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Ethnopharmacological Relevance: Fei-Yan-Qing-Hua decoction (FYQHD) is an empirical formula that has shown clinical success in treating community-acquired pneumonia (CAP) for two decades. Influenza viral infection is a significant trigger for severe pneumonia, yet the role of FYQHD in treating influenza remains unclear., Aim of the Study: This study aimed to assess the potential efficacy of FYQHD in treating influenza viral infection and to elucidate its underlying mechanisms., Materials and Methods: The protective effects of FYQHD against influenza were evaluated through survival assessments and pathological analyses. Transcriptomic analysis was performed to identify the genes and pathways influenced by FYQHD in influenza. The anti-inflammatory effects and molecular mechanisms of FYQHD were studied in macrophages stimulated by Toll-like receptor (TLR) 7 ligation in vitro. The key constituents of FYQHD absorbed in mouse sera were identified using untargeted metabolomics, and the anti-inflammatory activity of some of these compounds in macrophages was evaluated using ELISA., Results: Our findings demonstrate that FYQHD enhances survival and reduces lung damage in PR8-infected mice, primarily through its anti-inflammatory properties. Lung indexes and organ damage were significantly lower in the PR8 + OSV + FYQHD group compared to the PR8 + OSV group, indicating a potential complementary therapeutic effect of FYQHD and OSV in treating influenza. FYQHD effectively reduced chemokine expression, thereby decreasing the chemotaxis and infiltration of inflammatory monocytes/macrophages and neutrophils in the lungs. The anti-inflammatory effects of FYQHD in macrophages were achieved through the inhibition of NF-κB activation and p38 phosphorylation. The key constituents of FYQHD absorbed in mouse sera were identified, with some, such as wogonin, luteolin, kaempferol, and isorhamnetin, showing anti-inflammatory effects in primary macrophages., Conclusion: FYQHD demonstrates protective efficacy against influenza and shows promise as an adjuvant therapeutic agent, particularly when used in combination with antiviral drugs like OSV. The potent anti-inflammatory components within FYQHD provide a basis for further exploration in drug research and development aimed at combating influenza., 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.)

Integrating plant proteins into meat products offers a sustainable way to reduce the environmental impact of meat consumption while satisfying the growing flexitarian population. This study explored the effects of textured vegetable proteins (TVPs) on the physico-chemical attributes and flavour profile of hybrid salamis using 4D label-free proteomics. Results showed that hybrid salamis had lower pH, reduced water activity and increased weight loss compared with traditional salamis, along with greater hardness and a slightly rough, porous texture with a filamentous structure. TVPs substantially modified crucial meaty flavour compounds (nitrogen oxides, sulfides and pyrazine), increasing heightening sourness and bitterness while diminishing umami. Proteomic analysis revealed significant upregulation of myosin and actin in hybrid salamis; notably, these proteins were involved in glycerol-3-phosphate dehydrogenase activity and calcineurin-mediated signalling, underscoring their role in flavour enhancement. Therefore, hybrid salamis offer an attractive alternative to traditional salamis by merging meat-like taste and texture with plant protein., 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.)

Ethnopharmacological Relevance: Ganoderma lucidum (G. lucidum) has been widely used as adjuvant of anti-tumor therapy for variety tumors. The bioactive ingredients of G. lucidum mainly include triterpenes, such as Ganoderic acid A, Ganoderic acid B, Ganoderenic acid A, Ganoderenic acid B, Ganoderenic acid D, and Ganoderic acid X. However, the effects and underlying mechanisms of G. lucidum are often challenging in hepatocellular carcinoma (HCC) treatment., Aim of the Study: To explore the potential role and mechanism of enhancer-associated lncRNAs (en-lncRNAs) in G. lucidum treated HCC through the in vivo and in vitro experiments., Materials and Methods: Hepa1-6-bearing C57 BL/6 mice model were established to evaluate the therapeutic efficacy of G. lucidum treated HCC. Ki67 and TUNEL staining were used to detect the tumor cell proliferation and apoptosis in vivo. The Mouse lncRNA 4*180K array was implemented to identify the differentially expressed (DE) lncRNAs and mRNAs of G. lucidum treated tumor mice. The constructed lncRNA-mRNA co-expression network and bioinformatics analysis were used to selected core en-lncRNAs and its neighboring genes. The UPLC-MS method was used to identify the triterpenes of G. lucidum, and the in vitro experiments were used to verify which triterpene monomers regulated en-lncRNAs in tumor cells. Finally, a stable knockdown/overexpression cell lines were used to confirm the relationship between en-lncRNA and neighboring gene., Results: Ki67 and TUNEL staining demonstrated G. lucidum significantly inhibited tumor growth, suppressed cell proliferation and induced apoptosis in vivo. Transcriptomic analysis revealed the existence of 126 DE lncRNAs high correlated with 454 co-expressed mRNAs in G. lucidum treated tumor mice. Based on lncRNA-mRNA network and qRT-PCR validation, 6 core lncRNAs were selected and considered high correlated with G. lucidum treatment. Bioinformatics analysis revealed FR036820 and FR121302 might act as enhancers, and qRT-PCR results suggested FR121302 might enhance Popdc2 mRNA level in HCC. Furthermore, 6 main triterpene monomers of G. lucidum were identified by UPLC-MS method, and in vitro experiments showed FR121302 and Popdc2 were significantly suppressed by Ganoderenic acid A and Ganoderenic acid B, respectively. The knock/overexpression results demonstrated that FR121302 activating and enhancing Popdc2 expression levels, and Ganoderenic acid A and Ganoderenic acid B dramatically suppressed FR121302 and decreased Popdc2 level in Hepa1-6 cells., Conclusions: Enhancer-associated lncRNA plays a crucial role as an enhancer during hepatocarcinogenesis, and triterpenes of G. lucidum significantly inhibited tumor cell proliferation and induced apoptosis by regulating en-lncRNAs. Our study demonstrated Ganoderenic acid A and Ganoderenic acid B suppressed en-lncRNA FR121302 may be one of the critical strategies of G. lucidum inhibit hepatocellular carcinoma growth., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationship with other people or organizations that can inappropriately influence our work; there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor signaling inhibitors (ARSI) is often lethal. Liquid biopsy biomarkers for this deadly form of disease remain under investigation, and underpinning mechanisms remain ill-understood., Experimental Design: We applied targeted cell-free DNA (cfDNA) sequencing to 126 patients with mCRPC from three academic cancer centers and separately performed genome-wide cfDNA methylation sequencing on 43 plasma samples collected prior to the initiation of first-line ARSI treatment. To analyze the genome-wide sequencing data, we performed nucleosome positioning and differential methylated region analysis. We additionally analyzed single-cell and bulk RNA sequencing data from 14 and 80 patients with mCRPC, respectively, to develop and validate a stem-like signature, which we inferred from cfDNA., Results: Targeted cfDNA sequencing detected AR/enhancer alterations prior to first-line ARSIs that correlated with significantly worse progression-free survival (P = 0.01; HR = 2.12) and overall survival (P = 0.02; HR = 2.48). Plasma methylome analysis revealed that AR/enhancer lethal mCRPC patients have significantly higher promoter-level hypomethylation than AR/enhancer wild-type mCRPC patients (P < 0.0001). Moreover, gene ontology and CytoTRACE analysis of nucleosomally more accessible transcription factors in cfDNA revealed enrichment for stemness-associated transcription factors in patients with lethal mCRPC. The resulting stemness signature was then validated in a completely held-out cohort of 80 patients with mCRPC profiled by tumor RNA sequencing., Conclusions: We analyzed a total of 220 patients with mCRPC, validated the importance of cell-free AR/enhancer alterations as a prognostic biomarker in lethal mCRPC, and showed that the underlying mechanism for lethality involves reprogramming developmental states toward increased stemness. See related commentary by Nawfal et al., p. 7., (©2024 American Association for Cancer Research.)

