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Oxygen (O 2 ) electroreduction offers a green approach for singlet oxygen ( 1 O 2 ) synthesis in wastewater contaminants detoxification. However, traditional single O 2 activation on single-metal catalytic sites seriously suffers from the kinetically-unfavorable desorption of adsorbed superoxide species (•O 2 - */•OOH*). Here, we demonstrate a novel dual O 2 coactivation pathway on shortened Fe 1 -O V -Ti sites for superior 1 O 2 electrosynthesis through a rapid disproportionate process between surface-confined •O 2 - */•OOH*. Theoretical calculations combined with in situ electrochemical spectroscopies demonstrated that the shortened distance between Fe single atom and adjacent unsaturated Ti atom facilitates the direct recombination of surface-confined Fe-•OOH and Ti-•OO - to yield 1 O 2 , bypassing the formidable •O 2 - */•OOH* desorption process. Impressively, Fe 1 -O V -Ti could realize an excellent 1 O 2 electrosynthesis rate of 54.5 μmol L -1  min -1 with an outstanding 1 O 2 selectivity of 97.6 % under neutral condition, surpassing that of Fe 1 -O-Ti (27.1 μmol L -1  min -1 , 91.7 %). Using tetracycline (TC) as a model pollutant, the resulting Fe 1 -O V -Ti electrode achieved nearly 100 % degradation in 120 min at -0.6 V, meanwhile preventing the generation of toxic intermediates. This study provides a new 1 O 2 electrosynthesis strategy by controlling the distance of adjacent catalytic sites for the coactivation of dual molecular oxygen., (© 2024 Wiley-VCH GmbH.)

Ammonium oxidation coupled with Fe(III) reduction, known as Feammox, and nitrate-dependent ferrous oxidation (NDFO) are two processes that can be synergistically achieved through the Fe(III)/Fe(II) cycle. This integrated approach enables the simultaneous removal of ammonia nitrogen (NH 4 + -N) and nitrate nitrogen (NO 3 - -N) from wastewater, representing a novel method for complete nitrogen removal. This study presents a systematic and exhaustive examination of the Feammox-NDFO coupled process. An initial thorough exploration of the underlying mechanisms behind the coupling process is conducted, highlighting how the Fe(III)/Fe(II) cycle enables the concurrent occurrence of these reactions. Further, the functional microorganisms associated with and playing a crucial role in the Feammox-NDFO process are summarized. Next, the key influencing factors that govern the efficiency of the Feammox-NDFO process are explored. These include parameters such as pH, temperature, carbon source, iron source, nitrogen source, and various electron shuttles that may mediate electron transfer. Understanding the impact of these factors is essential for optimizing the process. The most recent trends and endeavors on the Feammox-NDFO coupling technology in wastewater treatment applications are also examined. This includes examining both laboratory-scale studies and field trials, highlighting their successes and challenges. Finally, an outlook is presented regarding the future advancement of the Feammox-NDFO technology. Areas of improvement and novel strategies that could further enhance the efficiency of simultaneous nitrogen removal from the iron cycle are discussed. In summary, this study aspires to offer a thorough comprehension of the Feammox-NDFO coupled process, with a focus on its mechanisms, influencing factors, applications, and prospects. It is anticipated to yield invaluable insights for the advancement of process optimization, thus sparking fresh ideas and strategies aimed at accomplishing the thorough elimination of nitrogen from wastewater via the iron cycle., 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.)

In the context of increasing global nitrogen pollution, traditional biological nitrogen removal technologies like nitrification and denitrification are hindered by high energy consumption. Additionally, the deployment of anaerobic ammonium oxidation (Anammox) technology is constrained due to the slow growth rate of Anammox bacteria and there is a bottleneck in nitrogen removal efficiency. To overcome these technical bottlenecks, researchers have discovered a revolutionary nitrogen removal technology that cleverly combines the redox cycling of manganese with nitrification and denitrification reactions. In this new process, manganese dependent anaerobic ammonium oxidation (Mnammox) bacteria can convert NH 4 + to N 2 under anaerobic conditions, while nitrate/nitrite dependent manganese oxidation (NDMO) bacteria use NO 3 - /NO 2 - as electron acceptors to oxidize Mn 2+ to Mn 4+ . Mn 4+ acts as an electron acceptor in Mnammox reaction, thereby realizing the autotrophic nitrogen removal process. This innovative method not only simplifies the steps of biological denitrification, but also significantly reduces the consumption of oxygen and organic carbon, providing a more efficient and environmentally friendly solution to the problem of nitrogen pollution. The article initially provides a concise overview of prevalent nitrogen removal technologies and the application of manganese in these processes, and discusses the role of manganese in biogeochemical cycles, including its discovery, mechanism of action, microbial communities involved, and its impact on these key factors in the process. Subsequently, metabolic principles, benefits, advantages, and environmental considerations of Mnammox coupled with the NDMO process are analyzed in detail. Finally, this article summarizes the shortcomings of current research and looks forward to future research directions. The goal of this article is to provide a valuable reference for researchers to fully understand the application of manganese in nitrogen removal processes., 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.)

Abstract: Gilteritinib is the current standard of care for relapsed or refractory fms related receptor tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or nonintensive chemotherapy with venetoclax) are uncertain. Moreover, reported data on toxicity and health care resource use is limited. Here, we describe a large real-world cohort of 152 patients receiving single-agent gilteritinib in 38 UK hospitals. Median age was 61 years, and 36% had received ≥2 prior lines of therapy, including a FLT3 inhibitor in 41% and venetoclax in 24%. A median of 4 cycles of gilteritinib were administered, with 56% of patients requiring hospitalization in the first cycle (median, 10 days). Over half of patients required transfusion in each of the first 4 cycles. Complete remission (CR) was achieved in 21%, and CR with incomplete recovery (CRi) in a further 9%. Remission rates were lower for patients with FLT3-tyrosine kinase domain or adverse karyotype. Day-30 and day-60 mortality were 1% and 10.6%, respectively, and median overall survival was 9.5 months. On multivariable analysis, increasing age, KMT2A rearrangement, and complex karyotype were associated with worse survival whereas RUNX1 mutations were associated with improved survival. Twenty patients received gilteritinib as first salvage having progressed after first-line therapy with venetoclax, with CR/CRi achieved in 25% and median survival 4.5 months. Real-world results with gilteritinib mirror those seen in the clinical trials, but outcomes remain suboptimal, with more effective strategies needed., (© 2024 by The American Society of Hematology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

In systemic lupus erythematosus (SLE), neutrophil dysregulation and neutrophil extracellular traps (NETs) formation contribute to disease pathogenesis, potentially worsening the autoimmune response. Although research indicates NETs' involvement in various autoimmune conditions, their relationship with regulatory T cells (Tregs) in SLE remains elusive. In this study, in vivo experiments were involved in administering NET injections to C57BL/6 and MRL/Ipr mice. In vitro, a co-culture system facilitated interaction between Tregs and NETs. Proteomic analysis elucidated NET composition, while RNA sequencing delineated their impact on Treg differentiation. We demonstrated that increased NET levels correlate inversely with Treg abundance in SLE patients, influencing both their proportion and functionality. NET administration reduced Treg levels and induced lupus-like symptoms in C57BL/6 mice, exacerbating symptoms in MRL/Ipr mice. DNase I treatment mitigated NET effects, restoring Treg levels and alleviating symptoms. RNA sequencing revealed altered gene expression in naïve CD4 + T cells exposed to NETs. Additionally, proteomic analysis showed S100A10 protein changes between SLE patients and healthy controls, hindering Treg differentiation. NETs influence TLR-4 of naïve CD4 + T cells via S100A10, thereby modulating Treg proportion and functionality. These findings highlight the critical role of NETs in Treg differentiation in SLE, suggesting that targeting NETs may provide a novel therapeutic approach., (© 2024 Wiley‐VCH GmbH.)

