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This study provides the first systematic data on the distribution of short- (SCCPs) and medium chlorinated paraffins (MCCPs) in the atmosphere and surface soils of Lahore, Pakistan. The spatial distribution of SCCPs and MCCPs in air (n = 12) and soil (n = 15) was investigated from industrial, residential, commercial, conventional e-waste burning and background areas of Lahore. The concentrations ranged from below the limit of detection (3 . Higher CPs contaminated soil and air were observed in industrial and commercial areas likely due to the use of CPs as flame retardants/plasticizers in products and metalworking. Total organic carbon (TOC), SCCPs and MCCPs in soil were not correlated with each other however, a significant association between SCCPs and MCCPs was observed in air samples. Among all the samples of soil and air C 10, Cl 7 - 8 and C 14,16 Cl 7 - 8 were the predominant congeners for SCCPs and MCCPs, respectively. The comprehensive investigation of soil-air exchange for SCCPs and MCCPs revealed approximately 67 % of fugacity fractions (ffs) above 0.7, indicating net volatilization for most of the congeners. This study also revealed a notably high emission flux for SCCPs and MCCPs compared to their deposition flux, indicating that soil acted as a major source of CPs. Additionally, the emission flux for SCCPs was higher than for MCCPs, owing to their greater volatility and transport potential. A preliminary risk assessment suggested limited risks (Risk quotient <0.02) to the soil community while, the adult and toddler community had daily intakes of 5.7 and 7.2 ng/kg/day of CPs, respectively via different pathways highlighting the hotspots with high risk areas., 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.)

Ensuring the interpretability of machine learning models in chemical engineering remains challenging due to inherent limitations and data quality issues, hindering their reliable application. In this study, a qualitatively implicit knowledge-guided machine learning framework is proposed to improve plasma gasification modelling. Starting with a pre-trained machine learning model, parameters are further optimized by integrating the heuristic algorithm to minimize the data fitting errors and resolving implicit monotonic inconsistencies. The latter is comprehensively quantified through Monte Carlo simulations. This framework is adaptive to different machine learning techniques, exemplified by artificial neural network (ANN) and support vector machine (SVM) in this study. Validated by a case study on plasma gasification, the results reveal that the improved models achieve better generalizability and scientific interpretability in predicting syngas quality. Specifically, for ANN, the root mean square error (RMSE) and knowledge-based error (KE) reduce by 36.44% and 83.22%, respectively, while SVM displays a decrease of 2.58% in RMSE and a remarkable 100% in KE. Importantly, the improved models successfully capture all desired implicit monotonicity relationships between syngas quality and feedstock characteristics/operating parameters, addressing a limitation that traditional machine learning struggles with., 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.)

Background: We aimed to investigate the effect and underlying mechanism of titanium (Ti) implant on the polarization of macrophages and subsequent effects on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs) affected by macrophages., Methods: Firstly, the regulatory effect of Ti implant on macrophage polarization was investigated. Levels of M1 polarization markers and M2 polarization markers in macrophages were evaluated by immunofluorescence staining method and qPCR analysis. The osteogenic differentiation capacity of PDLSCs cultured with supernatants of macrophages of each group was evaluated by the Alizarin Red S (ARS) staining method and qPCR. Angiogenesis related genes were also evaluated in HUVECs cultured in supernatants of macrophages. To explore whether RNA m 5 C modification can modulate the effects of Ti implant on macrophage regulation of osteogenic differentiation and angiogenesis, we analyzed the main genes related to m 5 C in macrophages using RNA m 5 C dot blotting and qPCR methods. The interaction between NSUN2 and IRF4 was verified by m 5 C-RIP, RIP, and double-luciferase gene report experiments., Results: Macrophages were activated as M1 macrophages under the interference of LPS, and macrophages attached to Ti implants were more easily activated as M2 macrophages under the action of LPS. Macrophages activated by Ti implant enhanced osteogenic differentiation of PDLSCs and angiogenesis of HUVECs. NSUN2 level was up-regulated in macrophages treated with LPS and was down-regulated by Ti implant. Over-expression of NSUN2 attenuated the effect of Ti implant on M1 polarization promotion of macrophages and enhanced the M2 polarization promotion of macrophages. Up-regulation of NSUN2 weakened the effects of Ti implant on promotion the capacity of macrophages on osteogenic differentiation of PDLSCs and angiogenesis of HUVECs. The KEGG analysis suggested that IRF4 was enriched in several inflammatory signaling pathways. Moreover, NSUN2 methylates IRF4 to affect the capacity of macrophages on osteogenic differentiation of PDLSCs and angiogenesis of HUVECs., Conclusions: Taken together, macrophages of M1 type can be stimulated by Ti implants in vitro, promoting osteogenic differentiation of PDLSCs and angiogenesis in HUVECs through NSUN2-mediated methylation of IRF4., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Raman and surface-enhanced Raman scattering (SERS) spectroscopy are highly specific and sensitive optical modalities that have been extensively investigated in diverse applications. Noise reduction is demanding in the preprocessing procedure, especially for weak Raman/SERS spectra. Existing denoising methods require manual optimization of parameters, which is time-consuming and laborious and cannot always achieve satisfactory performance. Deep learning has been increasingly applied in Raman/SERS spectral denoising but usually requires massive training data, where the true labels may not exist. Aiming at these challenges, this work presents a generic Raman spectrum denoising algorithm with self-supervised learning for accurate, rapid, and robust noise reduction. A specialized network based on U-Net is established, which first extracts high-level features and then restores key peak profiles of the spectra. A subsampling strategy is proposed to refine the raw Raman spectrum and avoid the underlying biased interference. The effectiveness of the proposed approach has been validated by a broad range of spectral data, exhibiting its strong generalization ability. In the context of photosafe detection of deep-seated tumors, our method achieved signal-to-noise ratio enhancement by over 400%, which resulted in a significant increase in the limit of detection thickness from 10 to 18 cm. Our approach demonstrates superior denoising performance compared to the state-of-the-art denoising methods. The occlusion method further showed that the proposed algorithm automatically focuses on characterized peaks, enhancing the interpretability of our approach explicitly in Raman and SERS spectroscopy.

Competing Interests: The authors declare no conflicts of interest.

Background: Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells., Methods: LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 μM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling., Results: The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment., Conclusion: Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC., (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Graphene-based two-dimensional (2D) heterostructures exhibit excellent mechanical and electrical properties, which are expected to exhibit better performances than graphene for nanoelectromechanical pressure sensors. Here, we built pressure sensor models based on suspended heterostructures of graphene/h-BN, graphene/MoS 2 , and graphene/MoSe 2 by using COMSOL Multiphysics finite element software. We found that suspended circular 2D membranes show the best sensitivity to pressures compared to rectangular and square ones. We simulated the deflections, strains, resonant frequencies, and Young's moduli of suspended graphene-based heterostructures under the conditions of different applied pressures and geometrical sizes, built-in tensions, and the number of atomic layers of 2D membranes. The Young's moduli of 2D heterostructures of graphene, graphene/h-BN, graphene/MoS 2, and graphene/MoSe 2 were estimated to be 1.001 TPa, 921.08, 551.11, and 475.68 GPa, respectively. We also discuss the effect of highly asymmetric cavities on device performance. These results would contribute to the understanding of the mechanical properties of graphene-based heterostructures and would be helpful for the design and manufacture of high-performance NEMS pressure sensors.

Graphene is being increasingly used as an interesting transducer membrane in micro- and nanoelectromechanical systems (MEMS and NEMS, respectively) due to its atomical thickness, extremely high carrier mobility, high mechanical strength, and piezoresistive electromechanical transductions. NEMS devices based on graphene feature increased sensitivity, reduced size, and new functionalities. In this review, we discuss the merits of graphene as a functional material for MEMS and NEMS, the related properties of graphene, the transduction mechanisms of graphene MEMS and NEMS, typical transfer methods for integrating graphene with MEMS substrates, methods for fabricating suspended graphene, and graphene patterning and electrical contact. Consequently, we provide an overview of devices based on suspended and nonsuspended graphene structures. Finally, we discuss the potential and challenges of applications of graphene in MEMS and NEMS. Owing to its unique features, graphene is a promising material for emerging MEMS, NEMS, and sensor applications., (© 2024. The Author(s).)

Graphene ribbons with a suspended proof mass for nanomechanical systems have been rarely studied. Here, we report three types of nanomechanical devices consisting of graphene ribbons (two ribbons, four ribbons-cross and four ribbons-parallel) with suspended Si proof masses and studied their mechanical properties. The resonance frequencies and built-in stresses of three types of devices ranged from tens of kHz to hundreds of kHz, and from 82.61 MPa to 545.73 MPa, respectively, both of which decrease with the increase of the size of proof mass. The devices with four graphene ribbons featured higher resonance frequencies and spring constants, but lower built-in stresses than two ribbon devices under otherwise identical conditions. The Young's modulus and fracture strain of double-layer graphene were measured to be 0.34 TPa and 1.13% respectively, by using the experimental data and finite element analysis (FEA) simulations. Our studies would lay the foundation for understanding of mechanical properties of graphene ribbons with a suspended proof mass and their potential applications in nanoelectromechanical systems., (© 2024. The Author(s).)