Background: To determine outcomes of MRI-assisted radiosurgery (MARS) for salvage brachytherapy using the radioisotope 103 Pd after various upfront treatments including surgery, external beam radiotherapy, and brachytherapy., Methods: We retrospectively reviewed data for patients who underwent salvage MARS for intraprostatic lesions or prostate bed recurrences from 2016 to 2022. Biochemical recurrence, prostate cancer-specific, and overall survival, and the cumulative incidences of toxicities, were determined by Kaplan-Meier estimates. Cox proportional hazards models were used to determine associations between clinical and treatment variables and risk of toxicity., Results: Study included 31 patients with local recurrence after initial definitive treatment. Four (13%) were initially treated with prostatectomy and salvage radiation, twenty-four (77%) with external beam radiation, and three with brachytherapy. Most had intermediate- or high-risk prostate cancer at the time of diagnosis. Twenty-two patients (71%) had focal-gland and nine (29%) had whole-gland MARS LDR salvage brachytherapy. Median follow-up was 35-28 months. By last follow-up, 5 patients (16%) experienced recurrence and started ADT, 3 patients started ADT before experiencing recurrence due to physician discretion, and 23 patients (74%) remained without recurrence. No patients died of prostate cancer. Median PSA nadir for recurrence-free patients was 0.2 ng/mL (range, 0-0.9 ng/mL). Grade 3 toxicities occurred in 4 patients (13%) including 3 patients (13%) with genitourinary events only and 1 patient (3%) with both a grade 3 genitourinary and a grade 3 gastrointestinal event., Conclusions: In this modern series of patients undergoing salvage MARS with 103 Pd, we observed acceptable toxicity and early, promising biochemical disease control. These findings highlight the broader applicability of salvage MARS regardless of upfront treatment modality., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Recent advancements in biological technologies have enabled the measurement of spatially resolved multi-omics data, yet computational algorithms for this purpose are scarce. Existing tools target either single omics or lack spatial integration. We generate a graph neural network algorithm named COSMOS to address this gap and demonstrated the superior performance of COSMOS in domain segmentation, visualization, and spatiotemporal map for spatially resolved multi-omics data integration tasks., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Given the potential role of brown adipose tissue (BAT) in stimulating energy expenditure, activating BAT can be an effective anti-obesity treatment. Here, we aimed to use adenoviruses to establish the effect of the inducible degrader of the low density lipoprotein receptor (IDOL) in the formation of BAT., Methods: IDOL or green fluorescent protein was overexpressed by adenovirus and injected into the scapula of C57BL/6J mice and fed with high-fat diet for 12 weeks. We measured the body weight, morphology of lipid droplets, lipid profiles and adipogenesis protein expression levels. BAT was isolated, and RNA sequencing was performed to identify the differentially expressed genes and related signaling pathways. Finally, we conducted western blot to verify the authenticity and reliability of the RNA sequencing results., Results: Compared with the control group, IDOL overexpression led to a significant reduction in body weight, consistent with the weight of adipose tissues and organs. Further studies show IDOL promotion increased ATGL, perilipin 1 and UCP-1 expression in BAT. However, perilipin 1 protein expression was significantly reduced in the Ad-IDOL group in epididymal white adipose tissue, while there was no significant difference in adiponectin, ATGL and perilipin 1 protein expression in inguinal white adipose tissue. Notably, serum FGF21 and leptin protein expression were negatively related to the adipose tissue decrease after Ad-IDOL administration. RNA sequencing analysis identified 1256 differentially expressed genes that were prominently enriched across nine signalling pathways. Additionally, the protein expression of PGAM2, G6PC1 and phosphorylation-AMPK was significantly increased after overexpression IDOL in BAT, which was consistent with the results of the RNA sequencing analysis., Conclusions: Our research demonstrated that IDOL overexpression alleviates the body weight by promoting the phosphorylation of AMPK to upregulate the UCP-1 and ATGL exacerbating lipolysis in BAT., (© 2025 John Wiley & Sons Ltd.)