In this study, we aimed to investigate disparities in the tumor immune microenvironment (TME) between primary and metastatic malignant melanoma (MM) using single-cell RNA sequencing (scRNA-seq) and to identify metastasis-related T cell marker genes (MRTMGs) for predicting patient survival using machine learning techniques. We identified 6 distinct T cell clusters in 10×scRNA-seq data utilizing the Uniform Manifold Approximation and Projection (UMAP) algorithm. Four machine learning algorithms highlighted SRGN, PMEL, GPR143, EIF4A2, and DSP as pivotal MRTMGs, forming the foundation of the MRTMGs signature. A high MRTMGs signature was found to be correlated with poorer overall survival (OS) and suppression of antitumor immunity in MM patients. We developed a nomogram that combines the MRTMGs signature with the T stage and N stage, which accurately predicts 1-year, 3-year, and 5-year OS probabilities. Furthermore, in an immunotherapy cohort, a high MRTMG signature was associated with an unfavorable response to anti-programmed death 1 (PD-1) therapy. In conclusion, primary and metastatic MM display distinct TME landscapes with different T cell subsets playing crucial roles in metastasis. The MRTMGs signature, established through machine learning, holds potential as a valuable biomarker for predicting the survival of MM patients and their response to anti-PD-1 therapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The domestication of edible mushrooms, including Flammulina filiformis, offers valuable insights into the genetic changes driven by artificial selection. Understanding these changes is crucial for uncovering the mechanisms behind genome evolution in domesticated mushrooms., Objectives: This study aims to investigate the population structure, genetic diversity, and domestication-related genomic changes in F. filiformis. By comparing the genome sequences of 199 wild and cultivated strains, we aim to elucidate the impact of domestication on F. filiformis., Methods: We performed de novo genome assembly and gene-based pan-genome analysis on the 199 strains, which included both wild and cultivated strains. We also conducted genome-wide association studies (GWAS) using presence-absence variation (PAV) and SNP data, combined with RNA sequencing, to identify genes associated with domestication traits, such as cap color and stipe length. Gene functional confirmation was achieved through genetic transformation experiments., Results: Our analysis grouped the strains into four distinct populations, which correlated with varying intensities of artificial selection. The three cultivated populations exhibited smaller genome sizes, fewer genes, lower genetic variation, reduced gene expression diversity, and lower heterozygosity compared to the wild population. The analysis revealed the loss of genes related to the beta-lactam antibiotic catabolic process and specific MAPK pathway genes during domestication, rendering domesticated strains more susceptible to diseases. Four genes closely associated with cap color and stipe length were identified, but genetic transformation experiments confirmed the functional relevance of only two (FfB and FfD) identified through PAV-based GWAS., Conclusion: This study uncovered significant genomic variations between cultivated and wild F. filiformis populations, including the loss of pathogen resistance genes during domestication. We also identified key genes linked to cap color and stipe length, demonstrating for the first time the important role of PAV variation in mushroom domestication. These insights provide a foundation for future mushroom breeding and evolutionary research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The immune system plays a pivotal role in maintaining physiological homeostasis and influencing disease processes. Dysregulated immune responses drive chronic inflammation, which in turn results in a range of diseases that are among the leading causes of death globally. Traditional immune interventions, which aim to regulate either insufficient or excessive inflammation, frequently entail lifelong comorbidities and the risk of severe side effects. In this context, intrinsic immunomodulatory hydrogels, designed to precisely control the local immune microenvironment, have recently attracted increasing attention. In particular, these advanced hydrogels not only function as delivery mechanisms but also actively engage in immune modulation, optimizing interactions with the immune system for enhanced tissue repair, thereby providing a sophisticated strategy for managing chronic inflammation. In this tutorial review, we outline key elements of chronic inflammation and subsequently explore the strategic design principles of intrinsic immunomodulatory hydrogels based on these elements. Finally, we examine the challenges and prospects of such immunomodulatory hydrogels, which are expected to inspire further preclinical research and clinical translation in addressing chronic inflammation.

Objectives: Spontaneous intracerebral hemorrhage (sICH) is a severe cerebrovascular disease with high mortality and disability. And its treatment strategies have always been a hotspot in clinical research. Endoscopic surgery (ES) is widely used for treating sICH. A comprehensive review of ES for sICH is warranted to provide better understanding and guidance for clinicians. We provide an updated overview of the surgical equipment, surgical indications and timing, and technical advancements, as well as therapeutic effect and future directions., Materials and Methods: A narrative review of current literature in ES for sICH was performed based on publications from the databases of PubMed, Scopus and Google Scholar databases up to December, 2023., Results: ES has shown promising safety and efficacy, emerging as a favorable minimally invasive alternative to conventional craniotomy. It reduces peri-operative risks associated with long procedures and significant intra-operative bleeding. Recent advancements in ES techniques have led to superior outcomes in mortality reduction and functional recovery. Scholars' systematic studies and summaries underscore ES's role in improving long-term outcomes for sICH patients. However, its limitations, including reduced depth perception, difficulty in managing deep hematomas, and reduced ability to control rapid bleeding control, should be noted., Conclusions: ES represents a significant advancement in the treatment of sICH. Its minimally invasive features, coupled with continuous methodological refinement, contribute to lower mortality rate and better functional recovery compared to traditional methods. ES should be considered a significant option in the surgical management of sICH, necessitating further research and standardization to enhance patient care and outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to evaluate the prognostic value of the Mayo additive staging system (MASS) and minimal residual disease (MRD) in newly diagnosed multiple myeloma (NDMM) patients., Methods: A total of 238 NDMM patients were enrolled in Beijing Chaoyang Hospital. Fluorescence in-situ hybridization and next-generation flow cytometry were used to examine cytogenetic abnormalities and MRD, respectively. The patients were classified into three groups to compare the effects on progression-free survival (PFS). Univariate and multivariate analyses were applied to identify the survival-related factors., Results: For MASS group, the PFS was significant difference in MASS I, II, and III patients (p = 0.0006); the patients with sustained MRD-negative, non-sustained MRD-negative, sustained MRD-positive, and non-sustained MRD-positive were divided into Groups 1, 2, 3, and 4, respectively. The Group 1 patients had superior PFS than Groups 2 and 3 patients (p < 0.05), but no difference in PFS was observed for Group 2 versus Group 3, Group 2 versus Group 4, and Group 3 versus Group 4 patients. For the MASS and MRD groups, among Groups 2, 3, and 4, MASS I patients had a superior PFS, while III patients showed the opposite result. Strikingly, no difference in PFS for Group 1 patients regardless of the MASS stage was observed. Despite being in MASS II and III, the PFS of Group 1 patients was longer than those with the other three groups. Response to treatment was an independent prognostic factor for MM patients., Conclusion: Patients with an accumulation of high-risk factors and MRD-positive have poor outcomes. Sustained MRD-negative may improve high-risk patients' prognoses., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: The KRAS mutation is highly prevalent in NSCLC and is associated with poor efficacy of immunotherapy. Nevertheless, the impact of KRAS mutation, mutation subtypes, and co-mutations on the effectiveness of immunotherapy remains uncertain. This study aimed to assess the influence of the KRAS mutation on the effectiveness of immunotherapy in NSCLC, specifically examining different subtypes of KRAS mutations and co-mutations., Methods: We performed an extensive search of multiple databases, covering the period from January 1, 2000, to December 5, 2023. A total of 24 articles met our inclusion criteria and were included in this study. A comparative analysis assessed the influence of different subgroups, including KRAS mutation, KRAS wild-type, KRAS G12C mutation, KRAS G12D mutation, and KRAS with co-mutations in NSCLC with immunotherapy. The study outcomes include HR, with corresponding 95% CI and P-values for OS and PFS using Review Manager 5.4 software for the meta-analysis., Result: The KRAS mutation appears to have a more beneficial impact on OS (HR 0.54 [95% CI: 0.41-0.71]; P < 0.00001) and PFS (HR 0.63 [95% CI: 0.53-0.76]; P < 0.00001) in NSCLC patients receiving immunotherapy compared to those without immunotherapy. The presence of KRASG12C mutation has been found to have a positive impact on PFS (HR 0.39 [95% CI: 0.25-0.62]; P < 0.0001) in NSCLC patients who undergo immunotherapy, compared to those who did not receive immunotherapy. KRAS non-G12D mutation is considerably associated with longer OS (HR 1.52 [95% CI: 1.10-2.10]; P = 0.01). The clinical benefit in OS between patients without STK11 co-mutation and those who have KRAS mutation with STK11 is significant (HR 1.46 [95% CI: 1.10-1.93]; P = 0.008). Comparing the impact of OS patients without KEAP1/NFE2L2 mutation to those with KRAS and KEAP1/NFE2L2 co-mutations showed a significant impact (HR 1.89 [95% CI: 1.33-2.68]; P = 0.0004)., Conclusion: The KRAS mutation and KRAS G12C mutation confer benefits that impact OS and PFS in NSCLC patients treated with immunotherapy. However, the KRAS G12D mutation negatively impacts OS compared to the KRAS non-G12D mutation. Furthermore, KRAS co-mutations involving STK11 and KEAP1/NFE2L2 are associated with a negative impact on the efficacy of immunotherapy in NSCLC patients., (© 2024. The Author(s).)

