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Yuan Xu, Jing-Yan Wang, Yang Zou, Xue-Wei Ma, Tian Meng College of Health Industry, Sichuan Tourism University, Chengdu, Sichuan, 610100, People’s Republic of ChinaCorrespondence: Yuan Xu, Email 230973159@qq.comAbstract: Inflammatory cytokines, interleukin-36 (IL-36), IL-37, IL-38 belong to IL-1 family. The IL-36 subfamily obtains pro- and anti-inflammatory effects on various immune responses. Cytokine IL-37, has anti-inflammatory functions in immunity, and the recently identified IL-38 negatively associated with disease pathogenesis. To date, expression of IL-36, IL-37, IL-38 is reported dysregulated in osteoarthritis (OA) and rheumatoid arthritis (RA), and may be disease markers for arthritis-related diseases. Interestingly, expression of IL-38 was different either in OA patients or animal models, and expression of IL-36Ra in synovium was different in OA and RA patients. Moreover, functional studies have demonstrated significant role of these cytokines in OA and RA progress. These processes were related to immune cells and non-immune cells, where the cytokines IL-36, IL-37, IL-38 may regulate downstream signalings in the cells, and then involve in OA, RA development. In this review, we comprehensively discuss recent advancements in cytokines and the development of OA, RA. We hope that targeting these cytokines will become a potential treatment option for OA and RA in the future.Keywords: IL-36, IL-37, IL-38, osteoarthritis, rheumatoid arthritis

In our investigation, we investigated the role of macrophage migration inhibitory factor (MIF), a key cytokine, in chronic nonbacterial prostatitis (CNP), an underexplored pathology. Elevated MIF expression was observed in the serum of individuals with chronic prostatitis-like symptoms (CP-LS) as well as in serum and tissue samples from experimental autoimmune prostatitis (EAP) mouse model. Treatment with ISO-1, a specific MIF antagonist, effectively mitigated prostatic inflammation and macrophage infiltration, thereby emphasizing the critical role of MIF in orchestrating immune responses within the prostate microenvironment. Further analyses revealed that MIF stimulates the PI3K/AKT and NLRP3 inflammasome pathways, which are integral to inflammation and cellular immunity. Pharmacological inhibition of the PI3K/AKT pathway by LY294002 substantially reduced prostatic inflammation and macrophage infiltration, potentially by inhibiting NLRP3 inflammasome activation. These findings collectively suggest that MIF is a potential diagnostic marker for CNP and suggest that targeting MIF or its downstream signalling pathways, PI3K/AKT and NLRP3, might represent a novel therapeutic strategy for this condition., 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.)

Supramolecular polymers hold promise in thermal management applications due to their multistability, high responsiveness, and cost-effectiveness. In this work, we successfully regulate phonon transport at the molecular level in supramolecular polymers by adjusting the strength of intermolecular hydrogen bonding. We synthesized three supramolecular polymer fibers with thermal conductivity differences of up to 289% based on melamine (M) and three simple positional isomers of hydroxybenzoic acid. Differential Scanning Calorimetry (DSC) measurement revealed discrepancies in thermal stability of the polymers, where structures with higher stability exhibited enhanced thermal conductivity. Fourier Transform Infrared Spectroscopy (FTIR) measurement and Density Functional Theory (DFT) calculations indicate that these differences arise from variations in hydrogen-bonding strengths at different bonding sites. Higher hydrogen-bonding strength leads to more stable thermal pathways, reduces phonon scattering, and increases thermal conductivity. Our findings provide valuable insights into controlling the thermal conductivity of polymer fibers, paving the way for applications in phonon-based thermal devices.

Pesticide contamination in ambient air due to spray drifting has received extensive attention. Quantifying the associated health risk highlights the importance of incorporating bioaccessibility into inhalation exposure assessments rather than using the total inhaled concentration of airborne pesticides. In this study, we measured the inhalation unit exposure (UE) of three typical pesticides (lambda-cyhalothrin, phoxim, and acetamiprid) during application and post-application drift at the recommended application dosage. The UE values were found to be 1.74-424.37 ng/m 3 and 0.07-1.40 ng/m 3 , respectively, with marked variation between different spraying nozzles and formulations. For the inhalation exposure assessment, an in vitro method was developed to determine the inhalation bioaccessibility of lambda-cyhalothrin, phoxim, and acetamiprid and its applicability was validated based on in vivo-in vitro correlations (IVIVC) analysis. Their conservative inhalation bioaccessibility values estimates were 46.09 %, 67.12 %, and 40.31 %, respectively. The calculated average daily dose values of the analyzed pesticides in both single and mixed formulations ranged from 8.03 × 10 -8 to 4.35 × 10 -5  mg/kg·day based on the bioaccessible UE, corresponding to 22.99-67.11 % of the total exposure. Collectively, these findings are of guiding significance for improving risk management in pesticide application., 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.)

The emergence of trastuzumab deruxtecan (T-DXd), a new-generation antibody-drug conjugate (ADC), has profoundly altered the therapeutic paradigm for HER2-positive solid tumors, demonstrating remarkable clinical benefits. However, the combined outcomes of T-DXd with immunotherapy agents remain ambiguous. In this study, we introduce Tras-DXd-MTL1, an innovative HER2 targeting ADC that integrates the topoisomerase inhibitor DXd and a toll like receptor 7 (TLR7) agonist MTT5, linked to trastuzumab via a GGFG tetrapeptide linker. Mechanistically, Tras-DXd-MTL1 retains the DNA-damaging and cell-killing properties of topoisomerase inhibitors while simultaneously enhancing the immune response within the tumor microenvironment. This is achieved by promoting immune cell infiltration and activating dendritic cells and CD8+T cells via MTT5. In vivo evaluation of Tras-DXd-MTL1's antitumor potency revealed a notably superior performance compared with the T-DXd (Tras-DXd) or Tras-MTL1 in immunocompetent mice with trastuzumab-resistant EMT6-HER2 tumor and immunodeficient mice with JIMT-1 tumor. This improved efficacy is primarily attributed to its dual functions of immune stimulation and cytotoxicity. Our findings highlight the potential of incorporating immunostimulatory agents into ADC design to potentiate antitumor effects and establish durable immune memory, thereby reducing tumor recurrence risks. Therefore, our study offers a novel strategy for the design of immune-activating ADCs and provides a potential approach for targeting solid tumors with different levels of HER2 expression., (©2024 American Association for Cancer Research.)

The realization of persistent luminescence and in particular circularly polarized luminescence (CPL) of organic radicals remains a challenge due to their sensitivity to oxygen at ambient conditions and elusive excited state chirality control. Here, it is reported that UV-irradiation on a supramolecular gel from a chiral triarylamine derivative, TPA-Ala, led to the formation of luminescent radicals with bright CPL. TPA-Ala can form an organogel in chloroform with blue emission and supramolecular chirality as demonstrated by both CD and CPL signals. Upon UV 365 nm irradiation, an emission color change from blue to cyan is observed due to the formation of photo-induced radicals. Interestingly, it is found that the supramolecular gel radicals showed stable luminescence with a lifetime ≈ 10 days in dark environments and inverted CPL, which represents a scarce example with persistent CPL from doublet-state due to oxygen isolation ability of the gel network. Furthermore, doping a guest dye, Rhodamine B (RhB), into the supramolecular gel (RhB/TPA-Ala = 30% in molar ratio) successfully obtained a transient white-light CPL through the superposition of photo-induced radical and guest dye emissions. This work provides a useful methodology for the fabrication of radical-based CPL materials via a supramolecular assembly approach., (© 2024 Wiley‐VCH GmbH.)