Diquat (DQ), a contact herbicide extensively utilized in both agricultural and nonagricultural domains, exhibits a high correlation with neuronal disorders. Nevertheless, the toxicity and underlying mechanisms associated with exposure to environmental concentrations of DQ remain ambiguous. Here, we report dose-dependent cellular neurotoxicity of DQ in Caenorhabditis elegans . First, DQ significantly compromised the development and brood size of worms, shortened the lifespan, and caused epidermal abnormalities. An unbiased transcriptomic analysis disclosed several pathways related to cell death and peroxisome homeostasis underlying this organismal-level toxicity. Moreover, exposure of DQ to C. elegans led to a notable increase of embryonic cell death. Concurrently, DQ exposure specifically caused the loss of dopamine neurons but not two other types of neurons in adulthood, which is in accordance with DQ-induced muscle-related defects such as pharyngeal pumping, body bends, and head thrashes. Mechanistically, DQ exposure induces the generation of reactive oxygen species (ROS) and enhances glutathione-related ROS scavenging pathway. Protein levels and activities of mitochondrial electron transport chain complexes were specifically impaired in the DQ-treated worms. Collectively, this study suggests an ROS-mediated cell death pathway involving the neuronal and behavioral toxicity of DQ, which offers a novel mitochondria-related perspective to elucidate the general toxicity caused by a widely distributed herbicide, DQ, at near-environment concentrations.

Nucleic acid and protein co-condensates exhibit diverse morphologies crucial for fundamental cellular processes. Despite many previous studies that advanced our understanding of this topic, several interesting biophysical questions regarding the underlying molecular mechanisms remain. We investigated DNA and human transcription factor p53 co-condensates-a scenario where neither dsDNA nor the protein demonstrates phase-separation behavior individually. Through a combination of experimental assays and theoretical approaches, we elucidated: (1) the phase diagram of DNA-protein co-condensates at a certain observation time, identifying a phase transition between viscoelastic fluid and viscoelastic solid states, and a morphology transition from droplet-like to "pearl chain"-like co-condensates; (2) the growth dynamics of co-condensates. Droplet-like and "pearl chain"-like co-condensates share a common initial critical microscopic cluster size at the nanometer scale during the early stage of phase separation. These findings provide important insights into the biophysical mechanisms underlying multi-component phase separation within cellular environments., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Contact prelithiation is widely used to compensate for the initial capacity loss of lithium-ion batteries (LIBs). However, the low utilization of the Li source, which suffers from the deteriorated contact interfaces, results in cycling degeneration. Herein, Li-Ag alloy-based artificial electron channels (AECs) are established in Li source/graphite anode contact interfaces to promote Li-source conversion. Due to the shielding effect of the Li-Ag alloy (50 at. % Li) on Li-ion diffusion, the dry-state interfacial corrosion is restricted. The unblocked electronic conduction across the AEC-involved interface not only facilitates the Li-source conversion but also accelerates the prelithiation kinetics during the wet-state process, resulting in an ultrahigh Li-source utilization (90.7 %). Implementing AEC-assisted prelithiation in a LiNi 0.5 Co 0.2 Mn 0.3 O 2 pouch cell yields a 35.8 % increase in energy density and stable cycling over 600 cycles. This finding affords significant insights into the construction of an efficient prelithiation technology for the development of high-energy LIBs., (© 2024 Wiley-VCH GmbH.)

A novel protocol to access vinyl sulfones and internal/terminal olefins via cobalt-catalyzed acceptorless dehydrogenation coupling (ADC) has been established. This system enables the divergent synthesis of three kinds of olefin compounds through the coupling of alcohols and sulfones under oxidant-free conditions. The broad applicability of this procedure is demonstrated by over forty olefin products, including pharmaceutical-related compounds and complex substrates, in a one-pot process. Preliminary mechanistic studies were conducted, and a proposed reaction pathway was presented., (© 2024 Wiley-VCH GmbH.)

