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Glutathione (GSH) levels have been well validated to correlate with a variety of physiological and pathological conditions, such as malignancy, cardiovascular disease and aging, making the development of accurate, robust and sensitive GSH detection methods highly desirable. In this study, a novel metal-organic framework (MOF-Fe(DTNB))-based colorimetric method with a favorable dual-triggering function was proposed. MOF-Fe(DTNB) exhibits high peroxidase activity, which can catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue ox-TMB by hydrogen peroxide (H 2 O 2 ). This oxidation process of TMB can be inhibited not only by the reducing action of GSH, but also by the thiol exchange reaction between DTNB and GSH, in which the disulfide bond of DTNB in MOF-Fe(DTNB) is cleaved. Thus, with this dual triggering mechanism, the GSH concentration can be robustly measured in the MOF-Fe(DTNB)-derived colorimetric strategy. Significantly, this method is accurate (RSD < 6 %), selective and sensitive in biological plasma samples, with satisfactory recovery rates (96.7-103.3 %). It requires less instrumentation and has less interference from other substances. The linear range of the method is 0-80 µM, and the detection limit is as low as 0.28 µM. This dual-triggering MOF-Fe(DTNB)-derived colorimetric strategy has greatly simplified the GSH detection processes with improved accuracy, in both acidic and basic environments, which has potent applications in biochemical analysis and point-of-care testing., 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.)

N49P9.6-FR-LS and PGT121 are promising antibodies with significant therapeutic potential against HIV infection, but they are prone to precipitation at concentrations greater than 12 to 13 mg/mL. This study evaluates the influence of six excipients─arginine, alanine, sucrose, trehalose, methionine, and glutamate─on the biophysical stability of antibodies. We employed a comprehensive approach, combining computational mAb-excipient interaction analysis via the site-identification by ligand competitive saturation (SILCS) method with extensive experimental characterization. Our experimental matrix included viscosity measurements across temperature gradients, particle size distribution, zeta potential, pH value, and solution appearance, alongside a short-term stability product study at 30 °C and 65% relative humidity, with assessments at t 0 (initial), t 1 (14 days), and t 2 (28 days). Results indicated that sucrose, arginine, alanine, and trehalose provided varying degrees of stabilization for both antibodies. Conversely, glutamate destabilized PGT121 but stabilized N49P9.6-FR-LS, while methionine had a negative effect on N49P9.6-FR-LS but a positive one on PGT121. SILCS-Biologics analysis suggested that stabilization by these excipients is linked to their ability to occupy regions involved in self-protein interactions. Debye-Hückel-Henry charge calculations further indicated that neutral excipients like sucrose and trehalose could alter mAb charges by affecting buffer binding, influencing aggregation propensity. These findings offer valuable insights for optimizing antibody formulations, ensuring enhanced product stability and therapeutic efficacy for HIV treatment.

Rabies, caused by rabies virus (RABV), is a zoonotic disease with a high mortality rate that has attracted global attention with the goal of eradication by 2030. However, rabies can only be prevented by appropriate and multiple vaccinations, which impede widespread vaccination in developing countries due to its high expenditure. Designing single-dose vaccines is a pressing challenge in the prevention of rabies and other infectious diseases. Herein, a metal-phenolic network (MPN)-based hydrogel vaccine (designated as CGMR) was developed to stimulate potent humoral immunity against RABV infection by a single immunization, resulting in 4.3-fold and 1.8-fold enhancements of virus-neutralizing antibody compared with that induced by inactivated RABV and alum adjuvant. The CGMR, cross-linked by phenol-modified chitosan with manganese ion, could prolong residence time by confining the antigen to the network of hydrogel, acting as a "hydrogel antigen depot". It also stimulated the activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) pathway, facilitating dendritic cell maturation and antigen presentation. The vaccine formulation recruited immunocytes and activated the germinal center, enhancing and sustaining humoral immune responses against the virulent RABV challenge. Collectively, this injectable manganese-based hydrogel vaccine provides a universal and ideal avenue for rabies and other infectious diseases.

Despite progress in reducing global hunger, micronutrient deficiencies and imbalanced diets linked to urbanization remain pressing health threats. Protected cultivation offers a promising avenue for sustainable intensification of vegetable production. Additionally, indoor and vertical farming have recently emerged as cutting-edge strategies, particularly in densely populated urban areas and mega-cities. However, research has focused on maximizing yield, neglecting the impact of pre-harvest conditions on produce quality. Here, we explore strategies for manipulating environmental factors within protected cultivation systems to enhance vegetable nutritional value. Research suggests moderate stress can positively influence nutrient composition while plants exhibit stage-specific metabolic responses to environmental factors. For instance, seedlings thrive under a higher blue-to-red ratio, while green light benefits leafy vegetables. Additionally, increased blue light or supplemental UV-A benefits flowering and fruiting vegetables. When other environmental factors are optimal, light intensity significantly impacts vegetable nutritional quality, followed by CO 2 levels, light spectrum, temperature, and humidity. Further research is needed to fully understand the mechanisms, the complex interplay of environmental factors, and their interaction with genetic material and cultural practices on nutritional quality., (© 2025 The Author(s). Comprehensive Reviews in Food Science and Food Safety published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Background: Hyperaldosteronism is an endocrine disorder leading to persistent and severe hypertension. G protein-coupled estrogen receptor 1(GPER1) is regarded as a potential receptor of aldosterone (ALDO)., Objective: This study aimed to investigate the effects of GPER1 on aldosterone (ALDO)-induced hypertension and inflammation in mice., Methods: GPER1-knockout (KO) and wild-type (WT) C57BL/6j mice were divided into control (CON, normal saline treatment), ALDO (subcutaneous injections of 600 g/kg/d ALDO), and ALDO + eplerenone (EPL) (subcutaneous injections of 600 g/kg/d ALDO and 100 mg/kg/d EPL) groups (n = 5 per group). Fourteen days after drug administration, the heart rate and tail blood pressure of the mice in the different groups were measured. S100A8 and IL-1β protein expression in arterial tissues were detected by western blotting, NLRP3 expression was assessed using immunofluorescence, and CD68 expression was investigated using immunohistochemistry., Results: GPER1 deficiency alleviated ALDO-induced diastolic blood pressure (P< 0.05). In addition, the protein expression levels of IL-1β, S100A8, and CD68 showed significant decreases in the arterial tissues of GPER1-KO mice after combination treatment with ALDO and EPL (all P < 0.05)., Conclusion: We discovered attenuation of hypertension and vascular inflammation of GPER1 KO mice only on the basis of mineralocorticoid receptor (MR) blocking. Collectively, our study indicates that GPER1 might become a therapeutic target of hyperaldosteronism in controlling the residual risk of cardiovascular disease when MR antagonist alone is not satisfying., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Ethical approval: All animal procedures were approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (2020-734)., (© 2024. The Author(s).)

