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Purpose: This study aimed to investigate the microbiological characteristics of clinically isolated Staphylococcus aureus with different hemolytic phenotypes in China., Materials and Methods: Using the three-point inoculation method, the hemolytic phenotypes of 1295 clinically isolated S. aureus strains were detected and categorized. Antimicrobial susceptibility testing of all strains was performed using a VITEK 2 Compact System. After sample size matching, plasma coagulase activity, catalase activity, mRNA expression of hemolysin genes ( hla, hlb, hlc , and hld ), biofilm formation, growth kinetics, inflammatory response of macrophages and cytotoxicity of S. aureus with different hemolytic phenotypes using the rabbit plasma kit, the catalase test on slides, qRT-PCR, crystal violet staining, the microcultivation assay, the ELISA kits, and the CCK-8 assay, respectively., Results: Seven categories of hemolytic phenotypes were identified. Accordingly, strains were categorized into seven different groups, including S. aureus with complete hemolytic phenotype (SCHP), S. aureus with weak hemolytic phenotype (SWHP), S. aureus with incomplete hemolytic phenotype 1 (SIHP-1), SIHP-2, SIHP-3, SIHP-4 and SIHP-5, the last three of which were reported for the first time. Except for the hemolytic phenotype, all seven groups differed in clinical isolation rates, antibiotic resistance profile, plasma coagulase activity, mRNA expression of hemolysin genes, biofilm formation, growth kinetics, inflammatory response of macrophages, and cytotoxicity., Conclusion: S. aureus with different hemolytic phenotypes have distinctive microbiological characteristics. Clinical microbiologists need to be vigilant about the hemolytic phenotypes when culturing S. aureus strains, and actively enhance communication with clinicians to optimize the treatment of infection., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Tang et al.)

Background: Ubiquitination is an enzymatic modification involving ubiquitin chains, that can be reversed by deubiquitination (DUB) enzymes. Ubiquitin-specific protease 7 (USP7), which is also known as herpes virus-associated ubiquitin-specific protease (HAUSP), has been shown to play a vital role in cardiovascular diseases. However, the underlying molecular mechanism by which USP7 regulates cardiomyocyte function has not been reported., Methods: To understand the physiological function of USP7 in the heart, we constructed cardiomyocyte-specific USP7 conditional knockout mice., Results: We found that homozygous knockout mice died approximately three weeks after birth, while heterozygous knockout mice grew normally into adulthood. Severe cardiac dysfunction, hypertrophy, fibrosis, and cell apoptosis were observed in cardiomyocyte-specific USP7 knockout mice, and these effects were accompanied by disordered mitochondrial dynamics and cardiometabolic-related proteins., Conclusions: In summary, we investigated changes in the growth status and cardiac function of cardiomyocyte-specific USP7 knockout mice, and preliminarily explored the underlying mechanism., Competing Interests: Declaration of competing interest Authors declared that there were no known conflicts of interest associated with this publication., (Copyright © 2024. Published by Elsevier B.V.)

Objective: We aimed to evaluate the mitral valve calcification and mitral structure detected by cardiac computed tomography (cardiac CT) and establish a scoring model based on cardiac CT and clinical factors to predict early good mitral valve repair (EGMR) and guide surgical strategy in rheumatic mitral disease (RMD)., Materials and Methods: This is a retrospective bi-center cohort study. Based on cardiac CT, mitral valve calcification and mitral structure in RMD were quantified and evaluated. The primary outcome was EGMR. A logical regression algorithm was applied to the scoring model., Results: A total of 579 patients were enrolled in our study from January 1, 2019, to August 31, 2022. Of these, 443 had baseline cardiac CT scans of adequate quality. The calcification quality score, calcification and thinnest part of the anterior leaflet clean zone, and papillary muscle symmetry were the independent CT factors of EGMR. Coronary artery disease and pulmonary artery pressure were the independent clinical factors of EGMR. Based on the above six factors, a scoring model was established. Sensitivity = 95% and specificity = 95% were presented with a cutoff value of 0.85 and 0.30 respectively. The area under the receiver operating characteristic of external validation set was 0.84 (95% confidence interval [CI] 0.73-0.93)., Conclusions: Mitral valve repair is recommended when the scoring model value > 0.85 and mitral valve replacement is prior when the scoring model value < 0.30. This model could assist in guiding surgical strategies for RMD., Clinical Relevance Statement: The model established in this study can serve as a reference indicator for surgical repair in rheumatic mitral valve disease., Key Points: • Cardiac CT can reflect the mitral structure in detail, especially for valve calcification. • A model based on cardiac CT and clinical factors for predicting early good mitral valve repair was established. • The developed model can help cardiac surgeons formulate appropriate surgical strategies., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Conductive metal-organic frameworks (c-MOFs) and ionic liquids (ILs) have emerged as auspicious combinations for high-performance supercapacitors. However, the nanoconfinement from c-MOFs and high viscosity of ILs slow down the charging process. This hindrance can, however, be resolved by adding solvent. Here, constant-potential molecular simulations are performed to scrutinize the solvent impact on charge storage and charging dynamics of MOF-IL-based supercapacitors. Conditions for >100% enhancement in capacity and ≈6 times increase in charging speed are found. These improvements are confirmed by synthesizing near-ideal c-MOFs and developing multiscale models linking molecular simulations to electrochemical measurements. Fundamentally, the findings elucidate that the solvent acts as an "ionophobic agent" to induce a substantial enhancement in charge storage, and as an "ion traffic police" to eliminate convoluted counterion and co-ion motion paths and create two distinct ion transport highways to accelerate charging dynamics. This work paves the way for the optimal design of MOF supercapacitors., (© 2024 Wiley‐VCH GmbH.)

Diabetic cardiomyopathy (DCM) is a major complication of diabetes and is characterized by left ventricular dysfunction. Currently, there is a lack of effective treatments for DCM. Ubiquitin-specific protease 7 (USP7) plays a key role in various diseases. However, whether USP7 is involved in DCM has not been established. In this study, we demonstrated that USP7 was upregulated in diabetic mouse hearts and NMCMs co-treated with HG+PA or H9c2 cells treated with PA. Abnormalities in diabetic heart morphology and function were reversed by USP7 silencing through conditional gene knockout or chemical inhibition. Proteomic analysis coupled with biochemical validation confirmed that PCG1β was one of the direct protein substrates of USP7 and aggravated myocardial damage through coactivation of the PPARα signaling pathway. USP7 silencing restored the expression of fatty acid metabolism-related proteins and restored mitochondrial homeostasis by inhibiting mitochondrial fission and promoting fusion events. Similar effects were also observed in vitro. Our data demonstrated that USP7 promoted cardiometabolic metabolism disorders and mitochondrial homeostasis dysfunction via stabilizing PCG1β and suggested that silencing USP7 may be a therapeutic strategy for DCM., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The essence of compartmentalization in cells is the inspiration behind the engineering of synthetic counterparts, which has emerged as a significant engineering theme. Here, we report the formation of ultra-stable water-in-water (W/W) emulsion droplets. These W/W droplets demonstrate previously unattained stability across a broad pH spectrum and exhibit resilience at temperatures up to 80℃, overcoming the challenge of insufficient robustness in dispersed droplets of aqueous two-phase systems (ATPS). The exceptional robustness is attributed to the strong anchoring of micelle-like casein colloidal particles at the PEO/DEX interface, which maintains stability under varying environmental conditions. The increased surface hydrophobicity of these particles at high temperatures contributes to the formation of thermally-stable droplets, enduring temperatures as high as 80℃. Furthermore, our study illustrates the adaptable affinity of micelle-like casein colloidal particles towards the PEO/DEX-rich phase, enabling the formation of stable DEX-in-PEO emulsions at lower pH levels, and PEO-in-DEX emulsions as the pH rises above the isoelectric point. The robust nature of these W/W emulsions unlocks new possibilities for exploring various biochemical reactions within synthetic subcellular modules and lays a solid foundation for the development of novel biomimetic materials., 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.)

