Incident Benzodiazepine and Z-Drug Use and Subsequent Risk of Serious Infections.

BACKGROUND AND OBJECTIVES: Animal studies have suggested a link between benzodiazepine and related Z-drug (BZDR) use and immune dysfunction. Corresponding evidence in humans is limited and focuses mainly on pneumonia. This study aimed to assess the association of incident BZDR use with subsequent development of serious infections. METHODS: This Swedish register-based study included a population-based demographically matched cohort, a co-twin control cohort, and an active comparator cohort. Out of 7,362,979 individuals aged below 65 years who were BZDR naïve by 2007, 713,896 BZDR recipients with incident dispensation of any BZDRs between 2007 and 2019 were 1:1 matched to 713,896 nonrecipients from the general population; 9197 BZDR recipients were compared with their 9298 unexposed co-twins/co-multiples; and 434,900 BZDR recipients were compared with 428,074 incident selective serotonin reuptake inhibitor (SSRI) recipients. The outcomes were identified by the first inpatient or specialist outpatient diagnosis of serious infections in the National Patient Register, or death from any infections recorded as the underlying cause in the Cause of Death Register. Cox proportional hazards regression models were fitted and controlled for multiple confounders, including familial confounding and confounding by indication. To study a possible dose-response association, the cumulative dosage of BZDRs dispensed during the follow-up was estimated for each BZDR recipient and modeled as a time-varying exposure with dose categories in tertiles [≤ 20 defined daily doses (DDDs), > 20 DDDs ≤ 65, and > 65 DDDs). The risk of infections was assessed in BZDR recipients within each category of the cumulative BZDR dosage compared to their demographically matched nonrecipients. RESULTS: In the demographically matched cohort (average age at incident BZDR use 42.8 years, 56.9% female), the crude incidence rate of any serious infections in BZDR recipients and matched nonrecipients during 1-year follow-up was 4.18 [95% confidence intervals (CI) 4.13-4.23] and 1.86 (95% CI 1.83-1.89) per 100 person-years, respectively. After controlling for demographic, socioeconomic, clinical, and pharmacological confounders, BZDR use was associated with 83% relative increase in risk of any infections [hazard ratio (HR) 1.83, 95% CI 1.79-1.89]. The risk remained increased, although attenuated, in the co-twin cohort (HR 1.55, 95% CI 1.23-1.97) and active comparator cohort (HR 1.33, 95% CI 1.30-1.35). The observed risks were similar across different types of initial BZDRs and across individual BZDRs, and the risks increased with age at BZDR initiation. We also observed a dose-response association between cumulative BZDR dosage and risk of serious infections. CONCLUSIONS: BZDR initiation was associated with increased risks of serious infections, even when considering unmeasured familial confounding and confounding by indication. The exact pathways through which BZDRs may affect immune function, however, remain unclear. Further studies are needed to explore the neurobiological mechanisms underlying the association between BZDR use and serious infections, as it can lead to safer therapeutic strategies for patients requiring BZDR.

Design and Feasibility Verification of Novel AC/DC Hybrid Microgrid Structures.

To enhance the power supply reliability of the microgrid cluster consisting of AC/DC hybrid microgrids, this paper proposes an innovative structure that enables backup power to be accessed quickly in the event of power source failure. The structure leverages the quick response characteristics of thyristor switches, effectively reducing the power outage time. The corresponding control strategy is introduced in detail in this paper. Furthermore, taking practical considerations into account, two types of AC/DC hybrid microgrid structures are designed for grid-connected and islanded states. These microgrids exhibit strong distributed energy consumption capabilities, simple control strategies, and high power quality. Additionally, the aforementioned structures are constructed within the MATLAB/Simulink R2023a simulation software. Their feasibility is verified, and comparisons with the existing studies are conducted using specific examples. Finally, the cost and efficiency of the application of this study are discussed. Both the above results and analysis indicate that the structures proposed in this paper can reduce costs, improve efficiency, and enhance power supply stability.

Role of exosomal non­coding RNAs in ovarian cancer (Review).

