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Piezocatalysis portrays a promising alternative for producing hydrogen (H 2 ) and hydrogen peroxide (H 2 O 2 ) in a clean and safe way, but the simultaneous enhancement of both properties remains challenging. In this study, a BiFeO 3 -based bifunctional piezocatalytic strategy via Sm doping and g-C 3 N 4 compositing (Bi 0.98 Sm 0.02 FeO 3 /g-C 3 N 4 ) was proposed for efficient simultaneous H 2 and H 2 O 2 production. Benefiting from the synergistic effect between the optimized energy band structure and piezo-generated charges, the performances of hydrogen evolution reaction (HER) and water oxidation reaction (WOR) are both enhanced remarkably. As a result, the evolution rates of BSFO/g-C 3 N 4 for pure water splitting into H 2 and H 2 O 2 simultaneously reach 988 and 214 μmol g -1 h -1 without any sacrificial agent, which is 4.6 and 7.6 times higher than those of pure BiFeO 3 . Theoretical calculations reveal the critical role of this optimization in reducing the adsorption energy barriers of HER and WOR intermediates by factors of 10.83 and 12.38, respectively. This study broadens new insight into the design of efficient piezocatalysts for water splitting.

Objectives: This paper demonstrates International Caries Detection and Assessment System (ICDAS) training procedures and inter/intra-examiner reliability for lesion severity, activity, and filling criteria in an elementary school setting., Methods: ICDAS training was conducted in December 2021 prior to a school-based cluster-randomized controlled trial. A total of 59 children (6-8 years old) in grades 1-2 from one school in Houston, Texas were recruited. Two licensed dentists received a 5-day training from an ICDAS trainer at the participating school. Thirty-eight children were evaluated at least once by each dental trainee, and 18 had repeat examinations. The ICDAS criteria were used to classify dental caries lesion severity (0-6), lesion activity (active/inactive), and filling material (0-9) of all visually available primary and permanent tooth surfaces. Inter and intra-examiner reliability between each dental trainee and the "gold standard" trainer was evaluated using Kappa statistics., Results: For lesion severity, the examination indicated an inter-rater weighted Kappa of 0.77 (95% CI 0.71-0.82) and 0.82 (95% CI 0.77-0.87) for each trainee examiner compared to the gold standard examiner. The Kappas increased slightly from the first to second examinations (lesion-weighted Kappa: 0.76 to 0.84 and 0.82 to 0.84). The intra-rater reliability indicated excellent reliability for lesion and filling (0.83 to 0.94) and moderate for activity (0.58)., Conclusions: ICDAS training/calibration were essential to ensure accuracy and reliability of dental caries measurements. The study demonstrated that ICDAS training of dentists with no prior criteria experience is feasible in a community setting and can lead to high reliability and repeatability., (© 2024 American Association of Public Health Dentistry.)

We meticulously designed a triflate porous layer on Zn anodes to enhance the overall performance of Zn-ion batteries. During battery operation, it stabilizes the surface pH of Zn anodes and facilitates the formation of a ZnF 2 -containing interphase. Therefore, both the reversibility and reaction kinetics of Zn anodes are effectively promoted.

Objective: Given the high disease and cost burden of ischemic stroke, evaluating the clinical efficacy and cost-effectiveness of new approaches to prevent and treat ischemic stroke is critical. Effective ischemic stroke management depends on timely administration of thrombolytics after stroke onset. This study evaluates the cost-effectiveness associated with the use of mobile stroke units (MSUs) to expedite tissue plasminogen activator (tPA) administration, as compared with standard management through emergency medical services (EMS)., Methods: This study is a prospective, multicenter, alternating-week, cluster-controlled trial of MSU versus EMS. One-year and life-time cost-effectiveness analyses, using the incremental cost-effectiveness ratio (ICER) method, were performed from the perspective of CMS's Medicare. Quality-adjusted life years (QALYs) estimated using patient-reported EQ-5D-5L data were used as the effectiveness measure. Health care utilizations were converted to costs using average national Medicare reimbursements. ICERs excluding patients with pre-existing disability, and limited to stroke-related costs were also calculated., Results: The first-year ICER for all tPA-eligible patients using total cost differences between MSU and EMS groups was $238,873/QALY; for patients without pre-existing disability was $61,199/QALY. The lifetime ICERs for all tPA-eligible patients and for those without pre-existing disability were $94,710 and $31,259/QALY, respectively. All ICERs were lower when restricted to stroke-related costs and were highly dependent on the number of patients treated per year in an MSU., Interpretation: MSUs' cost-effectiveness is borderline if we consider total first-year costs and outcomes in all tPA-eligible patients. MSUs are cost-effective to highly cost-effective when calculations are based on patients without pre-existing disability, patients' lifetime horizon, stroke-related costs, and more patients treated per year in an MSU. ANN NEUROL 2024., (© 2024 American Neurological Association.)

Wildfire and stubble burning release substantial amounts of black carbon (BC) into natural environments that experience frequent redox oscillations, such as wetlands and farmlands. Here, we report that redox oscillations can effectively drive ROS production from BC. Following sequential microbial reduction and air exposure, 6.5 ± 0.2 μM/g C hydrogen peroxide (H 2 O 2 ) and 285.3 ± 9.5 nM/g C hydroxyl radical (•OH) were produced from BC. Moreover, BC derived from various biomass sources, temperatures, and particle sizes exhibits 111.5-fold variations in ROS production. Electrochemical analyses revealed that both the electron transfer capacity and the ROS production selectivity are critical determinants of ROS generation under redox oscillations. The variation in electron transfer capacity (0.3-5.7 mmol e - /g C ) is primarily governed by the abundance of electron-storing moieties such as quinones, while the ROS generation selectivity (26.2-72.0%) is influenced by the presence of competitive sites for oxygen reduction reactions, such as carbon defects. These findings provide insights into ROS production from BC under fluctuating redox conditions, with potential implications for elemental cycles and pollutant dynamics in regions prone to wildfire and stubble burning events and substantial BC deposition (e.g., wetlands and rice paddies).

Purpose: To establish the repeatability of choriocapillaris flow deficit (CCFD) measurements within a macular grid and then demonstrate the use of this registered grid strategy to follow CCFD measurements over time., Methods: Swept-source optical coherence tomography angiography scans were acquired (nominal size of 6 × 6 mm). For each scan, masks of hyperreflective foci, calcified drusen, and persistent choroidal hypertransmission defects (hyperTDs) were generated. These masks were then used to exclude these prespecified regions when calculating the CCFD percentages (CCFD%). Scans were registered, and CCFD% measurements were performed within 3-mm and 5-mm fovea-centered circles and within a fovea-centered grid (one box: 74 × 74 pixels). The 95% minimal detectable changes (MDC95) for CCFD% were calculated for each of the regions. This longitudinal grid workflow was then used to study eyes before and after drusen resolved., Results: Ninety eyes of 63 patients were identified: 30 normal eyes, 30 eyes with intermediate age-related macular degeneration (iAMD), and 30 eyes with hyperTDs. The MDC95 for the normal, iAMD, and hyperTD eyes within the 3-mm and 5-mm circles ranged from 0.85% to 1.96%. The MDC95 for an individual grid's box ranged from 3.35% to 4.67%, and for the total grid area, the MDC95 ranged from 0.91% to 1.40%. When tested longitudinally before and after the resolution of drusen using grid strategy, no significant differences in the CCFD% were observed., Conclusions: A grid strategy was developed to investigate targeted longitudinal changes in CCFD% associated with changes in optical coherence tomography biomarkers, and this strategy was validated using eyes in which drusen resolved.