Functional magnetic resonance imaging (fMRI) has been widely used in studying the neural mechanisms of pain in the human brain, primarily focusing on where in the brain pain-elicited neural activities occur (i.e., the spatial distribution of pain-related brain activities). However, the temporal dynamics of pain-elicited hemodynamic responses (HDRs) measured by fMRI may also contain information specific to pain processing but have been largely neglected. Using high temporal resolution fMRI (TR = 0.8 s) data acquired from 62 healthy participants, in the present study we aimed to test whether pain-distinguishing information could be decoded from the spatial pattern of the temporal dynamics (i.e., the spatiotemporal pattern) of HDRs elicited by painful stimuli. Specifically, the peak latency and the response duration were used to characterize the temporal dynamics of HDRs to painful laser stimuli and non-painful electric stimuli, and then were compared between the two conditions (i.e., pain and no-pain) using a voxel-wise univariate analysis and a multivariate pattern analysis. Furthermore, we also tested whether the two temporal characteristics of pain-elicited HDRs and their spatial patterns were associated with pain-related behaviors. We found that the spatial patterns of HDR peak latency and response duration could successfully discriminate pain from no-pain. Interestingly, we also observed that the Pain Vigilance and Awareness Questionnaire (PVAQ) scores were correlated with the average response duration in bilateral insula and secondary somatosensory cortex (S2) and could also be predicted from the across-voxel spatial patterns of response durations in the middle cingulate cortex and middle frontal gyrus only during painful condition but not during non-painful condition. These findings indicate that the spatiotemporal pattern of pain-elicited HDRs may contain pain-specific information and highlight the importance of studying the neural mechanisms of pain by taking advantage of the high sensitivity of fMRI to both spatial and temporal information of brain responses., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

A self-corrosion microelectrolysis (SME)-enhanced membrane-aerated biofilm reactor (eMABR) was developed for the removal of pollutants and reduction of antibiotic resistance genes (ARGs). Fe 2+ and Fe 3+ formed iron oxides on the biofilm, which enhanced the adsorption and redox process. SME can induce microorganisms to secrete more extracellular proteins and up-regulate the expression of ammonia monooxygenase (AMO) (0.92 log 2 ). AMO exposed extra binding sites (ASP-69) for antibiotics, weakening the competition between NH 4 + -N and sulfamethoxazole (SMX). The NH 4 + -N removal efficiency in the S-eMABR (adding SMX and IC) increased by 44.87 % compared to the S-MABR (adding SMX). SME increased the removal performance of SMX by approximately 1.45 times, down-regulated the expressions of sul1 (-1.69 log 2 ) and sul2 (-1.30 log 2 ) genes, and controlled their transfer within the genus. This study provides a novel strategy for synergistic reduction of antibiotics and ARGs, and elucidates the corresponding mechanism based on metatranscriptomic and molecular docking analyses., 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.)

Objectives: To evaluate deep learning reconstruction (DLR)-based accelerated rectal magnetic resonance imaging (MRI) compared with standard MRI., Materials and Methods: Patients with biopsy-confirmed rectal adenocarcinoma between November/2022 and May/2023 in a single centre were prospectively enrolled for an intra-individual comparison between standard fast spin-echo (FSE standard ) and DLR-based FSE (FSE DL ) sequences. Quantitative and qualitative image quality metrics of the pre-therapeutic MRIs were evaluated in all patients; diagnostic performance and evaluating time for T-staging, N-staging, extramural vascular invasion (EMVI), and mesorectal fascia (MRF) status was further analysed in patients undergoing curative surgery, with histopathologic results as the diagnostic gold standard., Results: A total of 117 patients were enrolled, with 60 patients undergoing curative surgery. FSE DL reduced the acquisition time by 65% than FSE standard . FSE DL exhibited higher signal-to-noise ratios, contrast-to-noise ratio, and subjective scores (noise, tumour margin clarity, visualisation of bowel wall layering and MRF, overall image quality, and diagnostic confidence) than FSE standard (p < 0.001). Reduced artefacts were observed in FSE DL for patients without spasmolytics (p < 0.05). FSE DL provided higher T-staging accuracy by junior readers than FSE standard (reader 1, 58.33% vs 70.00%, p = 0.016; reader 3, 60.00% vs 76.67%, p = 0.021), with similar N-staging, EMVI, and MRF performance. No significant difference was observed for senior readers. FSE DL exhibited shorter diagnostic time in all readers' T-staging and overall evaluation, and junior readers' EMVI and MRF (p < 0.05)., Conclusion: FSE DL provided improved image quality, reading time, and junior radiologists' T-staging accuracy than FSE standard , while reducing the acquisition time by 65%., Clinical Relevance Statement: DLR is clinically applicable for rectal MRI, providing improved image quality with shorter scanning time, which may ease the examination burden. It is beneficial for diagnostic optimisation in improving junior radiologists' T-staging accuracy and reading time., Key Points: The rising incidence of rectal cancer has demanded enhanced efficiency and quality in imaging examinations. FSE DL demonstrated superior image quality and had a 65% reduced acquisition time. FSE DL can improve the diagnostic accuracy of T-staging and reduce the reading time for assessing rectal cancer., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Chiral inversions of enantiomers have significantly different biological activities, so it is important to develop simple and effective methods to efficiently identify optically pure compounds. Inspired by enzyme catalysis, the construction of chiral microenvironments resembling enzyme pockets in the pore space structure of metal-organic frameworks (MOFs) to achieve asymmetric enantioselective recognition and catalysis has become a new research hotspot. Here, a super-stable porphyrin-containing material PCN-224 is constructed by solvothermal method and a chiral microenvironment around the existing catalytic site of the material is created by post-synthesis modifications of the histidine (His) enantiomers. Experimental and theoretical calculations results show that the modulation of chiral ligands around Zr oxide clusters produces different spatial site resistances, which can greatly affect the adsorption and catalytic level of the enantiomeric molecules of tryptophan guests, resulting in a good enantioselective property of the material. It provides new ideas and possibilities for future chiral recognition and asymmetric catalysis., (© 2024 Wiley‐VCH GmbH.)

As a potential source of the hydroxyl (OH) radical and nitrous acid (HONO), photolysis of o -nitrophenol (ONP) is of significant interest in both experimental and theoretical studies. In the atmospheric environment, the number of water molecules surrounding ONP changes with the humidity of the air, leading to an anisotropic chemical environment. This may have an impact on the photodynamics of ONP and provide a mechanism that differs from previously reported ones in the gas phase or in solution. Herein, the high-level MS-CASPT2//CASSCF method was performed to elucidate the excited-state decay and the generation of the OH radical for ONP before proton transfer in the microsolvated surrounding. We found that the varying number of water molecules affects the ground-state structures and alters the energy levels of nπ* and ππ* at the Franck-Condon (FC) region. Nevertheless, this is not the case for the excited-state minima, which exhibit very similar adiabatic excitation properties. In addition, the presence of water molecules also significantly influences the intersection structures since hydrogen bonds will hinder or alleviate the rotation or pyramidalization of the nitro (NO 2 ) group. This will, in turn, change the excited-state relaxation mechanism of ONP. Finally, we speculated that the OH radical might be formed in the hot ground state of ONP in the microsolvated surrounding after exploring all possible electronic states.

Ferroptosis is a newly discovered type of cell death that exerts a crucial role in hepatic fibrosis. Formononetin (FMN), a natural isoflavone compound mainly isolated from Spatholobus suberectus Dunn, shows multiple biological activities, including antioxidant, anti-inflammatory, and hepatoprotection. This research aims to explore the regulatory mechanism of FMN in liver fibrosis and the relationship between NADPH oxidase 4 (NOX4) and ferroptosis. The effects of FMN on HSC ferroptosis were evaluated in rat model of CCl 4 -induced hepatic fibrosis. In vitro, N-acetyl-L-cysteine (NAC) and deferoxamine (DFO) were used to block ferroptosis and then explored the anti-fibrotic effect of FMN. The target protein of FMN was identified by bio-orthogonal click chemistry reaction as well as drug affinity responsive target stability (DARTS), cellular thermal shift (CETSA), surface plasmon resonance (SPR) assays, and isothermal titration calorimetry (ITC) analysis. Here, we found that FMN exerted anti-fibrotic effects via inducing ferroptosis in activated HSCs. NAC and DFO prevented FMN-induced ferroptotic cell death and collagen reduction. Furthermore, FMN bound directly to NOX4 through possible active amino acid residues sites, and increased NOX4-based NADPH oxidase activity to enhance levels of NADP + /NADPH, thus promoting ferroptosis of activated HSCs and relieving liver fibrosis. These results demonstrate that the direct target and mechanism by which FMN improves liver fibrosis, suggesting that FMN may be a natural candidate for further development of liver fibrosis therapy., (© 2024 John Wiley & Sons Ltd.)

