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Reducing toxic metal concentrations to extremely low levels has long posed a challenge. Polyoxometalate supported ionic liquids (POM-SILs) offer significant potential for advanced water remediation, but their application is limited by complex preparation, toxic solvents, and poor stability due to leaching, compromising sustainability. We introduced a sustainable approach for selectively removing Pb(II) in complex electroplating wastewater using charged POM-SILs composite, synthesized by directly grafting lacunary Keggin ions ([α-SiW 11 O 39 ] 8- , SiW 11 ) onto charged ammoniated polystyrene via a straightforward, solvent-free process. These POM-SILs featured monodisperse nanoclusters (<5 nm) in a cross-linked polymer matrix, ensuring optimal site accessibility and enhanced stability with negligible leaching. They achieved exceptional Pb(II) selectivity, boasting a distribution coefficient (K d ) of 23,605 mL g -1 -over 120 times greater than conventional ion-exchange resins-and a Pb(II) removal efficiency exceeding 97.6%, even in high-salinity, diverse heavy metal environments. They reached a large Q 0.01 value of 0.371 mg g -1 , effectively treating up to 2,200 liters of wastewater per kg composite, reducing Pb(II) concentrations to below 0.01 mg L -1 , meeting drinking water standards. This method marks a substantial advancement in heavy metal remediation, offering an efficient and sustainable solution for industrial wastewater 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 Ltd. All rights reserved.)

Tissue engineering aims to repair damaged tissues with physiological functions recovery. Although several therapeutic strategies are there for tissue regeneration, the functional recovery of regenerated tissues still poses significant challenges due to the lack of concerns of tissue innervation. Design rationale of multifunctional biomaterials with both tissue-induction and neural induction activities shows great potential for functional tissue regeneration. Recently, the research and application of inorganic biomaterials attracts increasing attention in innervated multi-tissue regeneration, such as central nerves, bone, and skin, because of its superior tunable chemical composition, topographical structures, and physiochemical properties. More importantly, inorganic biomaterials are easily combined with other organic materials, biological factors, and external stimuli to enhance their therapeutic effects. This review presents a comprehensive overview of recent advancements of inorganic biomaterials for innervated multi-tissue regeneration. It begins with introducing classification and properties of typical inorganic biomaterials and design rationale of inorganic-based material composites. Then, recent progresses of inorganic biomaterials in regenerating various nerves and nerve-innervated tissues with functional recovery are systematically reviewed. Finally, the existing challenges and future perspectives are proposed. This review may pave the way for the direction of inorganic biomaterials and offers a new strategy for tissue regeneration in combination of innervation., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

MXene is a new family of two-dimensional nanomaterials with outstanding electrical conductivity, tunable structure, biocompatibility, and a large surface area. Thanks to these unique physicochemical properties, MXene has been used for constructing electrochemical sensors (MECSens) with excellent performance. In particular, the abundant surface termination of MXene can contribute to greatly enhancing the analytical sensitivity and selectivity of MECSens. Recently, MECSens have been widely applied in many fields including clinical diagnosis, infectious disease surveillance, and food security. However, not all MXene materials are suitable for building electrochemical sensors. In this article, we present an overview of different MECSens that have been developed so far. We begin with a short summary of the preparation and characterization of MECSens. Subsequently, the electrochemical performance, detection strategies, and application scenarios of MECSens are classified and briefly discussed. The article ends with a short conclusion and future perspectives. We hope this article will be helpful for designing and constructing MECSens with outstanding activity for electrochemical analysis.

Progressive follicle and vascular atrophy, insufficient nutrient supply, and hormonal imbalance are direct causes of androgenic alopecia (AGA), limiting treatment options. Nitric oxide (NO) has demonstrated significant advantages in cell proliferation, vascular repair, and inflammation regulation. However, precise control of NO concentration and efficient utilization limit its clinical application for AGA treatment. To address this, we developed a near-infrared (NIR) light-triggered NO-releasing delivery system (Gel@L-Arg). The system uses Chlorin e6 (Ce6) grafted onto oxidized hyaluronic acid, reacting with L-Arg-loaded polyethyleneimine via Schiff base to form hyaluronic acid hydrogel. Under NIR light, Ce6 generates ROS, oxidizing L-Arg to release NO, after 5 min of irradiation, the NO concentration in Gel@L-Arg (1 %) is >1.5 times that in Gel@L-Arg (0.5 %), enabling on-demand release of NO. Gel@L-Arg (0.5 %) effectively promotes angiogenesis while significantly repairing damaged human dermal papilla cells (HDPCs), with cell viability reaching 131.6 ± 4.6 %. In animal models, the system reduced inflammation (IL-6, TNF-α), enhanced nutrient supply (VEGF, CD31), regulated androgens, and improved the follicular microenvironment, effectively treating AGA. This hyaluronic acid hydrogel, combining NIR light-triggered release with gas therapy, offers a new strategy for the treatment of AGA with good biocompatibility, providing insight into controlled gas release therapies for disease 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 © 2025 Elsevier B.V. All rights reserved.)

Background: Internet-based Cognitive Behavioral Therapy (ICBT) is effective in treating anxiety disorders, yet there is room for improvement in treatment response and reduction in dropout rates. This study proposes a personalized, modular ICBT intervention that leverages the extended evolutionary meta-model to provide a dynamic and adaptive treatment approach, aiming to enhance usability and efficacy., Methods: The trial will be conducted in two phases. Phase I involves 182 participants who will undergo a 30-day ecological momentary assessment to record functional processes and anxiety levels three times a day. The data collected will help in identifying key functional predictors of anxiety for each participant through group iterative multiple model estimation. In Phase II, participants who complete Phase I will be randomized into three groups: personalized CBT, standard CBT, and a waiting list. Outcome measures will include Brief Symptom Inventory, specific measures of anxiety, usability metrics, and dropout rates. Assessments will be conducted at baseline, immediately post-treatment, and at 1- and 3-month follow-ups. A linear mixed model will be utilized to analyze the data and determine the intervention's efficacy., Discussion: Anticipated outcomes from this study include advancements in personalized CBT for anxiety disorders, contributing valuable insights into their potential benefits and addressing existing challenges in the field., 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., (© 2025 The Authors.)

High-altitude hypoxic brain injury (HHBI) is a kind of acute mountain sickness and the survival rate of patients with HHBI can be improved only if it is detected and treated at the early stage. However, limited by speediness and accuracy, it is still very difficult for most of current approaches to realize the early detection of HHBI. We propose herein a novel strategy for this goal based on spatiotemporal changes in the brain oxygen level. As revealed by in vivo electrochemistry, the characteristic changes of brain oxygen level under the high-altitude exposure are directly associated with the brain hypoxia status. Given brain hypoxia is the main pathogenesis of HHBI, the degree of HHBI can be diagnosed by the variation of brain oxygen, making the early detection of HHBI feasible. In addition, the risk of HHBI for mouse exposed to high-altitude hypoxia environments can be also prognosed days in advance., (© 2024 Wiley-VCH GmbH.)