Hibiscus mutabilis, commonly known as the cotton rose, is a widely cultivated ornamental and has been acclaimed as the representative flower of the 2024 World Horticultural Exposition. The growth and ornamental characteristics of Hibiscus mutabilis can be affected by drought stress. Therefore, we investigated the physiological and metabolic responses of drought-sensitive Hibiscus mutabilis JRX-1 and drought-tolerant Hibiscus mutabilis CDS-4 under drought stress. The results of the physiological analyses revealed that, compared to JRX-1,CDS-4 maintained good growth and greater water use efficiency through stronger antioxidant defences, osmoregulatory capacity and stomatal regulation. A total of 3277 metabolites were identified in positive and negative ion modes, of which 663 metabolites presented changes in expression under drought conditions, including 306 upregulated metabolites and 357 downregulated metabolites. Secondary metabolites, such as flavonoids and diterpenoids, are crucial in the plant response to drought stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the differentially aboundant metabolites were significantly enriched in the pathways valine, leucine and isoleucine degradation; linoleic acid metabolism; one carbon pool by folate; and folate biosynthesis. The results of this study will not only help to elucidate and apply the physiological and metabolic regulatory strategies of Hibiscus mutabilis to improve its adaptation to water deficit conditions, but will also provide valuable guidance to breeders and molecular biologists in the screening and use of drought resistant genes in ornamental plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Importance: Sleep disturbances in Parkinson's disease (PD) are common and often adversely affect quality of life. Light therapy has benefited sleep quality and mood outcomes in various populations but results to date with conventional light therapy boxes in PD patients have been mixed. We hypothesized that a passive lighting intervention, applied in the morning and designed to maximally affect the circadian system, would improve measures of sleep and mood in PD patients., Methods: In this single-arm, within-subjects intervention study, baseline objective sleep (actigraphy), subjective sleep quality (questionnaires), and subjective mood (questionnaires) data were collected for 1 week. Lighting was then administered to participants via table/floor lamps installed in the home or via personal light therapy glasses for 2 h in the morning, 7 days per week, over the following 4-week period. Post-intervention data for the same outcomes were collected during the final week of the intervention period., Results: Among 20 participants (12 women, 8 men; mean [SD] age 72.1 [9.5] years, disease duration 9.0 [5.2] years), objective sleep duration increased significantly by 28.5 min (p = 0.029) and objective sleep time increased significantly by 19.9 min (p = 0.026)., Conclusion: Passive and easily administered lighting interventions for improving sleep in PD patients hold promise as a treatment for mitigating symptoms and improving quality of life in PD., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024. Published by Elsevier Ltd.)

As the demand for specialized and diversified pressure sensors continues to increase, excellent performance and multi-applicability have become necessary for pressure sensors. Currently, flexible pressure sensors are primarily utilized in fields such as health monitoring and human-computer interaction. However, numerous complex extreme environments in reality, including deep sea, corrosive conditions, extreme cold, and high temperatures, urgently require the services of flexible devices. Here, a piezoresistive flexible pressure sensor based on expanded polytetrafluoroethylene/functionalized carbon nanotubes (EPTFE/FCNT) is proposed. Benefiting from the unique fiber-segment architecture, chemical stability, and strong chemical binding force between EPTFE and FCNT, the fabricated sensor exhibits remarkable sensing capabilities and can be employed in multifarious extreme environments. It demonstrates a sensitivity of 862.28 kPa -1 , a response time of 6-7 ms, and a detection limit below 1 Pa. Furthermore, it possesses a pressure resolution of 0.0018% under 111 kPa and can withstand over 10,000 loading and unloading cycles under 1 MPa. Additionally, the EPTFE/FCNT sensor retains its outstanding pressure response and work efficiency in extreme conditions such as an ultra-low temperature of -80 °C, high temperature (200 °C), acidic and alkaline corrosion, and underwater. These notable attributes enormously broaden the sensors' real-world application range., (© 2024 Wiley‐VCH GmbH.)

DNA has shown great biocompatibility, programmable mechanical properties, and precise structural addressability at the nanometer scale, rendering it a material for constructing versatile nanorobots for biomedical applications. Here, we present the design principle, synthesis, and characterization of a DNA nanorobotic hand, called DNA NanoGripper, that contains a palm and four bendable fingers as inspired by naturally evolved human hands, bird claws, and bacteriophages. Each NanoGripper finger consists of three phalanges connected by three rotatable joints that are bendable in response to the binding of other entities. NanoGripper functions are enabled and driven by the interactions between moieties attached to the fingers and their binding partners. We demonstrate that the NanoGripper can be engineered to effectively interact with and capture nanometer-scale objects, including gold nanoparticles, gold NanoUrchins, and SARS-CoV-2 virions. With multiple DNA aptamer nanoswitches programmed to generate a fluorescent signal that is enhanced on a photonic crystal platform, the NanoGripper functions as a highly sensitive biosensor that selectively detects intact SARS-CoV-2 virions in human saliva with a limit of detection of ~100 copies per milliliter, providing a sensitivity equal to that of reverse transcription quantitative polymerase chain reaction (RT-qPCR). Quantified by flow cytometry assays, we demonstrated that the NanoGripper-aptamer complex can effectively block viral entry into the host cells, suggesting its potential for inhibiting virus infections. The design, synthesis, and characterization of a sophisticated nanomachine that can be tailored for specific applications highlight a promising pathway toward feasible and efficient solutions to the detection and potential inhibition of virus infections.

Background: Intake of ultra-processed foods provides more than half of the daily energy U.S. adults consume. Still, the prospective association of ultra-processed food consumption with mortality in the general U.S. population remains understudied., Objective: To investigate the prospective association of ultra-processed food consumption with mortality in a nationally representative sample of U.S. adults., Design: A prospective cohort analysis was conducted by linking baseline measurement from the National Health And Nutrition Examination Survey (NHANES) with mortality information from the National Death Index. The percentage of total energy (%E) consumed from ultra-processed foods, defined by the Nova classification system, was computed based on dietary data collected using 24-hour diet recalls., Participants/setting: This study included 38148 nationally representative U.S. adults aged 20 years and above who participated in NHANES between 2003-2004 to 2017-2018 and provided dietary intake data, with linkage to mortality data., Main Outcome Measures: Information on all-cause and cause-specific mortality was obtained from linkage to the National Death Index through December 31, 2019., Statistical Analysis Performed: Cox proportional hazard models estimated the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ultra-processed food intake and mortality., Results: During a median follow-up of 8.0 years, 4,611 deaths were confirmed, including 2064 deaths from cardiometabolic disorders (CMD) and 1046 deaths from cancer. After multivariable adjustments, each 10-point increment in usual %E from ultra-processed foods was associated with a 9% higher risk of all-cause mortality (HR=1.09, 95% CI, 1.04-1.14). The association remained significant after adjusting for the overall diet quality measured by the Health Eating Index 2015 (HR=1.06, 95% CI, 1.00-1.11, P<0.05). Among subgroups, sugar-sweetened beverages, ready-to-eat or -heat mixed dishes, ultra-processed dairy products, and ultra-processed oil/fat, condiments, and sauces were associated with an increased risk of all-cause or cause-specific mortality. Ultra-processed vegetables and legumes were associated with a reduced risk., Conclusions: In this nationally representative study of U.S. adults, higher consumption of ultra-processed food was associated with a higher risk of all-cause mortality, and this association was not fully explained by overall diet quality., (Copyright © 2024. Published by Elsevier Inc.)

Low-temperature chemical vapor deposition growth of graphene films is a long-term pursuit in the graphene synthesis field because of the low energy consumption, short heating-cooling process and low wrinkle density of as-obtained films. However, insufficient energy supply at low temperature (below 850 °C) usually leads to the difficulty in carbon source dissociation, graphene growth, and defect healing. Herein, a Carbon-Oxygen (C─O) radical assisted strategy is proposed for low-temperature growth of defect-free, wrinkle-free, and single-crystalline graphene films by using methanol precursor. We provide a deep insight into the growth process fueled by methanol precursor, unveiling the dissociation pathway of methanol and the roles of intermediate C─O radicals in carbon attaching and assembling to graphene lattice without defect formation. This method shows promising prospects in the cost-effective production of high-quality graphene films and provides inspiration for growing other 2D materials., (© 2024 Wiley‐VCH GmbH.)