Graphene has great potential to be used for humidity sensing due to its ultrahigh surface area and conductivity. However, the impact of different atomic layers of graphene on the SiO 2 /Si substrate on humidity sensing has not been studied yet. In this paper, we fabricated three types of humidity sensors on the SiO 2 /Si substrate based on one to three atomic layers of graphene, in which the sensing areas of graphene are 75 μm × 72 μm and 45 μm × 72 μm, respectively. We studied the impact of both the number of atomic layers of graphene and the sensing areas of graphene on the responsivity and response/recovery time of the prepared graphene-based humidity sensors. We found that the relative resistance change of the prepared devices decreased with the increase of number of atomic layers of graphene under the same change of relative humidity. Further, devices based on tri-layer graphene showed the fastest response/recovery time, while devices based on double-layer graphene showed the slowest response/recovery time. Finally, we chose devices based on double-layer graphene that have relatively good responsivity and stability for application in respiration monitoring and contact-free finger monitoring.

Per-and polyfluoroalkyl substances (PFAS) have been a global concern in relation to human exposure. Dust has been proven to be an important source of human exposure to many groups of organic pollutants, however, no study so far has systematically evaluated human exposure to PFAS depending on time spent in different indoor environments i.e., houses, offices and public transport vehicles. Archived dust samples were collected from residential houses (n = 38), offices (n = 15), and public transport vehicles (n = 12) in Australia to assess human exposures to PFAS via dust ingestion and dermal contact. Amongst the 19 target analytes, 14 compounds were detected in >50% of the samples. Significantly higher PFAS concentrations were found in dust samples collected from offices with mean ± SD of 400 ± 810 ng/g than houses (170 ± 350 ng/g) and public transport vehicles (39 ± 33 ng/g). Composition patterns of PFAS varied among indoor environments with Perfluorohexanoic acid (PFHxA) (median 2.5 ng/g dust) and perfluorooctanoic acid (PFOA) (median 5.7 ng/g) were the most prevalent compounds detected (DF = 100%). PFOA was the dominant PFAS compound in both offices (median 11 ng/g) and houses (median 5.8 ng/g). Perfluorododecanoic acid (PFDoA) (median 3.6 ng/g) was found to be the most abundant compounds in public transport vehicles. Considering the time spent in indoor environments, relatively higher estimated daily intakes (EDIs) were identified in offices than in houses and public transport vehicles. EDIs for PFOA and perfluorooctane sulfonic acid (PFOS) for adults and toddlers were well below the acceptable levels of 20 ng/kg/day proposed by U.S Environmental Protection Agency (USEPA) and Food Standard Australia and New Zealand (USEPA, 2016; FSANZ et al. (2016)), suggesting low or negligible exposure pathways via dust ingestion and dermal contact., 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.)

Background: Recent randomized trial data showed fewer strokes with left atrial appendage occlusion (LAAO) after cardiac surgery in patients with atrial fibrillation. This study developed a quality initiative to increase LAAO adoption., Methods: Among 11,099 patients who underwent isolated coronary artery bypass grafting (CABG) between January 2019 and March 2021 at 33 hospitals in Michigan, those patients with atrial fibrillation who underwent first-time, on-pump CABG were eligible (n = 1241). A goal LAAO rate of 75% was selected as a quality improvement target through a statewide collaborative. An interrupted time series analysis evaluated the change in LAAO rate before implementation (January to December 2019) vs after implementation (January 2020 to March 2021)., Results: Implementation of the quality metric improved the LAAO rate from 61% (357 of 581) before implementation to 79% (520 of 660) after implementation (P < .001). Compared with patients who did not undergo concomitant LAAO, patients who underwent LAAO (71%; 877 of 1241) were older, more frequently male, and had a lower The Society of Thoracic Surgeons Predicted Risk of Mortality score (2.9% ± 3.5% vs 3.7% ± 5.7%; P = .003), whereas other baseline characteristics, including CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex category) scores, were similar. Mean bypass and cross-clamp times were 7 and 6 minutes longer, respectively, in the LAAO group among patients who did not undergo concomitant ablation. Operative mortality, major morbidity, blood product administration, and thromboembolic events were similar between the groups. Interrupted time series analysis showed a significant increase in LAAO rate after implementation (P = .009)., Conclusions: LAAO in patients with atrial fibrillation who underwent isolated CABG did not add operative risk vs isolated CABG without LAAO. A statewide quality improvement initiative was successful in increasing the rate of concomitant LAAO and could be further evaluated as a potential quality metric in cardiac surgery., Competing Interests: Disclosures Alexander A. Brescia has served as an Associate Editor for Digital Media and Digital Scholarship for The Annals of Thoracic Surgery. Steven F. Bolling has served as a consultant for Abbott Laboratories, Boston Scientific Corporation, Medtronic, and W.L. Gore and Associates. Gorav Ailawadi has served as a consultant for Abbott Vascular, Admedus Corporation, Edwards Lifesciences, Medtronic, and W.L. Gore and Associates; and has served on the Data and Safety Monitoring Board of AtriCure. All other authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Iron-nitrogen-carbon (Fe-N-C) materials have been identified as a promising class of platinum (Pt)-free catalysts for the oxygen reduction reaction (ORR). However, the dissolution and oxidation of Fe atoms severely restrict their long-term stability and performance. Modulating the active microstructure of Fe-N-C is a feasible strategy to enhance the ORR activity and stability. Compared with common 3d transition metals (Co, Ni, etc.), the 4d transition metal atom Nb has fewer d electrons and more unoccupied orbitals, which could potentially forge a more robust interaction with the Fe site to optimize the binding energy of the oxygen-containing intermediates while maintaining stability. Herein, an asymmetric Fe-Nb diatomic site catalyst (FeNb/c-SNC) was synthesized, which exhibited superior ORR performance and stability compared with those of Fe single-atom catalysts (SACs). The strong interaction within the Fe-Nb diatomic sites optimized the desorption energy of key intermediates (*OH), so that the adsorption energy of Fe-*OH approaches the apex of the volcano plot, thus exhibiting optimal ORR activity. More importantly, introducing Nb atoms could effectively strengthen the Fe-N bonding and suppress Fe demetalation, causing an outstanding stability. The zinc-air battery (ZAB) and hydroxide exchange membrane fuel cell (HEMFC) equipped with our FeNb/c-SNC could deliver high peak power densities of 314 mW cm -2 and 1.18 W cm -2 , respectively. Notably, the stable operation time for ZAB and HEMFC increased by 9.1 and 5.8 times compared to Fe SACs, respectively. This research offers further insights into developing stable Fe-based atomic-level catalytic materials for the energy conversion process.

Massive hemorrhage and chronic wounds caused by bacterial infections after trauma are significant challenges in clinical practice. An ideal hemostatic wound dressing should simultaneously manage bleeding and prevent bacterial infections and also hold excellent biocompatibility and bioactivities to successfully modulate immune microenvironments to promote wound healing. In this study, a silk fibroin-based light-responsive film was demonstrated to possess effective capacity of light-induced non-compressible hemostasis on liver hemorrhage and tail bleeding in vivo by binding with blood platelets to promote the clotting cascade. The blood loss of the rats was significantly less after C-MASiF films were applied, which were 1223.33 ± 347.9 mg (liver trauma) and 363.33 ± 60.28 mg (tail trimming). Importantly, the films exhibited photo-controllable modulation activity on macrophages through repeated near-infrared irradiation to regulate the immune microenvironment to enhance photodynamic antibacterial therapy. Moreover, the light-responsive silk fibroin film effectively promoted Staphylococcus aureus infected burn wound healing in vivo . The quantity of residual bacteria in the wound sites of mice in the C-MASiF films group (0.05 ± 0.0047 × 10 8 CFU mL -1 ) was considerably less than that in the control group (3.18 ± 0.75 × 10 8 CFU mL -1 ), and the wound area in the C-MASiF group (78.03% ± 4.12%) was considerably smaller than that in the control group (60.33% ± 8.81%) after 14 days. Overall, this light-responsive silk fibroin film can provide a powerful strategy for wound healing of burns.