Yarn-woven triboelectric nanogenerators (TENGs) have greatly advanced wearable sensor technology, but their limited sensitivity and stability hinder broad adoption. To address these limitations, Poly(VDF-TrFE) and P(olyadiohexylenediamine (PA66)-based nanofibers coaxial yarns (NCYs) combining coaxial conjugated electrospinning and online conductive adhesive coating are developed. The integration of these NCYs led to enhanced TENGs (NCY-TENGs), notable for their flexibility, stretchability, and improved sensitivity, which is ideal for capturing body motion signals. One significant application of this technology is the fabrication of smart insoles from NCY-TENG plain-woven fabrics. These insoles are highly sensitive and possess antibacterial, breathable, and washable properties, making them ideal for real-time gait monitoring in patients with diabetic foot conditions. The NCY-TENGs and their derivatives show immense potential for a variety of wearable electronic devices, representing a considerable advancement in the field of wearable sensors., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Although previous studies have suggested that subtype B HIV-1 proviruses in the brain are associated with physiological changes and immune activation accompanied with microgliosis and astrogliosis, and indicated that both HIV-1 subtype variation and geographical location might influence the neuropathogenicity of HIV-1 in the brain. The natural course of neuropathogenesis of the most widespread subtype C HIV-1 has not been adequately investigated, especially for people living with HIV (PLWH) in sub-Saharan Africa. To characterize the natural neuropathology of subtype C HIV-1, postmortem frontal lobe and basal ganglia tissues were collected from nine ART-naïve individuals who died of late-stage AIDS with subtype C HIV-1 infection, and eight uninfected deceased individuals as controls. Histological staining was performed on all brain tissues to assess brain pathologies. Immunohistochemistry (IHC) against CD4, p24, Iba-1, GFAP, and CD8 in all brain tissues was conducted to evaluate potential viral production and immune activation. Histological results showed mild perivascular cuffs of lymphocytes only in a minority of the infected individuals. Viral capsid p24 protein was only detected in circulating immune cells of one infected individual, suggesting a lack of productive HIV-1 infection of the brain even at the late-stage of AIDS. Notably, similar levels of Iba-1 or GFAP between HIV + and HIV- brain tissues indicated a lack of microgliosis and astrogliosis, respectively. Similar levels of CD8 + cytotoxic T lymphocyte (CTL) infiltration between HIV + and HIV- brain tissues indicated CTL were not likely to be involved within subtype C HIV-1 infected participants of this cohort. Results from this subtype C HIV-1 study suggest that there is a lack of productive infection and limited neuropathogenesis by subtype C HIV-1 even at late-stage disease, which is in contrast to what was reported for subtype B HIV-1 by other investigators., (© 2024. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)

This study aimed to systematically evaluate the efficacy of liraglutide in treating type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) by comparing liraglutide with placebo or other drugs (mainly insulin). The PubMed, Web of Science, and National Library of Medicine databases were systematically searched from their inception until December 1, 2023. A meta-analysis was performed using Stata 15.1 software. A total of 12 studies with 13 outcome measures were included. The meta-analysis results revealed that liraglutide significantly reduced body mass index (mean difference [MD] = -1.06, 95%CI: -1.41, -0.70, p < 0.001), triglycerides (MD = -0.35, 95%CI: -0.61, -0.09, p = 0.0009), visceral adipose tissue (MD = -21.06, 95%CI: -34.58, -7.55, p = 0.002), and subcutaneous adipose tissue (MD = -20.53, 95%CI: -29.15, -11.90, p < 0.001) levels in patients with T2DM and NAFLD. Of the 11 studies, 2 reported the occurrence of adverse reactions, which were primarily gastrointestinal. Compared with placebo and other drugs (e.g., insulin), liraglutide may improve glucose metabolism, lipid and liver function parameters, and visceral and subcutaneous fat in patients with T2DM and NAFLD, thus constituting an effective treatment for these patients.

The involvement of Interferon-stimulated exonuclease gene 20 (ISG20) has been reported in renal clear cell carcinoma, hepatocellular carcinoma, and cervical cancer. However, its role in ovarian cancer chemotherapy remains unclear. In this study, we conducted a comparative analysis of TGF-β1 and ISG20 in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells and tissues using qRT-PCR and a tissue immunofluorescence analysis. We also investigated the impact of ISG20-targeted drugs (IFN-γ) and TGF-β1 inhibitors on cisplatin response both in vivo and in vitro. Additionally, we assessed the effects of TGF-β1 or ISG20 on the polarization of tumor-associated macrophages through flow cytometry and ELISA analysis. Our findings revealed that ISG20 expression was lower in cisplatin-resistant tissues compared to cisplatin-sensitive tissues; however, overexpression of ISG20 sensitized ovarian cancer to cisplatin treatment. Furthermore, activation of ISG20 expression with IFN-γ or TGF-β1 inhibitors enhanced the sensitivity of ovarian cancer cells to cisplatin therapy. Notably, our results demonstrated that TGF-β1 promoted M2-type macrophage polarization as well as PI3K/mTOR pathway activation by suppressing ISG20 expression both in vivo and in vitro. In conclusion, our study highlights the critical role played by ISG20 within the network underlying cisplatin resistance in ovarian cancer. Targeting ISG20 using IFN-γ or TGF-β1 inhibitors may represent a promising therapeutic strategy for treating ovarian cancer., 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.)

Perovskite/silicon tandem solar cells hold great promise for realizing high power conversion efficiency at low cost. However, achieving scalable fabrication of wide-bandgap perovskite (~1.68 eV) in air, without the protective environment of an inert atmosphere, remains challenging due to moisture-induced degradation of perovskite films. Herein, this study reveals that the extent of moisture interference is significantly influenced by the properties of solvent. We further demonstrate that n-Butanol (nBA), with its low polarity and moderate volatilization rate, not only mitigates the detrimental effects of moisture in air during scalable fabrication but also enhances the uniformity of perovskite films. This approach enables us to achieve an impressive efficiency of 29.4% (certified 28.7%) for double-sided textured perovskite/silicon tandem cells featuring large-size pyramids (2-3 μm) and 26.3% over an aperture area of 16 cm 2 . This advance provides a route for large-scale production of perovskite/silicon tandem solar cells, marking a significant stride toward their commercial viability., (© 2024. The Author(s).)

Biofilms produced by Candida albicans present a challenge in treatment with antifungal drug. Enhancing the sensitivity to fluconazole (FLC) is a reasonable method for treating FLC-resistant species. Moreover, several lines of evidence have demonstrated that berberine (BBR) can have antimicrobial effects. The aim of this study was to clarify the underlying mechanism of these effects. We conducted a comparative study of the inhibition of FLC-resistant strain growth by FLC treatment alone, BBR treatment alone, and the synergistic effect of combined FLC and BBR treatment. Twenty-four isolated strains showed distinct biofilm formation capabilities. The antifungal effect of combined FLC and BBR treatment in terms of the growth and biofilm formation of Candida albicans species was determined via checkerboard, time-kill, and fluorescence microscopy assays. The synergistic effect of BBR and FLC downregulated the expression of the efflux pump genes CDR1 and MDR, the hyphal gene HWP1, and the adhesion gene ALS3; however, the gene expression of the transcriptional repressor TUP1 was upregulated following treatment with this drug combination. Furthermore, the addition of BBR led to a marked reduction in cell surface hydrophobicity. To identify resistance-related genes and virulence factors through genome-wide sequencing analysis, we investigated the inhibition of related resistance gene expression by the combination of BBR and FLC, as well as the associated signaling pathways and metabolic pathways. The KEGG metabolic map showed that the metabolic genes in this strain are mainly involved in amino acid and carbon metabolism. The metabolic pathway map showed that several ergosterol (ERG) genes were involved in the synthesis of cell membrane sterols, which may be related to drug resistance. In this study, BBR + FLC combination treatment upregulated the expression of the ERG1, ERG3, ERG4, ERG5, ERG24, and ERG25 genes and downregulated the expression of the ERG6 and ERG9 genes compared with fluconazole treatment alone (p < 0.05)., (© 2024. The Author(s).)