Paclitaxel-resistant triple negative breast cancer (TNBC) remains one of the most challenging breast cancers to treat. Here, using an epigenetic chemical probe screen, we uncover an acquired vulnerability of paclitaxel-resistant TNBC cells to protein arginine methyltransferases (PRMTs) inhibition. Analysis of cell lines and in-house clinical samples demonstrates that resistant cells evade paclitaxel killing through stabilizing mitotic chromatin assembly. Genetic or pharmacologic inhibition of PRMT5 alters RNA splicing, particularly intron retention of aurora kinases B (AURKB), leading to a decrease in protein expression, and finally results in selective mitosis catastrophe in paclitaxel-resistant cells. In addition, type I PRMT inhibition synergies with PRMT5 inhibition in suppressing tumor growth of drug-resistant cells through augmenting perturbation of AURKB-mediated mitotic signaling pathway. These findings are fully recapitulated in a patient-derived xenograft (PDX) model generated from a paclitaxel-resistant TNBC patient, providing the rationale for targeting PRMTs in paclitaxel-resistant TNBC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Advanced biofabrication techniques can create tissue-like constructs that can be applied for reconstructive surgery or as in vitro three-dimensional (3D) models for disease modeling and drug screening. While various biofabrication techniques have recently been widely reviewed in the literature, acoustics-based technologies still need to be explored. The rapidly increasing number of publications in the past two decades exploring the application of acoustic technologies highlights the tremendous potential of these technologies. In this review, we contend that acoustics-based methods can address many limitations inherent in other biofabrication techniques due to their unique advantages: noncontact manipulation, biocompatibility, deep tissue penetrability, versatility, precision in-scaffold control, high-throughput capabilities, and the ability to assemble multilayered structures. We discuss the mechanisms by which acoustics directly dictate cell assembly across various biostructures and examine how the advent of novel acoustic technologies, along with their integration with traditional methods, offers innovative solutions for enhancing the functionality of organoids. Acoustic technologies are poised to address fundamental challenges in biofabrication and tissue engineering and show promise for advancing the field in the coming years., Competing Interests: Conflict of interest T.J.H. has co-founded a start-up company, Ascent Bio-Nano Technologies Inc., to commercialize technologies involving acoustofluidics and acoustic tweezers., (© 2024. The Author(s).)

Small molecules targeting G-quadruplexes (G4s) in viruses could inhibit viral proliferation. The 1a protein of cucumber mosaic virus (CMV) act as RNA-dependent RNA polymerase (RdRp) that plays a crucial role in regulating the replication of CMV. In this study, four putative G4 sequences (CMV PQS1-PQS4) in the genetic coding region of CMV 1a were identified, and three of them (PQS2, PQS3, and PQS4) were confirmed to fold into G4 structures. The G4-ligand, RHPS4, could bind to CMV PQS2 and PQS4 with a strong binding affinity and preferred to interact with the 3' terminal G-quartet surfaces of CMV PQS2, and 5' terminal of CMV PQS4. RHPS4 was also found to stabilize the CMV PQS2 and PQS4 G4s. Further studies revealed that RHPS4 exhibited an excellent anti-CMV activity. This study suggested that CMV PQS2 and PQS4 could be considered potential targets for screening viral inhibitors.

This research aims to evaluate and monitor the effectiveness of vegetation ecological restoration by integrating Multispectral Remote Sensing (MRS) and laser point cloud (LPC) monitoring technologies. Traditional vegetation restoration monitoring methods often face challenges of inaccurate data and insufficient coverage, and the use of MRS or LPC techniques alone has its limitations. Therefore, to more accurately monitor the vegetation restoration status, this study proposes a new monitoring method that combines the advantages of the large-scale coverage of MRS technology and the high-precision three-dimensional structural data analysis capability of LPC technology. This new method was applied in the Daqing oilfield area of China, aiming to provide effective ecological restoration assessment methods through the precise monitoring and analysis of regional vegetation growth and coverage. The results showed that there was a negative correlation between the vegetation humidity index and vegetation growth in the Daqing oilfield in 2023. The estimated monitoring effect of the research method could reach over 90%, and the coverage area of hydrangea restoration in the monitoring year increased by 7509 km 2 . The research technology was closer to the actual coverage situation. The simulation image showed that the vegetation coverage in the area has significantly improved after returning farmland to forests. Therefore, the technical methods used can effectively monitor the ecological restoration of vegetation, which has great research significance for both vegetation restoration and monitoring.

Polycomb repressive complex 2 (PRC2) catalyzes the writing of the tri-methylated histone H3 at Lys27 (H3K27me3) epigenetic marker and suppresses the expression of genes, including tumor suppressors. The function of the complex can be partially antagonized by the SWI/SNF chromatin-remodeling complex. Previous studies have suggested that PRC2 is important for the proliferation of tumors with SWI/SNF loss-of-function mutations. In the present study, we have developed an EED-directed allosteric inhibitor of PRC2 termed BR0063, which exhibits anti-proliferative properties in a subset of solid tumor cell lines harboring mutations of the SWI/SNF subunits, SMARCA4 or ARID1A. Tumor cells sensitive to BR0063 exhibited several distinct phenotypes, including cell senescence, which was mediated by the up-regulation of CDKN2A/p16. Further experiments revealed that the expression of p16 was suppressed in the BR0063-resistant cells via DNA hypermethylation in the CpG island (CGI) promoter region, rather than via PRC2 occupancy. The expression of TET1, which is required for DNA demethylation, was found to be inversely correlated with p16 CGI methylation, and this may serve as a biomarker for the prediction of resistance to PRC2 inhibitors in SWI/SNF LOF tumors., (© 2024. The Author(s).)

Extracellular vesicles (EVs) and their cargoes are increasingly being recognized as noninvasive diagnostic markers, necessitating the isolation of EVs from complex biological samples. Herein, a distearoyl phospholipid ethanolamine-functionalized single-crystal ordered macroporous three-dimensional zeolitic imidazolate framework (SOM-ZIF-8-DSPE) was developed, which combines the surface charge interaction of ZIF-8 with the synergistic effect of DSPE insertion into the phospholipid membrane of EVs to improve the isolating selectivity of EV capture. The materials have porous structures larger than 300 nm in diameter, providing enough space and active sites to trap EVs. Benefiting from this feature, the entire isolation process takes only 10 min and is well compatible with the subsequent analysis of RNA in EVs. Consequently, 10 upregulated miRNA of plasma EVs in the primary colorectal cancer (pCRC) patients is found over the healthy donors, and 6 upregulated miRNA of plasma EVs in the metastatic colorectal cancer (mCRC) patients over pCRC patients. These findings suggest that the isolation of EV-based SOM-ZIF-8-DSPE is a promising strategy to identify biomarkers for disease diagnosis, such as miRNAs in plasma EVs for the early detection of CRC.

Tire wear particles (TWPs) pollution is widely present in soil, especially in areas severely affected by traffic. Herein, regular variation of fungal biomass with TWPs was found in soils with different distances from the highway. In addition, the concentrations of benzothiazole compounds (BTHs), an important class of rubber vulcanization accelerators, were found to be positively correlated to the TWPs abundance. Sixty days' soil microcosm experiments were conducted to further confirm the adverse effect of TWPs and BTHs on soil fungi. TWPs spiking at 1000 mg/kg, a detectable level in the roadside, resulted in significant reduction of biomass and significant changes of soil fungal community structure, with Eurotium and Polyporales being the sensitive species. BTH+ 2-hydroxybenzothiazole (OHBT) (the dominant BTHs in soil) spiking at 200 ng/kg, the dose equivalent to 1000 mg/kg TWPs pollution, also caused a similar magnitude of soil fungal biomass reduction. Adonis demonstrated no significant difference of fungal community structure between TWPs and BTH+OHBT spiked soil, suggesting the adverse effect of TWPs on soil fungi may be explained by the act of BTHs. Pure culture using the representative soil fungi Eurotium and Polyporales also confirmed that BTHs were the main contributors to the adverse effect of TWPs on soil fungi., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study investigates the relationship of neutrophil-lymphocyte ratio (NLR) with the risk of all-cause and cardiovascular mortality in patients with cardiovascular disease. The data for this analysis came from 2239 participants with cardiovascular disease of the National Health and Nutrition Examination Survey conducted between 1999-2018. The optimal cutoff point for NLR was determined using maximally selected rank statistics. Survival analysis was performed using Cox regression models to assess the impact of NLR on the risk of all-cause mortality and cardiovascular mortality. Restricted cubic spline was used to visualize the association of NLR with mortality risk. Subgroup analysis was performed to examine the relationship between NLR and mortality within subgroups based on age, sex, diabetes and hypertension. During a median follow-up period of 6.7 (IQR, 3.3-10.9) years, 992 all-cause deaths occurred, including 381 cardiovascular deaths. Our study revealed that NLR is a risk factor for all-cause mortality (HR: 1.15 95%Cl: 1.11 ~ 1.19) and cardiovascular mortality (HR: 1.14 95%Cl: 1.08 ~ 1.2) among patients with cardiovascular disease. The restricted cubic spline regression analysis showed a non-linear association between NLR and all-cause mortality (p < 0.05 for nonlinearity) in cardiovascular patients. This association remained robust in subgroup analyses stratified by age, sex, diabetes, and hypertension. Conclusion NLR stands as a significant risk factor for both all-cause and cardiovascular mortality among patients with cardiovascular disease., (© 2024. The Author(s).)