Background: Dry eye disease (DED) is highly prevalent worldwide, leading to increased medical costs, economic burdens on families and society, and a diminished quality of life for patients. The utilization of autologous serum eye drops (ASEDs) for the treatment of DED is progressively rising., Objective: To further evaluate the efficacy and safety of ASEDs in the treatment of DED., Methods: A thorough search for randomized controlled trials (RCTs) was conducted across eight databases, including PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed, and VIP. This search encompassed the inception of each database up to April 1, 2024, with a specific focus on identifying RCTs evaluating the efficacy and safety of ASEDs for the treatment of DED. Data analysis was conducted utilizing Stata 15.0 software and the Cochrane Risk of Bias Assessment Tool was utilized to appraise the literature's quality., Results: The study encompassed 12 RCTs. In comparison to the use of artificial tears (AT), patients diagnosed with DED who utilized ASEDs displayed elevated the Schirmer test (ST) scores [WMD = 2.35, 95% CI (1.45, 3.24), p < 0.001] and tear-film breakup time (TBUT) scores [WMD = 2.83, 95% CI (2.27, 3.39), p < 0.001], decreased Corneal fluorescence staining (CFS) scores [SMD = -2.11, 95% CI (-3.07, -1.15), p < 0.001] and the Ocular Surface Disease Index (OSDI) scores [WMD = -10.54, 95% CI (-13.31, -7.77), p < 0.001], and experienced a reduced frequency of adverse events [RR = 0.36, 95% CI (0.13, 0.99), p = 0.048]., Conclusion: In this study, ASEDs had been shown to enhance tear secretion, extend tear film break-up time, mitigate corneal epithelial damage, ameliorate OSDI scores, and exhibit greater safety compared to AT., 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 He, Zeng, Liu, Qiu and He.)

Purpose: To objectively quantify posterior capsule opacification (PCO) using swept-source anterior segment optical coherence tomography (SS-ASOCT) in pseudophakic eyes., Setting: Zhongshan Ophthalmic Center, Guangzhou, China., Design: Prospective cross-sectional study., Methods: One hundred and eighty eyes with PCO (37 multifocal intraocular lenses [MfIOLs] and 143 monofocal intraocular lenses [MoIOLs]) were enrolled. The PCO Irregular Degree (PID), defined to evaluate the surface irregularity of PCO, the average and maximum thickness of PCO (AT-PCO, MT-PCO) were applied to quantify PCO based on SS-ASOCT (CASIA2) images. Corrected distance visual acuity (CDVA), high order aberrations (HOAs), modulation transfer function (MTF) and Strehl ratio were recorded. The associations between SS-ASOCT parameters and visual function parameters were assessed by Spearman's correlation analysis., Results: PID, AT-PCO and MT-PCO showed significant correlations with CDVA, Strehl ratio and HOAs (CDVA: r = 0.702, 0.741, 0.736; Strehl ratio: r = -0.746, -0.719, -0.740; HOAs: r = 0.762, 0.734, 0.752). The correlations of these three parameters with Strehl ratio and HOAs were significantly higher than those of clinical PCO grading with Strehl ratio and HOAs (all P < 0.05). Particularly, PID demonstrated notable correlations with Strehl ratio and HOAs. In addition, patients with MfIOLs presented worse Strehl ratio and HOAs than those with MoIOLs after matching age, PID, AT-PCO and MT-PCO., Conclusions: This study provides a novel method for objectively quantifying PCO using successive cross-sectional SS-ASOCT images. AT-PCO, MT-PCO and PID are presented as new indicators to document PCO severity, with PID offering a unique perspective by considering the irregularity aspect of PCO., (Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

During the COVID-19 pandemic, one of Australia's biggest cities, Melbourne, experienced three major isolation ("lockdown") periods in 2020 (160 days) and in 2021 (111 days) which makes it one of the most locked down cities world-wide. This study assessed how the pandemic affected temporal trends in methamphetamine, MDMA and cocaine consumption using wastewater-based epidemiology. Daily samples were collected for most of 2020 and 2021 (n = 660 days). Concentrations were measured using direct-injection LC-MS/MS and back-calculated to consumption estimates. Results indicate that methamphetamine use was increasing before the first lockdown and decreased after the end of the first lockdown in 2020. Methamphetamine trends appeared to have remained steady throughout the second lockdown period before increasing steeply after it ended. For most of 2020, cocaine use remained steady, with an increase after the second lockdown. MDMA use decreased after the start of the first lockdown and remained steady throughout most of 2020 and 2021. In comparison to 2020, trends in 2021 were less variable and stimulant use did not appear to be as associated with COVID-19 restrictions. Overall, this study was able to show the impact of lockdown periods and the related social restrictions on illicit stimulant use. ENVIRONMENTAL IMPLICATION: Illicit drugs are hazardous chemicals, of concern both to humans and the environment. While studies have been undertaken to understand their temporal trends, this work utilizes wastewater-based epidemiology and daily sampling to provide a comprehensive understanding of the impact of the COVID-19 pandemic on the use of methamphetamine, MDMA and cocaine on one of the most locked-down cities in the world. Understanding the consequences of this significant intervention on illicit drug use could provide valuable insights into its potential environmental impact., 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 B.V. All rights reserved.)

Purpose: The objective of this study was to analyze proposed Korean nursing legislation as depicted in newspaper articles, to highlight issues related to the legislative process for this potential law, and to better understand social awareness regarding this matter., Methods: The study focused on articles from 11 leading newspapers in Korea, published between February 2020 and August 2023, that pertained to nursing legislation. The articles were retrieved from the BigKinds database. Following text preprocessing, analytical methods including term frequency-inverse document frequency were employed, along with latent Dirichlet allocation (LDA), for word and topic modeling analysis. Additionally, LDA was applied across time periods to examine temporal changes in topics., Results: Following preprocessing, a total of 7,967 words were extracted from the 991 articles selected for analysis. The primary themes identified in newspaper articles concerning the nursing legislation were organized into three main topics: 1) the necessity and impact of enactment of the nursing law, 2) the political context surrounding enactment of the law, and 3) the conflicts between and actions of healthcare organizations related to enactment of the law., Conclusions: The findings confirmed that media coverage regarding the proposed nursing legislation primarily concentrated on the political and social conflicts associated with the law's passage, rather than its necessity and substance. More compelling evidence must be presented concerning the influence of the nursing workforce and the work environment of nurses on patient safety and health outcomes. Additionally, strategies should be devised to improve public comprehension of the nursing law's provisions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

For fractured gas reservoirs with strong water drive, gas phase trapping affects the gas recovery significantly. The recovery may be less than 50% for some reservoirs while it is only 12% for Beaver River gas field. The gas phase trapping mechanism has been revealed by the results of depletion experimental test. The residual pressure of the trapped gas is as high as 11.75 MPa with a 12.8 cm imbibition layer resulting in gas recovery deceased 49.5% compared with that without imbibition layer. A mathematical model is built to calculate the imbibition thickness based on capillary pressure and relative permeability of the matrix. The gas phase trapping are analyzed by two representative wells in Weiyuan gas field, the intermittent production reinforces the imbibition thickness and result in gas trapped in the matrix block with high residual pressure for the low performace gas wells, the extremely low gas recovery can be explained more rationally. That lays a foundation of improving the gas recovery for fractured reservoirs., (© 2024. The Author(s).)

The present study, as one part of a larger project that aimed to investigate the effects of dietary berberine (BBR) on fish growth and glucose regulation, mainly focused on whether miRNAs involve in BBR's modulation of glucose metabolism in fish. Blunt snout bream Megalobrama amblycephala (average weight of 20.36 ± 1.44 g) were exposed to the control diet (NCD, 30% carbohydrate), the high-carbohydrate diet (HCD, 43% carbohydrate) and the berberine diet (HCB, HCD supplemented with 50 mg/kg BBR). After 10 weeks' feeding trial, intraperitoneal injection of glucose was conducted, and then, the plasma and liver were sampled at 0 h, 1 h, 2 h, 6 h, and 12 h. The results showed the plasma glucose levels in all groups rose sharply and peaked at 1 h after glucose injection. Unlike the NCD and HCB groups, the plasma glucose in the HCD group did not decrease after 1 h, while remained high level until at 2 h. The NCD group significantly increased liver glycogen content at times 0-2 h compared to the other two groups and then liver glycogen decreased sharply until at times 6-12 h. To investigate the role of BBR that may cause the changes in plasma glucose and liver glycogen, miRNA high-throughput sequencing was performed on three groups of liver tissues at 2 h time point. Eventually, 20 and 12 differentially expressed miRNAs (DEMs) were obtained in HCD vs NCD and HCB vs HCD, respectively. Through function analyzing, we found that HCD may affect liver metabolism under glucose loading through the NF-κB pathway; and miRNAs regulated by BBR mainly play roles in adipocyte lipolysis, niacin and nicotinamide metabolism, and amino acid transmembrane transport. In the functional exploration of newly discovered novel:Chr12&#95;18892, we found its target gene, adenylate cyclase 3 (adcy3), was widely involved in lipid decomposition, amino acid metabolism, and other pathways. Furthermore, a targeting relationship of novel:Chr12&#95;18892 and adcy3 was confirmed by double luciferase assay. Thus, BBR may promote novel:Chr12&#95;18892 to regulate the expression of adcy3 and participate in glucose metabolism., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Neuroinflammation is a characteristic feature of neurodegenerative diseases. Mesenchymal stem cell-derived exosomes (MSC-exo) have shown neuroprotective effects through immunoregulation, but the therapeutic efficacy remains unsatisfactory. This study aims to enhance the neuroprotective capacity of MSC-exo through IL-23 priming for treating retinal degeneration in mice., Methods: MSC were primed with IL-23 stimulation in vitro, and subsequently, exosomes (MSC-exo and IL-23-MSC-exo) were isolated and characterized. Two retinal degenerative disease models (NaIO3-induced mice and rd10 mice) received intravitreal injections of these exosomes. The efficacy of exosomes was assessed by examining retinal structural and functional recovery. Furthermore, exosomal microRNA (miRNA) sequencing was conducted, and the effects of exosomes on the M1 and M2 microglial phenotype shift were evaluated., Results: IL-23-primed MSC-derived exosomes (IL-23-MSC-exo) exhibited enhanced capability in protecting photoreceptor cells and retinal pigment epithelium (RPE) cells against degenerative damage and fostering the restoration of retinal neural function in both NaIO3-induced retinal degeneration mice and rd10 mice when compared with MSC-exo. The exosomal miRNA suppression via Drosha knockdown in IL-23-primed MSC would abolish the neuroprotective role of IL-23-MSC-exo, highlighting the miRNA-dependent mechanism. Bioinformatic analysis, along with further in vivo biological studies, revealed that IL-23 priming induced a set of anti-inflammatory miRNAs in MSC-exo, prompting the transition of M1 to M2 microglial polarization., Conclusions: IL-23 priming presents as a potential avenue for amplifying the immunomodulatory and neuroprotective effects of MSC-exo in treating retinal degeneration.