Ovarian cancer (OC) is a common gynecological disease with a high mortality rate worldwide due to its insidious nature and undetectability at an early stage. The standard treatment, combining platinum­based chemotherapy with cytoreductive surgery, has suboptimal results. Therefore, early diagnosis of OC is crucial. All cell types secrete extracellular vesicles, particularly exosomes. Exosomes, which contain lipids, proteins, DNA and non­coding RNAs (ncRNAs), are novel methods of intercellular communication that participate in tumor development and progression. ncRNAs are categorized by size into long ncRNAs (lncRNAs) and small ncRNAs (sncRNAs). sncRNAs further include transfer RNAs, small nucleolar RNAs, PIWI­interacting RNAs and microRNAs (miRNAs). miRNAs inhibit protein translation and promote messenger RNA (mRNA) cleavage to suppress gene expression. By sponging downstream miRNAs, lncRNAs and circular RNAs can regulate target gene expression, thereby weakening the interactions between miRNAs and mRNAs. Exosomes and exosomal ncRNAs, commonly present in human biological fluids, are promising biomarkers for OC. The present article aimed to review the potential role of exosomal ncRNAs in the diagnosis and prognosis of OC by summarizing the characteristics, processes, roles and isolation methods of exosomes and exosomal ncRNAs.

Site-specific tethering nanobodies on recombinant adeno-associated virus vectors for retargeted gene therapy.

Recombinant adeno-associated viruses (rAAVs) have been extensively studied for decades as carriers for delivering therapeutic genes. However, designing rAAV vectors with selective tropism for specific cell types and tissues has remained challenging. Here, we introduce a strategy for redirecting rAAV by attaching nanobodies with desired tropism at specific sites, effectively replacing the original tropism. To demonstrate this concept, we initially modified the genetic code of rAAV2 to introduce an azido-containing unnatural amino acid at a precise site within the capsid protein. Following a screening process, we identified a critical site (N587+1) where the introduction of unnatural amino acid eliminated the natural tropism of rAAV2. Subsequently, we successfully redirected rAAV2 by conjugating various nanobodies at the N587+1 site, using click and SpyTag-Spycatcher chemistries to form nanobody-AAV conjugates (NACs). By investigating the relationship between NACs quantity and effect and optimizing the linker between rAAV2 and the nanobody using a cathepsin B-susceptible valine-citrulline (VC) dipeptide, we significantly improved gene delivery efficiency both in vitro and in vivo. This enhancement can be attributed to the facilitated endosomal escape of rAAV2. Our method offers an exciting avenue for the rational modification of rAAV2 as a retargeting vehicle, providing a convenient platform for precisely engineering various rAAV2 vectors for both basic research and therapeutic applications. STATEMENT OF SIGNIFICANCE: AAVs hold great promise in the treatment of genetic diseases, but their clinical use has been limited by off-target transduction and efficiency. Here, we report a strategy to construct NACs by conjugating a nanobody or scFv to an rAAV capsid site, specifically via biorthogonal click chemistry and a spy-spycatcher reaction. We explored the structure-effect and quantity-effect relationships of NACs and then optimized the transduction efficiency by introducing a valine-citrulline peptide linker. This approach provides a biocompatible method for rational modification of rAAV as a retargeting platform without structural disruption of the virus or alteration of the binding capacity of the nanobody, with potential utility across a broad spectrum of applications in targeted imaging and gene delivery.

Bioinspired High-Linearity, Wide-Sensing-Range Flexible Stretchable Bioelectronics Based on MWCNTs/GR/Nd2Fe14B/PDMS Nanocomposites for Human-Computer Interaction and Biomechanics Detection.

In recent years, flexible and stretchable strain sensors have emerged as a prominent area of research, primarily due to their remarkable stretchability and extremely low strain detection threshold. Nevertheless, the advancement of sensors is currently constrained by issues such as complexity, high costs, and limited durability. To tackle the aforementioned issues, this study introduces a lepidophyte-inspired flexible, stretchable strain sensor (LIFSSS). The stretchable bioelectronics composites were composed of multiwalled carbon nanotubes, graphene, neodymium iron boron, and polydimethylsiloxane. Unique biolepidophyted microstructures and magnetic conductive nanocomposites interact with each other through synergistic interactions, resulting in the effective detection of tensile strain and magnetic excitation. The LIFSSS exhibits a 170% tensile range, a linearity of 0.99 in 50-170% strain (0.96 for full-scale range), and a fine durability of 7000 cycles at 110% tensile range. The sensor accurately detects variations in linear tensile force, human movement, and microexpressions. Moreover, LIFSSS demonstrates enhanced efficacy in sign language recognition for individuals with hearing impairments and magnetic grasping for robotic manipulators. Hence, the LIFSSS proposed in this study shows potential applications in various fields, including bioelectronics, electronic skin, and physiological activity monitoring.

