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Bile acids (BAs) are significantly altered in the liver and serum of patients with nonalcoholic steatohepatitis (NASH). However, the underlying mechanisms of these changes, particularly BA alternative pathways (BAP) responsible for non12-OH BAs, remain unclear. RNA-seq data were initially analyzed to reveal the changes of gene expression in NASH patients. Targeted metabolomics were conducted on plasma from NASH mice induced by high-fat or western diet with CCl 4 for 10-24 weeks. Liver tissues were examined using proteomics, RT-qPCR, and western blotting. An integrated approach was then employed to analyze protein interactions and network correlations. Analysis of RNA-seq data revealed the inhibition of CYP7B1 in NASH patients, indicating the dysregulation of BAP. In NASH mouse models, dysregulation of BA circulation was observed by increased plasma total BA (TBA) levels and decreased liver TBA, with liver swelling and histopathological changes. Targeted metabolomics revealed suppressed levels of non12-OH BAs, which inversely correlated with increased liver injury markers. The reduced mRNA and protein expression of Fxr and upregulation of Lxr signaling in livers suggested the suppressed BAP was modulated by Fxr-Lxr signaling. Moreover, BAP interactions predominantly implicated multiple metabolism disruptions, involving 7 hub proteins (Hk1, Acadsb, Pklr, Insr, Ldlr, Cyp27a1, and Cyp7b1), offering promising therapeutic targets for NASH. We presented the metabolic and proteomic map of BAP and its regulatory network in NASH progression. Therapeutic targeting of BAP or its co-regulatory proteins holds promise for NASH treatment and metabolic syndrome management., (© 2024 Federation of American Societies for Experimental Biology.)

Particulate nitrate is an important component of particulate matter and poses a significant threat to the ecosystem and human health. The gas-phase formation pathway of nitrate is extremely important, which mainly comprises the NO 2 oxidation process triggered by OH radicals and the nitrate partitioning process. The response of nitrate to source emission reduction during different pollution periods remains unclear. Here, we applied the chemical kinetic and thermodynamics model to explore the importance oxidation process and partitioning process during different pollution periods based on high-time resolution observation data. The result indicated that with the aggravation of pollution, the partitioning process gradually ceases to be a limiting step in the formation of nitrates. The results of the influencing factor analysis indicate that NO 2 concentration and aerosol pH values play a more significant role in the formation of nitrates. Specifically, during the clean period, nitrate formation is sensitive to both NO 2 concentration and pH values, but during the pollution period, it becomes sensitive only to NO 2 concentration. By combining source apportionment, we explored the response of nitrate formation to source emission reduction, and the results showed that the control of vehicle exhaust emissions and coal combustion sources is more effective in mitigating nitrate pollution. Additionally, this study also emphasized the importance of early prevention and control of pollution sources. This research provides scientific evidence for the precise management and control of nitrates., 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.)

METTL3 has emerged as a promising therapeutic target in cancer treatment, although its oncogenic functions in melanoma development and potential for therapeutic targeting drug have not been fully explored. In this study, we define the oncogenic role of METTL3 in melanoma development and progression. Building on this insight, we examine our recently designed peptide inhibitor RM3, which targets the binding interface of METTL3/14 complex for disruption and subsequent ubiquitin-mediated proteasomal degradation via the E3 ligase STUB1. RM3 treatment reduces proliferation, migration, and invasion, and induces apoptosis in melanoma cells in vitro and in vivo. Subsequent transcriptomic analysis identified changes in immuno-related genes following RM3-mediated suppression of METTL3/14 N 6 -methyladenosine (m 6 A) methyltransferase activity, suggesting a potential for interaction with immunotherapy. A combination treatment of RM3 with anti-PD-1 antibody results in significantly higher beneficial tumor response in vivo, with a good safety profile. Collectively, these findings not only delineate the oncogenic role of METTL3 in melanoma but also showcase RM3, acting as a peptide degrader, as a novel and promising strategy for melanoma treatment., (© 2024 Wiley-VCH GmbH.)

The large anomalous Nernst effect in magnetic Weyl semimetals is one of the most intriguing transport phenomena, which draws significant attention for its potential applications in topological thermoelectrics. Despite frequent reports of substantial anomalous Nernst conductivity (ANC), methods to optimize Nernst thermoelectrics remain limited. The research reveals that the magnitude of the ANC is directly related to the sum of the anomalous Nernst and Hall angles. While the sign of the anomalous Hall angle is relatively stable in a certain material, the sign of the anomalous Nernst angle can be intrinsically tuned. Therefore, the ANC can be effectively optimized by regulating these angles to work in concert. This finding is verified by experimental modulation from iron-doped magnetic topological material Co 3 Sn 2 S 2 . Additionally, a robust TlnT scaling law of the ANC over the temperature range of 40 to 140 K is observed in all studied samples, suggesting an intrinsic origin of the ANC. Considering the common opposite sign of the anomalous Nernst and Hall angles in many magnetic topological materials, the research offers an applicable scheme for optimizing the Nernst thermoelectrics., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The Insect Cell-Baculovirus Expression Vector System (IC-BEVS) is widely used for the generation of a variety of gene products, including proteins, vaccines, and gene therapy vectors; however, it has some limitations, including a constrained host range and low protein yields. In a previous study, we established the RIRI-PA1 cell line, which was derived from Periplaneta americana. This cell line is susceptible to Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infection, which results in a higher yield production of recombinant protein within a short post-infection period of 24-48 h compared to the commonly used engineered cell line Sf21. To elucidate the basis for this phenomenon, we used RNA sequencing and transcriptome analysis of RIRI-PA1 and Sf21 cells infected with AcMNPV-GFP at 24, 72, and 168 h post-infection. Differentially expressed genes (DEGs) were identified in both cell lines. GO, eggNOG, and KEGG annotation analyses were used to identify DEGs and select candidate genes that could regulate recombinant protein expression. The results indicated a significant link between ribosomal pathway regulation and recombinant protein expression. After 24 h of AcMNPV-GFP infection, relatively high levels of protein were produced in RIRI-PA1 cells compared to Sf21 cells, which exhibited lesser enrichment of ribosomal protein-related DEGs (7 : 12). Moreover, a correlation was observed in the gene expression patterns between AcMNPV-GFP infection and recombinant protein synthesis, including genes associated with the ribosome, Toll and Imd signaling, and the cytochrome P450 pathway. Overall, our findings suggested that the ribosomal pathway might be more involved in regulation of protein expression during the early stages of RIRI-PA1 infection. The mechanisms underlying this process could have potential future applications in engineering cell modifications to reduce production time for recombinant proteins and to promote the use of IC-BEVS., (© 2024 Federation of European Biochemical Societies.)

The development of dielectric capacitors toward high voltage and high power density requires materials with excellent insulation and energy storage performances. In this work, a polymer dielectric with polyetherimide (PEI) as the matrix and calcium barium zirconate titanate (BZCT) coated by barium titanate fiber (BT) as the filler (BZCT@BT) was constructed. The (0.5%-10% BZCT@BT/PEI) polymer dielectric has an excellent discharge energy density (Ue) of 6.66 J/cm3 and maintains an advanced charge/discharge efficiency (η) of 93.29% when the BT content was 0.5% and the BZCT particle content was 10%. The addition of BZCT endows the polymer dielectric with a higher relative dielectric constant (εr), while BT, maintaining a lower εr than BZCT, could reduce the electric field (E) distortion caused by the dielectric mismatch between PEI and BZCT. Oriented fiber fillers increase the breakdown strength of the polymer dielectric, ultimately increasing the performance of energy storage. A new strategy for the design of energy storage polymer dielectrics was provided by this work., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Natural products play a pivotal role in the advancement of state-of-the-art pharmaceuticals. To augment their therapeutic efficacy, structural modifications of these compounds are routinely performed. In this study, we introduce an efficient and environmentally benign electrochemical oxidative method for site-selective direct C-H activation of tanshinone IIA under metal-free, oxidant-free, and base-free conditions. Moderate to excellent yields up to 92% of the desired tanshinone IIA derivatives were obtained with a broad substrate scope. Biological activity assays demonstrate that compounds 2k, 2q and 2w possess superior antitumor efficacy compared to tanshinone IIA.