Background: Triggering receptor expressed in myeloid cells-1 (TREM1) is an important regulator of innate and adaptive immunity, which can directly amplify an inflammatory response. Current studies have found the immunomodulatory role of TREM1 in tumor microenvironment. However, the role of TREM1 in ovarian cancer (OV) remains unclear. Methods: Based on TCGA and GEO database, we performed bioinformatics analysis to evaluate the expression profile of TREM1. Then, the prognostic value of TREM1 was determined through Kaplan-Meier survival analyses. GO and KEGG enrichment along with GSEA analyses were performed to identify potential biological functions of TREM1 based on the gene co-expression network. IHC and RT-qPCR on clinical samples were performed to validate our database-derived results. Additionally, ESTIMATE and CIBERSORT analyses were used to assess the correlation between TREM1 and tumor microenvironment. Finally, the expression, prognosis and immune regulation patterns of TREM1 in pan-cancer were further explored to validate the role of TREM1 as a biomarker. Results: The expression of TREM1 is abnormally high in OV than in normal tissues. Patients with high TREM1 expression were linked with poor overall survival (OS) and disease-free survival (DFS). Then, cox regression analysis and a nomogram indicated that TREM1 was an independent prognostic factor and proved the effective predictive performance in OV. Enrichment analysis showed that TREM1 was highly enriched in cancer-and immune-related pathways. Additionally, immune analysis revealed that TREM1 was robustly positively associated with tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) infiltrating. Moreover, pan-cancer analysis showed TREM1 was closely associated with prognosis and immune-related genes expression in various types of cancer. Conclusions: Through a systematic and comprehensive analysis, our study revealed that TREM1 could serve as a prognostic and immunological biomarker in ovarian cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Adult glioblastomas (GBMs) are associated with high recurrence and mortality. Personalized treatment based on molecular markers may help improve the prognosis. We aimed to evaluate whether apparent diffusion coefficient (ADC) histogram analysis can better predict MGMT and TERT molecular characteristics and to determine the prognostic relevance of genetic profile in patients with GBM., Materials and Methods: MRI, clinical, and pathological data of 79 patients with GBM were retrospectively collected. The ADC values based on histogram analysis were described using 10th percentile (p10), 90th percentile (p90), mean, median, minimum, maximum, skewness, kurtosis, and entropy. The independent-sample t test, linear correlation analysis, receiver operating characteristics (ROC) curve analysis, Kaplan-Meier analysis, and Cox proportional hazard regression were performed., Results: MGMT promoter methylation and TERT promoter mutation were detected in 53.2% and 44.3% of GBM patients, respectively. The ADC p10 in MGMT promoter unmethylated group was significantly lower than that in the MGMT promoter methylated group (p = 0.005). There were significant differences in ADC min , ADC p10 , ADC mean , and entropy between TERT promoter mutant and wild-type groups. Entropy showed the best diagnostic performance in differentiating between positive and negative TERT groups (AUC = 0.722, p = 0.001). Overall survival (OS) showed a positive correlation with ADC min . The TERT promoter mutation was the only independent prognostic factor for GBM., Conclusions: ADC histogram analysis may be a potential noninvasive biomarker for differentiating MGMT and TERT molecular markers and providing prognostic information for GBM patients., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Clavicle emergency fixation can prevent fractured end from piercing heart and lung organs, which is crucial for wounded life. Clavicle with complex structure, great individual differences, and adjacent to important organs, which places high-requirements on performance of fixation materials. Developing advanced clavicle fixation material is a prominent hot-topic in the field of emergency-engineering. We prepared a Polymethyl-methacrylate (PMMA) "bone-Locking" foam dressing via novel polymer foaming process. Innovatively used aliphatic-acid and bio-polar macromolecule nanoparticles to adjust structure in non-traditional self-curing polymer melts to achieve high-performance. Stearic acid coating was prepared on the surface of foaming agent can delay nucleation period, increasing the initial Polymer-Bubble interface viscosity and effectively retard nuclei growth and escape. Nano-chitosan was compounded synchronously to induce in-situ nucleation and construct polar hydrogen bonds between chains, improve the crystallinity of PMMA matrix, reduce the relaxation ability of PMMA molecular chains and increase the interface viscosity again to inhibit nuclei growth and escape, realizing spontaneous coordination between viscosity and the bubble holes formation process. Obtained high-performance foam with uniform and regular bubble holes structure eventually. More, Dynamic Dual-Variable Field Bubble-Growth Dynamics was proposed, revealing the Bubble-Growth behavior synergistic driven by Viscosity and Temperature theoretically, providing reference for improving theory in polymer foaming field. Prepared foam dressing can be directly and softly coated on clavicle and spontaneously conform to the contour of clavicle with remarkable precision, then quickly (3.5 min) curing into a lightweight (0.57 g/cm 3 ), high-strength (40.5 MPa), breathable (224.73 mm/s) "Armor", showing great application value in wound emergency engineering. The developed foaming method and theory provide technical and theoretical value for polymer foaming system. The foam dressing provides a promising new scheme for fixing various wound sites and ensuring the life safety of the wounded at the emergency scene., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The rates of chronic respiratory disease (CRD) is rising in Asia. Pulmonary rehabilitation (PR) has been shown to be a highly efficacious intervention for people with CRD. While PR models are well established in Western countries, environmental, cultural and societal factors may influence how rehabilitation programs for people with CRD are conducted in Asia. This review aims to identify the characteristics of rehabilitation programs for people with CRD within Asia and identify differences between these rehabilitation programs to the recently updated American Thoracic Society (ATS) PR guidelines. Utilising the PRISMA scoping review guidelines, five databases- CINAHL, Medline, Embase, Web of Science and Health and Medical Collection were searched from inception until 13th December 2023. A total of 137 studies (n = 19,128) were included in the review. As many as 113 studies (83 %) included aerobic exercises as part of rehabilitation, only 90 studies (66 %) included resistance training. Thirty-nine studies included interventions such as Tai Chi, Qigong and Yoga. Comparing to the 2023 ATS PR guidelines, only 22 % of the included studies evaluated a rehabilitation program that was consistent with the guidelines. Improvement in exercise capacity (76 %) and quality of life (QOL) (73 %) were the most frequent outcomes used to evaluate program efficacy. The results suggest that models of rehabilitation varied greatly within the Asia region, with some more heavily adapted to suit the local context as compared to others. Further consideration on how to balance adaptation of PR with fidelity of the intervention needs to be taken., 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 Ltd.. All rights reserved.)