Background: Interleukin-23 (IL-23) inhibitors and the IL-12/23 inhibitor ustekinumab constitute a pivotal class of therapeutic agents employed in the clinical management of Psoriasis, a chronic immune-mediated skin disorder. Notwithstanding their therapeutic efficacy, concerns have arisen due to the emergence of multiple adverse events (AEs) associated with their usage. This study aims to provide a comprehensive examination of the distribution and characteristics of these AEs concerning IL-23 and IL-12/23 inhibitors, with a specific focus on guselkumab, tildrakizumab, risankizumab, and ustekinumab., Methods: In this research endeavor, we conducted an extensive analysis of data extracted from the FDA Adverse Event Reporting System (FAERS), spanning the timeframe from January 1, 2014, to September 30, 2022. To identify potential signals of AEs, we rigorously applied disproportionality analysis, utilizing both reporting odds ratio (ROR) and information component (IC) metrics. A signal was considered present when the lower limit of the 95% confidence interval (CI) for ROR (ROR025) exceeded one or when IC (IC025) surpassed zero, with a minimum requirement of three or more reported cases., Results: Our investigation encompassed a substantial dataset, comprising a total of 41,408,408 reports detailing drug-AE associations and involving 13,271,168 individuals. Among these, 704, 13,164, and 11,399 patients were identified as users of the IL-23 inhibitors tildrakizumab, guselkumab, and risankizumab, respectively, while 62,853 patients were identified as users of the IL-12/23 inhibitor ustekinumab. The analysis revealed the presence of 8, 20, 107, and 115 signals for these respective drugs. Significantly, the System Organ Class (SOC) exhibiting the highest incidence was "infections and infestations," with documented occurrences in tildrakizumab (6/8), guselkumab (5/20), ustekinumab (50/107), and risankizumab (25/115)., Conclusion: Our pharmacovigilance analysis has brought to light a substantial frequency of AEs linked to IL-23 and IL-12/23 inhibitors. These findings underscore the pivotal role of IL-23 and IL-12/23 inhibitors in modulating immune function and raise concerns regarding their potential to heighten susceptibility to infections and malignancies. However, limitations inherent to the FAERS database, including underreporting, lack of denominator data, potential duplicate records, and inability to confirm causality, should be acknowledged of particular significance is risankizumab, which, despite having fewer reported cases and a later market introduction compared to ustekinumab, exhibited a higher incidence of AEs. These results emphasize the necessity for ongoing vigilance, further investigation, and a reevaluation of the safety profile of IL-23 and IL-12/23 inhibitors in the clinical management of Psoriasis., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Ethical guidelines: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Activating protein 1 (AP-1) is a transcription factor composed of several protein families, Jun proteins and Fos proteins are the components of AP-1. AP-1 is involved in various cellular processes, such as proliferation, differentiation, apoptosis and inflammation. For tumor cells, AP-1 is considered to be a driver whose activity is associated with dysfunction and the onset, development, invasion, and migration of cancer. In addition, AP-1 has been reported to be involved in the drug resistance and radiation resistance of tumor cells during the treatment process. Therefore, AP-1 is a potential target for cancer therapy. At present, a number of inhibitors targeting AP-1 have been developed and have shown certain anti-cancer effects. However, due to the complex structure and function of AP-1, different structures of AP-1 show different effects in different tumor cells, and more studies are needed to reveal its mechanism of action. This article introduces the relationship between AP-1 and tumor development, summarize the current studies and developments of AP-1 related drugs, and provide the future development values of AP-1., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Acute kidney injury (AKI) has become a disease of global concern due to its high morbidity and mortality. This has highlighted the need for renoprotective agents. Astragaloside IV (AS-IV) is a saponin isolated from Astragalus membranaceus with good antioxidant, anti-inflammatory and anti-tumor properties. In this study, HK2 cells and rat model were utilized to explore the protective effect of AS-IV against cadmium chloride-induced oxidative stress-induced apoptosis. CdCl 2 -induced apoptosis, ROS production, and mitochondrial membrane potential alterations were significantly inhibited in AS-IV -treated HK2 cells. Expression of the mitochondria-associated apoptotic proteins Cleaved-Caspase3, Cleaved-Caspase9, and Cleaved-PARP was significantly reduced after AS-IV intervention. In addition, AS-IV inhibited Rat weight loss and also alleviated the symptoms of CdCl 2 -induced nephrotoxicity in a rat model of CdCl 2 -induced kidney injury. Further experiments showed that AS-IV suppresses heavy metal Cd-induced mitochondria-mediated apoptosis by regulating the Nrf2/HO-1 pathway. In conclusion, AS-IV could protect the kidney from heavy metal-induced toxicity and could be used as a nephroprotective agent., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Autologous fat grafting is widely used in plastic surgery. However, its main limitation is the low survival rate of fat grafts after transplantation. Transplantation of single adipocytes in combination with adipose-derived stem cells (ADSCs) could largely preserve the activity of the fat and improve graft survival., Objective: To verify the long-term survival rate of single adipocyte graft in vivo and its viable fat morphology for future fat grafting., Methods: Healthy adipose tissue was harvested and disassociated using fat dissociation solution, the Single-cell Suspension Preparation System (SSPS) was used to obtain a mixture of single adipocytes, ADSCs and stromal vascular fraction (SVF), and the structure of single adipocytes was verified by cell mask red and DAPI double staining. Nine male Balb/c nude mice were used, and three different graft volumes were established (0.05, 0.1 and 0.2 ml). For each mouse, four sites were selected for transplantation, one for macrofat and the other three for single adipocytes, and different transplant volumes 30, 60 and 90 days after transplantation. In each period, 3 mice were selected to measure the volume of fat graft., Results: Double staining with cell mask red and DAPI confirmed that the nucleus was identified intracellularly, which also indicated that the adipocytes in the single-cell suspension were structurally complete. When evaluating the transplantation, the groups with a volume of 0.05 ml and 0.2 ml performed better in the single-cell fat group in all transplantation periods, the group with a volume of 0.1 ml performed better in the single-cell group in the 30- and 60-day transplantation, and the differences were significant (P<0.05)., Conclusion: In this study, the SSPS was used to obtain a new transplant material containing single adipocytes and ADSCs by enzymatic hydrolysis of adipose tissue and converted into single cells. It effectively improved the survival rate of fat grafting and the long-term effect of transplantation., No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266., Competing Interests: Declarations. Conflict of interest: The SoniConvert® Single-cell Suspension Preparation System and the fat dissociation solution were provided by the Chengdu DosSense Biotech Co., LTD for free, and the authors declare that they have no conflicts of interest to disclose. Ethical Approval: The study protocol about patient was approved by the Ethics Committee of West China Hospital, Sichuan University, on October 2, 2020 (No. 2020(806)). All experimental procedures about animals used in this study were reviewed and approved by the Animal Ethics Committee of West China Hospital, Sichuan University, on October 19, 2020 (2020303A). Informed Consent: We have got the consent for publication from our patient, and the copy is available., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or anti-tumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of Lkb1 fl/fl p53 fl/fl transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the Lkb1 fl/fl p53 fl/fl mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer.

Although trivalent manganese (Mn(III)) species have been recognized as crucial intermediates in the degradation of organic contaminants by Mn oxides, quantitative research on their specific roles remains scarce. Our study investigated the degradation processes of an organic pollutant, Bisphenol A (BPA), by dissolved Mn(III) and Mn(III)-bearing oxides, and elucidated the differences of the underlying mechanisms and reaction pathways between several Mn oxides and dissolved Mn(III). Our results indicated that BPA degradation rates with Mn(III)-bearing oxides alone follow the order: δ-MnO 2 ≫ γ-MnOOH > Mn 3 O 4 . Adding pyrophosphate (PP) significantly enhanced BPA degradation by promoting the formation of Mn(III)-PP complexes and exposing more reactive sites, achieved through destabilizing the crystal structure and mitigating of Mn(II) readsorption, particularly in γ-MnOOH and Mn 3 O 4 . Our kinetic model revealed that heterogeneous degradation by Mn oxides is the predominant reaction pathway, accounting for 61.4 %, 87.8 %, and 73.8 % of the total degraded BPA for δ-MnO 2 , γ-MnOOH, and Mn 3 O 4 , respectively, even in the presence of significant amount of dissolved Mn(III) intermediates due to high PP concentrations. These results offer mechanistic details on BPA degradation by Mn oxides and the influence of ligand concentration, providing helpful insights for optimizing degradation strategies of organic pollutants., 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.)