Bifunctional phase change materials (PCMs) with efficient energy storage and photothermal conversion capabilities have tremendous potential to be applied in advanced thermal management. However, classical organic PCMs with high latent heat are challenged by poor light harvesting, low thermal conductivity, and leakage risks. Here, we design a unique dual-carbon network with Ni nanoparticles (NPs), confined carbon nanotubes (CNTs) shuttling in carbon honeycombs (CH), namely, CH@Ni-CNTs, to encapsulate paraffin wax (PW) that can facilitate the light capture and photothermal conversion dynamics. Benefiting from the physical adsorption of the hierarchical porous structure, the obtained PW/CH@Ni-CNTs composite PCMs show a high phase change enthalpy of 131.0 J g -1 and long-lasting thermal stability of up to 300 heating-cooling cycles. Moreover, an outstanding photothermal energy conversion efficiency of 96.9% is achieved due to the synergistic effect of the dual carbon network and confined Ni NPs. The CNTs shuttled CH network affords multiple reflection chambers and a thermal conductive pathway, while the localized surface plasmon resonance (LSPR) effects of Ni NPs concentrate the incident light energy to generate and accelerate the transport of active "hot electron", thus collectively contributing to the excellent photothermal properties of the composite PCMs. This study presents a bifunctional Ni-induced dual-carbon network system for the controllable preparation of composite PCMs, and it sheds light on the photothermal conversion mechanisms.

The production of hybrid alkali-activated cement (HAAC) has generated considerable interest in environmental issues. In this research, the environmental impacts of utilizing red mud (RM) as a partial activator of alkali-activated ground granulated blast furnace slag (GBFS) in HAAC production have been evaluated. A contribution analysis was carried out using life cycle assessment (LCA) to assess the environmental significance of six important substances in HAAC production. A comparative analysis of the environmental consequences of producing ordinary portland cement (OPC) and two HAACs using various activators in the same plant was conducted. The results showed that the calcination and preparation of alkali-activated cementitious materials are the two processes with the highest environmental impacts. Marine ecotoxicity was identified as the primary impact category, followed by freshwater ecotoxicity and fossil depletion. HAAC provides better benefits than OPC in most environmental impact categories. Additionally, the inclusion of RM as a partial alkali activator to HAAC results in even more pronounced environmental benefits when compared to NaOH alone, particularly in terms of cleaner production areas., Competing Interests: Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent to publish: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The sulfion oxidation reaction (SOR) could offer an energy-efficient and tech-economically favorable alternative to the oxygen evolution reaction (OER) for H2 production. Transition metal (TM) based catalysts have been considered promising candidates for SOR but suffer from limited activity due to the excessive bond strength from TM-S2- d-p orbit coupling. Herein, we propose a feasible strategy of screening direct d-p orbit hybridization between TM and S2- by constructing the Turing structure composed of lamellar stacking carbon-confined nickel nanosheets. The optimized p-p orbit coupling between electron-injected carbon and S2- enables exceptional catalytic activity and stability for sulfion degradation and energy-efficient yet value-added H2 production. Specifically, it achieves a current density of 500 mA cm-2 at an ultralow potential of 0.67 V vs. RHE for alkaline SOR. Theoretical calculations indicate that the electron transfer from Ni imparts metallicity and a higher p-band center to carbon shells, thereby contributing to optimized p-p orbit hybridization and a thermodynamically favorable stepwise sulfion degradation. Practically, a two-electrode flow cell achieves an industrial current density of 1 Acm-2 at an unprecedented low voltage of 0.91 V while maintaining stability for over 300 hours, and exhibits high productivities of 3.83 and 0.32 kgh-1m-2 for sulfur and H2, respectively., (© 2024 Wiley‐VCH GmbH.)

Bronchopulmonary dysplasia (BPD) is one of the most prevalent complication in preterm infants, primarily characterized by arrested alveolar growth. The involvement of epithelial-mesenchymal transition (EMT) of AECII cells is proposed to have a crucial role in the pathogenesis of BPD; however, the underlying mechanism remains unclear. The present study reveals a significant reduction of WHAMM (WASP homolog associated with actin, membranes, and microtubules) in hyperoxia-induced BPD mice, highlighting its crucial role in suppressing the progression of BPD through the inhibition of EMT in AECIIs. We demonstrated that hyperoxia-induced downregulation of WHAMM leads to the accumulation of TGF-β1 primarily through its mediation of the autophagic degradation pathway. Mechanistically, WHAMM enhanced the autophagosomal localization of TGF-β1 and concurrently promoted the process of autophagy, thereby comprehensively facilitating the autophagic degradation of TGF-β1. These findings reveal the important role of WHAMM in the development of BPD, and the proposed WHAMM/autophagy/TGF-β1/EMT pathway may represent a potential therapeutic strategy for BPD treatment., (© 2024 Wiley Periodicals LLC.)

Efficient bioassimilation of one-carbon (C1) feedstocks is often hindered by the toxicity of C1 substrates and/or intermediates. We compared the toxicity of several common C1 substrates/intermediates and found that formaldehyde imposes the highest toxicity on the representative bacterium Escherichia coli . Besides causing chromosomal DNA and protein damage effects, here, we revealed that formaldehyde greatly impairs cell membranes. To this end, here, we sought to remodel the cell membrane of E. coli by introducing a non-native, eukaryote-featured membrane phospholipid composition, phosphatidylcholine (PC). This engineered E. coli strain exhibited significantly increased membrane integrity, resulting in enhanced formaldehyde tolerance. When applied to C1 assimilation, the PC-harboring E. coli consumed up to 4.7 g/L methanol, which is 23-fold higher than that of the control strain (0.2 g/L). In summary, the present study highlights the detrimental impact of formaldehyde-induced membrane damage and thus underscores the significance of membrane remodeling in enhancing formaldehyde tolerance and facilitating the assimilation of C1 substrates.

Sepsis-associated encephalopathy (SAE), one of the common complications of sepsis, is associated with higher ICU mortality, prolonged hospitalization, and long-term cognitive decline. Sepsis can induce neuroinflammation, which negatively affects hippocampal neurogenesis. Dexmedetomidine has been shown to protect against SAE. However, the potential mechanism remains unclear. In this study, we added lipopolysaccharide (LPS)-stimulated astrocytes-conditioned media (LPS-CM) to neural stem cells (NSCs) culture, which were pretreated with dexmedetomidine in the presence or absence of the α2-adrenoceptor antagonist yohimbine or the α2A-adrenoceptor antagonist BRL-44408. LPS-CM impaired the neurogenesis of NSCs, characterized by decreased proliferation, enhanced gliogenesis, and declined viability. Dexmedetomidine alleviated LPS-CM-induced impairment of neurogenesis in a dose-dependent manner. Yohimbine, as well as BRL-44408, reversed the effects of dexmedetomidine. We established a mouse model of SAE via cecal ligation and perforation (CLP). CLP-induced astrocyte-related neuroinflammation and hippocampal neurogenesis deficits, accompanied by learning and memory decline, which were reversed by dexmedetomidine. The effect of dexmedetomidine was blocked by BRL-44408. Collectively, our findings support the conclusion that dexmedetomidine can protect against SAE, likely mediated by the combination of inhibiting neuroinflammation via the astrocytic α2A-adrenoceptor with attenuating neuroinflammation-induced hippocampal neurogenesis deficits via NSCs α2A-adrenoceptor.

