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Human activities have significantly altered the biogeochemical cycles of carbon, nitrogen, and sulfur in aquatic ecosystems, leading to ecological problems.This study utilized 16S rRNA gene high-throughput sequencing and excitation-emission matrix parallel factor analysis (EEM-PARAFAC) to evaluate the bacterial community composition and dissolved organic matter structure in the upstream (less impacted) and downstream (severely impacted) sections of the river, with a focus on the interactions between bacterial diversity and dissolved organic matter (DOM) characteristics.Results indicated significant spatial diversity in bacterial communities, with a higher α-diversity upstream compared to the more polluted downstream sections. Environmental parameters, particularly total phosphorus (TP) and dissolved oxygen (DO), were found to significantly influence the distribution and composition of bacterial phyla through redundancy analysis. The pattern of bacterial community assembly has shifted from predominantly deterministic to predominantly stochastic as a result of human activities. The analysis of DOM through EEM-PARAFAC identified three main fluorescent components, reflecting varied sources and interactions with bacterial communities. Upstream, microbial activities predominantly contributed to autochthonous DOM, while downstream, increased inputs of allochthonous DOM from human activities were evident. Furthermore, the study revealed that through the introduction of various organic pollutants and nutrient loads that shift microbial metabolic functions towards increased degradation and transformation of complex organic compounds downstream. Structural equation modeling (SEM) revealed that upstream human activities primarily affected bacterial communities indirectly by altering DOM properties. In contrast, downstream activities had both direct and indirect effects due to higher pollutant loads and more complex environmental conditions. These interactions underline the profound effect of anthropogenic factors on riverine ecosystems and emphasize the importance of managing human impacts to preserve microbial biodiversity and water quality., 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.)

Natural products dispirocochlearoids A-C, which are meroterpenoids derived from Ganoderma fungi, feature a 6/6/5/6/6/6 ring system and exhibit selective COX-2 inhibitory activity. Herein, the concise total synthesis of the tetracyclic core structure of dispirocochlearoids A-C was achieved through an aldol reaction/cyclization/deprotection/cyclization cascade sequence. A series of simplified tetracyclic analogues was successfully constructed and their anti-inflammatory activity was further explored, with several tetracyclic analogues (such as compound 8ab ) exhibiting strong inhibitory activity against IL-1β expression in lipopolysaccharide-stimulated bone marrow-derived macrophage cells (IC 50 = 2.8 μM).

Dissolved organic matter (DOM) and recalcitrant dissolved organic matter (RDOM) play distinct roles in shaping microbial communities. However, characterizing these roles is difficult, especially in ecosystems subjected to varying degrees of anthropogenic influence. This study investigated the molecular compositions and ecological impacts of DOM and RDOM in the Fen River, Shanxi Taiyuan, comparing pristine upstream regions with highly urbanized downstream areas. Using 16S rRNA gene sequencing and LC-MS-based metabolomics, we observed significant shifts in microbial community composition, diversity, and metabolic functions. Upstream communities, characterized by higher diversity, were dominated by Bacteroidota, Proteobacteria, and Cyanobacteria, while downstream communities, influenced by pollution, exhibited increased expression of genes related to amino acid metabolism. Fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) revealed that upstream DOM contained higher proportions of complex, high molecular weight compounds, including significant proportions of carboxyl-rich alicyclic molecules (CRAM) and island of stability (IOS) compounds, which play key roles in long-term carbon storage and microbial carbon sequestration. In contrast, downstream DOM was characterized as having lower aromaticity and more saturated compounds, with reduced proportions of CRAM and IOS, reflecting the impact of anthropogenic activities. These findings underscored the critical roles of CRAM and IOS in regulating DOM stability and microbial communities, further highlighting the need for targeted pollution control strategies to preserve ecosystem function in urbanized water bodies., 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.)