Prostate cancer (PCa) is the most prevalent cancer in men and the leading cause of cancer-related mortality. Recent studies have highlighted the pivotal role of glycolysis in tumor progression. This study aimed to investigate the involvement of the EDNRB gene and its ligand endothelin 3 (EDN3) in glycolysis in PCa and to elucidate its underlying molecular mechanism. Quantitative reverse transcription PCR (RT-qPCR) and methylation-specific PCR (MSP) were used to probe EDNRB expression and methylation in PCa tissues. Cell proliferation and glycolysis in PCa cells were evaluated using Cell Counting Kit-8 (CCK-8), EDU staining, Seahorse assay, and biochemical kits to analyze the effects of EDN3/EDNRB. The underlying molecular mechanism was further explored through Western blotting. The in vivo effect of EDNRB on tumor growth was examined using a xenograft tumor model. Our findings revealed that EDNRB was hypermethylated and downregulated in PCa tissues and cell lines. Overexpression of EDNRB or EDN3 led to reduced cell proliferation and downregulation of glycolytic markers. EDNRB also decreased the extracellular acidification rate (ECAR) baseline and increased the oxygen consumption rate (OCR) baseline, indicating a shift away from glycolysis. Additionally, the anticancer effects of EDNRB or EDN3 was reversed upon inhibition of the cGMP/PKG pathway. In vivo, enhanced EDNRB expression significantly suppressed tumor growth. Therefore, EDNRB or EDN3 possess anticancer potential in PCa, primarily through the regulation of glycolysis via the cGMP/PKG pathway., Competing Interests: Declaration of competing interest The authors state that there are no conflicts of interest to disclose., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Sarcomas (SARC) are a diverse group of malignant tumors originating from mesenchymal tissues, characterized by poor prognosis under conventional therapies. CX3CR1, a chemokine receptor involved in immune cell migration, has emerged as a key player in SARC. Post-translational modifications (PTMs) such as phosphorylation and ubiquitination critically modulate CX3CR1, influencing cancer progression, immune responses, and treatment resistance., Methods: This study investigates CX3CR1 expression, its biological functions, and prognostic value in SARC. Using data from The Cancer Genome Atlas (TCGA), we analyzed CX3CR1 gene expression, methylation patterns, CRISPR screening results, and immune infiltration metrics. Functional experiments included knockout and overexpression models, CCK-8 assays and flow cytometry to assess apoptosis., Results: CX3CR1 expression was significantly elevated in SARC tissues and positively correlated with overall survival, disease-specific survival, and progression-free intervals. Methylation analysis identified CpG sites associated with CX3CR1 expression, differentiating tumor and adjacent tissues. CRISPR screening highlighted CX3CR1's essential role in tumor growth, while immune infiltration analysis underscored its impact on the tumor microenvironment. PTMs were found to stabilize CX3CR1, enhancing its activity in key signaling pathways. Overexpression of CX3CR1 amplified inflammatory and apoptotic responses, while knockdown showed protective effects in vitro., Conclusions: CX3CR1 serves as a promising prognostic biomarker and therapeutic target in sarcoma. Targeting CX3CR1's PTMs could advance personalized treatments and improve outcomes for sarcoma patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests, personal relationships, or other conflicts of interest that could have influenced the research, analysis, or interpretation of the findings presented in this study., (Copyright © 2025. Published by Elsevier Inc.)

In this study, we explored how cadmium and lead co-exposure affects sleep status among residents of a polluted area and nature reserve in rural northwestern China. Cadmium and lead levels were measured using blood samples, and sleep status was evaluated using sleep questionnaires, with the main sleep indicators including sleep duration, sleep quality, bedtime, and staying up. Furthermore, cadmium-lead co-exposure levels were divided into three groups: high exposure, medium exposure, and low exposure. Subjects in the contaminated area had significantly higher exposure levels (p < 0.001) and more negative sleep indicators (p < 0.01). Significant differences were found for all four sleep indicators in the high exposure group compared to the low exposure group (p < 0.01). Moreover, the overall evaluation of sleep status with high cadmium-lead co-exposure had a negative impact. Our data suggest that cadmium-lead co-exposure has a negative effect on sleep status and may have a synergistic effect on sleep., Competing Interests: Declarations. Ethical Approval: The protocol of this study was approved by the First Hospital of Lanzhou University Medical Ethics Committee (research ethics code: LDYYLL2015-0027, LDYYLL2020-103). Informed Consent: Informed consent was obtained from all individual participants included in the study. The informed consent was written. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To determine the effects of roxadustat on calcification when treating renal anemia in end-stage kidney disease (ESKD) patients., Methods: A prospective cohort study enrolled participants with ESKD that either received roxadustat or no roxadustat treatment. The primary outcome was the change in the degree of hydroxyapatite (HAP) crystals deposition. The secondary outcome was calcification propensity, a measure of calcification, allowing an evaluation of the conversion process from primary to secondary calciprotein particles., Results: A total of 205 patients were enrolled, and 187 (91.2%) completed follow-up for inclusion in the analysis and were divided into the roxadustat group (n = 92) and the control group (n = 95) based on whether or not they were taking roxadustat regularly over a 6-month period. After roxadustat administration for 6 months, patients exhibited increases in total red blood cell counts, hematocrit, hemoglobin, calcium, total ferritin binding, iFGF23, SPP24, and calcification propensity relative to pre-treatment levels. No significant differences were observed in patients who were not treated with roxadustat. The deposition degree of HAP crystals increased by 5% and 0.01% following treatment with roxadustat in the roxadustat group and control group, respectively. Linear regression analysis found that the use of roxadustat was an independent risk factor for calcification propensity and changes in the degree of HAP crystals deposition., Conclusion: Roxadustat treatment may increase iFGF23, SPP24, and calcification propensity in patients with ESKD when treating these patients for renal anemia. Therefore, the clinicians should aware of this risk when treating patients with PHIs., (© The Author(s) 2025. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Covalent inhibition of the KRAS G12C oncoprotein has emerged as a promising therapeutic approach for the treatment of nonsmall cell lung cancer (NSCLC). The identification of KRAS G12C inhibitors has typically relied on the high-throughput screening (HTS) of libraries of cysteine-reactive small molecules or on the attachment of cysteine-reactive warheads to noncovalent binders of KRAS. Such screening approaches have historically been limited in the size and diversity of molecules that could be effectively screened. DNA-encoded library (DEL) screening has emerged as a promising approach to accelerate the preparation and screening of incredibly large and diverse chemical libraries. Here, we describe the design and synthesis of a covalent DEL to screen ∼16 million compounds against KRAS G12C . We additionally describe the hit identification, validation, and structure-based optimization that culminated in the identification of a series of structurally novel, potent, and selective covalent inhibitors of KRAS G12C with good pharmacokinetic profiles and promising in vivo pharmacodynamic effects.

Background: Lysine acetylation is a critical post-translational modification regulating tumor initiation and progression. Lysine acetyltransferase 7 (KAT7)-mediated lysine acetylation is frequently dysregulated in cancer. However, the role of KAT7-mediated lysine acetylation in hepatocellular carcinoma (HCC) progression remains unclear., Methods: Bioinformatic analysis was used to investigate the expression, clinicopathological characteristics and diagnostic prognostic value of KAT7 in HCC. CCK-8 assays, colony-forming assays, apoptosis assays and nude mouse xenograft models were utilized to detect the oncogenic functions of KAT7 in HCC. Immunoprecipitation (IP) assay and mass spectrometry (MS) analysis were performed to identify the KAT7-binding protein Y-box binding protein 1 (YBX1). Transcriptome sequencing and functional enrichment analysis were employed to elucidate the downstream pathway regulated by KAT7 and YBX1. Chromatin immunoprecipitation (ChIP) assay was used to evaluate YBX1 binding to the promoter regions of ribonucleotide reductase regulatory subunit M2 (RRM2) and thymidine kinase 1 (TK1). Weighted gene co-expression network analysis and selection operator regression analysis were used to build risk prediction models., Results: This study demonstrated that elevated KAT7 expression is associated with poor prognosis in HCC patients. Knockdown of endogenous KAT7 in HCC cells attenuated tumorigenic phenotypes associated with cell proliferation, colony formation and orthotopic xenograft tumor growth, indicating a pro-tumorigenic role of KAT7 in HCC. YBX1 was identified as a novel non-histone substrate for KAT7, and the E508 residue of KAT7 is essential for binding. Following the functional enrichment analysis, KAT7 and YBX1 were correlated with nucleotide metabolism. Furthermore, KAT7 binds to YBX1 and modulates its post-translational expression, which enhances the transcriptional activity of the central nucleotide metabolism enzymes RRM2 and TK1. Additionally, we constructed a novel prognostic prediction model based on KAT7, YBX1, RRM2 and TK1, which validated the predictive accuracy and prognostic value of KAT7-mediated acetylation is consistent with clinical outcomes in HCC., Conclusions: Our findings highlight that KAT7 acetylates YBX1 and promotes HCC progression by reprogramming nucleotide metabolism, offering therapeutic implications., Competing Interests: Declarations. Ethics approval and consent to participate: The use of human samples was approved by the Ethics Committee of the First Hospital of Lanzhou University (number: LDYYLL-2023–266), following the Declaration of Helsinki Principles. The animal study protocols were approved by the Ethics Committee of the First Hospital of Lanzhou University (number: LDYYLL-2022–511). All animal experiments were performed according to legal and ethical requirements and the 3Rs (Replacement, Refinement and Reduction of Animals in Research). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Lattice oxygen redox (LOR) in P2-type layered oxides is an effective strategy to break through the limit of energy density of conventional cathodes due to its high redox potential (>4 V vs Na + /Na) as well as extra capacity. Nevertheless, LOR-induced local structure distortion and irreversible phase transitions cause serious electrochemical performance degradation, hindering practical applications. Herein, we propose that the generation of the OP4 phase can be replaced with the Z phase by introducing the Sb element with a higher ionic potential and strong covalent bonds within the TMO 6 octahedron. Z phase transition is realized by constraining interlayer slipping between adjacent transition metal (TM) layers compared to OP4, which reduces the strain in the layered structure, lowers the Na + diffusion energy barrier, and creates more efficient Na + diffusion channels. Consequently, Sb-substituted oxides demonstrate excellent kinetics, rate capability (79 mAh g -1 at 1 A g -1 ) in half cells, and a high energy density of 487 Wh kg -1 (on cathode) in full cells.