Leaves are the primary vegetative organs of plants, and their morphology is an important trait affecting plant architecture, light energy utilization, environmental adaptation, and fruit quality and yield. Leaf development is highly flexible; however, understanding the regulatory mechanisms of factors coordinating leaf morphogenesis and differentiation remains limited. In this study, we obtained a double mutant for SlTCP29 and SlTCP24 genes from the CRISPR/Cas9 mutant population, both belonging to the CINCINNATA-like TCP (TEOSINTE BRANCHED, CYCLOIDEA and PCF1/2) transcription factor subfamily. Simultaneous mutations of SlTCP29 and SlTCP24 genes increase the complexity of tomato leaves, characterized by deeper leaf margin notches and increased number of leaflets. In conjunction with RNA-seq analysis, determination of plant hormone content, and molecular interaction assays, we identified the KNOXII gene SlTKNII5, SlMIR164a, and 1-aminocyclopropane-1-carboxylic acid synthase gene SlACS1A as direct downstream targets of SlTCP29 and SlTCP24, among which SlTKNII5 can physically interact with other KNOXII members to form heterodimers. Our study provides insight into the mechanisms by which SlTCP29 and SlTCP24 are involved in the morphological development of tomato compound leaves by integrating multiple pathways, including transcription factor, microRNA, and phytohormone., (© 2024 Scandinavian Plant Physiology Society.)

In age-related macular degeneration (AMD), large choroidal hypertransmission defects (hyperTDs) are identified on en face optical coherence tomography (OCT) images as bright lesions measuring at least 250 μm in greatest linear dimension (GLD). These choroidal hyperTDs arise from focal attenuation or loss of the retinal pigment epithelium (RPE). We previously reported that once large hyperTDs formed, they were likely to persist compared with smaller lesions that were more likely to be transient. Due to their relative persistence, these large persistent choroidal hyperTDs are a point-of-no-return in the progression of intermediate AMD to the late stage of atrophic AMD. Moreover, the onset of these large choroidal hyperTDs can serve as a clinical trial endpoint when studying therapies that might slow disease progression from intermediate AMD to late atrophic AMD. To confirm the persistence of these large choroidal hyperTDs, we studied an independent dataset of AMD eyes enrolled in an ongoing prospective swept-source OCT (SS-OCT) natural history study to determine their overall persistence. We identified a total of 202 eyes with large choroidal hyperTDs containing 1725 hyperTDs followed for an average of 46.6 months. Of the 1725 large hyperTDs, we found that 1718 (99.6%) persisted while only 7 hyperTDs (0.4%) were non-persistent. Of the 7 non-persistent large hyperTDs in 6 eyes, their average GLD at baseline was 385 μm. Of the large hyperTDs ranging in size between 250 and 300 μm when first detected, only one was not persistent with a baseline GLD of 283 μm. In 6 of the non-persistent hyperTDs, the loss of a detectable large hyperTD was due to the accumulation of hyperreflective material along the retinal pigment epithelium (RPE) and in the retina over the area where the hyperTD was located. This hyperreflective material is thought to represent the migration and aggregation of RPE cells into this focal region where the choroidal hyperTD arose due to attenuated or lost RPE., Competing Interests: Declaration of competing interest Giovanni Gregori, Philip J. Rosenfeld and Ruikang K. Wang received research support from Carl Zeiss Meditec, Inc. Giovanni Gregori and the University of Miami co-own a patent that is licensed to Carl Zeiss Meditec, Inc. Dr. Rosenfeld also received research funding from Gyroscope Therapeutics. He is also a consultant for Abbvie, Annexon, Apellis, Bayer Pharmaceuticals, Boehringer-Ingelheim, Carl Zeiss Meditec, Chengdu Kanghong Biotech, Genentech/Roche, InflammX Therapeutics, Ocudyne, Regeneron Pharmaceuticals, and Unity Biotechnology. He also has equity interest in Apellis, InflammX, Ocudyne, and Valitor. Ruikang K. Wang received other financial support from Colgate Palmolive Company, Estee Lauder lnc, and is a consultant for Carl Zeiss Meditec. He also has several patents: US8, 750, 586, US8, 180, 134, US9, 282,905, US9, 759,544, US10, 354,378, US10, 529,061. The remaining authors have no disclosures., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: The association between the total macular burden of hyperreflective foci (HRF) in eyes with intermediate AMD (iAMD) and the onset of persistent choroidal hypertransmission defects (hyperTDs) was studied using swept-source optical coherence tomography (SS-OCT)., Design: Post hoc subgroup analysis of a prospective study., Methods: A retrospective review of iAMD eyes from subjects enrolled in a prospective SS-OCT study was performed. All eyes underwent 6×6 mm SS-OCT angiography (SS-OCTA) imaging at baseline and follow-up visits. En face sub-retinal pigment epithelium (subRPE) slabs with segmentation boundaries positioned 64 to 400 µm beneath Bruch's membrane (BM) were used to identify persistent choroidal hyperTDs. None of the eyes had persistent hyperTDs at baseline. The same subRPE slab was used to identify choroidal hypotransmission defects (hypoTDs) attributable to HRF located either intraretinally (iHRF) or along the RPE (rpeHRF) based on corresponding B-scans. A semiautomated algorithm was used by 2 independent graders to validate and refine the HRF outlines. The HRF area and the drusen volume within a 5 mm fovea-centered circle were measured at each visit., Results: The median follow-up time for the 171 eyes from 121 patients included in this study was 59.1 months (95% CI: 52.0-67.8 months). Of these, 149 eyes (87%) had HRF, and 82 (48%) developed at least one persistent hyperTD during the follow-up. Although univariable Cox regression analyses showed that both drusen volume and total HRF area were associated with the onset of the first persistent hyperTD, multivariable analysis showed that the area of total HRF was the sole significant predictor for the onset of hyperTDs (P < .001). ROC analysis identified an HRF area ≥ 0.07 mm² to predict the onset of persistent hyperTDs within 1 year with an area under the curve (AUC) of 0.661 (0.570-0.753), corresponding to a sensitivity of 55% and a specificity of 74% (P < .001)., Conclusions: The total macular burden of HRF, which includes both the HRF along the RPE and within the retina, is an important predictor of disease progression from iAMD to the onset of persistent hyperTDs and should serve as a key OCT biomarker to select iAMD patients at high risk for disease progression in future clinical trials., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Electroencephalogram (EEG) alpha-band oscillations may reflect executive and processing function in patients with cerebral small vessel disease (CSVD). We aimed to assess such association and its relationship with CSVD severity, and to identify specific alpha-band parameters and the cut-off values for cognitive screening. We analysed the dispersion of amplitude-frequency characteristics of EEG alpha-band and different alpha-band parameters (PFα , ΔPFα , PPα , NCL) in different brain locations. We also assessed patients' executive and processing functions using verbal fluency test (VFT) and color trails test (CTT), and CSVD severity using total burden and Fazekas scores. 129 patients were recruited in the study. After adjusting for age, gender and education, PFα(F3), PFα(F4) and NCL were significantly associated with VFT-composite performance ( p <  0.05). CTT-1 time and error were associated with PFα(F3), PFα(F4), ΔPFα(O1;F3) and CSVD severity ( p <  0.05), whereas CTT-2 time was only associated with CSVD severity. Moreover, the correlations between alpha-band oscillations and cognitive function were higher in low than in high disease-severity group (ρ: -0.58 vs. -0.38, p <  0.05). The AUC of selected alpha-band parameters were higher than 0.8 for VFT and CTT. Specific alpha-band parameters in the frontal lobe were identified to correspond to executive and processing function. Assessing EEG alpha-band oscillations may assist in screening cognitive impairment., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To identify vulnerable areas and populations with limited access to dental care in Virginia, the study aimed (1) to calculate travel time and accessibility scores to dental care in Virginia using a transit-based accessibility model for all dental clinics and dental clinics participating in the Medicaid dental program and (2) to estimate factors associated with accessibility to dental clinics participating in the Medicaid dental program in Virginia., Methods: The study used building footprints as origins of transit trips to dental care services (or destinations). The study then computed transit-based origin-destination travel time matrices based on the detailed trip information, including in-vehicle and out-of-vehicle travel time. Accessibility scores were calculated by counting the number of dental clinics that can be reached within 60 min. Regression analysis was used to measure factors associated with accessibility scores to dental clinics participating in Medicaid., Results: Residents in smaller regions spent longer travel time to dental clinics by public transit compared with those who resided in larger regions. Medicaid participants also faced longer travel time compared with the general population. Residents spent more than three-fourths of the time waiting for public transit and walking to clinics regardless of where they live and what type of insurance they have. Associations between sociodemographic factors and accessibility scores to dental clinics participating in the Medicaid dental program varied across regions., Conclusions: Disparities in dental care accessibility exist depending on the size of regions and Medicaid participation in Virginia. The disparities in transit-based access to dental clinics and a disproportionate amount of time spent waiting for public transit and walking to dental clinics could be improved through tailored interventions taking into account the sociodemographic and geographic characteristics of each region., (© 2024 The Author(s). Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