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition and ranks as the fourth leading cause of mortality worldwide. Despite extensive research efforts, a reliable diagnostic or prognostic tool for COPD remains elusive. The identification of novel biomarkers may facilitate improved therapeutic strategies for patients suffering from this debilitating disease. MicroRNAs (miRNAs), which are small non-coding RNA molecules, have emerged as promising candidates for the prediction and diagnosis of COPD. Studies have demonstrated that dysregulation of miRNAs influences critical cellular and molecular pathways, including Notch, Wnt, hypoxia-inducible factor-1α, transforming growth factor, Kras, and Smad, which may contribute to the pathogenesis of COPD. Extracellular vesicles, particularly exosomes, merit further investigation due to their capacity to transport various biomolecules such as mRNAs, miRNAs, and proteins between cells. This intercellular communication can significantly impact the progression and severity of COPD by modulating signaling pathways in recipient cells. A deeper exploration of circulating miRNAs and the content of extracellular vesicles may lead to the discovery of novel diagnostic and prognostic biomarkers, ultimately enhancing the management of COPD. The current review focus on the pathogenic role of miRNAs and their exosomal counterparts in chest and respiratory diseases, centering COPD., Competing Interests: Declarations Competing interests No. Ethics approval and consent to participate Not applicable. Consent for publication Not applicable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Freshwater systems are critical yet often underestimated components of global carbon cycling, functioning both as carbon sinks and sources. Cyanobacteria play a key role in this cycle by capturing atmospheric carbon dioxide through photosynthesis. The captured carbon is either released back into the atmosphere or sequestered in sediments following organismal decay. This study examines the pivotal role of cyanobacteria, specifically Microcystis aeruginosa PCC 7806, in the biogeochemical cycling of carbon in freshwater ecosystems, with a focus on how light influences the degradation of cyanobacteria-derived organic matter. Using a combination of 16S rDNA sequencing and excitation-emission matrix coupled with parallel factor (EEM-PARAFAC) analysis, we conducted a 50-day experiment to investigate the dynamics of dissolved organic matter (DOM) and lysate organic matter (LOM) derived from M. aeruginosa PCC 7806 under light and dark conditions. Our results demonstrate that light significantly impacts bacterial community composition, gene functionality, and the decomposition of organic matter. The findings emphasize the crucial role of light in facilitating microbial adaptation, stabilizing microbial networks and driving organic substrate transformation. These insights underscore the influence of light on microbial community dynamics and organic matter degradation, revealing shifts in microbial populations under varying light conditions. This suggests a strong link between photochemical processes and microbial activity, with significant ecological implications., 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: The genus Hydrurus contains a solitary species, Hydrurusfoetidus . Its thalli exhibit a remarkable structure, consisting of a firm central axis surrounded by peripheral branches, all enveloped within a viscous, gelatinous coating. Molecular data pertaining to the genus Hydrurus are scarce, necessitating further investigation into its phylogenetic relationships., New Information: A new site with benthic freshwater alga Hydrurusfoetidus (Villars) Trevisan has been discovered in the Fenhe River in Shanxi Province, China. The physical and chemical parameters of water were meticulously measured and documented. Detailed morphological observations were conducted on the specimen, measuring different cell categories. The SSU, LSU, ITS and rbc L DNA sequence data of H.foetidus collected from Shanxi were determined. An extensive three-gene phylogenetic tree was constructed, revealing a strong relationship between the specimen in this study and H.foetidus specimen from Norway. Time-calibrated molecular phylogenetic analysis further indicated that the genus Hydrurus diverged approximately 125 million years ago (Early Cretaceous), while the two H.foetidus strains from Shanxi, China and Norway diverged approximately 6 million years ago (Neogene). The results of this study supplement new molecular evidence for H.foetidus and contribute significantly to our understanding of the geographical distribution and evolutionary history of the genus Hydrurus ., (Junxue Hao, Yalu An, Fangru Nan, Junping Lv, Qi Liu, Xudong Liu, Shulian Xie, Jia Feng.)

The optimal conditions were explored for the preparation of Spirulina blended liquor (SBL) and Spirulina fermented wine (SFW), respectively. The parameters obtaining highest alga polysaccharide were calculated by response surface methodology. The optimal conditions for SBL preparation were base liquor of 42% vol, ultrasonication time of 37-min and ultrasonic power of 80 W with polysaccharide content (PC) and alcohol content (AC) of 0.2181 g/L and 39.7% vol, respectively. In the case of SFW, optimum fermentation occurred at 22°C, with a 4% inoculum and 6-day period with PC and AC of 8.533 g/L and 11.2% vol, respectively. Headspace solid-phase microextraction-gas chromatography-mass spectrometry was used to quantitatively analyze the volatile components of SBL and SFW. There were 32 and 40 main aroma compounds in SBL and SFW, respectively. Volatile organic compounds, including α-ionone and β-ionone, produced by Spirulina were detected in both SBL and SFW. Comparative evaluation of scavenging activity and total reducing power revealed the antioxidant capacity of SFW significantly outperformed that of SBL., (© 2024 Institute of Food Technologists.)

