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Heparin is the most widely used anticoagulant in clinical practice, with enoxaparin being one of the most important low molecular weight heparins (LMWHs). In this study, an antithrombin III (ATIII) affinity column was used. Enoxaparin and its oligosaccharides of varying sizes, prepared using preparative size exclusion chromatography (SEC), were fractionated through the ATIII affinity column. The different affinity fractions from each oligosaccharide size were profiled using strong anion exchange (SAX) chromatography. Each peak was automatically transferred to an SEC column for desalting prior to mass spectrometry (MS) analysis, which enabled structural identification using a multiple heart-cut (MHC) 2D LC-MS system (SAX-SEC-MS). The high-affinity fraction from enoxaparin was further analyzed using the MHC 2D LC system (SEC-SAX). SAX profiles of the high-affinity oligosaccharides, prepared by both size and affinity fractionation, were consistent with those obtained by direct SEC-SAX analysis. The possible sequences of several high-affinity hexasaccharides and the domain compositions of high-affinity octa- and decasaccharides in enoxaparin were further elucidated by disaccharide analysis after manual collection of the oligosaccharides. This work advances the understanding of enoxaparin's structural features and offers a potential approach to improve the quality of enoxaparin, as well as to identify key structural motifs in heparin/LMWHs that contribute to protein binding., Competing Interests: Declaration of competing interest There is no conflict of interest for authors of this manuscript., (Copyright © 2024. Published by Elsevier B.V.)

CeO 2 nanomaterials expose various crystal facets with distinct surface geometry, resulting in different surface reactivities and material behaviors that ultimately determine their performances and suitability for a wide range of applications. Here, we apply 17 O solid-state nuclear magnetic resonance (NMR) to follow the facet transformation of CeO 2 at increased temperatures, observing a transition from (100) to (110) and finally to the more stable (111), based on the characteristic NMR shifts associated with the unique surface structure of each facet. In addition, we explore the effects of Pt ions on the conversion of different facets, which are found to promote the formation of the thermally stable (111) facet. Furthermore, 17 O solid-state NMR provides a semiquantitative method for measuring the fractions of exposed facets. This work offers new insights and a more comprehensive understanding of crystal facet structures, and the new approach can be readily extended to study the facets of other oxide-based materials.

Green indium phosphide (InP)-based quantum dot light-emitting diodes (QD-LEDs) still suffer from low efficiency and short operational lifetime, posing a critical challenge to fully cadmium-free QD-LED displays and lighting 1-3 . Unfortunately, the factors that underlie these limitations remain unclear and, therefore, no clear device-engineering guidelines are available. Here, by using electrically excited transient absorption spectroscopy, we find that the low efficiency of state-of-the-art green cadmium-free QD-LEDs (which ubiquitously adopt the InP-ZnSeS-ZnS core-shell-shell structure) originates from the ZnSeS interlayer because it imposes a high injection barrier that limits the electron concentration and trap saturation. We demonstrate, both experimentally and theoretically, that replacing the currently widely used ZnSeS interlayer with a thickened ZnSe interlayer enables improved electron injection and depressed leakage simultaneously, allowing to achieve a peak external quantum efficiency of 26.68% and T 95 lifetime (time for the luminance to drop to 95% of the initial value) of 1,241 h at an initial brightness of 1,000 cd m -2 in green InP-based QD-LEDs emitting at 543 nm-exceeding the previous best values by a factor of 1.6 and 165, respectively 3,4 ., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Mitochondria play a pivotal role in maintaining normal physiological functions. Mitochondrial autophagy, namely, mitophagy, is a selective catabolic disposal of impaired mitochondria through an autophagic mechanism during episodes of mitochondrial harm. This selective removal, e.g., mitophagy, is essential for mitochondrial quality control and is closely related to the pathogenesis of many diseases. The abnormal buildup of defective mitochondria in vivo was used as a target to prevent the development of cancer. The mitochondrial autophagy process of disease-related cells is usually accompanied by a decrease in polarity and pH, and the fluorescence sensing effects caused by these two factors are usually contradictory. Here, we propose a reinventing strategy to develop a dual-channel and dual-responsive fluorescent probe HDTVB that is capable of tracking mitochondrial autophagy by monitoring fluctuations in mitochondrial pH and polarity. Based on the aggregation-induced emission (AIE) moiety and hemicarpine moiety push-pull system with activated near-infrared (NIR) emission and pH-activatable cyclization reaction, HDTVB was able to differentiate tumors from normal sites via polarity- and acidity-triggered structural changes of the probe in the course of mitochondrial autophagy. HDTVB is expected to be applied to clinical diagnosis and tumor excision guided by fluorescence, offering a new route in physiological and biochemical research.

Background: Efforts to build and foster adult social care research in England have historically encountered more challenges to its growth and expansion compared with health research, with a sector facing significant barriers in facilitating research activity due to a lack of resourcing, poor valuation or understanding of the profile of social care research. The landscape for supporting the social care workforce to use, engage in and undertake research in adult social care has been rather bleak, but in recent years there has been recognition of the need to foster a social care workforce research community. The National Institute for Health and Care Research in England have committed to investing in social care research capacity by funding six adult social care partnerships, with one based in Southeast England. Setting up Communities of Practice (COPs) offers a model to build a shared learning space to foster a social care research community. Process developing COPs: Three online networking events were held in the first year of the project to engage managers and practitioners from the local authority and from the wider adult social care sector, taking place in July and November 2021, and March 2022. Two COPs were identified, following an ordering and thematising process of feedback from the networking events, of: (a) Supporting people with complex needs throughout the lifespan, and (b) Enhancing, diversifying and sustaining the social care workforce. Whilst it would be premature to identify their long-term impacts, the COPs have provided a space for regular communication, knowledge sharing and networking between members., Conclusions: The COP framework offers a collaborative approach to initiating research from the grass-roots level in adult social care. This paper focuses on how the COP model offers great promise for knowledge-exchange providing a forum to generate and disseminate knowledge around social care in two COP domains., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Hashem F et al.)

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency condition caused by ablation of functional WAS protein (WASP) expression, and associated with susceptibility to infections, eczema, and autoimmunity. Regulatory T cell (Treg) defects are an important cause of autoimmunity in WAS. Currently, the mechanisms underlying cytoskeleton involvement in Treg-regulated autoimmunity remain unclear, and WAS is an excellent model for investigation of this question. Here, we examined patients with WAS and WASP knockout (WASp -/- ) mice to uncover a new mechanism involving the actin nucleation promoting factor, WASP, in regulating Treg tolerance by modulating their surface IL-2 receptor (IL-2R) levels. Surface expression levels of IL-2R and its downstream signaling molecules, phosphoinositide 3-kinase/pSTAT5, are decreased in WASp -/- Tregs. Low dosage IL-2 combined with anti-IL-2 monoclonal antibody (IL2 complex) treatment can compensate for Treg deficiency in WAS in vitro and in vivo. Moreover, IL2 complex treatment relieved autoimmune colitis in WASp -/- mice. Reduced surface IL-2R is primarily caused by elevated IL-2R internalization and degradation, and lysosomal and endosomal genes associated with these processes are upregulated in WASp -/- Tregs. Finally, spatiotemporal analysis of dynamin and Neural Wiskott Aldrich Syndrome Protein (N-WASP) recruitment, by generating lipid bilayers and total internal reflection fluorescence microscopy, showed that WASP deficiency promoted IL-2R internalization and degradation by enhancing N-WASP activation. Consistently, N-WASP inhibition in Tregs using wiskostatin reduced IL-2R internalization. Together, our results reveal a novel intrinsic role of WASP in regulation of surface IL-2R dynamics in Tregs, highlighting a potential new therapeutic approach for autoimmune diseases., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

