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Age gelation is undesirable for direct UHT (dUHT) milk, which is closely related to protein hydrolysis. However, little information is available for the role of serum peptides during the age gelation. In this study, the composition and protein morphology of serum phase were characterized by RP-HPLC, ICP-MS and TEM. The results showed significant increases in soluble proteins, free amino acids, calcium, and phosphorus from casein micelles, indicating protein hydrolysis and peptide release into the serum phase. 23,466 peptides derived from caseins and other proteins were identified in serum phase by peptidomics. The serum peptide profiles of age gelation milk changed dramatically. Peptide fingerprinting revealed that plasmin and cathepsin contributed to the protein hydrolysis during age gelation, with a significant increase in their activity observed. 23 characteristic peptides were ultimately selected as potential indicators for age gelation. These findings provide new insights into the age gelation of UHT milk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the frequency and the clinical relevance of thyroid disease in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients., Methods: A total of 305 AAV patients admitted to the Second Affiliated Hospital of Chongqing Medical University between October 2010 and December 2023 were analyzed. Demographic, clinical, and laboratory data were compared between AAV patients with and without thyroid disease. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with thyroid disease in AAV patients., Results: Among the 305 AAV patients, 52 (17.0%) had concurrent thyroid disease. In univariate analysis, gender, coronary artery disease, renal involvement, anti-Ro/SSA antibodies, anti-Ro52 antibodies, anti-thyroglobulin antibodies (TgAb), and anti-thyroid peroxidase antibodies (TPOAb) exhibited significant differences between AAV patients with and without thyroid disease (P < 0.05). Multivariate analysis revealed that female gender (odds ratio (OR) = 2.423, 95% confidence interval (95% CI) 1.241, 4.729; P = 0.009), concurrent coronary artery disease (OR = 2.998, 95% CI 1.280, 7.019; P = 0.011), and positive anti-Ro/SSA antibodies (OR = 4.697, 95% CI 1.960, 11.257; P = 0.001) were associated with thyroid disease in AAV patients., Conclusion: AAV patients have a higher incidence of thyroid disease. Regular monitoring of thyroid function is advised for AAV patients, particularly for women, those with coronary artery disease, and those who are positive for anti-Ro/SSA antibodies. Key Points • AAV patients have a higher incidence of thyroid disease. • The potential clinical relevance of AAV patients with thyroid disease was explored. • Regular monitoring of thyroid function is advised for AAV patients., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer, lacks targeted therapies, posing a substantial challenge for treatment. Therefore, investigating its pathogenesis is a crucial research focus. FOXA1 and miR-634 are involved in tumorigenesis. However, the molecular mechanisms underlying the aberrant upregulation of FOXA1 expression in TNBC remain unclear. Therefore, we explore the role of miR-634 in the FOXA1-positive TNBC subtype., Methods: Quantitative reverse transcription polymerase chain reaction was used to detect miR-634 expression in breast cancer tissues and cell lines. Aberrantly activated signaling pathways and related genes in TNBC were analyzed using The Cancer Genome Atlas. The potential target of miR-634 was predicted by TargetScan, the TNBC cell proliferation rate was detected using an MTT assay, the in vitro metastatic capacity was determined by transwell assay and the cell cycle distribution was tested using flow cytometry. Western blotting was performed to measure the expression of proteins involved in the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway., Results: The expression of miR-634 was significantly down-regulated in both TNBC tissues and cells, compared with adjacent non-cancerous tissues and MCF10A, respectively. Ectopic expression of miR-634 inhibits breast cancer cell proliferation and in vitro metastasis. The TCGA-based expression profile analysis of TNBC revealed that aberrantly activated PI3K/AKT signaling may contribute to its malignant phenotype. FOXA1, the top hit of aberrantly upregulated genes in TNBC, was a direct target of miR-643. Moreover, forced expression of miR-643 drastically suppressed FOXA1 expression by the inactivation PI3K/AKT signaling., Conclusion: MiR-634 suppresses FOXA1 to inhibit the proliferation and metastasis of TNBC cells by inactivating the PI3K/AKT signaling pathway., (© 2024. The Author(s).)

The prolyl hydroxylase domain-containing (PHD or EGL9-homologs) enzyme family is mainly known for its role in the cellular response to hypoxia. HIF-PH inhibitors can stabilize hypoxia-inducible factors (HIFs), activating transcriptional programs that promote processes such as angiogenesis and erythropoiesis to adapt to changes in oxygen levels. HIF-PH inhibitors have been clinically approved for treating several types of anaemia. While most discussions of the HIF-PH signalling axis focus on hypoxia, there is a growing recognition of its importance under normoxic conditions. Recent advances in PHD biology have highlighted the potential of targeting this pathway therapeutically for a range of aging-related diseases. In this article, we review these recent discoveries, situate them within the broader context of aging and disease, and explore current therapeutic strategies that target PHD enzymes for these indications., Competing Interests: Declaration of Competing Interest All authors are affiliated with Insilico Medicine: Insilico Medicine is a global clinical-stage commercial generative artificial intelligence company with several hundred patents, pending patent applications, and commercially available software., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bisphenol analogues (BPs) are prevalent in diverse foodstuff samples worldwide. However, the occurrence of conjugated bisphenol A (BPA) and bisphenol S (BPS) metabolites in foodstuff remains poorly understood. This study analyzed eight BPs, and four conjugated BPA and BPS metabolites, in three animal-derived foodstuff and five plant-derived foodstuff samples from China. Results showed that fish foodstuff (9.7 ng/g ww) contained the highest mean concentration of BPA, followed by rice (5.1 ng/g ww) and beans foodstuff (3.6 ng/g ww). BPA-sulfate had higher mean concentrations than BPA-glucuronide in different foodstuff categories, except that in eggs foodstuff (p < 0.05). Compared with other foodstuff items, fish (3.4 ng/g ww) and vegetable (1.6 ng/g ww) foodstuff samples exhibited comparatively higher mean concentrations of BPS. Mean concentrations of BPS-sulfate were consistently higher than BPS-glucuronide in vegetables, meats, and fish foodstuff (p < 0.05). BPA contributed the major total dietary intake (DI) of BPs, with the mean DI of 435 ng/kg bw/day for women and 374 ng/kg bw/day for men, respectively. To our knowledge, this study is the first to investigate the occurrence of conjugated BPA and BPS metabolites in foodstuff, which enhances our comprehension of the origins of these conjugated metabolites in the human body., 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.)

LiCl is a promising solid electrolyte, providing it possesses high ionic conductivity. Numerous efforts have been made to enhance its ionic conductivity through aliovalent doping. However, aliovalent substitution changes the intrinsic structure of LiCl, compromising its cost-effectiveness and electrochemical stability. Here, we report nanocrystalline LiCl embedded in amorphous AlOCl compounds with a heterogeneous structure to enhance its ionic conductivity. Nanocrystallization enlarges the LiCl unit cell, while amorphization facilitates interfacial ion transport. As a result, the amorphous AlOCl-modified LiCl nanocrystal (AlOCl-nanoLiCl) demonstrates a high ionic conductivity of 1.02 mS cm -1 , which is 5 orders of magnitude higher than that of LiCl. Additionally, it exhibits high oxidative stability, low cost ($19.87 US kg -1 ), and low Young's modulus (2-3 GPa). When AlOCl-nanoLiCl is coupled with Li-rich cathodes (Li 1.17 Mn 0.55 Ni 0.24 Co 0.05 O 2 , 4.8 V vs Li + /Li), all-solid-state batteries exhibit remarkable long-term cycling stability (>1000 cycles). This work presents a novel strategy to enhance the ionic conductivity of alkaline chlorides without compromising their intrinsic advantages.