Bestrophin isoform 4 ( BEST4 ) is a newly identified subtype of the calcium-activated chloride channel family. Analysis of colonic epithelial cell diversity by single-cell RNA-sequencing has revealed the existence of a cluster of BEST4 + mature colonocytes in humans. However, if the role of BEST4 is involved in regulating tumour progression remains largely unknown. In this study, we demonstrate that BEST4 overexpression attenuates cell proliferation, colony formation, and mobility in colorectal cancer (CRC) in vitro, and impedes the tumour growth and the liver metastasis in vivo. BEST4 is co-expressed with hairy/enhancer of split 4 ( HES4 ) in the nucleus of cells, and HES4 signals BEST4 by interacting with the upstream region of the BEST4 promoter. BEST4 is epistatic to HES4 and downregulates TWIST1, thereby inhibiting epithelial-to-mesenchymal transition (EMT) in CRC. Conversely, knockout of BEST4 using CRISPR/Cas9 in CRC cells revitalises tumour growth and induces EMT. Furthermore, the low level of the BEST4 mRNA is correlated with advanced and the worse prognosis, suggesting its potential role involving CRC progression., Competing Interests: ZW, BX, SQ, XZ, XZ, YL, HW, MZ, ZZ, DK, LY, SC, JY No competing interests declared, (© 2023, Wang et al.)

Hyperuricemia is a common disorder induced by purine metabolic abnormality, which will further cause chronic kidney disease, cardiovascular disease, and gout. Its main pathological characteristic is the high uric acid (UA) level in the blood, so that the detection of UA is highly important for hyperuricemia diagnosis and therapy. Herein, we report a biocompatible and minimally invasive microneedle electrode patch (MEP) for continuous UA monitoring and diet management in hyperuricemia. The composite of graphene oxide and carboxylated multiwalled carbon nanotubes was modified on the microneedle electrode surface to enhance its sensitivity, selectivity, and stability, thus realizing the continuous detection of UA in the interstitial fluid to accurately predict the UA level in the blood. This further allowed us to study the hypouricemic effect of anthocyanins on the hyperuricemia model mouse. It was found that anthocyanins extracted from blueberry can effectively inhibit the activity of xanthine oxidase to reduce the production of UA. The UA level of hyperuricemia model mice fed with anthocyanins is ∼1.7 fold lower than that of the control group. We believe that this MEP offers enormous promise for continuous UA monitoring and diet management in hyperuricemia.

Meat quality is a complex trait that exhibits significant variation across pig breeds, and the regulatory mechanisms governing pork meat quality are not fully elucidated. We compared the transcriptomics and metabolomics of the longissimus dorsi (LD) muscle between the Songliao Black Pig (SBP) and Large White × Landrace Pig (LWLDP) to investigate breed-specific differences in meat quality and underlying regulatory pathways. The results showed that SBP meat had a higher marbling score and backfat thickness, a richer color, a lower shear force, and reduced drip loss. Fatty acid (FA) analysis identified 15 significant FAs in the LWLDP, with docosahexaenoic acid (DHA) in the SBP, while amino acid (AA) analysis revealed no breed-based differences. Transcriptome analysis identified 134 upregulated and 362 downregulated genes in the SBP. Protein-protein interaction (PPI) network analysis found 25 key genes, which are associated with muscle development, fat deposition, and overall meat quality, while genes in the insulin signaling pathway, such as PPP1R3B, PPARGC1A, SOCS1, EIF4E, PRKAR2A, PRKAG2, and FASN, play a crucial role in balancing fat metabolism and catabolism. Metabolomic analysis identified 89 upregulated and 10 downregulated metabolites in the SBP, primarily involved in fructose and mannose metabolism, amino acid biosynthesis, nucleotide sugar metabolism, and glucagon signaling pathways. Gene-metabolite association analysis found that the PPP1R3B gene had a strong association with Thr-Leu, Maltol, D-myo-Inositol-4-phosphate, and Fructose-6-phosphate, while MYOG correlated with Mannose-6-phosphate, Fructose-1-phosphate, Mannose-1-phosphate, and Glucose-6-phosphate. In contrast, NR4A3 and PPARGC1A showed a strong negative correlation with most upregulated metabolites. In conclusion, this study identified functional genes, elucidated the mechanisms associated with meat quality traits, and identified gene-metabolite associations involved in energy metabolism, muscle development, and fat deposition, providing valuable insights into the molecular mechanisms that regulate meat quality between pig breeds.

Introduction: Endometrial cancer is the most common malignancy of the female reproductive system in the United States. Asparagus officinalis is a versatile, nutrient-dense, low-calorie vegetable that contains various bioactive metabolites that have shown a variety of biologic functions beneficial to health. The metabolites from asparagus officinalis extracts or asparagus officinalis extracts exhibit significant anti-tumorigenic activity in some pre-clinical models of cancer., Methods: Endometrial cancer cells were used to study the effects of asparagus officinalis on anti-proliferation, anti-invasion and increased sensitivity to cisplatin, and obese and lean Lkb1 fl/fl p53 fl/fl mouse model of endometrial cancer was used to study the role of asparagus officinalis in tumor growth., Results: Treatment with increasing concentrations of Asparagus officinalis extracts significantly inhibited cell proliferation, reduced glycolytic activity, induced cellular stress and apoptosis, caused cell cycle G1 arrest, increased the sensitivity of cells to cisplatin, reduced cell adhesion and invasion, and activation of AMPK and inhibition of the AKT/mTOR and MAPK signaling pathways in endometrial cancer cells. Moreover, asparagus officinalis extracts suppressed cell adhesion and invasion through the modulation of the epithelial-to-mesenchymal transition process. Asparagus officinalis extract treatment for 4 weeks resulted in a significant reduction in tumor growth in Lkb1 fl/fl p53 fl/fl mice under both obese and lean conditions, with a decrease in Ki-67 and vascular endothelial growth factor expression and an increase in Bip expression in endometrial tumors., Discussion: These findings provide strong preclinical evidence for the potential therapeutic benefit of asparagus officinalis extract as a novel dietary strategy in the treatment of endometrial cancer. Further clinical trials of dietary intervention of asparagus officinalis or combination with cisplatin in patients with endometrial cancer are warranted., Competing Interests: Author LZ was employed by Shandong Juxinyuan Agricultural 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 Fang, Kong, Zhao, Sun, Xu, Clark, Sullivan, Tran, Zhou, Sun, Zhao, Wang, Zhou and Bae-Jump.)

The bacterial stressosome is a supramolecular multiprotein complex that acts as a critical signal integration and transduction hub, orchestrating cellular responses to environmental stimuli. Recent studies have resolved near-atomic stressosome structures from various bacterial species, revealing assemblies that should be capable of altering their configuration in response to external changes. Further genetic, biochemical, and cell biology research has elucidated interactions and phosphorylation status within the stressosome complex as well as its subcellular localization and mobility within living cells. These insights enhance our comprehension of the stressosome pathways and their roles in directing various survival responses during environmental stress., 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 Ltd.)