The development of thermoelectric devices provides an ideal solution for self-sustaining Internet of Things (IoT) applications. However, existing thermoelectric devices face issues such as low integration levels and poor stability. To address these challenges, this paper presents a novel method for fabricating flexible thermoelectric devices using Ag 2 Se/MgAgSb, which combines MEMS lithographic lift-off techniques to achieve precise control over the dimensions of the thermoelectric functional layer while also reducing fabrication costs. The optimal cell dimensions were identified through simulations. The device achieved an open circuit voltage of 0.49 mV at a temperature difference of 50 K. Additionally, the output power density of the Ag₂Se/MgAgSb flexible Y-type thermoelectric device reached 3.39 µW/m² at a temperature difference of 5 K. The device also demonstrated excellent flexibility; even after being bent 800 times around a glass rod with a diameter of 4 mm, its conductivity decreased by only 12%. Furthermore, it maintained stability under high humidity conditions. This work offers a novel strategy for the miniaturization and large-area controllable fabrication of flexible and reliable thermoelectric devices, as well as an enhancement in their reliability., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Enterovirus-A71 (EV-A71) is the second most common causative agent after coxsackievirus A16 of hand, foot, and mouth disease. The capsids of EV-A71 consist of 60 copies of each of the four viral structural proteins (VP1-VP4). VP1 is highly exposed and surface accessible, playing a central role in virus particle assembly, attachment, and entry. To gain insight into the role of highly conserved residues at positions 75, 78, and 88 in the capsid protein VP1 in these processes, an alanine-scanning analysis was performed using an infectious cDNA clone of EV-A71. Our study revealed that the substitutions of VP1-T75A, VP1-T78A, and VP1-G88A could affect the assembly of the virus capsid proteins, resulting in the production of abnormal virions with reduced infectivity. Specifically, the substitution of VP1-T75A affected the maturation cleavage of the VP0 precursor, leading to deficiencies in binding to receptor scavenger receptor class B2 (SCARB2), viral attachment, internalization, and even uncoating. For the mutants of T78A and G88A, a significant reduction in virion-associated genomic RNA was observed, suggesting that more noninfectious empty particles were produced during viral assembly. Interestingly, the VP1-T75A variant showed weak replication in cell cultures but demonstrated increased virulence in BALB/c neonatal mice, which might be due to the difference in viral receptors among mammalian species. Taken together, our data revealed the important role of the highly conserved residues T75, T78, and G88 in VP1 protein in the infectivity of EV-A71. Characterizing these novel determinants of EV-A71 virulence would contribute to rationally developing effective treatments and broadly protective vaccine candidates., Importance: EV-A71 causes hand, foot, and mouth disease in children. In this study, we discovered three highly conserved residues at positions 75, 78, and 88 of the capsid protein VP1 as the potential virulence determinants of EV-A71, which can influence viral replication by regulating the assembly of EV-A71. Mechanistic studies revealed that VP1-T75A could affect the maturation cleavage of the VP0 precursor, resulting in deficiencies in binding to the receptor SCARB2, viral attachment, internalization, and even uncoating. For the mutants of T78A and G88A, more noninfectious empty particles were produced during viral assembly. The discovery of these novel determinants of EV-A71 virulence will promote the study of the pathogenesis of enteroviruses.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions and severe itching. However, its pathogenesis has not yet been fully elucidated. The aim of this study was to investigate the causal relationship between plasma proteins and AD, as well as to identify and quantify the potential roles of immune cell phenotypes as mediators., Methods: We utilized summary-level data from genome-wide association studies and conducted a two-sample Mendelian randomization (MR) analysis involving 4907 circulating plasma proteins, 731 immune cell phenotypes, and AD. Initially, we conducted bidirectional univariate MR analyses to forecast causal effects linking circulating plasma proteins and AD. Subsequently, we employed a two-step MR analysis to scrutinize the immune cell phenotypes that could mediate these effects. The inverse variance weighted was the main method employed for MR analysis, while the Cochran's Q test and MR-Egger intercept test were used to assess the presence of heterogeneity and pleiotropy, respectively. We then determined whether our results could be influenced by individual single-nucleotide polymorphisms using the "leave-one-out" test., Results: Positive correlations were observed between KRT1, IL18R1, and SEMA6A and the risk of AD, whereas BDH2, ADAMTS3, ANKRD1, TIAM1, MID2, and IFNA16 all showed negative correlations with the risk of AD. Mediation analysis indicated that CD8 on CM CD8br cells acted as a mediator between IFNA16 and AD, with a mediation effect proportion of 11.2%. In addition, sensitivity analyses did not reveal significant heterogeneity or level pleiotropy., Conclusion: Our findings indicated the presence of a one-way causal relationship between the circulating plasma protein IFNA16 and AD. This study also explored immune cell phenotypes that may serve as mediators, offering novel insights into the etiology, pathogenesis, and potential clinical interventions in AD. Nevertheless, these findings need to be validated by clinical and laboratory studies., (S. Karger AG, Basel.)

Background: While Parkinsonism plus syndrome (PPS) is one of several atypical manifestations in neurosyphilis patients, its clinical features and brain-related manifestations are inadequately documented. In this cross-sectional study, we endeavored to indicate some key clinical and imaging features of neurosyphilis patients, particularly those specific to PPS., Methods: We retrospectively included all syphilis patients enrolled in the study from January 2021 to February 2024. All in all, 54 neurosyphilis patients with PPS were recruited. Their socio-demographical features, clinical status, presentations, laboratory manifestations and neuroimaging were analyzed retrospectively., Results: The predominant phenotype was general paresis (GP). Median age at onset was 50 years, and 87.0 % of the patients were male. Bradykinesia (53.7 %) was the most common manifestation of PPS in neurosyphilis patients. The most frequent physical sign was orofacial dyskinesia (the Candy sign), which accounted for 51.9 % of cases. In nearly three quarters (71.1 %), magnetic resonance imagery revealed temporal, hippocampal lobe, or whole brain atrophy, while 13.3 % exhibited basal ganglia lacunar infarction, and 22.2 % cases had focal demyelination in the cerebral peduncle, cerebellum, frontal lobe, parietal lobe, hippocampus and/or lateral vertical., Conclusions: Neurosyphilis patients exhibited PPS in involving bradykinesia, tremor rigidity and, in most cases, GP. Brain atrophy and basal ganglia lesion were the most common imaging findings in neurosyphilis patients with PPS. Our results should help to elucidate PPS characteristics PPS and neuroimaging mechanisms in neurosyphilis patients with PPS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Tyrosine Kinase Inhibitors (TKIs) is an important therapy for patients with oncogene-mutated Non-Small Cell Lung Cancer (NSCLC). However, acquired resistance remains a major challenge. The efficacy of TKIs plus thoracic radiotherapy (RT) in oncogene-mutated NSCLC patients is uncertain. Therefore, we performed a meta-analysis to comprehensively evaluate the efficacy and safety of thoracic RT plus TKIs in oncogene-mutated NSCLC patients., Methods: The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane Library. Studies comparing the efficacy and safety of TKIs plus RT with TKIs alone in oncogene-mutated NSCLC patients were included in this analysis. Outcomes were median progression-free survival (mPFS), median overall survival (mOS), and incidence of adverse events (AEs). This analysis performed a subgroup analysis of the efficacy of first-line TKIs in combination with RT., Results: This meta-analysis included 12 studies with 2936 patients (n = 823 patients with TKIs plus thoracic RT, n = 2113 patients with TKIs alone). The results showed that patients who received treatment with TKIs plus thoracic RT were associated with superior mPFS and mOS than those who were treated with TKIs alone (hazard ratio [HR]: 0.42, 95% CI 0.30-0.59, p < 0.00001; HR: 0.56, 95% CI 0.41-0.70, p < 0.00001, respectively). Subgroup analyses showed that TKIs plus thoracic RT as first-line treatment was associated with better mPFS and OS (HR: 0.37, 95% CI 0.26-0.52, p < 0.00001; HR: 0.47, 95% CI 0.31-0.70, p = 0.0002, respectively). Although the combination of TKIs with thoracic RT was associated with an increased risk of total AEs (odds ratio [OR]: 1.17, 95% CI 1.06-1.29, P = 0.002), there was no significant difference in serious AEs (grade ≥ 3) (OR: 1.06, 95% CI 0.58-1.92, P = 0.86). The most frequently occurring radiation-related AEs were radiation pneumonitis, radiation esophagitis, and radiation dermatitis, with overall rates of 41.3%, 15.4%, and 11.1%, respectively. The incidence of severe radiation pneumonitis and radiation esophagitis was 4.5% and 6.2%, respectively., Conclusions: In comparison to TKIs alone, TKIs plus thoracic RT are associated with survival benefits, especially as a first-line treatment option. Although TKIs plus thoracic RT may increase the risk of total AEs, it did not increase the risk of severe AEs. Therefore, TKIs plus thoracic RT may be a promising therapeutic regimen for oncogene-mutated NSCLC patients., (© 2024. The Author(s).)