Background: Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia, including Alzheimer's dementia, vascular dementia, and dementia in other diseases classified elsewhere. However, the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain unclear., Aim: To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization (MR) analysis., Methods: A bidirectional, two-sample, MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study (GWAS) summary data from the MiBioGen consortium alongside GWAS summary statistics for dementia and its subtypes from the FinnGen consortium. Instrumental variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the F -statistic. Five MR methods were employed, and the robustness of our findings was validated. To account for multiple comparisons, we applied the Bonferroni method for P -value adjustment., Results: We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes, potentially serving as risk or protective factors for the disease. In addition, reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its subtypes. An exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal pleiotropy. After applying correction for multiple testing, we observed that the order Bacillales (odds ratio: 0.830, 95% confidence interval: 0.740-0.932, P = 0.00155, P adjust = 0.0311) exhibited a strong association with Alzheimer's disease-related dementia., Conclusion: The results suggest that gut microbiota is causally associated with dementia. Our findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aims: Although there are various model-based approaches to individualized vancomycin (VCM) administration, few have been reported for adult patients with periprosthetic joint infection (PJI). This work attempted to develop a machine learning (ML)-based model for predicting VCM trough concentration in adult PJI patients., Methods: The dataset of 287 VCM trough concentrations from 130 adult PJI patients was split into a training set (229) and a testing set (58) at a ratio of 8:2, and an independent external 32 concentrations were collected as a validation set. A total of 13 covariates and the target variable (VCM trough concentration) were included in the dataset. A covariate model was respectively constructed by support vector regression, random forest regression and gradient boosted regression trees and interpreted by SHapley Additive exPlanation (SHAP)., Results: The SHAP plots visualized the weight of the covariates in the models, with estimated glomerular filtration rate and VCM daily dose as the 2 most important factors, which were adopted for the model construction. Random forest regression was the optimal ML algorithm with a relative accuracy of 82.8% and absolute accuracy of 67.2% (R 2  =.61, mean absolute error = 2.4, mean square error = 10.1), and its prediction performance was verified in the validation set., Conclusion: The proposed ML-based model can satisfactorily predict the VCM trough concentration in adult PJI patients. Its construction can be facilitated with only 2 clinical parameters (estimated glomerular filtration rate and VCM daily dose), and prediction accuracy can be rationalized by SHAP values, which highlights a profound practical value for clinical dosing guidance and timely treatment., (© 2024 British Pharmacological Society.)

Bacterial cellulose/oxidized bacterial cellulose nanofibrils (BC/oxBCNFs) macro-fibers are developed as a novel scaffold for vascular tissue engineering. Utilizing a low-speed rotary coagulation spinning technique and precise solvent control, macro-fibers with a unique heterogeneous structure with dense surface and porous core are created. Enhanced by a polydopamine (PDA) coating, these macro-fibers offer robust mechanical integrity, high biocompatibility, and excellent cell adhesion. When cultured with endothelial cells (ECs) and smooth muscle cells (SMCs), the macro-fibers support healthy cell proliferation and exhibit a unique spiral SMC alignment, demonstrating their vascular suitability. This innovative strategy opens new avenues for advances in tissue engineering., (© 2024 Wiley‐VCH GmbH.)

Deep sowing is an efficient strategy for maize to ensure the seedling emergence rate under adverse conditions such as drought or low temperatures. However, the genetic basis of deep-sowing tolerance-related traits in maize remains largely unknown. In this study, we performed a genome-wide association study on traits related to deep-sowing tolerance, including mesocotyl length (ML), coleoptile length (CL), plumule length (PL), shoot length (SL), and primary root length (PRL), using 255 maize inbred lines grown in three different environments. We identified 23, 6, 4, and 4 quantitative trait loci (QTLs) associated with ML, CL, PL, and SL, respectively. By analyzing candidate genes within these QTLs, we found a γ-tubulin-containing complex protein, ZmGCP2 , which was significantly associated with ML, PL, and SL. Loss of function of ZmGCP2 resulted in decreased PL, possibly by affecting the cell elongation, thus affecting SL. Additionally, we identified superior haplotypes and allelic variations of ZmGCP2 with a longer PL and SL, which may be useful for breeding varieties with deep-sowing tolerance to improve maize cultivation.

Background: The stem or progenitor antecedents confer developmental plasticity and unique cell identities to cancer cells via genetic and epigenetic programs. A comprehensive characterization and mapping of the cell-of-origin of breast cancer using novel technologies to unveil novel subtype-specific therapeutic targets is still absent. Methods: We integrated 195,144 high-quality cells from normal breast tissues and 406,501 high-quality cells from primary breast cancer samples to create a large-scale single-cell atlas of human normal and cancerous breasts. Potential heterogeneous origin of malignant cells was explored by contrasting cancer cells against reference normal epithelial cells. Multi-omics analyses and both in vitro and in vivo experiments were performed to screen and validate potential subtype-specific treatment targets. Novel biomarkers of identified immune and stromal cell subpopulations were validated by immunohistochemistry in our cohort. Results: Tumor stratification based on cancer cell-of-origin patterns correlated with clinical outcomes, genomic aberrations and diverse microenvironment constitutions. We found that the luminal progenitor (LP) subtype was robustly associated with poor prognosis, genomic instability and dysfunctional immune microenvironment. However, the LP subtype patients were sensitive to neoadjuvant chemotherapy (NAC), PARP inhibitors (PARPi) and immunotherapy. The LP subtype-specific target PLK1 was investigated by both in vitro and in vivo experiments. Besides, large-scale single-cell profiling of breast cancer inspired us to identify a range of clinically relevant immune and stromal cell subpopulations, including subsets of innate lymphoid cells (ILCs), macrophages and endothelial cells. Conclusion: The present single-cell study revealed the cellular repertoire and cell-of-origin patterns of breast cancer. Combining single-cell and bulk transcriptome data, we elucidated the evolution mimicry from normal to malignant subtypes and expounded the LP subtype with vital clinical implications. Novel immune and stromal cell subpopulations of breast cancer identified in our study could be potential therapeutic targets. Taken together, Our findings lay the foundation for the precise prognostic and therapeutic stratification of breast cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Gestational diabetes mellitus (GDM) is a highly prevalent disease and poses a significant risk to the health of pregnant women. Abdominal adipose tissue (AT) contributes to insulin resistance (IR) associated with GDM. However, the underlying mechanisms remain unclear., Methods: In this study, we developed a mouse model of GDM by subjecting mice to a high-fat diet. We collected adipose-derived stem cells (ADSCs) from the abdominal and inguinal regions and examined their role in inducing IR in normal tissues through the secretion of small extracellular vesicles (sEVs). The sEVs derived from ADSCs isolated from GDM mice (ADSC/GDM) were found to inhibit cell viability and insulin sensitivity in AML12, a normal mouse liver cell line., Results: Through proteomic analysis, we identified high levels of the thrombospondin 1 (Thbs1) protein in the sEVs derived from ADSC/GDM. Subsequent overexpression of Thbs1 protein in AML12 cells demonstrated similar IR as observed with ADSC/GDM-derived sEVs. Mechanistically, the Thbs1 protein within the sEVs interacted with CD36 and transforming growth factor (Tgf) β receptors in AML12 cells, leading to the activation of Tgfβ/Smad2 signaling. Furthermore, the administration of LSKL, an antagonistic peptide targeting Thbs1, suppressed Thbs1 expression in ADSC/GDM-derived sEVs, thereby restoring insulin sensitivity in AML12 cells and GDM mice in vivo., Conclusions: These findings shed light on the intercellular transmission mechanism through which ADSCs influence hepatic insulin sensitivity and underscore the therapeutic potential of targeting the Thbs1 protein within sEVs., (© 2024. The Author(s).)

The relationship between the Systemic Inflammatory Response Index (SIRI) and the Fibrinogen-to-albumin ratio (FAR) has not been extensively investigated. The objective of this study was to determine the independent relationship between FAR and SIRI in people with osteoporotic fractures (OPF). A cross-sectional study was conducted using retrospective data from 3431 hospitalized OPF patients. The exposure variable in this study was the baseline FAR, while the outcome variable was the SIRI. Covariates, including age, gender, BMI, and other clinical and laboratory factors, were adjusted. Cross-correlation analysis and linear regression models were applied. The generalized additive model (GAM) investigated non-linear relationships. Adjusted analysis revealed an independent negative association between FAR and SIRI in OPF patients (β = - 0.114, p = 0.00064, 95% CI - 0.180, - 0.049). A substantial U-shaped association between FAR and SIRI was shown using GAM analysis (p < 0.001). FAR and SIRI indicated a negative association for FAR below 6.344% and a positive correlation for FAR over 6.344%. The results of our study revealed a U-shaped relationship between SIRI and FAR. The lowest conceivable FAR for a bone-loose inflammatory disease might be 6.344%, suggesting that this has particular significance for the medical diagnosis and therapy of persons with OPF. Consequently, the term "inflammatory trough" is proposed. These results offer fresh perspectives on controlling inflammation in individuals with OPF and preventing inflammatory osteoporosis., (© 2024. The Author(s).)