Variation of Chemical Microenvironment of Pores in Hydrazone-Linked Covalent Organic Frameworks for Photosynthesis of H2O2.

Photocatalytic synthesis of H2O2 is an advantageous and ecologically sustainable alternative to the conventional anthraquinone process. However, achieving high conversion efficiency without sacrificial agents remains a challenge. In this study, two covalent organic frameworks (COF-O and COF-C) were prepared with identical skeletal structures but with their pore walls anchored to different alkyl chains. They were used to investigate the effect of the chemical microenvironment of pores on photocatalytic H2O2 production. Experimental results reveal a change of hydrophilicity in COF-O, leading to suppressed charge recombination, diminished charge transfer resistance, and accelerated interfacial electron transfer. An apparent quantum yield as high as 10.3 % (λ=420 nm) can be achieved with H2O and O2 through oxygen reduction reaction. This is among the highest ever reported for polymer photocatalysts. This study may provide a novel avenue for optimizing photocatalytic activity and selectivity in H2O2 generation.

Incorporation of Pd Single-atom Sites in Perovskite with an Excellent Selectivity toward Photocatalytic Semihydrogenation of Alkynes.

Semihydrogenation is a crucial industrial process. Noble metals such as Pd have been extensively studied in semihydrogenation reactions, owing to their unique catalytic activity toward hydrogen activation. However, the overhydrogenation of alkenes to alkanes often happens due to the rather strong adsorption of alkenes on Pd active phases. Herein, we demonstrate that the incorporation of Pd active phases as single-atom sites in perovskite lattices such as SrTiO3 can greatly alternate the electronic structure and coordination environment of Pd active phases to facilitate the desorption of alkenes rather than further hydrogenation. Furthermore, the incorporated Pd sites can be well stabilized without sintering by a strong host-guest interaction with SrTiO3 during the activation of H species in hydrogenation reactions. As a result, the Pd incorporated SrTiO3 (Pd-SrTiO3) exhibits an excellent time-independent selectivity (> 99.9 %) and robust durability for the photocatalytic semihydrogenation of phenylacetylene to styrene. This strategy based on incorporation of active phases in perovskite lattices will have broad implications in the development of high-performance photocatalysts for selective hydrogenation reactions.

Maintenance proton pump inhibitor use and risk of colorectal cancer: a Swedish retrospective cohort study.

OBJECTIVES: We aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort. DESIGN: Retrospective cohort study. SETTING: This research was conducted at the national level, encompassing the entire population of Sweden. PARTICIPANTS: This study utilised Swedish national registries to identify all adults who had ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding participants who were followed up for less than 1 year. A total of 754 118 maintenance PPI users were included, with a maximum follow-up of 7.5 years. INTERVENTIONS: Maintenance PPI use (cumulative≥180 days), with a comparator of maintenance histamine-2 receptor antagonist (H2RA) use. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the risk of CRA, presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Subgroup analyses were performed to explore the impact of indications, tumour locations, tumour stages and the duration of follow-up. A multivariable Poisson regression model was fitted to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus H2RA use. RESULTS: Maintenance PPI users exhibited a slightly elevated risk of CRA compared to the general population (SIR 1.10, 95% CI=1.06 to 1.13) for both men and women. Individuals aged 18-39 (SIR 2.79, 95% CI=1.62 to 4.47) and 40-49 (SIR 2.02, 95% CI=1.65 to 2.45) had significantly higher risks than the general population. Right-sided CRA showed a higher risk compared to the general population (SIR 1.26, 95% CI=1.20 to 1.32). There was no significant difference in the risk of CRA between maintenance PPI users and maintenance H2RA users (IRR 1.05, 95% CI=0.87 to 1.27, p<0.05). CONCLUSIONS: Maintenance PPI use may be associated with an increased risk of CRA, but a prolonged observation time is needed.

Molecular characterization, spatiotemporal expression, and background adaptation regulation of tyrosinase in loach (Misgurnus anguillicaudatus).