Brain alterations associated with illness severity in schizophrenia remain poorly understood. Establishing linkages between imaging biomarkers and symptom expression may enhance mechanistic understanding of acute psychotic illness. Constructing models using MRI and clinical features together to maximize model validity may be particularly useful for these purposes. A multi-task deep learning model for standard case/control recognition incorporated with psychosis symptom severity regression was constructed with anatomic MRI collected from 286 patients with drug-naïve first-episode schizophrenia and 330 healthy controls from two datasets, and validated with an independent dataset including 40 first-episode schizophrenia. To evaluate the contribution of regression to the case/control recognition, a single-task classification model was constructed. Performance of unprocessed anatomical images and of predefined imaging features obtained using voxel-based morphometry (VBM) and surface-based morphometry (SBM), were examined and compared. Brain regions contributing to the symptom severity regression and illness identification were identified. Models developed with unprocessed images achieved greater group separation than either VBM or SBM measurements, differentiating schizophrenia patients from healthy controls with a balanced accuracy of 83.0% with sensitivity = 76.1% and specificity = 89.0%. The multi-task model also showed superior performance to single-task classification model without considering clinical symptoms. These findings showed high replication in the site-split validation and external validation analyses. Measurements in parietal, occipital and medial frontal cortex and bilateral cerebellum had the greatest contribution to the multi-task model. Incorporating illness severity regression in pattern recognition algorithms, our study developed an MRI-based model that was of high diagnostic value in acutely ill schizophrenia patients, highlighting clinical relevance of the model., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Periodontitis and severe trauma are major causes of damage to the periodontal ligament (PDL). Repairing the native conditions of the PDL is essential for the stability of the tissue and its interfaces. Bioprinting periodontal ligament stem cells (PDLSCs) is an interesting approach to guide the regeneration of PDL and interfacial integration. Herein, a collagen-based bioink mimicking the native extracellular matrix conditions and carrying PDLSCs was tested to guide the periodontal ligament organization. The bioink was tested at two different concentrations (10 and 15 mg/mL) and characterized by swelling and degradation, microstructural organization, and rheological properties. The biological properties were assessed after loading PDLSCs into bioinks for bioprinting. The characterization was performed through cell viability, alizarin red assay, and expression for ALP , COL1A1 , RUNX2 , and OCN . The in vivo biocompatibility of the PDLSC-laden bioinks was verified using subcutaneous implantation in mice. Later, the ability of the bioprinted PDLSC-laden bioinks on dental root fragments to form PDL was also investigated in vivo in mice for 4 and 10 weeks. The bioinks demonstrated typical shear-thinning behavior, a porous microstructure, and stable swelling and degradation characteristics. Both concentrations were printable and provided suitable conditions for a high cell survival, proliferation, and differentiation. PDLSC-laden bioinks demonstrated biocompatibility in vivo , and the bioprinted scaffolds on the root surface evidenced PDLSC alignment, organization, and PDLSC migration to the root surface. The versatility of collagen-based bioinks provides native ECM conditions for PDLSC proliferation, alignment, organization, and differentiation, with translational applications in bioprinting scaffolds for PDL regeneration.

Background: Fatigue is a prevalent issue that can lead individuals to a sub-health condition, impacting their work efficiency and quality of life. There are limited effective treatment options available for fatigue. Ren-Shen-Bu-Qi decoction (RSBQD) is a proprietary herbal remedy that is designed to address fatigue. However, the specific pharmacological mechanisms and basis of RSBQD are not yet fully understood., Purpose: This study aimed to investigate the pharmacological effects and mechanisms of RSBQD in a mouse model of exercise fatigue., Materials and Methods: UPLC-Q-Orbitrap HRMS was used to analyze the chemical composition of RSBQD. The pharmacological basis and molecular mechanism of RSBQD on exercise fatigue were predicted using network pharmacology analysis. Subsequently, an exercise fatigue mouse model was established and used to analysis the effects of RSBQD. The potential mechanisms were verified by hematoxylin-eosin (HE) staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking., Results: The results showed that 88 main components of RSBQD were identified, which have mainly belonged to flavonoids and carboxylic acid compounds. The network pharmacology analysis indicated that RSBQD ameliorate fatigue through PI3K/AKT signaling pathway. Notably, RSBQD prolonged the swimming time and diminished body weight loss of exercise fatigue mice (P < 0.05). Meanwhile, RSBQD significantly alleviated the injury of liver and kidney induced by exhaustive exercise, and decreasing the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and BUN levels (P < 0.05). In addition, RSBQD was found could relieve exercise fatigue by decreasing the content of creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid (LA), but increasing the blood glucose (GLU) and liver glycogen (HG) levels (P < 0.05). RSBQD also significantly increased the hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) but decreased hepatic malondialdehyde (MDA) levels. Moreover, RSBQD was able to upregulate protein level of activated Nrf2 and PI3K/AKT signaling pathways., Conclusions: RSBQD mitigates exercise fatigue by reversing metabolic changes and reducing oxidative damage through the PI3K/AKT/Nrf2 signaling pathway. This study offers pharmacological support for the utilization of RSBQD in exercise fatigue treatment., (© 2024. The Author(s).)

Background: Currently developed molecular markers can predict the effectiveness of cancer immunotherapy and screen beneficiaries to some extent, but they are not stable enough. Therefore, there is an urgent need for discovering novel biomarkers. At the same time, sex factor plays a vital role in the response to immunotherapy, so it is particularly important to identify sex-related molecular indicators., Methods: We integrated a pan-cancer cohort consisting of 2348 cancer patients who received immune checkpoint inhibitors and targeted sequencing. Using somatic mutation profiles, we identified mutational signatures, molecular subtypes, and frequently mutated genes, and analyzed their relationships with immunotherapeutic outcomes. We also explored sex disparities of determined biomarkers in response to treatments., Results: We found that male patients exhibited better immunotherapy outcomes and higher tumor mutational burden. A total of seven mutational signatures were identified, among which signatures 1 and 3 were associated with worse immunotherapy outcomes, while signatures 2 and 6 correlated with better outcomes. Gender-based analysis revealed that mutational signature 1 continued to show a worse immunotherapy outcome in female patients, whereas signature 6 demonstrated a better outcome in male patients. Based on mutational activities, we identified four potential molecular subtypes with gender differences and relevance to treatment outcomes. PI3K-AKT, RAS signaling pathways, and 68 significantly mutated genes were identified to be associated with immunotherapy outcomes, with nine genes (i.e., ATM, ATRX, DOT1L, EP300, EPHB1, NOTCH1, PBRM1, RBM10, and SETD2) exhibiting gender differences. Finally, we discovered co-mutated gene pairs and TP53 p.R282W mutations related to treatment outcomes, highlighting their gender-specific differences., Conclusion: This study identified several molecular biomarkers related to cancer immunotherapy outcomes in terms of mutational signatures, molecular subtypes, and mutated genes, and explored their gender-relatedness in order to provide clues and basis for clinical treatment efficacy evaluation and patient selection., 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, Wang, Gao, Zheng, Zhang, Ren, Shen, Su and Lu.)