Chemical additives play a critical role in the crystallization kinetics and film morphology of perovskite solar cells (pero-SCs), thus affecting the device performance and stability. Especially, carboxylic acids and their congeners with a -COOH group can effectively serve as ligands to fortify the structural integrity and mitigate the risk of lead efflux. However, direct addition of -COOH into the precursor solution could retard the crystallization kinetics of the perovskite during film formation due to the strong coordination. Here, we present a novel approach of in situ functional group conversion using Bis(2,5-dioxopyrrolidin-1-yl) 4,7,10,13-tetraoxahexadecanedioate (Bis-PEG4-NHS ester) as an additive in the antisolvent, which underwent a functional group transformation from -COOR to -COOH during the annealing process through a hydrolysis reaction of Bis-PEG4-NHS ester. The corresponding hydrolysates exhibit enhanced interactions with PbI 2 and FAI, contributing to the structural integrity and the defect passivation. Our findings offer valuable insights into the chemical interactions within the crystal growth process, achieving the p-i-n pero-SC device with an efficiency of 25.79% (certified as 25.47%) and notable long-term stability.

Knowledge of antibiotic desorption from high-temperature biochar is essential for assessing their environmental risks, and for the successful application of biochar to remove antibiotics. In previous studies, irreversible pore deformation, formation of charge-assisted hydrogen bonds or amide bonds were individually proposed to explain the desorption hysteresis of antibiotics on biochars, leading to a debate on hysteresis mechanism. In this study, desorption of sulfamethoxazole (SMX), ciprofloxacin (CFX) and tetracycline (TET) on a wood chip biochar produced at 700 °C (WBC700) and its oxidized product (O-WBC700) was investigated to explore the underlying hysteresis mechanism. Significant desorption hysteresis was observed for SMX, CFX and TET on WBC700 and O-WBC700. Hysteresis index (HI) of each antibiotic was higher on O-WBC700 with more oxygen-containing groups than WBC700, and was higher at lower equilibrium concentration. HI of antibiotics on WBC700 (or O-WBC700) increased in the order of SMX < CFX < TET. The calculated adsorption enthalpy of each antibiotic on WBC700 was positive, indicating an endothermic process. These phenomena together with FTIR, XPS spectra confirmed that the desorption hysteresis mechanism of antibiotics on high-temperature biochar is the formation of amide bonds by amidation reaction, but not the pore deformation or the hydrogen bond. Moreover, antibiotic can form amide bonds with WBC700 only if the amine group with pK a  > 4.0, and the HI values were positively correlated with their pK a values. Amine group of antibiotics with higher pK a value show more nucleophilicity and could form stronger amide bonds with carboxyl group of biochar. The obtained results could help to solve the debate on desorption hysteresis mechanism of antibiotics on high-temperature biochars, and provide a new insight into the role of amine groups and amidation reaction on the hysteresis., 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.)

Purpose: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME., Methods: This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS)., Results: Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group)., Conclusion: This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.

Non-cystic fibrosis bronchiectasis is a progressive respiratory disease with limited treatment options, prompting the exploration of regenerative therapies. This study investigates the safety and efficacy of autologous P63 + progenitor cell transplantation in a randomized, single-blind, controlled, phase 1/2 trial. Thirty-seven patients receive bronchoscopic airway clearance (B-ACT) (n = 19) or B-ACT plus P63 + progenitor cells (n = 18). Results show that compared to the control group, the change in D LCO levels from baseline to 24 weeks post therapy is significantly higher in the cell treatment group (p value = 0.039). Furthermore, the patients in the cell treatment group demonstrate significantly reduced lung damaged area, improved SGRQ score, and ameliorated BSI and FACED scores within 4-12 weeks post therapy. Transcriptomic analysis reveals that progenitor cells with higher expression of P63 gene have better therapeutic efficacy. These findings suggest that P63 + progenitor cells may offer a promising therapeutic approach for bronchiectasis. This study was registered at ClinicalTrials.gov(NCT03655808)., Competing Interests: Declaration of interests W. Zuo and T.Z. have an equity interest in Regend Therapeutics, holding the patent for human lung progenitor cell isolation and expansion technique., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Gliomas exhibit high heterogeneity and poor prognosis. Despite substantial progress has been made at the genomic and transcriptomic levels, comprehensive proteomic characterization and its implications remain largely unexplored. In this study, we perform proteomic profiling of gliomas using 343 formalin-fixed and paraffin-embedded tumor samples and 53 normal-appearing brain samples from 188 patients, integrating these data with genomic panel information and clinical outcomes. The proteomic analysis uncovers two distinct subgroups: Subgroup 1, the metabolic neural subgroup, enriched in metabolic enzymes and neurotransmitter receptor proteins, and Subgroup 2, the immune subgroup, marked by upregulation of immune and inflammatory proteins. These proteomic subgroups show significant differences in prognosis, tumorigenesis, microenvironment dysregulation, and potential therapeutics, highlighting the critical roles of metabolic and immune processes in glioma biology and patient outcomes. Through a detailed investigation of metabolic pathways guided by our proteomic findings, dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP) emerge as potential prognostic biomarkers linked to the reprogramming of nucleotide metabolism. Functional validation in patient-derived glioma stem cells and animal models highlights nucleotide metabolism as a promising therapy target for gliomas. This integrated multi-omics analysis introduces a proteomic classification for gliomas and identifies DPYD and TYMP as key metabolic biomarkers, offering insights into glioma pathogenesis and potential treatment strategies., Competing Interests: Competing interests T.G. is a shareholder of Westlake Omics Inc. The other authors declare no potential competing of interest., (© 2024. The Author(s).)

Allergen-specific immunotherapy (AIT) is an aetiology-targeting therapy for allergic diseases. The therapeutic mechanism of AIT is not fully understood yet. Endoplasmic reticulum stress is associated with the pathogenesis of allergic disorders. This study aims to elucidate the effects of AIT on suppressing allergic response through regulating endoplasmic reticulum stress. In this study, patients with perennial allergic rhinitis were recruited. AIT was conducted for the patients. An allergic rhinitis (AR) mouse model was established with mite extracts as allergens. We found that AIT modulated the endoplasmic reticulum stress status in peripheral CD4 + T cells in patients with allergic rhinitis. The intensity of endoplasmic reticulum stress associated the PERK (protein kinase RNA-like endoplasmic reticulum kinase)-eIF2a (eukaryotic translation initiation factor 2a) axis in CD4 + T cells was upregulated by AIT, which was closely associated with the improvement in allergic rhinitis response after AIT. eIF2a interacted with GATA3 to downregulate the IL4 gene transcription in CD4 + T cells. High doses of aluminium hydroxide (alum) in AIT vaccines enhanced the activity of XBP1 to suppress eIF2a in CD4 + T cells. AIT containing a low dose of alum effectively mitigated the experimental allergic rhinitis, while the AIT without alum or a high dose of alum exacerbated the experimental allergic rhinitis. In conclusion, the alum adjuvant in allergen vaccines can regulate the activity of eIF2a to regulate the expression of Th2 cytokines in CD4 + T cells. Manipulating the alum dose in AIT vaccines has the potential to enhance the therapeutic effects of AIT., (© 2024 The Scandinavian Foundation for Immunology.)