Purpose: With the increasing aging of the population and the increasing incidence of chronic diseases in China, home hospice care services can meet the desire of the older adult with chronic diseases to receive care and die at home. In order to ensure the real application of hospice in families, the goal of the study was to construct a home hospice care program for the older adult at the end of life with chronic diseases based on Harmony Nursing Theory (composed of three parts: harmony needs assessment, harmony mechanism establishment and interpersonal interaction)., Methods: Through literature review, a qualitative interview and group discussion, the first draft of a home hospice care program for the older adult at the end of life with chronic diseases based on the harmony nursing theory was developed, which was further revised and finalized by combining the Delphi method of expert correspondence with 19 experts and a pilot study with a home hospice care team., Results: A total of two rounds of expert correspondence were conducted. In the first round, 21 questionnaires were distributed and 19 were returned, yielding a recovery rate of 90.48%. In the second round, 19 questionnaires were distributed, and 19 questionnaires were collected. The recovery rate was 100%. The authority of the two rounds of expert correspondence was 0.96, and Kendall's coefficient of concordance (W) was 0.268 and 0.310, respectively. After the first round of Delphi expert consultation, 3 items were deleted, and 12 items were revised. In the second round of Delphi expert consultation, two items were revised. The final version of the home hospice program includes 4 first-level items, 20 second-level items, and 59 third-level items., Conclusion: The home hospice care program based on harmony nursing theory is authoritative and scientific and can provide a reference for the practice of home hospice care for the older adult with chronic diseases., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

Patients taking atypical antipsychotics (AAPs), especially clozapine, are often associated with hyperglycaemia. Here, clozapine served as a representative agent for investigating how AAPs induce hyperglycaemia. In normal mice and mice fed a high fat diet (HFD), clozapine impaired glucose tolerance and glucose-stimulated insulin secretion (GSIS) following intraperitoneal glucose administration and increased plasma 5-HT levels. Intraperitoneal 5-HT administration also impaired glucose tolerance and GSIS in mice. In INS-1 cells, high 5-HT levels impaired GSIS, which was attenuated by the 5-HTR 3 antagonist tropisetron or by silencing 5-HTR 3a . The 5-HTR 2a agonist TCB2 attenuated clozapine-induced GSIS impairment. Silencing 5-HTR 2a or the 5-HTR 2a antagonist ketanserin impaired GSIS. In mice, 5-HT administration impaired GSIS, which was attenuated by tropisetron but aggravated by clozapine. Clozapine increased plasma [ 2 H]5-HT exposure following intravenous administration to mice. In HEK293-OCT1 cells, clozapine inhibited [ 2 H]5-HT and MPP + uptake. Clozapine or OCT1 silencing impaired 5-HT metabolism in mouse primary hepatocytes, demonstrating that clozapine increased plasma 5-HT levels via the inhibition of OCT1-mediated hepatic 5-HT uptake. Liver-specific silencing of OCT1 increased plasma [ 2 H]5-HT exposure and 5-HT levels and impaired GSIS and glucose tolerance in mice. In conclusion, clozapine impaired GSIS and glucose tolerance by increasing plasma 5-HT levels via the inhibition of OCT1-mediated hepatic 5-HT uptake. Increased 5-HT impaired GSIS by activating islet 5-HTR 3a . The antagonistic effect of clozapine on islet 5-HTR 2a also contributed to GSIS impairment. The finding that clozapine-induced GSIS impairment was attributed to increased 5-HT levels via the inhibition of OCT1-mediated hepatic 5-HT uptake may partly explain hyperglycaemia caused by other AAPs., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Oral cancer (ORCA) is the most prevalent histological subtype of oral malignancies in which immune modulation is relevant. The goal of this work was to employ Mendelian randomization (MR) to investigate the causal connection between the immune-related proteins MICB, CTSA, MMP9, and ORCA. The Open GWAS database of the Integrative Epidemiology Unit (IEU) was accessed to collect GWAS data for ORCA (ieu-b-4961), MICB (prot-a-1898), CTSA (prot-a-717) and MMP9 (prot-a-1921). From 372,373 samples, the ORCA dataset comprises 7,723,107 single nucleotide polymorphisms (SNPs). MICB, CTSA, and MMP9 all have 10,534,735 SNPs and 3,301 sample sizes. Then, the primary SVMR implementation approaches were weighted mode, simple mode, inverse variance weighted (IVW), weighted median, and MR-Egger. IVW was the most effective technique. A sensitivity study was also carried out to assess the correctness of SVMR data, with special focus devoted to heterogeneity, horizontal pleiotropy, and Leave-One-Out (LOO). MVMR was eventually implemented as well. A Mendelian randomization analysis of the three exposure factors in the dataset (ieu-b-94, ebi-a-GCST012237) was also performed to validate the study results. According to the SVMR results, there was a noteworthy causal interaction between ORCA and MICB (P = 0.0014), MMP9 (P = 0.0343), and CTSA (P = 0.0003). Furthermore, odds ratios (ORs) values revealed that MMP9 (OR = 1.0005) was an ORCA risk factor, whereas MICB (OR = 0.9994) and CTSA (OR = 0.9993) were security factors. The robustness of the SVMR findings was confirmed by the p-values of the heterogeneity and horizontal pleiotropy, both of which were greater than 0.05. The MVMR result did not affect any of the safety or hazard features of these three exposure factors. However, the P value for MMP9 was greater than 0.05, implying that MICB and CTSA may have a greater influence on ORCA than MMP9. The validation outcomes in both datasets harmonized with the findings from previous research, thereby solidifying the reliability of results. Our investigation provided a crucial resource for further research on the subject by demonstrating a causal relationship between ORCA and MICB, CTSA, and MMP9., (© 2024. The Author(s).)

Background: The influence of the small Rho GTPase Rif (RHOF) on tumor growth, glycolysis, endothelial-mesenchymal transition (EMT), and the potential mechanism of RHOF in pancreatic cancer (PC) were explored., Methods: RHOF expression in PC tissues and cells was assessed by qRT-PCR and western blotting. The viability, proliferation, apoptosis, migration, and invasion of PC cells were assessed using CCK-8, colony formation, EdU, flow cytometry, scratch, and Transwell assays. The expression of EMT- and glycolysis-related proteins was determined using western blotting. The potential mechanisms of action of RHOF in PC were identified using bioinformatic analysis. The effects of RHOF were assessed in vivo using a xenograft mouse model., Results: PC cell proliferation, migration, and invasion are accelerated by RHOF overexpression, which inhibited apoptosis. RHOF overexpression promoted EMT and glycolysis as evidenced by a decrease in E-cadherin expression and an increase in N-cadherin, Vimentin, HK2, PKM2, and LDHA expression. Bioinformatic analysis indicated that RHOF activated EMT, glycolysis, and Myc targets and that c-Myc could bind to the PKM2 promoter. RHOF overexpression promotes the lactylation and nuclear translocation of Snail1. Silencing Snail1 reversed the promoting effects of RHOF and lactate on cell migration, invasion, and EMT. Moreover, in vivo tumor growth and EMT were inhibited by RHOF silencing., Conclusion: RHOF plays an oncogenic role in PC. c-Myc is upregulated by RHOF and promotes PKM2 transcription. PKM2 further induces glycolysis, and the lactate produced by glycolysis causes the lactylation of Snail1, ultimately promoting EMT., (© 2024. The Author(s).)

Objective: This study aims to explore the role of serum aquaporin 8 (AQP8) expression in evaluating the degree of hydrolabyrinth and predicting prognosis in patients with Meniere's disease., Methods: One hundred and five patients diagnosed with Meniere's disease in our hospital were enrolled in the Meniere's disease group. Another 102 healthy subjects were enrolled as the control group. The expression of serum AQP8 mRNA was determined by the quantitative real-time PCR (qRT-PCR) method. Receiver operating characteristic (ROC) curve analysis was carried out to analyse the predictive value of serum AQP8 mRNA expression for poor prognosis in Meniere's disease patients. Multivariate logistic regression was used to analyse the influencing factors of poor prognosis in patients with Meniere's disease., Results: The expression level of serum AQP8 mRNA in the Meniere's disease group was significantly higher than that in the control group (p < 0.05). In the severe hydrops group, serum AQP8 mRNA expression levels were higher than in the mild hydrops group and the no endolymphatic hydrops group. Additionally, the mild hydrops group had higher serum AQP8 mRNA levels than the no endolymphatic hydrops group (p < 0.05). The disease course, proportion of severe hydrops and serum AQP8 mRNA expression were all higher in the poor prognosis group compared to the good prognosis group (p < 0.05). The area under the curve (AUC) for serum AQP8 mRNA in predicting poor prognosis in Meniere's disease patients was 0.812 (95%CI: 0.702-0.922)., Conclusion: AQP8 mRNA is associated with the degree of hydrolabyrinth in patients with Meniere's disease and plays an important role in predicting prognosis., (© 2024 John Wiley & Sons Ltd.)