Penicillium camembertii lipase (PCL) is a glycerol-biased enzyme isolated from P. camembertii, exhibiting high esterification activity. The PCL activity was enhanced by combining fermentation optimization with atmospheric and room temperature plasma (ARTP) mutagenesis. Following multiple rounds of high-throughput screening and serial passages, a genetically stable mutant, P12, was obtained. In shake flask culture, P12 exhibited a lipase activity of 1600 U/g, representing an 800 % increase compared to the wild type (WT), with improved thermostability and methanol stability. Subsequently, P12 was used as a whole-cell biocatalyst to catalyze the esterification of oleic acid with glycerol in a solvent-free system to prepare 1,3-diacylglycerol (1,3-DAG). With an oleic acid /glycerol molar ratio of 4:1, 8 % biocatalyst, and a reaction temperature of 40 °C, the content of 1,3-DAG was 74.7 % after 24 h. These results suggest that the mutant P12 demonstrates considerable potential as a whole-cell biocatalyst for synthesizing high-purity 1,3-DAG., 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.)

Dislocations in van der Waals (vdW) layered nanomaterials induce strain and structural changes that substantially impact thermal transport. Understanding these effects could enable the manipulation of dislocations for improved thermoelectric and optoelectronic applications, but experimental insights remain limited. In this study, we use synthetic Eshelby twisted vdW GeS nanowires (NWs) with single screw dislocations as a model system to explore the interplay between dislocation-induced structural modifications and lattice thermal conductivity. Our measurements reveal a monoclinic structure stabilized by the dislocation, leading to a substantial drop in thermal conductivity for larger-diameter NWs (70% at room temperature), supported by first-principles calculations. Interestingly, we also find an anomalous enhancement of thermal conductivity with decreasing diameter in twisted NWs, contrary to typical trends in non-twisted GeS NWs. This is attributed to increased conductivity near the NW cores due to compressive strain around the central dislocations, and aligns with a density-functional-theory-informed core-shell model. Our results highlight the critical role of dislocations in thermal conduction, providing fundamental insights for defect and strain engineering in advanced thermal applications., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Evaluating the post-discharge health-related quality of life (HRQoL) in hemophagocytic lymphohistiocytosis (HLH) and exploring its influencing factors., Patients and Methods: The study was conducted at a regional pediatric medical center and involved pediatric patients diagnosed with HLH between July 2017 and July 2022. Healthy children of the same age and sex were included as the control group. The HRQoL and its associated factors in pediatric patients were assessed using the PedsQL 4.0 Parent Proxy Report and a general information survey., Results: In the first year following diagnosis, psychological health and overall score in HLH patients were worse than those of the control group. However, scores for emotional functioning, school functioning, physical health, psychosocial health, and overall scores in the HLH group increased over the years since diagnosis. By the 5-year post diagnosis, there were no significant differences between the HLH group and the control group in social functioning, school functioning, physical health, psychosocial health, and overall scores (p > 0.05). Generalized linear model analysis revealed that HLH patients who underwent transplantation have worse social functioning, physical health, overall score, while HLH patients with HLH recurrence have worse social functioning, psychosocial health, overall score (p < 0.05)., Conclusion: The HRQoL of HLH patients is compromised after discharge; however, it progressively returns to levels comparable to those of healthy cohorts over time since diagnosis. Transplantation, and HLH recurrence are identified as factors affecting the HRQoL in HLH patients., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Acute coronary syndrome (ACS) is a leading cause of death worldwide. Prompt and accurate diagnosis of acute myocardial infarction (AMI) or ACS is crucial for improved management and prognosis of patients. The rapid growth of machine learning (ML) research has significantly enhanced our understanding of ACS. Most studies have focused on applying ML to detect ACS, predict prognosis, manage treatment, identify risk factors, and discover potential biomarkers, particularly using data from electrocardiograms (ECGs), electronic medical records (EMRs), imaging, and omics as the main data modality. Additionally, integrating ML with smart devices such as wearables, smartphones, and sensor technology enables real-time dynamic assessments, enhancing clinical care for patients with ACS. This review provided an overview of the workflow and key concepts of ML as they relate to ACS. It then provides an overview of current ML algorithms used for ACS diagnosis, prognosis, identification of potential risk biomarkers, and management. Furthermore, we discuss the current challenges faced by ML algorithms in this field and how they might be addressed in the future, especially in the context of medicine., Competing Interests: Declarations. Conflict of Interest: Shanshan Nie, Shan Zhang, Yuhang Zhao, Xun Li, Huaming Xu, Yongxia Wang, Xinlu Wang, and Mingjun Zhu have nothing to disclose. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)

Obesity increases the risk of kidney injury, involving various pathological events such as inflammation, insulin resistance, lipid metabolism disorders, and hemodynamic changes, making it a significant risk factor for the development and progression of chronic kidney disease. Diosmin, a natural flavonoid glycoside, exhibits anti-inflammatory, antioxidant, anti-lipid, and vasodilatory effects. However, whether diosmin has a protective effect on obesity-related kidney injury remains unclear. The molecular formula of diosmin was obtained, and diosmin and target genes related to obesity-related kidney injury were screened. The interaction between overlapping target genes was analyzed. GO functional enrichment and KEGG pathway enrichment analyses were performed on overlapping target genes. Molecular docking was employed to assess the binding strength between overlapping target genes. Palmitic acid-induced damage to HK-2 cells, which were then treated with diosmin. Subsequently, the expression levels of relevant mRNAs and proteins were measured. Network analysis identified 219 potential diosmin target genes, 6800 potential target genes related to obesity-related kidney injury, and 93 potential overlapping target genes. Protein-protein interaction networks and molecular docking results revealed that AKT1, TNF-α, SRC, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3β, and MMP2 were identified as key therapeutic targets, and they exhibited stable binding with diosmin. GO analysis indicated that these key targets may participate in inflammation, chemical stress, and protein phosphorylation. KEGG revealed that pathways in cancer, AGE-RAGE signaling pathway, PI3K-AKT signaling pathway, PPAR signaling pathway, and insulin resistance as crucial in treating obesity-related kidney injury. CCK-8 assay showed that diosmin significantly restored the viability of HK-2 cells affected by palmitic acid. Oil Red O staining demonstrated that diosmin significantly improved lipid deposition in HK-2 cells induced by palmitic acid. PCR results showed that diosmin inhibited the mRNA levels of AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, GSK-3β, and MMP2 while promoting the mRNA level of PPAR-γ. Western blot analysis revealed that diosmin restored PPAR-γ protein expression, inhibited NF-kB p-p65 protein expression, and reduced TNF-α protein expression. Diosmin demonstrated multi-target and multi-pathway effects in the treatment of obesity-associated renal injury, with key targets including AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3β, and MMP2. The mechanism may be through the modulation of the PPAR-γ/NF-κB signaling pathway, which can attenuate inflammatory responses and protect the kidney., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Prolonged retention of tracheostomy tubes post-procedure often leads to complications, including granulation tissue overgrowth, airway narrowing, and laryngeal edema, necessitating delayed removal of the tracheostomy tube. Currently, a definitive therapeutic regimen capable of simultaneously resolving these complications and expediting tracheostomy decannulation remains elusive. Herein, we present an efficacious strategy addressing these airway morbidities and facilitating rapid tube removal. A 44-year-old male patient, who had undergone tracheostomy due to underlying disease, demonstrated substantial recovery following rehabilitation and was poised for tracheostomy tube extraction. However, bronchoscopic examination revealed severe granulation tissue at the stoma site and laryngeal edema, posing challenges to immediate decannulation. To tackle these issues concurrently while aiming for swift tube removal, we performed bronchoscopic intervention for granulation tissue excision, subsequently replacing the conventional tracheostomy tube with a Montgomery T tube as a transitional measure to restore normal ventilation. With additional rehabilitation fostering respiratory function enhancement, follow-up bronchoscopies confirmed no recurrence of granulations and significant reduction in laryngeal edema, thereby enabling the successful removal of the Montgomery T tube 2 months later, restoring the patient's unassisted respiratory capacity. This case underscores a clinically pertinent insight: following resolution of local airway abnormalities impeding tracheostomy decannulation, the strategic implementation of a Montgomery T tube as a transitional phase merits serious consideration among clinicians managing patients with long-term tracheostomies. Our findings contribute to the development of more streamlined approaches to overcoming complexities associated with tracheostomy tube removal in clinical practice., 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 © 2025 Wang, Li, Xu, Jiang, Yang and Chen.)