Previous research has shown that blood flow abnormalities affect major depressive disorder (MDD) from multiple perspectives. Therefore, this study aims to investigate the relationship between middle cerebral artery (MCA) blood flow velocity parameters and clinical symptom scores (Hamilton Depression Rating Scale [HAMD] and Montgomery-Åsberg Depression Rating Scale [MADRS]) in patients with MDD. We compared the MCA blood flow velocity parameters, including peak systolic velocity (MCA-PSV), end-diastolic velocity (MCA-EDV), and mean velocity (MCA-MV), between 50 MDD patients and 50 control subjects. Additionally, we analyzed the correlation between these parameters and HAMD and MADRS scores. Hemodynamic parameters such as pulsatility index and resistance index were also compared between the 2 groups. MCA-PSV, MCA-EDV, and MCA-MV were significantly lower in MDD patients compared to the control group, while pulsatility index and resistance index were significantly higher. Correlation analysis revealed that MCA-PSV, MCA-EDV, and MCA-MV were significantly negatively correlated with HAMD and MADRS scores in MDD patients, indicating that cerebral blood flow velocity decreases as depressive symptoms worsen. Furthermore, regression analysis confirmed the negative relationship between blood flow velocity parameters and clinical symptom scores. The results of this study suggest that the reduction in cerebral blood flow velocity in MDD patients may be associated with the severity of depressive symptoms. This finding provides new insights into the pathophysiological mechanisms of MDD and offers a potential theoretical basis for developing depression treatment strategies based on cerebral blood flow velocity parameters., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Traf2- and Nck-interacting kinase (TNIK) has been identified as a promising therapeutic target for the treatment of fibrosis-driven diseases. Utilizing a structure-based drug design workflow, we developed a series of potent TNIK inhibitors that modulate the conformation of the gatekeeper Met105 side chain and access the TNIK back pocket. The lead optimization efforts culminated in the discovery of the recently reported compound 4 (INS018&#95;055), a novel TNIK inhibitor. This molecule demonstrated excellent activity in both enzymatic and cell-based assays, along with high selectivity in a kinome panel. Further, in vitro and in vivo preclinical studies revealed favorable in vitro and in vivo DMPK properties. Results from multiple cell-based and animal models proved that compound 4 exhibits considerable antifibrotic and anti-inflammatory efficacy. Currently, phase II clinical trials of compound 4 are underway for the treatment of idiopathic pulmonary fibrosis (IPF).

Fibrosis, an aberrant reparative response to tissue injury, involves a disruption in the equilibrium between the synthesis and degradation of the extracellular matrix, leading to its excessive accumulation within normal tissues, and culminating in organ dysfunction. Manifesting in the terminal stages of nearly all chronic ailments, fibrosis carries a high mortality rate and poses a significant threat to human health. Heme oxygenase-1 (HO-1) emerges as an endogenous protective agent, mitigating tissue damage through its antioxidant, anti-inflammatory, and antiapoptotic properties. Numerous studies have corroborated HO-1's potential as a therapeutic target in anti-fibrosis treatment. This review delves into the structural and functional attributes, and the upstream and downstream pathways of HO-1. Additionally, the regulatory networks and mechanisms of HO-1 in cells associated with fibrosis are elucidated. The role of HO-1 in various fibrosis-related diseases is also explored. Collectively, this comprehensive information serves as a foundation for future research and augments the viability of HO-1 as a therapeutic target for fibrosis., (© 2024 Wiley Periodicals LLC.)

The complex symbiotic relationship between inflammation, the gut microbiota, and the central nervous system (CNS) has become a pivotal focus of contemporary biomedical research. Inflammation, as a physiological defense mechanism, plays a dual role as both a protective and pathological factor, and is intricately associated with gut microbiota homeostasis, often termed the "second brain." The gutbrain axis (GBA) exemplifies this multifaceted interaction, where gut health exerts significantly regulatory effects on CNS functions. Antibacterial therapies represent both promising and challenging strategies for modulating inflammation and gut microbiota composition to confer CNS benefits. However, while such therapies may exert positive modulatory effects on the gut microbiota, they also carry the potential to disrupt microbial equilibrium, potentially exacerbating neurological dysfunction. Recent advances have provided critical insights into the therapeutic implications of antibacterial interventions; nevertheless, the application of these therapies in the context of CNS health warrants a judicious and evidence-based approach. As research progresses, deeper investigation into the microbial-neural interface is essential to fully realize the potential of therapies targeting inflammation and the gut microbiota for CNS health. Future efforts should focus on refining antibacterial interventions to modulate the gut microbiota while minimizing disruption to microbial balance, thereby reducing risks and enhancing efficacy in CNS-related conditions. In conclusion, despite challenges, a more comprehensive understanding of the GBA, along with precise modulation through targeted antibacterial therapies, offers significant promise for advancing CNS disorder treatment. Continued research in this area will lead to innovative interventions and improved patient outcomes., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the author(s)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The Plant-specific AP2/ERF gene family encodes proteins involved in various biological and physiological processes. Although the genome of Coptis chinensis Franch, a plant producing benzylisoquinoline alkaloids (BIAs), has been sequenced at the chromosome level, studies on the AP2/ERF gene family in C. chinensis are lacking. Thus, a genome-wide identification of AP2/ERF gene family in C. chinensis was conducted to explore its role in BIAs biosynthesis., Results: A total of 96 CcAP2/ERF genes were identified and categorized into five subfamilies, including 43 ERFs, 32 DREBs, 17 AP2s, 3 RAVs, and 1 Soloist, based on their structural domains. These CcAP2/ERF genes were unevenly distributed across nine chromosomes. Analysis of gene duplication events identified 17 CcAP2/ERF gene pairs in the genome, with 7 involved in tandem duplication events and 10 involved in segmental duplicate events, indicating that both types of duplications contributed to the expansion of the AP2/ERF gene family. The Ka/Ks ratio analysis suggested that the CcAP2/ERF gene family underwent strong purifying selection. Two phytohormones, methyl jasmonate and abscisic acid, were identified as potential key inducers of BIAs biosynthesis due to the cis-acting element prediction. Analysis of the spatial transcriptomic data revealed that 28 differentially expressed AP2/ERF genes had the highest or relatively higher expression levels in the rhizome, 17 of which positively correlated with the tissue-specific accumulation of BIAs. Further real-time PCR verification and protein-protein interaction analysis indicated that DREB1B might be one of the central regulators in a highly complex BIAs biosynthesis network., Conclusion: These findings provide significant insight into the function of AP2/ERF genes in C. chinensis, particularly in the regulatory network of BIAs biosynthesis in C. chinensis. This study also identifies candidate genes for metabolic engineering to increase BIAs content in C. chinensis., (© 2024. The Author(s).)