This study leverages accelerated reactions at the solution/air interface of microdroplets generated by desorption electrospray ionization (DESI) to explore the chemical space. DESI is utilized to synthesize drug analogs at an overall rate of 1 reaction mixture per second, working on the low-nanogram scale. Transformations of multiple drug molecules at specific functionalities (phenol, hydroxyl, amino, carbonyl, phenyl, thiophenyl, and alkenyl) are achieved using electrophilic/nucleophilic, redox, C-H functionalization, and coupling reactions. These transformations occur under ambient conditions on the millisecond time scale with direct detection of products being successful in all but three of the reaction types studied. The large scope (22 bioactive compounds, >20 chemical transformations, and >300 functionalization reagents) and high speed (>3000 reactions/hour) provide access to a wide array of drug analogs that can be used for bioactivity testing. A total of ∼6800 unique reactions were examined through a data-driven workflow, and more than 3000 unique derivatives (∼44%) were identified tentatively by the m / z value and signal-to-control ratio in single-stage mass spectrometry (MS) analysis, with over 1000 being further characterized by tandem MS. The speed of the DESI-MS reaction screen provides potential advantages for emerging machine learning-based predictions of organic synthesis, and it sets the stage for future online DESI-MS bioassays and scaled-up microdroplet synthesis before formal characterization of hit compounds is sought using traditional methods of drug discovery.

Targeting the lysine residue of protein kinases to develop covalent inhibitors is an emerging hotspot. Herein, we have reported an approach to develop lysine-targeted covalent inhibitors of PI3Kδ by in situ interaction upgradation of the H-bonding to covalent bonding. Several warhead groups were introduced and screened in situ, leading to lysine-targeted covalent inhibitors bearing aromatic esters with high bioactivity and PI3Kδ selectivity. Compound A11 bearing phenolic ester was finally optimized to show a long duration of action in SU-DHL-6 cells by multiple assays. Docking simulation and further protein mass spectrometry confirmed that A11 bound to PI3Kδ by covalent-bonding interactions with Lys779. Furthermore, A11 exhibited potently antitumor efficacy without obvious toxicity in the SU-DHL-6 and Pfeiffer xenograft mouse models. This study identified A11 to be a much more effective antitumor agent in vitro and in vivo as a lysine-targeted covalent inhibitor, and it also provided a practical approach for the development of lysine-targeted covalent inhibitors.

The phylum Gemmatimonadota is widespread but rarely cultured and, in fact, there are only six described species isolated from soil, freshwater, and wastewater treatment. However, no isolates of Gemmatimonadota from marine environment have been described; thus, little is known about the physiology and metabolism of members of the marine lineages. In this study, four novel facultatively anaerobic bacterial strains belonging to Gemmatimonadota were isolated from marine sediments collected from Xiaoshi Island in Weihai, China, using an aerobic enrichment method. The integrated results of phylogenetic and phenotypic characteristics supported that these four strains represent one novel species in a novel genus, for which the name Gaopeijia maritima gen. nov., sp. nov. is proposed, as the first representative of novel taxa, Gaopeijiales ord. nov., Gaopeijiaceae fam. nov. in the class Longimicrobiia. Gaopeijiales was detected in 22,884 out of 95,549 amplicon data sets, mainly from soil. However, the highest mean relative abundances were in sponge (0.7%) and marine sediment (0.35%), showing salt-related character. Most of the Gaopeijiales subgroups potentially belong to the rare bacterial biosphere. The aerobic enrichment in this study could significantly increase the relative abundance of Gaopeijiales (from 0.37% to 2.6%). Furthermore, the metabolic capabilities inferred from high-quality representative Gaopeijiales genomes/MAGs suggest that this group primarily performs chemoorganoheterotrophic metabolism with facultatively anaerobic characteristics and possesses various secondary metabolite biosynthesis gene clusters (BGCs), mirroring those observed in the four novel strains.IMPORTANCEDespite rapid advances in molecular and sequencing technologies, obtaining pure cultures remains a crucial research goal in microbiology, as it is essential for a deeper understanding of microbial metabolism. Gemmatimonadota is a widespread but rarely cultured bacterial phylum. Currently, there are only six cultured strains of this interesting group, all isolated from non-marine environments. Little is known about the physiology and metabolism of members of the marine lineages. Here we isolated and characterized four novel marine strains, and proposed a new order Gaopeijiales within Gemmatimonadota . Furthermore, the global distribution, environmental preference, and metabolic potential of Gaopeijiales are analyzed using public data. Our work enriches the resources available for the under-represented phylum Gemmatimonadota and provides insights into the physiological and metabolic characteristics of the marine lineage ( Gaopeijiales ) through culturology and omics.

Purpose: The relationship between metabolic syndrome (MetS) and the risk of Alzheimer's disease (AD) remains unclear. This meta-analysis aims to clarify the prospective association between MetS and AD risk and to explore how individual MetS components contribute to this relationship. Methods: Comprehensive searches of MEDLINE, Web of Science, and Embase were conducted up to April 12, 2024. Relevant prospective cohort studies were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the associations. A random-effects model was used to incorporate the potential impact of heterogeneity. Findings: Six prospective cohort studies with seven datasets, including 484,994 participants and a follow-up of 3.5 to 13.0 years, were included. The pooled analysis showed no significant association between MetS and AD risk (HR: 0.96, 95% CI: 0.89-1.04, P = 0.37; I 2 = 0%). Sensitivity and subgroup analyses confirmed these findings. Individual MetS components exhibited varied effects as follows: abdominal obesity was linked to a reduced AD risk (Risk ratio (RR): 0.70, 95% CI: 0.56-0.88, P = 0.002), whereas high blood pressure (BP) (RR: 1.15, 95% CI: 1.04-1.27, P = 0.007) and hyperglycemia (RR: 1.24, 95% CI: 1.08-1.42, P = 0.002) were associated with an increased risk. Low high-density lipoprotein cholesterol and high triglycerides showed no significant associations. Conclusions: This meta-analysis found no significant overall association between MetS and AD risk. However, specific MetS components, such as abdominal obesity, high BP, and hyperglycemia, may influence AD risk differently.

Efficient lithium recovery from geothermal brines is crucial for the battery industry. Current electrochemical separation methods struggle with the simultaneous presence of Na + , K + , Mg 2+ , and Ca 2+ because these cations are similar to Li + , making it challenging to separate effectively. We address these challenges with a three-chamber reactor featuring a polymer porous solid electrolyte in the middle layer. This design improves the transference number of Li + (t Li + ) by 2.1 times compared to the two-chamber reactor and also reduces the chlorine evolution reaction, a common side reaction in electrochemical lithium extraction, to only 6.4% in Faradaic Efficiency. Employing a lithium-ion conductive glass ceramic (LICGC) membrane, the reactor achieved high t Li + of 97.5% in LiOH production from simulated brine, while the concentrations of Na + K + , Mg 2+ , and Ca 2+ are below the detection limit. Electrochemical experiments and surface analysis elucidated the cation transport mechanism, highlighting the impact of Na + on Li + migration at the LICGC interface., Competing Interests: Competing interests statement:Y.F., Z.F., H.W., and S.L.B. are inventors on a provisional United States patent application titled “Electrochemical Manufacturing of Lithium Hydroxide from Geothermal Brines in a Three-chamber Solid Electrolyte Reactor using a LICGC membrane” for the technology related to this work.