Background: Children and adolescents with cerebral palsy (CP) commonly have behaviour problems. The present study aimed to determine which of the most common clinical features experienced by children and adolescents with CP and intellectual disability are associated with behaviour problems., Method: We investigated 11 possible associated variables including epilepsy, visual and hearing impairments, motor difficulties, communication and speech difficulties, pain, sleep disturbance, executive function (EF) deficits, type of CP, and parent stress. Thirty-eight parents or guardians of children aged 6 to 17 years with CP and intellectual disability (parent informed) completed proxy and self-report standardised questionnaires., Results: EF deficits and parent stress were significantly associated with behavioural problems., Conclusion: For children and adolescents with CP and intellectual disability, the present study suggests close attention should be placed on specific clinical features including EF deficits and parent stress when considering variables associated with behaviour problems.

The off-stoichiometric compound Na 3.12 Fe 2.44 (P 2 O 7 ) 2 (NFPO) is a highly promising, cost-effective, and structurally robust cathode material for sodium-ion batteries (SIBs). However, the slowing Na-ion migration kinetics and poor interface stability have seriously limited its rate capability and air stability. In this work, we successfully synthesis a sodium titanium pyrophosphate (NaTiP 2 O 7 donated as NTPO) coating NFPO (denoted as NFPO-NTPO) cathode material via a liquid phase coating method for SIBs. After optimizing NTPO content, at 0.1C, NFPO-NTPO-4 % cathode achieves a reversible specific capacity of 108.4 mAh g -1 . Remarkably, it maintains 88.39 % capacity at 10C comparing to 0.1C and stabilizes over 3000 cycles with 92.66 % retention rate. Moreover, it retains 88.89 % capacity after 5000 cycles at 20C, even after 28 days of air exposure. The NFPO-Ti cathode, alongside the complete battery system, exhibits remarkable electrochemical performance across a broad temperature range spanning from -40 to 60 ℃., 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 Inc.)

Rationale: Peliosis hepatis (PH) is a rare disease with few clinical reports and complex etiology. However, there have been no reports of hyperprolactinemia (HPRL) leading to PH at present. This paper, through case reports, expands the understanding of the etiology of PH and the pathological damage effect of prolactin (PRL)., Patient Concerns: The patient reported in this paper had jaundice, menstrual disorders, menopause, weight gain, and other symptoms. Laboratory examination found increased levels of PRL and transaminase in liver function, and imaging examination indicated pituitary tumor and PH., Diagnoses: Comprehensive patient history and auxiliary examination, the clinical diagnosis was pituitary PRL tumor and PH., Interventions and Outcomes: After treatment with bromocriptine, menstruation recovered and liver function returned to normal. In addition, the follow-up imaging examination indicated that pituitary tumors and PH lesions were shrinking, and clinical phenomena indicated that HPRL caused by pituitary prolactinoma was correlated with PH occurrence., Lessons: Since there is no report of HPRL causing PH, the specific pathogenesis is unknown. This paper reviews the relevant literature and puts forward the theoretical consideration of the pathogenesis. Through this case, for clinically similar patients, it is warned that we need to consider the possibility of PH and further improve the examination, evaluation and treatment in time., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

The incidence of prostate cancer (PCa) is increasing annually, making it the leading cause of tumor-related mortality in males. The available treatment options for metastatic PCa are limited. Vasculogenic mimicry (VM), an emerging phenomenon involving aggressive tumor cells, has a significant impact on patient survival. Misregulation of Wnt5a expression is commonly observed during cancer progression. However, there is a lack of comprehensive studies investigating the effects of Wnt5a on tumor VM formation. In this study, we demonstrate that alterations in wnt5a expression, either through gain or loss, have a significant influence on the formation of VM in tumor cells mediated by cell stemness and EMT progression. Further research has demonstrated that Wnt5a regulates the formation of VM through the PI3K/JNK signaling pathway. These experimental findings offer a novel avenue for the clinical management of prostate cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: A precise model for predicting outcomes is needed to guide perioperative management. With the development of the liver transplantation (LT) discipline, previous models may become inappropriate or noncomprehensive. Thus, we aimed to develop a novel model integrating variables from donors and recipients for quick assessment of transplant outcomes., Methods: The risk model was based on Cox regression in a randomly selected derivation cohort and verified in a validation cohort. Perioperative data and overall survival were compared between stratifications grouped by X-tile. Receiver-operating characteristic curve and decision curve analysis were used to compare the models. Violin and raincloud plots were generated to present post-LT complications distributed in different stratifications., Results: Overall, 528 patients receiving LT from 2 centers were included with 2/3 in the derivation cohort and 1/3 in the validation cohort. Cox regression analysis showed that cold ischemia time (CIT) ( P = 0.012) and Model for End-Stage Liver Disease (MELD) ( P = 0.007) score were predictors of survival. After comparison with the logarithmic models, the primitive algorithms of CIT and MELD were defined as the CIT-MELD Index (CMI). CMI was stratified by X-tile (grade 1 ≤1.06, 1.06 < grade 2 ≤ 1.87, grade 3 >1.87). In both cohorts, CMI performed better in calculating transplant outcomes than the balance of risk score, including perioperative incidents and prevalence of complications., Discussion: The model integrating variables from graft donors and recipients made the prediction more accurate and available. CMI provided new insight into outcome evaluation and risk factor management of LT., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Clostridium perfringens (C. perfringens) type C exhibits strong pathogenicity, often leading to swine dysentery, severely affecting the economic efficiency of the pig farming industry. Bacteriophages as bacterial viruses have many natural advantages and are potent candidates for controlling bacterial infections. In this study, a lytic C. perfringens phage designed as vB&#95;CpeP&#95;15N3 was isolated with the host C. perfringens type C CVCC1155, and its potential for therapy was determined in vitro and in vivo. Despite the narrow host range, phage vB&#95;CpeP&#95;15N3 exhibited a large burst size of 102 PFU/cell following a short latent period of 10 min. In addition, phage vB&#95;CpeP&#95;15N3 remained stable at temperatures ranging from 4 to 50°C and pH levels from 5 to 9 and had a strong antibacterial effect in vitro. Through whole-genome analysis, phage vB&#95;CpeP&#95;15N3 belongs to the family Guelinviridae, genus Brucesealvirus with no genes related to lysogeny and bacterial virulence or resistance. We further demonstrated that phage vB&#95;CpeP&#95;15N3 by oral administration for preventive purposes could significantly alleviate clinical symptoms and jejunal lesions of newborn piglets through the reduced colonization of C. perfringens type C in the jejunum and the level of CPB toxin in the content of jejunum in the newborn piglet model of CVCC1155 infection. In addition, phage vB&#95;CpeP&#95;15N3 by oral administration for preventive purposes could improve the diversity and abundance of the jejunum microbiota in newborn piglets. Moreover, the prevention by phage vB&#95;CpeP&#95;15N3 obtained more effective therapeutic results than phage and gentamicin treatments. Taken together, these findings suggested that phage vB&#95;CpeP&#95;15N3 is a promising alternative of antibiotics for preventing and controlling C. perfringens type C infection of newborn piglets., Competing Interests: Declaration of Competing Interest All of the authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Enhancing the oral bioavailability of hydrophobic nutraceuticals and protecting bioactive components through encapsulation systems has gained significant attention in food science. This study explored the preparation and characterization of kafirin (Kaf)/carboxymethyl cellulose (CMC) composite nanoparticles for encapsulating andrographolide (AG) using the antisolvent precipitation method. The optimal Kaf to CMC mass ratio was identified as 4:1, resulting in nanoparticles with an average diameter of 146.4 nm. CMC markedly improved the water dispersibility of the nanoparticles compared to Kaf alone. The formation of these composite nanoparticles was mainly driven by hydrophobic interactions, hydrogen bonding, and electrostatic interactions. Compared to Kaf nanoparticles, the Kaf/CMC nanoparticles showed enhanced encapsulation efficiency, gastrointestinal release characteristics, and stability. Additionally, AG-loaded composite nanoparticles showed exhibited superior biological safety and anti-cancer effects, highlighting their potential for therapeutic applications. In conclusion, Kaf/CMC composite nanoparticles present a promising delivery system for hydrophobic nutraceuticals and drugs, contributing to advancements in drug delivery technologies and nutraceutical 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 B.V. All rights reserved.)