Background: Currently, the applicant has chosen a target plasma trough concentration for nirmatrelvir, which is adjusted to 292 ng/mL based on the drug's molecular weight (499.54 Daltons), its binding to human plasma proteins (69%), and the in vitro antiviral EC 90 value (181 nM). However, the current exposure-effect relationships (ER) analysis of viral load in patients enrolled in the EPIC-HR study has not revealed clinically significant trends in the ER. Given that the lungs are the primary site of COVID-19 infection, we aim to further understand this exposure relationship by exploring and analyzing the penetration characteristics of nirmatrelvir in the lungs., Objectives: To explore and understand the target plasma concentration of 292 ng/mL in antiviral activity., Methods: We identified all critically ill patients with coronavirus disease 2019 who received nirmatrelvir/ritonavir treatment in the respiratory intensive care unit of Changhai hospital between January 2023 and October 2023. Samples of plasma and bronchoalveolar lavage fluid were obtained at pre-dose trough concentrations after administration of nirmatrelvir (NMV). The relationship between NMV levels in plasma and the epithelial lining fluid (ELF) was assessed by determining concentrations of NMV., Results: There was a significant relationship between NMV levels in plasma and ELF (ELF = 0.4976*PLASMA- 204; R = 0.96), with a correlation whose slope (0.4976) suggested that the blood-to-ELF ratio of drug penetration was 2:1. A negative value from the equation indicates that NMV requires to reach baseline concentration to penetrate the ELF., Conclusions: The relationship between NMV levels in plasma and ELF with low permeability and a negative baseline value suggests that the target plasma concentration of 292 ng/mL is insufficient for antiviral activity. This study provides a unique perspective to explore and understand no clinically meaningful trend of exposure-response relationships in patients enrolled in EPIC-HR., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

To examine the permeability alterations in coal seams induced by liquid CO 2 injection, we employed COMSOL simulations to recreate the flow, force, and temperature fields, along with the corresponding physical parameters of the geological formation. We established a mathematical model to track the evolution of the coal body's permeability, enabling us to capture the phase distribution of CO 2 , the dynamics of fluid transportation, and the coal body's mechanical responses during the liquid CO 2 injection process. Our findings revealed that the coal seam undergoes significant changes due to low-temperature freezing and shrinkage, gas-liquid phase transitions, and expansion impacts from solid-liquid phase changes. These factors collectively modify the pore structure, subsequently influencing the coal seam's permeability. Notably, the coal body's permeability, influenced by the pore structure and the Klinkenberg effect, increases logarithmically with rising injection pressure and falling temperatures. The structural changes in the coal body are markedly impacted by seepage and phase change pressures, with the permeability enhancement from secondary phase changes being 2.28 times greater than that from primary phase changes, and five times greater than in scenarios without phase change., (© 2024. The Author(s).)

This work demonstrated an innovative antimicrobial and biodegradable food packaging film CBDA-10-SA which was prepared by crosslinking a natural polyphenolic truxillic acid (cyclobutane-dicarboxylic acid, CBDA-10) and sodium alginate (SA). The CBDA-10-SA film exhibited improved tensile strength (148 MPa) and UV shielding capabilities. The maximum thermal decomposition temperature was achieved of 249 °C. Compared to SA film, CBDA-10-SA showed increased antibacterial activities. In food packaging test, the CBDA-10-SA inhibited the rapid growth of potential of hydrogen (pH) value, slowed down the weight loss, reduced total plate count (TPC) value of pork, and delayed the spoilage process of pork. Notably, CBDA-10-SA displayed remarkable degradability in soil, with 60 % degrading in four weeks. In this study, CBDA-10-SA showed enhanced physicochemical and mechanical properties compared to traditional SA film. Those improvements make it anticipated to be used in not only food packaging but also mechanical, pharmaceutical, and agricultural fields., 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: Sensing dietary components in the gut is important to ensure an appropriate hormonal response and metabolic regulation after food intake. The fall webworm, Hyphantria cunea, is a major invasive pest in China and has led to significant economic losses and ecosystem disruption. The larvae's broad host range and voracious appetite for leaves make H. cunea a primary cause of serious damage to both forests and crops. To date, however, the gustatory receptors (Grs) of H. cunea and their regulatory function remain largely unknown., Results: We identified the fall webworm gustatory receptor HcGr76 as a fructose and chlorogenic acid receptor using Ca 2+ imaging and determination of intracellular Ca 2+ concentration by a microplate reader. Moreover, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis revealed that HcGr76 is highly expressed in the anterior and middle midgut. Knockdown of HcGr76 caused a significant reduction in the expression of neuropeptide F 1 (NPF1) and CCHamide-2, and led to a decrease in carbohydrate and lipid levels in the hemolymph., Conclusion: Our studies provide circumstantial evidence that HcGr76 expressed in the midgut is involved in sensing dietary components, and regulates the expression of relevant peptide hormones to alter metabolism in H. cunea larvae, thus providing a promising molecular target for the development of new insect-specific control products. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

In this study, isothermal annealing experiments were conducted on copper-nickel-silicon alloys containing continuous precipitates (CP) and discontinuous precipitates (DP) to investigate the effects of different types of precipitate phases on the microstructural evolution and softening temperature during annealing, as well as to analyze the differences in softening mechanisms. The experimental results revealed that the softening temperature of the CP alloy, subjected to 75% cold deformation, was 505 °C. In contrast, the DP alloy achieved softening temperatures of 575 °C and 515 °C after 75% and 97.5% cold deformation, respectively. This indicates that the DP alloy exhibits significantly superior softening resistance compared to the CP alloy, attributed to the distinct softening mechanisms of the two alloys. In the CP alloy, softening is primarily influenced by factors such as the coarsening of the precipitate phase, the occurrence of recrystallization, and the reduction in dislocation density. In the DP alloy, the balling phenomenon of the DP phase is more pronounced, and its unique microstructure exerts a stronger hindrance to dislocation and grain boundary motion. This hindrance effect reduces the extent of recrystallization and results in a smaller decrease in dislocation density. In summary, the DP alloy, due to its unique microstructure and softening mechanisms, demonstrates better softening resistance, providing higher durability and stability for high-temperature applications.

As n-type and wide-bandgap semiconductor materials which are widely found in nature, tungsten oxides (WO x ) have attracted extensive attention because of their rich phase structures and unique sub-stoichiometric properties. Tungsten oxides have a good chromogenic response to optical, electrical, and gaseous stimuli, in which their phase changes with the change of temperature and ionic embeddedness, accompanied by significant changes in their optical properties. In addition, due to the presence of oxygen defects, the conductivity and adsorption capacity of tungsten oxides for surface substances are enhanced. These properties endow tungsten oxides with promising application potential in the optical and electronic device areas. This paper reviews the structural and optoelectrical properties of tungsten oxide-based chromogenic materials. Then we focus on the working mechanisms, performance indexes, and preparation methods of tungsten oxides in the field of intelligent chromogenic technology, including photochromism, electrochromism, and gasochromism of tungsten oxide-based chromogenic materials. Finally, a conclusion and outlook are provided, which may help to further advance the application of tungsten oxides in the field of smart chromogenic changes.

In this article, AlSi10Mg aluminum alloy was used as the substrate to prepare aluminum alloy/diamond composite materials with laser cladding technology. The effects of the composition and laser power on the microstructure and thermal properties of the composite materials were studied. The results show that the prefabrication of tungsten carbide layer on the diamond surface enhances the wettability of diamond with aluminum alloy and reduces the laser reflection, which ensures the implementability of laser cladding technology for the preparation of aluminum alloy/diamond composites. The laser power and components determine the temperature of the molten pool and thus the state of the organization of the composite material to be formed by cladding. With the increase in the diamond content, the density, specific heat, mechanical properties, and average linear thermal expansion coefficient of the composite material gradually decrease, while the thermal conductivity first increases and then decreases. The thermal conductivity of the aluminum alloy/diamond composite material prepared by laser cladding is 200.68 W/mK, and the linear thermal expansion coefficient is 1.904 × 10 -5 /K, which are superior to those of the matrix AlSi10Mg aluminum alloy.