Background: The intraocular injections of anti-vascular endothelial growth factor (anti-VEGF) demonstrates significant efficacy in inhibiting the formation of ocular neovascularization in neovascular glaucoma (NVG). Ahmed glaucoma valve implantation (AGVI) is extensively employed for the management of diverse glaucoma types., Objective: To further evaluate the efficacy and safety of anti-VEGF combined with AGVI in the treatment of neovascular glaucoma., Methods: A thorough search for randomized controlled trials (RCTs) was conducted across eight databases: PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, SinoMed, and VIP. The search period was set from the inception of each database until March 2, 2024, to identify RCTs investigating the effectiveness and safety of combining AGVI with anti-VEGF therapy for NVG. We used the Cochrane Risk of Bias Assessment Tool to evaluate the quality of the literature and performed statistical analysis using Stata 15.0 software., Results: Fourteen RCTs were included in this study. Compared with AGVI alone, the combination of anti-VEGF drugs and AGVI can reduce postoperative intraocular pressure (IOP) at 1 week [WMD = -4.03, 95% CI (-5.73, -2.34), p  < 0.001], 1 month [WMD = -5.39, 95% CI (-7.05, -3.74), p  < 0.001], 3 months [WMD = -6.59, 95% CI (-7.85, -5.32), p  < 0.001], 6 months [WMD = -4.99, 95% CI (-9.56, -0.43), p  = 0.032], and more than 12 months [WMD = -3.86, 95% CI (-6.82, -0.90), p  = 0.011], with a higher Effective rate [RR = 1.27, 95% CI (1.18, 1.37), p  < 0.001], decreased incidence of postoperative hyphema [RR = 0.24, 95% CI (0.15, 0.39), p  < 0.001], reduced use of postoperative antiglaucoma medications [WMD = -0.48, 95% CI (-0.61, -0.35), p  < 0.001], and decreased aqueous humor VEGF levels [SMD = -2.84, 95% CI (-4.37, -1.31), p  < 0.001]., Conclusion: In comparison to AGVI alone, the combination of AGVI with anti-VEGF therapy has better effects in reducing IOP at various time intervals, diminishing postoperative antiglaucoma medication requirements and reducing aqueous humor VEGF levels. Furthermore, it effectively minimizes the incidence of postoperative hyphema. Nevertheless, due to the variability in the quality of the trials included, further high-quality experiments will be required in the future to substantiate this conclusion., Systematic Review Registration: PROSPERO, identifier CRD42024519862, https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42024519862., 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 He, Lu, Zeng, Liu, Qiu, Xue and He.)

There is no reliable causal evidence for the effect of statins on diabetic nephropathy (DN) and diabetic retinopathy (DR), and the results of previous observational studies are contradictory. Genetic variants linked to low-density lipoprotein cholesterol (LDL-C) from a UK biobank genome-wide association study and located within a 100kb window around HMGCR were used to proxy statins, comparing with PCSK9 inhibitors (control). DN and DR genome-wide association study summary statistics were obtained from the FinnGen study. Secondary MR analyses and NHANES cross-sectional data were used for validation. Drug-target Mendelian randomization (MR) was applied to investigate the association between the genetically proxied inhibition of HMGCR and PCSK9 with DN and DR, p < 0.0125 was considered significant after Bonferroni Correction. To triangulate the findings, genetic variants of whole blood-derived targets gene expression (cis-eQTL) and plasma-derived protein (cis-pQTL) levels were used to perform secondary MR analyses and data from the National Health and Nutrition Examination Survey were used for cross-sectional analysis. Genetically proxied inhibition of HMGCR was associated with higher risks of DN and DR (DN: OR = 1.79, p = 0.01; DR: OR = 1.41, p = 0.004), while no such association was found for PCSK9. Secondary MR analyses confirmed these associations. Cross-sectional analysis revealed a positive link between statin use and DR incidence (OR = 1.26, p = 0.03) and a significant negative association with glomerular filtration rate (Beta = - 1.9, p = 0.03). This study provides genetic evidence that genetically proxied inhibition of HMGCR is associated with increased risks of DN/DR, and this effect may not be attributed to their LDL-C-lowering properties. For patients with diabetic dyslipidemia, PCSK9 inhibitors may be a preferable alternative., (© 2024. The Author(s).)

Background: Surface-enhanced Raman spectroscopy (SERS) has gained increasing importance in molecular detection due to its high specificity and sensitivity. Complex biofluids (e.g., cell lysates and serums) typically contain large numbers of different bio-molecules with various concentrations, making it extremely challenging to be reliably and comprehensively characterized via conventional single SERS spectra due to uncontrollable electromagnetic hot spots and irregular molecular motions. The traditional approach of directly reading out the single SERS spectra or calculating the average of multiple spectra is less likely to take advantage of the full information of complex biofluid systems., Results: Herein, we propose to construct a spectral set with unordered multiple SERS spectra as a novel representation strategy to characterize full molecular information of complex biofluids. This new SERS representation not only contains details from each single spectra but captures the temporal/spatial distribution characteristics. To address the ordering-independent property of traditional chemometric methods (e.g., the Euclidean distance and the Pearson correlation coefficient), we introduce Wasserstein distance (WD) to quantitatively and comprehensively assess the quality of spectral sets on biofluids. WD performs its superiority for the quantitative assessment of the spectral sets. Additionally, WD benefits from its independence of the ordering of spectra in a spectral set, which is undesirable for traditional chemometric methods. With experiments on cell lysates and human serums, we successfully achieve the verification for the reproducibility between parallel samples, the uniformity at different positions in the same sample, the repeatability from multiple tests at one location of the same sample, and the cardinality effect of the spectral set. SERS spectral sets also manage to distinguish different classes of human serums and achieve higher accuracy than the traditional prostate-specific antigen in prostate cancer classification., Significance: The proposed SERS spectral set is a robust representation approach in accessing full information of biological samples compared to relying on a single or averaged spectra in terms of reproducibility, uniformity, repeatability, and cardinality effect. The application of WD further demonstrates the effectiveness and robustness of spectral sets in characterizing complex biofluid samples, which extends and consolidates the role of SERS., 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.)