The aim of the study was to understand healthcare professionals, pharmacists, and patients perspectives and experiences on clinical practice of herb-drug interactions (HDIs). A systematic review of qualitative studies was conduct. 10 electronic databases were searched from inception through September 2023. Qualitative studies, mixed-method studies, and unstructured or semi-structured cross-sectional surveys focused on healthcare professionals, pharmacists and patients' perspectives, attitudes, clinical practice behaviors, and information needs regarding HDI were included. Thematic synthesis employed Nvivo 12 software. Of 6655 studies identified, 1267 full-text articles were retrieved. Of these, 18 studies conducted in 11 countries/regions were eligible for inclusion, involving 1273 patients, 302 healthcare professionals, and 230 pharmacists. Five over-arching explanatory themes were identified: perspectives, attitudes, practices, experiences, expectations, and information needs. Complementary and alternative (CAM) physicians, pharmacists, and general practitioners were considered by patients to possess the ability or responsibility to assess potential HDIs. Pharmacists yet encountered difficulties due to conflicting information sources and inadequate training. Healthcare professionals, including pharmacists, usually only assessed HDIs when they were deemed to cause serious adverse effects. Regarding expectations and information needs, patients were particularly concerned about the risk of adverse HDIs, the severity of HDIs, and the appropriate intervals between drug doses. They would like to receive relevant HDI alerts. Results suggest that government, policy makers, healthcare professionals, and the education system should give attention to HDIs and improve health professional-patient communication. Further research should also be conducted on the understanding and practices of CAM practitioners in China. Trial Registration: CRD42022324777 (https://www.crd.york.ac.uk/PROSPERO/#recordDetails)., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Lung squamous cell carcinoma (LUSC), a subtype of non-small cell lung cancer, represents a significant portion of lung cancer cases with distinct histologic patterns impacting prognosis and treatment. The current pathological assessment methods face limitations such as interobserver variability, necessitating more reliable techniques. This study seeks to predict lymph node metastasis in LUSC using deep learning models applied to histopathology images of primary tumors, offering a more accurate and objective method for diagnosis and prognosis. Whole slide images (WSIs) from the Outdo-LUSC and the cancer genome atlas cohorts were used to train and validate deep learning models. Multiinstance learning was applied, with patch-level predictions aggregated into WSI-level outcomes. The study employed the ResNet-18 network, transfer learning, and rigorous data preprocessing. To represent WSI features, innovative techniques like patch likelihood histogram and bag of words were used, followed by training of machine learning classifiers, including the ExtraTrees algorithm. The diagnostic model for lymph node metastasis showed strong performance, particularly using the ExtraTrees algorithm, as demonstrated by receiver operating characteristic curves and gradient-weighted class activation mapping visualizations. The signature generated by the ExtraTrees algorithm, named lymph node status-related in situ LUSC histopathology (LN&#95;ISLUSCH), achieved an area under the curve of 0.941 (95% CI: 0.926-0.955) in the training set and 0.788 (95% CI: 0.748-0.827) in the test set. Kaplan-Meier analyses confirmed that the LN&#95;ISLUSCH model was a significant prognostic factor (P = .02). This study underscores the potential of artificial intelligence in enhancing diagnostic precision in pathology. The LN&#95;ISLUSCH model stands out as a promising tool for predicting lymph node metastasis and prognosis in LUSC. Future studies should focus on larger and more diverse cohorts and explore the integration of additional omics data to further refine predictive accuracy and clinical utility., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Hepatectomy is the primary therapeutic intervention for liver disorders. Nonetheless, an increased risk of liver failure and postoperative mortality exists due to the rapid reduction in liver size after surgery. Human umbilical cord mesenchymal stem cell (hucMSC) exosomes (Exos) have been recognized in the promotion of liver regeneration. However, intravenous administration of Exos faces several challenges including poor targeting and rapid clearance. Herein, we employed CMCS/OHA/LA-loaded hucMSCs derived Exos (hydrogel-Exos) to address liver regeneration after hepatectomy. Release and uptake studies showed hydrogel-Exos enables localized release of Exos, prolonging their presence and concentration in liver tissue. Meanwhile, the hydrogel-Exos exhibited good characteristics in injectability, self-healing, biocompatibility, liver adhesion, swelling performance, postoperative hemostasis and minimization of peritoneal adhesions post-resection. Moreover, proliferation and scratch wound healing assays demonstrated the ability of hydrogel-Exos to promote liver cell proliferation and migration. During in vivo studies, the Exos-containing hydrogel was injected into the resected surface of a 70 % hepatectomy rat model. The result indicated Exos was released into the liver tissue through the hydrogel to promote angiogenesis and liver regeneration. Bioinformatics analysis revealed liver regeneration mechanisms involve cell cycle-related pathways. As such, hydrogel-encapsulated Exos appeared promising to be employed following hepatectomy., Competing Interests: Declaration of competing interest The authors affirm that they have no known financial or interpersonal issues that would have appeared to have an impact on the research described in this publication., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Due to the advantages of resource abundance and low reduction potential of calcium, calcium-ion battery (CIB) becomes one of the potential candidates for energy storage devices. Prussian blue analogues (PBAs) are promising cathode materials for CIB, but they suffer from limited capacity and poor cyclability. Herein, a new PBA cathode NiCoHCF is designed with electrochemical active Co and inactive Ni. During charge and discharge process, active Co with limited redox contributes extra reversible capacity along with Fe, while inactive Ni stabilizes the structure and elevates the activity of low-spin Fe, thus enhancing rate capability and contributing capacitance capacity. By the synergistic effect of Co and Ni, the obtained PBAs cathode exhibits much better electrochemical performance than PBAs with only Co (CoHCF) or Ni (NiHCF). In-situ X-ray diffraction proves highly reversible structure evolution of NiCoHCF during cycling. X-ray adsorption spectroscopy and theoretical calculation reveal that, the activity of Co is suppressed, while that of Fe is promoted in NiCoHCF compared with CoHCF. The design strategy opens up new opportunities for the development of CIB cathode materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To solve the coverage problem caused by the random deployment of wireless sensor network nodes in the forest fire-monitoring system, a modified marine predator algorithm (MMPA) is proposed. Four modifications have been made based on the standard marine predator algorithm (MPA). Firstly, tent mapping is integrated into the initialization step to improve the searching ability of the early stage. Secondly, a hybrid search strategy is used to enhance the ability to search and jump out of local optimum. Thirdly, the golden sine guiding mechanism is applied to accelerate the convergence of the algorithm. Finally, a stage-adjustment strategy is proposed to make the transition of stages more smoothly. Six specific test functions chosen from the CEC2017 function and the benchmark function are used to evaluate the performance of MMPA. It shows that this modified algorithm has good optimization capability and stability compared to MPA, grey wolf optimizer, sine cosine algorithm, and sea horse optimizer. The results of coverage tests show that MMPA has a better uniformity of node distribution compared to MPA. The average coverage rates of MMPA are the highest compared to the commonly used metaheuristic-based algorithms, which are 91.8% in scenario 1, 95.98% in scenario 2, and 93.88% in scenario 3, respectively. This demonstrates the superiority of this proposed algorithm in coverage optimization of the wireless sensor network.