The constrained enzymatic activity and aggregation challenges encountered of nanozymes pose an obstacle to their practical utility, necessitating a strategy to alleviate this problem and improve the enzymatic catalytic efficiency. Herein, MOF-confined ultrafine ZnIrO x clusters (ZnIrO x /ZnIrMOFs) nanozyme have been synthesized by controlling the in-situ growth of ZnIrO x via a one-pot method. Notably, due to the domain-limiting effect of MOF, the ZnIrO x clusters with small size grew uniformly in the structure of ZnIrMOFs nanosheets, while the presence of Zn atoms improved the crystallinity of the MOF phase and the dispersion of ZnIrO x clusters. Moreover, the obtained ZnIrO x /ZnIrMOFs exhibited excellent oxidase- and peroxidase-like activities and better substrate affinity, which can directly and effectively catalyze chromogenic reaction to produce corresponding color and signal changes. Adopting this strategy, we established a visual, sensitive, and selective colorimetric method for glucose detection with a linear range and detection limit of 2.66-319 μM and 1.9 μM, respectively. The successful detection of glucose in real serum and food samples implies the promising MOF-confined ultrafine nanozymes in biomedical diagnostics and in food industry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: This study explores the global disease burden associated with high Body Mass Index (BMI) from 1990 to 2021, using data from the Global Burden of Disease Study 2021 (GBD 2021)., Methods: We applied Joinpoint regression to assess trends in deaths and Disability-Adjusted Life Years (DALYs) and employed ARIMA models to project future BMI-related burdens., Results: From 1990 to 2021, global deaths linked to high BMI surged by 153.97%, rising from 1.46 million to 3.71 million. DALYs increased by 167.57%, with the highest rises in North Africa, the Middle East, and South Asia. Women, particularly those aged 75 and above, experienced the most significant burden, with a faster rate of increase in disease burden compared to men post-2000. Future projections indicate a continued rise in BMI-related health impacts, particularly in low- and middle-income countries., Conclusions: The global disease burden attributable to high BMI is increasing rapidly, particularly in low- and middle-income regions. Targeted public health interventions, especially for women and the elderly, are crucial to addressing this growing health challenge., 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.)

Acute myocardial infarction (AMI) remains a leading cause of death among patients with cardiovascular diseases. Percutaneous coronary intervention (PCI) has been the preferred clinical treatment for AMI due to its safety and efficiency. However, research indicates that the rapid restoration of myocardial oxygen supply following PCI can lead to secondary myocardial injury, termed myocardial ischemia-reperfusion injury (MIRI), posing a grave threat to patient survival. Despite ongoing efforts, the mechanisms underlying MIRI are not yet fully elucidated. Among them, oxidative stress and inflammation stand out as critical pathophysiological mechanisms, playing significant roles in MIRI. Natural compounds have shown strong clinical therapeutic potential due to their high efficacy, availability, and low side effects. Many current studies indicate that natural compounds can mitigate MIRI by reducing oxidative stress and inflammatory responses. Therefore, this paper reviews the mechanisms of oxidative stress and inflammation during MIRI and the role of natural compounds in intervening in these processes, aiming to provide a basis and reference for future research and development of drugs for treating MIRI., (© 2024 John Wiley & Sons Ltd.)

Medullary thyroid carcinoma (MTC) can only be cured through the excision of all metastatic lesions, but 29-60% patients failed to localize the disease in the current clinical practice. Previously, we developed a fibroblast activation protein inhibitor (FAPI)-based covalent targeted radioligand (CTR) for improved detection sensitivity and accuracy. In this first-in-class clinical trial, we head-to-head compared [68Ga]Ga-CTR-FAPI PET-CT and [18F]FDG PET-CT in 50 MTC patients. The primary endpoint was the patient-based detection rate, with [68Ga]Ga-CTR-FAPI exhibiting higher detection than [18F]FDG (98% vs. 66%, p=0.0002). This improved detection was attributed to increased tumor uptake (SUVmax 11.71±9.16 vs. 2.55±1.73, p<0.0001). Diagnostic accuracy, validated on lesions with gold-standard pathology, was greater for [68Ga]Ga-CTR-FAPI compared to [18F]FDG (96.7% vs. 43.3%, p<0.0001). Notably, 32% patients altered management following [68Ga]Ga-CTR-FAPI PET-CT, and 66.7% patients changed their surgical plan. Overall, [68Ga]Ga-CTR-FAPI PET-CT provided superior detection and diagnostic accuracy compared to [18F]FDG PET-CT, enabling precision management of MTC patients.

Background: The Platelet to High-Density Lipoprotein cholesterol Ratio (PHR) is a novel indicator of inflammatory response and metabolic disorders, linked to various chronic diseases. This study aims to investigate the relationship between PHR and hypertension., Methods: Data from the National Health and Nutrition Examination Survey (NHANES), collected across seven consecutive cycles from 2005 to 2018, were analyzed. The dataset included participants' hypertension status as reported by a doctor, their use of antihypertensive medications, and the average of three blood pressure measurements to identify hypertensive adults, along with complete information for PHR calculation. PHR was calculated based on Platelet (PLT) count and High-Density Lipoprotein cholesterol (HDL-C) using the following formula: PHR = [PLT (1000 cells/µL) / HDL-C (mmol/L)]. A multivariable logistic regression model was employed to assess the association between PHR and hypertension, and subgroup analyses were conducted to explore potential influencing factors. Additionally, Restricted Cubic Spline (RCS) curves were applied for threshold effect analysis to describe nonlinear relationships., Results: Higher PHR was associated with an increased prevalence of hypertension. After adjusting for various covariates, including race, education level, Family Poverty Income Ratio (PIR), smoking, alcohol consumption, sleep disturbances, waist circumference, diabetes, coronary heart disease, angina, heart attack, and stroke, the results remained significant (OR = 1.36; 95% CI, 1.32, 1.41, P < 0.001). Participants with the highest PHR levels had a 104% higher risk of hypertension compared to those with the lowest PHR levels (OR = 2.04; 95% CI, 1.89, 2.21, P < 0.001)., Conclusion: Elevated PHR levels are strongly associated with an increased risk of hypertension. Specifically, when PHR is below 280, the risk of hypertension increases in proportion to PHR. This suggests that regular monitoring of PHR may help identify patients at risk of hypertension early, allowing for timely interventions to slow disease progression. Larger cohort studies are necessary to confirm these findings., (© 2024. The Author(s).)

Background: Epidemiological and observational studies demonstrate a comorbid relationship between hypothyroidism and atherosclerotic cardiovascular disease (ASCVD). The nature and direction of this causal relationship, however, remain unclear., Objective: This study aims to elucidate the causal relationship between hypothyroidism and ASCVD using a bidirectional Mendelian randomization approach., Method: Single nucleotide polymorphisms (SNPs) associated with hypothyroidism were identified and selected as genetic instrumental variables from aggregated data of genome-wide association studies (GWAS). The outcome of interest, ASCVD, included seven conditions: coronary artery disease (CAD), angina pectoris (AP), myocardial infarction (MI), ischemic stroke (IS), and subtypes IS-large artery atherosclerosis (IS-LAA), IS-small vessels (IS-SV), and peripheral artery disease (PAD). MR analysis employed multiple methods-chiefly inverse variance weighting (IVW), along with MR Egger, weighted median, and weighted mode-to assess causality. Cochrane's Q test was utilized to evaluate heterogeneity in the MR findings. Causal association reliability was assessed using the MR-Egger intercept, MR-PRESSO tests, and leave-one-out analysis. Reverse MR analysis ensued if forward MR identified a positive exposure-outcome association. Moreover, the DAVID database facilitated GO functional and KEGG pathway enrichment analyses of neighboring genes to instrumental variables, exploring potential disease mechanisms., Result: GWAS pooled data yielded 122 SNPs as potential instrumental variables for hypothyroidism. Forward MR analysis, using the IVW method, indicated hypothyroidism as a risk factor for CAD (OR = 2.34, 95% CI = 1.39-3.94, P  = 0.001), AP (OR = 2.01, 95% CI = 1.28-3.16, P  = 0.002), MI (OR = 1.02, 95% CI = 1.01-1.04, P  = 0.004), and IS-SV (OR = 6.92, 95% CI = 2.45-19.55, P  < 0.001). However, no significant link was found between hypothyroidism and the remaining three diseases, with sensitivity analysis reinforcing result robustness. In contrast, reverse MR analysis did not corroborate a causal link from ASCVD to hypothyroidism. The R package identified 83 neighboring genes as instrumental variables. GO enrichment analysis via the DAVID database yielded 53 entries, predominantly involving cAMP catabolic processes, protein binding, and signal transduction. KEGG analysis identified 31 pathways, notably those related to Th1/Th2 and Th17 cell differentiation, and Herpes simplex virus 1 infection., Conclusion: The marked association between hypothyroidism and CAD, AP, MI, and IS suggests that thyroid function assessment could be integral to preventing and diagnosing specific ASCVD types. This underscores the need for individuals with hypothyroidism to be proactive regarding ASCVD risk factors. A balanced Th1/Th2 and Th17/Treg ratio may offer a novel strategy in preventing CAD and enhancing the prognosis for hypothyroid patients., 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., (© 2024 Li, Wang, Luo, Meng, Li, Li and Du.)