With the high yield of many wells represented by Well JT1 in the Maokou Formation, has catalyzed a surge in exploration activities along the platform margin facies of the Maokou Formation in central Sichuan and further showed the significant exploration potential of the Maokou Formation in the northern slope. However, the fracture cave body of the Maokou Formation exhibits a high degree of development, strong longitudinal and horizontal heterogeneity, large formation pressure differences, and drilling events such as gas kicks and lost circulation occur frequently, which seriously affects the efficient implementation of drilling. Understanding the spatial distribution of the three-pressure in the formation can help better deal with and solve the above problems. Therefore, in order to help the safe, high-quality and rapid drilling of the Maokou Formation in the study area, and enhance the efficiency of oil and gas development, this paper explores the research on the prediction method of the three-pressure of jointing well-seismic data based on the geomechanical experimental data and the actual drilling data. In the process of prediction of pore pressure, this study found that the pore pressure and formation velocity in the study area have an exponential relationship. In order to enhance the applicability of the Filippone's method in the study area and improve the prediction accuracy of pore pressure, the linear relationship between pore pressure and formation velocity in the Filippone's method is modified to an exponential relationship, and a pore pressure prediction model suitable for the work area was established. Based on the Mohr-Coulomb criterion and Huang's model, the prediction models of collapse pressure and fracture pressure applicable to the study area were established, respectively. Then, the elastic parameters were obtained through pre-stack inversion, and the three-pressure bodies were calculated based on the elastic parameter bodies. The results indicate that: (1) The three-pressure prediction method of the jointing well-seismic data in this paper can predict the formation's longitudinal and transverse pressure anomaly zones in advance. (2) The Maokou Formation in the study area is characterized by abnormally high pressure, to balance the pressure of the high-ground formation, high-density drilling fluid is necessary. (3) The prediction results of three-pressure in this paper are highly consistent with the actual drilling engineering events, which verifies the reliability of the three-pressure prediction results presented in this study. The results of the study can provide a basis for decision-making in drilling geological design, such as the determination of drilling fluid density, the evaluation of borehole stability and other engineering problems that require support from three-pressure data., (© 2024. The Author(s).)

The Pearl River Estuary (PRE), one of the primary e-waste recycling centers in the world, has been suffering from the pollution of Liquid Crystal Monomers (LCMs), critical materials with persistent, bio-accumulative, and toxic substances used in electronic devices. It has been detected in seabed sediment with both high frequency and concentration near PRE - Hong Kong (HK) waters. In the same area, dredging operations with in-situ sediment have been frequently used in the last decades for coastal land reclamation projects. Dredging is known to cause a huge amount of sediment re-suspension into water columns, with potential damage to marine ecosystems and biodiversity. In this study, we proposed a new risk assessment strategy to estimate the secondary pollution due to the re-suspension sediment highly contaminated by LCMs. We formulate a robust and reliable probabilistic approach based on unsupervised machine learning and hydrodynamic and sediment transport numerical simulation. New risk indexes were also proposed to better quantify the impact of contaminated sediments. We applied the methodology to assess the potential impact of dredging operations in the PRE and Hong Kong waters on the local marine ecosystem. The results of the analysis showed how the potentially contaminated areas depended on the dredging locations., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Morchella importuna polysaccharide (MIP) has been proven to have obvious hypoglycemic effects on mice with type 2 diabetes (T2DM). This study looked at the functional and rheological characteristics of MIP, and investigated the effects of MIP on the human fecal microbiota through in vitro fermentation experiments. The outcomes demonstrate the excellent oil-holding capacity, emulsifying, foaming, and rheological characteristics of MIP. After salivary gastrointestinal digestion, the Mw of MIP decreased from 398.2 kDa and 21.5 kDa to 21.9 kDa and 11.7 kDa. By 16S rRNA sequencing of bacteria fermented in vitro, it was found that MIP did not improve the richness and diversity of intestinal microorganisms, but it may exert an anti-T2DM function by significantly increasing the relative abundance of Firmicutes and promoting Ruminococcaceae&#95;UCG&#95;014 , Bacteroides , and Blautia proliferation. Escherichia-Shigella could also be inhibited to improve the intestinal microenvironment. In addition, the fermentation of MIP increased the total short-chain fatty acid (SCFA) concentration from 3.23 mmol/L to 39.12 mmol/L, and the propionic acid content increased significantly. In summary, MIP has excellent processing performance and is expected to exert potential anti-T2DM activity through the human intestinal microbiota, which has broad market prospects.

Compelling evidence has shown that geomagnetic disturbances in vertical intensity polarization before great earthquakes are promising precursors across diverse rupture conditions. However, the geomagnetic vertical intensity polarization method uses the spectrum of smooth signals, and the anomalous waveforms of seismic electromagnetic radiation, which are basically nonstationary, have not been adequately considered. By combining pulse amplitude analysis and an experimental study of the cumulative frequency of anomalies, we found that the pulse amplitudes before the 2022 Luding M6.8 earthquake show characteristics of multiple synchronous anomalies, with the highest (or higher) values occurring during the analyzed period. Similar synchronous anomalies were observed before the 2021 Yangbi M6.4 earthquake, the 2022 Lushan M6.1 earthquake and the 2022 Malcolm M6.0 earthquake, and these anomalies indicate migration from the periphery toward the epicenters over time. The synchronous changes are in line with the recognition of previous geomagnetic anomalies with characteristics of high values before an earthquake and gradual recovery after the earthquake. Our study suggests that the pulse amplitude is effective for extracting anomalies in geomagnetic vertical intensity polarization, especially in the presence of nonstationary signals when utilizing observations from multiple station arrays. Our findings highlight the importance of incorporating pulse amplitude analysis into earthquake prediction research on geomagnetic disturbances.

Transient transformation is extremely useful for rapid in vivo assessment of gene function, especially for fruit-related genes. Grape berry, while an important fruit crop, is recalcitrant to transient transformation, due to the high turgor pressure in its mesocarp cells that limits the ability of Agrobacterium to penetrate into the tissue. It is urgent to establish a simple transient transformation system for rapid analysis of gene function. In this study, different injection methods, grape genotypes, and developmental stages were tested in order to develop a rapid and efficient Agrobacterium-mediated transient transformation methodology for grape berries. Two injection methods, namely punch injection and direct injection, were evaluated using the β-glucuronidase (GUS) gene and by x-gluc tissue staining and 4-methylumbelliferyl-β-D-glucuronide fluorescence analysis. The results indicated that there were no significant differences on transformation effects between the two methods, but the latter was more suitable because of its simplicity and convenience. Six grape cultivars ('Hanxiangmi', 'Moldova', 'Zijixin', 'Jumeigui', 'Shine-Muscat', and 'A17') were tested for transient transformation. 'Hanxiangmi', 'Moldova', and 'Zijixin' grape berries were not suitable for agroinfiltration due to frequently fruit cracking, browning, and formation of scar skin. The fruit integrity rates of 'Jumeigui', 'Shine-Muscat', and 'A17' berries were all above 80%, and GUS activity was detected in the berries of the three cultivars 3-14 days after injection with the Agrobacterium culture, while higher GUS activities were observed in the 'Jumeigui' berries. The levels of GUS activity in injected berries at 7-8 weeks after full blooming (WAFB) were more than twice at 6 WAFB. In subsequent assays, the over-expression of MYB transcription factor VvMYB44 via transient transformation accelerated the anthocyanin accumulation and fruit coloring through raising the expression levels of VvLAR1, VvUFGT, VvLDOX, VvANS, and VvDFR, which verified the effectiveness of this transformation system. These experiments finally identified the reliable grape cultivars and suitable operational approach for transient transformation and further indicated that this Agrobacterium-mediated transient transformation system was efficient and suitable for the elucidation of gene function in grape berries., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Diabetic retinopathy (DR) is a highly hazardous and widespread complication of diabetes mellitus (DM). The accumulated reactive oxygen species (ROS) play a central role in DR development. The aim of this research was to examine the impact and mechanisms of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEV) on regulating ROS and retinal damage in DR. Intravitreal injection of sEV inhibited Cullin3 neddylation, stabilized Nrf2, decreased ROS, reduced retinal inflammation, suppressed Müller gliosis, and mitigated DR. Based on MSC-sEV miRNA sequencing, bioinformatics software, and dual-luciferase reporter assay, miR-143-3p was identified to be the key effector for MSC-sEV's role in regulating neural precursor cell expressed developmentally down-regulated 8 (NEDD8)-mediated neddylation. sEV were able to be internalized by Müller cells. Compared to advanced glycation end-products (AGEs)-induced Müller cells, sEV coculture decreased Cullin3 neddylation, activated Nrf2 signal pathway to combat ROS-induced inflammation. The barrier function of endothelial cells was impaired when endothelial cells were treated with the supernatant of AGEs-induced Müller cells, but was restored when treated with supernatant of AGEs-induced Müller cells cocultured with sEV. The protective effect of sEV was, however, compromised when miR-143-3p was inhibited in sEV. Moreover, the protective efficacy of sEV was diminished when NEDD8 was overexpressed in Müller cells. These findings showed MSC-sEV delivered miR-143-3p to inhibit Cullin3 neddylation, stabilizing Nrf2 to counteract ROS-induced inflammation and reducing vascular leakage. Our findings suggest that MSC-sEV may be a potential nanotherapeutic agent for DR, and that Cullin3 neddylation could be a new target for DR therapy., 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 Inc. All rights reserved.)