Aim: To evaluate the real-life effectiveness and safety of hydrogen inhalation (HI) therapy as an additional treatment in Chinese adults with hypertension., Methods: This observational, retrospective clinical study included hypertensive patients receiving routine antihypertensives with or without HI initiation from 2018 to 2023. Participants were assigned to the HI group or non-HI group (control group) after propensity score matching. The changes in mean systolic blood pressure (SBP) level during the 24-week follow-up period in different groups were examined primarily. The secondary outcome was the changes in diastolic blood pressure (DBP) and blood pressure (BP) control rate during the study. Several subgroup and sensitivity analyses were performed to confirm the robustness of our main findings. Adverse event (AE) was also assessed in patients of both groups., Results: In total, we selected 2,364 patients into the analysis. Both mean SBP and DBP levels significantly decreased in the HI group compared to control group at each follow-up visit with the between group difference of -4.63 mm Hg (95% CI, -6.51 to -2.74) at week 8, -6.69 mm Hg (95% CI, -8.54 to -4.85) at week 16, -7.81 mm Hg (95% CI, -9.57 to -6.04) at week 24 for SBP, and -1.83 mm Hg (95% CI, -3.21 to -0.45) at week 8, -2.57 mm Hg (95% CI, -3.97 to -1.17) at week 16, -2.89 mm Hg (95% CI, -4.24 to -1.54) at week 24 for DBP. Patients in the HI group were more likely to attain controlled BP at the follow-up period with odds ratio of 1.44 (95% CI, 1.21-1.72) at week 8, 1.90 (95% CI, 1.59-2.27) at week 16, and 2.24 (95% CI, 1.87-2.68) at the end. The trends of subgroup and sensitivity analyses were mostly consistent with the main analysis. The incidences of AEs were similar between the HI group and control group with all p -value >0.05., Conclusion: The HI therapy is related to significant amelioration in BP levels with acceptable safety profile in Chinese hypertensive adults after 24 weeks of treatment, building a clinical ground for further research to evaluate the antihypertensive effect of HI 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., (© 2024 Ji, Sun, Zhang, Zhao, Gao, Wang, Yang, Zhang, Gao, Man, Yang, Yang, Yue, Chen, Ding and Ni.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with a low 5-year survival rate. Treatment options for PDAC patients are limited. Recent studies have shown promising results with MRTX1133, a KRAS G12D inhibitor that demonstrated potent antitumor activity in various types of tumors with KRAS G12D mutation. Resistance to KRAS inhibitors is frequently occurred and one of the main reasons for treatment failure. Understanding resistance mechanisms to novel KRAS inhibitors is crucial to ensure sustained and durable remissions., Methods: Two KRAS G12D inhibitor MRTX1133-resistant PDAC cell lines were established in vitro. The resistance mechanisms to KRAS G12D inhibitor MRTX1133 against PDAC in vitro and in vivo were characterized by RNA sequencing, reverse transcript polymerase chain reaction, cytotoxicity test, plasmid transfection, lentivirus transfection, lipid peroxidation detection, malondialdehyde levels detection, glutathione levels detection, western blot, immunofluorescence, nude mice tumorigenesis experiment and immunohistochemistry., Results: The bioinformatics analysis and transcriptome sequencing showed that ferroptosis was involved in the resistant effect of the KRAS G12D inhibitor treatment, and MGST1 was the key molecule against MRTX1133-induced ferroptosis. Increased expression of MGST1 weakened the cytotoxicity of MRTX1133 by inhibiting lipid peroxidation-induced ferroptosis in KRAS G12D inhibitor-resistant PDAC cells. Knockdown or overexpression of MGST1 conferred sensitivity or resistance to KRAS G12D inhibitor MRTX1133, respectively. Mechanismly, increased nuclear localization and higher levels of active β-catenin were observed in MRTX1133-resistant PDAC cells, which contributed to higher MGST1 expression. Knockdown of CTNNB1 or TCF4 can decreased MGST1 expression. Additionally, we found that PKF-118-310, an antagonist of β-catenin/Tcf4 complex, repressed MGST1 expression. In both in vitro and in vivo models, a synergistic effect was observed when combining MRTX1133 and PKF-118-310 in KRAS G12D inhibitor MRTX1133-resistant PDAC cells and tumors., Conclusion: Our data showed that KRAS G12D inhibitor MRTX1133 combined with PKF-118-310 could enhance the effectiveness of MRTX1133 treatment response through induction of ferroptosis via inhibiting MGST1 expression in MRTX1133-resistant PDAC cells and tumors. This evidence may provide a promising strategy to overcome KRAS G12D inhibitor MRTX1133 resistance in PDAC patients with KRAS G12D mutations., (© 2024. The Author(s).)

The development of industrial mining has resulted in a large amount of Cd and Pb polluting the soil in mining areas, and leads to adverse health effects on the life of both plants and animals. Here, a soft template method was conducted to prepare hydrothermal carbon (HC) with regular morphology, which assisted with Bacillus pasteurii to induce calcite precipitation for decontamination of mining soil. Soil remediation experiments over 30 days of remediation with an HC microbial agent (HCMA) resulted in 89.4% and 87.8% decrease in the amount of leached Cd and Pb, respectively. The content of exchangeable Cd and Pb decreased by 76.1% and 81.0%, respectively. At the same time, soil fertility significantly improved. The electrostatic potential and surface charge distribution of extracellular polymeric substances (EPS) and sodium citrate (NaCit) were analyzed using DFT simulations, their nucleophilic and electrophilic regions were determined, and the nucleation mechanism was determined. The DFT results indicated that the oxygen-containing groups of EPS and NaCit had strong negative electrostatic potential and electronegativity, which could cause Cd 2+ , Pb 2+ , and Ca 2+ to aggregate on their surfaces. They also combined with CO 3 2- produced by urease during the decomposition of urea, resulting in Cd 2+ and Pb 2+ being encapsulated by calcium carbonate to form a coprecipitate. X-ray diffraction analyses revealed that the precipitate was mainly calcite calcium carbonate, which is more stable and less prone to secondary leaching of HMs. The gathered data prove the significant role of HCMA in remediation of mining soil contaminated with Cd and Pb., 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: Our study aims to assess alendronate-related adverse events (AEs) from the US FDA adverse event reporting system database., Methods: The AE data associated with alendronate between the first quarter of 2004 and the first quarter of 2024 were selected. Various signal quantification methods, including the ROR, PRR, BCPNN, and EBGM, were applied for analysis., Results: In 34,943 reports where alendronate was the primary suspected drug for the AE, 24 affected system organ classes and 1046 significant preferred terms were identified in this study. Several significant AEs beyond drug instructions with strong signals were determined, including low turnover osteopathy, fracture delayed union, fracture nonunion, loss of anatomical alignment after fracture reduction, fracture malunion, periprosthetic fracture, carotid bruit, oral fibroma, traumatic occlusion, and phlebolith. The median time to onset of alendronate-related AEs was 306 days (interquartile range [IQR] 12-1,461 days), and the majority of cases occurred 2 years later (18.80%) and within 30 days (14.49%)., Conclusions: The current study detected multiple potential new AE signals for alendronate, and more clinical research is required to further validate our results and clarify their associations.

Exercise is one of the preferred management strategies for diabetic patients, but the exercise mode including type, intensity, and duration time is quite different for each patient because of individual differences. Inadequate exercise has no effect on the blood glucose control, while overexercise may cause serious side effects, such as hypoglycemia and loss of blood glucose control. In this work, we report a closed-loop feedback mode for exercise management in diabetes. A minimally invasive, biocompatible microneedle electrode patch was fabricated and used for continuously monitoring the glucose in the interstitial fluid. Further, in conjunction with using a wireless electrochemical device, the glucose signals can be analyzed to output the potency of exercise and give advice on exercise management. A custom exercise given by this closed-loop feedback mode can reduce the used dose of insulin and avoid side effect during and after exercise. We believe that this work can provide a novel comprehensive guidance for diabetic patients., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Boyu Zhu et al.)

Background: Existing research indicates that the personality traits of miners influence their emotional regulation strategies, and these strategies in turn affect their performance in work fatigue. However, whether there is an intermediary or moderating role among these factors remains unclear. Additionally, while some studies suggest an increased likelihood of unsafe behavior among miners following fatigue, physiological data concerning their cognition remains incomplete and requires further exploration. This study aims to explore the mediating and moderating effects of emotional regulation strategies among miners regarding their personality traits and work fatigue, and to expand understanding of the cognitive and physiological data related to miners' risk decision-making following fatigue., Method: Fifty adult miners (Mage = 25, aged 18-40, 100% male) were selected as participants. Emotional regulation tendency, significant levels of personality traits based on the Big Five Personality Traits questionnaire, and the three-dimensional levels of work fatigue were measured using emotional regulation strategy scale, Big Five Personality Traits questionnaire, and work fatigue scale, respectively. The eye-brain consistency hypothesis posits that eye movement trajectories and fixation points reflect the brain's cognitive processes and focus. Therefore, combining eye-tracking experiments, miners' preferences in risk decision-making were further measured., Results: Expressive suppression strategies mediated between conscientiousness and depersonalization; expressive suppression strategies moderated between agreeableness and emotional exhaustion. In eye-tracking physiological experiments, significant differences were found in eye movement data among miners with varying levels of emotional exhaustion., Conclusion: Preferences in emotional regulation strategies play mediating and moderating roles between miners' Big Five Personality Traits and work fatigue. The levels and dimensions of work fatigue are influenced not only by personality traits but also by individual tendencies in emotional regulation strategies, which significantly affect performance in risk decision-making. The findings of this study can further enrich theories related to work fatigue among miners and provide insights for personalized safety management in mining., 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 Tian, Qiu, Li and Zhao.)