Background: Air pollution-related neoplasms are a major global public health issue and are one of the leading causes of death worldwide. Air pollution is one of the important risk factors of air pollution-related neoplasms and is associated with a variety of air pollution-related neoplasms.The primary objective of this study was to estimate the epidemiological patterns of death rates and disability-adjusted life years (DALYs) associated with air pollution-related neoplasms on a global scale, covering the period from 1990 to 2019. Furthermore, we aimed to predict the trends in these epidemiological patterns up to 2050. By achieving these goals, our study seeks to provide a comprehensive understanding of the potential causes underlying the observed disparities in neoplasm-related health outcomes, ultimately contributing to the development of effective strategies for addressing this major public health issue., Methods: Based on data from the 2019 Global Burden of Disease (GBD) study, the indicators of the air pollution-related neoplasms disease burden was the numbers and age-standardized rates (ASR) of deaths and disability-adjusted life years (DALYs) from 1990 to 2019. First, we compared the burden of air pollution-related neoplasms and temporal trends by gender, age, socio-demographic index (SDI), region, and country. Furthermore, driving factors and improvement potential were evaluated using decomposition and frontier analysis. Finally, forecasting analyses of the changing trend in the burden of air pollution-related neoplasm up to 2050 was conducted based on time series forecasting models., Results: In 2019, air pollution-related neoplasms accounted for 387.45 million (95 % UI 288.04-490.06 million) deaths and 8951.97 million (95 % UI 6680.89-11342.60 million) DALYs globally. Deaths and DALYs demonstrated an upward trend from 1990 to 2019, while their ASR showed a downward trend. The disease burden and the decline degree of males were both significantly higher than that of females, and the high burden was mainly in the elderly groups. The middle SDI region possessed the highest burden with the most significant upward trend, while the high SDI region had the lowest burden with the most significant downward trend. Decomposition analyses represented that the increase in the overall deaths and DALYs of air pollution-related neoplasms was mainly driven by population growth. The predictive analyses expected that the deaths and DALYs of air pollution-related neoplasms will continue to rise, while their corresponding ASR will decrease by 2050., Conclusion: The global burden of air pollution-related neoplasms remained high, and deaths and DALYs will be on upward trends up to 2050, with differences among genders, ages, SDI levels, GBD regions, and countries. It is essential to understand the air pollution-related neoplasm burden and contributing epidemiological factors for implementing effective and factor-tailored interventions to reduce the global burden., Competing Interests: Declaration of Competing Interest All authors disclosed no relevant relationships, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The repair of critical-sized bone defects remains a major challenge for clinical orthopedic surgery. Here, we develop a surface biofunctionalized three-dimensional (3D) porous polyether-ether-ketone (PEEK) scaffold that can simultaneously promote osteogenesis and regulate macrophage polarization. The scaffold is created using polydopamine (PDA)-assisted immobilization of silk fibroin (SF) and the electrostatic self-assembly of nanocrystalline hydroxyapatite (nano-HA) on a 3D-printed porous PEEK scaffold. The SF/nano-HA functionalized surface provides a bone-like microenvironment for osteoblastic cells' adhesion, proliferation, mineralization and osteogenic differentiation. Moreover, the biofunctionalized surface can effectively drive macrophages polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Integrin β1-specific cell-matrix binding and the activation of Ca 2+ receptor-mediated signaling pathway play critical roles in the regulation of macrophage polarization. Compared with the as-printed scaffold, the SF/nano-HA functionalized porous PEEK scaffold induces minimal inflammatory response, enhanced angiogenesis, and substantial new bone formation, resulting in improved osseointegration in vivo . This study not only develops a promising candidate for bone repair but also demonstrates a facile surface biofunctionalization strategy for orthopedic implants to improve osseointegration by stimulating osteogenesis and regulating immunity.

Toxic metal content testing, environmental magnetic monitoring and in vitro bioaccessibility experiments each have their own advantages and are often used independently for environmental monitoring, but there are few studies that combine the three to evaluate the hazards of toxic metals to humans. This paper investigated the total content, magnetic properties and bioaccessibility of nine potentially toxic metal elements (Zn, Sn, Pb, Cu, Fe, Ni, Cr, Sr, Mn) in dustfall from different functional zones in Shanghai, China, and systematically compared the related results. The results show that these nine metal elements have different degrees of contamination and enrichment in outdoor dustfall, and their content distribution shows the following trend: Zn > Sn > Pb > Cu > Fe > Ni > Cr > Sr > Mn. Magnetic characteristics χ lf and SIRM are mostly positively correlated with the metal elements, indicating that the higher the content of magnetic minerals in the sample, the higher the concentration of metal elements. It was also found that χ lf , SIRM, and χ ARM can well reflect the characteristics of dustfall pollution. The magnetic minerals have a certain degree of enrichment, and the particle size of the magnetic minerals is relatively coarse, mainly in the form of coarse multi-domain and pseudo-single-domain particles, which are largely derived from anthropogenic pollution. The χ lf and PM 10 concentrations in the precipitation show relatively similar spatial trends, so χ lf , SIRM, and χ ARM can be used as air pollution indices to facilitate the evaluation of metal elements pollution in dustfall. The overall trend in gastric bioaccessibility is Pb > Zn > Mn > Cu > Cr. Due to the increase in the pH of digestive fluid, the bioavailability of toxic metals decreases significantly from the gastric stage to the intestinal stage. χ lf , SIRM, and χ ARM /SIRM are all related to the bioaccessibility of toxic metals in the intestinal stage, so they can be used as toxicity indicators to evaluate the bioaccessibility of toxic metals in dustfall., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Gastric cancer (GC) is a common upper gastrointestinal tumor. However, the evaluation of prognosis and treatment response in patients with gastric cancer remains a challenge. Programmed cell death (PCD) is one of the important terminal paths for the cells of metazoans, and is involved in a variety of biological events that include morphogenesis, maintenance of tissue homeostasis, and elimination of harmful cells. The objective of this project is to investigate the predictive significance of cell death pathways and create prognostic signatures associated to cell death, with the purpose of forecasting prognosis and providing guidance for the treatment of gastric cancer., Methods: Gene transcription profiles and corresponding clinical data of gastric cancer patients were collected from The Cancer Genome Atlas (TCGA-STAD, n = 448) and the Gene Expression Comprehensive Database (GSE84437, n = 483). Thirteen types of cell death-related genes, including apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy, cuprotosis, parthanatos, entotic cell death, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, and disulfidptosis, were analysed. Cell death-related genes associated with prognosis were identified in the TCGA-STAD training cohort using Lasso-Cox regression to generate a risk score. Patients were categorized into high and low-risk groups based on the median risk score for survival difference analysis. Cell death-related genes associated with prognosis were identified in the TCGA-STAD training cohort using Lasso-Cox regression to generate a risk score. Additionally, the response to immunotherapy in the high-risk and low-risk groups was calculated using the oncoPredict algorithm. Futhermore, the model genes were validated in the GEO validation set., Results: A total of 324 differential programmed cell death (PCD)-related genes were identified, and 65 were selected through single-factor Cox analysis. Six PCD-related genes were ultimately identified by Lasso regression to construct a prognostic risk score model. The log-rank test revealed that patients in the high-risk group had inferior survival time compared with those in the low-risk group. The area under the ROC curve (AUC) for the training group at years 1, 3, and 5 were 0.684, 0.713, 0.743, respectively, while the AUC for the validation cohort at years 1, 3, and 5 were 0.695, 0.704, and 0.707, respectively. Unsupervised clustering identified potential subtypes included in the model, and a survival difference was also observed between the two subgroups. Multifactor Cox results, combined with clinical information, demonstrated that the prognostic risk score can serve as an independent prognostic factor, irrespective of other clinical features., Conclusion: By comprehensively analyzing multiple cell death patterns, we have established a novel model that accurately forecasts the clinical prognosis and drug sensitivity of gastric cancer. It was found that all 12 representative drugs may not be suitable for patients in high-risk groups., (© 2024. The Author(s).)

Aberrant lipid metabolism has been widely recognized as a hallmark of various diseases. However, the comprehensive analysis of distinct lipids is challenging due to the complexity of lipid molecular structures, wide concentration ranges, and numerous isobaric and isomeric lipids. Usually, liquid chromatography-mass spectrometry (LC-MS)-based lipidomics requires a long time for chromatographic separation to achieve optimal separation and selectivity. Ion mobility (IM) adds a new separation dimension to LC-MS, significantly enhancing the coverage, sensitivity, and resolving power. We took advantage of the rapid separation provided by ion mobility and optimized a fast and broad-coverage lipidomics method using the LC-IM-MS technology. The method required only 8 minutes for separation and detected over 1000 lipid molecules in a single analysis of common biological samples. The high reproducibility and accurate quantification of this high-throughput lipidomics method were systematically characterized. We then applied the method to comprehensively measure dysregulated lipid metabolism in patients with colorectal cancer (CRC). Our results revealed 115 significantly changed lipid species between preoperative and postoperative plasma of patients with CRC and also disclosed associated differences in lipid classes such as phosphatidylcholines (PC), sphingomyelins (SM), and triglycerides (TG) regarding carbon number and double bond. Together, a fast and broad-coverage lipidomics method was developed using ion mobility-mass spectrometry. This method is feasible for large-scale clinical lipidomic studies, as it effectively balances the requirements of high-throughput and broad-coverage in clinical studies.