Oral melanomas are the most common oral malignancies in dogs and are characterized by an aggressive nature, invasiveness, and poor prognosis. With biological and genetic similarities to human oral melanomas, they serve as a valuable spontaneous comparative model. Primary cell cultures are widely used in human medicine and, more recently, in veterinary medicine to study tumorigenesis, cancer progression, and innovative therapeutic approaches. This study aims to establish two- and three-dimensional primary cell lines from oral canine melanomas using fine-needle aspiration as a minimally invasive sampling method. For this study, samples were collected from six dogs, represented by four primary oral melanomas and five lymph nodal metastases. The cells were digested to obtain single-cell suspensions, seeded in flasks, or processed with Matrigel ® to form organoids. The cell cultures were characterized through flow cytometry using antibodies against Melan-A, PNL2, and Sox-10. This technique offers a minimally invasive means to obtain cell samples, particularly beneficial for patients that are ineligible for surgical procedures, and enables the establishment of in vitro models crucial for comparative studies in mucosal melanoma oncology. To the best of our knowledge, this is the first work establishing neoplastic primary cell cultures via fine-needle aspiration in dogs.

Objective: To explore clinical effect of vancomycin calcium sulfate combined with internal fixation on calcaneal beak-like fracture secondary to calcaneal osteomyelitis caused by diabetic foot., Methods: From April 2018 to October 2021, a retrospective analysis was performed on 5 patients with calcaneal bone osteomyelitis secondary to diabetic foot, including 2 males and 3 females, aged from 48 to 60 years old;diabetes course ranged from 5 to 13 years;the courses of diabetic foot disease ranged from 18 to 52 days;5 patients were grade Ⅲ according to Wagner classification. All patients were treated with debridement, vancomycin bone cement implantation, negative pressure aspiration at stageⅠ, vancomycin calcium sulfate and internal fixation at stageⅡfor calcaneal beak-like fracture. Surgical incision and fracture healing time were recorded, and the recurrence of osteomyelitis was observed. American Orthopedic Foot Andankle Society (AOFAS) score and exudation at 12 months after operation were evaluated., Results: Five patients were successfully completed operation without lower extremity vascular occlusion, and were followed up for 16 to 36 months. The wound healing time after internal fixation ranged from 16 to 26 days, and healing time of fractures ranged from 16 to 27 weeks. AOFAS score ranged from 65 to 91 at 12 months after operation, and 2 patients got excellent result, 2 good and 1 fair. Among them, 1 patient with skin ulcer on the back of foot caused by scalding at 5 months after operation (non-complication), was recovered after treatment;the wound leakage complication occurred in 2 patients, and were recovered after dressing change. No osteomyelitis or fracture occurred in all patients., Conclusion: Vancomycin calcium sulfate with internal fixation in treating calcaneal osteomyelitis secondary to calcaneal osteomyelitis caused by diabetic foot could not only control infection, but also promote fracture healing, and obtain good clinical results.

The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases., (© 2024. The Author(s).)

A three-dimensional porous bacterial cellulose/graphene oxide (BC/GO) composite hydrogel (BC/GO) was synthesized with multi-layer graphene oxide (GO) as the modifier and bacterial cellulose as the skeleton via an ultrasonic shaking process to absorb lead ions effectively. The characteristics of BC/GO were investigated through TEM, SEM, FT-IR, NMR and Zeta potential experiments. Compared to bacterial cellulose, the ultrasonic method and the carboxyl groups stemming from GO helped to enhance the availability of O(3)H of BC, in addition to the looser three-dimensional structure and enriched oxygen-containing groups, leading to a significantly higher adsorption capacity for Pb(II). In this paper, the adsorption behavior of BC/GO is influenced by the GO concentration, adsorption time, and initial concentration. The highest adsorption capacity for Pb(II) on BC/GO found in this study was 224.5 mg/g. The findings implied that the pseudo-second-order model explained the BC/GO adsorption dynamics and that the data of its adsorption isotherm fit the Freundlich model. Because of the looser three-dimensional structure, the complexation of carboxyl groups, and the enhanced availability of O(3)H, bacterial cellulose exhibited a much better adsorption capacity.

Molecular phenotypic variations in metabolites offer the promise of rapid profiling of physiological and pathological states for diagnosis, monitoring, and prognosis. Since present methods are expensive, time-consuming, and still not sensitive enough, there is an urgent need for approaches that can interrogate complex biological fluids at a system-wide level. Here, we introduce hyperspectral surface-enhanced Raman spectroscopy (SERS) to profile microliters of biofluidic metabolite extraction in 15 min with a spectral set, SERSome, that can be used to describe the structures and functions of various molecules produced in the biofluid at a specific time via SERS characteristics. The metabolite differences of various biofluids, including cell culture medium and human serum, are successfully profiled, showing a diagnosis accuracy of 80.8% on the internal test set and 73% on the external validation set for prostate cancer, discovering potential biomarkers, and predicting the tissue-level pathological aggressiveness. SERSomes offer a promising methodology for metabolic phenotyping., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A 3-month-old kitten was presented after successful cardiopulmonary resuscitation, including a presumed intracardial injection by its primary care veterinarian. Throughout the subsequent hospitalization in the intensive care unit, the cat exhibited recurrent hemorrhagic pericardial effusions, along with concurrent pleural and abdominal effusions, resulting in multiple clinical deteriorations, necessitating pericardiocentesis and thoracocentesis. Despite more than 3 days of intensive care, the cat experienced another cardiopulmonary arrest with unsuccessful attempts to achieve the return of spontaneous circulation. Necropsy and histopathological findings revealed diffuse chronic-active pericarditis and hemorrhagic pericardial effusion, a condition that has not been documented in the context of cardiopulmonary resuscitation or pericardiocentesis., 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 Weingand, He, Grau-Roma and Adamik.)

Autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematous, are regulated by polymorphisms in genes contributing to the NOX2 complex. Mutations in both Ncf1 and Ncf4 affect development of arthritis in experimental models of RA, but the different regulatory pathways mediated by NOX2-derived reactive oxygen species (ROS) have not yet been clarified. Here we address the possibility that intracellular ROS, regulated by the NCF4 protein (earlier often denoted p40phox) which interacts with endosomal membranes, could play an important role in the oxidation of cysteine peptides in mononuclear phagocytic cells, thereby regulating antigen presentation and activation of arthritogenic T cells. To study the role of NCF4 we used mice with an amino acid replacing mutation (NCF4 R58A ), which is known to affect interaction with endosomal membranes, leading to decreased intracellular ROS production. To study the impact of NCF4 on T cell activation, we used the glucose phosphate isomerase peptide GPI 325-339 , which contains two cysteine residues (325-339c-c). Macrophages from mice with the NCF4 58A mutation efficiently presented the peptide when the two cysteines were intact and not crosslinked, leading to a strong arthritogenic T cell response. T cell priming occurred in the draining lymph nodes (LNs) within 8 days after immunization. Clodronate treatment, which depletes antigen-presenting mononuclear phagocytes, ameliorated arthritis severity, whereas treatment with FYT720, which traps activated T cells in LNs, prohibited arthritis. We conclude that NCF4-dependent intracellular ROS maintains cysteine peptides in an oxidized crosslinked state, which prevents presentation of peptides recognized by non-tolerized T cells and thereby protects against autoimmune arthritis., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The changes of inflammation and metabolism are two features in nonalcoholic steatohepatitis (NASH). However, how they interact to regulate NASH progression remains largely unknown. Our works have demonstrated the importance of solute carrier family 7 member 11 (SLC7A11) in inflammation and metabolism. Nevertheless, whether SLC7A11 regulates NASH progression through mediating inflammation and metabolism is unclear. In this study, we found that SLC7A11 expression was increased in liver samples from patients with NASH. Upregulated SLC7A11 level was also detected in two murine NASH models. Functional studies showed that SLC7A11 knockdown or knockout had augmented steatohepatitis with suppression of inflammatory markers in mice. However, overexpression of SLC7A11 dramatically alleviated diet-induced NASH pathogenesis. Mechanically, SLC7A11 decreased reactive oxygen species (ROS) level and promoted α-ketoglutarate (αKG)/prolyl hydroxylase (PHD) activity, which activated AMPK pathway. Furthermore, SLC7A11 impaired expression of NLRP3 inflammasome components through AMPK-mitophagy axis. IL-1β release through NLRP3 inflammasome recruited myeloid cells and promoted hepatic stellate cells (HSCs) activation, which contributed to the progression of liver injury and fibrosis. Anti-IL-1β and anakinra might attenuate the hepatic inflammatory response evoked by SLC7A11 knockdown. Moreover, the upregulation of SLC7A11 in NASH was contributed by lipid overload-induced JNK-c-Jun pathway. In conclusions, SLC7A11 acts as a protective factor in controlling the development of NASH. Upregulation of SLC7A11 is protective by regulating oxidation, αKG and energy metabolism, decreasing inflammation and fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Short (SCCPs) and medium (MCCPs) chain chlorinated paraffins being the emerging organic pollutants have raised serious concerns due to their widespread use and related human health risks. However, their occurrence in aquatic bodies like rivers and associated damage to ecological integrity is yet unknown in some regions of the world. The current study is the first ever assessment of SCCPs and MCCPs in sediment and water of river Ravi, Pakistan. Spatial occurrence and associated ecological risks were investigated from sediments (n = 16) and composite water samples (n = 8) collected at eight locations along the stretch of river Ravi. The concentrations of SCCPs and MCCPs varied from below limit of detection (10,12,13 Cl 7-8 and C 14,16,17 Cl 7-8 were dominant of SCCPs and MCCPs in water and sediments, respectively. The partitioning coefficient for organic carbon (log K oc ) varied parabolically with chlorine number (P < 0.01) of SCCPs and MCCPs suggesting increased adsorption of medium chlorinated congeners in sediments. Ecological risk assessment illustrated limited effects on aquatic organism as a result of CPs exposure, however, their elevated concentrations predict ecological damage in future. Thus, in-depth investigation of CPs encompassing spatio-temporal distribution in water and sediments of rivers as well as their toxicity in aquatic organism including fish and human health is needful in future studies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest at personal and/or organizational level., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The propagation pattern of pressure drawdown effectively reflects the recoverable reserves range around the gas well and serves as a crucial basis for development strategies. However, it is not easy to detect the pressure propagation boundary near the producing well, especially in low-permeability reservoirs where the drainage radius is small. Physical simulation experiments can serve as a crucial method as the whole pressure profile and gas rate can be obtained in real time. Using long core plugs with permeabilities of 2.300 mD, 0.486 mD, and 0.046 mD, physical simulation experiments were carried out under varying initial water saturation (Swi) conditions of 0%, 20%, 40%, and 55% to observe the dynamic variations in pressure profiles of the core plugs during pressure depletion. Based on the material balance equation and pressure profile characteristics of the core plugs, a method for evaluating recoverable reserves within a well-spacing radius through laboratory experiments was proposed and performed. Mechanism analysis was conducted based on mercury injection tests, and suggestions for enhancing gas recovery were presented. Research findings indicate that lower permeability, higher initial water saturation, and higher abandonment gas rates result in reduced reserve utilization range and degree. Under abandoned gas rate conditions, for type I and II rocks, the pore radius is primarily distributed between 0.1 and 1 μm, the pressure drawdown can reach the well-spacing radius of 600 m, and the ultimate recovery efficiencies are more than 70.6%. For type III rocks, the pore radius mainly falls below 0.1 μm, the drainage radius is smaller than 10 m with Swi greater than 40%, and the ultimate recovery is below 10%. This paper provides an experimental method for recoverable reserves evaluation while formulating gas reservoir development strategies before well testing., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: This study aims to investigate the process of small cell lung cancer (SCLC) patients from achieving optimal efficacy to experiencing disease progression until death. It examines the predictive value of the treatment response on progression free survival (PFS) and overall survival (OS) of SCLC patients., Patients and Methods: We conducted a retrospective analysis on 136 SCLC patients diagnosed from 1992 to 2018. Important prognostic factors were identified to construct nomogram models. The predictive performance of the models was evaluated using the receiver operating characteristic curves and calibration curves. Survival differences between groups were compared using Kaplan-Meier survival curves. Subsequently, an independent cohort consisting of 106 SCLC patients diagnosed from 2014 to 2021 was used for validation., Results: We constructed two nomograms to predict first-line PFS (PFS1) and OS of SCLC. The area under the receiver operating characteristic curves for the PFS1 nomogram predicting PFS at 3-, 6-, and 12-months were 0.919 (95% CI: 0.867-0.970), 0.908 (95% CI: 0.860-0.956) and 0.878 (95% CI: 0.798-0.958), and for the OS nomogram predicting OS at 6-, 12-, and 24-months were 0.814 (95% CI: 0.736-0.892), 0.819 (95% CI: 0.749-0.889) and 0.809 (95% CI: 0.678-0.941), indicating those two models with a high discriminative ability. The calibration curves demonstrated the models had a high degree of consistency between predicted and observed values. According to the risk scores, patients were divided into high-risk and low-risk groups, showing a significant difference in survival rate. And these findings were validated in another independent validation cohort., Conclusion: Based on the patients' treatment response after standardized treatment, we developed and validated two nomogram models to predict PFS1 and OS of SCLC. The models demonstrated good accuracy, reliability and clinical applicability by validating in an independent cohort., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Li et al.)

Purpose: To investigate the post-operative refractive stabilisation time and provide evidence for the optimal timing of a spectacle prescription in myopic post-cataract surgery patients., Methods: A total of 116 consecutive myopic cataract patients were recruited from the Zhongshan Ophthalmic Center in this prospective study. Post-operative subjective refraction was assessed after 1 week and 1 month (4-6 weeks), with the interval for the new spectacle acquisition being recorded. Visual Function Index-14 (VF-14) questionnaires were used to assess the vision-related quality of life., Results: There was no significant difference in spherical (p = 0.33), cylindrical (p = 0.65) or spherical equivalent refractions (p = 0.45) obtained 1 week and 1 month post-operatively, indicating that subjects achieved refractive stability within 1 week. In subgroups having differing age and axial lengths, there were also no significant differences between the 1 week and 1 month findings. The spherical equivalent refractive shift between 1 week and 1 month was significantly correlated with the post-operative prediction error (R = 0.35; p < 0.001). Only five (4.3%) out of 116 patients obtained new spectacles 1 week post-surgery. The VF-14 values improved from 85.77 ± 7.24 to 90.45 ± 5.39 after acquiring new spectacles (p < 0.01)., Conclusions: The stabilisation of subjective refraction occurred within 1 week in myopic cataract patients. Shortening the interval before prescribing a new spectacle prescription is recommended for myopic patients following cataract surgery to improve their vision-related quality of life., (© 2024 College of Optometrists.)

Purpose: To develop an early diagnosis model of prostate cancer based on clinical-radiomics to improve the accuracy of imaging diagnosis of prostate cancer., Methods: The multicenter study enrolled a total of 449 patients with prostate cancer from December 2017 to January 2022. We retrospectively collected information from 342 patients who underwent prostate biopsy at Minhang Hospital. We extracted T2WI images through 3D-Slice, and used mask tools to mark the prostate area manually. The radiomics features were extracted by Python using the "Pyradiomics" module. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for data dimensionality reduction and feature selection, and the radiomics score was calculated according to the correlation coefficients. Multivariate logistic regression analysis was used to develop predictive models. We incorporated the radiomics score, PI-RADS, and clinical features, and this was presented as a nomogram. The model was validated using a cohort of 107 patients from the Xuhui Hospital., Results: In total, 110 effective radiomics features were extracted. Finally, 9 features were significantly associated with the diagnosis of prostate cancer, from which we calculated the radiomics score. The predictors contained in the individualized prediction nomogram included age, fPSA/tPSA, PI-RADS, and radiomics score. The clinical-radiomics model showed good discrimination in the validation cohort (C-index = 0.88)., Conclusion: This study presents a clinical-radiomics model that incorporates age, fPSA/PSA, PI-RADS, and radiomics score, which can be conveniently used to facilitate individualized prediction of prostate cancer before prostate biopsy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Women are less likely to receive guideline-recommended cardiovascular care, but evaluation of sex-based disparities in cardiac surgical procedures is limited. Receipt of concomitant atrial fibrillation (AF) procedures during nonmitral cardiac surgery was compared by sex for patients with preoperative AF., Methods: Patients with preoperative AF undergoing coronary artery bypass grafting and/or aortic valve replacement at any of the 33 hospitals in Michigan from 2014 to 2022 were included. Patients with prior cardiac surgery, transcatheter AF procedure, or emergency/salvage status were excluded. Hierarchical logistic regression identified predictors of concomitant AF procedures, account for hospital and surgeon as random effects., Results: Of 5460 patients with preoperative AF undergoing nonmitral cardiac surgery, 24% (n = 1291) were women with a mean age of 71 years. Women were more likely to have paroxysmal (vs persistent) AF than men (80% vs 72%; P < .001) and had a higher mean predicted risk of mortality (5% vs 3%; P < .001). The unadjusted rate of concomitant AF procedure was 59% for women and 67% for men (P < .001). After risk adjustment, women had 26% lower adjusted odds of concomitant AF procedure than men (adjusted odds ratio, 0.74; 95% CI, 0.64-0.86; P < .001). Female sex was the risk factor associated with the lowest odds of concomitant AF procedure., Conclusions: Women are less likely to receive guideline recommended concomitant AF procedure during nonmitral surgery. Identification of barriers to concomitant AF procedure in women may improve treatment of AF., Competing Interests: Conflict of Interest Statement Dr Ailawadi is a consultant for Abbott, Edwards, Medtronic, Anteris, Atricure, and Gore. All other authors reported no conflicts of interest. Support for MSTCVS-QC is provided by Blue Cross and Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program. Although BCBSM and MSTCVS-QC work collaboratively, the opinions, beliefs and viewpoints expressed by the author do not necessarily reflect the opinions, beliefs and viewpoints of BCBSM or any of its employees. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Utilizing hydrogen as a viable substitute for fossil fuels requires the exploration of hydrogen storage materials with high capacity, high quality, and effective reversibility at room temperature. In this study, the stability and capacity for hydrogen storage in the Sc-modified C 3 N 4 nanotube are thoroughly examined through the application of density functional theory (DFT). Our finding indicates that a strong coupling between the Sc-3d orbitals and N-2p orbitals stabilizes the Sc-modified C 3 N 4 nanotube at a high temperature (500 K), and the high migration barrier (5.10 eV) between adjacent Sc atoms prevents the creation of metal clusters. Particularly, it has been found that each Sc-modified C 3 N 4 nanotube is capable of adsorbing up to nine H 2 molecules, and the gravimetric hydrogen storage density is calculated to be 7.29 wt%. It reveals an average adsorption energy of -0.20 eV, with an estimated average desorption temperature of 258 K. This shows that a Sc-modified C 3 N 4 nanotube can store hydrogen at low temperatures and harness it at room temperature, which will reduce energy consumption and protect the system from high desorption temperatures. Moreover, charge donation and reverse transfer from the Sc-3d orbital to the H-1s orbital suggest the presence of the Kubas effect between the Sc-modified C 3 N 4 nanotube and H 2 molecules. We draw the conclusion that a Sc-modified C 3 N 4 nanotube exhibits exceptional potential as a stable and efficient hydrogen storage substrate.