There is no consensus on the surgical options for repairing mild-to-moderate eyebrow defects due to burns, trauma, and skin tumors, and the outcome of the surgery is unclear. In this study, the authors evaluated the surgical outcomes and patient-reported outcomes of eyebrow defect repair with the "kite flap" in a cross-sectional study. Case data and imaging data of twelve patients with eyebrow defects undergoing repair from July 2018 to June 2021 were retrospectively analyzed, and the surgical outcomes were statistically analyzed by the Face-Q subjective evaluation scale and the surgical objective evaluation scale. In the postoperative objective evaluation, 66.67% of the patients were "very satisfied," and the scores of the Face-Q scale for the assessment of appearance and psychosocial function were significantly improved compared with those of the preoperative period, with a statistically significant difference in the data changes (P<0.05). The study showed that the "kite flap" is an excellent surgical method for repairing mild-to-moderate defects of the eyebrow, and it can meet the requirements of both function and appearance after surgery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Objective: The transcription factor MAFB is part of the MAF family and is known to promote hepatocellular carcinoma (HCC) by upregulating cyclin D1. However, its role in HCC immunity and prognosis remains unclear. This study explores the biological function, prognostic significance, and immune impact of MAFB in HCC., Methods: Immunohistochemistry was used to analyze MAFB expression in HCC and adjacent non-tumor tissues. RT-qPCR and Western blotting measured MAFB levels in HCC cell lines. Specific siRNA was used to knockdown MAFB in HCCLM3 and MHCC97H cells, followed by assays to evaluate cell proliferation, migration, and colony formation. Data from the TCGA database and online tools TIMER and TISDB were used to assess the relationship between MAFB and immune responses. A prognostic model based on MAFB-related immune genes was established, and drug sensitivity analysis was performed., Results: MAFB was significantly overexpressed in HCC tissues. Knockdown of MAFB in HCC cell lines reduced their proliferation and migration abilities. The risk model based on MAFB-related immune genes effectively predicted patient prognosis, supported by ROC curves. Gene set enrichment analysis indicated that MAFB is involved in immune-related pathways. Several drugs were identified as potentially sensitive to MAFB expression levels., Conclusion: MAFB plays a significant role in HCC development and immune regulation. The prognostic model combining MAFB-related immune genes provides valuable insights for predicting patient outcomes and identifying potential therapeutic targets., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

To identify what are the dominant lactic acid bacteria (LAB) involved in the fermentation of salt-free sauerkraut, and optimize its industrial culture conditions, we isolated and identified a strain of LAB, which is referred to as Lactobacillus sp. DF&#95;001, with the preservation number CCTCC NO: M20232593, from five different regions in Guizhou Province. Industrial culture conditions were optimized using Plackett-Burman and Central Composite design experiments, and the potential role of this LAB in salt-free sauerkraut fermentation was validated. Bioproduction was optimal with a culture time of 66 h, starch/water ratio of 1.7% and inoculum of 0.02%, which gave approximately three-fold higher yield than the basal culture medium DeMan-Rogosa-Sharpe medium (MRS). The LAB was used in small-scale industrial experiments. The Dafang LAB significantly enhanced the sensory score of the salt-free sauerkraut products by about 32% compared to the control group. The total acid content increased by about 32% and the sugar and nitrite contents were reduced by 67.27 and 69.58%, respectively. The total number of bacterial colonies decreased by 37.5%. All other indicators complied with the national standard, providing overall the basis to improve salt-free sauerkraut fermentation., 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 Wang, Li, Huang, Yang, Liu, Yu, Yuan, He, Hu, Li, Meng, Chen, Liao, Chen, Yu and Zhang.)

PEG-enzyme nanocomplexes are prepared and stabilized in an oil-in-water-type emulsion for Pickering interfacial biocatalysis, and these nanocomplexes function as catalysts and emulsifiers at the emulsion interface. The nanocomplexes are self-assembled by cross-linking mPEG-ALD with lipase, without complicated synthesis steps, toxic chemical reagents, and external carriers. Moreover, the mild cross-linking process preserves the original structure of the enzyme, the retention rate of enzyme activity is 82.1%, and the nanocomplexes are used to emulsify biphasic aqueous-organic solution into Pickering emulsion. The system exhibits excellent reusability, with enzyme activity remaining at 86.05% after five cycles, providing a desirable eco-friendly platform for carrier-free Pickering interfacial biocatalysis.

Purpose: Currently, a range of electromagnetic therapies, including magnetic field therapy, micro-currents therapy, and tumor treating fields, are under investigation for their potential in central nervous system tumor research. Each of these electromagnetic therapies possesses distinct effects and limitations. Our focus is on overcoming these limitations by developing a novel electric field generator. This generator operates by producing alternating induced currents within the tumor area through electromagnetic induction., Methods: Finite element analysis was employed to calculate the distribution of electric fields. Cell viability was assessed using the CCK-8 assay. Tumor volumes and weights served as indicators to evaluate the effectiveness of TTIF. The in-vivo imaging system was utilized to confirm tumor growth in the brains of mice., Results: TTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo ., Conclusion: TTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo . Consequently, TTIF emerges as a potential treatment option for patients with progressive or metastatic GBM., Competing Interests: YL, HonZ, TM, CN, and JY were employed by Kunlun Tripot (Beijing) Medical Technology Co., Ltd. The remaining 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 Cai, Yang, Wang, Li, Zhao, Zhao, Yang, Wang, Meng, Tong, Zheng, He, Niu, Yang, Chen, Yang, Zou and Li.)

Teratomas are germ cell tumors, commonly affecting ovaries. Teratomas rarely affect extragonadal tissues. Few cases of teratomas occurring in extragonadal tissues have been reported in the past. However, no studies have reported cases of primary teratomas occurring in the broad ligament. In this study, we report a case of a sexually inactive young woman with a 3-day history of lower abdominal pain. B-ultrasound examination revealed an abnormal strong echogenicity mass in the left adnexal area. An exploratory laparotomy was performed on her. The surgery revealed normal size and appearance of both ovaries and uterus. However, a cyst was observed in the left broad ligament, which was diagnosed as benign mature teratoma based on pathology. In this study, we report a rare case of broad ligament teratoma. The clinical data enrich our understanding of teratomas and provide a reference for further studies., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Introduction: Plasmids, the most important and versatile bacterial extrachromosomal DNA Molecules, has have been a center central topic for bacterial genetics and biology. However, the inability of short-read high-throughput sequencing methods to reliably assemble plasmids makes it difficult to investigate the diversity of plasmid structures and functions., Methods: In this work, we used the long-read Nanopore sequencing method to address this issue, by producing high quality whole genome sequences of 33 bacterial strains from 11 perianal abscess-suffering patients., Results and Discussion: Successful high quality assemblies were generated with this method, including 20 perfect assemblies out of 33 genomes. A total of 47 plasmids were identified from the bacterial strains, including 12 unique, newly identified, high quality circular plasmids. These plasmids were further subject to structural analysis, leading to the finding of significant diversification from previously known plasmids, suggesting the diversity of plasmid structure and function. Particularly, two mcr-10.1 -harboring conjugative plasmids were found from Citrobacter portucalensis and Enterobacter kobei , which were not previously reported. This works shows the feasibility of using long-read sequencing to identify plasmids, and the high diversity of plasmid structure and function that awaits further surveillance., 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 Xu, Shi, Meng, Luo, Zhu, Wang and Shen.)