Purpose: This study aimed to explore metabolic tumor volume (tMTV) as assessed 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT), and understand its biological meaning in patients with NSCLC exposed to immune checkpoint blockers(ICBs)., Experimental Design: In this study, patients with advanced NSCLC and a positive PET scan within 42 days of first line treatment were enrolled in 11 institutions across 4 countries. Total MTV (tMTV) was analyzed, with a 42% SUVmax threshold. Survival was analyzed according to high tMTV (≥ median). Plasma proteomic profile, whole exome, transcriptome and other analysis were performed on monocentric cohorts to explore its biological correlates., Results: Of the 518 patients included, 167 received ICBs, 257 had chemotherapy plus ICBs, and 94 had chemotherapy. Median tMTV was 99 cm3. Median overall survival (OS) for patients with high tMTV treated with ICBs was 11.4 months vs 29.6 months (P<0.0012) for those with low tMTV. In patients receiving chemotherapy-ICB tMTV did not correlate with OS (P=0.099). In patients with PD-L1≥1% and high tMTV, chemotherapy-ICB combination was associated with longer OS compared with ICBs alone (20 vs 11.4 months,p=0.026), while no survival differences observed in low tMTV group. High tMTV correlated (and its detrimental effect seems to be driven by) a specific proteomic profile and increase in genomic instability., Conclusion: Our analysis indicates high tTMV is linked to an increase in systemic inflammation, specific cytokines production and chromosomal instability. tTMV may serve as one of the biomarker to select the best upfront strategy in patients with PD-L1 positive advanced NSCLC.

Major depressive disorder (MDD) is a common mental disorder that severely disrupts psychosocial function and decreases the quality of life. Although the pathophysiological mechanism underlying MDD is complex and remains unclear, emerging evidence suggests that autophagy dysfunction plays a role in MDD occurrence and progression. Natural products serve as a major source of drug discovery and exert tremendous potential in developing antidepressants. Recently published reports are paying more attention on the autophagy regulatory effect of antidepressant natural products. In this review, we comprehensively discuss the abnormal changes occurred in multiple autophagy stages in MDD patients, and animal and cell models of depression. Importantly, we emphasize the regulatory mechanism of antidepressant natural products on disturbed autophagy, including monomeric compounds, bioactive components, crude extracts, and traditional Chinese medicine formulae. Our comprehensive review suggests that enhancing autophagy might be a novel approach for MDD treatment, and natural products restore autophagy homeostasis to facilitate the renovation of mitochondria, impede neuroinflammation, and enhance neuroplasticity, thereby alleviating depression., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Precise calling of promiscuous adenosine-to-inosine RNA editing sites from transcriptomic datasets is hindered by DNA mutations and sequencing/mapping errors. Here, we present a stepwise computational framework, called DEMINING, to distinguish RNA editing and DNA mutations directly from RNA sequencing datasets, with an embedded deep learning model named DeepDDR. After transfer learning, DEMINING can also classify RNA editing sites and DNA mutations from non-primate sequencing samples. When applied in samples from acute myeloid leukemia patients, DEMINING uncovers previously underappreciated DNA mutation and RNA editing sites; some associated with the upregulated expression of host genes or the production of neoantigens., (© 2024. The Author(s).)

Although fat is a crucial source of energy in diets, excessive intake leads to obesity. Fat absorption in the gut is prevailingly thought to occur organ-autonomously by diffusion 1-3 . Whether the process is controlled by the brain-to-gut axis, however, remains largely unknown. Here we demonstrate that the dorsal motor nucleus of vagus (DMV) plays a key part in this process. Inactivation of DMV neurons reduces intestinal fat absorption and consequently causes weight loss, whereas activation of the DMV increases fat absorption and weight gain. Notably, the inactivation of a subpopulation of DMV neurons that project to the jejunum shortens the length of microvilli, thereby reducing fat absorption. Moreover, we identify a natural compound, puerarin, that mimics the suppression of the DMV-vagus pathway, which in turn leads to reduced fat absorption. Photoaffinity chemical methods and cryogenic electron microscopy of the structure of a GABA A receptor-puerarin complex reveal that puerarin binds to an allosteric modulatory site. Notably, conditional Gabra1 knockout in the DMV largely abolishes puerarin-induced intestinal fat loss. In summary, we discover that suppression of the DMV-vagus-jejunum axis controls intestinal fat absorption by shortening the length of microvilli and illustrate the therapeutic potential of puerarin binding to GABRA1 in fat loss., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Persistent luminescence nanoparticles (PLNPs) can achieve autofluorescence-free afterglow imaging, while near-infrared (NIR) emission realizes deep tissue imaging. Nanozymes integrate the merits of nanomaterials and enzyme-mimicking activities with simple preparation. Here PLNPs are prepared of Zn 1.2 Ga 1.6 Ge 0.2 O 4 :Cr 0.0075 with NIR emission at 700 nm. The PLNPs are then incubated with IrCl 3 solution, and the nanoparticles are collected and annealed at 750 °C to obtain iridium@PLNPs. Iridium is observed on the PLNPs at the atomic level as a single-atom nanozyme with peroxidase-like catalytic activity, photothermal conversion, and computed tomography (CT) contrast capability. After coating with exosome membrane (EM), the Ir@PLNPs@EM composite exhibits long-lasting NIR luminescence, peroxidase-like catalytic activity, photothermal conversion, and CT contrast capability, with the targeting capability and biocompatibility from EM. Thus, NIR afterglow/photothermal/CT trimodal imaging-guided photothermal-chemodynamic combination therapy is realized as validated with the in vitro and in vivo inhibition of tumor growth, while toxicity and side effects are avoided as drug-free treatment. This work offers a promising avenue for advanced single-atom nanozyme@PLNPs to promote the development of nanozymes and PLNPs for clinical applications., (© 2024 Wiley‐VCH GmbH.)