In this work, a synthetical glycan fingerprinting strategy using a multiple heart-cut two-dimensional liquid chromatography system linked to mass spectrometry (MHC 2D LC-MS) was developed to analyze enoxaparin, a widely used low molecular weight heparin (LMWH). Glycans from an enoxaparin standard were prepared offline based on size, and the derived tetra-, hexa-, octa- and decasaccharides were profiled using a qualitative analytical platform. Strong anion exchange chromatography (SAX) was employed as the first-dimensional chromatography ( 1 D) to separate glycans of the same size but with different charges or sequences, while size exclusion chromatography (SEC) was used in the second dimension ( 2 D) for desalting before MS analysis. The retention times (RTs), accurate masses and structural compositions of the glycans were fully characterized. Real samples were analyzed using the same platform but with 1 D and 2 D exchanged: SEC was used to separate enoxaparin glycans by size, followed by SAX using the same parameters as in the qualitative platform to separate glycans by charge or sequence. Glycans in real samples were identified by matching their RTs to those assigned in the qualitative analysis and semi-quantitated after normalization of peaks in each SAX chromatogram of glycans of different sizes. The analyses were performed automatically and robustly using this synthetical platform, enabling the fingerprinting and differentiation of enoxaparins from various sources. This platform could serve as a powerful tool for structural analysis, quality control, and heparin-related drug development., Competing Interests: Declaration of competing interest There is no conflict of interest for authors of this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The treatment of refractory bone defects is a major clinical challenge, especially in steroid-associated osteonecrosis (SAON), which is characterized by insufficient osteogenesis and angiogenesis. Herin, a microenvironment responsiveness scaffold composed of poly-L-lactide (PLLA), and manganese dioxide (MnO 2 ) nanoparticles is designed to enhance bone regeneration by scavenging endogenous reactive oxygen species (ROS) and modulating immune microenvironment in situ. A catalase-like catalytic reaction between MnO 2 and endogenous hydrogen peroxide (H 2 O 2 ) generated at the bone defect area, which typically becomes acidic and ROS-rich, triggers on-demand release of oxygen and Mn 2+ , significantly ameliorating inflammatory response by promoting M2-type polarization of macrophages, reprograming osteoimmune microenvironment conducive to angiogenesis and osteogenesis. Furthermore, the fundamental mechanisms were explored through transcriptome sequencing analysis, revealing that PLLA/MnO 2 scaffolds (PMns) promote osteogenic differentiation by upregulating the TGF-β/Smad signaling pathway in human bone marrow mesenchymal stem cells (hBMSCs). Overall, the PMns exhibit superior immunomodulatory, excellent osteogenic-angiogenic properties and promising candidates as bone graft substitutes for therapy clinical refractory bone defects., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Authors.)

Background: Affective and anxiety disorders including major depression disorder (MDD), post-traumatic stress disorder (PTSD), and social anxiety disorder (SAD) are characterized by network dysconnectivity. Network controllability quantifies the capability of specific brain regions to impact functional dynamics based on the underlying structural connectome. This study aimed to investigate transdiagnostic and illness-specific network controllability alterations across these three disorders., Materials and Methods: The study enrolled 233 currently untreated and non-comorbid subjects, including 68 MDD patients, 51 PTSD patients, 46 SAD patients, and 68 healthy controls (HCs). White matter network controllability was compared among the four groups, and its associations with symptom severity and duration of untreated illness were evaluated., Results: Compared with HCs, patients with PTSD, MDD and SAD exhibited reduced average controllability in the somatomotor, subcortical, and default mode network, notably in brain regions such as the superior frontal gyrus, postcentral gyrus, paracentral gyrus, pallidum, posterior cingulate, and putamen. MDD and SAD patients exhibited reduced average controllability in the left lateral occipital gyrus and bilateral accumbens. SAD patients showed reduced average controllability in the dorsal attention network. These controllability changes did not correlate with illness duration or symptom severity., Limitations: The cross-sectional design limits causal inference, and adjusting for age and sex differences may not completely eliminate their influence on the results., Conclusion: The present study revealed shared and specific alterations of network controllability in MDD, PTSD, and SAD, suggesting reduced ability of specific brain regions/networks in driving the brain system into different functional states across these disorders., Competing Interests: Declaration of competing interest Dr. Wenjing Zhang consult to VeraSci. The remaining authors have no competing interests or financial support to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Solid fuel combustion exposure is a leading global health risk factor, yet evidence on its effects, especially on vulnerable children, is sparse. This large-scale, multi-center prospective study aimed to address this gap by involving 9997 schoolchildren across China between 2013 and 2015. Here we show that lung function levels exhibited a marginally significant decline among children exposed to solid fuel usage. Specifically, FVC and FEV1 decreased by 21.2 mL (95% CI: -15.7, 58.1) and 24.1 mL (-8.4, 56.6), respectively. Additionally, PEF, FEF 25 and FEF 75 decreased by 25.7 mL/s (-46.5, 98.0), 32.7 mL/s (-42.7, 108.2), and 35.4 mL/s (-5.9, 76.7), respectively. Persistent exposure to solid fuel usage in children led to greater lung damage. Children with allergy history were more susceptible to solid fuel exposure. Our study highlights the adverse impact of solid fuel usage on children and the need to promote clean fuel usage for this vulnerable population., (© 2024. The Author(s).)

Background: Pacemaker lead-induced tricuspid regurgitation is a common complication after cardiac implantable electronic device (CIED) implantation. Cardiac implantable electronic device lead removal is a challenge procedure., Case Summary: A 72-year-old lady was admitted due to worsening heart failure. She had a history of permanent atrial fibrillation and had a permanent single-chamber pacemaker implanted 8 years ago due to complete heart block. Transthoracic echocardiography identified severe lead-related tricuspid regurgitation. The patient underwent successful lead extraction and received a new implantation of left bunch bundle area pacing. Transthoracic echocardiographic examination 2 days after the procedure showed a significant decrease of the tricuspid regurgitation. The patient also reported an improvement in heart failure symptoms., Discussion: Pacemaker lead-related tricuspid regurgitation introduces negative haemodynamic overload, carrying high risk for the development of heart failure and worse outcome. The present case shows a rapid relief of symptom and improvement of echocardiography findings, indicating the significance of mechanistic approach in the treatment of lead-related tricuspid mechanical interference., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

A cell membrane-derived vesicle (MV) that has cell-mimicking features with characteristic functionalities holds vast appeal for biomimetic nanomedicine and drug delivery but suffers from a major limitation of innate fragility and poor stability. Herein, we report a lipid-anchoring strategy for stabilizing MV for enhanced drug delivery. An array of amphiphilic mono-acyl phosphatidylcholines (MPCs) with specific hydrophobic moieties are synthesized and readily engineered on MV based on their commendable aqueous solubility and efficient membrane insertability. Incorporation of MPCs containing rigid ring structures in the hydrophobic segment demonstrates the potency of stabilizing MV by the combined ordering and condensing effects. The optimized MPC-stabilized MV exhibits prolonged circulation in the bloodstream, elevated accumulation within a tumor, and enhanced therapeutic effects of chemotherapeutic and photothermal drugs. Moreover, doxorubicin-loaded MV, engineered with mono-all- trans retinoyl phosphatidylcholine as an MV stabilizer and a therapeutic prodrug, potently suppresses growth and metastasis of high-stemness tumors.

Heazlewoodite nickel sulfide (Ni 3 S 2 ) is advocated as a promising nonnoble catalyst for electrochemical water splitting because of its unique structure configuration and high conductivity. However, the low active sites and strong sulfur-hydrogen bonds (S-H ads ) formed on Ni 3 S 2 surface greatly inhibit the desorption of H ads and reduce the hydrogen and oxygen evolution reaction (HER and OER) activity. Doping is a valid strategy to stimulate the intrinsic catalytic activity of pristine Ni 3 S 2 via modifying the active site. Herein, the Ni foam supported Fe and Mo co-doped Ni 3 S 2 electrocatalysts (Fe-MoS 2 /Ni 3 S 2 @NF) have been constructed using Keplerate polyoxomolybdate {Mo 72 F 30 } as precursor through a facile hydrothermal process. Experimental results certificate that Fe and Mo co-doping can effectively tune the local electronic structure, facilitate the interfacial electron transfer, and improve the intrinsic activity. Consequently, the Fe-MoS 2 /Ni 3 S 2 @NF display more excellent HER and OER activity than MoS 2 /Ni 3 S 2 @NF and bare Ni 3 S 2 @NF by delivering the 10 and 50 mA cm -2 current densities at ultra-low overpotentials of 74/175 and 80/160 mV for HER and OER. Moreover, when coupled in an alkaline electrolyzer, Fe-MoS 2 /Ni 3 S 2 @NF approached the current of 10 mA cm -2 under a cell voltage of 1.60 V and exhibit excellent stability. The strategy to realize tunable catalytic behaviors via foreign metal doping provides a new avenue to optimize the water splitting catalysts., 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.)