Addressing the issue of inactive dead lithium deposition on the anode side remains a significant challenge for anode-free lithium metal batteries. While lithium compensation techniques can mitigate lithium depletion, directly introducing lithium compounds into the cathode material may degrade the electrode structure. Here the design and fabrication of a novel lithium replenishment separator (LRS) using a lithium compensation agent of Li 2 C 4 O 4 is reported. The electrospun LRS demonstrates excellent ionic conductivity of 1.82 mS cm -1 and a high Li + transference number of 0.51. Such a functionalized LRS not only provides additional active lithium for anode-free lithium metal batteries but also promotes uniform deposition of lithium metal. Compared with conventional polyolefin-based separators, the LRS effectively boosts LiFePO 4 ||Cu anode-free batteries with enhanced cyclability. These results suggest this LRS strategy can find promising applications in next-generation anode-free batteries with high energy densities., (© 2024 Wiley‐VCH GmbH.)

Chordoma is a rare and heterogeneous mesenchymal malignancy, with distinct clinical and biological behaviors. Till now, its comprehensive clinical-molecular characteristics and accurate molecular classification remain obscure. In this research, we enroll 102 patients with chordoma and describe their clinical, imageological, and histopathological features. Through tandem mass tag-based proteomic analysis and nonnegative matrix factorization clustering, we classify chordoma into three molecular subtypes: bone microenvironment-dominant, mesenchymal-derived, and mesenchymal-to-epithelial transition-mediated pattern. The three subtypes exhibit discrete clinical prognosis and distinct biological attributes of osteoclastogenesis and immunogenicity, oxidative phosphorylation, and receptor tyrosine kinase activation, suggesting targeted therapeutic strategies of denosumab, S-Gboxin, and anlotinib, respectively. Notably, these approaches demonstrate positive treatment outcomes for each subtype in vitro and in vivo. Altogether, this work sheds light on the clinical-proteomic characteristics of chordoma and provides a candidate precision treatment strategy for chordoma according to molecular classification, underscoring their potential for clinical application., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Diet is an important determinant of health and may moderate genetic susceptibility to obesity, but meta-analyses of available evidence are lacking., Objectives: This study aimed to systematically review and meta-analyze evidence on the moderating effect of diet on genetic susceptibility to obesity, assessed with polygenic risk scores (PRS)., Methods: A systematic search was conducted using MEDLINE, EMBASE, Web of Science, and the Cochrane Library to retrieve observational studies that examined PRS-diet interactions on obesity-related outcomes. Dietary exposures of interest included diet quality/dietary patterns and consumption of specific food and beverage groups. Random-effects meta-analyses were performed for pooled PRS- healthy eating index (HEI) interaction coefficients on body mass index (BMI) (on the basis of data from 4 cohort studies) and waist circumference (WC) (on the basis of data from 3 cohort studies)., Results: Out of 36 retrieved studies, 78% were conducted among European samples. Twelve out of 21 articles examining dietary indices/patterns, and 16 out of 21 articles examining food/beverage groups observed some significant PRS-diet interactions. However, within many articles, findings are inconsistent when testing different combinations of obesity PRS-dietary factors and outcomes. Nevertheless, higher HEI scores and adherence to plant-based dietary patterns emerged as the more prominent diet quality/patterns that moderated genetic susceptibility to obesity, whereas higher consumption of fruits and vegetables, and lower consumption of fried foods and sugar-sweetened beverages emerged as individual food/beverage moderators. Results from the meta-analysis suggest that a higher HEI attenuates genetic susceptibility on BMI (pooled PRS∗HEI coefficient: -0.08; 95% confidence interval (CI): -0.15, 0.00; P = 0.0392) and WC (-0.37; 95% CI: -0.60, -0.15; P = 0.0013)., Conclusions: Current observational evidence suggests a moderating role of overall diet quality in polygenic risk of obesity. Future research should aim to identify genetic loci that interact with dietary exposures on anthropometric outcomes and conduct analyses among diverse ethnic groups., Trial Registration Number: This study was registered at the International Prospective Register of Systematic Reviews as CRD42022312289., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Highly sensitive and specific imaging of ATP in living cells remains a challenge. Here, a novel aptasensor based endogenous enzyme-powered DNA walker for imaging ATP was proposed. The strategy leverages the highly expressed APE1 in tumor cells as the driving force of the DNA walker, achieving high sensitivity and superior imaging contrast. The method can detect ATP as low as 3.43 μM within 1 h. The approach can also effectively monitor intracellular ATP expression fluctuations and successfully differentiate between normal and cancer cells with high contrast.

Background: Poor sperm quality is a major cause of male infertility. However, evidence remains scarce on how greenness affects male sperm quality., Objectives: To assess the associations of residential greenness with male sperm quality and the modification effect of air pollution exposure on the relationship., Methods: A total of 78,742 samples from 33,184 sperm donors from 6 regions across China during 2014-2020 were included and analyzed. Individual residential greenness exposures of study subjects were estimated using the Normalized Difference Vegetation Index (NDVI) during the entire (0-90 lag days) and two key stages (0-37, and 34-77 lag days) of sperm development. Contemporaneous personal exposure levels to air pollutants were estimated using a spatio-temporal deep learning method. Linear mixed models were employed to assess the impact of greenspace in relation to sperm quality. The modification effect of air pollution on the greenspace-sperm quality relationship was also estimated., Results: Per IQR increment in NDVI exposure throughout spermatogenesis were statistically associated with increasing sperm count by 0.0122 (95 % CI: 0.0007, 0.0237), progressive motility by 0.0162 (95 % CI: 0.0045, 0.0280), and total motility by 0.0147 (95 % CI: 0.0014, 0.0281), respectively. Similar results were observed when the model added air pollutants (PM 1 , PM 2.5 or O 3 ) for adjustment. Additionally, specific air pollutants, including PM 1 , PM 2.5 , and O 3 , were found to modify this association. Notably, the protective effects of greenness exposure were more pronounced at higher concentrations of PM 1 and PM 2.5 and lower concentrations of O 3 (all P interaction  < 0.05). Statistically significant positive effects of NDVI were observed on sperm motility in early spermatogenesis and sperm count in late spermatogenesis., Conclusions: Exposure to residential greenness may have beneficial effects on sperm quality and air pollution modifies their relationship. These findings highlight the importance of adopting adaptable urban greenspace planning and policies to safeguard male fertility against environmental factors., 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.)

Superinsulation aerogels are characterized by low tensile strength and brittleness due to their high porosity. To address these limitations, multiscale architectural design inspired by nacre can be employed. This materials design approach offers a promising strategy for enhancing the mechanical strength of aerogel thermal insulation. In this study, we present nacre-inspired multilayer cellulose-silica aerogel configurations. The cellulose "brick" network imparts structural strength to effectively redistribute energy, while the nanoporous "mortar" silica blocks heat transfer, maintaining insulation and fire retardance. The multilayer composites, with a layering configuration of five cellulose layers with four silica layers (5 + 4) and a cellulose layer thickness of 1.42 mm, exhibit a thermal conductivity of 31.3 mW/(m·K), a flexural modulus of 505 MPa, and an impact strength of 7.33 kJ/m 2 . The hydrophobic composite shows a water contact angle of 127°, enhanced soundproofing with a 27% noise reduction, and a carbon footprint of 0.49 kgCO 2 eq/kg. The multilayer cellulose-silica aerogel design provides a robust, eco-friendly thermal insulation solution for green building applications.