The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456-2.785; P = 0.456, HR 0.685, 95%CI 0.256-1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188-11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163-1.117; P = 0.014, HR 0.317, 95%CI 0.113-0.887). By COX analysis, poor baseline performance status (ECOG-PS ≥ 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL., (© 2024. The Author(s).)

Glioblastoma multiforme (GBM), a highly malignant invasive brain tumor, is associated with poor prognosis and survival and lacks an effective cure. High expression of the human cytomegalovirus (HCMV) immediate early protein 1 (IE1) in GBM tissues is strongly associated with their malignant progression, presenting a novel target for therapeutic strategies. Here, the bioluminescence imaging technology revealed remarkable tumor shrinkage and improved survival rates in a mouse glioma model treated with HCMV IE1/IE1mut vaccine. In addition, immunofluorescence data demonstrated that the treated group exhibited significantly more and larger tertiary lymphoid structures (TLSs) than the untreated group. The presence of TLS was associated with enhanced T cell infiltration, and a large number of proliferating T cells were found in the treated group. Furthermore, the flow cytometry results showed that in the treatment group, cytotoxic T lymphocytes exhibited partial polarization toward effector memory T cells and were activated to play a lethal role in the peripheral immunological organs. Furthermore, a substantial proportion of B cells in the draining lymph nodes expressed CD40 and CD86. Surprisingly, quantitative polymerase chain reaction indicated that a high expression of cytokines, including chemokines in brain tumors and immune tissues, induced the differentiation, development, and chemokine migration of immune cells in the treated group. Our study data demonstrate that IE1 or IE1mut vaccination has a favorable effect in glioma mice models. This study holds substantial implications for identifying new and effective therapeutic targets within GBM., (© 2024. The Author(s).)

We present a novel and stable laminated structure to enhance the performance and stability of silicon (Si) photocathode devices for photoelectrochemical (PEC) water splitting. First, by utilizing Cu nanoparticle catalysts to work on a n + p-black Si substrate via the metal-assisted chemical etching, we can achieve the black silicon with a porous pyramid structure. The low depth holes on the surface of the pyramid caused by Cu etching not only help enhance the light capture capability with quite low surface reflectivity (<5%) but also efficiently protect the p-n junction from damage. To improve the charge migration efficiency and mitigate parasitic light absorption from cocatalysts at the same time, we drop casted quantum dots (QDs) MoS 2 with the size of nanometer scale as the first layer of catalyst. Hence, we then can safely electrodeposit cocatalyst Co nanoparticles to further enhance interface transfer efficiency. The synergistic effects of cocatalysts and optimized light absorption from the morphology and QDs contributed to the overall enhancement of PEC performance, offering a promising pathway for an efficient, low cost, and stable (over 100 h) hydrogen production photocathode.

Robotic nanomanipulation emerges as a cutting-edge technique pivotal for in situ nanofabrication, advanced sensing, and comprehensive material characterization. In this study, we develop an optical robotic platform (ORP) for the dynamic manipulation of colloidal nanoparticles (NPs). The ORP incorporates a human-in-the-loop control mechanism enhanced by real-time visual feedback. This feature enables the generation of custom optical landscapes with adjustable intensity and phase configurations. Based on the ORP, we achieve the parallel and reconfigurable manipulation of multiple NPs. Through the application of spatiotemporal phase gradient-reversals, our platform demonstrates capabilities in trapping, binding, rotating, and transporting NPs across custom trajectories. This presents a previously unidentified paradigm in the realm of in situ nanomanipulation. Additionally, the ORP facilities a "capture-and-print" assembly process, utilizing a strategic interplay of phase and intensity gradients. This process operates under a constant laser power setting, streamlining the assembly of NPs into any targeted configuration. With its precise positioning and manipulation capabilities, underpinned by the spatiotemporal modulation of optical gradients, the ORP will facilitate the development of colloid-based sensors and on-demand fabrication of nanodevices.