This paper discusses the influence of the digital economy (DE) on carbon emissions based on evidence at the global level. Specifically, based on the panel data from 80 countries from 2010 to 2020, this paper creates a DE measurement index and uses the System-GMM model to assess the influence of DE on carbon emissions. The results show that: (1) The development of DE significantly promotes carbon emissions reduction. (2) The development of DE significantly promotes carbon emissions reduction through technological advancement, structural optimization, and educational enhancement; (3) Regulatory quality and financial development play a positively moderating role in DE's promoting effect on carbon emissions reduction; (4) DE of European and North American nations have stronger promoting effect on carbon emissions reduction than DE of other countries. Compared to DE of developing countries, DE of developed countries has a stronger promoting effect on carbon emissions reduction. Additionally, this paper also finds that institutional differences can impact the carbon emission reduction effects of DE. Based on the results, this paper suggests that governments globally should promote the development of DE and foster international cooperation to enhance DE's driving role in promoting carbon emissions reduction., 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.)

Background: The anti-angiogenic agent anlotinib offers a new treatment option for triple-negative breast cancer (TNBC) patients with brain metastases. This study aimed to evaluate the efficacy and safety of anlotinib in the treatment of TNBC patients with brain metastases., Methods: Between October 2019 and April 2024, 29 TNBC patients with brain metastases who had failed prior therapy and were treated with anlotinib were retrospectively analyzed. The primary endpoint was central nervous system (CNS) progression-free survival (PFS), and secondary endpoints included overall survival (OS), intracranial disease control rate (iDCR), intracranial objective response rate (iORR), and safety., Results: The median CNS PFS of 29 patients was 7.2 months (95% confidence interval [CI], 3.5-10.9 months), and the median OS was 10.2 months (95% CI, 5.6-14.8 months). The iORR and iDCR were 31.0% and 86.2%, respectively. Five patients (17.2%) experienced grade 3-4 adverse events (AEs), with bone marrow suppression (2/29, 6.9%) being the most common. Most AEs were clinically manageable, and no treatment-related death was observed., Conclusion: Anlotinib demonstrated encouraging efficacy and manageable toxicity in the treatment of TNBC patients with brain metastases who had failed standard treatment., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Li, Zhao, Liu and Sun.)

Background: Traditional methodologies for diagnosing post-traumatic stress disorder (PTSD) primarily rely on interviews, incurring considerable costs and lacking objective indices. Integrating biomarkers and machine learning techniques into this diagnostic process has the potential to facilitate accurate PTSD assessment by clinicians., Methods: We assembled a dataset encompassing recordings from 76 individuals diagnosed with PTSD and 60 healthy controls. Leveraging the openSmile framework, we extracted acoustic features from these recordings and employed a random forest algorithm for feature selection. Subsequently, these selected features were utilized as inputs for six distinct classification models and a regression model., Results: Classification models employing a feature set of 18 elements yielded robust binary prediction outcomes for PTSD. Notably, the RF model achieved peak accuracy at 0.975 with the highest AUC of 1.0. In terms of the regression model, it exhibited significant predictive capability for PCL-5 scores (MSE = 0.90, MAE = 0.76, R 2  = 0.10, p < 0.001). Noteworthy was the correlation coefficient of 0.33 (p < 0.01) between predicted and actual values., Limitations: Firstly, the process of feature selection may compromise the stability of models, which leads to potentially overestimating results. Secondly, it is hard to elucidate the nature of biological mechanisms behind between PTSD patients and healthy individuals. Lastly, the regression model has a limited prediction for PTSD., Conclusions: Distinct speech patterns differentiate PTSD patients and controls. Classification models accurately discern both groups. Regression model gauges PTSD severity, but further validation on larger datasets is needed., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chemoresistance remains a principal culprit for the treatment failure in colorectal cancer (CRC), especially for patients with recurrent or metastatic disease. Deciphering the molecular basis of chemoresistance may lead to novel therapeutic strategies for this fatal disease. Here, UBR5, an E3 ubiquitin ligase frequently overexpressed in human CRC, is demonstrated to mediate chemoresistance principally by inhibiting ferroptosis. Paradoxically, UBR5 shields oxaliplatin-activated Smad3 from proteasome-dependent degradation via Lys 11-linked polyubiquitination. This novel chemical modification of Smad3 facilitates the transcriptional repression of ATF3, induction of SLC7A11 and inhibition of ferroptosis, contributing to chemoresistance. Consequently, targeting UBR5 in combination with a ferroptosis inducer synergistically sensitizes CRC to oxaliplatin-induced cell death and control of tumor growth. This study reveals, for the first time, a major clinically relevant chemoresistance mechanism in CRC mediated by UBR5 in sustaining TGFβ-Smad3 signaling and tuning ferroptosis, unveiling its potential as a viable therapeutic target for chemosensitization., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The abundance of biodegradable microplastics (BMPs) is increasing in soil due to the widespread use of biodegradable plastics. However, the influence of BMPs on soil metal biogeochemistry, especially arsenic (As), under different water regimes is still unclear. In this study, we investigated the effects of two types of BMPs (PLA-MPs and PBAT-MPs) on As fractionation in two types of soils (black soil and fluvo-aquic soil) under three water regimes including drying (Dry), flooding (FL), and alternate wetting and drying (AWD). The results show that BMPs had limited indirect effects on As fractionation by altering soil properties, but had direct effects by adsorbing and releasing As during their degradation. Enzyme degradation experiments show that the degradation of PLA-MPs led to an increased desorption of 4.76 % for As(III) and 15.74 % for As(V). Synchrotron-based X-ray fluorescence (μ-XRF) combined with micro-X-ray absorption near edge structure (μ-XANES) analysis show that under Dry and AWD conditions, As on the BMPs primarily bind with Fe hydrated oxides in the form of As(V). Conversely, 71.57 % of As on PBAT-MP under FL conditions is in the form of As(III) and is primarily directly adsorbed onto its surface. This study highlights the role of BMPs in soil metal biogeochemistry., 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.)

Background: Previous conventional epidemiological studies found a J-shape relationship between alcohol consumption and dementia, but this result was subject to confounding biases and reverse causation. Therefore, we aimed to investigate the potential linear or non-linear causal association between alcohol consumption and the incident risk of dementia in current drinkers., Methods: This study used data from the UK Biobank to investigate the relationship between alcohol consumption and dementia risk. 313,958 White British current drinkers, who were free of dementia during 2006-2010, were followed up until 2021. Alcohol consumption was self-reported and calculated according to the National Health Service guideline. The primary outcome was all-cause dementia identified through hospital and mortality records. We used multivariable Cox models with restricted cubic splines for conventional analysis and both non-linear and linear Mendelian Randomization (MR) analyses to assess causal relationships, employing a genetic score based on 95 SNPs identified from a meta-genome-wide association study of 941,280 people from Europe., Findings: 313,958 current drinkers consumed an average of 13.6 [IQR: 7.1-25.2] units/week alcohol (men averaged 20.2 [11.1-33.9] units/week and women 9.5 [5.3-16.7] units/week). During a mean follow-up of 13.2 years, 5394 (1.7%) developed dementia. Multivariable Cox model with restricted cubic spline functions identified a J-shaped relationship between alcohol consumption and dementia risk, with the lowest risk at 12.2 units/week. The non-linear MR failed to identify a significant non-linear causal relationship ( p  = 0.45). Both individual-level (HR: 2.22 95%CI [1.06-4.66]) and summary-level (1.89 [1.53-2.32]) linear MR analyses indicated that higher genetically predicted alcohol consumption increased dementia risk., Interpretation: This study identified a positive linear causal relationship between alcohol consumption and dementia among current drinkers. The J-shaped association found in conventional epidemiological analysis was not supported by non-linear MR analyses. Our findings suggested that there was no safe level of alcohol consumption for dementia., Funding: The Shenzhen Science and Technology Program and the Strategic Priority Research Program of Chinese Academy of Sciences., Competing Interests: All authors declare no competing interests., (© 2024 The Author(s).)