The reserves of sodium resources are much larger than those of lithium resources, and they are widely distributed and easy to produce and can be widely used in photovoltaic energy storage and other industries on the premise of this advantage. However, how to produce hard carbon anodes at a low cost for the preparation of energy storage materials requires continuous exploration and experimentation to find the optimal solution. Here, we used waste sour date shell biomass as a precursor for a hard carbon anode obtained by simple acid treatment and two pyrolyses. It is shown that acid washing after prepyrolysis has a significant effect on the electrochemical performance of the sour date shell-derived hard carbon (ZJ), constructing a stable structure that makes it easier for sodium ions to be embedded and dislodged, and the carbon particles are homogeneous and free of bonding and electrode cracking. The ZJ-1500-HCl pyrolyzed at 1500 °C has a high reversible capacity of 329.1 mAh g -1 , 94.1% initial Coulombic efficiency (ICE), 90.54% capacity retention efficiency cycling 300 cycles at a current density of 300 mA g -1 , and a resistivity below 10 Ω. It has good cycle stability and a good multiplier performance. It is expected to be used in practical production and photovoltaic energy storage in the future.

We pioneered a dual-targeted trinity of antibody-peptide-drug delivery consortium to combat HER2+ tumors. This innovative approach leverages the self-assembly of peptides with high affinity to antibodies to create nanofibers for antibody encapsulation, offering a novel strategy in antibody drug delivery.

Effective angiogenesis is essential for creating complex vascular networks in tissue engineering; however, there is a scarcity of safe and potent pro-angiogenic factors. Although a decellularized extracellular matrix (dECM) offers excellent biocompatibility and is widely used in tissue engineering as a pro-angiogenic additive, its conventional extraction technique resulting in significant loss of bioactivity limits clinical potential. The dorsal dermal tissue has rich blood perfusion and its dECM is rich in angiogenic factors. In this study, the dECM components from the dorsal dermis of mice (DD) were produced to enhance in vitro and in vivo pro-angiogenic abilities using a novel physical method. Morphological studies showed no significant difference between DD-wild-type (DD-wt) and DD-wild-type-newborn (DD-wtn), and there was also no difference in DNA or RNA concentration. In addition, DD-wtn outperformed DD-wt in maintaining the stemness of MSCs, promoting inflammatory response and facilitating endothelial cell differentiation. It is of greater significance to note that the dermal combined fibrous capsule thickness is greater in the DD-wt treated group than in the DD-wtn group. Furthermore, the number of blood vessels in the subcutaneously implanted scaffold with DD-wtn increased by 233%. Consequently, our current finding provides a promising strategy to produce a novel pro-angiogenic bioink additive for enhancing vascularization in 3D bioprinting.

The photocatalytic hydrogen evolution reaction has been considered as an efficient route to addressing energy and environmental issues. As an interesting class of multi-electron transfer catalysts, polyoxometalates (POMs) have been widely used for photocatalytic hydrogen evolution due to their tunable geometrical and electronic structures, reversible electron storage capacity, and preeminent redox properties. This Frontier article highlights our recent advances in the construction of efficient POM-based photocatalytic hydrogen evolution systems in terms of three aspects, including polyoxometalate-based catalysts, light-absorbing photosensitizers, and sacrificial reagents.

Clinically, patients with lipid metabolism disorders caused by factors such as high-fat diet (HFD) developed severer liver damage and lipid metabolism disorders after treatment with cyclophosphamide (CTX). This can lead to elevated levels of inflammatory cytokines, which in turn lead to changes in levels of various liver and kidney transporters, to increase drug accumulation, which may be a way to exacerbate liver injury. The role of organic anion transport peptides (OATPs), an important uptake transporter, in the transport process of CTX and in the aggravation of liver injury induced by CTX in HFD mice is unclear. The aim of this study was to characterize the hepatotoxicity and lipid metabolism disorders of HFD mice exposed to CTX and to investigate the possible mechanism from the perspective of drug in vivo process and transporter regulation. It has been verified that CTX induced severer liver injury in HFD mice compared with the control group, accompanied with upregulated Interleukin-1β (IL-1β) expression and down-regulated OATPs expression in liver and renal, and increased blood CTX concentration. This suggested that the down-regulation of OATPs involved in IL-1β may play an important role in HFD-CTX-induced liver injury, and then experiments in Hep G2 cells was used to validate the hypothesis. Pharmacokinetic and primary hepatocyte uptake experiments confirmed that OATPs may be an important factor involved in the in vivo process of CTX. In summary, this study demonstrated that HFD mice exhibited severer liver toxicity after exposure to CTX, which may be caused by the disorder of lipid levels and the up-regulation of inflammatory factors, and then the downregulation of liver and renal OATPs to increase the accumulation of CTX in vivo. These findings suggest that IL-1β and OATPs may be involved in the interactive regulation of CTX accumulation and endogenous lipid disturbance, and play very important role in the aggravation of liver injury induced by CTX in HFD mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Surrounding rock pressure prediction for fully mechanized coal face (FMCF) roof management and control is of great significance. The key challenge is to effectively combine various factors to evolve the surrounding rock pressure trend with high temporal-spatial correlation and heterogeneity. The hydraulic support load is an important indicator that reflects the change in the surrounding rock pressure. Inspired by the research on 'support-surrounding rock' and the massive data collected by sensors, this paper proposes a data-driven prediction framework for surrounding rock pressure in FMCFs. The framework includes the multidimensional working condition matrix (MWCM) building module, the hydraulic support group temporal-spatial feature fusion (HTSFF) network, and the adaptive deployment strategy (ADS). The MWCM generating methods of hydraulic support in combination with the mining process and the data quality and quantity requirements of the conventional supervised learning method are weakened by the treatment of missing data adapting to the working conditions. The HTSFF network focuses on capturing the spatial correlation of the surrounding rock pressure along the mining direction and the temporal periodicity along the advancing direction of the FMCF and fully considers the dependencies between them. ADS aims to solve the problem of missing data in model deployment and reduce the interference of abnormal data in the model prediction process by adaptively generating MWCM. The rationality and practicability of various designs of the proposed framework were verified on our dataset. Quantitative experiments show that the average error of the surrounding rock pressure prediction is 1.2406 MPa, and the accuracy, precision, and recall rate of periodic pressure prediction are all above 95%. This method can effectively assist FMCF roof management and control. Although the method is effective, it may require further fine-tuning of the model to adapt to different geological conditions and varying sensor quality, ensuring broader applicability., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