Recently, synthesized N-linked-disalicylaldehyde H 2 Q JI probes have been used to detect heavy metal ions in the experiment conveniently. Nevertheless, there needs to be a more in-depth examination of the excited state intramolecular proton transfer (ESIPT) mechanism and photophysical properties of the probe. This work remedied it based on quantum chemistry calculations. We contained due hydrogen bond (O1-H2 ⋯ N3 and O4-H5 ⋯ O6) and then analyzed bond parameters, IR vibration spectra, and non-covalent interaction. The bond strength is enhanced under photoexcitation, and the former is significantly stronger. The calculated electron spectra are in agreement with the experimental values. The results of the S 0 and S 1 potential energy curves and IRC calculations also confirm the unique ESIPT behavior, which isan excited stated stepwise double proton transfer. The fluorescence, internal conversion, and intersystem crossing rate of KD molecules (twisted-, double proton transfer) were calculated respectively to reveal the radiative and non-radiative pathways. It proved that the corresponding spectra are not obtained since the electrons are mainly deactivated by the ISC (S 1 ->T 1 ). Furthermore, the interfragment charge transfer (IFCT) approach indicates that the molecule possesses twisted intramolecular charge transfer (TICT) characteristics, which lead to the quenching of fluorescence introduction., 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.)

Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11β-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11β-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11β-HSD1 by using bone-targeted 11β-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11β-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity., (© 2024. The Author(s).)

Aims: Volatile organic compounds (VOCs) have an important function in plant growth-promoting rhizobacteria (PGPR) development and plant growth. This study aimed to identify VOCs of the PGPR strain, Stutzerimonas stutzeri NRCB010, and investigate their effects on NRCB010 biofilm formation, swarming motility, colonization, and tomato seedling growth., Methods and Results: Solid-phase microextraction and gas chromatography-mass spectrometry were performed to identify the VOCs produced during NRCB010 fermentation. A total of 28 VOCs were identified. Among them, seven (e.g. γ-valerolactone, 3-octanone, mandelic acid, 2-heptanone, methyl palmitate, S-methyl thioacetate, and 2,3-heptanedione), which smell well, are beneficial for plant, or as food additives, and without serious toxicities were selected to evaluate their effects on NRCB010 and tomato seedling growth. It was found that most of these VOCs positively influenced NRCB010 swarming motility, biofilm formation, and colonization, and the tomato seedling growth. Notably, γ-valerolactone and S-methyl thioacetate exhibited the most positive performances., Conclusion: The seven NRCB010 VOCs, essential for PGPR and crop growth, are potential bioactive ingredients within microbial fertilizer formulations. Nevertheless, the long-term sustainability and replicability of the positive effects of these compounds across different soil and crop types, particularly under field conditions, require further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by synovial hyperplasia, and fibroblast-like synoviocytes (FLSs) constitute the majority of cells in the synovial tissue, playing a crucial role in the onset of RA. Dysregulation of FLSs function is a critical strategy in treating joint damage associated with RA. Non-coding RNAs, a class of RNA molecules that do not encode proteins, participate in the development of various diseases. This article aims to review the progress in the study of long non-coding RNAs, microRNAs, and circular RNAs in FLSs. Non-coding RNAs are involved in the pathogenesis of RA, directly or indirectly regulating FLSs' proliferation, migration, invasion, apoptosis, and inflammatory responses. Furthermore, non-coding RNAs also influence DNA methylation and osteogenic differentiation in FLSs. Therefore, non-coding RNAs hold promise as biomarkers for diagnosing RA. Targeting non-coding RNAs in FLSs locally represents a potential strategy for future therapies in RA., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Purpose: Hashimoto's thyroiditis (HT) is a significant public health concern, particularly among females. While existing studies have explored the correlation between serum iron levels and HT, limited research has specifically focused on this association in reproductive-age females. Our study aims to investigate the relationship between serum iron and HT., Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) database (2007-2012), we employed weighted multivariate logistic regression models, an XGBoost model, and smooth curve fitting. We assessed the correlation between serum iron and HT and examined linear and non-linear relationships with thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb)., Results: Among 2,356 participants, each unit increase in serum iron was associated with a 43% reduced risk of HT (Odds Ratios (OR) 0.574; 95% Confidence Interval (CI) 0.572, 0.576). Quartile analysis confirmed these effects. The XGBoost model identified serum iron as the most significant variable correlated with HT. Smooth curves revealed a linear association between log2-transformed serum iron and HT. Additionally, log2-transformed serum iron inversely correlated with TPOAb levels ( β -15.47; 95% CI -25.01, -5.92), while a non-linear relationship was observed with TgAb., Conclusion: Our study reveals that in reproductive-age women, every unit increase in serum iron is associated with a 43% lower risk of HT, demonstrating an inverse relationship. Additionally, serum iron exhibits a negative correlation with TPOAb and a non-linear association with TgAb., 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 Zhang, Li, Yang, Luo, Wu, Wang, Qin, Ren and Hu.)

Competing Interests: Both authors have disclosed no conflicts of interest.

Background: Desmoglein-2 (DSG2) has been reported to play pivotal roles in various diseases. However, its roles in cervical cancer (CC) remain insufficiently elucidated. Here, we aimed to comprehensively explore the functional mechanisms of DSG2 in CC using bioinformatics and experimental methods., Methods: Several online databases, including Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE, LinkedOmics, MetaScape, Human protein atlas (HPA), OMICS and single-cell RNA sequencing (scRNA-seq) data were used to explore the expression, prognosis, gene mutations, and potential signaling pathway of DSG2 in CC. Quantitative real-time PCR (qRT-PCR) and western blotting were used to measure DSG2 expression in collected samples. Experimental assays were conducted to verify the effects of dysregulated DSG2 on cervical cell lines in vitro., Results: Bioinformatic analyses revealed that DSG2 was significantly up-regulated in CC compared to normal cervical tissues at both mRNA and protein levels. Elevated DSG2 levels were also associated with poor prognosis and clinical parameters (e.g., cancer stages, tumor grade, nodal metastasis status, etc.). DSG2 expression was predominantly observed in epithelial cells, increasing with disease progression on a single-cell resolution. Additionally, up-regulation of DSG2 significantly enhanced tumor purity by reducing the infiltration of immune cells (e.g., B cells, T cells, NK cells, etc.). Over-expression of DSG2 was further validated in collected CC samples at both mRNA and protein levels. Knockdown of DSG2 markedly reduced the proliferation and invasion of CC cell lines in vitro., Conclusions: In summary, elevated levels of DSG2 were significantly associated with poor prognosis and diminished immune infiltration in CC. Thus, DSG2 may serve as a potential therapeutic and diagnostic biomarker for CC., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier GmbH.)

Lysosomal transmembrane acetylation of heparan sulfates (HS) is catalyzed by HS acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT), whose dysfunction leads to lysosomal storage diseases. The mechanism by which HGSNAT, the sole non-hydrolase enzyme in HS degradation, brings cytosolic acetyl-coenzyme A (Ac-CoA) and lysosomal HS together for N-acyltransferase reactions remains unclear. Here, we present cryogenic-electron microscopy structures of HGSNAT alone, complexed with Ac-CoA and with acetylated products. These structures explain that Ac-CoA binding from the cytosolic side causes dimeric HGSNAT to form a transmembrane tunnel. Within this tunnel, catalytic histidine and asparagine approach the lumen and instigate the transfer of the acetyl group from Ac-CoA to the glucosamine group of HS. Our study unveils a transmembrane acetylation mechanism that may help advance therapeutic strategies targeting lysosomal storage diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Hyperuricemia (HUA) is one of the most common chronic diseases today, with a prevalence exceeding 14 % in both the United States and China. Current clinical treatments for HUA focus on promoting uric acid (UA) excretion and inhibiting UA production, but often neglect the strain on the liver and kidneys. The fruit of Alpinia oxyphylla (A. oxyphylla) is known to improve renal function, regulate metabolism, and exhibit anti-inflammatory effects; however, its effectiveness and mechanisms in treating HUA are not well understood. In this study, HUA mice induced by potassium oxonate and adenine were treated with A. oxyphylla polysaccharide (AFP) for 21 days. The levels associated with HUA were quantified using assay kits to evaluate the impact of AFP on HUA. Serum metabolomics and 16S rRNA sequencing were used to investigate the mechanisms by which AFP ameliorates HUA. The results showed that AFP treatment reduced abnormal biochemical levels, including UA, blood urea nitrogen, and creatinine, in HUA mice. AFP inhibited UA synthesis by regulating pyrimidine metabolism and the metabolism of alanine, aspartate and glutamate, reduced kidney inflammation, and promoted UA excretion by regulating intestinal flora. Thus, AFP appears to be an effective agent for alleviating HUA symptoms., 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 protein aggregation induced by UHT treatment shortens the shelf life of UHT milk. However, the mechanism of β-Lg induced casein micelle aggregation remains unclear. Herein, the dynamic interaction between β-Lg and casein micelles during UHT processing was investigated by experimental techniques and molecular dynamics simulations. Results showed that β-Lg decreased the stability of casein micelles, increased their size and zeta potential. Raman and FTIR spectra analysis suggested that hydrogen and disulfide bonds facilitated their interaction. Cryo-TEM showed that the formation of the casein micelle/β-Lg complex involved rigid binding, flexible linking, and severe cross-linking aggregation during UHT processing. SAXS and MST demonstrated β-Lg bound to κ-casein on micelle surfaces with a dissociation constant (Kd) of 3.84 ± 1.14 μm. Molecular docking and dynamic simulations identified the interacting amino acid residues and clarified that electrostatic and van der Waals forces drove the interaction. UHT treatment increased hydrogen bonds and decreased total binding energy. The non-covalent binding promoted the formation of disulfide bonds between β-Lg and casein micelles under heat treatment. Ultimately, it was concluded that non-covalent interaction and disulfide bonding resulted in casein micelle/β-Lg aggregates. These findings provided scientific insights into protein aggregation in UHT milk., 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.)