Background: There is a significant global demand for precise diagnosis and effective treatment of IgA nephropathy (IgAN), with innate immunity, particularly the complement system, exerting a profound influence on its pathogenesis. Additionally, the gut-kidney axis pathway is vital in the emergence and development of IgAN., Methods: We conducted a comprehensive search in the Web of Science database, spanning from January 1, 2000 to December 18, 2023. The gathered literature underwent a visual examination through CiteSpace, VOSviewer, and Scimago Graphica to delve into authors, nations, organizations, key terms, and other pertinent elements., Result: Between 2000 and 2023, a total of 720 publications were identified, out of which 436 publications underwent screening for highly relevant literature analysis. The average annual number of articles focusing on IgAN, innate immunity, and the gut-kidney axis is approximately 31, with an upward trend observed. In terms of research impact encompassing publication count and authorship, the United States emerged as the leading contributor. Prominent keywords included "complement", "activation", "microbe", "gut-kidney axis", "C4d deposition", "alternative pathway" and "B cells" along with other prospective hot topics., Conclusion: The correlation between IgAN and innate immunity is a focal point in current scientific research. Recent literature underscores the significance of the gut-kidney axis, where intestinal microorganisms and metabolites may influence IgAN. The complement system, a key component of innate immunity, also has a crucial function.Advancements in prevention, diagnosis, and treatment hinge on unraveling this intricate relationship., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Advanced gastric tumors are extremely prone to metastasize the in 20%-30% of gastric cancer, and patients have a poor prognosis despite systemic chemotherapy. Peritoneal metastases from gastric cancer usually indicate the end stage of the disease without curative treatment., Aim: To peritoneal metastasis for facilitating clinical therapy are urgently needed., Methods: Immunohistochemical staining and immunofluorescence staining were used to demonstrate the high expression of cathepsin L (CTSL) in human gastric cancer tissues and its localization in cells. Lentivirus transfection was used to construct stable cell lines. Transwell invasion assays, wound healing assays, and animal tests were used to determine the relationships between CTSL and epithelial-mesenchymal transition (EMT) and tumorigenic potential in vivo ., Results: We observed that macrophage-derived CTSL promoted gastric cancer cell migration and metastasis via the EMT pathway in vitro and in vivo , which involved macrophage polarization. Our findings suggest that macrophages improve extracellular matrix remodeling and hence facilitate tumor metastasis. Ablation of CTSL in macrophages within the tumor microenvironment may improve tumor therapy and the prognosis of patients with gastric cancer peritoneal metastasis., Conclusion: In consideration of our findings, tumor-associated macrophage-derived CTSL is an important factor that promotes the metastasis and invasion of gastric cancer cells, and the targeting of CTSL may potentially improve the prognosis of patients with gastric cancer with peritoneal metastasis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

A dual lipase system has been developed to convert soybean oil into biodiesel through synergistic catalysis of Thermomyces lanuginosus lipase (TLL) and Yarrowia lipolytica lipase 2 (YLL) in this study. Pichia pastoris recombinant strains expressing lipases were successfully constructed, and the activities of TLL and YLL in the fermentation supernatant reached 23,142.71 ± 280.54 U/mL and 895.44 ± 27.31 U/mL, respectively. Immediately thereafter, free lipase was used to catalyze the preparation of biodiesel from soybean oil. After optimizing reaction conditions, 80 U/g oil TLL and 20 U/g oil YLL were used to catalyze the production of biodiesel, and a 95.56% biodiesel yield was obtained at 40 °C, 40% moisture content (water/oil, w/w), and stepwise addition of five molar equivalents of methanol. Double lipase plasmids (tll gene and yll gene in different proportions) were constructed in vitro and introduced into P. pastoris to construct a recombinant strain with optimal activity. Under the reaction conditions of 40% moisture content, 8% whole-cell biocatalyst dosage, and stepwise addition of five molar equivalents of methanol, the biodiesel yield reached 95.35% after 24 h at 40 °C. These results show that synergistic catalysis is an effective strategy for biodiesel synthesis and can not only improve the biodiesel yield but also shorten the reaction time. This study provides a scientific basis for biodiesel production by multi-enzyme compounding, with potential industrial applications., Competing Interests: Declarations. Ethical Approval: This study does not contain any experiments involving human or animal subjects. Consent to Participate: Informed consent was obtained from all individual participants included in the study. Consent for Publication: The authors affirm that provided informed consent for publication. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Alzheimer's disease is a degenerative condition that causes patients to experience progressive memory decline and a significant decline in overall cognitive ability at any given moment. The increase in the elderly population has resulted in a notable surge in the prevalence of Alzheimer's disease, as has the global impact of the disease. Significant clinical efficacy of traditional Chinese medicine in combination with Western medicine for the treatment of Alzheimer's disease has been demonstrated in previous studies. The main purpose of this trial is to assess the effectiveness and safety of Shenxiong Huanglian Detoxification Granule combined with donepezil in individuals diagnosed with mild-to-moderate Alzheimer's disease., Methods: This is a multicenter, pragmatic, randomized controlled trial. A total of 386 eligible individuals with mild to moderate Alzheimer's disease will receive random assignment and equal access to the test or control group. The effectiveness and safety of Shenxiong Huanglian Detoxification Granule in combination with donepezil will be observed. The primary outcome is the alteration in scores acquired from the Alzheimer's Disease Assessment Scale-Cognitive Subscale. Secondary outcomes include the assessments of the Traditional Chinese Medicine Syndrome score scale, Mini-Mental State Examination, Clinical Dementia Rating, and Activity of Daily Living scale. We will also analyze blood biomarkers of Alzheimer's disease, inflammatory indicators, oxidative stress indicators, and hemorheology indicators. In addition, safety assessments will be conducted at baseline, after 12 weeks, and after 24 weeks of treatment., Discussion: These findings will offer reliable clinical evidence regarding the effectiveness and safety of Shenxiong Huanglian Detoxification Granule in combination with donepezil for treating patients with mild-to-moderate Alzheimer's disease. Additionally, this study will support the integration of traditional Chinese and Western medicine into mainstream treatment for Alzheimer's disease, promoting a multitarget strategy., Trial Registration: Chinese Clinical Trial Registry, Registration Number: ChiCTR2300072768. Registered on 25 June 2023. https://www.chictr.org.cn/showproj.html?proj=195457., Competing Interests: The authors declare that they have no competing interests., (© 2024 Lin et al.)

In this study, the liquid lipase Yarrowia lipolytica lipase 2 (YLLip2) expressed by Pichia pastoris GS115 was used to produce biodiesel from waste oil. Four signal peptides were compared to express YLLip2 in P. pastoris, among which SP23 exhibited greater secretion performance. In a 1.3-L bioreactor with FM22 medium for 7 days incubation, the maximum YLLip2 activity and total protein content reached 895.44 ± 27.31 U/mL and 3.83 ± 0.31 g/L, respectively. Under the optimal reaction conditions of 30 °C, 20% moisture content, 50 U/g oil of enzyme dosage, and distributed methanol addition, the reaction yield reached 80.99% after 12 h. To further improve the biodiesel yield, some additives were used to assist with YLLip2. The results showed that adding G50 (approximately 1/20 of YLLip2) increased the yield by approximately 90% after 6 h cultivation without changing the enzyme dosage. Compared with previous studies, the reaction time for biodiesel production from waste oil in this study was significantly shortened. This study provides a workable method for converting low-quality feedstocks containing high free fatty acids into biodiesel using a liquid lipase as the catalyst., Competing Interests: Declarations. Ethical Approval: This study does not contain any experiments involving human or animal subjects. Consent to Participate: Informed consent was obtained from all individual participants included in the study. Consent for Publication: The authors affirm that provided informed consent for publication. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Emamectin·chlorfenapyr is a compound comprising chlorfenapyr and emamectin benzoate that is widely used in agriculture. Chlorfenapyr toxicity has been verified in animals; however, its true mechanism and progression in humans remain to be elucidated. Cases of emamectin·chlorfenapyr poisoning are seldom., Case Presentation: We present a case of a 65-year-old female who attempted suicide by consuming 30 g of 9.5% chlorfenapyr and 0.5% emamectin benzoate 14 days before admission to our hospital. Laboratory tests revealed extremely high creatinine kinase levels upon admission. Magnetic resonance imaging revealed diffuse and symmetric T2 hyperintensities in the entire white matter tract of the brain and spinal cord, and cytological smears of the cerebrospinal fluid showed abnormal lymphocyte aggregation. The patient died 19.5 h after admission owing to cardiopulmonary arrest and hyperthermia., Conclusion: Further research is needed on how to perform flow cytometry in patients with emamectin·chlorfenapyr intoxication, and to elucidate the immunological mechanism underlying the inflammatory response caused by emamectin·chlorfenapyr and provide new insights into antidote development., 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 Li, Yang, Zhang, Zhang, Zhao and Yue.)