Nitrification is highly crucial for both anammox systems and the global nitrogen cycle. The discovery of complete ammonia oxidation (comammox) challenges the inherent concept of nitrification as a two-step process. Its wide distribution, adaptability to low substrate environments, low sludge production, and low greenhouse gas emissions may make it a promising new nitrogen removal treatment process. Meanwhile, anammox technology is considered the most suitable process for future wastewater treatment. The diverse metabolic capabilities and similar ecological niches of comammox bacteria and anammox bacteria are expected to achieve synergistic nitrogen removal within a single system. However, previous studies have overlooked the existence of comammox, and it is necessary to re-evaluate the conclusions drawn. This paper outlined the ecophysiological characteristics of comammox bacteria and summarized the environmental factors affecting their growth. Furthermore, it focused on the enrichment, regulatory strategies, and nitrogen removal mechanisms of comammox and anammox, with a comparative analysis of hydroxylamine, a particular intermediate product. Overall, this is the first critical overview of the conclusions drawn from the last few years of research on comammox-anammox, highlighting possible next steps for research., 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.)

Multi-omics studies of breast ductal carcinoma (BRDC) have advanced the understanding of the disease's biology and accelerated targeted therapies. However, the temporal order of a series of biological events in the progression of BRDC is still poorly understood. A comprehensive proteogenomic analysis of 224 samples from 168 patients with malignant and benign breast diseases is carried out. Proteogenomic analysis reveals the characteristics of linear multi-step progression of BRDC, such as tumor protein P53 (TP53) mutation-associated estrogen receptor 1 (ESR1) overexpression is involved in the transition from ductal hyperplasia (DH) to ductal carcinoma in situ (DCIS). 6q21 amplification-associated nuclear receptor subfamily 3 group C member 1 (NR3C1) overexpression helps DCIS&#95;Pure (pure DCIS, no histologic evidence of invasion) cells avoid immune destruction. The T-cell lymphoma invasion and metastasis 1, androgen receptor, and aldo-keto reductase family 1 member C1 (TIAM1-AR-AKR1C1) axis promotes cell invasion and migration in DCIS&#95;adjIDC (DCIS regions of invasive cancers). In addition, AKR1C1 is identified as a potential therapeutic target and demonstrated the inhibitory effect of aspirin and dydrogesterone as its inhibitors on tumor cells. The integrative multi-omics analysis helps to understand the progression of BRDC and provides an opportunity to treat BRDC in different stages., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Tetraspanins are key players in various physiological and pathological processes, including malignancy, immune response, fertilization, and infectious disease. Affinity ligands targeting the interactions between tetraspanins and partner proteins are promising for modulating downstream signaling pathways, thus emerging as attractive candidates for interfering related biological functions. Due to the involvement in vesicle biogenesis and cargo trafficking, tetraspanins are also regarded as exosome markers, and become molecular targets for drug loading and delivery. Given the rapid development in these areas, this minireview focuses on recent advances in design and engineering of affinity binders toward tetraspanins including CD63, CD81, and CD9. Their mechanism of actions in modulating protein interactions at cell interfaces and treatment of malignant diseases are discussed. Strategies for constructing exosome-based drug delivery platforms are also reviewed, with emphasis on the important roles of tetraspanins and the affinity ligands. Finally, challenges and future development of tetraspanin-targeting therapy and exosomal drug delivery platforms are also discussed., (© 2024 Wiley-VCH GmbH.)

In this study, we address the challenge of developing highly conductive hydrogels with enhanced stretchability for use in wearable sensors, which are critical for the precise detection of human motion and subtle physiological strains. Our novel approach utilizes amylopectin, a biopolymer, for the uniform integration of liquid metal gallium into the hydrogel matrix. This integration results in a conductive hydrogel characterized by remarkable elasticity (up to 7100 % extensibility) and superior electrical conductance (Gauge Factor = 31.4), coupled with a minimal detection limit of less than 0.1 % and exceptional durability over 5000 cycles. The hydrogel demonstrates significant antibacterial activity, inhibiting microbial growth in moist environments, thus enhancing its applicability in medical settings. Employing a synthesis process that involves ambient condition polymerization of acrylic acid, facilitated by a hydrophobic associative framework, this hydrogel stands out for its rapid gelation and robust mechanical properties. The potential applications of this hydrogel extend beyond wearable sensors, promising advancements in human-computer interaction through technologies like wireless actuation of robotic systems. This study not only introduces a viable material for current wearable technologies but also sets a foundation for future innovations in bio-compatible sensors and interactive devices., 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.)

The identification of waste composition based on target-detection is crucial in promoting sustainable solid waste management. However, discrimination of different solid waste categories in the presence of incomplete and insufficient feature information remains a challenge in multi-target detection. This paper proposes an improved You Only Look Once (YOLOX-S) model that enables the effective recognition of different waste components in complex environments, which enhances feature-information extraction ability regarding different dimensions by introducing a convolutional block attention module, an adaptive spatial feature fusion module, and an improved efficient intersection-over-union loss function. The improved model was trained on a self-constructed image dataset with multiple waste components and targets in various complex scenarios, including interference from similar color backgrounds, similar waste localization, and mutual waste occlusion. The experimental results showed that the improved model achieved a mean average precision (mAP) of 85.02 %, an increase of 5.32 % over the original YOLO model's mAP, and that it reduced incidents related to inaccurate positioning and false and missed detection. Moreover, the improved model outperformed classical detection models including support vector machine, RestNet-18, and RestNet-50 on a public dataset, achieving a mAP of 94.85 %. The improved model is expected to be applied to intelligent monitoring for waste components in scenarios including indiscriminate waste disposal and illegal dumping, providing decision support for emergency management., 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.)

Purpose: The infiltration of immune cells and their roles of the infiltrating-immune cells in gastrointestinal stromal tumor (GIST) is still unclear. We aimed to discover the infiltration cell types and the relationship between the infiltrating-immune cells and the progression of GIST., Experimental Design: Single-cell RNA sequencing were performed to discover types of the infiltrating-immune cells and to analyze CellChat between cells. Immunohistochemistry of 80 GIST samples were used to clarify the relation between macrophages and recurrence risk. In vitro , flow cytometry and Real-time PCR were performed to uncover a potential mechanism of tumor cell regulation of macrophages., Results: Tumor cells, macrophages, and T-cells were the predominant cell types. The MIF/CXCR4 axis was the most common ligand-receptor interaction between macrophages and tumor cells. As the risk increased, expression levels of CD68, CD206, MIF, and CXCR4 gradually increased. In vitro , we found that GIST882 was able to secrete MIF and GIST882 cell supernatant upregulated M2 polarization. Real-time PCR showed that expression levels of IL-10 mRNA and Arginase-1 mRNA were also the highest in the GIST882 cell supernatant group., Conclusions: These findings identify that macrophages are the most abundant infiltrating cells in GIST. The MIF/CXCR4 axis is the most common ligand-receptor interaction between macrophages and tumor cells. GIST cells can regulate macrophage M2 polarization through the MIF/CXCR4 axis., 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 Xiao, Xu, Yang, Zhao, Xie, Lei and Wu.)

Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Roux-en-Y gastric bypass (LRYGB) are the most common bariatric modalities. There is ongoing debate on the two modalities' long-term effects on weight loss and comorbidity resolution.PubMed, EMbase, and Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) comparing LRYGB versus LSG were searched by March 2024. Quality assessment was conducted by Assessing the Methodological Quality of Systematic Reviews (AMSTAR) guidelines, following the procedures outlined in the Cochrane Collaborations tool (RoB 2.0 Assessment Form).In total, 13 datasets were included from 10 RCTs that involved 1106 individuals. Both the percentage of excess weight loss (%EWL) and percentage of total weight loss (%TWL) were greater in LRYGB compared to LSG at 3 years (MD: 13.04, 95%CI: 6.95-19.13; P < 0.0001) and 1 year (MD: 5.97, 95%CI: 5.23-6.71; P < 0.00001), respectively. When comparing LRYGB to LSG, the remission percentage for type 2 diabetes mellitus was greater at one (RR: 0.15, 95%CI: 0.03-0.27; P = 0.02) and 3 years (RR: 0.17, 95 % CI: 0.07-0.28; P = 0.001). Moreover, early (RR: 1.72, 95%CI: 1.19-2.46; P = 0.003) and late (RR: 1.40, 95%CI: 1.15-1.71; P = 0.001) adverse events were more common with LRYGB. Regarding remission from obstructive sleep apnea syndrome, dyslipidemia, and hypertension, no significant changes were seen. LRYGB and LSG are both viable bariatric surgery options for resolving long-term comorbidities. While the rate of adverse events is greater with LRYGB than LSG, the former may provide more long-term sustainable weight reduction.Additional research of a higher quality is necessary., Competing Interests: Declarations 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 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