Objective: Our aim was to develop and validate a nomogram for predicting the in-hospital 14-day (14 d) and 28-day (28 d) survival rates of patients with coronavirus disease 2019 (COVID-19)., Methods: Clinical data of patients with COVID-19 admitted to the Renmin Hospital of Wuhan University from December 2022 to February 2023 and the north campus of Shanghai Ninth People's Hospital from April 2022 to June 2022 were collected. A total of 408 patients from Renmin Hospital of Wuhan University were selected as the training cohort, and 151 patients from Shanghai Ninth People's Hospital were selected as the verification cohort. Independent variables were screened using Cox regression analysis, and a nomogram was constructed using R software. The prediction accuracy of the nomogram was evaluated using the receiver operating characteristic (ROC) curve, C-index, and calibration curve. Decision curve analysis was used to evaluate the clinical application value of the model. The nomogram was externally validated using a validation cohort., Result: In total, 559 patients with severe/critical COVID-19 were included in this study, of whom 179 (32.02 %) died. Multivariate Cox regression analysis showed that age >80 years [hazard ratio ( HR ) = 1.539, 95 % confidence interval ( CI ): 1.027-2.306, P  = 0.037], history of diabetes ( HR  = 1.741, 95 % CI : 1.253-2.420, P  = 0.001), high APACHE II score ( HR  = 1.083, 95 % CI : 1.042-1.126, P  < 0.001), sepsis ( HR  = 2.387, 95 % CI : 1.707-3.338, P  < 0.001), high neutrophil-to-lymphocyte ratio (NLR) ( HR  = 1.010, 95 % CI : 1.003-1.017, P  = 0.007), and high D-dimer level ( HR  = 1.005, 95 % CI : 1.001-1.009, P  = 0.028) were independent risk factors for 14 d and 28 d survival rates, whereas COVID-19 vaccination ( HR  = 0.625, 95 % CI : 0.440-0.886, P  = 0.008) was a protective factor affecting prognosis. ROC curve analysis showed that the area under the curve (AUC) of the 14 d and 28 d hospital survival rates in the training cohort was 0.765 ( 95 % CI : 0.641-0.923) and 0.814 ( 95 % CI : 0.702-0.938), respectively, and the AUC of the 14 d and 28 d hospital survival rates in the verification cohort was 0.898 ( 95 % CI : 0.765-0.962) and 0.875 ( 95 % CI : 0.741-0.945), respectively. The calibration curves of 14 d and 28 d hospital survival showed that the predicted probability of the model agreed well with the actual probability. Decision curve analysis (DCA) showed that the nomogram has high clinical application value., Conclusion: In-hospital survival rates of patients with COVID-19 were predicted using a nomogram, which will help clinicians in make appropriate clinical decisions., Competing Interests: 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., (© 2024 The Authors.)

Background: Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis's effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored., Methods: To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1β, IL-6, IL-10, and TGF-β1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use., Results: The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1β and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower., Conclusions: Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease that is substantially associated with obesity-induced chronic inflammation. Macrophage activation and macrophage-medicated inflammation play crucial roles in the development and progression of NAFLD. Furthermore, fibroblast growth factor receptor 1 (FGFR1) has been shown to be essentially involved in macrophage activation. This study investigated the role of FGFR1 in the NAFLD pathogenesis and indicated that a high-fat diet (HFD) increased p-FGFR1 levels in the mouse liver, which is associated with increased macrophage infiltration. In addition, macrophage-specific FGFR1 knockout or administration of FGFR1 inhibitor markedly protected the liver from HFD-induced lipid accumulation, fibrosis, and inflammatory responses. The mechanistic study showed that macrophage-specific FGFR1 knockout alleviated HFD-induced liver inflammation by suppressing the activation of MAPKs and TNF signaling pathways and reduced fat deposition in hepatocytes, thereby inhibiting the activation of hepatic stellate cells. In conclusion, the results of this research revealed that FGFR1 could protect the liver of HFD-fed mice by inhibiting MAPKs/TNF-mediated inflammatory responses in macrophages. Therefore, FGFR1 can be employed as a target to prevent the development and progression of NAFLD., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The aim of this study was to investigate the prognostic factors of haploid hematopoietic stem cell transplantation in the treatment of X-linked lymphoproliferative syndrome. Seven children with X-linked lymphoproliferative syndrome diagnosed by XIAP gene analysis were enrolled. The conditioning regimens were tolerated in all seven patients, and the median time of neutrophil engraftment was 10 days (8-13 days), and that of platelet engraftment was 21 days (14-24 days). STR-PCR analysis on the peripheral blood cells showed complete donor origins. Four cases developed Grade I acute graft versus host disease (aGVHD), one developed Grade III aGVHD (intestinal tract), and two cases had limited chronic GVHD. Four cases had cytomegalovirus (CMV) reactivation, and two cases had Epstein-Barr virus (EBV) reactivation. One case was diagnosed as pneumocystosis, and thrombotic microangiopathy (TMA) occurred in three cases. During the follow-up period (median time of 42 months), one patient died of TMA and six patients survived. Statistical analysis showed that the status of disease remission and the positive result of virus in blood before transplantation were independent prognostic factors. Haplo-HSCT might be a curative option for children with refractory X-linked lymphoproliferative syndrome. Low-intensity conditioning regimens may reduce transplant-related mortality and improve overall survival., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Background: Impaired glucose utilization influences myocardial contractile function. However, the prognostic importance of left ventricular global radial strain (LV-GRS), left ventricular global circumferential strain (LV-GCS), and left ventricular global longitudinal strain (LV-GLS) in predicting new-onset heart failure (HF) in a population with diabetes is unclear., Methods: The study design is prospective cohort from the UK Biobank. Totally 37,899 participants had a complete data of cardiac magnetic resonance (CMR), of which 940 patients with diabetes were included, and all the participants completed follow-up. LV-GRS, LV-GCS, and LV-GLS were measured by completely automated CMR with tissue tagging. Cox proportional hazards regression analysis and C-index was performed to evaluate the association between the strain parameters and the new-onset HF in patients suffering from diabetes., Results: The average age of the 940 participants was 57.67 ± 6.97 years, with males comprising 66.4% of the overall population. With an average follow-up period of 166.82 ± 15.26 months, 35 (3.72%) patients reached the endpoint (emergence of new-onset HF). Significant associations were found for the three strain parameters and the new-onset HF (LV-GRS-hazard ratio [HR]: 0.946, 95% CI: 0.916-0.976; LV-GCS-HR: 1.162, 95% CI: 1.086-1.244; LV-GCS-HR: 1.181, 95% CI: 1.082-1.289). LV-GRS, LV-GCS, and LV-GLS were closely related to the related indicators to HF, and showed a high relationship to new-onset HF in individuals with diabetes at 5 and 10 years: LV-GRS: 0.75 (95% CI, 0.41-0.94) and 0.76 (95% CI, 0.44-0.98), respectively; LV-GCS: 0.80 (95% CI, 0.50-0.96) and 0.75 (95% CI, 0.41-0.98), respectively; LV-GLS: 0.72 (95% CI, 0.40-0.93) and 0.76 (95% CI, 0.48-0.97), respectively. In addition, age, sex, body mass index (BMI), and presence of hypertension or coronary artery disease (CAD) made no impacts on the association between the global strain parameters and the incidence of HF., Conclusion: LV-GRS, LV-GCS, and LV-GLS is significantly related to new-onset HF in patients with diabetes at 5 and 10 years., 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 Chen, Chen, Zheng, Cheng, Bu and Liu.)

Background: Cancer-associated cachexia is a multi-organ disorder associated with progressive weight loss due to a variable combination of anorexia, systemic inflammation and excessive energy wasting. Considering the importance of immunoregulation in cachexia, it still lacks a complete understanding of the immunological mechanisms in cachectic progression., Aim of Review: Our aim here is to describe the complex immunoregulatory system in cachexia. We summarize the effects and translational potential of the immune system on the development of cancer-associated cachexia and we attempt to conclude with thoughts on precise and integrated therapeutic strategies under the complex immunological context of cachexia., Key Scientific Concepts of Review: This review is focused on three main key concepts. First, we highlight the inflammatory factors and additional mediators that have been identified to modulate this syndrome. Second, we decipher the potential role of immune checkpoints in tissue wasting. Third, we discuss the multilayered insights in cachexia through the immunometabolic axis, immune-gut axis and immune-nerve axis., 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. Production and hosting by Elsevier B.V.)