Introduction: Policies aiming to prevent ill health and reduce health inequalities need to consider the full complexity of health systems, including environmental determinants. A learning health system that incorporates environmental factors needs healthcare, social care and non-health data linkage at individual and small-area levels. Our objective was to establish privacy-preserving household record linkage for England to ensure person-level data remain secure and private when linked with data from households or the wider environment., Methods: A stakeholder workshop with participants from our regional health board, together with the regional data processor, and the national data provider. The workshop discussed the risks and benefits of household linkages. This group then co-designed actionable dataflows between national and local data controllers and processors., Results: A process was defined whereby the Personal Demographics Service, which includes the addresses of all patients of the National Health Service (NHS) in England, was used to match patients to a home identifier, for the time they are recorded as living at that address. Discussions with NHS England resulted in secure and quality-assured data linkages and a plan to flow these pseudonymised data onwards into regional health boards. Methods were established, including the generation of matching algorithms, transfer processes and information governance approvals. Our collaboration accelerated the development of a new data governance application, facilitating future public health intervention evaluations., Conclusion: These activities have established a secure method for protecting the privacy of NHS patients in England, while allowing linkage of wider environmental data. This enables local health systems to learn from their data and improve health by optimizing non-health factors. Proportionate governance of health and linked non-health data is practical in England for incorporating key environmental factors into a learning health system., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Learning Health Systems published by Wiley Periodicals LLC on behalf of University of Michigan.)

Background: Measures of cortical topology are believed to characterize large-scale cortical networks. Previous studies used region of interest (ROI)-based approaches with predefined templates that limit analyses to linear pair-wise interactions between regions. As cortical topology is inherently complex, a non-linear dynamic model that measures the brain complexity at the voxel level is suggested to characterize topological complexities of brain regions and cortical folding., Methods: T1-weighted brain images of 150 first-episode antipsychotic-naïve schizophrenia (FES) patients and 161 healthy comparison participants (HC) were examined. The Chaos analysis approach was applied to detect alterations in brain structural complexity using the largest Lyapunov exponent (Lambda) as the key measure. Then, the Lambda spatial series was mapped in the frequency domain using the correlation of the Morlet wavelet to reflect cortical folding complexity., Results: A widespread voxel-wise decrease in Lambda values in space and frequency domains was observed in FES, especially in frontal, parietal, temporal, limbic, basal ganglia, thalamic, and cerebellar regions. The widespread decrease indicates a general loss of brain topological complexity and cortical folding. An additional pattern of increased Lambda values in certain regions highlights the redistribution of complexity measures in schizophrenia at an early stage with potential progression as the illness advances. Strong correlations were found between the duration of untreated psychosis and Lambda values related to the cerebellum, temporal, and occipital gyri., Conclusions: Our findings support the notion that defining brain complexity by non-linear dynamic analyses offers a novel approach for identifying structural brain alterations related to the early stages of schizophrenia., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

This study aims to investigate the associations of caring for grandchildren and/or great-grandparents with depressive symptoms, as well as life satisfaction in Chinese grandparents, and analyze the moderating roles of urban-rural residence and social participation. A nationally representative sample of 2973 grandparents in families with great-grandparents and grandchildren were selected from the 2018 China Health and Retirement Longitudinal Study (CHARLS). The Center for Epidemiologic Studies Depression (CESD-10) and the single-item were used to measure depressive symptoms and life satisfaction. Social participation included participation in social and intellectual activities. The binary logistic regression model was employed to explore the relationship between caring and depressive symptoms, as well as life satisfaction in the whole participants, different urban-rural residence, and social participation groups, respectively. Caring was associated with depressive symptoms and life satisfaction (p < 0.05). A significant interaction existed between caring and urban-rural residence for depressive symptoms (interaction p = 0.029) and life satisfaction (interaction p = 0.027). Significant interactions were also found among caring, urban-rural residence, and social activities with depressive symptoms (interaction p = 0.025). In urban, caring for both was negatively related to depressive symptoms for the non-social activists, while in rural, caring for great-grandparents was positively associated with depressive symptoms for social activists (p < 0.05). Any new policy design related to preventing and reducing the possibility of mental disorders in Chinese grandparents should be tailored to heterogeneous subgroups who live in different rural-urban and social activities participation., (© 2024 Family Process Institute.)

Commercial metalized plastic current collector (MPCC) is receiving widespread attention from the business and academic communities, due to its properties of excellent electrical conductivity and low mass density. However, the application of MPCC on the side of copper is rarely studied. Herein, sandwich-like polyethylene terephthalate-based (PET) and polypropylene-based (PP) copper (Cu) current collectors via magnetron sputtering and electroplating are fabricated. Most importantly, the electrical performance, mechanical safety quality, and revealed the corresponding failure mechanism for the MPCC cells are first systematically evaluated. First, during the 45 °C electrical cycling tests, PET-Cu CC (82.67%) and PP-Cu CC (82.32%) cells both have comparable capacity retention with the traditional Cu CC (Tra-Cu CC) cell (84.55%) after 500 cycles. The slight reduction in the cycling performance is induced by the crack of the Cu layer around the embedded SiO 2 particle for PET-Cu CC cell and the detachment of Cu layer for PP-Cu CC cell. Second, during the nail-penetration test, MPCC cells maintain no fire and explosion for more than 5 min, since the heat-shrinkable function of polymeric film can interrupt the continuous Joule heat released by internal short-circuit. This work provides important guidance for the large-scale application of MPCC in the field of lithium-ion batteries., (© 2024 Wiley‐VCH GmbH.)

Human adenovirus (HAdV) infection in newborns is a rare condition that typically affects multiple organ systems and has a high mortality rate. We report a case of neonatal HAdV-D37 infection that presented with fever and respiratory distress that was confirmed by metagenomic next-generation sequencing using blood and bronchoalveolar lavage fluid. We treated the patient with intravenous immunoglobulin, methylprednisolone, and anticoagulants, and the patient recovered. Our review of 41 cases of HAdV found that treatment with intravenous immunoglobin might have improved the outcome of HAdV-D infection. We further suggest that glucocorticoid therapy may have additional therapeutic validity in the setting of severe or disseminated disease and that monitoring coagulation function and timely anticoagulation treatment should be considered to prevent complications associated with disseminated intravascular coagulation., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Hepatic fibrosis is a reversible pathological phenomenon caused by the abnormal proliferation of connective tissues in the liver for self-repair after persistent liver injury. Among these tissues, the activation status of hepatic stellate cells (HSCs) is crucial. Glycyrrhizic acid (GA) agents have been proven to have excellent anti-fibrosis effects, but their targets are unclear., Purpose: To investigate the anti-hepatic fibrosis effect of GA and its target in activated HSCs., Methods: A mouse model of hepatic fibrosis was prepared with 20 % carbon tetrachloride (CCl 4 ) and GA was administered continuously for 4 weeks. Subsequently, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅲ procollagen peptide (P III P), laminin (LN), hyaluronic acid (HA), and type Ⅳ collagen (Col Ⅳ) were measured. Liver tissues were subjected to hematoxylin and eosin (HE), Masson, and Sirius red staining and proteome sequencing analysis. Based on LX-2 cells, activity-based protein profiling (ABPP) was used to investigate the potential targets of GA, which was further validated by the cellular thermal shift assay (CETSA), immunofluorescence co-localization, molecular docking, small interfering RNA (siRNA) and western blot (WB) assays., Results: In vivo, GA significantly reduced serum ALT, AST, HA, P III P, Col IV, and LN levels. HE, Masson, and Sirius red staining showed that GA significantly ameliorated hepatic inflammatory response and collagen deposition in CCl 4- treated mice. Proteome sequencing results showed that GA mainly regulated glutathione S-transferase family members involved in glutathione metabolism. In vitro, GA significantly inhibited LX-2 cell proliferation and reduced reactive oxygen species accumulation. ABPP suggested that aldo-keto reductase family 7 member A2 (AKR7A2) was the major binding protein of GA in LX-2 cells. CETSA, fluorescence co-localization, molecular docking, and surface plasmon resonance further validated GA binding to AKR7A2. The WB results showed that GA up-regulated AKR7A2 expression both in vitro and in vivo and was corroborated by siRNA experiments., Conclusion: GA targeted AKR7A2 in LX-2 cells to defend against sustained oxidative stress injury, thereby inhibiting the proliferation of activated HSCs and reversing hepatic 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 GmbH. All rights reserved.)