The treatment of infected pressure ulcers (IUPs) requires addressing diverse microenvironments. A pressing challenge is to effectively enhance the regenerative microenvironment at different stages of the healing process, tailoring interventions as needed. Here, a dual enzyme mimetic and bacterial responsive self-activating antimicrobial hydrogel designed to enhance IPUs healing is introduced. This hydrogel incorporates pH-responsive dual enzyme-active nanoplatforms (HNTs-Fe-Ag) encapsulated within a methacrylate-modified silk fibroin (SFMA) and dopamine methacrylamide (DMA) matrix. This composite hydrogel exhibits adaptive microenvironment regulation capabilities. Under the low pH microenvironment of bacterial infection, it has excellent antimicrobial activity by self-activating the •OH generation in conjunction with photothermal effects. Under the neutral and alkaline microenvironment of chronic inflammation, it catalyzes the decomposition of hydrogen peroxide (H 2 O 2 ) to produce oxygen (O 2 ), thereby alleviating hypoxia and scavenging reactive oxygen species (ROS), which in turn remodulates the phenotype of macrophages. The composite hydrogel demonstrates on-demand therapeutic effects in the microenvironment of infected wounds, significantly enhancing the regenerative microenvironment of IUPs by promoting wound closure, inflammation regulation, and collagen deposition through self-activated antimicrobial action during infection and adaptive hypoxia relief during recovery. This approach offers a novel strategy for developing smart wound dressings., (© 2024 Wiley‐VCH GmbH.)

Background: Allergic contact dermatitis (ACD) is a dermal inflammatory disease caused by allergic reactions to substances that contact the skin. The hyperactivation of T cells plays an important role in its pathogenesis. Photobiomodulation (PBM) is an efficacious therapeutic approach for suppressing inflammatory diseases., Objective: This study aimed to evaluate the potentially beneficial role of PBM in ACD models and investigate its possible mechanisms., Methods: In this study, the ACD model of C57BL/6 mice was produced and treated with PBM, and the number of T cells was evaluated. In an in vitro study, naïve T cells were isolated and intervened with PBM. The markers of T cell activation were detected by flow cytometer. Transforming growth factor-β (TGF-β) and reactive oxygen species (ROS) were detected to investigate the mechanism., Results: PBM effectively inhibited the inflammatory response by impeding the number of T cells in the ACD model. And in vitro studies showed that PBM could directly moderate the activation of naïve T cells and possess the capability to impede T cell activation via TGF-beta signaling pathway., Conclusion: Our finding elucidates the potential mechanism underlying the inhibitory effects of PBM in inflammatory diseases and furnishes a theoretical foundation for its clinical application., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Obesity is a significant risk factor for the progression of non-alcoholic fatty liver disease (NAFLD). However, a convenient and efficacious non-invasive test for monitoring NAFLD progression in patients with obesity is currently lacking. This study aims to investigate the associations between CT-based body composition and the progression of biopsy-proven NAFLD in patients with obesity., Methods: Liver biopsy was conducted in patients with obesity, and the progression of NAFLD was evaluated by the NAFLD activity score (NAS). Body composition was assessed through abdominal computed tomography (CT) scans., Results: A total of 602 patients with an average age of 31.65 (±9.33) years old were included, comprising 217 male patients and 385 female patients. The wall skeletal muscle index (SMI), total SMI, and visceral fat index (VFI) were positively correlated with NAS in both male and female patients. Multivariate regression analysis demonstrated significant associations between high liver steatosis and wall SMI (HR: 1.60, 95% CI: 1.12 to 2.30), total SMI (HR: 1.50, 95% CI: 1.02 to 2.08), VSI (HR: 2.16, 95% CI: 1.48 to 3.14), visceral fat to muscle ratio (HR: 1.51, 95% CI: 1.05 to 2.18), and visceral to subcutaneous fat ratio (HR: 1.51, 95% CI: 1.07 to 2.12). Non-alcoholic steatohepatitis (NASH) was significantly associated with wall SMI (HR: 1.52, 95% CI: 1.06 to 2.19) and VSI (HR: 1.50, 95% CI: 1.03 to 2.17). Liver fibrosis ≥ F2 was significantly associated with psoas muscle index (HR: 0.64, 95% CI: 0.44 to 0.93) and psoas skeletal muscle density (HR: 0.61, 95% CI: 0.41 to 0.89)., Conclusions: Our study suggested that certain CT-based body composition indicators, notably high VFI, were significantly associated with the progression of NAFLD in patients with obesity. Great attentions and timely managements should be given to these patients with body composition characteristics associated with the risk of NAFLD progression., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

As some of the richest sources of natural antioxidants, small berry fruits have attractive colors and special tastes, with recognized benefits for human health. However, sour tastes in small berry juices result in a poor flavor and low acceptance among consumers, greatly limiting their marketability. Among the most commonly used deacidification methods, chemical deacidification methods can neutralize fruit juice via the addition of a deacidification agent, while physical deacidification methods include freezing deacidification, ion-exchange resin deacidification, electrodialysis deacidification, and chitosan deacidification. All of these methods can markedly improve the pH of fruit juice, but they introduce new substances into the juice that may have an influence on its color, taste, and stability. Biological deacidification can effectively remove malic acid from fruit juice, reducing the content from 15 g/L to 3 g/L; additionally, it maintains the taste and stability of the juice. Therefore, it is widely applied for fruit juice deacidification. On this basis, some compound deacidification technologies have also emerged, but they also present problems such as high costs and complicated working procedures. This review of deacidification methods for small berry juice provides a foundation for the industrial development of such juices.

To explore the characteristics of phytoplankton communities and their relationship with environmental factors in different habitats of Hedi Reservoir, the inflow rivers, estuaries, and reservoir area of Hedi Reservoir were investigated in February （recession period）, April （flood period）, July （flood period）, and December （recession period） of 2022. During the investigation, 231 species of phytoplankton that belong to seven phyla were identified, and the cell density of phytoplankton ranged from 2.94 × 10 6 - 8.04 × 10 8 cells·L -1 . Phytoplankton cell density in flood periods were higher than that in recession periods, and that was higher in estuaries and the reservoir area than that in inflow rivers. Meanwhile, the cell density of phytoplankton in the estuarine and reservoir area was dominated by Cyanobacteria throughout the year, especially Raphidiopsis raciborskii , whereas the cell density of phytoplankton in inflow rivers was dominated by Cyanophyta, Chlorophyta, and Bacillariophyta. In the inflow river area, the dominant species of cyanobacteria were Microcystis aeruginosa , Limnothrix redekei , Pseudanabaena circinalis, and Merismopedia punctata ； the dominant species of Chlorophyta were Chlorella vulgaris and Crucigenia tetrapedia ； and the dominant species of Bacillariophyta were Chlorella vulgaris and Melosira granulate . The highest biodiversity （Shannon-Wiener Index, Pielou index, and Margalef index） were observed in the inflow river area of Hedi Reservoir. The correlation analysis （Pearson） indicated that the environmental factors that were significantly correlated to phytoplankton communities included water temperature, dissolved oxygen, pH, conductivity, nitrogen, and phosphorus concentration. The RDA analysis indicated that phytoplankton communities in the inflow river area were mainly affected by pH and total nitrogen concentration, which were majorly affected by water temperature and pH in the estuarine area and chiefly affected by turbidity and pH in the reservoir. The pH affected the changes in phytoplankton communities in all three different habitats, whereas the inflow river area was significantly affected by total nitrogen concentration, and the estuarine and reservoir were significantly affected by water temperature and turbidity, respectively.

Lead-free dielectric ceramics exhibiting excellent energy storage capacity, long service life, and good safety have been considered to have immense prospects in next-generation pulsed power capacitors. However, it is still challenging to simultaneously achieve large recoverable energy density ( W rec ), high efficiency (η), and excellent charge-discharge performance. Herein, we fabricated lead-free (1 - x )(Bi 0.5 Na 0.5 )TiO 3 - x (Sr 0.7 Bi 0.1 La 0.1 )TiO 3 ((1 - x )BNT- x SBLT) dielectric ceramics, and a good balance between W rec ∼ 4.15 J/cm 3 and η ∼ 93.89% under 333 kV/cm, as well as superior charge-discharge properties (power density P D ∼ 185.42 MW/cm 3 , discharge energy density W d ∼ 2.2 J/cm 3 , and discharge time t 0.9 ∼ 53.8 ns under 250 kV/cm), was achieved in 0.6BNT-0.4SBLT ceramics. The good energy storage performance can be attributed to the synergistic contributions of significantly enhanced E b caused by grain refinement and the large Δ P values induced by polar nanoregions (PNRs) under a high external electric field. Moreover, the 0.6BNT-0.4SBLT ceramics also present excellent temperature stability of energy storage properties (the variations of W rec and η less than 0.45% and 0.14%, respectively) over a temperature range of 25-185 °C. These figures of merit make 0.6BNT-0.4SBLT ceramics the most promising candidate for energy storage capacitors in advanced pulse power systems.