Universal stress proteins are a class of proteins widely present in bacteria, archaea, plants, and invertebrates, playing essential roles in bacterial adaptation to various environmental stresses. The functions of bacterial universal stress proteins are versatile, including resistance to oxidative stress, maintenance of cell wall integrity, DNA damage repair, regulation of cell division and growth, among others. When facing stresses such as temperature changes, pH shifts, fluctuations in oxygen concentration, and exposure to toxins, these proteins can bind to specific DNA sequences and rapidly adjust bacterial metabolic pathways and gene expression patterns to adapt to the new environment. In summary, bacterial universal stress proteins play a crucial role in bacterial adaptability and survival. A comprehensive understanding of bacterial stress response mechanisms and the development of new antibacterial strategies are of great significance. This review summarizes the research progress on the structure, function, and regulatory factors of universal stress proteins in clinically relevant bacteria, aiming to facilitate deeper investigations by clinicians and researchers into universal stress proteins., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To investigate how vault and other biometric variations affect postoperative refractive error of implantable collamer lenses (ICLs) by integrating artificial intelligence and modified vergence formula., Setting: Eye and ENT Hospital of Fudan University, Shanghai, China., Design: Artificial intelligence and big data-based prediction model., Methods: 2845 eyes that underwent uneventful spherical ICL or toric ICL implantation and with manifest refraction results 1 month postoperatively were included. 1 eye of each patient was randomly included. Random forest was used to calculate the postoperative sphere, cylinder, and spherical equivalent by inputting variable ocular parameters. The influence of predicted vault and modified Holladay formula on predicting postoperative refractive error was analyzed. Subgroup analysis of ideal vault (0.25 to 0.75 mm) and extreme vault (<0.25 mm or >0.75 mm) was performed., Results: In the test set of both ICLs, all the random forest-based models significantly improved the accuracy of predicting postoperative sphere compared with the Online Calculation & Ordering System calculator ( P < .001). For ideal vault, the combination of modified Holladay formula in spherical ICL exhibited highest accuracy ( R = 0.606). For extreme vault, the combination of predicted vault in spherical ICL enhanced R values ( R = 0.864). The combination of predicted vault and modified Holladay formula was most optimal for toric ICL in all ranges of vault (ideal vault: R = 0.516, extreme vault: R = 0.334)., Conclusions: The random forest-based calculator, considering vault and variable ocular parameters, illustrated superiority over the existing calculator on the study datasets. Choosing an appropriate lens size to control the vault within the ideal range was helpful to avoid refractive surprises., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Background: Diabetic individuals often encounter various sleep-related challenges. Although the association between sleep duration and atrial fibrillation (AF) have been explored, the association of other sleep traits with the incidence of AF remains unclear. A comprehensive understanding of these traits is essential for a more accurate assessment of sleep conditions in patients with diabetes and the development of novel AF prevention strategies., Methods: This study involved 23,785 patients with diabetes without any pre-existing cardiovascular disease, drawn from the UK Biobank. Sleep behaviour traits examined encompassed sleep duration, chronotype, insomnia, snoring and daytime sleepiness. Sleep duration was categorised into three groups: low (≤ 5 h), proper (6-8 h) and long (≥ 9 h). We assessed associations using multivariate Cox proportional risk regression models. Furthermore, four poor sleep behaviours were constructed to evaluate their impact on the risk of new-onset AF., Results: Over a mean follow-up period of 166 months, 2221 (9.3%) new cases of AF were identified. Short (hazard ratio (HR), 1.28; 95% confidence interval (CI) 1.10-1.50) and long sleep durations (HR 1.16; 95% CI 1.03-1.32) consistently exhibited an elevated risk of AF compared to optimal sleep duration. Early chronotype, infrequent insomnia and daytime sleepiness were associated with 11% (HR 0.89; 95% CI 0.82-0.97), 15% (HR 0.85; 95% CI 0.77-0.95) and 12% (HR 0.88; 95% CI 0.81-0.96) reduced risk of new-onset AF, respectively. However, no significant association was found between snoring and the incidence of AF (HR 0.99; 95% CI 0.91-1.07)., Conclusions: In diabetic populations, sleep duration, chronotype, insomnia and daytime sleepiness are strongly associated with AF incidence. An optimal sleep duration of 6-8 h presents the lowest AF risk compared to short or long sleep duration. Additionally, poor sleep patterns present a greater risk of new-onset AF in women than in men., (© 2024. The Author(s).)

Ventilator-associated pneumonia (VAP) is a prevalent disease caused by microbial infection, resulting in significant morbidity and mortality within the intensive care unit (ICU). The rapid and accurate identification of pathogenic bacteria causing VAP can assist clinicians in formulating timely treatment plans. In this study, we attempted to differentiate bacterial species in VAP by utilizing the volatile organic compounds (VOCs) released by pathogens. We cultured 6 common bacteria in VAP in vitro , including Acinetobacter baumannii , Enterobacter cloacae , Escherichia coli , Pseudomonas aeruginosa , Stenotrophomonas maltophilia , and Staphylococcus aureus , which covered most cases of VAP infection in clinic. After the VOCs released by bacteria were collected in sampling bags, they were quantitatively detected by a proton transfer reaction-mass spectrometry (PTR-MS), and the characteristic ions were qualitatively analyzed through a fast gas chromatography-proton transfer reaction-mass spectrometry (FGC-PTR-MS). After conducting principal component analysis (PCA) and analysis of similarities (ANOSIM), we discovered that the VOCs released by 6 bacteria exhibited differentiation following 3 h of quantitative cultivation in vitro . Additionally, we further investigated the variations in the types and concentrations of bacterial VOCs. The results showed that by utilizing the differences in types of VOCs, 6 bacteria could be classified into 5 sets, except for A. baumannii and E. cloacae which were indistinguishable. Furthermore, we observed significant variations in the concentration ratio of acetaldehyde and methyl mercaptan released by A. baumannii and E. cloacae. In conclusion, the VOCs released by bacteria could effectively differentiate the 6 pathogens commonly associated with VAP, which was expected to assist doctors in formulating treatment plans in time and improve the survival rate of patients.

Scalable fabrication of all-perovskite tandem solar cells is challenging because the narrow-bandgap subcells made of mixed lead-tin (Pb-Sn) perovskite films suffer from nonuniform crystallization and inferior buried perovskite interfaces. We used a dopant from Good's list of biochemical buffers, aminoacetamide hydrochloride, to homogenize perovskite crystallization and used it to extend the processing window for blade-coating Pb-Sn perovskite films and to selectively passivate defects at the buried perovskite interface. The resulting all-perovskite tandem solar module exhibited a certified power conversion efficiency of 24.5% with an aperture area of 20.25 square centimeters.

Due to the increasing antibiotic resistance, developing novel antimicrobials to fight infections caused by resistant bacteria is imperative. Herein, a series of novel bis-substituted aromatic amides were designed and synthesized through modifying the hit compound 1 , and their antimicrobial activities were evaluated. Among them, compound 4t , as the most potent lead, exhibited excellent antimicrobial activities against Gram-positive bacteria, including clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, while keeping weak hemolytic and mammalian cytotoxic activities. Furthermore, compound 4t displayed rapid bactericidal capabilities, low tendency to produce resistance, and favorable capacities to destroy bacterial biofilms. Further explorations indicated that compound 4t induces bacterial death by binding to cardiolipin (CL) on the bacterial membrane, disrupting the cell membrane, and facilitating the accumulation of reactive oxygen species (ROS). Additionally, compound 4t showed remarkable anti-MRSA activity in vivo , demonstrating compound 4t could be developed as a potential candidate to combat MRSA infections.

Hierarchical compartmentalization, a hallmark of both primitive and modern cells, enables the concentration and isolation of biomolecules, and facilitates spatial organization of biochemical reactions. Coacervate-based compartments can sequester and recruit a large variety of molecules, making it an attractive protocell model. In this work, we report the spontaneous formation of core-shell cell-sized coacervate-based compartments driven by spontaneous evaporation of a sessile droplet on a thin-oil-coated substrate. Our analysis reveals that such far-from-equilibrium architectures arise from multiple, coupled segregative and associative liquid-liquid phase separation, and are stabilized by stagnation points within the evaporating droplet. The formation of stagnation points results from convective capillary flows induced by the maximum evaporation rate at the liquid-liquid-air contact line. This work provides valuable insights into the spontaneous formation and maintenance of hierarchical compartments under non-equilibrium conditions, offering a glimpse into the real-life scenario., (© 2024. The Author(s).)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases. This study aimed to investigate the clinical significance of changes in interleukin-18 (IL-18) and neutrophil/lymphocyte ratio (NLR) in the pathogenesis of AAV and the impact of NLR on the prognosis of patients. The clinical data of 52 AAV patients (AAV group) who met the conditions of hospitalization, 30 patients with mild mesangial proliferative glomerulonephritis (disease controls), and 30 healthy volunteers (normal controls) in Nephrology Department of Liuzhou People's Hospital from May 2020 to August 2022 were selected. A total of 52 AAV patients were divided into active phase (>15 points) and remission phase (≤15 points) based on the Birmingham vasculitis activity score (BVAS). Serum IL-18 level was detected by enzyme-linked immunosorbent assay in three groups. Pearson product moment correlation analysis was performed to investigate the correlation between serum IL-18 levels and clinical laboratory indicators, and receiver operating characteristic (ROC) curve analysis was performed on serum IL-18, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels, and NLR in AAV patients. The levels of serum creatinine, parathyroid hormone, β2-microglobulin (β2-MG), ESR, CRP, and IL-18 in active stage of AAV were significantly higher than those in remission stage of AAV. Moreover, the serum IL-18 level of active AAV patients was significantly higher than that of disease control group ( P < 0.05). The levels of eGFR, hemoglobin, and complement C3 were significantly lower than those during the remission ( P < 0.05). Pearson product moment correlation analysis showed that serum IL-18 level in AAV patients was positively correlated with BVAS score and ESR level. The area under the curve of serum IL-18, NLR, CRP, ESR levels evaluated by ROC curve was 0.921, 0.899, 0.83, and 0.75, respectively. Kaplan-Meier survival curve showed that the cumulative survival rate of patients in low NLR group was significantly higher than that in high NLR group (68.36 vs 42.89%), with significant difference (Log-Rank = 6.745, P = 0.025 < 0.05). IL-18 may be adopted as one of the important biological markers to judge the disease of AAV, and the cumulative survival rate of patients with high NLR is low, which may be applied as an indicator to evaluate the poor prognosis of patients with AAV., Competing Interests: Conflict of interest: Author states no conflicts of interest., (© 2024 the author(s), published by De Gruyter.)