On the basis of the law of conservation of energy, the three stages of rock creep are analyzed. The reasons for the difficulty in studying the accelerated creep stage of rocks using the traditional creep model are expounded. The triaxial creep deformation law and critical point parameter values of rocks are obtained by carrying out rock creep tests under different confining pressures. Based on strain energy theory, the law of conservation of energy, and Perzyna viscoplastic theory, a creep constitutive model, which can describe the whole process of primary creep, steady-state creep, and accelerated creep, is established. Results show that the model can well reflect the creep characteristics of rocks, especially when the load of rocks is greater than the long-term strength. It has an obvious effect on highlighting the accelerated creep stage of rocks. The fitting degree of the creep model curve and test curve is considerably greater than that of the Nishihara model curve and test curve. The model not only describes the whole process of rock primary creep, steady-state creep, and accelerated creep thoroughly but also compensates for the shortcomings of traditional models in describing accelerated creep. This model can provide a theoretical basis for further revealing the objective law of rock creep., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Radiotherapy is a primary modality in cancer treatment but is accompanied by severe side effects to healthy tissues and radiation resistance to some extent. To overcome these limitations, we developed a H 2 O 2 -responsive photosensitizer, CyBT, which could be activated by the upregulated H 2 O 2 induced by radiotherapy, enabling near-infrared fluorescence imaging-guided combination photodynamic and radiotherapy. The synthesis of CyBT began with the covalent linkage of hemicyanine and a free radical TEMPO through the click reaction, which demonstrated superior photodynamic properties. Shielding of fluorescence and photodynamic activity was achieved by incorporating phenylboronic acid pinacol ester. In X-ray irradiated tumor cells, the upregulation of H 2 O 2 activated CyBT, thereby restoring its fluorescence and photodynamic activity. Additionally, the positive charge of CyBT facilitated its targeting to the mitochondria within tumor cells for more efficiently triggering cell apoptosis. CyBT was co-assembled with a polymer PEG- b -PDPA to form acid-responsive nanoparticles (NPs-CyBT). This formulation enhanced tumor targeting, improved water solubility of CyBT, and extended in vivo circulation time. Utilizing fluorescence imaging to guide photodynamic and radiotherapy, NPs-CyBT can accurately target solid tumors in mice, and lead to tumor elimination, suggesting that it is a potential strategy for the effective treatment of malignant tumors.

New strategies for enhancing the fluorescence emission of metal nanoclusters (MNCs) are very crucial for the highly sensitive sensing of food hazards. In this work, we prepared MNC supraparticles (Sc-CB/AuNCs) by simultaneously introducing cucurbit[7]uril (CB[7]) and Sc 3+ ions into ATT-AuNCs for the first time. The obtained supraparticles exhibited strong emission enhancement due to synergistic aggregation-induced emission enhancement and restriction of intramolecular motion effects. Notably, the fluorescence of ATT-AuNCs was enhanced by 24-fold due to the combination of CB[7] and Sc 3+ ions, and the quantum yield reached 69.1%. Moreover, we found that tetracycline (TC) could bind to the Sc-CB/AuNCs through simultaneous host-guest recognition and ionic complexation, which effectively quenched the Sc-CB/AuNCs through the synergy of photoinduced electron transfer and inner filter effect. Based on the above multiple interactions between TC and Sc-CB/AuNCs, an ultrasensitive sensing method for TC was constructed with an LOD of 0.3 nM. Furthermore, a portable fluorescent gel sensor was constructed and successfully used for TC detection in honey samples. The test took only 2 min. This work not only provided a simple and effective fluorescence enhancement strategy for MNCs but also offered a novel sensing strategy, which may largely extend the potential of host-guest recognition-based sensors for food and environmental hazards.

Impending myasthenic crisis (IMC) is an emergent situation requiring aggressive management to prevent patients from developing myasthenic crisis (MC) in patients with myasthenia gravis (MG). Efgartigimod has been proved to be well tolerated and efficacious in MG patients. The present study aimed to compare the efficacy of efgartigimod and intravenous immunoglobulin (IVIg) in rescuing IMC. IMC patients treated with efgartigimod or IVIg were retrospectively enrolled. The primary outcome was determined as the mean change in MG activities of daily living (MG-ADL) score from baseline to week 1 and 4 after treatment, respectively. Safety was assessed based on medical records during the hospitalization to monitor the adverse events. A total of 9 patients treated with efgartigimod and 10 patients treated with IVIg were enrolled. There were no significant differences in the clinical characteristics at baseline between the two groups (P > 0.05). Compared with the IVIg group, the efgartigimod group had a greater reduction in the MG-ADL score at week 1 (P = 0.035) and week 4 (P = 0.005). One patient in the efgartigimod group had an upper respiratory infection. These findings suggest that efgartigimod is a treatment option for IMC in addition to IVIg and plasma exchange., Competing Interests: Declarations Competing interests The authors declare no competing interests. Consent for publication All authors agreed with the content of the manuscript, and all patients or legal guardians consented to the publication. Ethical approval We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines., (© 2024. The Author(s).)

The application of seawater splitting is crucial for hydrogen production; therefore, efficient electrocatalysts are necessary to prevent chlorine evolution and severe corrosion. A synergistic method is employed on CoFe LDH by integrating a conductive Ti3C2Tx MXene layer and subsequently applying anionic modulation. Robust metal-substrate interaction along with subsequent phosphidation facilitates efficient electron transfer and optimises the electronic structure of Co and Fe sites. The CoFe-P-1000@Ti3C2Tx/CC demonstrates commendable electrochemical performance, requiring overpotentials of 106.6 mV and 276 mV for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) at 10 mA cm-2 in 1M KOH electrolyte, while 292 mV is necessary for OER in a simulated seawater electrolyte (1 M KOH + 0.5 M NaCl). Furthermore, the CoFe-P-1000@Ti3C2Tx/CC exhibits an encouraging cell voltage of 1.59 V (j = 10 mA cm-2) for comprehensive alkaline seawater splitting, maintaining exceptional stability for over 50 hours., (© 2024 Wiley‐VCH GmbH.)

Developing metal-organic frameworks (MOFs) with specific structures is critical for improving the activity of embedded enzymes, and defects may be one of the effective methods. Several methods have been demonstrated to be effective in creating defects in MOFs, including post-synthetic treatments, the use of acid as a modulator, and the use of ordinary or thermally sensitive linkers. However, these methods necessitate the utilization of additional substances. Metal azolate framework-7 (MAF-7) is a kind of MOF that was formed by the coordination of Zn 2+ with 3-methyl-1,2,4-triazole (Hmtz). This paper presents a method for the preparation of defect MAF-7 by changing the sequence of reactants without the introduction of additional substances. The defects were characterized by a range of techniques, including scanning electron microscopy, transmission electron microscopy, Brunauer-Emmett-Teller, X-ray photoelectron spectroscopy, and powder X-ray diffraction. The activity of microcystinase A (MlrA) encapsulated in defective MAF-7 (CMlrA@DMAF-7) was found to be significantly increased in comparison to non-porous MAF-7 (NMAF-7), and was largely unaffected by alterations in synthesis conditions. It is also noteworthy that lysozyme (LZ) and horseradish peroxidase (HRP), which are commonly used in industry, also demonstrated enhanced activity when encapsulated in DMAF-7. It was therefore anticipated that modifying the sequence of reactant addition would be a straightforward and simple method of introducing defects into MAF-7, thereby improving enzyme utilization., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024. Published by Elsevier B.V.)

Catalytic methanolysis of ammonia borane (NH 3 BH 3 ) is a prospective technology in the field of hydrogen energy in which hydrogen production and hydrogen storage can be integrated together. The splitting of the O-H bond is identified as the rate-determining step (RDS) in this reaction. Thus, a deep understanding of the relationship between the electronic structure of the catalyst, especially the localized electron density of active sites, and the breaking behaviors of the O-H bond is of extreme importance for the rational design of robust catalysts for the reaction. In this work, sea urchin-like tricobalt tetroxide/copper oxide (Co 3 O 4 /CuO) nanostructures with rich oxygen vacancies (O v ) were fabricated by a simple synthetic route. In NH 3 BH 3 methanolysis, the optimal Co 3 O 4 /CuO sample exhibited ultrahigh catalytic activity with a turnover frequency (TOF) of 87.5 min -1 . Interestingly, when NH 3 BH 3 methanolysis was carried out under visible-light illumination, the TOF further increased to 116.4 min -1 , which is the highest TOF value among those of the noble-metal-free catalysts ever documented in the literature. Theoretical calculation results evidenced that the Cu site in the Co 3 O 4 /CuO sample was in charge of the adsorption and activation of methanol molecules. Both the O v and visible-light illumination can help electrons on the Cu site flow to the adsorbed methanol molecule, thus leading to localized electron redistribution of the methanol molecule and the extension of the O-H bond. The cooperation of O v and visible light makes splitting of the O-H bond easier, which is favorable for fast hydrogen release from NH 3 BH 3 methanolysis. This study helps us to gain an insight into the influence of localized electron redistribution of methanol molecules on the RDS, which conduces to the rational design of highly effective nanocatalysts. Moreover, the coinduction strategy for localized electron redistribution with oxygen vacancy engineering and visible-light illumination opens up a route to boost catalytic activity in NH 3 BH 3 methanolysis.