Considering the surface soil （0-20 cm） from a typical abandoned antimony smelting factory area in Dachang Town, Qinglong County, Guizhou Province, as a case study, a total of 14 soil samples were systematically collected from both within and outside the smelting factory area. The analysis focused on the pollution status, distribution characteristics, and potential ecological risks of heavy metals such as Sb, As, Cd, Cr, Pb, Cu, Zn, Ni, and V in the soil. Additionally, an evaluation and analysis of pollution sources were conducted. The results showed that the mean concentrations of heavy metals including ω （Sb）, ω （As）, ω （Cd）, ω （Cr）, ω （Pb）, ω （Cu）, ω （Zn）, ω （Ni）, and ω （V） in the surface soil of the abandoned antimony smelting factory ranged from 4.58 to 15 049.33 mg·kg -1 . With the exception of Cr and Ni, all values exceeded the background values of soils in Guizhou province. The single factor pollution indices of Sb and As were 83.61 and 7.01, respectively, indicating severe contamination. In contrast, Pb fell within the non-polluted to slightly polluted range. The comprehensive potential ecological risk of soil heavy metals was characterized by severe potential ecological risk levels for Sb, As, and Cd, while the remaining heavy metals fell within a range of moderate to substantial potential ecological risk levels. The assessment of the geoaccumulation index revealed that the soil in the study area was primarily contaminated by Sb and As, predominantly exhibiting contamination levels ranging from moderate to severe. The results from the RAC method suggested that Sb was the dominant focus for remediation in this abandoned smelting factory. The two primary pollutants, Sb and As, exhibited elevated levels in leachate toxicity, acid-soluble fraction, available fraction, gastric phase, and intestinal phase in terms of bioavailable content, indicating a certain potential hazard. Further, correlation analysis indicated a certain correlation between the total amount of heavy metals and leachate toxicity, available fraction, acid-soluble fraction, reducible fraction, oxidizable fraction, gastric phase extractable fraction, and intestinal phase extractable fraction. The APCS-MLR model indicated that the sources of Sb, As, Zn, Cu, and Cd were primarily industrial, while the sources of Cr and V were mainly natural, and Pb originated mainly from mixed sources.

Flexible strain sensors are broadly investigated in electronic skins and human-machine interaction due to their light weight, high sensitivity, and wide sensing range. Hydrogels with unique three-dimensional network structures are widely used in flexible strain sensors for their exceptional flexibility and adaptability to mechanical deformation. However, hydrogels often suffer from damage, hardening, and collapse under harsh conditions, such as extreme temperatures and humidity levels, which lead to sensor performance degradation or even failure. In addition, the failure mechanism in extreme environments remains unclear. In this review, the performance degradation and failure mechanism of hydrogel flexible strain sensors under various harsh conditions are examined. Subsequently, strategies towards the environmental tolerance of hydrogel flexible strain sensors are summarized. Finally, the current challenges of hydrogel flexible strain sensors in harsh environments are discussed, along with potential directions for future development and applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Chronic Pulmonary Heart Disease (CPHD) significantly impacts global health, especially among middle-aged and older adults. In China, the Traditional Chinese Medicine (TCM) technique of Resolving Phlegm and Activating Blood (RPAB) is widely used to treat CPHD, although high-quality evidence supporting its efficacy remains limited., Objectives: The purpose of this study was to rigorously assess the clinical efficacy of RPAB for CPHD and elucidate the mechanisms underlying its primary herbal components., Methods: Through a detailed search of literature in both Chinese and English and strict inclusion and exclusion criteria, 18 randomized controlled trials (RCTs) were selected for meta-analysis. We identified RPAB's core herbal combinations using association rule analysis. This method statistically analyzes the frequency and correlation of herbal medicine usage. We then analyzed the chemical components of these combinations and investigated their potential intervention mechanisms on CPHD through network pharmacology., Results: The combination of RPAB with Western medicine was superior to Western medicine alone in improving blood gas analysis and pulmonary function and reducing plasma viscosity in CPHD patients. The core herbal combination identified was Astragalus membranaceus (Fisch.) Bunge, Ligusticum chuanxiong Hort. ex S. H. Qiu & al., and Stellaria alsine Grimm (ALS). This combination targeted 588 therapeutic and 27 core targets. It influenced ten core compounds across 34 pathways, primarily through the chemokine signaling pathway and the JAK-STAT signaling pathway., Conclusion: RPAB with Western medicine significantly improves CPHD treatment outcomes. The study highlights the therapeutic potential of the ALS combination, which operates through multiple pathways to remodel pulmonary arteries, decrease inflammation, and lessen oxidative stress. These insights support the clinical application of RPAB in CPHD treatment and open new avenues for research and therapeutic development., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Low-level viraemia (LLV) occurs in chronic hepatitis B (CHB) patients despite antiviral treatment, which may cause failed histological regression. Our study aimed to investigate the impact of different LLV types on fibrosis regression. The prospective study enrolled CHB patients with paired liver biopsies before and after 260 weeks of entecavir treatment. Fibrosis regression was defined by the Ishak score or P-I-R system. Patients were grouped as the SVR (HBV DNA < 20 IU/mL persistently) or LLV (HBV DNA between 20 and 2000 IU/mL), which were further grouped as very low-level viraemia (VLLV, HBV DNA < 50 IU/mL), occasionally LLV (OLLV, HBV DNA ≥ 50 IU/mL only once) and multiple LLV (MLLV, HBV DNA ≥ 50 IU/mL more than once). Logistic regression models were used to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CIs). The analysis included 111 CHB patients. In the SVR group (n = 54), 39 (72.2%) patients had fibrosis regression, which was higher than the LLV (56.1%, p = 0.080). The fibrosis regression rates for VLLV (30 patients), OLLV (17 patients) and MLLV (10 patients) were 70.0%, 52.9% and 30.0%, respectively. Compared with SVR, VLLV (aOR = 0.78; 95% CI: 0.28-2.21; p = 0.644) was not associated with fibrosis regression, but patients with non-VLLV (aOR = 0.27; 95% CI: 0.09-0.85; p = 0.025), especially with MLLV (aOR = 0.19; 95% CI: 0.04-0.97; p = 0.046) is significantly associated with hindered fibrosis regression. Our study suggests that patients with detectable serum HBV DNA levels higher than 50 IU/mL need to be monitored carefully, especially in those with more than once. Trial Registration: ClinicalTrials.gov identifiers NCT01938781 and NCT01938820., (© 2024 John Wiley & Sons Ltd.)