Wide-bandgap (WBG) perovskite solar cells hold tremendous potential for realizing efficient tandem solar cells. However, nonradiative recombination and carrier transport losses occurring at the perovskite/electron-selective contact (e.g. C 60 ) interface present significant obstacles in approaching their theoretical efficiency limit. To address this, a sequential interface engineering (SIE) strategy that involves the deposition of ethylenediamine diiodide (EDAI 2 ) followed by sequential deposition of 4-Fluoro-Phenethylammonium chloride (4F-PEACl) is implemented. The SIE technique synergistically narrows the conduction band offset and reduces recombination velocity at the perovskite/C 60 interface. The best-performing WBG perovskite solar cell (1.67 eV) delivers a power conversion efficiency (PCE) of 21.8% and an impressive open-circuit voltage of 1.262 V. Moreover, through integration with double-textured silicon featuring submicrometer pyramid structures, a stabilized PCE of 29.6% is attained for a 1 cm 2 monolithic perovskite/silicon tandem cell (certified PCE of 29.0%)., (© 2023 Wiley-VCH GmbH.)

Myocardial ischemia reperfusion injury (MIRI) represents a prevalent and severe cardiovascular condition that arises primarily after myocardial infarction recanalization, cardiopulmonary bypass surgery, and both stable and unstable angina pectoris. MIRI can induce malignant arrhythmias and heart failure, thereby increasing the morbidity and mortality rates associated with cardiovascular diseases. Hence, it is important to assess the potential pathological mechanisms of MIRI and develop effective treatments. The role of circular RNAs (circRNAs) in MIRI has increasingly become a topic of interest in recent years. Moreover, significant evidence suggests that circRNAs play a critical role in MIRI pathogenesis, thereby representing a promising therapeutic target. This review aimed to provide a comprehensive overview of the current understanding of the role of circRNAs in MIRI and discuss the mechanisms through which circRNAs contribute to MIRI development and progression, including their effects on apoptosis, inflammation, oxidative stress, and autophagy. Furthermore, the potential therapeutic applications of circRNAs in MIRI treatment, including the use of circRNA-based therapies and modulation of circRNA expression levels, have been explored. Overall, this paper highlights the importance of circRNAs in MIRI and underscores their potential as novel therapeutic targets., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Recent studies have shown that there exists a significant correlation between oral microbiome and the occurrence of malignancies. However, the prognostic significance of oral microbiome for cancer patients remains unclear. The purpose of this meta-analysis is to evaluate the impact of oral microbiome on the survival of patients with malignant neoplasms., Methods: We conducted a thorough literature search of PubMed, Embase, and Cochrane Library databases until September 2022. The hazard ratio (HR) with a corresponding 95% confidence interval (CI) was analyzed using Review Manager 5.4 software for survival outcomes, including overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and disease-free survival (DFS)., Results: A total of 15 studies, covering 5191 samples with various types of cancers, were selected based on specified inclusion and exclusion criteria. In both univariate and multivariate analysis, patients with low diversity of the oral microbiome, or those with Fusobacterium-high/positive, or P. gingivalis positive in cancer tissue displayed poorer OS (univariate HR = 1.74; 95% CI 1.15-2.62; P = 0.009; multivariate HR = 1.56; 95% CI 1.07-2.27; P = 0.02), DSS (univariate HR = 2.06; 95% CI 1.50-2.84; P < 0.00001; multivariate HR = 1.80; 95% CI 1.48-2.20; P < 0.00001), and PFS/DFS (univariate HR = 2.00; 95% CI 1.12-3.58; P = 0.002; multivariate HR = 1.78; 95% CI 1.05-3.02; P = 0.003). Subgroup analysis revealed that Fusobacterium positive or high abundance in cancer tissues was associated with poor OS in multivariate analysis but had no statistical differences in PFS or DFS in univariate and multivariate analysis. Additionally, P. gingivalis positive in cancer tissue was also associated with worse OS., Conclusions: Our meta-analysis suggests that the composition of the oral microbiome may play a significant role in predicting survival outcomes for cancer patients., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) represents an estrogen-dependent tumor. The action of estrogen is regulated via estrogen receptor (ER). Polymorphisms in ERα gene, ESR1, are known to be related to HCC susceptibility among people carrying chronic hepatitis B (CHB). But the effect of ERβ on HCC is still largely unclear, and studies about the genetic variability of ESR2 and HCC are rare. For understanding ESR2's effect on HCC, this work tested two polymorphisms in the ESR2 gene promoter as well as the associations with CHB, HCC, and hepatitis B virus (HBV)-related liver cirrhosis (LC) among the Guangxi population. This work enrolled a total of 137 CHB, 136 LC, and 149 HBV-related HCC patients, together with 146 normal subjects. ESR2 polymorphisms rs3020449 and rs2978381 were examined using the SNaPshot genotyping technique. The AG genotype and dominant model of rs3020449 were related to the decreased CHB susceptibility. In both the overall and subgroup analyses, no associations were observed with the remaining models in all patient groups (those with CHB, HBV-related LC, and HCC), but associations were found between the dominant (TC+CC vs TT) and allele models (C vs T) of rs2978381 and increased HBV-related LC and HCC susceptibility, but not CHB. These findings suggest that rs3020449 polymorphism of ESR2 gene makes great contribution to the decreased CHB risk and that rs2978381 significantly contributed to higher risks of HBV-related LC and HCC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson's disease (PD), a prevalent non-motor symptom contributing significantly to patients' morbidity. A marked alteration in the gut microbiota, predominantly an increase in the abundance of Proteobacteria and Bacteroidetes , is observed in PD-related constipation. Conventional treatments, although safe, have failed to effectively alleviate symptoms, thereby necessitating the development of novel therapeutic strategies. Microbiological interventions such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) hold therapeutic potential. While prebiotics improve bowel movements, probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort. FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD. Despite promising developments, the causal relationship between changes in gut microbiota and PD-related constipation remains elusive, highlighting the need for further research in this expanding field., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective. Nuclei segmentation is crucial for pathologists to accurately classify and grade cancer. However, this process faces significant challenges, such as the complex background structures in pathological images, the high-density distribution of nuclei, and cell adhesion. Approach. In this paper, we present an interactive nuclei segmentation framework that increases the precision of nuclei segmentation. Our framework incorporates expert monitoring to gather as much prior information as possible and accurately segment complex nucleus images through limited pathologist interaction, where only a small portion of the nucleus locations in each image are labeled. The initial contour is determined by the Voronoi diagram generated from the labeled points, which is then input into an optimized weighted convex difference model to regularize partition boundaries in an image. Specifically, we provide theoretical proof of the mathematical model, stating that the objective function monotonically decreases. Furthermore, we explore a postprocessing stage that incorporates histograms, which are simple and easy to handle and prevent arbitrariness and subjectivity in individual choices. Main results. To evaluate our approach, we conduct experiments on both a cervical cancer dataset and a nasopharyngeal cancer dataset. The experimental results demonstrate that our approach achieves competitive performance compared to other methods. Significance. The Voronoi diagram in the paper serves as prior information for the active contour, providing positional information for individual cells. Moreover, the active contour model achieves precise segmentation results while offering mathematical interpretability., (© 2024 Institute of Physics and Engineering in Medicine.)