Objectives: The performance of cell blocks (CBs) can vary significantly depending on the specimen collection and processing techniques used. This study compared the efficiency of three distinct specimen collection methods for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples., Materials and Methods: From June 2021 to June 2023, the study involved 1450 patients who underwent EBUS-TBNA, resulting in the sampling of 1941 lesions. For these samples, three distinct specimen processing methods were employed to prepare tissue coagulum clot-based CBs. Specifically, the filter paper method was employed in 470 cases (yielding 626 samples), the centrifugation method in 500 cases (yielding 673 samples), and the funnel filtration method in 480 cases (yielding 642 samples)., Results: Out of these 1941 samples, the diagnostic yield for samples obtained using filter paper, centrifugation, and funnel filtration methods was 84.7 %, 87.7 %, and 92.5 %, respectively. In the subgroup of patients diagnosed with non-small cell lung cancer, the adequacy rate for molecular testing in samples processed through filter paper, centrifugation, and funnel filtration methods was 57.7 %, 82.0 %, and 88.3 %, respectively. In the centrifugation group, the combination of the CBs and cell pellet achieved an adequacy rate of 96.5 %., Discussion: The cellular yield of CBs from EBUS-TBNA was significantly enhanced using centrifugation and funnel filtration methods. The funnel filtration method offered a more convenient and cost-effective approach, reducing cellular loss due to sample dispersion in the fixative medium. The use of the centrifugation method to prepare CBs, along with the retrieval of cell pellets from the residual fixative medium, can maximize the specimen adequacy rate for molecular 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 GmbH. All rights reserved.)

Background: Lipoapoptosis in Proximal tubular epithelial cells (PTCs) are substantial in the etiology of diabetic kidney disease (DKD), yet the underlying mechanisms warrant further investigation. Acyl-CoA synthetase long-chain family member 5 (ACSL5) facilitates the formation of acyl-CoA, however, the precise role of ACSL5 in lipoapoptosis of PTCs in DKD remains inconclusive., Methods: Transcriptomic data analysis identified the hub gene Acsl5 associated with lipid metabolism in DKD. The expression of ACSL5 was examined in high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice and high glucose/palmitic acid (HGPA)-induced mouse proximal tubular epithelial cell (BUMPT). Oil Red O staining, free fatty acids (FFA) ELISA assay, Western Blot, and morphological changes were employed to assess lipid deposition and lipoapoptosis. Furthermore, knockdown and overexpression of ACSL5 were conducted in BUMPT cells, followed by morphological assessment, Oil Red O staining, FFA ELISA assay and Western Blot analysis. Using the ChEA3 database, we predicted that STAT3 may transcriptionally regulate ACSL5. Subsequently, we knocked down STAT3 and evaluated Acsl5 expression via RT-qPCR. Additionally, we investigated whether STAT3 modulates the impact of ACSL5 on lipoapoptosis through Western Blot analysis., Results: We demonstrated, for the first time, a notable upregulation of ACSL5 expression in PTCs in HFD/STZ-induced diabetic mice, accompanied by increased the expression of FATP2, lipid accumulation and heightened lipoapoptosis. In HGPA-treated BUMPT cells, ACSL5 knockdown reduced the expression of FATP2, lipid deposition and lipoapoptosis, whereas its overexpression elevated the expression of FATP2 and exacerbated these effects. These findings strongly suggest that ACSL5 may exacerbate lipoapoptosis in PTCs within a diabetic milieu. From a molecular mechanism perspective, ACSL5 expression decreased after Stat3 knockdown. Concurrent knockdown of Stat3 and overexpression of Acsl5 led to a mitigation of lipoapoptosis compared to sole Acsl5 overexpression. Furthermore, STAT3 promotes the activation of ACSL5 promoter under HGPA conditions., Conclusions: In summary, our research identified ACSL5 as an important contributor exacerbating lipoapoptosis in the renal proximal tubules within diabetic environments. In addition, we found that ACSL5 is transcriptionally regulated by STAT3., 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 adsorption and removal of heavy metal ions Cr(VI) is of great significance for human health and ecological environment. Here, an ultrafast and high efficient adsorbent for Cr(VI) was developed based on cetyltrimethylammonium bromide (CTAB)-modified zein nanoparticles (C-ZNPs). In comparison to pristine zein nanoparticles (ZNPs) (11.199 m 2  g -1 ), the surfactant-modified C-ZNPs exhibited larger specific surface area (17.002 m 2  g -1 ). Moreover, C-ZNPs had superior dispersion and more positive charge distribution, which contributed to the improvement for adsorption performance. The results showed that the saturated adsorption of Cr(VI) was reached up to 192.27 mg/g using the C-ZNPs nanosorbent at T = 298 K, pH = 4, t = 10s, and C 0  = 125 mg/L. The removal rate was significantly faster than that reported natural polymer-based adsorbents. The experimental values were followed Freundich isothermal model and pseudo-second-order kinetic model, indicating that the adsorption occurred primarily through a multimolecular layer adsorption process, with a strong emphasis on chemisorption. Mechanistic investigations further revealed that the adsorption of Cr(VI) onto C-ZNPs was mediated by various interactions, including electrostatic attraction, complexation, and ion exchange. These findings provide insights into the efficient removal of Cr(VI) by C-ZNPs and suggest potential applications in water treatment and environmental remediation., 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.)

Purpose: Radiation treatment planning is highly complex and can have significant inter- and intra-planner inconsistency, as well as variability in planning time and plan quality. Knowledge-based planning (KBP) is a tool that can be used to efficiently produce high-quality, consistent, clinically acceptable plans, independent of planner skills and experience. In this study, we created and validated multiple clinically acceptable and fully automatable KBP models, with the goal of creating VMAT plans without user intervention., Methods: Ten KBP models were configured using high quality clinical plans from a single institution. They were then honed to be part of a fully automatable system by incorporating scriptable planning structures, plan creation, and plan optimization. These models were verified and validated using quantitative (model statistics) and qualitative (dose-volume histogram estimation review) analysis. The resulting KBP-generated plans were reviewed by physicians and rated for clinical acceptability., Results: Autoplanning models were created for anorectal, bladder, breast/chest wall, cervix, esophagus, head and neck, liver, lung/mediastinum, prostate, and prostate with nodes treatment sites. All models were successfully created to be part of a fully automated system without the need for human intervention to create a fully optimized plan. The physician review indicated that, on average, 88% of all KBP-generated plans were "acceptable as is" and 98% were "acceptable after minor edits.", Conclusion: KBP models for multiple treatment sites were used as a basis to generate fully automatable, efficient, consistent, high-quality, and clinically acceptable plans. These plans do not require human intervention, demonstrating the potential this work has to significantly impact treatment planning workflows., 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 B.V. All rights reserved.)