The sustainability of water industry management model is one of the essential means to achieve sustainable utilization of water resources. Based on existing research on the sustainability of water industry, this study explores the factors affecting the sustainable competitiveness of water industry management model. It constructs a more complete sustainable competitiveness evaluation indicator system. Evidences taken from France and China were selected as the references for the study, and the principal component analysis was used to evaluate the overall sustainable competitiveness and main component dimensions. It is found through this study that the overall competitiveness indicator in the sustainable water industry management model and the sub-dimensional competitiveness indicators in resource support, development base, and environmental impact of water industry of France are better than those of China. China is more competitive in social inclusion, technological innovation, and sustainability of water industry. Based on the research results, this study provides insights into solving the existing issues in the sustainable development of China's water industry to support how China can adjust its water industry management model to improve its sustainable competitiveness., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis; however, their specific involvement in colon cancer remains largely unknown. Here we report that the splicing factor RBM25 is overexpressed in colon cancer, and this increased expression correlates with a poor prognosis of patients with colon cancer. Functionally, RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in vivo. Mechanistically, our transcriptome-wide analysis of splicing events revealed that RBM25 regulates a large number of cancer-related alternative splicing events across the human genome in colon cancer. Particularly, RBM25 regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a, thereby inhibiting the selection of the proximal 3' splice site (ss), resulting in the production of the oncogenic short isoform, MNK2b. Knockdown of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b isoform. Importantly, re-expression of MNK2b or blocking the 3' ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor suppression. Moreover, MNK2b levels were significantly increased in colon cancer tissues, which is positively correlated with the expression level of RBM25. Collectively, our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer, suggesting its potential as a prognostic marker and therapeutic target., (© 2024. Science China Press.)

Hydrogels based on biopolymers have attracted considerable interest in the last decades. Herein, an interpenetrating network hydrogel (IPN-Gel) adsorbent from starch-chitosan was fabricated facilely in one-pot through tandem Schiff base reaction and photopolymerization. First, aldehyde starch (DAS) was synthesized by the reaction of soluble starch with sodium periodate. Afterward, acrylamide (AM), 2-acrylamido-2-methylpropanesulfonic acid (AMPS), polyethylene glycol dimethacrylate (PEGDMA), photoinitiator, chitosan and DAS were dissolved in water to obtain a clear solution. Schiff base reaction between chitosan and DAS took place quickly to form the first network, and then photopolymerization of AM, AMPS, and PEGDMA occurred under ultraviolet radiation to form the second network. The preparation conditions of the as-prepared IPN-Gel were optimized with two indexes of gel mass fraction and swelling ratio. Its swelling behavior with pH and temperature change was explored. Finally, its adsorption performance was characterized with methylene blue (MB) as a model contaminant. The maximum adsorption capacity of IPN-Gel can reach 2039 mg·g -1 at pH =10. Its adsorption performance accords with Langmuir isothermal model and pseudo-second-order kinetic model and it was mainly controlled by chemisorption. This strategy is expected to found broad application prospects in the preparation of hydrogel adsorbents., 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 an important cellulose macromolecular-based material, cotton/polyamide and cotton/polyester fabrics are widely utilized in the textile and garment field due to their combination of the advantages of both cotton and synthetic fibers, such as excellent breathability, hygroscopicity, and abrasion performance. However, the synthetic dyes used in fabric coloration are derived from non-renewable resources, and the long-time dyeing procedure poses large pollution problems. Herein, microbial prodigiosins fermented by Serratia marcescens were employed for cotton/polyamide and cotton/polyester fabric dyeing and functionalizing. The results demonstrated that the prodigiosins suspension exhibited outstanding stability. Synthetic fibers contributed significantly to the overall color of fabrics and provided good dimensional stability and durability. In contrast, cotton fibers imparted relatively lighter color but played an essential role in enhancing the softness and comfort of fabrics. The dyed fabrics presented bright overall color light with good uniformity. Furthermore, the antibacterial rates of the dyed cotton/polyamide and cotton/polyester fabrics were 87.31 % and 89.70 %, respectively. The UPF values of the dyed cotton/polyamide and cotton/polyester fabrics were recorded as 52.3 and 93.5, respectively. This study provided a novel approach for cleaner functional dyeing of cotton/synthetic fiber two-component fabrics using prodigiosins., 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.)

Aim: Cerebello-cortical functional dysconnectivity plays a key role in the pathology of schizophrenia (SZ). We aimed to investigate the changes in cerebello-cortical directional connectivity in patients with SZ., Methods: A total of 180 drug-naïve patients with first-episode SZ (54 reassessed after 1 year of treatment) and 166 healthy controls (HCs) were included. Resting-state functional magnetic resonance imaging was used to perform Granger causal analysis, in which each of the nine cerebellar functional systems was defined as a seed. The observed effective connectivity (EC) alterations at baseline were further assessed at follow-up and were associated with changes in psychotic symptom., Results: We observed increased bottom-up EC in first-episode SZ from the cerebellum to the cerebrum (e.g. from the cerebellar attention and cingulo-opercular systems to the bilateral angular gyri, and from the cerebellar cingulo-opercular system to the right inferior frontal gyrus). In contrast, decreased top-down EC in the first-episode SZ was mainly from the cerebrum to the cerebellum (e.g. from the right inferior temporal gyrus, left middle temporal gyrus, left putamen, and right angular gyrus to the cerebellar language system). After 1 year of antipsychotic treatment, information projections from the cerebrum to the cerebellum were partly restored and positively related to symptom remission., Conclusion: These findings suggest that decreased top-down EC during the acute phase of SZ may be a state-dependent alteration related to symptoms and medication. However, increased bottom-up EC may reflect a persistent pathological trait., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)

The incidence of Alzheimer's disease (AD) has been increasing in recent years as the world's population ages, which poses a significant challenge to public health. Due to the complexity of pathogenesis of AD, currently there is no effective treatment for it. In recent years, cell and gene therapy has attracted widespread attention in the treatment of neurodegenerative diseases. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) represent a novel cell-free therapy with numerous advantages over cell-based therapies owing to their low immunogenicity and high safety profile. We summarize recent progress in the application of EVs for treating AD and the specific mechanisms and outline the underlying mechanisms. We also explore various methods for optimizing the function of MSC-EVs, including gene editing, modifying stem cell culture conditions and peptide modification. In addition, we discuss the therapeutic potentials of MSC-EVs, as well as the obstacles that currently impede their clinical utilization.

The O 2 content of the global ocean has been declining progressively over the past decades, mainly because of human activities and global warming. Despite this situation, the responses of macrobenthos under hypoxic conditions remain poorly understood. In this study, we conducted a long-term observation (2015-2022) to investigate the intricate impact of summer hypoxia on macrobenthic communities in a semi-enclosed bay of the North Yellow Sea. Comparative analyses revealed higher macrobenthos abundance (1956.8 ± 1507.5 ind./m 2 vs. 871.8 ± 636.9 ind./m 2 ) and biomass (8.2 ± 4.1 g/m 2 vs. 5.6 ± 3.2 g/m 2 ) at hypoxic sites compared to normoxic sites during hypoxic years. Notably, polychaete species demonstrated remarkable adaptability, dominating hypoxic sites, and shaping community structure. The decline in biodiversity underscored the vulnerability and diminished resilience of macrobenthic communities to hypoxic stressors. Stable isotope analysis provided valuable insights into food web structures. The average trophic level of macrobenthos measured 2.84 ± 0.70 at hypoxic sites, contrasting with the higher value of 3.14 ± 0.74 observed at normoxic sites, indicating the absence of predators at high trophic levels under hypoxic conditions. Moreover, trophic interactions were significantly altered, resulting in a simplified and more vulnerable macrobenthic trophic structure. The findings underscored the importance of comprehensive research to understand the complex responses of macrobenthic communities to hypoxia, thereby informing future conservation efforts in impacted ecosystems., 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.)