Spodoptera frugiperda is a notorious pest that develops a high resistance to many insecticides. Recently, insect odorant-binding proteins (OBPs) have been proven to participate in insecticide resistance. However, the functional evidence supporting the cross-link between OBPs and insecticide resistance remains unexplored. Here, we identified 50 SfruOBPs from the larval transcriptome and genome. Notably, SfruOBP18 was highly expressed in the larval cuticle and could be induced to upregulate its expression by multi-insecticides. Ligand-binding assays revealed that SfruOBP18 bound strongly with four insecticides; RNAi and insecticide bioassay demonstrated that the knockdown of SfruOBP18 did not affect larval survival and development. However, it can significantly increase the larval susceptibility to multi-insecticides, suggesting an uncommon role of SfruOBP18 in multi-insecticide susceptibility. Our study provides a comprehensive understanding of SfruOBPs and furthermore proves that a larval cuticle-enriched OBP can bind with and confer larval tolerance to multi-insecticides. SfruOBP18 could be a new insecticidal target for controlling Lepidoptera pests.

Diesel exhaust (DE) is a major contributor to air pollution. Iron-doping could improve diesel burning efficacy and decrease emission, however, it will also change the composition of DE, potentially enhancing the toxicities. This study is aimed to assess iron-doped DE-induced cardiopulmonary toxicity in an established in ovo early-in-life inhalation exposure chicken embryo model, and to explore potential mechanisms. Ferrocene (205, 410, 820,1640 mg/L, equivalent to 75, 150, 300, 600 ppm iron mass) was added to diesel fuel, DE was collected from a diesel generator, and then exposed to embryonic day 18-19 chicken embryo via in ovo inhalation. Hatched chickens were kept for 0, 1, or 3 months, and then sacrificed. Histopathology, electrocardiography along with biochemical methods were used to assess cardiopulmonary toxicities. For mechanistic investigation, inhibitor for ferroptosis (ferrostatin-1) or Acyl hydrocarbon receptor (PDM2) were administered before DE (with or without iron-doping), and the cardiopulmonary toxicities were compared. Characterization of DE particles indicated that addition of ferrocene significantly elevated iron content. Additionally, the contents of major toxic polycyclic aromatic hydrocarbons decreased following addition of 820 mg/L ferrocene, but increased at other doses. Remarkable cardiopulmonary toxicities, in the manifestation of elevated heart rates, cardiac remodeling and cardiac/pulmonary fibrosis were observed in animals exposed to iron-doped DEs, in which the addition of ferrocene significantly enhanced the toxicities. Both ferrostatin-1 and PDM2 pretreatment could effectively alleviate the observed effects in animals exposed to iron-doped DE. Inhibition of AhR signaling seems to be capable of alleviating changes to ferroptosis related molecules following exposure to iron-doped DE, while inhibition of ferroptosis does not seem to affect AhR signaling molecules. In summary, iron-doping with ferrocene to diesel enhanced DE-induced cardiopulmonary toxicities in chicken embryos. Ferroptosis and AhR signaling both seem to participate in this process, in which AhR signaling seems to affect ferroptosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Qixiao Jiang reports financial support was provided by National Natural Science Foundation of China. Junhua Yuan reports financial support was provided by National Natural Science Foundation of China. Yuxu Zhong reports financial support was provided by Logistics Scientific Research Plan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Constructing a demand-oriented Internet + community home care service indicator system, starting from the actual needs of the elderly, and quantifying the demand into specific service contents that can be provided, so as to realize the effective supply of services. It aims to provide a theoretical basis for the government to formulate relevant aging policies and provide a reference basis for promoting the innovation and development of the Internet + elderly care model., Methods: Based on existence needs, relationship needs and growth needs abbreviated as "Existence, Relatedness, Growth (ERG)" demand theory, through the discussion in the group meeting, form the expert consultation questionnaire of the demand-oriented Internet + community home care service indicator system, select experts in related fields to conduct two rounds of Delphi expert consultation, summarize the experts' opinions to determine the indicator system items, and use the Analytic Hierarchy Process (AHP) method to construct the judgment matrix to derive the weighting coefficients of the indicators, and establish the ultimate demand-oriented Internet + community home care service indicator system., Results: The effective recovery rates for the two rounds of expert consoulation questionnaires were 100%, with expert authority coefficients of 0.852 and 0.868, respectively. The Kendall coefficients for the second round of expert views varied from 0.226 to 0.431, with coefficients of variation for all indexes less than 0.25.The finalized demand-oriented Internet + community home care service indicator system includes 3 first-level indicators, 10 s-level indicators, and 46 third-level indicators. The consistency ratios of indicator judgment matrices at all levels are less than 0.10, suggesting that the hierarchical analysis findings are consistent, implying that the weight coefficient distribution is appropriate., Conclusion: The demand-oriented Internet + community home care service Indicator System, which was created through expert consultation and AHP method, has reasonable content and is more dependable as an evaluation tool for reliably assessing demand for elderly servic., (© 2024. The Author(s).)

Background: In clinical practice, the incidence of hypofibrinogenemia (HF) after tigecycline (TGC) treatment significantly exceeds the probability claimed by drug manufacturers., Objective: We aimed to identify the risk factors for TGC-associated HF and develop prediction and survival models for TGC-associated HF and the timing of TGC-associated HF., Methods: This single-center retrospective cohort study included 222 patients who were prescribed TGC. First, we used binary logistic regression to screen the independent factors influencing TGC-associated HF, which were used as predictors to train the extreme gradient boosting (XGBoost) model. Receiver operating characteristic curve (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were used to evaluate the performance of the model in the verification cohort. Subsequently, we conducted survival analysis using the random survival forest (RSF) algorithm. A consistency index (C-index) was used to evaluate the accuracy of the RSF model in the verification cohort., Results: Binary logistic regression identified nine independent factors influencing TGC-associated HF, and the XGBoost model was constructed using these nine predictors. The ROC and calibration curves showed that the model had good discrimination (areas under the ROC curves (AUC) = 0.792 [95% confidence interval (CI), 0.668-0.915]) and calibration ability. In addition, DCA and CICA demonstrated good clinical practicability of this model. Notably, the RSF model showed good accuracy (C-index = 0.746 [95%CI, 0.652-0.820]) in the verification cohort. Stratifying patients treated with TGC based on the RSF model revealed a statistically significant difference in the mean survival time between the low- and high-risk groups., Conclusions: The XGBoost model effectively predicts the risk of TGC-associated HF, whereas the RSF model has advantages in risk stratification. These two models have significant clinical practical value, with the potential to reduce the risk of TGC therapy., (© 2024. The Author(s).)

The electrochemical reduction of nitrate to ammonia (NO 3 RR) provides a desired alternative of the traditional Haber-Bosch route for ammonia production, igniting a research boom in the development of electrocatalysts with high activity. Among them, molecular electrocatalysts hold considerable promise for the NO 3 RR, suppressing the competing hydrogen evolution reaction. However, the complicated synthesis procedure, usage of environmentally unfriendly organic solvents, and poor stability of Cu-based molecular electrocatalysts greatly limit their employment in NO 3 RR, and the development of desired Cu-based molecular catalysts remains challenging. Herein, a simple nonorganic solvent involving a one-step strategy was proposed to synthesize d-π-conjugated molecular electrocatalysts metal-amidinothiourea (M-ATU). Cu-ATU is composed of Cu coordinated with two S and two N atoms, whereas Ni-ATU is formed by Ni with four N atoms from two ATU ligands. Remarkably, Cu-ATU with a Cu-N 2 S 2 coordination configuration exhibits superior NO 3 RR activity with a NH 3 yield rate of 159.8 mg h -1 mg cat -1 (-1.54 V) and Faradaic efficiency of 91.7% (-1.34 V), outperforming previously reported molecular catalysts. Compared to Ni-ATU, Cu-ATU transfers more electrons to the *NO intermediate, effectively breaking the strong sp 2 hybridization system and weakening the energy of N═O bonds. The increase in free energy of *NO reduced the energy barriers of the rate-determining step, facilitating the further hydrogenation process over Cu-ATU. Our work opened up a new horizon for exploring molecular electrocatalysts for nitrate activation and paved a way for the in-depth understanding of catalytic behaviors, aligning more closely with industrial demands.