This study used samples processed with an innovative manufacturing process to explore the dynamic changes of large-leaf yellow tea (LYT) in color, aroma, and taste substances, and the quality components were most significantly affected in the stages of first pile-yellowing (FP) and over-fired drying (TD). In this process, the moisture and temperature conditions caused chlorophyll degradation, Maillard reactions, caramelization reactions, and isomerization of phenolic substances, forming the quality of LYT. Specifically, chlorophyll degradation favored the formation of color quality; the taste quality was determined by the content of soluble sugars, amino acids, catechins, etc.; the aroma quality was dependent on the content changes of alcohols and aldehydes, as well as the increase of sweet and roasting aroma substances in the third drying stage. Additionally, twelve key aroma components, including linalool, (E)-β-ionone, 2,3-diethyl-5-methyl-pyrazine, etc., were identified as contributors to revealing LYT rice crust-like and sweet aroma formation mechanism., 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 © 2023 Elsevier Ltd. All rights reserved.)

Pharmacological strategies to delay aging and combat age-related diseases are increasingly promising. This study explores the anti-aging and therapeutic effects of two novel 18-norspirostane steroidal saponins from Trillium tschonoskii Maxim, namely deoxytrillenoside CA (DTCA) and epitrillenoside CA (ETCA), using Caenorhabditis elegans (C. elegans). Both DTCA and ETCA significantly extended the lifespan of wild-type N2 worms and improved various age-related phenotypes, including muscle health, motility, pumping rate, and lipofuscin accumulation. Furthermore, these compounds exhibited notable alleviation of pathology associated with Parkinson's disease (PD) and Huntington's disease (HD), such as the reduction of α-synuclein and poly40 aggregates, improvement in motor deficits, and mitigation of neuronal damage. Meanwhile, DTCA and ETCA improved the lifespan and healthspan of PD- and HD-like C. elegans models. Additionally, DTCA and ETCA enhanced the resilience of C. elegans against heat and oxidative stress challenges. Mechanistic studies elucidated that DTCA and ETCA induced mitophagy and promoted mitochondrial biogenesis in C. elegans, while genetic mutations or RNAi knockdown affecting mitophagy and mitochondrial biogenesis effectively eliminated their capacity to extend lifespan and reduce pathological protein aggregates. Together, these compelling findings highlight the potential of DTCA and ETCA as promising therapeutic interventions for delaying aging and preventing age-related diseases., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Our statewide thoracic quality collaborative has implemented multiple quality improvement initiatives to improve lung cancer nodal staging. We subsequently implemented a value-based reimbursement initiative to further incentivize quality improvement. We compare the impact of these programs to steer future quality improvement initiatives., Methods: Since 2016, our collaborative focused on improving lymph node staging for lung cancer by leveraging unblinded, hospital-level metrics and collaborative feedback. In 2021, a value-based reimbursement initiative was implemented with statewide yearly benchmark rates for (1) preoperative mediastinal staging for ≥T2N0 lung cancer, and (2) sampling ≥5 lymph node stations. Participating surgeons would receive additional reimbursement if either benchmark was met. We reviewed patients from January 2015 to March 2023 at the 21 participating hospitals to determine the differential effects on quality improvement., Results: We analyzed 6228 patients. In 2015, 212 (39%) patients had ≥5 nodal stations sampled, and 99 (51%) patients had appropriate preoperative mediastinal staging. During 2016 to 2020, this increased to 2253 (62%) patients and 739 (56%) patients, respectively. After 2020, 1602 (77%) patients had ≥5 nodal stations sampled, and 403 (73%) patients had appropriate preoperative mediastinal staging. Interrupted time-series analysis demonstrated significant increases in adequate nodal sampling and mediastinal staging before value-based reimbursement. Afterward, preoperative mediastinal staging rates briefly dropped but significantly increased while nodal sampling did not change., Conclusions: Collaborative quality improvement made significant progress before value-based reimbursement, which reinforces the effectiveness of leveraging unblinded data to a collaborative group of thoracic surgeons. Value-based reimbursement may still play a role within a quality collaborative to maintain infrastructure and incentivize participation., Competing Interests: Conflict of Interest Statement R.R. receives consulting fees from Intuitive, Genentech, AtriCure, Medtronic, and On Target Labs. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to investigate the association of sodium-glucose cotransporter 2 inhibitors (SGLT2i) use with cardiovascular (CV) clinical outcomes in type 2 diabetes (T2D) patients with acute coronary syndrome (ACS)., Methods: Data of T2D patients hospitalized for ACS at Civil Aviation General Hospital from January 2019 to December 2022 were collected. Based on SGLT2i use or not, patients were stratified as SGLT2i group and SGLT2i-free group. A 1:1 nearest-neighbor propensity score-matched (PSM) was performed to adjust for the confounding factors and facilitate the robust comparisons between groups. The first occurrence of major adverse cardiovascular events (MACE) with 1 year follow-up, which consisted of CV death, all cause death, non-fatal myocardial infarction or stroke, coronary revascularization or heart failure readmission, was assessed. Kaplan-Meier analysis and Cox regressions were conducted to evaluate the prognostic significance of SGLT2i use. Subgroup analyses were performed to assess the interaction between subgroups and SGLT2i use., Results: A total of 925 patients were included, and the SGLT2i use increased from 9.9% in 2019 to 43.8% in 2022. 226 pairs were finally matched using the PSM model. During 1 year follow-up period, a total of 110 patients experienced MACE in the matched cohort, with a rate of 24.3%. Survival analyses showed cumulative incidence of MACE, CV death, and heart failure readmission in the SGLT2i group were significantly lower than the SGLT2i-free group. Additionally, the adjusted Cox analyses demonstrated that SGLT2i was associated with a 34.1% lower risk of MACE (HR 0.659, 95% CI 0.487-0.892, P = 0.007), which was primarily driven by a decrease in the risk of CV death by 12.0% (HR 0.880, 95% CI 0.7830.990, P = 0.033), and heart failure readmission by 45.5% (HR 0.545, 95% CI 0.332-0.893, P = 0.016). This MACE preventive benefit was consistent across different subgroups (P interaction > 0.05 for all comparisons)., Conclusions: In T2D patients with ACS, there was a clear increasing trend in SGLT2i use. SGLT2i was associated with a significantly lower risk of MACE, driven by the decrease in the risk of CV death, and heart failure readmission. Our study confirmed real-world use and efficacy of SGLT2i in a general T2D population with ACS., (© 2024. The Author(s).)

The mechanical characteristics of graphene ribbons with an attached proof mass that can be used as NEMS transducers have been minimally studied, which hinders the development of graphene-based NEMS devices. Here, we simulated the mechanical characteristics of graphene ribbons with an attached proof mass using the finite element method. We studied the impact of force, residual stress, and geometrical size on displacement, strain, resonant frequency, and fracture strength of graphene ribbons with an attached proof mass. The results show that the increase of width and thickness of graphene ribbons would result in a decrease of the displacement and strain but also an increase of resonant frequency. The increase of the length of graphene ribbons has an insignificant impact on the strain, but it could increase the displacement and decrease the resonant frequency. The increase of residual stress in the graphene ribbons decreases its strain and displacement. The estimated fracture strength of graphene shows limited dependence on its thickness, with an estimated value of around 148 GPa. These findings contribute to the understanding of the mechanical characteristics of graphene ribbons with an attached proof mass and lay the solid foundation for the design and manufacture of high-performance graphene-based NEMS devices such as accelerometers.