Background: Patients with multiple myeloma (MM) are commonly managed by multidisciplinary oncology teams in concordance with the neurological, oncological, mechanical, and systematic decision framework. Surgery is indicated for mechanical instability and/or neurological deficits. In neurologically intact and mechanically stable patients, chemo- and radiotherapy alone are often the mainstay treatment., Observations: A 66-year-old male patient presented with a kyphotic chin-on-chest deformity due to undiagnosed spinal MM. He experienced progressive neck pain and difficulty with activities of daily living (ADLs). Imaging revealed systematic bony element destruction and burst deformities at T1-2 with cervicothoracic central canal stenosis. Due to his disease burden and neurological preservation, spinal alignment was initially achieved via halo traction and immobilization, allowing him to begin systemic therapy almost immediately after diagnosis and improving vertebral bone density and construct integrity prior to surgery. He underwent C2-T10 decompression and instrumented fusion with cement augmentation. At 12 months postoperatively, the patient reported improvement in symptomology and ADLs without radiographic evidence of hardware failure or spinal instability., Lessons: Spinal MM with instability can be successfully managed with gradual deformity realignment and external orthosis before surgery in a neurologically intact patient with a significant disease burden. https://thejns.org/doi/10.3171/CASE2441.

Understanding the early features and characteristics of hemophagocytic lymphohistiocytosis (HLH) is essential for identifying high-risk individuals and also providing valuable pathological insights. This study aims to investigate the characteristics and trends of blood and hepatic parameters before an HLH diagnosis was established. Longitudinal hematological and hepatic test results from pediatric patients with HLH and an age- and sex-matched control group were analyzed. According to the length of time between hospital admission and the establishment of the HLH diagnosis, the HLH cases were divided into early-onset (≤ 7 days) and late-onset (> 7days) groups. Among the 229 pediatric HLH patients, the length of time between hospital admission and the establishment of an HLH diagnosis ranged from 0 to 41 days (median = 4 days). Over 80% of pediatric HLH patients presented abnormal laboratory results for aspartate aminotransferase (AST), triglycerides, lactate dehydrogenase (LDH), and hemoglobin at admission. The abnormal rates in the initial platelet count, neutrophil count, and fibrinogen tests were 67.3%, 48.3%, and 52.2%, respectively. The initial test results for AST, alanine aminotransferase (ALT), LDH, serum sodium, and albumin showed AUCs > 80% for discriminating early-onset HLH. For the discrimination of late-onset HLH, the performance of initial test results was poor. To conclude, abnormalities in AST, triglycerides, LDH, and hemoglobin are early presentations of pediatric HLH; platelet, neutrophil, and fibrinogen levels may become abnormal at a relatively late stage of the HLH disease trajectory; and the initial test results for AST, ALT, LDH, serum sodium, and albumin can be used to identify suspected early-onset HLH., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was reviewed and approved by the Medical Ethics Committee of the Hunan Children’s Hospital (HCHLL-2023-97). Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Salmonellosis is a disease caused by non-typhoid Salmonella, and although some lactic acid bacteria strains have been shown previously to relieve Salmonellosis symptoms, little has been studied about the preventive mechanism of Lentilactobacillus buchneri (L. buchneri) against Salmonella infection in vivo. Therefore, the L. buchneri was fed to C57BL/6 mice for 10 days to build a protective system of mice to study its prevention and possible mechanisms. The results showed that L. buchneri GX0328-6 alleviated symptoms caused by Salmonella typhimurium infection among C57BL/6 mice, including low survival rate, weight loss, increase in immune organ index and hepatosplenomegaly, and modulated serum immunoglobulin levels and intrinsic immunity. Importantly, the L. buchneri GX0328-6 enhanced the mucosal barrier of the mouse jejunum by upregulating the expression of tight junction proteins such as ZO-1, occludins, and claudins-4 and improved absorptive capacity by increasing the length of mouse jejunal villus and the ratio of villus length to crypt depth and decreasing the crypt depth. L. buchneri GX0328-6 reduced the intestinal proliferation and invasion of Salmonella typhimurium by modulating the expression of antimicrobial peptides in the intestinal tract of mice, and reduced intestinal inflammation and systemic spread in mice by downregulating the expression of IL-6 and promoting the expression of IL-10. Furthermore, L. buchneri GX0328-6 increased the relative abundance of beneficial bacteria colonies and decreased the relative abundance of harmful bacteria in the cecum microflora by modulating the microflora in the cecum contents., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics Approval All of the experiments were performed in accordance with the guidelines of the regional Animal Ethics Committee and were approved by the Guangxi University Ethical Committee (Project ID GXU2020-069), which are in accordance with the guidelines for the care and use of laboratory animals described by the US National Institutes of Health. Consent to Participate Not applicable. Consent for Publication Not applicable. Conflict of Interest The authors declare no competing interests., (© 2023. The Author(s).)

Competing Interests: The authors declare that they have no conflict of interest.

Although combining 5-fluorouracil (5-FU) and Interferon-beta (IFNb) improves response rates in Hepatocellular Carcinoma (HCC), the outcomes remain suboptimal. This study investigates the feasibility of using highly transfected Mesenchymal Stem Cells (MSCs) to deliver a chemotherapeutic (5-FU) and an immunomodulator (IFNb) for localized HCC treatment. Considering the crucial role of cold-chain transportation in off-the-shelf allogeneic therapy, the study also assesses the quality and efficacy of frozen-thawed engineered MSCs, simulating a multisite study process. The engineered MSCs maintained their phenotypes and tumour tropism. With just 10 % engineered MSCs, a killing efficiency of over 70 % was achieved in Huh-7 and HepG2 cell lines in vitro. Coculture studies, soft agar assays, and in vivo experiments confirmed that MSCs are neither tumorigenic nor tumour-promoting. Tumour mass growth was inhibited by >80 % in the treated mice group. TUNEL, Annexin-V, and Ki67 staining confirmed DNA damage, cell death, and proliferation inhibition post-treatment. Blood chemistry and the weight of the mice were comparable to the control group, indicating a good safety profile. This proof-of-concept study demonstrates the efficacy and safety of off-the-shelf CDUPRT-IFNβ&#95;MSCs in targeting hepatocellular carcinoma (HCC) growth. Evaluating the complete value chain of MSC therapy in early-stage preclinical studies is essential for justifying further investigation and clinical translation of this cell product., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study investigates the utility of 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography/computed tomography (PET/CT) in assessing skull-base bone invasion (SBBI) and predicting treatment response in advanced nasopharyngeal carcinoma (NPC). A retrospective analysis was conducted on 142 patients with newly diagnosed advanced NPC who underwent 18 F-NaF PET/CT for initial staging from December 2020 to December 2023. 18 F-NaF PET/CT scans were analyzed for uptake values at the skull-base bone, and these were correlated with treatment outcomes of primary tumor using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Statistical analyses involved Mann-Whitney U tests for group comparisons and logistic regression for evaluating risk factors. Higher 18 F-NaF uptake at the skull-base bone was significantly associated with advanced T stages (p < 0.0001) and the presence of bone metastases (p = 0.01). Patients exhibiting complete response (CR) to treatment had significantly lower skull-base 18 F-NaF uptake compared to those with non-CR (p < 0.001). Receiver operating characteristic (ROC) analysis identified an SUV max  > 10.0 and SUV mean  > 5.2 as predictive of non-CR, with AUC values of 0.77 and 0.76, respectively. Univariate and multivariable analysis confirmed SUV max as a significant predictor of treatment response (OR = 7.03, 95% CI: 1.97-25.13, p < 0.05). Elevated 18 F-NaF uptake at the skull-base bone is predictive of poorer treatment outcomes, highlighting its potential as a prognostic biomarker in advanced NPC. This study demonstrates that 18 F-NaF PET/CT is a valuable imaging modality for evaluating SBBI in NPC, offering metabolic information that complements the anatomical findings from MRI., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: This retrospective study received ethical clearance and the requirement to obtain informed consent was waived by the institutional review boards of Affiliated Hospital of Guilin Medical University (ID: 2023QTLL-16). The study protocol adheres to the tenets of the 1964 Declaration of Helsinki., (© 2024. The Author(s).)

PTD-FNK, a synthetic anti-apoptotic protein, has been shown to potently alleviate cellular injuries. However, the effects of PTD-FNK on oxidative defense in boar testicular Sertoli cells (SCs) against oxidative injury has not been explored. In this study, we show that exposure of SCs to 100 mg/L lipopolysaccharide (LPS) for 12 h leads to decreased survival rate, superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA). Treatment with 0.01 nmol/L PTD-FNK for 4 h significantly enhanced the activity of SOD, catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) in SCs. Concurrently, PTD-FNK treatment effectively reduced the production of reactive oxygen species (ROS) and the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in SCs. Moreover, using His pull-down and LC-MS techniques, we identified PTD-FNK-interacting proteins and confirmed that this protective effect may be mediated by the regulation of the Keap1 - Nrf2 signaling pathway by PTD-FNK. Therefore, PTD-FNK alleviates LPS-induced oxidative stress via the Keap1 / Nrf2 pathway, providing novel insights for the development of therapeutic agents targeting testicular oxidative damage.