Arachnoid cysts (ACs) are frequently encountered as incidental findings in the brain, with most cases being asymptomatic and not requiring intervention. However, severe brain malformations caused by ACs are rare. In this study, we describe the case of an 8-day-old female infant with a left mandibular mass that was diagnosed as an insular operculum, which has become disconnected and herniated into the parapharyngeal space through an incompletely ossified greater wing of the sphenoid, caused by a fetal Galassi Type III AC. The newborn also exhibited left hearing impairment, which did not improve at the 6-month follow-up after the cyst peritoneal shunt. This report highlights that ACs that manifest during the early fetal period may protrude from the cranial cavity through an unossified skull, potentially affecting the development of brain tissues., 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, Zhang, Yang, Ji, Zhao and Gu.)

Favourable outcomes with CPX-351 versus conventional 7 + 3 were demonstrated in the pivotal phase III trial in adults aged 60-75 years with newly diagnosed, highrisk/secondary acute myeloid leukaemia (AML). As a complement to the clinical trial and to address important data gaps, the CPX-351 Real-World Effectiveness and SafeTy (CREST-UK; NCT05169307) study evaluated the use of CPX-351 in routine clinical practice in the UK, in 147 patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Best response of complete remission or complete remission with incomplete platelet or neutrophil recovery was achieved by 53% of evaluable patients. Kaplan-Meier median overall survival (OS) was 12.8 months (95% confidence interval 9.2-15.3). Fifty (34%) patients proceeded to haematopoietic cell transplantation (HCT); median OS landmarked from the HCT date was not reached. There were no new safety concerns with CPX-351 identified in CREST-UK. Patients treated with CPX-351 in the outpatient setting spent an average of 24.4, 16.7, 28.2, and 27.7 fewer days on the ward compared with inpatients during first induction, second induction, first consolidation, and second consolidation, respectively. The results from CREST-UK provide valuable insights into the effectiveness, safety, and outpatient delivery of CPX-351 in routine clinical practice in the UK., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: Differentiating pulmonary lymphoma from lung infections using CT images is challenging. Existing deep neural network-based lung CT classification models rely on 2D slices, lacking comprehensive information and requiring manual selection. 3D models that involve chunking compromise image information and struggle with parameter reduction, limiting performance. These limitations must be addressed to improve accuracy and practicality., Methods: We propose a transformer sequential feature encoding structure to integrate multi-level information from complete CT images, inspired by the clinical practice of using a sequence of cross-sectional slices for diagnosis. We incorporate position encoding and cross-level long-range information fusion modules into the feature extraction CNN network for cross-sectional slices, ensuring high-precision feature extraction., Results: We conducted comprehensive experiments on a dataset of 124 patients, with respective sizes of 64, 20 and 40 for training, validation and testing. The results of ablation experiments and comparative experiments demonstrated the effectiveness of our approach. Our method outperforms existing state-of-the-art methods in the 3D CT image classification problem of distinguishing between lung infections and pulmonary lymphoma, achieving an accuracy of 0.875, AUC of 0.953 and F1 score of 0.889., Conclusion: The experiments verified that our proposed position-enhanced transformer-based sequential feature encoding model is capable of effectively performing high-precision feature extraction and contextual feature fusion in the lungs. It enhances the ability of a standalone CNN network or transformer to extract features, thereby improving the classification performance. The source code is accessible at https://github.com/imchuyu/PTSFE ., (© 2024. CARS.)

Fibrosis is a pathological change mainly characterized by an increase of fibrous connective tissue and decrease of parenchymal cells. Its continuous progress may lead to the destruction of organ structure and function decline. An excess of alternatively activated M2 macrophages have been considered crucial candidates in the progression of fibrosis. Bone morphogenetic proteins (BMPs), a group of multifunctional growth factors, are essential for organ development and pathophysiological process, however, the roles that BMPs play in innate immune homeostasis in the development of fibrosis and the downstream signals have not been fully explored. In the current study, we firstly found that the expression of BMP4 was significantly down-regulated in human and mouse fibrosis samples. Then we investigated the effects of BMP4 on macrophage polarization in IL-4 environment and related molecular mechanisms, and found that BMP4 caused a decrease in polarized response towards M2, reflected in the expression of the markers Fizz1, Ym1 and Arg1, together with an inhibition in Stat6 phosphorylation. This relied on the Smad1/5/8 signaling, which had a crosstalk with Stat6. Moreover, the in vivo study showed that BMP4 treatment can reduce collagen deposition and delay the development of experimental pulmonary fibrosis in mice by inhibiting M2 macrophages through adoptive transfer experiment. These findings revealed a novel role of BMP4 in regulating macrophages, offering potential strategies for treating pulmonary fibrosis., 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.)

As a recurrent climatic phenomenon in the context of climate change, extreme rainstorms induce vertical translocation of organic matter and increase moisture content in terrestrial ecosystems. However, it remains unclear whether heavy rainstorms can impact microbial communities in the deep biosphere by modulating organic matter input. In this study, we present findings on the different responses of bacterial and fungal communities in a subsurface cave to rainstorms and moisture variations through field surveys and microcosm experiments. During periods of rainstorms, the influx of dissolved organic matter (DOM) from soil overlying the cave into cave sediments significantly enhanced the correlation between core bacteria and environmental factors, particularly fluorescence spectral indices. The resource utilization of core bacteria was diminished, while the functional diversity of core fungi remained relatively unaltered. We also performed simulated experiments with restricted external DOM inputs, in which DOM content was observed to decrease and microbial diversity increase in response to artificially increased moisture content (MC). The niche breadth of core bacteria decreased and became more closely associated with DOM as the MC increased, while the niche breadth of core fungi remained predominantly unchanged. Compared to fungi, cave bacteria exhibited higher sensitivity towards variations in DOM. The core microbiome can efficiently utilize the available organic matter and participate in nitrogen- and sulfur-related metabolic processes. The study systematically revealed distinct microbial responses to rainstorm events, thereby providing valuable insights for future investigations into energy utilization within deep biospheres., 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.)

Uninterrupted breakthroughs in the room temperature piezoelectric properties of KNN-based piezoceramics have been witnessed over the past two decades; however, poor temperature stability presents a major challenge for KNN-based piezoelectric ceramics in their effort to replace their lead-based counterparts. Herein, to enhance temperature stability in KNN-based ceramics while preserving the high piezoelectric response, multilayer composite ceramics were fabricated using textured thick films with distinct polymorphic phase transition temperatures. The results demonstrated that the composite ceramics exhibited both outstanding piezoelectric performance (d 33 ~467 ± 16 pC/N; S~0.17% at 40 kV/cm) and excellent temperature stability with d 33 and strain variations of 9.1% and 2.9%, respectively, over a broad temperature range of 25-180 °C. This superior piezoelectric temperature stability is attributed to the inter-inhibitive piezoelectric fluctuations between the component layers, the diffused phase transition, and the stable phase structure with a rising temperature, as well as the permanent contribution of crystal orientation to piezoelectric performance over the studied temperature range. This novel strategy, which addresses the piezoelectric and strain temperature sensitivity while maintaining high performance, is well-positioned to advance the commercial application of KNN-based lead-free piezoelectric ceramics.

Background: Regulated cell death (RCD) has considerable impact on tumor progress and sensitivity of treatment. Lung adenocarcinoma (LUAD) show a high resistance for conventional radiotherapies and chemotherapies. Currently, regulation of cancer cell death has been emerging as a new promising therapeutic avenue for LUAD patients. However, the crosstalk in each pattern RCD is unclear., Methods: We integrated collected the hub-genes of 12 RCD subroutines and compressively analyzed these hub-genes synergistic effect in LUAD. The characters of RCD genes expression and prognosis were developed in The Cancer Genome Atlas (TCGA)-LUAD data. We developed and validated an RCD risk model based on TCGA and GSE70294 data set, respectively. Functional annotation and tumor immunotherapy based on the risk model were also investigated., Results: 28 RCD-related genes and two LUAD molecular cluster were identified. Survival analysis revealed that the prognosis in high-risk group was worser than those in low-risk group. Functional enrichment analysis indicated that the RCD risk model correlated with immune responses. Further analysis indicated that the high-risk group in RCD risk model exhibited an immunosuppressive microenvironment and a lowly immunotherapy responder ratio., Conclusions: We present an RCD risk model which have a promising ability in predicting LUAD prognosis and immunotherapy response., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)