Light-activated fluorescence represents a potent tool for investigating subcellular structures and dynamics, offering enhanced control over the temporal and spatial aspects of the fluorescence signal. While alkyl-substituted tetrazine has previously been reported as a photo-trigger for various fluorophore scaffolds, its limited photochemical efficiency and high activation energy have constrained its widespread application at the biomolecular level. In this study, we demonstrate that a single sulfur atom substitution of tetrazine greatly enhances the photochemical properties of tetrazine conjugates and significantly improves their photocleavage efficiency. Notably, the resulting sulfur-tetrazine can be activated using a lower-energy light source, thus transforming it into a valuable visible-light photo-trigger. To introduce this photo-trigger into biological systems, we have developed a series of visible-light activatable small molecular dyes, along with a photoactivatable noncanonical amino acid containing sulfur-tetrazine. Using the Genetic Code Expansion technology, this novel amino acid is genetically incorporated into fluorescent protein molecules, serving as a phototrigger to create an innovative photoactivatable protein. These advancements in tetrazine-scaffold photo-trigger design open up new avenues for generating photoactivatable biomolecules, promising to greatly facilitate the exploration of biological functions and structures.

The Cardiometabolic Index (CMI) represents an innovative metric that encompasses abdominal obesity and lipid levels, offering a comprehensive assessment of cardiometabolic health. It is derived through the multiplication of the waist-to-height ratio by the triglyceride-to-high-density lipoprotein cholesterol ratio. Although obesity and blood lipid levels are known factors affecting sleep quality, the direct correlation between CMI and sleep quality has yet to be elucidated. This study uses NHANES data to explore the potential correlation between CMI and sleep quality. Our research employed a cross-sectional design, utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2011 to 2014. CMI was used as the exposure variable, with sleep quality assessed through three self-reported measures: trouble sleeping, sleep disorders, and sleep duration. We employed multivariate logistic regression models and linear regression model as well as subgroup analyses to explore the independent relationship between CMI and sleep quality. Additionally, interaction tests were conducted to examine differences across various subgroups. The study included 4298 participants, comprising 2134 males and 2164 females. There was a positive correlation between CMI and trouble sleeping (OR = 1.63, 95% CI 1.28-2.08) and sleep disorders (OR = 1.96, 95% CI 1.43-2.67), while there was a negative correlation between CMI and sleep duration (β = - 0.17, 95% CI - 0.31 to - 0.03), indicating that a higher CMI was associated with shorter sleep duration. Subgroup analyses and interaction tests revealed a consistently positive association between CMI and sleep difficulty across various populations, including gender, age, hypertension, diabetes, and cardiovascular disease history. However, the relationship between CMI and sleep disorders was more prominent among participants aged 50 and above. In American adults, a higher CMI is linked to an increased prevalence of sleep disturbances. In clinical practice, CMI can be considered as a supplementary factor in the assessment and management of sleep problems. Our study also provided new insights for improving sleep quality., (© 2024. The Author(s).)

Introduction: Intersectional hybrids in lilies possess significant breeding value, but the lack of complete lily genomes and complex genotypes pose challenges for early identification of lily hybrids. This study aimed to use intersectional hybrid cultivars as female parents and wild lilies as male parents to facilitate early identification of hybrid offsprings and enhance the efficiency and convenience of the process., Methods: We investigated the nature of cross combinations using Non-denaturing Fluorescence In Situ Hybridization (ND-FISH) and Genomic In Situ Hybridization (GISH) techniques. Three novel oligonucleotide probes-Oligo-pTa794, Oligo-pITS and Oligo-telo-were developed for lily chromosome research., Results: Our results demonstrated successful hybridization between wild lilies and intersectional hybrid cultivars, producing a total of 130 hybrid progenies. The combination of ND-FISH and GISH analyses effectively revealed the genomic composition of the hybrid progeny and determined the parental origin of specific chromosomes., Discussion: This research provides significant guidance for lily breeding practices and offers a valuable reference for the application of ND-FISH and GISH techniques in interspecific hybridization breeding and molecular cytogenetic research across various plant species. The methods developed enable more precise, efficient, and convenient identification of hybrid offsprings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Yong, Zhu, Xu, Liu, Zhang, Mou, Zeng, Wu, Jiang, Jia, Zhang and Pan.)

Traditional methods, such as the use of fluorescent protein fusions and environment-sensitive fluorophores, have limitations when studying protein microenvironment changes at the finest spatial resolution. These techniques often rely on bulky proteins or tags restricted to the N- or C-terminus, which can disrupt the natural behavior of the target protein and dramatically limit the ability of their method to investigate noninvasively microenvironment effects. To overcome these challenges, we have developed an innovative strategy to visualize microenvironment changes of protein substructures in real-time by genetically incorporating environment-sensitive noncanonical amino acids (ncAAs) containing rotor-based fluorophores (RBFs) at specific positions within a protein of interest. Through computational redesign of aminoacyl-tRNA synthetase, we successfully incorporated these rotor-based ncAAs into various proteins in mammalian cells. By site-specifically placing these ncAAs in distinct regions of proteins, we detected microenvironmental changes of several different protein domains during events such as aggregation, clustering, aggregation disassembly, and cluster dissociation.

Limited and contradictory evidence has been reported regarding the prognostic effects of carcinoembryonic antigen (CEA) on the prognosis and metastasis of classical adenocarcinoma (CA), mucinous adenocarcinoma (MA), and signet-ring cell carcinoma (SRCC) in colorectal cancer patients. We investigated the associations between histological subtypes and preoperative serum CEA levels in determining the oncologic outcomes of colorectal cancer (CRC) patients. A total of 47,692 patients with clearly diagnosed CRC were selected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into two cohorts based on serum CEA levels: CEA-normal (C0) and CEA-elevated (C1). Chi-square analysis revealed a correlation between CEA levels and histological classification. We then included a newly defined interaction variable (H&CEA) in the Cox regression analysis, which demonstrated that this variable could serve as an independent prognostic factor (P<0.001). CA, in the context of elevated serum CEA levels, differed from the other two histopathological types, showing unexpectedly higher risks for both OS (HR = 1.70, 95% CI = 1.65-1.75, P<0.001) and CSS (HR = 1.78, 95% CI = 1.72-1.85, P<0.001). Furthermore, elevated CEA levels significantly increased the proportion of liver metastases in the CA group (25.43% vs. 3.95%, P<0.001). The interaction variable H&CEA can be used as an independent prognostic factor for CRC and should be considered in the diagnosis of CRC and the development of personalized treatment plans. Additionally, in the context of elevated CEA levels, CA is associated with poor prognosis and increased liver metastases. This CRC subgroup warrants special clinical attention from oncologists.