The Poyang Lake region is home to large-blackspot loaches (LBL), small-blackspot loaches (SBL), and non-blackspot loaches (NBL), Misgurnus anguillicaudatus. To investigate the impact of tyrosinase on spot development, the complementary DNAs (cDNA) of tyrosinase in M. anguillicaudatus (designated as Matyr) were cloned using the rapid amplification of cDNA ends (RACE)-PCR method. The full-length cDNA for Matyr was 2020 bp, and the open-reading frame comprised 1617 bp, encoding a predicted protein with 538 amino acids. Phylogenetic studies revealed that MaTyr was first grouped with Tyr of Triplophysa tibetana and Leptobotia taeniops, and then Tyr of other cyprinid fish. The quantitative reverse-transcription-PCR results show that Matyr was highly expressed in the muscle, caudal fin, and dorsal skin. The Matyr gene's messenger RNA expression pattern steadily increased from the fertilized ovum period to the somitogenesis period, and from the muscle effect stage to 6 days after fertilization, it considerably increased (p < 0.01). The Matyr hybridization signals with similar location could be found in all developmental stages of three kinds of loaches using whole-mount in situ hybridization (WISH) technology and were the strongest during the organ development period and melanin formation period. Dot hybridization signals in LBLs rapidly spread to the back of the body beginning at the period when the eyes first formed melanin, and their dimensions were larger than those of NBLs during the same time period. The body color of loaches could change reversibly with black/white background adaptation. The α-msh, mitfa, and tyr are mainly expressed in loaches adapted with a black background. Tyr gene could be involved in the development of blackspots and body color polymorphism, and contribute to organ development in the loach.

Motor development-focused exercise training enhances gross motor skills more effectively than ordinary physical activity in healthy preschool children: an updated meta-analysis.

Purpose: The growth of certain human brain structures peaks at early ages, and complex motor interventions could positively facilitate this process. This study aims to offer an updated meta-analysis regarding the effectiveness of motor development-focused exercise training on gross motor skills in preschool children. Methods: We searched English- and Chinese-language electronic databases as of March 2024. The main eligibility criteria were as follows: participants were healthy children aged 3 to 6 years old, and the experimental design was a randomized controlled trial, with the control arm participating in either free play or ordinary physical education curriculum. We conducted a Hartung-Knapp random-effects meta-analysis of the standardized mean difference for locomotor, object control, or gross motor quotient. Results: The search identified 23 eligible studies, of which approximately 75% were considered to have a low risk of bias. Compared with active control, exercise training showed a large to very large effect size. Cohen's d values were 1.13, 1.55, and 1.53 for locomotor, object control, and gross motor quotient, respectively. From a probabilistic viewpoint, these effect sizes correspond to events that are "very likely to occur" and "almost sure to occur." Due to variations in intervention programs, all outcome measures showed high heterogeneity. Conclusion: This updated meta-analysis offers a realistic synthesis of the current evidence, leading to the conclusion that targeted motor skill exercise training can almost certainly enhance preschool children's gross motor skills. Practical implications are discussed regarding the refinement of the instructional framework and the dissemination of these findings in preschool settings.

Exploring the relationship between heavy metals and diabetic retinopathy: a machine learning modeling approach.

Diabetic retinopathy (DR) is one of the leading causes of adult blindness in the United States. Although studies applying traditional statistical methods have revealed that heavy metals may be essential environmental risk factors for diabetic retinopathy, there is a lack of analyses based on machine learning (ML) methods to adequately explain the complex relationship between heavy metals and DR and the interactions between variables. Based on characteristic variables of participants with and without DR and heavy metal exposure data obtained from the NHANES database (2003-2010), a ML model was developed for effective prediction of DR. The best predictive model for DR was selected from 11 models by receiver operating characteristic curve (ROC) analysis. Further permutation feature importance (PFI) analysis, partial dependence plots (PDP) analysis, and SHapley Additive exPlanations (SHAP) analysis were used to assess the model capability and key influencing factors. A total of 1042 eligible individuals were randomly assigned to two groups for training and testing set of the prediction model. ROC analysis showed that the k-nearest neighbour (KNN) model had the highest prediction performance, achieving close to 100% accuracy in the testing set. Urinary Sb level was identified as the critical heavy metal affecting the predicted risk of DR, with a contribution weight of 1.730632 ± 1.791722, which was much higher than that of other heavy metals and baseline variables. The results of the PDP analysis and the SHAP analysis also indicated that antimony (Sb) had a more significant effect on DR. The interaction between age and Sb was more significant compared to other variables and metal pairs. We found that Sb could serve as a potential predictor of DR and that Sb may influence the development of DR by mediating cellular and systemic senescence. The study revealed that monitoring urinary Sb levels can be useful for early non-invasive screening and intervention in DR development, and also highlighted the important role of constructed ML models in explaining the effects of heavy metal exposure on DR.