Background: Observational studies have shown a link between autoimmune diseases and schizophrenia, with conflicting conclusions. Due to the existence of confounding factors, the causal link between autoimmune diseases and schizophrenia is still unknown., Method: We conducted a comprehensive Mendelian randomization (MR) analysis of schizophrenia and ten common autoimmune diseases in individuals of European descent using genome-wide association studies (GWASs). To evaluate the relationships between autoimmune diseases and schizophrenia, inverse variance weighted, MR-RAPS, Bayesian weighted MR, constrained maximum likelihood, debiased IVW, MR-Egger, and weighted median were utilized. Several sensitivity analyses were performed to ensure the reliability of the study's results., Results: Our findings reveal that genetically predicted ankylosing spondylitis is related to an increased risk of schizophrenia, whereas celiac disease, type 1 diabetes, and systemic lupus erythematosus are associated with a lower risk of schizophrenia. In the reverse MR analysis, our study indicated that genetically predicted schizophrenia is linked to higher risks of ankylosing spondylitis, Crohn's disease, ulcerative colitis, inflammatory bowel disease, and psoriasis. Neither multiple sclerosis nor rheumatoid arthritis have been linked to schizophrenia, and vice versa., Conclusion: Despite contradicting some other observational reports, this study showed support for a causal link between autoimmune diseases and schizophrenia. To gain a better understanding of the mechanisms underlying the development of immune-mediated schizophrenia, additional research is required to identify potential mechanisms identified in observational studies., Competing Interests: Declarations Ethics approval and consent to participate The data used in our MR analysis is entirely from previously reported summary data. Therefore, neither patient consent nor ethical approval was necessary for the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The important constituents of rosemary herb extract are carnosic acid (CarA), carnosol (Car) and rosmanol (Ros), which are burdensome to the human body when consumed in excessive amounts. Using a computer-assisted method, we prepared 3B10-antibody with both broad-spectrum and high affinity for CarA, Car and Ros with median inhibitory concentration of 0.41 ng/mL, 0.45 ng/mL, and 0.53 ng/mL, respectively. Subsequently, a quantitative lateral flow immunoassay (LFIA) was developed to identify CarA, Car and Ros in ham sausage and dairy within 30 min, and the respectively calculated limit of detection values of 0.044 μg/kg, 0.148 μg/kg and 0.169 μg/kg in sample, which could meet maximum additive limits. The quantitative results of LFIA method in positive samples were consistent with that of the instrumental method.These results also show that the high recognition performance and reliability of the LFIA strips validate the field test method., 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.)

Haemonchus contortus poses a severe threat to livestock, leading to substantial economic losses. The extensive use of ivermectin (IVM), an effective anthelmintic drug, has resulted in the development of resistant strains, reducing the drug's effectiveness and making disease management more challenging. Hence, understanding the underlying mechanisms of IVM resistance is crucial. IVM has been shown to induce apoptosis and oxidative stress imbalance in cancer cells, thereby inhibiting tumor growth; however, whether there is a similar impact on H. contortus has not been well-documented. In this study, the biological functions of previously identified resistance-associated genes were investigated, revealing their involvement in apoptosis and oxidative stress. Experiments were conducted to compare cell apoptosis, mitochondrial function, and oxidative stress markers in IVM-treated and untreated sensitive and resistant strains isolated from the field. The findings demonstrated that mitochondrial dysfunction and increased apoptosis were induced by IVM treatment in sensitive strains, as indicated by elevated mitochondrial membrane potential and apoptosis rates. Conversely, stable mitochondrial function and apoptosis levels under IVM exposure were observed in resistant strains. These results provide novel insights into the resistance mechanisms of H. contortus and offer a theoretical basis for future research on overcoming IVM resistance., 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.)

In bacteria, where gene transcription and translation occur concurrently, post-transcriptional regulation is acknowledged to be effective and precise. The 5' untranslated regions (5' UTRs) typically harbor diverse post-transcriptional regulatory elements, like riboswitches, RNA thermometers, small RNAs, and upstream open reading frames, that serve to modulate transcription termination, translation initiation, and mRNA stability. Consequently, exploring 5' UTR-derived regulatory elements is vital for synthetic biology and metabolic engineering. Over the past few years, the investigation of successive mechanisms has facilitated the development of various genetic tools from bacterial 5' UTRs. This review consolidates current understanding of 5' UTR regulatory functions, presents recent progress in 5' UTR -element design and screening, updates the tools and regulatory strategies developed, and highlights the challenges and necessity of establishing reliable bioinformatic analysis methods and non-model bacterial chassis in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Pulmonary delivery of small interfering RNAs (siRNAs) is an effective treatment for acute lung injury (ALI), which can modulate the expression of pro-inflammatory cytokines and alleviate the symptoms of ALI. However, the rapid degradation of siRNA in vivo and its limited ability to target and validate cells are important challenges it faces in clinical practice. In this work, we developed neutrophil membrane-coated Poly (lactic-co-glycolic acid) nanoparticles loaded with TLR4 siRNA (si-TLR4) (Neutrophil-NP-TLR4), which can target both inflammatory and macrophage cells to alleviate the pulmonary inflammation in lipopolysaccharide (LPS)-induced ALI mice. These Neutrophil-NP-TLR4 effectively reduce the TNF-α and IL-1β expressions both in vitro and in vivo. Meanwhile, they also reduced the expression of TLR4, and its downstream genes including TNF receptor-associated factor 6 (TRAF6), X-linked inhibitor of apoptosis protein (XIAP), and Nuclear Factor kappa-B (NF-κB), but elevated the levels of Aquaporin 1 (AQP1) and Aquaporin 5 (AQP5). Moreover, the Neutrophil-NP-TLR4 precisely targets the inflammatory site to attenuate the lung injury without causing toxicity to normal tissue. This system provides a promising approach to effective delivery of siRNA to precisely treat the ALI., 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 pollution of micro- and mesoplastic (MMP) in the Eastern Indian Ocean (EIO) remains poorly understood. The present study revealed that MMP abundance in nekton from EIO in 2022 (mean: 2.30 ± 0.39 items individual -1 and 1.81 ± 0.54 items g -1 ) was significantly higher than that in 2021 (mean: 1.60 ± 0.22 items individual -1 and 0.80 ± 0.13 items g -1 ). In contrast, MMP abundance in surface water varied insignificantly between 2021 (mean: 0.04 ± 0.01 items m -3 ) and 2022 (mean: 0.05 ± 0.02 items m -3 ). The rise in predominant polymers-polypropylene (PP), rayon (RA), and polyester (PES)-in nekton from 2021 to 2022 may suggest increased pollution from face masks and home textiles along coastal regions. Notable spatial variation in PP and RA between the northeastern and southeastern regions was observed only in nekton, suggesting they are better indicators of MMP spatiotemporal variation than surface water. Shadow driftfish ingested more MMPs than purpleback flying squid and mackerel scad, likely due to its deeper habitat. By simultaneously considering color, composition, and shape, integrated MMP analysis showed insignificant correlation between MMP pollution in surface water and nekton, suggesting that nekton may ingest MMPs through multiple pathways beyond surface water. Risk indices for surface water and nekton reached moderate to upper levels globally, emphasizing the need for continued monitoring in the EIO. Epoxy resin, rubber, and PP + acrylic were identified as the most hazardous polymers, providing a valuable basis for developing effective strategies to mitigate plastic pollution., 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.)

