a valid and efficient method to handle both unmeasured and undetectable values of the exposure variable in one-sample Mendelian randomization analysis with individual-level data. We estimate the causal effect of the exposure variable on the outcome using maximum likelihood estimation and develop an expectation maximization algorithm for the computation of the estimator. Simulation studies show that the proposed method performs well in making inference on the causal effect. We apply our method to the Hispanic Community Health Study/Study of Latinos, a community-based prospective cohort study, and estimate the causal effect of several metabolites on phenotypes of interest.

Multivariable Mendelian randomization with incomplete measurements on the exposure variables in the Hispanic Community Health Study/Study of Latinos.

Multivariable Mendelian randomization allows simultaneous estimation of direct causal effects of multiple exposure variables on an outcome. When the exposure variables of interest are quantitative omic features, obtaining complete data can be economically and technically challenging: the measurement cost is high, and the measurement devices may have inherent detection limits. In this paper, we propose a valid and efficient method to handle unmeasured and undetectable values of the exposure variables in a one-sample multivariable Mendelian randomization analysis with individual-level data. We estimate the direct causal effects with maximum likelihood estimation and develop an expectation-maximization algorithm to compute the estimators. We show the advantages of the proposed method through simulation studies and provide an application to the Hispanic Community Health Study/Study of Latinos, which has a large amount of unmeasured exposure data.

Dispersing carbon-based nanomaterials in aqueous phase by graphene oxides.

Graphene oxides (GO) can be considered as polyelectrolytes with surfactant-like characteristics. On one hand, due to the electrical repulsion between the negatively charged ionized edges, GO exhibits great water solubility; on the other hand, its hydrophobic central plane retains the potential of strong π-π interaction with other conjugated sp(2) network structures. Therefore, it is expected that GO can serve as an excellent dispersing agent for dispersion of various carbon-based nanomaterials in aqueous phase. Here we report a systematic study of dispersing various carbon-based nanomaterials, including SWNTs, C60, and graphene, by aqueous GO. The GO-dispersed all-carbon nanocomposites are characterized using various spectroscopic methods and electron microscopies, and their stabilities are tested. Compared to other dispersing agents, the GO concentration is much lower than the concentrations of other dispersing agents used when similar contents of carbon-based nanomaterials are dispersed. Involving only simple ultrasonication and centrifugation processes, GO dispersion thus offers an easy manipulation for large-scale solution-dispersed all-carbon nanocomposites.