Nanomaterials with intrinsic enzyme mimicking activity have achieved widespread application. However, developing novel nanomaterials with multienzyme mimicry activity remains challenging. Herein, Cu 3 (HITP) 2 (HITP = 2,3,6,7,10,11-hexaiminotriphenylene) with ascorbic acid oxidase (AAO)- and peroxidase (POD)-like activity are successfully synthesized. Cu 3 (HITP) 2 exhibits excellent AAO-like activity and can specifically catalyze the oxidation reaction of ascorbic acid (AA). Dehydroascorbic acid (DHAA) obtained from the oxidation of AA is allowed to react with nonfluorescent o-phenylenediamine (OPD) to form 3-(1,2-dihydrox-yethyl) furo[3,4-b]quinoxaline-1-one (DFQ) with strong fluorescence emission. Moreover, Cu 3 (HITP) 2 is able to catalyze the chemiluminescence (CL) reaction of ABEI-H 2 O 2 to generate a strong and glow-type emission based on its POD activity. Inspired by the multienzyme mimicry activity of Cu 3 (HITP) 2 , the simple and sensitive fluorescence and chemiluminescence sensing platforms are successfully constructed and applied for the detection of AA. The sensors show high sensitivity and excellent selectivity. We believe that this multienzyme mimicry activity nanomaterial not only can be used to construct the multiple-mode biosensing platform, but also enables the extensive applications in the fields of biomedicine, energy, and environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Eplet 52SK is unique in the HLA eplet registry as targeting the whole family of DQA1*01 alleles. It is proposed as an antibody-verified eplet but has not been validated enough to deserve this label. Especially, confusion can occur with reactivity targeting the 52PQ eplet which is present on the DQB1*05 and DQB1*06 alleles families, as DQ molecule stability imposes DQA1*01 to selectively associate with these DQ-β families only. Using two Luminex single antigen (LSA) assays from two vendors, beads bearing DR-α/DQ6 heterodimers, a special build LSA panel of additional DQ beads, and an adsorption/elution strategy relying on cells from deceased donors or recombinant cells solely expressing one DQ antigen, we definitely established the antibody-verified status of eplet 52SK using patients' sera reacting only against the DQ5 and DQ6 beads of the One Lambda LSA panel in routine patients' follow up. We also show that reactivity against this eplet is not a rare event among anti-DQ1 immunisation. This study further strengthens the importance of considering the DQA1 locus in immunological studies of HLA and in organ allocation strategies., (© 2024 The Author(s). HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)

Chloro-haloacetonitrile (Cl-HAN), belongs to a group of nitrogenous disinfection by-products (N-DBPs) found in surface water, and are known to pose a major risk to the safety of human drinking water. However, the exact biological toxicity mechanism and the extent of the stress response caused by Cl-HAN remain unclear, resulting in a lack of effective measures to control its presence. Thus, the quantitative toxicological genomics and bioinformatics methods were applied to explore the effects of three chloro-haloacetonitriles (Cl-HANs) on the transcription of fusion genes under varying concentrations of stress in E. coli over 2-hour period. The initial stress response and their toxic mechanism were analyzed. The study also identified the molecular toxicity endpoint, and the core genes that are responsible for the specific toxicity of different Cl-HANs. Cl-HANs exhibited concentration-dependent characteristics of toxic effects, and caused changes in gene expression related oxidative and membrane stress. The stress response results showed that dichloroacetonitrile (dCAN) still caused significant DNA damage under the lowest concentration stress. Chloroacetonitrile (CAN) and trichloroacetonitrile (tCAN) exhibited lower genetic toxicity levels at 513 μg/L and 10.7 μg/L, respectively. The toxic effects of tCAN were widespread. And there was a good correlation between the molecular endpoint (EC-TELI 1.5 ) and the phenotypic endpoint (LD50) with r p =-0.8634 (P=0.0593). In all concentrations of stress in CAN, dCAN, and tCAN, the number of overexpressed genes shared was 15, 2, and 14, respectively. Furthermore, bioinformatics analysis demonstrated that Cl-HANs affected genes associated with general stress pathways, such as cell biochemistry and physical homeostasis, resulting in changes in biological processes. And for CAN-induced DNA damage, polA played a dominant role, while katG, oxyR, and ahpC were the core genes involved in oxidative stress induced by dCAN and tCAN, respectively. These findings provide valuable data for the toxic effect of Cl-HANs., 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 Inc. All rights reserved.)

Cellular iron is inseparably related with the proper functionalities of mitochondria for its potential to readily donate and accept electrons. Though promising, the available endeavors of iron chelation antitumor therapies have tended to be adjuvant therapies. Herein, we conceptualized and fabricated an "iron-phagy" nanoparticle (Dp44mT@HTH) capable of inducing the absolute devastation of mitochondria via inhibiting the autophagy-removal of impaired ones for promoting cancer cell death. The Dp44mT@HTH with hyaluronic acid (HA) as hydrophilic shell can specifically target the highly expressed CD44 receptors on the surface of 4T1 tumor cells. After internalization and lysosomal escape, the nanoparticle disassembles in response to the reactive oxygen species (ROS), subsequently releasing the iron chelator Dp44mT and autophagy-inhibitory drug hydroxychloroquine (HCQ). Dp44mT can then seize cellular Fe 2+ to trigger mitochondrial dysfunction via respiratory chain disturbance, while HCQ not only lessens Fe 2+ intake, but also impedes fusions of autophagosomes and lysosomes. Consequentially, Dp44mT@HTH induces irreversible mitochondrial impairments, in this respect creating a substantial toxic stack state that induces apoptosis and cell death. Initiating from the perspective of endogenous substances, this strategy illuminates the promise of iron depletion therapy via irreversible mitochondrial damage induction for anticancer treatment., 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.)

We developed a method for making immune responses to bacterial glycans T cell-dependent, which involves attachment of short, synthetic glycans to a virus-like nanoparticle (VLP). This strategy enhances immune responses to glycans by facilitating cognate T cell help of B cells, leading to antibody class switching and affinity maturation yielding high-affinity, anti-glycan antibodies. This method requires synthesis of bacterial glycans as propargyl glycosides for covalent attachment to VLPs, and the resulting short linker between the VLP and glycan is important for optimal T cell receptor recognition. In this work, glycans that are part of the capsular polysaccharides (CPS) produced by Streptococcus pneumoniae serotypes Sp6A and Sp6B were synthesized as disaccharides and trisaccharides. The optimal glycan epitope for antibody binding to the CPS from these serotypes is unknown, and differing "frames" of disaccharides and trisaccharides were prepared to elucidate the optimal antigen for antibody binding., Competing Interests: Declaration of 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.

This paper presents the development of an intelligent sensing platform dedicated to accurately identifying terahertz (THz) spectra obtained from various biochemical substances. The platform currently has two distinct identification modes, which focus on identifying five amino acids, namely phenylalanine, methionine, lysine, leucine, and threonine, and five carbohydrates, namely aspartame, fructose, glucose, lactose monohydrate, and sucrose based on their THz spectra. The first mode, called One-dimensional THz Spectrum Identification (OTSI), combines THz time-domain spectroscopy (THz-TDS) with the proposed mini convolutional neural network (MCNN) model. THz-TDS detects biochemical substances, while the MCNN model identifies the THz spectra. The MCNN model has a simple structure and only needs to deal with the THz absorption coefficients of biochemical substances, which are less computationally intensive and easily converged. The model can achieve 99.07 % accuracy in identifying one-dimensional THz spectra of the ten biochemical substances. The second mode, THz Spectrum Image-based Identification (TSII), applies the YOLO-v5 target detection model to THz spectral image recognition. The YOLO-v5 model uses THz absorption peaks as identification features and can identify biochemical substances based on only one or several THz absorption peaks. The overall identifying accuracy of the YOLO-v5 model for ten biochemical substances is 96.20 %. We also compared the MCNN and YOLO-v5 models with other deep learning and machine learning models, which demonstrate that they have better performance. This feature broadens the platform's utility in biomolecular analysis and paves the way for further research and development in detecting and analyzing diverse biological compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Diabetic retinopathy (DR), the principal cause of acquired blindness among the working-age population, is the most frequent microvascular complication of diabetes. Although metabolic disorders are hypothesized to play a role in its pathogenesis, the underlying mechanism remains largely elusive., Methods: To elucidate the mechanism, we initially compared metabolite profiles of vitreous fluid between 23 patients with DR and 12 non-diabetic controls using liquid chromatography/tandem mass spectrometry, identifying the distinct metabolite indoxyl sulfate (IS). Subsequently, streptozotocin (STZ)-induced diabetic and IS-injected rat models were established to examine the effects of IS on retinal microvasculature. RNA sequencing was conducted to identify potential regulatory mechanisms in IS-treated human retinal endothelial cells (HREC). Finally, target gene knockdown in HREC and treatment of IS-injected rats with inhibitors (targeting IS production or downstream regulators) were employed to elucidate the detailed mechanisms and identify therapeutic targets for DR., Results: Metabolomics identified 172 significantly altered metabolites in the vitreous humor of diabetics, including the dysregulated tryptophan metabolite indoxyl sulfate (IS). IS was observed to breach the blood-retinal barrier and accumulate in the intraocular fluid of diabetic rats. Both in vivo and in vitro experiments indicated that elevated levels of IS induced endothelial apoptosis and disrupted cell junctions. RNA sequencing pinpointed prostaglandin E2 (PGE 2 ) synthetase-cyclooxygenase 2 (COX-2) as a potential target of IS. Validation experiments demonstrated that IS enhanced COX-2 expression, which subsequently increased PGE 2 secretion by promoting transcription factor EGR1 binding to COX-2 DNA following entry into cells via organic anion transporting polypeptides (OATP2B1). Furthermore, inhibition of COX-2 in vivo or silencing EGR1/OATP2B1 in HREC mitigated IS-induced microcapillary damage and the activation of COX-2/PGE 2 ., Conclusion: Our study demonstrated that indoxyl sulfate (IS), a uremic toxin originating from the gut microbiota product indole, increased significantly and contributed to retinal microvascular damage in diabetic retinopathy (DR). Mechanistically, IS impaired retinal microvascular integrity by inducing the expression of COX-2 and the production of PGE 2 . Consequently, targeting the gut microbiota or the PGE 2 pathway may offer effective therapeutic strategies for the treatment of DR., (© 2024. The Author(s).)