Association of diabetic retinopathy on all-cause and cause-specific mortality in older adults with diabetes: National Health and Nutrition Examination Survey, 2005-2008.

To evaluate the effect of diabetic retinopathy (DR) status or severity on all-cause and cause-specific mortality among diabetic older adults in the United States using the most recent National Health and Nutrition Examination Survey (NHANES) follow-up mortality data. The severity of DR was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale. Multiple covariate-adjusted Cox proportional hazards regression models, Fine and Gray competing risk regression models, and propensity score matching (PSM) methods were used to assess the risk of all-cause and cause-specific mortality in individuals with diabetes. All analyses adopted the weighted data and complex stratified design approach proposed by the NHANES guidelines. Time to death was calculated based on the time between baseline and date of death or December 31, 2019, whichever came first. Ultimately 1077 participants, representing 3,025,316 US non-hospitalized individuals with diabetes, were included in the final analysis. After a median follow-up of 12.24 years (IQR, 11.16-13.49), 379 participants were considered deceased from all-causes, with 43.90% suffering from DR, including mild DR (41.50%), moderate to severe DR (46.77%), and proliferative DR (PDR) (67.21%). DR was associated with increased all-cause, cardiovascular disease (CVD) and diabetes mellitus (DM)-specific mortality, which remained consistent after propensity score matching (PSM). Results of DR grading assessment suggested that the presence of mild, moderate to severe NPDR was significantly associated with increased risk of all-cause and CVD-specific mortality, while the presence and severity of any DR was associated with increased DM-specific mortality, with a positive trend. The presence of DR in elderly individuals with diabetes is significantly associated with the elevated all-cause and CVD mortality. The grading or severity of DR may reflect the severity of cardiovascular disease status and overall mortality risk in patients with diabetes.

Enriching surface-ordered defects on WO3 for photocatalytic CO2-to-CH4 conversion by water.

Defect engineering has been widely applied in semiconductors to improve photocatalytic properties by altering the surface structures. This study is about the transformation of inactive WO3 nanosheets to a highly effective CO2-to-CH4 conversion photocatalyst by introducing surface-ordered defects in abundance. The nonstoichiometric WO3-x samples were examined by using aberration-corrected electron microscopy. Results unveil abundant surface-ordered terminations derived from the periodic {013} stacking faults with a defect density of 20.2%. The {002} surface-ordered line defects are the active sites for fixation CO2, transforming the inactive WO3 nanosheets into a highly active catalyst (CH4: O2 = 8.2: 16.7 µmol h-1). We believe that the formation of the W-O-C-W-O species is a critical step in the catalytic pathways. This work provides an atomic-level comprehension of the structural defects of catalysts for activating small molecules.

Senolytics ameliorate the failure of bone regeneration through the cell senescence-related inflammatory signalling pathway.