A novel gingival retraction cord named P/TA@CSy was prepared using chitosan yarns (CSy) loaded with tranexamic acid (TA) and Propolis (P). P/TA@CSy has good toughness with a breaking strength of 41.3 Pa, benefiting from the twisting structure and Propolis coating. A short coagulation time of 456 s was achieved for P/TA@CSy because of the potent blood absorption ability from the effective attachment of tranexamic acid. Moreover, excellent antibacterial ability was obtained with the antibacterial rates against E. coli of 94.73 %, S. aureus of 99.99 % and S. mutans of 99.99 %, contributing to Propolis's antibacterial ability. In addition, suppression of the expression of pro-inflammatory cytokines (IL-6 and TNF-α) was found, which could prevent wound infection. P/TA@CSy displayed excellent cytocompatibility with the cell activity of 100 % after 24 h. Therefore, P/TA@CSy could rapidly respond to gingival hemostasis and infection prevention, showing excellent potential in dental treatment., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chemical investigation of soft coral the Sarcophyton elegans collected from the South China Sea led to the identification of four new cembranes, namely sarcoeleganolides H-K ( 1 - 4 ). Their structures and absolute configurations were established by 1D and 2D NMR spectroscopy, quantum chemical calculations of NMR chemical shifts and electronic circular dichroism (ECD) data analysis. Moreover, compound 2 exhibited moderate anti-thrombotic activity in zebrafish.

Chinese cabbage ( Brassica rapa L. ssp. pekinensis ) ranks among the most cultivated and consumed vegetables in China. A major threat to its production is Plasmodiophora brassicae, which causes large root tumors, obstructing nutrient and water absorption and resulting in plant withering. This study used a widely targeted metabolome technique to identify resistance-related metabolites in resistant (DH40R) and susceptible (DH199S) Chinese cabbage varieties after inoculation with P. brassicae . This study analyzed disease-related metabolites during different periods, identifying 257 metabolites linked to resistance, enriched in the phenylpropanoid biosynthesis pathway, and 248 metabolites linked to susceptibility, enriched in the arachidonic acid metabolism pathway. Key metabolites and genes in the phenylpropanoid pathway were upregulated at 5 days post-inoculation (DPI), suggesting their role in disease resistance. In the arachidonic acid pathway, linoleic acid and gamma-linolenic acid were upregulated at 5 and 22 DPI in resistant plants, while arachidonic acid was upregulated at 22 DPI in susceptible plants, leading to the conclusion that arachidonic acid may be a response substance in susceptible plants after inoculation. Many genes enriched in these pathways were differentially expressed in DH40R and DH199S. The research provided insights into the defense mechanisms of Chinese cabbage against P. brassicae through combined metabolome and transcriptome analysis.

Rationale: Acute pulmonary embolism (PE), which can lead to cardiac and respiratory arrest, is a rare complication of cerebral angiography. However, neurologists do not pay attention to this., Patient Concerns: A 47-year-old male with a history of type 2 diabetes was admitted to our hospital for evaluation of surgical indications for unruptured ophthalmic aneurysms. After cerebral angiography, a fatal PE occurred. Through rapid identification and effective drug treatment, the patient recovered and was discharged., Diagnoses: A diagnosis of fatal PE was made based on the bedside ultrasonography and blood d-dimer level., Interventions: Cardiopulmonary resuscitation and intravenous thrombolysis of "50 mg alteplase" for continuous intravenous drip for 2 hours., Outcomes: The patient was recovered and no special discomfort was reported., Lessons: PE is a rare complication of cerebral angiography, but the fatality rate is very high. Neurologists must not only early identify and effectively treat this complication, but more importantly, pay attention to this complication, prevent it in advance, and reduce the occurrence of catastrophic events., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Talaromyces marneffei (T. marneffei) is an opportunistic pathogen that causes endemic mycoses, which could lead to multiple organ damage. Talaromycosis is frequently disregarded as an early cautionary sign of immune system disorders in non-HIV-infected children., Objective: We conduct a comprehensive review of the genotypes and clinical features of talaromycosis in patients with IEI to enhance clinical awareness regarding T. marneffei as a potential opportunistic pathogen in individuals with immune deficiencies., Methods: A systematic literature review was performed by searching PubMed, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, and Scopus. Data on IEI patients with talaromycosis, including genotypes and their immunological and clinical features, were collected., Results: Fifty patients with talaromycosis and IEI were included: XHIM (30.0%), STAT3-LOF deficiency (20.0%), STAT1-GOF (20.0%), IL2RG (6.00%), IFNGR1 (6.0%), IL12RB1 (4.0%), CARD9 (4.0%), COPA (4.0%), ADA (2.0%), RELB deficiency (2.0%), and NFKB2 (2.0%). Common symptoms of respiratory (43/50, 86.0%), skin (17/50, 34.0%), lymph node (31/50, 62.0%), digestive (34/50, 68.0%), and hematologic (22/50, 44.0%) systems were involved. The CT findings of the lungs may include lymph node calcification (9/30), interstitial lesions (8/30), pulmonary cavities (8/30), or specific pathogens (4/30), which could be easily misdiagnosed as tuberculosis infection. Amphotericin B (26/43), Voriconazole (24/43) and Itraconazole (22/43) were used for induction therapy. Ten patients were treated with Itraconazole sequentially and prophylaxis. 68.0% (34/50) of patients were still alive, and 4.0% (2/50) of were lost to follow-up. The disseminated T. marneffei infection resulted in the deaths of 14 individuals., Conclusions: The XHIM, STAT1-GOF, and STAT3-LOF demonstrated the highest susceptibility to talaromycosis, indicating the potential involvement of cellular immunity, IL-17 signaling, and the IL-12/IFN-γ axis in T. marneffei defense. T. marneffei infection may serve as an early warning indicator of IEI. For IEI patients suspected of T. marneffei, metagenomic next-generation sequencing (mNGS) could rapidly and effectively identify the causative pathogen. Prompt initiation of antifungal therapy is crucial for optimizing patient outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Developing red fluorescence emitters with simple structures via convenient synthetic routes is highly desirable yet challenging. Herein, two novel donor-acceptor-type red emitters, DCFOPV-TPA and SCFOPV-TPA, featuring the intramolecular charge transfer effect were designed by integrating triphenylamine and trifluoromethyl into a CN-substituted oligo( p -phenylene vinylene) backbone. Both chromophores exhibited aggregation-induced enhanced emission and solvatochromic behavior. Moreover, DCFOPV-TPA also displayed reversible mechanofluorochromic properties under external force.

Rheumatoid arthritis (RA) is an autoimmune disease with features of synovial inflammation, cartilage erosion, bone destruction, and pain and is currently lacking a satisfactory treatment strategy. Dihydroartemisinin (DHA), the active metabolite of artemisinin, has exhibited outstanding suppressive effects on RA without obvious side effects. However, the underlying mechanisms remain unclear, which limits its further clinical application. The purpose of this study is to reveal the pharmacodynamic mechanism of DHA against RA by means of a combination of single-cell RNA sequencing (RNA-seq), proteomics, as well as transcriptomics both in vivo and in vitro. In our results, DHA effectively reduced the degree of redness, swelling, and pain in RA rats and dramatically changed the synovial tissue microenvironment under the pathological state. Within this microenvironment, fibroblasts, macrophages, B cells, and endothelial cells were the major affected cell types, primarily through DHA targeting the extracellular matrix (ECM) structural constituent signaling pathway. In addition, we confirmed that DHA regulated the ECM by modulating matrix metalloproteinase 2 (MMP2) and MMP3 in the synovial tissue of RA rats. Moreover, DHA induced apoptosis in MH7A cells, further validating the bioinformatics data. In conclusion, DHA effectively reduced the inflammatory response and improved the immune microenvironment in synovial tissue by inhibiting MMP2 and MMP3. Our findings provide a basis for the application of DHA in the treatment of RA., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Qiuyan Guo et al.)