Identifying the frequencies of drug-side effects is crucial for assessing drug risk-benefit. However, accurately determining these frequencies remains challenging due to the limitations of time and scale in clinical randomized controlled trials. As a result, several computational methods have been proposed to address these issues. Nonetheless, two primary problems still persist. Firstly, most of these methods face challenges in generating accurate predictions for novel drugs, as they heavily depend on the interaction graph between drugs and side effects (SEs) within their modeling framework. Secondly, some previous methods often simply concatenate the features of drugs and SEs, which fails to effectively capture their underlying association. In this work, we present HSTrans, a novel approach that treats drugs and SEs as sets of substructures, leveraging a transformer encoder for unified substructure embedding and incorporating an interaction module for association capture. Specifically, HSTrans extracts drug substructures through a specialized algorithm and identifies effective substructures for each SE by employing an indicator that measures the importance of each substructure and SE. Additionally, HSTrans applies convolutional neural network (CNN) in the interaction module to capture complex relationships between drugs and SEs. Experimental results on datasets from Galeano et al.'s study demonstrate that the proposed method outperforms other state-of-the-art approaches. The demo codes for HSTrans are available at https://github.com/Dtdtxuky/HSTrans/tree/master., 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.)

Aromatic volatile organic compounds (VOCs) are prevalent pollutants in chemically contaminated sites, posing threats to ecological safety and human health. To address the challenge of achieving low-carbon, low-cost, green, and sustainable in-situ remediation at these sites, a highly efficient synthetic bacterial consortium was constructed for biodegradation of selected pollutants (i.e., benzene, toluene, ethyl benzene, m-xylene, chlorobenzene, p-chlorotoluene, and p-chlorotrifluorotoluene). Under optimized conditions, the consortium achieved a total degradation efficiency of 77%. Biodegradation of benzene, toluene, ethyl benzene, and m-xylene followed first-order kinetics, while p-chlorotoluene and p-chlorotrifluorotoluene followed zero-order kinetics. The mechanisms were analyzed using microbiome technology at genetic, protein, and metabolic levels, identifying key enzymes and differences in protein expression and related metabolites. Carbon dioxide measurements and fluorescence spectrum analysis elucidated the transformation pathways. These findings underscore the consortium's significant potential for achieving effective, eco-friendly, and sustainable bioremediation of aromatic VOCs in chemically contaminated environments., 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.)

A robust interface for coupling capillary electrophoresis (CE) to mass spectrometry (MS) was critical to maintain high separation efficiency of CE while achieving high sensitivity of MS. Current interfaces often suffer from problems such as reproducibility and ruggedness. For this purpose, a new polymetallic-coated sheathless interface was developed for the coupling of CE with MS. The electrical contact of the interface was achieved by etching one end of the fused silica capillary into a tapered tip using hydrofluoric acid (HF) solution, and then depositing a thin layer of chromium followed by a layer of platinum on it via physical vapor deposition technique. The performance of the new sheathless interface was systematically evaluated for the effect of flow rate and electrospray ionization (ESI) voltage on MS signal intensity, as well as the sample loading volume on CE separation efficiency and repeatability by using peptide standards and tryptic digest of bovine serum albumin (BSA). The interface was capable of generating stable electrospray even at ultra-low flow rate of 12.2 nL/min. In addition, the acid and alkali resistance of the polymetallic-coated emitter was tested by immersing it into 1 M HCL and 1 M NaOH solution, respectively. The results showed that polymetallic coating was still intact even after continuous immersion in the alkaline solution for 8 days (192 h) and a longer period in the acidic solution, indicating its excellent chemical stability. All the experimental results indicated that the sheathless interface fabricated by the new method in this study was robust and stable, making it promising for both sensitive and robust CE-MS sample analysis., 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.)