Background: In low-dose computed tomography (LDCT) lung cancer screening, soft tissue is hardly appreciable due to high noise levels. While deep learning-based LDCT denoising methods have shown promise, they typically rely on structurally aligned synthesized paired data, which lack consideration of the clinical reality that there are no aligned LDCT and normal-dose CT (NDCT) images available. This study introduces an LDCT denoising method using clinically structure-unaligned but paired data sets (LDCT and NDCT scans from the same patients) to improve lesion detection during LDCT lung cancer screening., Methods: A cohort of 64 patients undergoing both LDCT and NDCT was randomly divided into training (n=46) and testing (n=18) sets. A two-stage training approach was adopted. First, Gaussian noise was added to NDCT data to create simulated LDCT data for generator training. Then, the model was trained on a clinically structure-unaligned paired data set using a Wasserstein generative adversarial network (WGAN) framework with the initial generator weights obtained during the first stage of training. An attention mechanism was also incorporated into the network., Results: Validated on a clinical CT data set, our proposed method outperformed other available methods [CycleGAN, Pixel2Pixel, block-matching and three-dimensional filtering (BM3D)] in noise removal and detail retention tasks in terms of the peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), and root mean square error (RMSE) metrics. Compared with the results produced by BM3D, our method yielded an average improvement of approximately 7% in terms of the three evaluation indicators. The probability density profile of the denoised CT output produced using our method best fit the reference NDCT scan. Additionally, our two-stage model outperformed the one-stage WGAN-based model in both objective and subjective evaluations, further demonstrating the higher effectiveness of our two-stage training approach., Conclusions: The proposed method performed the best in removing noise from LDCT scans and exhibited good detail retention, which could potentially enhance the lesion detection and characterization effects obtained for soft tissues in the scanning scope of LDCT lung cancer screening., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-403/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objectives: To investigate measurements derived from plain and enhanced spectral CT in differentiating osteoblastic bone metastasis (OBM) from bone island (BI)., Materials and Methods: From January to November 2020, 73 newly diagnosed cancer patients with 201 bone lesions (OBM = 92, BI = 109) having received spectral CT were retrospectively enrolled. Measurements including CT values of 40-140 keV, slope of the spectral curve, effective atomic number (Z eff ), water (calcium) density, calcium (water) density, and Iodine (calcium) density were derived from manually segmented lesions on plain and enhanced spectral CT, and then analyzed using Student t-test and Pearson's correlation. Multivariate analysis was performed to build models (plain spectral model, enhanced spectral CT model, and combined model) for the discrimination of OBM and BI with performance evaluated using receiver operator characteristics curve and DeLong test., Results: All features were significantly different between the BI group and OBM group (all p < 0.05), highly correlated with the corresponding features between plain and enhanced spectral CT both in OBM (r: 0.392-0.763) and BI (r: 0.430-0.544). As for the model performance, the combined model achieved the best performance (AUC = 0.925, 95% CI: 0.879 to 0.957), which significantly outperformed the plain spectral CT model (AUC = 0.815, 95% CI: 0.754 to 0.866, p < 0.001) and enhanced spectral CT model (AUC = 0.901, 95% CI: 0.852 to 0.939, p = 0.024) in differentiating OBM and BI., Conclusion: In addition to plain spectral CT measurements, enhanced spectral CT measurements would further significantly benefit the differential diagnosis., Clinical Relevance Statement: Measurements derived either from plain or enhanced spectral CT could provide additional valuable information to improve the differential diagnosis between OBM and BI in newly diagnosed cancer patients., Key Points: • We intend to investigate plain and enhanced spectral CT measurements in differentiating OBM from BI. • Both plain and enhanced spectral CT help in discriminating OBM and BI in newly diagnosed cancer patients. • Enhanced spectral CT measurements further improve plain spectral CT measurements-based differential diagnosis., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Neurodegenerative diseases are caused by the loss of neurons and/or their myelin sheaths, which deteriorate over time and become dysfunctional. Alzheimer's disease, Parkinson's disease, and multiple sclerosis are among the most prominent neurodegenerative diseases that affect millions of older adults worldwide. Despite extensive research over several decades, controversies still surround the etiology of neurodegenerative diseases, and many of them remain incurable. Meanwhile, an increasing number of new mechanistic studies related to the microbiota-gut-brain axis have emerged, among which the relationship between the function of the intestinal barrier and neurodegenerative diseases has received widespread attention. As one of the first lines of defense between the body and the external environment, the impaired function of the intestinal barrier is closely related to the development of neurodegenerative pathologies. Among them, the microbiota-gut-brain axis disorder characterized by intestinal barrier disruption mainly includes impaired function of the intestinal microbial barrier, chemical barrier, mechanical barrier, and immune barrier. This review focuses on the structure and molecular mechanisms of the various layers of the intestinal barrier as well as their relationship with neurodegenerative lesions. In recent years, intestinal barrier repair therapies have provided new ideas for the studied disease treatment modalities. We believe that a better understanding of the role of the intestinal barrier in neurodegenerative diseases would provide new insights for the development of viable therapeutic strategies for patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

All-perovskite tandem solar cells offer the potential to surpass the Shockley-Queisser (SQ) limit efficiency of single-junction solar cells while maintaining the advantages of low-cost and high-productivity solution processing. However, scalable solution processing of electron transport layer (ETL) in p-i-n structured perovskite solar subcells remains challenging due to the rough perovskite film surface and energy level mismatch between ETL and perovskites. Here, scalable solution processing of hybrid fullerenes (HF) with blade-coating on both wide-bandgap (≈1.80 eV) and narrow-bandgap (≈1.25 eV) perovskite films in all-perovskite tandem solar modules is developed. The HF, comprising a mixture of fullerene (C 60 ), phenyl C 61 butyric acid methyl ester, and indene-C 60 bisadduct, exhibits improved conductivity, superior energy level alignment with both wide- and narrow-bandgap perovskites, and reduced interfacial nonradiative recombination when compared to the conventional thermal-evaporated C 60 . With scalable solution-processed HF as the ETLs, the all-perovskite tandem solar modules achieve a champion power conversion efficiency of 23.3% (aperture area = 20.25 cm 2 ). This study paves the way to all-solution processing of low-cost and high-efficiency all-perovskite tandem solar modules in the future., (© 2023 Wiley-VCH GmbH.)

Objectives: To propose a novel model-free data-driven approach based on the voxel-wise mapping of DCE-MRI time-intensity-curve (TIC) profiles for quantifying and visualizing hemodynamic heterogeneity and to validate its potential clinical applications., Materials and Methods: From December 2018 to July 2022, 259 patients with 325 pathologically confirmed breast lesions who underwent breast DCE-MRI were retrospectively enrolled. Based on the manually segmented breast lesions, the TIC of each voxel within the 3D whole lesion was classified into 19 subtypes based on wash-in rate (nonenhanced, slow, medium, and fast), wash-out enhancement (persistent, plateau, and decline), and wash-out stability (steady and unsteady), and the composition ratio of these 19 subtypes for each lesion was calculated as a new feature set (type-19). The three-type TIC classification, semiquantitative parameters, and type-19 features were used to build machine learning models for identifying lesion malignancy and classifying histologic grades, proliferation status, and molecular subtypes., Results: The type-19 feature-based model significantly outperformed models based on the three-type TIC method and semiquantitative parameters both in distinguishing lesion malignancy (respectively; AUC = 0.875 vs. 0.831, p = 0.01 and 0.875vs. 0.804, p = 0.03), predicting tumor proliferation status (AUC = 0.890 vs. 0.548, p = 0.006 and 0.890 vs. 0.596, p = 0.020), but not in predicting histologic grades (p = 0.820 and 0.970)., Conclusion: In addition to conventional methods, the proposed computational approach provides a novel, model-free, data-driven approach to quantify and visualize hemodynamic heterogeneity., Clinical Relevance Statement: Voxel-wise intra-lesion mapping of TIC profiles allows for visualization of hemodynamic heterogeneity and its composition ratio for differentiation of malignant and benign breast lesions., Key Points: • Voxel-wise TIC profiles were mapped, and their composition ratio was compared between various breast lesions. • The model based on the composition ratio of voxel-wise TIC profiles significantly outperformed the three-type TIC classification model and the semiquantitative parameters model in lesion malignancy differentiation and tumor proliferation status prediction in breast lesions. • This novel, data-driven approach allows the intuitive visualization and quantification of the hemodynamic heterogeneity of breast lesions., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