Stress-induced premature senescent (SIPS) cells induced by various stresses deteriorate cell functions. Dasatinib and quercetin senolytics (DQ) can alleviate several diseases by eliminating senescent cells. α-tricalcium phosphate (α-TCP) is a widely used therapeutic approach for bone restoration but induces bone formation for a comparatively long time. Furthermore, bone infection exacerbates the detrimental prognosis of bone formation during material implant surgery due to oral cavity bacteria and unintentional contamination. It is essential to mitigate the inhibitory effects on bone formation during surgical procedures. Little is known that DQ improves bone formation in Lipopolysaccharide (LPS)-contaminated implants and its intrinsic mechanisms in the study of maxillofacial bone defects. This study aims to investigate whether the administration of DQ ameliorates the impairments on bone repair inflammation and contamination by eliminating SIPS cells. α-TCP and LPS-contaminated α-TCP were implanted into Sprague-Dawley rat calvaria bone defects. Simultaneously, bone formation in the bone defects was investigated with or without the oral administration of DQ. Micro-computed tomography and hematoxylin-eosin staining showed that senolytics significantly enhanced bone formation at the defect site. Histology and immunofluorescence staining revealed that the levels of p21- and p16-positive senescent cells, inflammation, macrophages, reactive oxygen species, and tartrate-resistant acid phosphatase-positive cells declined after administering DQ. DQ could partially alleviate the production of senescent markers and senescence-associated secretory phenotypes in vitro. This study indicates that LPS-contaminated α-TCP-based biomaterials can induce cellular senescence and hamper bone regeneration. Senolytics have significant therapeutic potential in reducing the adverse osteogenic effects of biomaterial-related infections and improving bone formation capacity.

Effects of wind-driven current and thermal dynamics in a temperate monomictic reservoir: Implications for manganese transport and treatment in water supply systems.

Increasing manganese (Mn) concentrations in source water contribute to aesthetic and health-related concerns in drinking water. The challenges with Mn in drinking water primarily arise from elevated Mn concentrations in the water supply reservoir, with the inefficacy of Mn treatment largely attributed to fluctuating Mn levels in the water source. A three-dimensional Mn cycle model in a temperate monomictic reservoir, Tarago Reservoir, and a decision support system reflecting Mn variations in the local water treatment plant have been established in previous research. This study aimed to examine Mn variations from the reservoir to raw water and treated water under the influence of wind conditions during different stages of thermal structure, and discover valuable recommendations for Mn treatment in the local water supply system. We crafted 12 scenarios to scrutinize the impact of varying intensities of offshore and onshore winds on hydrodynamic processes and Mn transport during strong thermal stratification, weak thermal stratification, and turnover. The scenario analysis revealed that, during the gradual weakening of thermal stratification, offshore wind induced a substantial amount of Mn to the upper layers near the water intake point. Conversely, onshore wind hindered the upward transport of Mn. The simulated Mn in the raw water under the 12 scenarios indicated that the timing of turnover in the Tarago Reservoir is the primary concern for Mn treatment in the water treatment plant. Additionally, close attention should be given to the frequency and intensity of offshore winds during the weakening of thermal stratification.

Association between ambient particulate matter exposure and mitochondrial DNA copy number: A systematic review and meta-analysis.

BACKGROUND: Ambient particulate matter (PM) has been recognized as inducing oxidative stress, which could contribute to mitochondrial damage and dysfunction. However, studies investigating the association between ambient PM and mitochondria, particularly mitochondrial DNA copy number (mtDNA-CN), have yielded inconsistent results. METHODS: We conducted comprehensive literature searches to identify observational studies published before July 17, 2023, examining the association between ambient PM exposure and mtDNA-CN. Meta-analysis using random effects model was employed to calculate the pooled effect estimates for general individual exposures, as well as for prenatal exposure with specific trimester. Additionally, the quality and level of evidence for each exposure-outcome pair was evaluated. RESULTS: A total of 10 studies were included in the systematic review and meta-analysis. The results indicated that general individual exposure to PM2.5 (ß = -0.084, 95 % CI: -0.521, 0.353; I2 = 93 %) and PM10 (ß = 0.035, 95 % CI: -0.129, 0.199; I2 = 95 %) did not significantly affect mtDNA-CN. Prenatal exposure to PM2.5 (ß = 0.023, 95 % CI: -0.087, 0.133; I2 = 0 %) and PM10 (ß = 0.006, 95 % CI: -0.135; 0.147; I2 = 51 %) were also not significantly associated with mtDNA-CN in offspring. The level of evidence for each tested exposure-outcome pair was assessed as "inadequate." CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that there is an "inadequate" strength of evidence for the association between general individual or prenatal exposure to ambient PM and mtDNA-CN. Future research necessitates studies with more rigorous design, enhanced control of confounding factors, and improved measures of exposure to substantiate our findings.

Photoelectron Migration Boosted by Hollow Double-Shell Dyads Based on Covalent Organic Frameworks for Highly Efficient Photocatalytic Hydrogen Generation.