Introduction: Oculomotor and gait dysfunctions are closely associated with cognition. However, oculo-gait patterns and their correlation with cognition in cerebral small vessel disease (CSVD) remain unclear., Methods: Patients with CSVD from a hospital-based cohort (n = 194) and individuals with presumed early CSVD from a community-based cohort (n = 319) were included. Oculo-gait patterns were measured using the artificial intelligence (AI) -assisted 'EyeKnow' eye-tracking and 'ReadyGo' motor evaluation systems. Multivariable linear and logistic regression models were employed to investigate the association between the oculo-gait parameters and cognition., Results: Anti-saccade accuracy, stride velocity, and swing velocity were significantly associated with cognition in both patients and community dwellers with CSVD, and could identify cognitive impairment in CSVD with moderate accuracy (area under the curve [AUC]: hospital cohort, 0.787; community cohort, 0.810) after adjusting for age and education., Discussion: The evaluation of oculo-gait features (anti-saccade accuracy, stride velocity, and swing velocity) may help screen cognitive impairment in CSVD., Highlights: Oculo-gait features (lower anti-saccade accuracy, stride velocity, and swing velocity) were associated with cognitive impairment in cerebral small vessel disease (CSVD). Logistic model integrating the oculo-gait features, age, and education level moderately distinguished cognitive status in CSVD. Artificial intelligence-assisted oculomotor and gait measurements provide quick and accurate evaluation in hospital and community settings., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Genetic Code Expansion technology offers significant potential in incorporating noncanonical amino acids into proteins at precise locations, allowing for the modulation of protein structures and functions. However, this technology is often limited by the need for costly and challenging-to-synthesize external noncanonical amino acid sources. In this study, we address this limitation by developing autonomous cells capable of biosynthesizing halogenated tryptophan derivatives and introducing them into proteins using Genetic Code Expansion technology. By utilizing inexpensive halide salts and different halogenases, we successfully achieve the selective biosynthesis of 6-chloro-tryptophan, 7-chloro-tryptophan, 6-bromo-tryptophan, and 7-bromo-tryptophan. These derivatives are introduced at specific positions with corresponding bioorthogonal aminoacyl-tRNA synthetase/tRNA pairs in response to the amber codon. Following optimization, we demonstrate the robust expression of proteins containing halogenated tryptophan residues in cells with the ability to biosynthesize these tryptophan derivatives. This study establishes a versatile platform for engineering proteins with various halogenated tryptophans., (© 2024 Wiley-VCH GmbH.)

The ovarian microenvironment plays a crucial role in ensuring the reproductive success of viviparous teleosts. However, the molecular mechanism underlying the interaction between spermatozoa and the ovarian microenvironment has remained elusive. This study aimed to contribute to a better understanding of this process in black rockfish (Sebastes schlegelii) using integrated multi-omics approaches. The results demonstrated significant upregulation of ovarian complement-related proteins and pattern recognition receptors, along with remodeling of glycans on the surface of spermatozoa at the early spermatozoa-storage stage (1 month after mating). As spermatozoa were stored over time, ovarian complement proteins were progressively repressed by tryptophan and hippurate, indicating a remarkable adaptation of spermatozoa to the ovarian microenvironment. Before fertilization, a notable upregulation of cellular junction proteins was observed. The study revealed that spermatozoa bind to ZPB2a protein through GSTM3 and that ZPB2a promotes spermatozoa survival and movement in a GSTM3-dependent manner. These findings shed light on a key mechanism that influences the dynamics of spermatozoa in the female reproductive tract, providing valuable insights into the molecular networks regulating spermatozoa adaptation and survival in species with internal fertilization., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

AgCuSe nanoparticles could contribute to the growth of strongly light-absorbing thin films and solids with fast ion mobility, among other potential properties. Nevertheless, few methods have been developed so far for the synthesis of AgCuSe nanoparticles, and those reported deliver nanostructures with relatively large sizes and broad size and shape distributions. In this work, a colloidal cation exchange method is established for the easy synthesis of AgCuSe NPs with ca. 8 nm diameters and narrow size dispersion. Notably, in this lower size range the conucleation and growth of two stoichiometric ternary compounds are generally observed, namely the well-known eucairite AgCuSe compound and the novel fischesserite -like Ag 3 CuSe 2 phase, the latter being less thermodynamically stable as predicted computationally and assessed experimentally. An optimal range of Cu/Ag precursor molar ratio has been identified to ensure the growth of ternary nanoparticles and, more specifically, that of the metastable Ag 3 CuSe 2 nanophase isolated for the first occasion. The attained size range for the material paves the way for utilizing AgCuSe nanoparticles in new ways within the field of biomedicine: the results obtained here confirm the antibacterial activity of the new Ag x Cu y Se z nanoparticles against Gram-positive bacteria, with significantly low values of the minimal inhibitory concentration., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

When fetuses are exposed to abnormally high levels of glucocorticoids in utero, irreversible damage to neuronal synaptogenesis occurs, leading to long-term cognitive and emotional behavioral abnormalities after birth. In this study, we investigated how maternal exposure to a novel environmental pollutant-synthetic glucocorticoid dexamethasone-affects offspring cognitive and emotional behaviors enduringly. We noted that offspring subjected to maternal dexamethasone exposure (MDE) displayed cognitive and emotional neurobehavioral deficits beginning in infancy, and these impairments persisted into adulthood. The principal mechanism involves MDE-induced damage to hippocampal neuronal synapse formation in the offspring, primarily due to a cholesterol deficiency which destabilizes neuronal membranes, thereby affecting normal synapse formation and ultimately leading to cognitive and emotional deficiencies. Specifically, we demonstrated abnormal activation of glucocorticoid receptors in hippocampal astroglial cells of MDE offspring, which triggers changes in the miR-450a-3p/HAT1/ABCG1 signaling axis, causing impaired cholesterol efflux in astroglial cells and insufficient cholesterol supply to neurons, further impairing synaptogenesis. This research not only underscores the significant impact of prenatal environmental pollutants on long-term health outcomes in offspring but also broadens our understanding of how prenatal exposure to glucocorticoids affects brain development in the progeny, providing new insights for interventions in neurodevelopmental and psychiatric disorders of fetal origin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study investigates how hibernation affects the surface activity of pulmonary surfactant with respect to temperature and breathing pattern. Surfactant was isolated from a hibernating species, the 13-lined ground squirrel, and a homeotherm, the rabbit, and analysed for biophysical properties on a constrained sessile drop surfactometer. The results showed that surfactant from ground squirrels reduced surface tension better at low temperatures, including when mimicking episodic breathing, as compared with rabbit surfactant. In addition, low temperature adaptation was also observed using only the hydrophobic components of surfactant from ground squirrels. Overall, the data support the conclusion that ground squirrel surfactant has adapted to maintain surface activity during low temperature episodic breathing patterns, and that temperature adaptation is maintained with the hydrophobic components of the surfactant., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Cytochrome P450 enzymes (CYPs) play a crucial role in phase I metabolic reactions. The activity of CYPs would affect therapeutic efficacy and may even induce toxicity. Given the complex components of traditional Chinese medicine, it is important to understand the effect of active ingredients on CYPs activity to guide their prescription. This study aimed to evaluate the effect of polyphyllin H on the activity of CYPs major isoforms providing a reference for the clinical prescription of polyphyllin H and its source herbs. The effects of polyphyllin H were evaluated in pooled human liver microsomes using probe substrates of CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 to determine their activities. The Lineweaver-Burk was used to model the inhibition, and a time-dependent inhibition experiment was performed to understand the characteristics of the inhibition. Polyphyllin H significantly suppressed the activity of CYP1A2, 2D6, and 3A4 with IC 50 values of 6.44, 13.88, and 4.52 μM, respectively. The inhibition of CYP1A2 and 2D6 was best fitted with a competitive model, yielding the inhibition constant (K i ) values of 3.18 and 6.77 μM, respectively. The inhibition of CYP3A4 was fitted with the non-competitive model with the K i value of 2.38 μM. Moreover, the inhibition of CYP3A4 was revealed to be time-dependent with the inhibition parameters inhibition constant (KI) and inactivation rate constant (K inact ) values of 2.26 μM -1 and 0.045 min -1 . Polyphyllin H acted as a competitive inhibitor of CYP1A2 and 2D6 and a non-competitive and time-dependent inhibitor of CYP3A4., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Zinc metal is a promising anode candidate for aqueous zinc ion batteries due to its high theoretical capacity, low cost, and high safety. However, its application is currently restricted by hydrogen evolution reactions (HER), by-product formation, and Zn dendrite growth. Herein, a "Zn 2+ in salt" (ZIS) interphase is in situ constructed on the surface of the anode (ZIS@Zn). Unlike the conventional "Zn 2+ in water" working environment of Zn anodes, the intrinsic hydrophobicity of the ZIS interphase isolates the anode from direct contact with the aqueous electrolyte, thereby protecting it from HER, and the accompanying side reactions. More importantly, it works as an ordered water-free ion-conducting medium, which guides uniform Zn deposition and facilitates rapid Zn 2+ migration at the interface. As a result, the symmetric cells assembled with ZIS@Zn exhibit dendrite-free plating/striping at 4500 h and a high critical current of 14 mA cm -2 . When matched with a vanadium-based (NVO) cathode, the full battery exhibits excellent long-term cycling stability, with 88% capacity retention after 1600 cycles. This work provides an effective strategy to promote the stability and reversibility of Zn anodes in aqueous electrolytes., (© 2024 Wiley‐VCH GmbH.)