The impact of different iron metabolism processes (DIMP) on ovarian cancer remains unclear. In this study, we employed various gene chips and databases to investigate the role of DIMP in the initiation and development of ovarian cancer. cBioPortal was used to determine mutations in DIMP-associated genes in ovarian cancer. Kaplan-Meier plotter was used to examine the influence of DIMP on the prognosis of ovarian cancer. By analyzing 1669 serous ovarian cancer cases, we identified a range of mutations in iron metabolism genes, notably in those coding for the transferrin receptor (19%), melanotransferrin (19%), and ceruloplasmin (10%) in the iron import process, and glucose-6-phosphate isomerase (9%), hepcidin antimicrobial peptide (9%), metal regulatory transcription factor 1 (8%), and bone morphogenetic protein 6 (8%) in the iron regulation process. Compared to the unaltered group, the group with gene alterations exhibited a higher tumor mutation burden count (43 vs . 54) and more advanced histologic grade (78.19% vs . 87.90%). Compared to the normal ovarian counterparts, a reduction in expression was observed in 9 out of the 14 genes involved in iron utilization and 4 out of the 5 genes involved in iron export in ovarian cancer; in contrast, an increase in expression was observed in 2 out of the 3 genes involved in iron storage in ovarian cancer. Furthermore, in cisplatin-resistant cells compared to cisplatin-sensitive ones, the expression of all genes in iron storage and 13 out of 14 genes in iron import was decreased, while that of 8 out of the 10 genes in iron utilization was increased. In addition, survival curve analysis indicated that a higher expression in the majority of genes in the iron import process (12/21), or a reduced expression in most genes in the iron export process (4/5) correlated with poor progression-free survival. Additionally, TGF-β could regulate the expression of most iron metabolism-associated genes; particularly, expression of genes involved in the iron storage process (2/2) was inhibited after TGF-β1 or TGF-β2 treatment. In conclusion, DIMP plays multifaceted roles in the initiation, chemo-resistance, and prognosis of ovarian cancer. Therapeutically targeting DIMP may pave the way for more tailored treatment approaches for ovarian cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (© 2024 Wu et al.)

Background: Postsurgical recurrence is of great concern for papillary thyroid carcinoma (PTC). We aim to investigate the value of computed tomography (CT)-based radiomics features and conventional clinical factors in predicting the recurrence of PTC., Methods: Two-hundred and eighty patients with PTC were retrospectively enrolled and divided into training and validation cohorts at a 6:4 ratio. Recurrence was defined as cytology/pathology-proven disease or morphological evidence of lesions on imaging examinations within 5 years after surgery. Radiomics features were extracted from manually segmented tumor on CT images and were then selected using four different feature selection methods sequentially. Multivariate logistic regression analysis was conducted to identify clinical features associated with recurrence. Radiomics, clinical, and combined models were constructed separately using logistic regression (LR), support vector machine (SVM), k-nearest neighbor (KNN), and neural network (NN), respectively. Receiver operating characteristic analysis was performed to evaluate the model performance in predicting recurrence. A nomogram was established based on all relevant features, with its reliability and reproducibility verified using calibration curves and decision curve analysis (DCA)., Results: Eighty-nine patients with PTC experienced recurrence. A total of 1218 radiomics features were extracted from each segmentation. Five radiomics and six clinical features were related to recurrence. Among the 4 radiomics models, the LR-based and SVM-based radiomics models outperformed the NN-based radiomics model (P = 0.032 and 0.026, respectively). Among the 4 clinical models, only the difference between the area under the curve (AUC) of the LR-based and NN-based clinical model was statistically significant (P = 0.035). The combined models had higher AUCs than the corresponding radiomics and clinical models based on the same classifier, although most differences were not statistically significant. In the validation cohort, the combined models based on the LR, SVM, KNN, and NN classifiers had AUCs of 0.746, 0.754, 0.669, and 0.711, respectively. However, the AUCs of these combined models had no significant differences (all P > 0.05). Calibration curves and DCA indicated that the nomogram have potential clinical utility., Conclusions: The combined model may have potential for better prediction of PTC recurrence than radiomics and clinical models alone. Further testing with larger cohort may help reach statistical significance., (© 2023. The Author(s).)

Intestinal microfold cells (M cells) play a critical role in the immune response of the intestinal mucosa by actively taking up antigens, facilitating antigen presentation to immune cells, and promoting the production of secretory immunoglobulin A by B cells. Despite their known important functions in the gut, the effect of M cells on the central nervous system remains unclear. We investigated the expression of M cell-related factor genes and protein levels in Peyer's patches (PPs) of 3-month-old and 9-month-old APP/PS1 mice, as well as the expression of intestinal barrier proteins in the ileum and colon of these mice. Furthermore, we employed intestinal M cell conditional ablation mice (i.e., Rank ΔIEC mice) to assess the influence of M cells on the intestinal barrier and Alzheimer's disease (AD)-like behavioral and pathological features. Our findings revealed that compared to wild-type mice, APP/PS1 mice showed altered M cell-related genes and disrupted intestinal barriers. In addition, there is a significant decrease in glycoprotein 2 (GP2) mRNA levels in the PPs of 3-month-old APP/PS1 mice, with the relative expression of GP2 mRNA tending to zero. Parameters related to the intestinal barrier (IgA, MUC2, Claudin-5, ZO-1) were significantly downregulated in both 3-month-old and 9-month-old APP/PS1 mice compared to wild-type controls, and the differences were more pronounced in the 9-month-old mice. Moreover, M cell ablation in APP/PS1 mice (i.e., APP/PS1ΔMC mice) resulted in more severe intestinal barrier destruction. Notably, we observed through water maze experiments that APP/PS1ΔMC mice at 6 months of age exhibited significantly poorer spatial learning memory compared to APP/PS1 mice. And the neuropathological alterations were also observed in APP/PS1ΔMC mice at 6 months of age that when intestinal M cells are damaged in APP/PS1 mice, brain microglia are activated, Tau phosphorylation is exacerbated, and the number of neurons is reduced. Our results suggest for the first time that the absence of intestinal M cells might further aggravate intestinal leakage, lead to neuropathological damage, and subsequently cause the impairment of learning memory ability in AD mice. Our research highlights the impact of intestinal M cells on the intestinal barrier and AD neuropathogenesis in AD mouse model., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit., Research Methodology/design: A prospective and multicentre study., Setting: This study was conducted in 24 intensive care units in Anhui, China., Main Outcome Measures: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay., Results: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition., Conclusion: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales., Implications for Clinical Practice: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units., 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.)

The mechanisms underlying neurodegenerative sequelae of traumatic brain injury (TBI) are poorly understood. The normal plasma protein, serum amyloid P component (SAP), which is normally rigorously excluded from the brain, is directly neurocytotoxic for cerebral neurones and also binds to A β amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of A β fibrils. Increased brain exposure to SAP is common to many risk factors for dementia, including TBI, and dementia at death in the elderly is significantly associated with neocortical SAP content. Here, in 18 of 30 severe TBI cases, we report immunohistochemical staining for SAP in contused brain tissue with blood-brain barrier disruption. The SAP was localized to neurofilaments in a subset of neurones and their processes, particularly damaged axons and cell bodies, and was present regardless of the time after injury. No SAP was detected on astrocytes, microglia, cerebral capillaries or serotoninergic neurones and was absent from undamaged brain. C-reactive protein, the control plasma protein most closely similar to SAP, was only detected within capillary lumina. The appearance of neurocytotoxic SAP in the brain after TBI, and its persistent, selective deposition in cerebral neurones, are consistent with a potential contribution to subsequent neurodegeneration.

Diabetic cardiomyopathy (DCM) is a pathophysiological condition triggered by diabetes mellitus (DM), which can lead to heart failure (HF). One of the most important cellular processes associated with DCM is the death of cardiomyocytes. Gasdermin D (GSDMD) plays a key role in mediating pyroptosis, a type of programmed cell death closely associated with inflammasome activation. Recent studies have revealed that pyroptosis is induced during hyperglycemia, which is crucial to the development of DCM. Although the effects of pyroptosis on DCM have been discussed, the relationship between DCM and GSDMD is not fully clarified. Recent studies gave us the impetus for clarifying the meaning of GSDMD in DCM. The purpose of this review is to summarize new and emerging insights, mainly discussing the structures of GSDMD and the mechanism of pore formation, activation pathways, molecular mechanisms of GSDMD-mediated pyroptosis, and the therapeutic potential of GSDMD in DCM. The implications of this review will pave the way for a new therapeutic target in DCM.