Photocatalytic hydrogen production based on noble metal-free systems is a promising technology for the conversion of solar energy into green hydrogen, it is pivotal and challenging to tailor-make photocatalysts for achieving high photocatalytic efficiency. Herein, we reported a hollow double-shell dyad through uniformly coating covalent organic frameworks (COFs) on the surface of hollow Co9S8. The double shell architecture enhances the scattering and refraction efficiency of incident light, shortens the transmission distance of the photogenerated charge carriers, and exposes more active sites for photocatalytic conversion. The hydrogen evolution rate is as high as 23.15 mmol g-1 h-1, which is significantly enhanced when compared with that of their physical mixture (0.30 mmol g-1 h-1) and Pt-based counterpart (11.84 mmol g-1 h-1). This work provides a rational approach to the construction of noble-metal-free photocatalytic systems based on COFs to enhance hydrogen evolution performance.

Albumin combined with neutrophil-to-lymphocyte ratio score and outcomes in patients with acute coronary syndrome treated with percutaneous coronary intervention.

BACKGROUND: Evidence about the association between albumin combined with neutrophil-to-lymphocyte ratio score (ANS) and survival outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is rare. This study aimed to evaluate the prognostic value of ANS in patients with ACS undergoing PCI by propensity score matching (PSM) analysis. PATIENTS AND METHODS: Patients with ACS undergoing PCI were consecutively enrolled in this prospective cohort study from January 2016 to December 2018. The albumin and neutrophil-to-lymphocyte ratio cutoff values for predicting major adverse cardiovascular events (MACEs) were calculated using receiver operating characteristic curves. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazard regression models and PSM. The study endpoint was the occurrence of a MACE, which included all-cause mortality and rehospitalization for severe heart failure during follow-up. RESULTS: Overall, 1549 patients with adequate specimens were identified and assigned into different groups for comparison. Before and after PSM, the Kaplan-Meier curves showed that a higher ANS value was associated with a higher risk of MACEs (all P  < 0.001). The multivariate Cox proportional hazard regression model showed that the ANS (per 1 score increase) [hazard ratio (HR), 2.016; 95% confidence interval (CI), 1.329-3.057; P  = 0.001 vs. HR, 2.166; 95% CI, 1.344-3.492; P  = 0.002] was an independent predictor for MACEs. CONCLUSION: This study tentatively confirms that ANS may be a valuable clinical indicator to identify high-risk ACS patients after PCI. More high-quality prospective studies are needed in the future.

Construction of Thiadiazole-Bridged sp2-Carbon-Conjugated Covalent Organic Frameworks with Diminished Excitation Binding Energy Toward Superior Photocatalysis.

Sp2-carbon-conjugated covalent organic frameworks (sp2c-COFs) have emerged as promising platforms for phototo-chemical energy conversion due to their tailorable optoelectronic properties, in-plane π-conjugations, and robust structures. However, the development of sp2c-COFs in photocatalysis is still highly hindered by their limited linkage chemistry. Herein, we report a novel thiadiazole-bridged sp2c-COF (sp2c-COF-ST) synthesized by thiadiazole-mediated aldol-type polycondensation. The resultant sp2c-COF-ST demonstrates high chemical stability under strong acids and bases (12 M HCl or 12 M NaOH). The electro-deficient thiadiazole together with fully conjugated and planar skeleton endows sp2c-COF-ST with superior photoelectrochemical performance and charge-carrier separation and migration ability. As a result, when employed as a photocathode, sp2c-COF-ST exhibits a significant photocurrent up to ∼14.5 µA cm-2 at 0.3 V vs reversible hydrogen electrode (RHE) under visible-light irradiation (>420 nm), which is much higher than those analogous COFs with partial imine linkages (mix-COF-SNT ∼ 9.5 µA cm-2) and full imine linkages (imi-COF-SNNT ∼ 4.9 µA cm-2), emphasizing the importance of the structure-property relationships. Further temperature-dependent photoluminescence spectra and density functional theory calculations demonstrate that the sp2c-COF-ST has smaller exciton binding energy as well as effective mass in comparison to mix-COF-SNT and imi-COF-SNNT, which suggests that the sp2c-conjugated skeleton enhances the exciton dissociation and carrier migration under light irradiation. This work highlights the design and preparation of thiadiazole-bridged sp2c-COFs with promising photocatalytic performance.