Objective: Both theoretical and empirical studies suggest that negative cognitive biases significantly influence the onset and persistence of posttraumatic stress disorder (PTSD) symptoms. However, the interplay among these cognitive biases and their conjoint contribution to the long-term trajectory of posttraumatic stress symptoms remains underexplored. This study delves into the interplay among attention, appraisal, and memory biases within a provisional PTSD population and evaluates the predictive effects of two integrative models (weakest link, additive approach) on posttraumatic stress symptoms reported 2 months later., Method: Sixty Chinese participants ( M age = 20.17, SD age = 2.11) with provisional PTSD undertook the scrambled sentences test (appraisal bias) with their eye movements recorded (attention bias) and then the free recall task (memory bias). Posttraumatic stress symptom was assessed at baseline and 2-month follow-up., Results: Selective attention bias toward negative words was positively associated with the negative appraisal of scrambled sentences, which subsequently showed a strong association with negative memory bias. Regarding the progression of posttraumatic stress symptoms, the additive approach was found to be a more reliable predictor of self-reported posttraumatic stress symptoms at 2 months than the weak link approach., Conclusions: This study provides initial evidence supporting the combined cognitive biases hypothesis in provisional PTSD. It also underscores potential avenues to enhance cognitive bias modification techniques. Replication of these findings in broader clinical samples is essential. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background and Objective: The value of circulating tumor DNA (ctDNA) in neoadjuvant therapy (NAT) for lung cancer remains controversial. Therefore, we conducted a review to further investigate the role of ctDNA in non-small cell lung cancer (NSCLC) patients undergoing NAT for individualized management., Methods: A search of online databases (PubMed, Embase, Web of Science, Science Direct, and Cochrane Library) was conducted to evaluate the value of ctDNA in predicting relapse, risk stratification, and efficacy of NAT in NSCLC. Only articles published in English within the last 25 years, between January 1st, 1998 and November 30th, 2023, were included. Additionally, the application of ctDNA in NSCLC is briefly reviewed., Key Content and Findings: ctDNA is a non-invasive and dynamic method that plays an important role in future treatment guidance. Additionally, ctDNA successfully predicted the effect of neoadjuvant immunotherapy before surgery, and positive testing was strongly correlated with a lower major pathological response or complete pathological response rate. Sequential testing of ctDNA may serve as a secondary indicator to guide the adjustment of treatment programs. However, the application of this method has been limited by false negative results, a lack of objective indicators, and high costs. These issues must be addressed by researchers., Conclusions: ctDNA has strong potential in NAT, based on positive preliminary studies. However, its widespread use is limited by the high cost of testing. Further research is needed to explore its value in risk stratification and treatment guidance in the future., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-265/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

The melanocortin 4 receptor ( MC4R ) gene plays a central role in regulating energy homeostasis and food intake in livestock, thereby affecting their economic worth and growth. In a previous study, the p.T117M mutation in the sheep MC4R gene, which leads to the transition of threonine to methionine, was found to affect the body weight at six months and the average daily gain in Hu sheep. However, there are still limited studies on the frequency of the sheep p.T117M missense mutation globally, and the underlying cellular mechanism remains elusive. Therefore, this study first used WGS to investigate the distribution of the MC4R gene p.T117M mutation in 652 individuals across 22 breeds worldwide. The results showed that the mutation frequency was higher in European breeds compared with Chinese sheep breeds, particularly in Poll Dorset sheep (mutation frequency > 0.5). The p.T117M mutation occurs in the first extracellular loop of MC4R . Mechanistically, the basal activity of the mutated receptor is significantly increased. Specifically, upon treatment with α-MSH and ACTH ligands, the cAMP and MAPK/ERK signaling activation of M117 MC4R is enhanced. These results indicate that the T117M mutation may change the function of the gene by increasing the constitutive activity and signaling activation of cAMP and MAPK/ERK, and, thus, may regulate the growth traits of sheep. In conclusion, this study delved into the global distribution and underlying cellular mechanisms of the T117M mutation of the MC4R gene, establishing a scientific foundation for breeding sheep with superior growth, thereby contributing to the advancement of the sheep industry.

Background: The Triglyceride-glucose (TyG) index is a marker of insulin resistance, but its role in sarcopenia is controversial. The purpose of this study was to investigate the association of the TyG index with sarcopenia., Methods: 4030 participants aged 20 years and above were selected from National Health and Nutrition Examination Survey for cross sectional study. Weighted logistic regression model was used to estimate the association between TyG index and sarcopenia. Threshold effect analysis and restricted cubic spline were employed to describe nonlinear link, with interaction tests and subgroup analyses performed., Results: It was found in the fully adjusted model that the TyG index was positively associated with sarcopenia (per 1-unit increase in the TyG index: OR = 1.31, 95%CI: 1.07, 1.60). This association was further highlighted in groups characterized by the absence of MetS or diabetes, as well as the absence of vigorous or moderate work activity. Furthermore, analysis of the curve fitting and threshold effects indicated a nonlinear relationship, which exhibited a turning point at 9.14., Conclusion: The study results indicated that the TyG index was positively associated with sarcopenia. Enhancing the management of insulin resistance could help reduce the risk of developing sarcopenia., (© 2024. The Author(s).)

Rationale: Neuromyelitis optica spectrum disorder (NMOSD) involves autoimmune and inflammatory responses in the central nervous system, primarily affecting the optic nerves and spinal cord. Atypical presentations such as ataxia and syncope complicate the diagnosis, and lesions in the medulla are easily mistaken for cerebral infarction. This case report emphasizes the need to recognize such manifestations to avoid misdiagnosis and ensure timely treatment., Patient Concerns: This case report presents an NMOSD female patient who experienced ataxia, syncope, and neuropathic pain during her illness., Diagnosis: NMOSD., Interventions: The patient managed her blood sugar with insulin, controlled neuropathic pain with pregabalin, and underwent 5 plasma exchanges., Outcomes: Significant improvement was noted 1 week post-plasma exchange, with complete resolution of neuropathic pain and no symptom recurrence reported at 6-month follow-up., Lessons: Atypical manifestations of NMOSD, such as ataxia, syncope, and trigeminal neuralgia, increase diagnostic difficulty. Recognizing these symptoms is crucial to avoid misdiagnosis and ensure timely and appropriate treatment for patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Poor mental health literacy (MHL) in the global population significantly contributes to the treatment gap associated with mental disorders. In the digital age, leveraging Internet-based MHL interventions offers scalability and broader accessibility. This meta-analysis aimed to evaluate the effects of Internet-based interventions in improving MHL and mental health., Method: Up to Feb 2024, seven databases were searched for Internet-based interventions on MHL (knowledge, stigma, help-seeking attitudes and intentions) and mental disorders (general distress, anxiety, and depressive symptoms). The random-effects meta-analyses at post-intervention and long-term follow-up assessments were performed., Results: Twenty-nine eligible studies involving 11,582 participants were included. Significant positive effects were observed across various domains: knowledge increase (immediate: g = 0.459, 95 %CI: 0.285 to 0.634; follow-up: g = 0.487, 95 %CI: 0.348 to 0.626), immediate stigma reduction ( g = -0.332, 95 %CI: -0.479 to -0.186), immediate enhancement of help-seeking attitudes ( g = 0.168, 95 %CI: 0.046 to 0.3291) and help-seeking intentions ( g = 0.135, 95 %CI: 0.072 to 0.198), as well as immediate mental health improvements ( g = -0.074, 95 %CI: -0.115 to -0.033)., Conclusion: Overall, these findings underscore the promising effects of internet-based interventions in improving MHL and mental health, while maintaining these effects over time remains challenging, particularly in reducing stigma and promoting long-term help-seeking behaviors. Addressing methodological limitations, adopting a more interactive approach, and implementing targeted interventions are crucial to maximizing the effectiveness and advancing mental health care worldwide., 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 Author(s).)

Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage by virtue of its anti-inflammatory, reparative, and antioxidative properties. However, due to its large molecular structure of HHA, HHA solution could only form a protective film on the skin surface in conventional application, failing to effectively penetrate the skin, which necessitates the development of new delivery strategies. Liposomes, with a structure similar to biological membranes, have garnered extensive attention as transdermal drug delivery carriers because of their advantages in permeability, dermal compatibility, and biosafety. Herein, we have developed a HHA-liposome transdermal system (HHL) by embedding HHA into the liposome structure using reverse evaporation, high-speed homogenization, and micro-jet techniques. The effective penetration and long-term residence of HHA in skin tissue were multidimensionally verified, and the kinetics of HHA in the skin were extensively studied. Moreover, it was demonstrated that HHL significantly strengthened the activity of human keratinocytes and effectively inhibits photo-induced cellular aging in vitro. Furthermore, a murine model of acute skin injury induced by laser ablation was established, where the transdermal system showed significant anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair, thereby demonstrating immense potential in accelerating skin wound healing. Meanwhile, HHL significantly ameliorated skin barrier dysfunction caused by simulated sunlight exposure, inhibited skin erythema, inflammatory responses, and oxidative stress, and promoted collagen expression in a chronic photodamage skin model. Therefore, this transdermal delivery system with biocompatibility represents a promising new strategy for the non-invasive application of HHA in skin photodamage, revealing the significant potential for clinical translation and broad application prospects. STATEMENT OF SIGNIFICANCE: The transdermal system utilizing hyaluronic acid-based liposomes enhances skin permeability and retains high molecular weight hyaluronic acid (HHL). In vitro experiments with human keratinocytes demonstrate significant skin repair effects of HHL and its effective inhibition of cellular aging. In an acute photodamage model, HHL exhibits stronger anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair. In a chronic photodamage model, HHL significantly improves skin barrier dysfunction, reduces oxidative stress induced by simulated sunlight, and enhances collagen expression., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: Overweight/obesity is the strongest risk factor for endometrial cancer (EC), and weight management can reduce that risk and improve survival. We aimed to establish the differential benefits of intermittent energy restriction (IER) and low-fat diet (LFD), alone and in combination with paclitaxel, to reverse the procancer effects of high-fat diet (HFD)-induced obesity in a mouse model of EC., Methods: Lkb1 fl/fl p53 fl/fl mice were fed HFD or LFD to generate obese and lean phenotypes, respectively. Obese mice were maintained on a HFD or switched to a LFD (HFD-LFD) or IER (HFD-IER). Ten weeks after induction of endometrial cancer, mice in each group received paclitaxel or placebo for 4 weeks. Body and tumor weights; tumoral transcriptomic, metabolomic and oxylipin profiles; and serum metabolic hormones and chemocytokines were assessed., Results: HFD-IER and HFD-LFD, relative to HFD, reduced body weight; reversed obesity-induced alterations in serum insulin, leptin and inflammatory factors; and decreased tumor incidence and mass, often to levels emulating those associated with continuous LFD. Concurrent paclitaxel, versus placebo, enhanced tumor suppression in each group, with greatest benefit in HFD-IER. The diets produced distinct tumoral gene expression and metabolic profiles, with HFD-IER associated with a more favorable (antitumor) metabolic and inflammatory environment., Conclusion: In Lkb1 fl/fl p53 fl/fl mice, IER is generally more effective than LFD in promoting weight loss, inhibiting obesity-related endometrial tumor growth (particularly in combination with paclitaxel), and reversing detrimental obesity-related metabolic effects. These findings lay the foundation for further investigations of IER as an EC prevention and treatment strategies in overweight/obesity women., Competing Interests: Declaration of competing interest The authors did not disclose potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Colitis is an important risk factor for the occurrence of colorectal cancer (CRC), and the colonization of Fusobacterium nucleatum (Fn) in the intestines accelerates this transformation process. Banxia Xiexin Decoction (BXD), originating from Shanghanlun, is a classic prescription for treating gastrointestinal diseases. Current researches indicate that BXD can effectively delay the colitis-to-cancer transition, but it is still unclear whether it can inhibit Fn colonization to achieve this delaying effect., Aim of Study: This study explored the effect and mechanism of BXD in inhibiting Fn intestinal colonization to delay colitis-to-cancer transition., Materials and Methods: We constructed a mouse model of colitis-to-cancer transition by regularly gavaging Fn combined with azoxymethane (AOM)/dextran sodium sulfate (DSS), and administered BXD by gavage. We monitored the body weight of mice, measured the length and weight of their colons, and calculated the disease activity index (DAI) score. The growth status of colon tumors was observed by hematoxylin and eosin (H&E) staining, and the changes in gut microbiota in each group of mice were detected by 16S rDNA analysis. Immunohistochemistry was used to detect the expression of E-cadherin and β-catenin in colon tissues, and immunofluorescence was used to observe the infiltration of M2 macrophages in colon tissues. In cell experiments, we established a co-culture model of Fn and colon cancer cells and intervened with BXD-containing serum. Malignant behaviors such as cell proliferation, invasion, and migration were detected, as well as changes in their cell cycle. We examined the protein levels of E-cadherin, β-catenin, Axin2, and Cyclin D1 in each group were detected by Western blot. We used US1 strain (fadA-) as a control and observed the effects of BXD-containing serum on Fn attachment and invasion of colon cancer cells through attachment and invasion experiments., Results: BXD can inhibit the colitis-to-cancer transition in mice infected with Fn, reduce crypt structure damage, improve gut microbiota dysbiosis, upregulate E-cadherin and decrease β-catenin expression, and reduce infiltration of M2 macrophages, thus inhibiting the process of colitis-to-cancer transition. Cell experiments revealed that BXD-containing serum can inhibit the proliferation, migration, and invasion of colon cancer cells infected with Fn and regulate their cell cycle. More importantly, we found that BXD-containing serum can inhibit the binding of Fn's FadA adhesin to E-cadherin, reduce Fn's attachment and invasion of colon cancer cells, thereby downregulating the E-cadherin/β-catenin signaling pathway., Conclusions: These findings show that BXD can inhibit Fn colonization by interfering with the binding of FadA to E-cadherin, reducing the activation of the E-cadherin/β-catenin signaling pathway, and ultimately delaying colitis-to-cancer transition., 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.)