A variety of per- and polyfluoroalkyl substances (PFASs) have been released into the environment via wastewater treatment plant (WWTP) effluent, with current target and nontarget analytical methods typically focusing on negatively ionized PFASs while largely overlooking positively ionized ones. In this study, five cationic PFASs, perfluoroalkyl sulfonyl quaternary ammonium substances (PFAQASs), were first identified in surface water impacted by the WWTP effluent, applying a metabolomics-based nontarget analysis method. Environmental behaviors of identified novel PFAQASs were further investigated. In surface water, sediment, and fish (Coilia mystus) samples collected from the Yangtze River, 8:3 PFAQA was consistently the predominant PFAQASs, with the mean concentrations of 90 ng/L (< LOD-558 ng/L), 92 ng/g dw (< LOD-421 ng/g dw), and 2.3 ng/g ww (< LOD-4.6 ng/g ww), respectively. This study highlights the necessity to discover other cationic PFASs in the environment. Among PFAQASs, 8:4 PFAQA (4.2, range 3.4 - 4.6) had the highest mean sediment-water partitioning coefficient (log K oc ), followed by 8:3 PFAQA (3.9, 2.8 - 4.5) and 6:3 PFAQA (3.7, 3.3 - 4.1). The log K oc of PFAQASs showed a general increase trend with the increasing carbon chain length. Mean bioaccumulation factor (BAF) values of PFAQASs calculated in the collected fish from the Yangtze River ranged from 1.9 ± 0.32 (4:3 PFAQA) to 2.9 ± 0.34 (8:4 PFAQA). The mean BAF values of PFAQASs generally increased with the carbon chain length. Further studies are warranted to elucidate the environmental fate, potential toxicity, and human exposure implications for these identified novel PFASs., 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.aaaa, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Metastasis, the primary cause of death in lung cancer patients, is facilitated by cytoskeleton remodeling, which plays a crucial role in cancer cell migration and invasion. However, the precise regulatory mechanisms of intracellular trafficking proteins involved in cytoskeleton remodeling remain unclear. In this study, we have identified Rabenosyn-5 (Rbsn) as an inhibitor of filopodia formation and lung cancer metastasis. Mechanistically, Rbsn interacts with CDC42 and functions as a GTPase activating protein (GAP), thereby inhibiting CDC42 activity and subsequent filopodia formation. Furthermore, we have discovered that Akt phosphorylates Rbsn at the Thr253 site, and this phosphorylation negates the inhibitory effect of Rbsn on CDC42 activity. Additionally, our analysis reveals that Rbsn expression is significantly downregulated in lung cancer, and this decrease is associated with a worse prognosis. These findings provide strong evidence supporting the role of Rbsn in suppressing lung cancer progression through the inhibition of metastasis., (© 2024. The Author(s).)

Amyotrophic lateral sclerosis as a fatal neurodegenerative disease currently lacks effective therapeutic agents. Thus, finding new therapeutic targets to drive disease treatment is necessary. In this study, we utilized brain and plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis to identify potential drug targets for amyotrophic lateral sclerosis. Additionally, we validated our results externally using other datasets. We also used Bayesian co-localization analysis and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets. Mendelian randomization analysis indicated that elevated levels of ANO5 (OR = 1.30; 95 % CI, 1.14-1.49; P = 1.52E-04), SCFD1 (OR = 3.82; 95 % CI, 2.39-6.10; P = 2.19E-08), and SIGLEC9 (OR = 1.05; 95% CI, 1.03-1.07; P = 4.71E-05) are associated with an increased risk of amyotrophic lateral sclerosis, with external validation supporting these findings. Co-localization analysis confirmed that ANO5, SCFD1, and SIGLEC9 (coloc.abf-PPH4 = 0.848, 0.984, and 0.945, respectively) shared the same variant with amyotrophic lateral sclerosis, further substantiating potential role of these proteins as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of amyotrophic lateral sclerosis. Our findings suggested that elevated levels of ANO5, SCFD1, and SIGLEC9 are connected with an increased risk of amyotrophic lateral sclerosis and might be promising therapeutic targets. However, further exploration is necessary to fully understand the underlying mechanisms involved., Competing Interests: Declaration of competing interest All authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

It has been demonstrated that ferulic acid (FA) can be effectively encapsulated using wheat gluten amyloid fibrils (AF) and chitosan (CS) in a double network hydrogel (DN) form, with cross-linking mediated by Genipin (GP). Within this system, the DN comprising gluten AF-FA and CS-FA exhibited optimal loading metrics at a formulation designated as DN8, achieving a load efficiency of 88.5 % and a load capacity of 0.78 %. Analysis through fluorescence quenching confirmed that DN8 harbored the highest quantity of FA. Fourier-transform infrared spectroscopy (FTIR) further verified a significant increase in β-sheet content post-hydrogel formation, enhancing the binding capacity for FA. Rheological assessments indicated a transition from solution to gel, delineating the phase state of the DN. Comprehensive in vitro digestion studies revealed that DN8 provided superior sustained release properties, exhibited the highest total antioxidant capacity, and displayed potent inhibitory activities against angiotensin I converting enzyme (ACE) and acetylcholinesterase (Ach-E). Additionally, the DN significantly bolstered the stability of FA against photothermal degradation. Collectively, these findings lay foundational insights for the advancement of the wheat gluten AF-based delivery system for bioactive compounds and provided a theoretical basis for the development of functional foods., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Huijuan Zhang reports financial support was provided by National Natural Science Foundation of China (No. 32372365). Huijuan Zhang reports financial support was provided by Beijing Natural Science Foundation (No. 6232001). If there are other authors, they 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.)