Immune dysfunction has been proposed to play a role in the pathophysiology behind the development and persistence of psychosis. Current immunophenotyping studies are limited by small sample sizes and the number of immune markers investigated. Pharmacological subtypes in schizophrenia based on antipsychotic response have been proposed, but few studies have investigated immunophenotypes in treatment-resistant schizophrenia. In this study, we perform comprehensive immunophenotyping on 196 subjects comprising 147 schizophrenia patients stratified by antipsychotic response (49 antipsychotic-responsive, 70 clozapine-responsive, 28 clozapine-resistant) and 49 healthy controls. We aim to identify significant immune cell populations associated with schizophrenia and increasing treatment resistance, as potential modulators of underlying psychosis and/or treatment response. Patients with schizophrenia were recruited and assessed on the Clinical Global Impression - Schizophrenia (CGI-SCH). Treatment response was defined as a rating of three (mild severity) or less on the CGI-SCH positive symptom item after at least 8 weeks of adequate antipsychotic or clozapine treatment. Peripheral blood mononuclear cells were collected and flow cytometry was performed to identify 66 immune cell populations. Differences in cell population proportions were compared between schizophrenia cases and controls, and across all 4 groups, with post-hoc pairwise comparisons. Mucosal-associated invariant T (MAIT) cells (specifically CD8 + and DN double-negative subsets), total, exhausted and memory CD8 + T cells, VD1 + ϒδ T cells, plasmablasts, IgG + B cells and conventional dendritic cells 2 (cDC2) were among the top cell populations downregulated in schizophrenia. We observed increased downregulation with increasing treatment resistance. Conversely, naïve and exhausted CD4 + T cells, CD4/CD8 ratio and CCR5 + CCR2 + HLA DR + Myeloid cells were found to be upregulated in schizophrenia - we observed increased upregulation with increasing treatment resistance. We show significant immunophenotypic differences between schizophrenia cases and healthy controls, and consistent trend differences across varying degrees of antipsychotic resistance. We also examined immune cell populations not previously reported in schizophrenia. Future studies may explore immune markers identified as potential biomarkers of treatment resistance, and clarify on the relationship between immunological changes and pharmacological subtypes in schizophrenia., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Circulating tumor cells (CTCs) are tumor cells that exist in human peripheral blood, which could spread to other tissues or organs via the blood circulation system and develop into metastatic foci, leading to tumor recurrence or metastasis in postoperative patients and thereby increasing the mortality of malignant tumor patients. Evaluation of CTC levels can be used for tumor metastasis prediction, prognosis evaluation, drug exploitation, individualized treatment, liquid biopsy, etc., which exhibit outstanding clinical application prospects. In recent years, accurately capturing and analyzing CTCs has become a research hotspot in the early diagnosis and precise treatment of tumors. This review summarized various enrichment and isolation technologies for evaluating CTCs based on the design principle and discussed the challenges and perspectives in this field., 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 and Objective: Delivering radiotherapy to the bladder is challenging as it is a mobile, deformable structure. Dose-escalated adaptive image-guided radiotherapy could improve outcomes. RAIDER aimed to demonstrate the safety of such a schedule., Methods: RAIDER is an international phase 2 noncomparative randomised controlled trial (ISRCTN26779187). Patients with unifocal T2-T4a urothelial bladder cancer were randomised (1:1:2) to standard whole bladder radiotherapy (WBRT), standard-dose adaptive radiotherapy (SART), or dose-escalated adaptive radiotherapy (DART). Two fractionation (f) schedules recruited independently. WBRT and SART dose was 55 Gy/20f or 64 Gy/32f, and DART dose was 60 Gy/20f or 70 Gy/32f. For SART and DART, a radiotherapy plan (small, medium, or large) was chosen daily. The primary endpoint was the proportion of patients with radiotherapy-related late Common Terminology Criteria for Adverse Events grade ≥3 toxicity; the trial was designed to rule out >20% toxicity with DART., Key Findings and Limitations: A total of 345 patients were randomised between October 2015 and April 2020: 41/46 WBRT, 41/46 SART, and 81/90 DART patients in the 20f/32f cohorts, respectively. The median age was 72/73 yr; 78%/85% had T2 tumours, 46%/52% had neoadjuvant chemotherapy, and 70%/71% had radiosensitising therapy. The median follow-up was 42.1/38.2 mo. Sixty-six of 77 (86%) 20f and 74 of 82 (90%) 32f participants planned for DART met the mandatory medium plan dose constraints. Radiotherapy-related grade ≥3 toxicity was reported in one of 58 patients (90% confidence interval [CI] 0.1, 7.9) with 20f DART and zero of 56 patients with 32f DART. Two-year overall survival was 77% (95% CI 69, 82) for WBRT + SART and 80% (95% CI 73, 85) for DART (hazard ratio = 0.84, 95% CI 0.59, 1.21, p = 0.4). Thirteen of 345 (3.8%) participants had salvage cystectomy., Conclusions and Clinical Implications: Grade ≥3 late toxicity was low. DART was safe and feasible to deliver, meeting preset toxicity thresholds. Disease-related outcomes are promising for dose-escalated treatments, with a low salvage cystectomy rate and overall survival similar to that seen in cystectomy cohorts., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Immunotherapy (ICIs) remains a mainstay for treatment of advanced clear-cell renal cell carcinoma (ccRCC). Biomarker analyses have demonstrated that gene expression profiles are associated with regimen-specific outcomes. These transcriptomic analyses used mixed sample cohorts (primary and metastatic tumor specimens) and it is unknown whether the clinical relevance of transcriptomic signatures is impacted by tissue site. We evaluated data for 1132 patients with metastatic ccRCC treated with ICI in prior studies (IMmotion151 and CheckMate-009, -010, and -025). We identified significant and reproducible differences in gene expression by tissue site. We tested the association between previously described molecular tissue clusters (MTCs) by tissue site (MTC1-primary and MTC1-metastasis) and progression-free survival (PFS) and objective response to systemic therapy. In IMmotion151, MTC2-metastasis was significantly associated with better PFS on sunitinib (hazard ratio [HR] 3.39, 95% confidence interval [CI] 1.32-8.69; p = 0.01) in comparison to MTC2-primary (HR 0.95, 95% CI 0.65-1.38; p = 0.80; p interaction  = 0.02). Evaluation of known RNA signatures in the CheckMate trials revealed that JAVELIN-metastasis was associated with better PFS on ICI (HR 0.77, 95% CI 0.62-0.97; p = 0.03) in comparison to JAVELIN-primary (HR 1.04, 95% CI 0.91-1.19; p = 0.56; p interaction  = 0.02). These results indicate that tissue site may be a relevant confounder in biomarker analyses., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: The disrupted homeostasis of branched-chain amino acids (BCAAs, including leucine, isoleucine, and valine) has been strongly correlated with diabetes with a potential causal role. However, the relationship between BCAAs and diabetic kidney disease (DKD) remains to be established. Here, we show that the elevated BCAAs from BCAAs homeostatic disruption promote DKD progression unexpectedly as an independent risk factor., Methods and Results: Similar to other tissues, the suppressed BCAAs catabolic gene expression and elevated BCAAs abundance were detected in the kidneys of type 2 diabetic mice and individuals with DKD. Genetic and nutritional studies demonstrated that the elevated BCAAs from systemic disruption of BCAAs homeostasis promoted the progression of DKD. Of note, the elevated BCAAs promoted DKD progression without exacerbating diabetes in the animal models of type 2 DKD. Mechanistic studies demonstrated that the elevated BCAAs promoted fibrosis-associated epithelial-mesenchymal transition (EMT) by enhancing the activation of proinflammatory macrophages through mTOR signaling. Furthermore, pharmacological enhancement of systemic BCAAs catabolism using small molecule inhibitor attenuated type 2 DKD. Finally, the elevated BCAAs also promoted DKD progression in type 1 diabetic mice without exacerbating diabetes., Conclusion: BCAA homeostatic disruption serves as an independent risk factor for DKD and restoring BCAA homeostasis pharmacologically or dietarily represents a promising therapeutic strategy to ameliorate the progression of DKD., 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.)