Valproate encephalopathy is one of the unusual and severe but treatable side effect. This research focuses on four female patients who had valproate medication for epilepsy and developed an increased frequency of seizures, exacerbated disruption of consciousness, gastrointestinal problems, cognitive dysfunction, ataxia, and psychobehavioral abnormalities. The patient's symptoms improved over time once sodium valproate was stopped. As a result, when using sodium valproate, one should be aware of the risk of sodium valproate encephalopathy and cease using the medication right once if any of the above symptoms of unknown etiology manifest clinically. We also go over the potential pathogenesis that lead to valproate encephalopathy and the heightened risk of encephalopathy from taking antiepileptic medications together. It was stressed how crucial it is to identify, diagnose, and treat sodium valproate encephalopathy as soon as possible., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: A reasonable and standardized dietary plan and procedure can help patients recovering quickly from lung cancer surgery. The aim of this study is to optimize the diet plan and procedure mainly based on medium chain triglyceride (MCT) diet and explore its clinical advantages for postoperative lung cancer patients., Methods: From October 2023 to December 2023, a total of 156 patients were collected, who underwent lung cancer surgery in Lung Cancer Center, West China Hospital of Sichuan University. The patients were randomized into MCT group (76 cases) and routine diet (RD) group (80 cases). Clinical symptoms, biochemical index, postoperative hospitalization time and cost, dietary satisfaction and hospitalization comfort between the two groups were analyzed., Results: The mean anus exhausting time in MCT group [24.00 (9.75, 36.97) h] was significantly shorter than that in RD group [28.50 (24.00, 48.00) h] (P<0.001). And the incidence of dizziness (18.42%), nausea and vomiting (6.58%) in MCT group were remarkably lower than those in RD group (51.25%, 31.25%) (P<0.001). Hospitalization comfort score in MCT group [(16.74±1.70)] was significantly higher than that in RD group [(14.83±2.34)] (P=0.016). Meanwhile, the average hospitalization cost in MCT group [(39,701.82±8105.47)¥] showed an obvious decrease compared with RD group [(44,511.79±9593.19)¥] (P=0.007)., Conclusions: Optimizing the dietary plan and procedure mainly based on MCT diet for postoperative lung cancer patients can help the recovery of gastrointestinal function and improve hospitalization comfort, which promoted overall postoperative rehabilitation of patients with lung cancer surgery.

The plastic waste issue has posed a series of formidable challenges for the ecological environment and human health. While conventional recycling strategies often lead to plastic down-cycling, the electrochemical strategy of recovering valuable monomers enables an ideal, circular plastic economy. Here a corrosion synthesized single atom Pt 1 /Ni(OH) 2 electrocatalyst with part-per-million noble Pt loading for highly efficient and selective upcycling of polyethylene terephthalate (PET) into valuable chemicals (potassium diformate and terephthalic acid) and green hydrogen is reported. Electro-oxidation of PET hydrolysate, ethylene glycol (EG), to formate is processed with high Faraday efficiency (FE) and selectivity (>90%) at the current density close to 1000 mA cm -2 (1.444 V vs RHE). The in situ spectroscopy and density functional theory calculations provide insights into the mechanism and the understanding of the high efficiency. Remarkably, the electro-oxidation of EG at the ampere-level current density is also successfully illustrated by using a membrane-electrode assembly with high FEs to formate integrated with hydrogen production for 500 h of continuous operation. This process allows valuable chemical production at high space-time yield and is highly profitable (588-700 $ ton -1 PET), showing an industrial perspective on single-atom catalysis of electrochemical plastic upcycling., (© 2024 Wiley‐VCH GmbH.)

As the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), the progression of nonalcoholic steatohepatitis (NASH) is associated with disorders of glycerophospholipid metabolism. Scoparone is the major bioactive component in Artemisia capillaris which has been widely used to treat NASH in traditional Chinese medicine. However, the underlying mechanisms of scoparone against NASH are not yet fully understood, which hinders the development of effective therapeutic agents for NASH. Given the crucial role of glycerophospholipid metabolism in NASH progression, this study aimed to characterize the differential expression of glycerophospholipids that is responsible for scoparone's pharmacological effects and assess its efficacy against NASH. Liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) was performed to get the concentrations of glycerophospholipids, clarify mechanisms of disease, and highlight insights into drug discovery. Additionally, pathologic findings also presented consistent changes in high-fat diet-induced NASH model, and after scoparone treatment, both the levels of glycerophospholipids and histopathology were similar to normal levels, indicating a beneficial effect during the observation time. Altogether, these results refined the insights on the mechanisms of scoparone against NASH and suggested a route to relieve NASH with glycerophospholipid metabolism. In addition, the current work demonstrated that a pseudotargeted lipidomic platform provided a novel insight into the potential mechanism of scoparone action., Competing Interests: The authors declare there are no competing interests., (©2024 Song et al.)

Epidemiological and clinical evidence have extensively documented the role of obesity in the development of endometrial cancer. However, the effect of fatty acids on cell growth in endometrial cancer has not been widely studied. Here, we reported that palmitic acid significantly inhibited cell proliferation of endometrial cancer cells and primary cultures of endometrial cancer and reduced tumor growth in a transgenic mouse model of endometrial cancer, in parallel with increased cellular stress and apoptosis and decreased cellular adhesion and invasion. Inhibition of cellular stress by N-acetyl-L-cysteine effectively reversed the effects of palmitic acid on cell proliferation, apoptosis, and invasive capacity in endometrial cancer cells. Palmitic acid increased the intracellular formation of lipid droplets in a time- and dose-dependent manner. Depletion of lipid droplets by blocking DGAT1 and DGAT2 effectively increased the ability of palmitic acid to inhibit cell proliferation and induce cleaved caspase 3 activity. Collectively, this study provides new insight into the effect of palmitic acid on cell proliferation and invasion and the formation of lipid droplets that may have potential clinical relevance in the treatment of obesity-driven endometrial cancer.

Ascorbate (vitamin C) is an essential vitamin for the human body and participates in various physiological processes as an important coenzyme and antioxidant. Furthermore, the role of ascorbate in the prevention and treatment of cancer including gynecological cancer has gained much more interest recently. The bioavailability and certain biological functions of ascorbate are distinct in males versus females due to differences in lean body mass, sex hormones, and lifestyle factors. Despite epidemiological evidence that ascorbate-rich foods and ascorbate plasma concentrations are inversely related to cancer risk, ascorbate has not demonstrated a significant protective effect in patients with gynecological cancers. Adequate ascorbate intake may have the potential to reduce the risk of human papillomavirus (HPV) infection and high-risk HPV persistence status. High-dose ascorbate exerts antitumor activity and synergizes with chemotherapeutic agents in preclinical cancer models of gynecological cancer. In this review, we provide evidence for the biological activity of ascorbate in females and discuss the potential role of ascorbate in the prevention and treatment of ovarian, endometrial, and cervical cancers.

Unsaturated furanic aldehydes are derived from lignocellulosic biomass resources and subsequently used to produce valuable chemicals. However, the highly efficient, selective hydrogenation of the biomass-derived unsaturated furan CO bond remains challenging. Here we report that graphene-like nitrogen doped porous carbon (GNPC) nanosheets are synthesized from carbon-rich, sustainable, and renewable biomass precursors (glucose, fructose and 5-hydroxymethylfurfural, HMF) with high surface areas, large pore volumes and narrow mesopores. GNPC derived from HMF is an excellent catalyst support for PtCo nanoparticles with ultrafine nanoparticles size and homogeneous distributions. This catalyst is highly efficient for hydrogenation of biomass-derived furan-based unsaturated aldehydes, with high yields, to the corresponding unsaturated alcohols under mild conditions. This design strategy should further allow the development of selective, simple, green heterogeneous catalysts for challenging chemical transformations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) in urban fugitive dust, known for their toxicity and ability to generate reactive oxygen species (ROS), are a major public health concern. This study assessed the spatial distribution and health risks of 15 PAHs in construction dust (CD) and road dust (RD) samples collected from June to November 2021 over the cities of Tongchuan (TC), Baoji (BJ), Xianyang (XY), and Xi'an (XA) in the Guanzhong Plain, China. The average concentration of ΣPAHs in RD was 39.5 ± 20.0 μg g -1 , approximately twice as much as in CD. Four-ring PAHs from fossil fuels combustion accounted for the highest proportion of ΣPAHs in fugitive dust over all four cities. Health-related indicators including benzo(a)pyrene toxic equivalency factors (BAP TEQ ), oxidative potential (OP), and incremental lifetime cancer risk (ILCR) all presented higher risk in RD than those in CD. The multilayer perceptron neural network algorithm quantified that vehicular and industrial emissions contributed 86 % and 61 % to RD and CD BAP TEQ , respectively. For OP, the sources of biomass and coal combustion were the key generator which accounted for 31-54 %. These findings provide scientific evidence for the direct efforts toward decreasing the health risks of fugitive dust in Guanzhong Plain urban agglomeration, China., 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.)