Background: Sarcopenia, a hallmark of age-related muscle function decline, significantly impacts elderly physical health. This systematic review aimed to investigate the impact of gut microbiota on sarcopenia., Methods: Publications up to September 24, 2023 were scrutinized on four databases - PubMed, Web of Science, Cochrane Library, and Embase - using relevant keywords. Non-English papers were disregarded. Data regarding gut microbiota alterations in sarcopenic patients/animal models were collected and examined., Results: Thirteen human and eight animal studies were included. The human studies involved 732 sarcopenic or potentially sarcopenic participants (aged 57-98) and 2559 healthy subjects (aged 54-84). Animal studies encompassed five mouse and three rat experiments. Results indicated an increase in opportunistic pathogens like Enterobacteriaceae, accompanied by changes in several metabolite-related organisms. For example, Bacteroides fluxus related to horse uric acid metabolism exhibited increased abundance. However, Roseburia, Faecalibacterium, Faecalibacterium prausnitzii, Eubacterium retale, Akkermansiaa, Coprococcus, Clostridium&#95;XIVa, Ruminococcaceae, Bacteroides, Clostridium, Eubacterium involved in urolithin A production, and Lactobacillus, Bacteroides, and Clostridium associated with bile acid metabolism displayed decreased abundance., Conclusions: Age-related sarcopenia and gut microbiota alterations are intricately linked. Short-chain fatty acid metabolism, urolithin A, and bile acid production may be pivotal factors in the gut-muscle axis pathway. Supplementation with beneficial metabolite-associated microorganisms could enhance muscle function, mitigate muscle atrophy, and decelerate sarcopenia progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Immune-mediated liver injury is a common characteristic of various liver diseases, including autoimmune and viral hepatitis. Here, we investigated the role of DEAD-box helicase 3, X-linked (DDX3X) in immune-mediated liver injury. Liver injury was induced in C57BL/6J mice via concanavalin A (Con A). DDX3X hepatocyte-specific knockout (DDX3X ΔHep ) mice and control (DDX3X fl/fl ) mice were utilized to investigate the role of DDX3X in liver injury. Primary hepatocytes were treated with tunicamycin (TM) to induce ER stress in vitro. The expression of DDX3X in patients with various liver diseases was evaluated. Hepatic DDX3X expression increased, and DDX3X translocated from the cytoplasm to the nucleus during Con A-induced liver injury. DDX3X deficiency ameliorated mouse liver injury and reduced ER stress in liver tissue. The inhibition of ER stress with 4-PBA significantly attenuated liver injury while decreasing DDX3X levels in liver tissue. However, the upregulation of hepatic DDX3X expression reversed Con A-induced liver injury and negated the protective effect of 4-PBA. Mechanistically, the nuclear translocation of DDX3X promoted ER stress-induced apoptosis through the transcriptional induction of CHOP. Moreover, DDX3X was elevated and translocated into the nucleus in patients with HBV-LF and AIH. Additionally, serum DDX3X levels markedly increased in patients with HBV-LF, and a consistent decrease in DDX3X was associated with a good prognosis. The cytoplasmic-to-nuclear translocation of DDX3X promotes ER stress-induced apoptosis, which is an obligatory step that drives hepatic necrosis and tissue damage. Notably, DDX3X is a potential therapeutic target for immune-mediated liver injury., (© 2024. The Author(s).)

Background: Excessive subchronic fluoride exposure can cause severe damage to detoxification organs, including the liver. Sodium butyrate has anti-inflammatory, antitumor, antioxidant and immunomodulatory properties. However, relatively few studies have investigated the effects of sodium butyrate on liver injury caused by subchronic fluoride exposure. The purpose of this research was to investigate the effect and mechanism of sodium butyrate on fluoride-induced hepatic inflammatory injury via the expression of nod-like receptor protein 3 (NLRP3)., Methods: Mice were subjected to randomization into four groups, control group (C), fluorosis group (F), sodium butyrate alone group (S), and treatment group (Y). The mice in groups F and F + S drank 100 mg/L sodium fluoride-containing distilled water freely every day. After fluoride exposure lasted for 3 months, the mice in group S and F + S were gavaged with sodium butyrate daily at a concentration of 1000 mg/kg. Following the treatment regimen, liver specimens were collected for analysis. The mRNA and protein expression levels of inflammatory factors and NLRP3 and its downstream gene were measured by RT-qPCR and western blotting., Results: The histological hematoxylin and eosin (H&E) staining of liver showed that the subchronic fluoride-exposed group were chronic inflammation. The liver of treatment group were less vacuolar degeneration and inflammatory infiltration. The results of the biochemical assay showed that the subchronic fluoride-exposed group were liver injury. In addition, the detection of oxidative stress indicators showed that chronic subchronic fluoride exposure could lead to an increase in the level of oxidative stress in the liver, and the treatment alleviated this increase. RT-qPCR results showed that compared with those in the control group, the mRNA levels of the inflammatory factors TNF-α, IL-6 and IL-1β, the NLRP3 inflammasome and its downstream factors NLRP3, caspase-1, gasdermin D (GSDMD) and IL-18 increased in the liver tissue of mice in the subchronic fluoride-exposed group. Sodium butyrate released inflammatory factors during subchronic fluoride exposure and inhibited the protein expression of activated NLRP3 to a certain extent., Conclusions: Sodium butyrate may play a protective role by antagonizing the production of activated inflammasomes and their downstream inflammatory factors in the livers of subchronic fluoride-exposed mice., (© 2024. The Author(s).)

The dynamic disulfide linkage plays a vital role in various biological processes as well as drugs and biomaterials. The conversion of thiols to their corresponding disulfides is a hallmark of sulfur chemistry, but notoriously difficult to control. Achieving optimal reactivity and selectivity continues to pose significant challenges. Here, we describe a click chemistry for disulfide formation from thiols in both batch and flow-mode using SO 2 F 2 , which display exceptional selectivity toward disulfide formation through an effective nucleophilic substitution cascade. This reaction's unique characteristics satisfy the stringent click-criteria with its high thermodynamic driving force, straightforward conditions, wide scope, quantitative yields, exceptional chemoselectivity, and non-chromatographic purification process. The modular synthesis of symmetrical, unsymmetrical, cyclic and polydisulfides is demonstrated, along with the formation of disulfide cross-linked hydrogels., (© 2024. The Author(s).)