Six-times more carbon dioxide (CO 2 ) is removed each year by terrestrial photosynthesis than fossil fuel emissions. However, the carbon is mostly returned to the atmosphere by decomposition. We found a 3775-year-old ancient wood log buried 2 meters belowground that was preserved far beyond its expected lifetime. The wood had near-perfect preservation, with carbon loss less than 5% compared to a modern sample. The lack of decay is likely due to the low permeability of the compact clay soil at the burial site. Our observation suggests a hybrid nature-engineering approach for carbon removal by burying woody biomass in similar anoxic environments. We estimate a global sequestration potential of up to 10 gigatonnes CO 2 per year with existing technology at a low cost of $30 to $100 per tonne after optimization.

Fluoride treatment of ZSM-5 zeolite can effectively adjust surface acidity and generate a secondary pore structure. In this study, a series of modified nano-HZSM-5 zeolites were prepared by NH 4 F-HF mixed solution treatment and applied to the selective conversion of bioethanol to propylene at 500 °C, atmospheric pressure, and a WHSV of 10 h -1 . The results showed that NH 4 F-HF modification weakened the surface acidity of nano-HZSM-5 zeolites, thus inhibiting coke formation. Additionally, the mesopores in the nano-HZSM-5 zeolites increased after NH 4 F-HF treatment, thereby enhancing the mass transfer rate and improving the coke-resistance ability. The NH 4 F-HF mixed solution modification significantly improved the stability of nano-HZSM-5 zeolites in catalyzing bioethanol to propylene and greatly extended the working life of nano-HZSM-5 zeolites. It can be seen from the characterization of the deactivated catalysts that coke deposition and weakening of acidity may be the key factors for catalyst deactivation.

Background: C-X-C receptor 4(CXCR4) is widely considered to be a highly conserved G protein-coupled receptor, widely involved in the pathophysiological processes in the human body, including fibrosis. However, its role in regulating macrophage-related inflammation in the fibrotic process of prostatitis has not been confirmed. Here, we aim to describe the role of CXCR4 in modulating macrophage M1 polarization through glycolysis in the development of prostatitis fibrosis., Methods: Use inducible experimental chronic prostatitis as a model of prostatic fibrosis. Reduce CXCR4 expression in immortalized bone marrow-derived macrophages using lentivirus. In the fibrotic mouse model, use adenovirus carrying CXCR4 agonists to detect the silencing of CXCR4 and assess the in vivo effects., Results: In this study, we demonstrated that reducing CXCR4 expression during LPS treatment of macrophages can alleviate M1 polarization. Silencing CXCR4 can inhibit glycolytic metabolism, enhance mitochondrial function, and promote macrophage transition from M1 to M2. Additionally, in vivo functional experiments using AAV carrying CXCR4 showed that blocking CXCR4 in experimental autoimmune prostatitis (EAP) can alleviate inflammation and experimental prostate fibrosis development. Mechanistically, CXCR4, a chemokine receptor, when silenced, weakens the PI3K/AKT/mTOR pathway as its downstream signal, reducing c-MYC expression. PFKFB3, a key enzyme involved in glucose metabolism, is a target gene of c-MYC, thus impacting macrophage polarization and glycolytic metabolism processes., (© 2024. The Author(s).)