Phosphodiesterases (PDEs) constitute a family of enzymes that play a pivotal role in the regulation of intracellular levels of cyclic nucleotides, including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Dysregulation of PDE activity has been implicated in diverse pathological conditions encompassing cardiovascular disorders, pulmonary diseases, and neurological disorders. Small-molecule inhibitors targeting PDEs have emerged as promising therapeutic agents for the treatment of these ailments, some of which have been approved for their clinical use. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation PDE inhibitors. The objective of this review is to provide an overview of the synthesis and clinical application of representative approved small-molecule PDE inhibitors, with the aim of offering guidance for further advancements in the development of novel PDE inhibitors., 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 Masson SAS. All rights reserved.)

Aims: The aim of this study was to explore the relationship of choroid plexus (CP) volume with hippocampal subregion volume and glymphatic system in patients with benzodiazepine use disorders (BUD)., Methods: Eighty-four participants were recruited including 23 patients with BUD, 29 patients with chronic insomnia (CI) and 32 healthy controls (HC). The morphological alterations in CP, hippocampal subfield volumes and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index were compared between the three groups and the relationships between CP volume and hippocampal subfield volumes and the glymphatic system were further investigated., Results: Compared with the HC individuals, the CP volumes augmented and hippocampal subfield volumes reduced in patients with BUD (P < .05) but not in patients with CI (P > .05). In patients with BUD, there were extensive relationships between augmented CP volume and decreased hippocampal subfield volumes (P < .05, r = -0.421--0.513). CP volume was negatively related with the DTI-ALPS index (r = -0.582, P = .004) within the BUD group. In patients with BUD, the volume of bilateral cornu ammonis (CA)1 body, molecular layer (ML) body, hippocampal tail, left CA1 head volumes, right dentate gyrus body volumes, and right CA4 body volumes were positively related with the Montreal Cognitive Assessment scores (P < .05, r = 0.422-0.683). Right CA1 and ML body volumes positively related with the Mini-Mental State Examination scores (P < .05, r = 0.503-0.575)., Conclusions: The enlarged CP related to atrophy of hippocampal subfield volumes and the glymphatic system dysfunction were shown in BUD patients., (© 2024 British Pharmacological Society.)

Advancements in remote sensing and autonomous vehicle technologies made lidars equally important for unmanned objects alongside cameras. Therefore, precise 3D lidar imaging and point cloud generation have become important subjects. Although existing coherent lidar technologies provide precise imaging results, the spectral linewidth of the laser sources becomes a key limitation over long distances as it defines the maximum detection range. Here, we present long-distance 3D lidar imaging which removes the coherence length limitations and therefore the necessity of high-coherence laser sources. Mainly, we generate optical sidebands, by modulating a continuous wave (CW) laser source with multiple radio-frequency (RF) tones. Then, using our own post-processing and triangulation methods, we use the relative phase changes between the sidebands which are free from laser phase noise to determine the target distance. We prove that the multi-tone coherent Lidar technique can perform precise 3D imaging and point cloud generation of various targets at sub-10pW optical power reception and distances up to ∼12× beyond the coherence length of the CW laser employed in the lidar architecture. Overall, it is demonstrated that coherence length restriction is removed by the suggested method, which makes precise long-distance 3D lidar imaging possible, particularly for applications such as spacecraft and aerial coherent lidars.

Alterations in heavy metals and trace element levels may be associated with various cancers. However, the role of this interaction in colorectal cancer (CRC) progression is unclear. In recent years, Principal Component Analysis (PCA) and Bayesian Kernel Machine Regression (BKMR) models have provided new ideas for analyzing the effects of metal mixtures on CRC progression. Herein, we assessed the differences in the levels of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), nickel (Ni), selenium (Se), and zinc (Zn) in tumors and adjacent healthy tissues, to investigate the relationship between heavy metals/trace elements and CRC progression. Surgical samples of CRC and noncancerous tissues were collected, and trace metal levels were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression, PCA, and BKMR models were used to investigate the relationship between heavy metals and trace elements and the degree of tumor differentiation and lymph node metastasis in CRC. Cancer tissues showed lower As, Cd, Co, and Cr concentrations, and higher Se concentrations than healthy tissues (P < 0.05). In addition, CRC patients with poorly differentiated tumors and/or positive lymph node metastases had lower levels of Cd, Zn, Cu, and Se (P < 0.05). Logistic regression showed that single metal concentration was negatively correlated with CRC progression. PCA and BKMR models also showed that the metal mixture concentration was negatively correlated with CRC progression, with Cd contributing the most. Overall, changes in heavy metal and trace element levels may be related to the development of CRC; however, further mechanistic studies are required., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The prevalence of age-related disorders, particularly in neurological and cardiovascular systems, is an increasing global health concern. Mesenchymal stem cell (MSC) therapy, particularly using human umbilical cord-derived MSCs (HUCMSCs), has shown promise in mitigating these disorders. This study investigates the effects of HUCMSCs on aging-related conditions in a senescence-accelerated mouse model (SAMP8), with a focus on DNA damage, gut microbiota alterations, and metabolic changes., Methods: SAMP8 mice were treated with clinical-grade HUCMSCs via intraperitoneal injections. Behavioral and physical assessments were conducted to evaluate cognitive and motor functions. The Single-Strand Break Mapping at Nucleotide Genome Level (SSiNGLe) method was employed to assess DNA single-strand breaks (SSBs) across the genome, with particular attention to exonic regions and transcription start sites. Gut microbiota composition was analyzed using 16S rRNA sequencing, and carboxyl metabolomic profiling was performed to identify changes in circulating metabolites., Results: HUCMSC treatment significantly improved motor coordination and reduced anxiety in SAMP8 mice. SSiNGLe analysis revealed a notable reduction in DNA SSBs in MSC-treated mice, especially in critical genomic regions, suggesting that HUCMSCs may mitigate age-related DNA damage. The functional annotation of the DNA breaktome indicated a potential link between reduced DNA damage and altered metabolic pathways. Additionally, beneficial alterations in gut microbiota were observed, including an increase in short-chain fatty acid (SCFA)-producing bacteria, which correlated with improved metabolic profiles., Conclusion: The administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism. The observed alterations in DNA break patterns, along with specific changes in microbiota and metabolic profiles, suggest that these could serve as potential biomarkers for evaluating the efficacy of HUCMSCs in treating age-related disorders. This highlights a promising avenue for the development of new therapeutic strategies that leverage these biomarkers, to enhance the effectiveness of HUCMSC-based treatments for aging-associated diseases., (© 2024. The Author(s).)

The adoptive transfer of autologous, long-lived, gene-repaired T cells is a promising way to treat inherited T-cell immunodeficiencies. However, adoptive T-cell therapies require a large number of T cells to be manipulated and infused back into the patient. This poses a challenge in primary immunodeficiencies that manifest early in childhood and where only small volumes of blood samples may be available. Our protocol describes the ex vivo expansion of potentially long-lived human T memory stem cells (T SCM ), starting from a limited number of peripheral blood mononuclear cells (PBMCs). Using the perforin gene as an example, we provide detailed instructions for precise gene repair of human T cells and the expansion of T SCM . The efficiency of precise gene repair can be increased by suppressing unintended non-homologous end-joining (NHEJ) events. Our protocol yields edited T-cell populations that are ready for phenotyping, genome-wide off-target analysis, and functional characterization. Key features • Expansion and enrichment of T SCM from PBMCs using IL-7 and IL-15. • Phenotyping of T SCM . • Design of "off-the-shelf" gene-repair strategies based on knock-in of a single exon or complete cDNA and design of effective guide RNAs and DNA donor templates. • High-efficiency gene targeting using CRISPR-Cas9, recombinant adeno-associated virus serotype 6 (rAAV6), and a selective small molecule inhibitor of DNA-dependent protein kinase (DNA-PK)., Competing Interests: Competing interestsX.L., V.T.C., and K.R. are inventors on an international patent (PCT/EP2022/073414, publication date 02 March 2023; Cas9 nickase-mediated gene editing). The remaining author (C.K.) declares that she has no financial or non-financial competing interests., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY license.)