Extracellular vesicles (EVs) are considered as promising candidates for predicting patients who respond to immunotherapy. Nevertheless, simultaneous detection of multiple EVs markers still presents significant technical challenges. In this work, we developed a high-throughput microdroplet-enhanced chip (MEC) platform, which utilizes thousands of individual microchambers (∼pL) as reactors, accelerating the detection efficiency of the CRISPR/Cas systems and increasing the sensitivity by up to 100-fold (aM level). Ten biomarkers (including 5 RNAs and 5 proteins) from patients' EVs are successfully detected on one chip, and the comprehensive markers show increased accuracy (AUC 0.911) than the individual marker for the efficacy prediction of immunotherapy. This platform provides a high-throughput yet sensitive strategy for screening immunotherapy markers in clinical., 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 and Objective: Radiofrequency ablation (RFA) is an emerging treatment of lung cancer, yet it is accompanied by certain safety concerns and operational limitations. This first multi-centre, large-scale clinical trial aimed to investigate the technical performance, efficacy and safety of an innovative transbronchial RFA system for lung tumours., Methods: The study enrolled patients with malignant lung tumours who underwent transbronchial RFA using an automatic saline microperfusion system between January 2021 and December 2021 across 16 medical centres. The primary endpoint was the complete ablation rate. The performance and safety of the technique, along with the 1-year survival rates, were evaluated., Results: This study included 126 patients (age range: 23-85 years) with 130 lung tumours (mean size: 18.77 × 14.15 mm) who had undergone 153 transbronchial RFA sessions, with a technique success rate of 99.35% and an average ablation zone size of 32.47 mm. At the 12-month follow-up, the complete ablation rate and intrapulmonary progression-free survival rates were 90.48% and 88.89%, respectively. The results of patients with ground-glass nodules (GGNs) were superior to those of the patients with solid nodules (12-month complete ablation rates: solid vs. pure GGN vs. mixed GGN: 82.14% vs. 100% vs. 96.08%, p = 0.007). No device defects were reported. Complications such as pneumothorax, haemoptysis, pleural effusion, pulmonary infection and pleural pain were observed in 3.97%, 6.35%, 8.73%, 11.11% and 10.32% of patients, respectively. Two subjects died during the follow-up period., Conclusion: Transbronchial RFA utilizing an automatic saline microperfusion system is a viable, safe and efficacious approach for the treatment for lung tumours, particularly for patients with GGNs., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Purpose: The aim of this review was to assess the effectiveness of multidisciplinary, activity-based interventions on adults with chronic musculoskeletal or widespread pain who identify as ethnoculturally diverse (ECD) compared to adults belonging to the predominant culture of the host country., Methods: Online databases Medline, CINAHL, AMED, Psych Info and PubMed were searched from the earliest date available until April 2023. The quality of the included studies were assessed against the Risk of Bias in Non Randomized Studies of Interventions (ROBINS-I). Postintervention data were analyzed using meta-analyses and the certainty of evidence determined using the Grading of Recommendation, Assessment, Development and Evaluation approach (GRADE)., Results: Nine cohort studies with 3467 participants living in America and north-western European countries were included. ECD adults had higher pain intensity (SMD 1.36, 95%CI 0.29 to 2.35, p  = 0.03), higher levels of depression (SMD 0.96, 95%CI 0.40 to 1.52, p  < 0.01) and a nonsignificant difference in pain-related disability (SMD -1.45, 95%CI -3.28 to 0.39, p  = 0.12) following multidisciplinary pain intervention compared to adults of the predominant culture., Conclusion: Adults from ECD backgrounds in Western nations have poorer outcomes after multidisciplinary, activity-based chronic pain interventions compared to adults from predominant cultural groups in these countries suggesting program adaptations may be required.

Harnessing the inexhaustible solar energy for water splitting is regarded one of the most promising strategies for hydrogen production. However, sluggish kinetics of oxygen evolution reaction (OER) and expensive photovoltaics have hindered commercial viability. Here, an adhesive-free electrodeposition process is developed for in-situ preparation of earth-abundant electrocatalysts on super-flat indium tin oxide (ITO) substrate. NiFe hydroxide exhibited prominent OER performance, achieving an ultra-low overpotential of 236 mV at 10 mA/cm 2 in alkaline solution. With the superior OER activity, we achieved an unassisted solar water splitting by series connected perovskite solar cells (PSCs) of 2 cm 2 aperture area with NiFe/ITO//Pt electrodes, yielding overall solar to hydrogen (STH) efficiency of 13.75 %. Furthermore, we upscaled the monolithic facility to utilize perovskite solar module for large-scale hydrogen production and maintained an approximate operating current of 20 mA. This creative strategy contributes to the decrease of industrial manufacturing expenses for perovskite-based photovoltaic-electrochemical (PV-EC) hydrogen production, further accelerating the conversion and utilization of carbon-free energy., 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.)