Nanoplastics (NPs) and polycyclic aromatic hydrocarbons (PAHs) are recognized as persistent organic pollutant (POPs) with demonstrated physiological toxicity. When present in aquatic environments, the two pollutants could combine with each other, resulting in cumulative toxicity to organisms. However, the combined impact of NPs and PAHs on microorganisms in seawater is not well understood. In this study, we conducted an exposure experiment to investigate the individual and synergistic effects of NPs and PAHs on the composition, biodiversity, co-occurrence networks of microbial communities in seawater. Exposure of individuals to PAHs led to a reduction in microbial community richness, but an increase in the relative abundance of species linked to PAHs degradation. These PAHs-degradation bacteria acting as keystone species, maintained a microbial network complexity similar to that of the control treatment. Exposure to individual NPs resulted in a reduction in the complexity of microbial networks. Furthermore, when PAHs and NPs were simultaneously present, the toxic effect of NPs hindered the presence of keystone species involved in PAHs degradation, subsequently limiting the degradation of PAHs by marine microorganisms, resulting in a decrease in community diversity and symbiotic network complexity. This situation potentially poses a heightened threat to the ecological stability of marine ecosystems. Our work strengthened the understanding of the combined impact of NPs and PAHs on microorganisms in seawater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tris(2,3-dibromopropyl) isocyanurate (TBC), recognized as an endocrine disruptor, can cause inflammatory injury to the lung tissue of mice. To investigate the specific respiratory effects of TBC, male C57BL/6J mice were administered a daily dose of 20 mg/kg of TBC over 14 days. Postexposure, these mice developed chronic obstructive pulmonary disease (COPD)-like symptoms characterized by inflammatory lung damage and functional impairment. In light of the antiestrogenic properties of TBC, we administrated estradiol (E2) to investigate its potential protective role against TBC-induced damage and found that the coexposure of E2 notably mitigated the COPD-like phenotypes. Immunohistochemical analysis revealed that TBC exposure reduced estrogen receptor alpha (ERα) expression and increased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression, while E2 treatment rebalanced the expression levels of ERα and NF-κB to their normative states. Our findings indicate that TBC, as an antiestrogenic agent, may contribute to the pathogenesis of COPD through an ERα-mediated inflammatory pathway, but that E2 treatment could reverse the impairment, providing a potentially promising remedial treatment. Given the lung status as a primary target of air pollution, the presence of antiestrogenic compounds like TBC in atmospheric particulates presents a significant concern, with the potential to exacerbate respiratory conditions such as COPD and pneumonia.

Perfluorohexane sulfonate (PFHxS) has been listed as a new persistent organic pollutant since 2022. Although the production and use of PFHxS are now restricted, it remains highly persistent in aquatic environments for decades. However, so far research about the toxic effects on early-life exposure of PFHxS and underlying mechanisms are still limited. In this study, we employed both wild type and specifically labeled transgenic zebrafish as model to investigate the developmental toxicity of PFHxS during early-stage exposure in zebrafish. A series of phenotypic and molecular indicators were analyzed at various time points between 24 h post-fertilization (hpf) and 7 days post-fertilization (dpf). Our data showed that the acute toxicity of PFHxS was much lower than PFOS, with a lethal concentration 50% of 508.11 ± 88.54 μM at 120 hpf. Low-dose PFHxS exposure significantly altered heart rates, blood flow, and swimming behavior in zebrafish larvae, suggesting potential cardiotoxicity and neurotoxicity of zebrafish. Data from transgenic zebrafish with specifically labeled hearts (CZ40) confirmed that PFHxS affects cardiovascular system development. PFHxS-induced changes in transgenic zebrafish with labeled liver and pancreas (CZ16) suggest that PFHxS may cause metabolic disorders and contribute to developmental defects. Gene expression analysis showed that PFHxS with potential estrogenic effect might also affect the gonadal development of zebrafish. Our study can offer an insight into the toxicity of PFHxS in aquatic environment and health risks of early-stage PFHxS exposure in humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Industrial emissions have been identified as significant contributors to polyhalogenated carbazoles (PHCZs), a novel pollutant in the environment. Enhancing the health risk assessment of PHCZs is imperative, particularly for 1,3,6,8-tetrabromocarbazole (1368BCZ), the most commonly detected PHCZs in the environment. This study revealed that 1368BCZ could bind to the important transporters, human serum albumin (HSA), with high binding constant (K A : 1.02 × 10 5  L/mol). 1368BCZ primary bound to the HSA binding site 2, and the impact of 1368BCZ on HSA structure was minimal, indicating 1368BCZ may has strong accumulation in human. Theoretical analysis indicated that the uniformly distributed molecular surface electrostatic potential of the 1368BCZ molecule was crucial for its strong binding affinity to HSA. van der Waals forces serve as the primary interaction force stabilizing this binding. Further model predictions results showed that 1368BCZ may cause various toxic effects including hepatotoxicity, neurotoxicology, mutagenicity, etc. In summary, this study revealed the potential human health risks associated with 1368BCZ, providing an important basis for the formulation of relevant environmental control standards., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Long-term exposure to ultraviolet radiation may cause photoaging of skin tissues. Coreopsis tinctoria Nutt. riches a variety of flavonoids with strong antioxidant activities. In the present study, the main antioxidant flavonoid was isolated from C. tinctoria and identified as okanin by Mass spectrum and Nuclear Magnetic Resonance Spectroscopy. Okanin was found to effectively reduce the malondialdehyde content, increase various intracellular antioxidant enzyme activities, relieve epidermal hyperplasia and dermal damage caused by UVB irradiation, and increase the collagen fibers' content in the dorsal skin tissue of mice. Immunohistochemical analysis showed that okanin effectively counteracted the photoaging effect of UVB-induced by down-regulating IL-1, IL-6, TNF-α, and COX-2, and up-regulating COL-1, COL-3, and HYP expression. In addition, okanin can inhibit skin photoaging by regulating TNF-β/Smad2-3, MAPK, P13K/AKT, and NF-κB signaling pathways. In particular, the three key markers of photoaging, MMP (MMP-1/-3/-9), were down-regulated and five collagen synthesis genes (COL1A1, COL3A1, COL5A2, COL6A1, and COL7A1) were up-regulated, underlines the direct anti-photoaging mechanism of okanin in preventing collagen degradation and promoting collagen synthesis. The current investigation provides new insights into the great potential of okanin in alleviating skin photoaging and lays theoretical references for the development ofanti-photoaging products., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [MJL and PS are from the Shenzhen Hujia Technology Co. but there is no conflict of interest.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

3,4-Dihydroxy-L-phenylalanine (DOPA) serves as a post-translational modification amino acid present in mussel foot proteins. Mussels exploit the exceptional adhesive properties of DOPA to adhere to a wide range of surfaces. This study presents the development of sticky proteins and bacteria through the site-specific incorporation of DOPA using Genetic Code Expansion Technology. Through the optimization of the DOPA incorporation system, proteins containing DOPA demonstrate significantly improved binding abilities to various organic and metallic materials. The material-binding capabilities of DOPA to combat different types of biofoulings are harnessed by integrating it into intrinsically disordered proteins. Beyond the creation of adhesive proteins for anti-biofouling purposes, this highly efficient DOPA incorporation system is also applied to engineer adhesive bacteria, resulting in a remarkable increase in their binding capability to diverse materials including 400 folds of improvement to polyethylene terephthalate (PET). This substantial enhancement in PET binding of these bacteria has allowed to develop a unique approach for PET degradation, showcasing the innovative application of Genetic Code Expansion in cell engineering., (© 2024 Wiley‐VCH GmbH.)