Background: Parkinson's disease (PD) is a neurodegenerative disorder marked by the loss of dopaminergic neurons and the formation of α-synuclein aggregates. Mitochondrial dysfunction and oxidative stress are pivotal in PD pathogenesis, with impaired mitophagy contributing to the accumulation of mitochondrial damage. Hederagenin (Hed), a natural triterpenoid, has shown potential neuroprotective effects; however, its mechanisms of action in PD models are not fully understood., Method: We investigated the effects of Hed on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in SH-SY5Y cells by assessing cell viability, mitochondrial function, and oxidative stress markers. Mitophagy induction was evaluated using autophagy and mitophagy inhibitors and fluorescent staining techniques. Additionally, transgenic Caenorhabditis elegans (C. elegans) models of PD were used to validate the neuroprotective effects of Hed in vivo by focusing on α-synuclein aggregation, mobility, and dopaminergic neuron integrity., Results: Hed significantly enhanced cell viability in 6-OHDA-treated SH-SY5Y cells by inhibiting cell death and reducing oxidative stress. It ameliorated mitochondrial damage, evidenced by decreased mitochondrial superoxide production, restored membrane potential, and improved mitochondrial morphology. Hed also induced mitophagy, as shown by increased autophagosome formation and reduced oxidative stress; these effects were diminished by autophagy and mitophagy inhibitors. In C. elegans models, Hed activated mitophagy and reduced α-synuclein aggregation, improved mobility, and mitigated the loss of dopaminergic neurons. RNA interference targeting the mitophagy-related genes pdr-1 and pink-1 partially reversed these benefits, underscoring the role of mitophagy in Hed's neuroprotective actions., Conclusion: Hed exhibits significant neuroprotective effects in both in vitro and in vivo PD models by enhancing mitophagy, reducing oxidative stress, and mitigating mitochondrial dysfunction. These findings suggest that Hed holds promise as a therapeutic agent for PD, offering new avenues for future research and potential drug development., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Dyslipidemia is increasingly common in people living with HIV (PLHIV), thereby increasing the risk of cardiovascular events and diminishing the quality of life for these individuals. The study of blood lipid metabolism of PLHIV has great clinical significance in predicting the risk of cardiovascular disease. Therefore, this study aims to examine the blood lipid metabolism status of HIV-infected patients in Huzhou before and after receiving highly active antiretroviral therapy (HAART) and to explore the impact of different HAART regimens on dyslipidemia., Method: PLHIV confirmed in Huzhou from June 2010 to June 2022 was included. The baseline characteristics and clinical data during the follow-up period were collected, including some blood lipid indicators (total cholesterol and triglycerides) and HAART regimens. A multivariate logistic regression model and the generalized estimating equation model were used to analyze the independent effects of treatment regimens on the risk of dyslipidemia., Result: The overall prevalence of dyslipidemia among PLHIV after HAART was 70.11%. PLHIV receiving lamivudine (3TC) + efavirenz (EFV) + zidovudine (AZT) had a higher prevalence of dyslipidemia compared to those receiving 3TC+EFV+tenofovir disoproxil fumarate (TDF). In a logistic analysis adjusted for important covariates such as BMI, age, diabetes status, etc., we found that the risks of dyslipidemia were higher with 3TC+EFV+AZT (dyslipidemia: odds ratio [OR] = 2.09, 95% confidence interval [Cl]: 1.28-3.41; TG ≥1.7: OR = 2.40, 95%Cl:1.50-3.84) than with 3TC+EFV+TDF. Furthermore, on PLHIV that was matched 1:1 by the HAART regimens, the results of the generalized estimation equation again showed that 3TC+EFV+AZT (TG ≥1.7: OR = 1.84, 95%Cl: 1.10-3.07) is higher for the risk of marginal elevations of TG than 3TC+EFV+TDF., Conclusion: The prevalence of dyslipidemia varies according to different antiretroviral regimens. Using both horizontal and longitudinal data, we have repeatedly demonstrated that AZT has a more adverse effect on blood lipids than TDF from two perspectives. Therefore, we recommend caution in using the 3TC+EFV+AZT regimen for people at clinical risk of co-occurring cardiovascular disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Metabolic and transcriptional reprogramming are crucial hallmarks of carcinogenesis that present exploitable vulnerabilities for the development of targeted anticancer therapies. Through controlling the balance of the cellular methionine (MET) metabolite pool, MET adenosyl transferase 2 alpha (MAT2A) regulates crucial steps during metabolism and the epigenetic control of transcription. The aberrant function of MAT2A has been shown to drive malignant transformation through metabolic addiction, transcriptional rewiring, and immune modulation of the tumor microenvironment (TME). Moreover, MAT2A sustains the survival of 5'-methylthioadenosine phosphorylase (MTAP)-deficient tumors, conferring synthetic lethality to cancers with MTAP loss, a genetic alteration that occurs in ∼15% of all cancers. Thus, the pharmacological inhibition of MAT2A is emerging as a desirable therapeutic strategy to combat tumor growth. Here, we review the latest insights into MAT2A biology, focusing on its roles in both metabolic addiction and gene expression modulation in the TME, outline the current landscape of MAT2A inhibitors, and highlight the most recent clinical developments and opportunities for MAT2A inhibition as a novel anti-tumor therapy., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Multisensor (MS) data fusion is important for improving the stability of vehicle environmental perception systems. MS joint calibration is a prerequisite for the fusion of multimodality sensors. Traditional calibration methods based on calibration boards require the manual extraction of many features and manual registration, resulting in a cumbersome calibration process and significant errors. A joint calibration algorithm for a Light Laser Detection and Ranging (LiDAR) and camera is proposed based on deep learning without the need for other special calibration objects. A network model constructed based on deep learning can automatically capture object features in the environment and complete the calibration by matching and calculating object features. A mathematical model was constructed for joint LiDAR-camera calibration, and the process of sensor joint calibration was analyzed in detail. By constructing a deep-learning-based network model to determine the parameters of the rotation matrix and translation matrix, the relative spatial positions of the two sensors were determined to complete the joint calibration. The network model consists of three parts: a feature extraction module, a feature-matching module, and a feature aggregation module. The feature extraction module extracts the image features of color and depth images, the feature-matching module calculates the correlation between the two, and the feature aggregation module determines the calibration matrix parameters. The proposed algorithm was validated and tested on the KITTI-odometry dataset and compared with other advanced algorithms. The experimental results show that the average translation error of the calibration algorithm is 0.26 cm, and the average rotation error is 0.02°. The calibration error is lower than those of other advanced algorithms.

Memristors are considered one of the most promising new-generation memory technologies due to their high integration density, fast read/write speeds, and ultra-low power consumption. Natural biomaterials have attracted interest in integrated circuits and electronics because of their environmental friendliness, sustainability, low cost, and excellent biocompatibility. In this study, a sustainable biomemristor with Ag/mugwort:PVDF/ITO structure was prepared using spin-coating and magnetron sputtering methods, which exhibited excellent durability, significant resistance switching (RS) behavior and unidirectional conduction properties when three metals were used as top electrode. By studying the conductivity mechanism of the device, a charge conduction model was established by the combination of F-N tunneling, redox, and complexation reaction. Finally, the novel logic gate circuits were constructed using the as-prepared memristor, and further memristor based encryption circuit using 3-8 decoder was innovatively designed, which can realize uniform rule encryption and decryption of medical information for data and medical images. Therefore, this work realizes the integration of memristor with traditional electronic technology and expands the applications of sustainable biomemristors in digital circuits, data encryption, and medical image security., 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.)

Scabrol B and Scabrol C, two newly identified iridoid derivatives ( 1 and 2 ) and six known compounds ( 3 - 8 ), were extracted from the roots of Patrinia scabra . The structures of these derivatives, including their absolute configurations, were elucidated via comprehensive NMR analysis, chemical derivatization, and quantum chemical ECD calculations. All isolated compounds were evaluated for their anti-renal fibrosis activity. The results demonstrate that compounds 1 and 2 showed dose-dependent protective effects against renal fibrosis in vitro by reducing the expression of fibronectin, collagen I, and alpha-smooth muscle actin ( α -SMA) in NRK-49f cells mediated by TGF- β 1.

In today's social environment, the objective reality of people's increasing life pressure, environmental deterioration, and enhanced ultraviolet rays caused by the destruction of the ozone layer has led to the aggravation of people's oxidative stress. Therefore, exogenous antioxidant peptides have become a hot topic in research. In the context of insufficient protein supply and resource recycling, almond meal was used as raw material in this study. As a by-product of oil processing, it has a protein content of 68 % and antioxidant-related amino acids accounted for 84.62 %, which can be used as a high-quality natural source of antioxidant peptides. Taking antioxidant activity as the only indicator, papain was screened as a hydrolase, and 7 antioxidant peptides such as YLSF, LPSYVN and SPHWNVN were separated and purified. The affinity energy of docking with Keap1-Nrf2-ARE protein molecules was -7.5--8.9 kal/mol, and hydrophobic stacking, hydrogen bonding and intermolecular forces were maintained. Seven antioxidant peptides were synthesized in solid phase, and the IC 50 values of in vitro ABTS + scavenging rates were 3.59 μg/mL-6.73 μg/mL, and the antioxidant capacity was stronger than that of glutathione and ascorbic acid. In the in vitro cellular ROS scavenging capacity, all seven peptides had the effect of scavenging intracellular ROS, among which YLSF and ESWNPRDPQF had stronger scavenging capacity than glutathione. Finally, the mouse skin staining method determined that apricot antioxidant peptides had a significant inhibitory effect on UV damage to mouse skin, and targeted proteomics was used to clarify that apricot antioxidant peptides inhibited UV damage by mainly affecting three pathways, including the base excision repair pathway. This study not only improved the economic value of processing by-products, but also obtained 7 highly active almond antioxidant peptides, tapping the potential ability of apricot antioxidant peptides to be incorporated into functional food or cosmetic formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Heart failure (HF) and kidney failure (KF) are closely related conditions that often coexist, posing a complex clinical challenge. Understanding the shared mechanisms between these two conditions is crucial for developing effective therapies., Methods: This study employed transcriptomic analysis to unveil molecular signatures and novel biomarkers for both HF and KF. A total of 2869 shared differentially expressed genes (DEGs) were identified in patients with HF and KF compared to healthy controls. Functional enrichment analysis was performed to explore the common mechanisms underlying these conditions. A protein-protein interaction (PPI) network was constructed, and machine learning algorithms, including Random Forest (RF), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), were used to identify key signature genes. These genes were further analyzed using Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA), with their diagnostic values validated in both training and validation sets. Molecular docking studies were conducted. Additionally, immune cell infiltration and correlation analyses were performed to assess the relationship between immune responses and the identified biomarkers., Results: The functional enrichment analysis indicated that the common mechanisms are associated with cellular homeostasis, cell communication, cellular replication, inflammation, and extracellular matrix (ECM) production, with the PI3K-Akt signaling pathway being notably enriched. The PPI network revealed two key protein clusters related to the cell cycle and inflammation. CDK2 and CCND1 were identified as signature genes for both HF and KF. Their diagnostic value was validated in both training and validation sets. Additionally, docking studies with CDK2 and CCND1 were performed to evaluate potential drug candidates. Immune cell infiltration and correlation analyses highlighted the immune microenvironment, and that CDK2 and CCND1 are associated with immune responses in HF and KF., Discussion: This study identifies CDK2 and CCND1 as novel biomarkers linking cell cycle regulation and inflammation in heart and kidney failure. These findings offer new insights into the molecular mechanisms of HF and KF and present potential targets for diagnosis and therapy., 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 Long, Zhang, Ren, Wu and Wang.)