Variants in HSPB8 are predominantly associated with peripheral neuropathies, but their occurrence in myopathies remains exceedingly rare. The genetic and clinical spectrum of HSPB8-related myopathy is not yet complete. Herein, we not only described the first Chinese case of HSPB8-related myopathy characterized by a novel heterozygous frameshift variant (c.576&#95;579delinsCAG, p.Glu192Aspfs*55) in the C-terminal region of HSPB8, but also established the first association between this specific HSPB8 variant and pediatric-onset axial and limb-girdle myopathy. Muscle pathology revealed myofibrillar myopathy features and the novel pathological findings of inflammatory responses and vacuoles with sarcolemmal features pathology. Functional studies demonstrated significant colocalization of HSPB8 with autophagy markers and upregulation of autophagy-related proteins, which suggested that autophagic dysregulation may contribute to the pathological process of this disease. Furthermore, comprehensive bioinformatics analysis and molecular dynamics simulations revealed an increased propensity for aggregation, as well as altered structural and biochemical properties in the mutant HSPB8. Our study highlights the importance of considering HSPB8 mutations in early-onset axial and limb-girdle myopathy, expanding the genetic and phenotypic spectrum of the disease. Notably, our results underscore the critical role of autophagy dysregulation and aberrant protein aggregation in the pathogenesis, providing novel insights into potential therapeutic targets., Competing Interests: Competing interests The authors declare no competing interests. Ethics Written informed consent was obtained from the patient and her legal guardians for the utilization of clinical data and biological materials for research purposes. The study protocol was reviewed and approved by the Ethics Committee of Qilu Hospital of Shandong University (KYLL-2023(ZM)-017)., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Natural silk nanofibers (SNF) are attractive conductive substrates due to their high aspect ratio, outstanding mechanical strength, excellent biocompatibility, and controllable degradability. However, the inherently non-conductivity severely restricts the potential sensor application of SNF-based aerogels. In this work, the conductive nanofibrous aerogels with low-density achieved through freeze-drying by dispersing carbon nanotubes (CNT) into SNF suspension. The addition of CNT significantly increases the conductivity with improved mechanical properties of composite aerogels. SEM results reveal that the distinct hierarchical structure comprising micropores and nanofibrous networks within the pores is formed when CNT content reached 30%. Furthermore, increased cell viability suggested the excellent biocompatibility of SNF-CNT-based conductive aerogel for tissue-engineering applications. Subsequently, the elastic water-borne polyurethane (WPU) is incorporated to SNF-CNT system to construct aerogel with good sensing properties. The introduction of WPU demonstrates enhanced compressive performances and an exceptionally high elastic recovery ratio of 99.8%, thereby exhibiting a stable and lossless strain-sensing signal output at 5% strain. This study provides a feasible choice and strategy for exploring the potential application of SNF in functional aerogels., (© 2024 Wiley‐VCH GmbH.)

Micro- and nanoplastics (MNPs), emerging environmental pollutants, infiltrate marine, terrestrial, and freshwater systems via diverse pathways, culminating in their accumulation in the human body through food chain transmission, posing potential health risks. Researches have demonstrated that MNPs disrupt gut microbiota equilibrium and compromise intestinal barrier integrity, as well as traverse the blood-brain barrier, leading to brain damage. Moreover, the complex interaction between the gut and the nervous system, facilitated by the "gut-brain axis," indicates an additional pathway for MNPs-induced brain damage. This has intensified scientific interest in the intercommunication between MNPs and the gut-brain axis. While existing studies have documented microbial imbalances and metabolic disruptions subsequent to MNPs exposure, the precise mechanisms by which the microbiota-gut-brain axis contributes to MNPs-induced central nervous system damage remain unclear. This review synthesizes current knowledge on the microbiota-gut-brain axis, elucidating the pathogenesis of MNPs-induced gut microbiota dysbiosis and its consequent brain injury. It emphasizes the complex interrelation between MNPs and the microbiota-gut-brain axis, advocating for the gut microbiota as a novel therapeutic target to alleviate MNP-induced brain harm., 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.)

Air pollutants have been investigated to be associated with many health issues. Recently, increasing epidemiological studies have suggested the association between air pollution exposure and risk of frailty with inconsistent findings. This systematic review and meta-analysis was to summarize and evaluate effects of exposure to various air pollutants on risk of frailty. PubMed, Embase, Scopus and Web of Science were systematically searched for relevant studies published before May 11, 2024. Studies that explored the potential relationship between exposure to air pollutants (PM 2.5 , PM 10 , O 3 , NO x , solid fuel, secondhand tobacco, and air quality) and risk of frailty were included. The quality of cross-sectional and cohort studies was evaluated using an eight-item assessment instrument for epidemiological studies and Newcastle-Ottawa Scale, respectively. A total of 9,929 papers were retrieved, of which 20 met the inclusion criteria. Meta-analysis indicated that PM 2.5 exposure was significantly associated with frailty assessed by the frailty index [OR (95% CI): 1.24 (1,11-1.38) per 10 μg/m 3 increment]. Moreover, solid fuel exposures were significantly associated with an increased risk of frailty assessed by the frailty phenotype [OR (95% CI): 1.91 (1.09-3.34)] or the frailty index [OR (95% CI): 1.25 (1.11-1.41)]. Exposure to PM 2.5 and solid fuel increases the risk of frailty. Environmental protection policies and public health measures should be developed to reduce PM 2.5 concentrations. Effective measures, such as improving stoves and using clean fuels, should be taken to reduce indoor air pollution levels., 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.)

Background: In 2016, China has implemented the World Health Organization's "treat all" policy. We aimed to assess the impact of significant improvements in the 95-95-95 targets on population-level human immunodeficiency virus (HIV) transmission dynamics and incidence., Methods: We focused on 3 steps of the HIV care continuum: diagnosed, on antiretroviral therapy, and achieving viral suppression. The molecular transmission clusters were inferred using HIV-TRACE. New HIV infections were estimated using the incidence method in the European Centre for Disease Prevention and Control HIV Modelling Tool., Results: Between 2004 and 2023, the national HIV epidemiology database recorded 2.99 billion person-times of HIV tests and identified 1 976 878 new diagnoses. We noted a roughly "inverted-V" curve in the clustering frequency, with the peak recorded in 2014 (67.1% [95% confidence interval, 63.7%-70.5%]), concurrent with a significant improvement in the 95-95-95 targets from 10-13-<71 in 2005 to 84-93-97 in 2022. Furthermore, we observed a parabolic curve for a new infection with the vertex occurring in 2010., Conclusions: In general, it was suggested that the improvements in the 95-95-95 targets were accompanied by a reduction in both the population-level HIV transmission rate and incidence. Thus, China should allocate more effort to the first "95" target to achieve a balanced 95-95-95 target., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)