Biomolecular interaction acts a pivotal part in understanding the mechanisms underlying the development of Alzheimer's disease (AD). Herein, we built a biosensing platform to explore the interaction between gelsolin (GSN) and different β-amyloid protein 1-42 (Aβ 1-42 ) species, including Aβ 1-42 monomer (m-Aβ), Aβ 1-42 oligomers with both low and high levels of aggregation (LLo-Aβ and HLo-Aβ) via dual polarization interferometry (DPI). Real-time molecular interaction process and kinetic analysis showed that m-Aβ had the strongest affinity and specificity with GSN compared with LLo-Aβ and HLo-Aβ. The impact of GSN on inhibiting aggregation of Aβ 1-42 and solubilizing Aβ 1-42 aggregates was evaluated by circular dichroism (CD) spectroscopy. The maintenance of random coil structure of m-Aβ and the reversal of β-sheet structure in HLo-Aβ were observed, demonstrating the beneficial effects of GSN on preventing Aβ from aggregation. In addition, the structure of m-Aβ/GSN complex was analyzed in detail by molecular dynamics (MD) simulation and molecular docking. The specific binding sites and crucial intermolecular forces were identified, which are believed to stabilize m-Aβ in its soluble state and to inhibit the fibrilization of Aβ 1-42 . Combined theoretical simulations and experiment results, we speculate that the success of GSN sequestration mechanism and the balance of GSN levels in cerebrospinal fluid and plasma of AD subjects may contribute to a delay in AD progression. This research not only unveils the molecular basis of the interaction between GSN and Aβ 1-42 , but also provides clues to understanding the crucial functions of GSN in AD and drives the development of AD drugs and therapeutic approaches., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To investigate the molecular mechanism of autophagy and apoptosis induced by ultrafine carbon black in human bronchial epithelial cells (BEAS-2B cells), and to study the intervention effect and mechanism of N-acetylcysteine (NAC) on ultrafine carbon black-induced oxidative damage in BEAS-2B cells. Methods: In March 2023, BEAS-2B cells were used as research object, an in vitro airway model exposed to ultrafine carbon black was constructed. A control group and three carbon black exposure groups (50, 100, 200 μg/ml) were set up, and the cells were treated with corresponding concentrations of ultrafine carbon black for 24 hours. In addition, the experiment was divided into control group, NAC+ control group, 100 μg/ml carbon black exposure group and NAC+ exposure group. The corresponding groups were treated with 2 mmol/L NAC for 1 h and 100 μg/ml ultrafine carbon black for 24 h, respectively. Cell viability was measured by CCK-8 assay. Intracellular reactive oxygen species (ROS) level was detected by chemical fluorescence method. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), as well as the content of malondialdehyde (MDA) were detected by colorimetry. The mRNA and protein expressions of autophagy-related genes[Atg5, Atg7, Beclin1, microtubule-associated protein light chain 3B (LC3B), p62 and lysosome-associated membrane protein 2 (LAMP2) ] and apoptosis-related genes [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase3, Caspase9 and poly (ADP-ribose) polymerase 1 (PARP1) ] were determined by fluorescence quantitative PCR and Western blot. Cell apoptosis was determined by flow cytometry. Results: Compared with the control group, the relative survival rates of BEAS-2B cells in 50, 100, 200 μg/ml carbon black exposure groups were significantly decreased, the levels of ROS and MDA were significantly increased, and the activities of SOD, GSH-Px and CAT were significantly decreased ( P <0.05). The relative survival rate, ROS and MDA levels, SOD, GSH-Px and CAT activities were significantly correlated with the exposure dose of ultrafine carbon black ( r (s)=-0.755, 0.826, 0.934, -0.810, -0.880, -0.840, P <0.05). Compared with the control group, the relative expression levels of Atg5, Atg7, Beclin1, LC3B, p62, LAMP2, Bax, Caspase3, Caspase9, PARP1 mRNA and Atg5, Atg7, Beclin1, LC3BⅡ, p62, LAMP2, Bax, cleaved Caspase3 (C-Caspase3), cleaved Caspase9 (C-Caspase9), cleaved PARP1 (C-PARP1) protein and the ratio of LC3BⅡ/LC3BⅠ in 50, 100 and 200 μg/ml carbon black exposure groups were significantly increased, while the relative expression levels of Bcl-2 mRNA and protein were significantly decreased ( P <0.05). The changes of the above indexes were significantly correlated with the exposure dose of carbon black ( r (s)=0.892, 0.879, 0.944, 0.892, 0.828, 0.880, 0.814, 0.794, 0.931, 0.918, 0.813, 0.866, 0.774, 0.695, 0.918, 0.761, 0.794, 0.944, 0.833, 0.866, 0.905, -0.886, -0.748, P <0.05). Compared with 100 μg/ml carbon black exposure group, the relative survival rate, the activities of SOD, GSH-Px and CAT in NAC+exposure group were significantly increased, while the levels of ROS and MDA were significantly decreased, and the relative expression levels of LC3B, p62 and Caspase3 mRNA and protein as well as the ratio of LC3BⅡ/LC3BⅠ were significantly decreased, and the differences were statistically significant ( P <0.05). Compared with the control group, the apoptosis rates of BEAS-2B cells in 50, 100, 200 μg/ml carbon black exposure groups were significantly increased ( P <0.05), and there was a significant positive correlation between ultrafine carbon black exposure dose and cell apoptosis rate ( r (s)=0.944, P <0.05). While compared with 100 μg/ml carbon black exposure group, the apoptosis rate of NAC+exposure group was significantly decreased, and the difference was statistically significant ( P <0.05) . Conclusion: Cell autophagy and apoptosis may be important pathophysiological mechanisms of ultrafine carbon black-induced oxidative damage in BEAS-2B cells. NAC can alleviate the occurrence of BEAS-2B cell damage caused by ultrafine carbon black by regulating oxidative stress and the cascading autophagy and apoptosis pathways.

Acinetobacter baumannii , a commonly multidrug-resistant Gram-negative bacterium responsible for large numbers of bloodstream and lung infections worldwide, is increasingly difficult to treat and constitutes a growing threat to human health. Structurally novel antibacterial chemical matter that can evade existing resistance mechanisms is essential for addressing this critical medical need. Herein, we describe our efforts to inhibit the essential A. baumannii lipooligosaccharide (LOS) ATP-binding cassette (ABC) transporter MsbA. An unexpected impurity from a phenotypic screening was optimized as a series of dimeric compounds, culminating with 1 (cerastecin D), which exhibited antibacterial activity in the presence of human serum and a pharmacokinetic profile sufficient to achieve efficacy against A. baumannii in murine septicemia and lung infection models.

The current research was designed to investigate the impact of whole-process high-quality nursing on acute pancreatitis (AP) patients' quality of life as well as the mechanism of miR-126-5p/HOXC8 axis promoting AP progression. One hundred AP patients admitted to our hospital were chosen and separated into control group (CG, n=50) and study group (SG, n=50). The CG took the routine nursing, while the SG adopted the whole-process high-quality nursing. Besides, cerulein (CE) was treated in AR42J cells to establish an experimental model of AP. The proliferation, apoptosis along with inflammation of CE-treated AR42J cells were assessed. The outcomes manifested that in contrast to the CG, the recovery time of bowel sound, the improvement time of abdominal distension, the improvement time of abdominal pain, the exhaust time and the defecation time in the SG presented shorter, the anxiety and depression scores in the SG presented lower, the WHOQOL-100 scores of patients in the SG presented higher in the fields of physiology, psychology, environment and social relations, the total incidence of complications of the SG presented lower, and the total nursing satisfaction of the SG was better. Besides, miR-126-5p presented upregulation in CE-stimulated AR42J cells, and miR-126-5p inhibition increased the proliferation along with repressed the apoptosis and inflammation in CE-stimulated AR42J cells. Moreover, HOXC8 could be the target mRNA of miR-126-5p, and HOXC8 elevation promoted the proliferation along with repressed the apoptosis and inflammation in CE-stimulated AR42J cells. In addition, rescue assays further validated that HOXC8 silence offset the protective impact of miR-126-5p repression on AP cell damage. In conclusion, our study indicated that whole-process high-quality nursing could promote the quality of life of AP patients, and revealed that miR-126-5p inhibition relieved CE-stimulated AR42J cells injury caused by AP via targeting HOXC8. Our study might offer novel insights for AP treatment and nursing.

Background: The remission rate of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients who received standard induction therapy is far from satisfactory. Improving the remission rate of MPO-AAV patients is essential. Hydroxychloroquine (HCQ), one of the classic antimalarial drugs, has been widely used in various autoimmune rheumatic diseases. This retrospective observational cohort study is aimed to evaluate the efficacy and safety of HCQ during induction treatment for MPO-AAV., Methods: The medical records of patients diagnosed with MPO-AAV at Xiangya Hospital, Central South University from January 2021 to September 2023 were collected. They were assigned to the HCQ group or control group according to whether they used HCQ. The patients included were screened by propensity score matching. To evaluate whether MPO-AAV patients benefited from HCQ, we compared the prognosis of the two groups. The adverse effects of HCQ during follow-up were recorded., Results: The composition ratio of complete remission, response and treatment resistance between HCQ group and control group were different statistically ( P  = .021). There was no significant difference between the two groups in 1-year renal survival ( P  = .789). The HCQ group had better 1-year patient survival than the control group ( P  = .049). No serious adverse effects were documented in the HCQ group., Conclusions: HCQ together with standard induction treatment may improve the remission rate of MPO-AAV patients, and HCQ had good safety in our study., 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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Sentrin/small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) perform pivotal roles in SUMO maturation and recycling, which modulate the balance of SUMOylation/de-SUMOylation and spatiotemporal functions of SUMOylation targets. The malfunction of SENPs often results in cellular dysfunction and various diseases. However, studies rarely investigated the correlation between SENP2 and lung cancer. This study revealed that SENP2 is a required contributor to lung cancer-cell growth and targets nuclear Dbf2-related 2 (NDR2, also known as serine/threonine kinase 38L or STK38L) for de-SUMOylation, which improves NDR2 kinase activity. This condition leads to the instability of downstream target p21 in accelerating the G 1 /S cell cycle transition and suggests SENP2 as a promising therapeutic target for lung cancer in the future. Specifically, astragaloside IV, an active ingredient of Jinfukang Oral Liquid (JOL, a clinical combination antilung cancer drug approved by the National Food and Drug Administration (FDA) of China), can repress lung cancer-cell growth via the SENP2-NDR2-p21 axis, which provides new insights into the molecular mechanism of JOL for lung cancer treatment., 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.)