Red pitaya has been demonstrated to strongly inhibit α-glucosidase activity; however, the impact of red pitaya fermentation by probiotic bacteria on α-glucosidase inhibition remains unclear. In this study, six strains of lactic acid bacteria ( Lactiplantibacillus plantarum , Lacticaseibacillus rhamnosus , Lactobacillus bulgaricus , Lacticaseibacillus casei , Lactobacillus acidophilus and Streptococcus thermophilus ) and one strain of Bifidobacterium breve were utilized for the fermentation of red pitaya pulp. The α-glucosidase and α-amylase inhibition rates of red pitaya pulp were significantly greater after fermentation by Bifidobacterium breve and Lacticaseibacillus casei than by the other abovementioned strains. The LC group exhibited an α-glucosidase inhibition rate of 99%, with an α-amylase inhibition rate of 89.91%. In contrast, the BB group exhibited an α-glucosidase inhibition rate of 95.28%, accompanied by an α-amylase inhibition rate of 95.28%. Moreover, red pitaya pulp fermented with Bifidobacterium breve and Lacticaseibacillus casei produced a notable quantity of oligosaccharides, which was more than three times greater than that in the other groups. Furthermore, 16S rRNA high-throughput sequencing analysis was conducted to assess alterations in the composition of the gut microbiota. This revealed an increase in the abundance of Lactobacillus and Faecalibacterium in the pulp fermented by Bifidobacterium breve and Lacticaseibacillus casei , whereas the abundance of Sutterella decreased. Further analysis at the species level revealed that Bifidobacterium longum , Faecalibacterium prausnitzii , and Lactobacillus zeae were the dominant strains present during colonic fermentation. These results indicate a beneficial health trend associated with probiotic bacterial fermentation of red pitaya pulp, which is highly important for the development of functional products.

Pyroptosis-related genes have great potential for prognosis, an accurate prognostic model based on pyroptosis genes has not been seen in Colorectal adenocarcinoma (COAD). Furthermore, understanding the mechanisms of gene expression characteristics and the Tumor Immune Microenvironment associated with the prognosis of COAD is still largely unknown. Constructing a prognostic model based on pyroptosis-related genes, and revealing prognosis-related mechanisms associated with the gene expression characteristics and tumor microenvironment. 59 pyroptosis-related genes were collected. The gene expression data and clinical data of COAD were downloaded from The Cancer Genome Atlas. External validation datasets were downloaded from the Gene Expression Omnibus database. 10 characteristic genes with prognostic values were obtained using univariate and LASSO Cox. 10-gene Riskscore prognostic model was constructed. Both gene set enrichment analysis and network propagation methods were used to find pathways and key genes leading to different prognostic risks. The area under the ROC curves were used to evaluate the performance of the model to distinguish between high-risk and low-risk patients, the results were 0.718, 0.672, and 0.669 for 1-, 3-, and 5-year survival times. A nomogram based on Riskscore and clinical characteristics showed the probability of survival at 1, 3, and 5 years, and the calibration curves showed good agreement between the predicted and actual observations, its C-index is 0.793. The decision curves showed that the net benefit of the nomogram was significantly superior to that of the other single variables. Four key pathways leading to different prognostic risks were obtained. Six key genes with prognostic value, significant expression differences (P < .05) and significant survival differences (P < .05) between high/low risk groups were obtained from the gene set of all 4 key pathways. This study constructed a prognostic model for COAD using 10 pyroptosis-related genes with prognostic value. This study also revealed significant differences in specific pathways and the tumor immune microenvironment (TME) between the high-risk group and the low-risk group, highlighted the roles of ALDH5A1 and Wnt signaling in promoting COAD and the suppressive effects of the IL-4/IL-13 pathway and RORC on COAD. The study will be helpful for precision therapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms with an increasing annual incidence and prevalence. Many are metastatic at presentation or recur following surgical resection and require systemic therapy, for which somatostatin analogs such as octreotide or lanreotide comprise typical first-line therapies. Nonetheless, treatment options remain limited. Epigenetic processes such as histone modifications have been implicated in malignant transformation and progression. In this study, we evaluated the anti-proliferative effects of a histone deacetylase (HDAC) inhibitor, entinostat, which was computationally predicted to show anti-cancer activity, as confirmed in in vitro and in vivo models of GEP-NETs., Methods: This was a phase II study to evaluate the efficacy and safety of entinostat in patients with relapsed or refractory abdominal NETs. The primary objective was to estimate the objective response rate to entinostat. Additionally, with each patient as his/her own control we estimated the rates of tumor growth prior to enrollment on study and while receiving entinostat. Patients received 5 mg entinostat weekly until disease progression or intolerable toxicity. The dose could be changed to 10 mg biweekly for patients who did not experience grade ≥ 2 treatment-related adverse events (AEs) in cycle 1, but was primarily administered at the starting 5 mg weekly dose., Results: The study enrolled only 5 patients due to early termination by the drug sponsor. The first patient that enrolled had advanced disease and died within days of enrollment before follow-up imaging due to a grade 5 AE unrelated to study treatment and was considered non-evaluable. Best RECIST response for the remaining 4 patients was stable disease (SD) with time on study of 154+, 243, 574, and 741 days. With each patient as his/her own control, rates of tumor growth on entinostat were markedly reduced with rates 17%, 20%, 33%, and 68% of the rates prior to enrollment on study. Toxicities possibly or definitely related to entinostat included grade 2/3 neutrophil count decrease [2/4 (50%)/ 2/4 (50%)], grade 3 hypophosphatemia [1/4, (25%)], grade 1/2 fatigue [1/4 (25%)/ 2/4 (50%)], and other self-limiting grade 1/2 AEs., Conclusion: In the treatment of relapsed or refractory abdominal NETs, entinostat 5 mg weekly led to prolonged SD and reduced the rate of tumor growth by 32% to 83% with an acceptable safety profile (ClinicalTrials.gov Identifier: NCT03211988)., (© The Author(s) 2024. Published by Oxford University Press.)

Dominant microorganisms and functional genes, including hgcA, hgcB, merA, and merB, have been identified to be responsible for mercury (Hg) methylation or methylmercury (MeHg) demethylation. However, their in situ correlation with MeHg levels and the processes of Hg methylation and MeHg demethylation in coastal areas remains poorly understood. In this study, four functional genes related to Hg methylation and MeHg demethylation (hgcA, hgcB, merA, and merB) were all detected in the sediments of the Eastern China Coastal Seas (ECCSs) (representative coastal seas highly affected by human activities) using metagenomic approaches. HgcA was identified to be the key gene controlling the in situ net production of MeHg in the ECCSs. Based on metagenomic analysis and incubation experiments, sulfate-reducing bacteria were identified as the dominant microorganisms controlling Hg methylation in the ECCSs. In addition, hgcA gene was positively correlated with the MeHg content and Hg methylation rates, highlighting the potential roles of Hg methylation genes and microorganisms influenced by sediment physicochemical properties in MeHg cycling in the ECCSs. These findings highlighted the necessity of conducting similar studies in other natural systems for elucidating the molecular mechanisms underlying MeHg production in aquatic environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)