Although immune checkpoint inhibitors (ICIs) have been a revelation for treating several cancers, an unmet need remains to broaden ICI therapeutic scope and increase their response rates in clinical trials. Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of T cell activation and has previously been identified as a promising target for immunotherapy. Herein, we report the discovery of a series of HPK1 inhibitors with novel 1(2H)-phthalazinone and 1(2H)-isoquinolinone scaffolds. Among them, compound 24 demonstrated potent in vitro activity (HPK1 IC 50 value of 10.4 nM) and cellular activity (pSLP76 EC 50  = 41 nM & IL-2 EC 50  = 108 nM). Compound 24 exhibited favorable mouse and rat pharmacokinetic profiles with reasonable oral exposure. Compound 24 showed potent in vivo anti-tumor activity in a CT26 syngeneic tumor model with 95 % tumor growth inhibition in combination with anti-PD-1., Competing Interests: Declaration of competing interest We declare that no conflict of interest exists in the submission of this manuscript, and all the authors listed have approved the manuscript that is enclosed. The work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. This work is being submitted to European Journal of Medicinal Chemistry exclusively., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Both copper (Cu 2+/+ ) and iodine (I - ) are essential elements in all living organisms. Increasing the intracellular concentrations of Cu or I ions may efficiently inhibit tumor growth. However, efficient delivery of Cu and I ions into tumor cells is still a challenge, as Cu chelation and iodide salts are highly water-soluble and can release in untargeted tissue. Here we report mitochondria-targeted Cu-I cluster nanoparticles using the reaction of Cu + and I - to form stable bovine serum albumin (BSA) radiation-induced phosphors (Cu-I@BSA). These solve the stability issues of Cu + and I - ions. Cu-I@BSA exhibit bright radioluminescence, and easily conjugate with the emission-matched photosensitizer and targeting molecule using functional groups on the surface of BSA. Investigations in vitro and in vivo demonstrate that radioluminescence under low-dose X-ray irradiation excites the conjugated photosensitizer to generate singlet oxygen, and combines with the radiosensitization mechanism of the heavy atom of iodine, resulting in efficient tumor inhibition in female mice. Furthermore, our study reveals that BSA protection causes the biodegradable Cu-I clusters to release free Cu and I ions and induce cell death by modulating mitochondrial function, damaging DNA, disrupting the tricarboxylic acid cycle, decreasing ATP generation, amplifying oxidative stress, and boosting the Bcl-2 pathway., (© 2024. The Author(s).)

Trees act as natural filters that mitigate roadside air pollution. However, the filtration impact of different tree arrangements on traffic pollutants with different particle diameters has rarely been analysed in real street canyon environments. To quantify how roadside tree arrangements impact pedestrian exposure to particle number concentrations (PNCs) of different diameters (0.25-32 μm), in situ field measurements were carried out in a boulevard-type street canyon in the city of Xi'an, China. This study analysed the experimental data of PNCs collected along segments of a pedestrian lane under four typical tree arrangements: open space without trees, a sparse-spaced tree arrangement, a medium-spaced tree arrangement, and a dense-spaced tree arrangement in a street canyon. Our results reveal that the effect of tree arrangement on PNCs depended on the particle diameter. In general, trees can significantly reduce coarse PNC (particles with diameters >2.5 μm) but not the fine PNC. Quantitative analysis showed that a medium-spaced tree arrangement, in which tree crowns are adjacent to each other but do not overlap, is the most capable of reducing PNC, followed by a sparse-spaced tree arrangement, while a the dense-spaced tree arrangement has the least impact. The attenuation effect of trees on the PNCs increased with increasing particle diameter. Moreover, the presence of trees altered the local microclimate, which also affected how exposure to PNCs changed. Our empirical findings further highlight the complexity of how trees affect particulate pollutants in street canyons and provide timely insights for enhancing tree-planning management in cities from the perspective of air quality improvement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this work, a novel reinforcing filler, millet gliadin (MG), was used for the improvement of the mechanical properties of zein nanofibers. The structural and physicochemical properties of MG were compared with those of zein, and the influence of MG on the morphology, physical properties, and molecular structure of zein nanofibers was investigated. The results indicated that MG has an obviously smaller weight-average molecular weight (7623) in comparison to zein (13,330). Transmission electron microscopy showed that zein molecules more easily form aggregates with larger diameters than MG molecules in acetic acid. At a concentration of 30% ( w / v ), MG exhibited a significantly higher viscosity (0.66 ± 0.03 Pa·s) than zein (0.32 ± 0.01 Pa·s), indicating the stronger interactions of MG molecules. With the incorporation of MG, the tensile strength was significantly increased to 49.32 MPa (ZM-1/2), which is 2.08 times and 4.45 times higher than that of pure zein nanofibers (ZM-1/0) and MG nanofibers (ZM-0/1-1), respectively. Moreover, zein/MG composite nanofibers exhibited improved water stability. Fourier transform infrared spectra showed evidence of the hydrogen bonding interaction between zein and MG. Therefore, MG is a good candidate for use as a natural reinforcing filler in electrospun nanofibers made of biopolymers.

Pneumolysin (Ply) of Streptococcus pneumoniae (pneumococcus) at relatively high and low levels facilitates pneumococcal invasion into the lung and brain, respectively; however, the regulatory mechanisms of Ply expression are poorly understood. Here, we find that a small RNA plyT, processed from the 3'UTR of the ply operon, is expressed higher in anaerobically- than in statically-cultured pneumococcus D39. Using bioinformatic, biochemical and genetic approaches, we reveal that PlyT inhibits Ply synthesis and hemolytic activities by pairing with an RBS-embedded intergenic region of the ply operon. The RNA-binding protein SPD&#95;1558 facilitates the pairing. Importantly, PlyT inhibition of Ply synthesis is stronger in anaerobic culture and leads to lower Ply abundance. Deletion of plyT decreases the number of pneumococci in the infected mouse brain and reduces the virulence, demonstrating that PlyT-regulated lower Ply in oxygen-void microenvironments, such as the blood, is important for pneumococcus to cross the blood-brain barrier and invade the brain. PlyT-mediated repression of Ply synthesis at anoxic niches is also verified in pneumococcal serotype 4 and 14 strains; moreover, the ply operon with a 3'UTR-embedded plyT, and the pairing sequences of IGR and plyT are highly conserved among pneumococcal strains, implying PlyT-regulated Ply synthesis might be widely employed by pneumococcus., (© 2024. The Author(s).)

The clinical data of a child with disseminated tuberculosis with osteomyelitis of the right little finger as the first manifestation who was admitted to Tianjin Children's Hospital on April 8, 2023 were retrospectively analyzed. The child, a 14-year-old female, presented with osteomyelitis of the right little finger as the first manifestation. She still had recurrent fever after focal incision and drainage. She was referred to our hospital. The samples from multiple sites were positive for molecular biology detection of Mycobacterium tuberculosis . She was considered as disseminated tuberculosis and was given anti-tuberculosis treatment. The child has recovered well. Pediatric disseminated tuberculosis has variable clinical manifestations and lacks specificity. It is often misdiagnosed and has a high mortality rate. Clinicians should improve their understanding of the disease and ensure early diagnosis and treatment.