Hypoxia is known as a specific signal of various diseases, such as liver fibrosis. We designed a hypoxia-sensitive fluorometric approach that cleaved the azo bond (N═N) in the presence of hypoxia-controlled agents (sodium dithionite and azoreductase). 4-(2-Pyridylazo) resorcinol (Py-N═N-RC) bears a desirable hypoxia-responsive linker (N═N), and its azo bond breakup can only occur in the presence of sodium dithionite and azoreductase and leads to the release of 2,4-dihydroxyaniline, which can react with 3-[2-(2-aminoethylamino)ethylamino]propyltrimethoxysilane to generate yellow fluorescent silicon nanoparticles. This approach exhibited high selectivity and sensitivity toward both sodium dithionite and azoreductase over other potential interferences. The mouse liver microsome, which is known to contain azoreductase, was applied and confirmed the feasibility of the designed platform. Py-N═N-RC is expected to be a practical substrate for hypoxia-related biological analyses. Furthermore, silicon nanoparticles were successfully applied for Hela cell imaging owing to their negligible cytotoxicity and superb biocompatibility.

GPR84 is a promising therapeutic target and biomarker for a range of diseases. In this study, we reported the discovery of BINOL phosphate (BINOP) derivatives as GPR84 antagonists. By investigating the structure-activity relationship, we identified 15S as a novel GPR84 antagonist. 15S exhibits low nanomolar potency and high selectivity for GPR84, while its enantiomer 15R is less active. Next, we rationally designed and synthesized a series of GPR84 fluorogenic probes by conjugating Nile red and compound 15S . The leading hybrid, probe F8 , not only retained GPR84 activity but also exhibited low nonspecific binding and a turn-on fluorescent signal in an apolar environment. F8 enabled visualization and detection of GPR84 in GPR84-overexpressing HEK293 cells and lipopolysaccharide-stimulated neutrophils. Furthermore, we demonstrated that F8 can detect upregulated GPR84 protein levels in mice models of inflammatory bowel disease and acute lung injury. Thus, compound F8 represents a promising tool for studying GPR84 functions.

Multimodal learning is widely used in automated early diagnosis of Alzheimer's disease. However, the current studies are based on an assumption that different modalities can provide more complementary information to help classify the samples from the public dataset Alzheimer's Disease Neuroimaging Initiative (ADNI). In addition, the combination of modalities and different tasks are external factors that affect the performance of multimodal learning. Above all, we summrise three main problems in the early diagnosis of Alzheimer's disease: (i) unimodal vs multimodal; (ii) different combinations of modalities; (iii) classification of different tasks. In this paper, to experimentally verify these three problems, a novel and reproducible multi-classification framework for Alzheimer's disease early automatic diagnosis is proposed to evaluate and verify the above issues. The multi-classification framework contains four layers, two types of feature representation methods, and two types of models to verify these three issues. At the same time, our framework is extensible, that is, it is compatible with new modalities generated by new technologies. Following that, a series of experiments based on the ADNI-1 dataset are conducted and some possible explanations for the early diagnosis of Alzheimer's disease are obtained through multimodal learning. Experimental results show that SNP has the highest accuracy rate of 57.09% in the early diagnosis of Alzheimer's disease. In the modality combination, the addition of Single Nucleotide Polymorphism modality improves the multi-modal machine learning performance by 3% to 7%. Furthermore, we analyse and discuss the most related Region of Interest and Single Nucleotide Polymorphism features of different modalities.

Hyperuricemia has become the second most prevalent metabolic disease after diabetes, but the limitations of urate-lowering treatment (ULT) drugs and patient nonadherence make ULT far less successful. Thus, more ULT approaches urgently need to be explored. Uric acid-degrading bacteria have potential application value in ULT. In this study, we isolated 44XB T , a uric acid-degrading bacterium, from black-headed gull ( Chroicocephalus ridibundus ) feces. Using a polyphasic taxonomic approach, strain 44XB T was identified as a novel genus within the family Bacillaceae ; subsequently, the name Aciduricibacillus chroicocephali was proposed. Strain 44XB T had a unique uric acid-dependent phenotype and utilized uric acid and allantoin as the sole carbon and nitrogen sources, but not common carbon sources or complex media. In the genome, multiple copies of genes involved in uric acid metabolic pathway ( pucL , pucM , uraD , and allB ) were found. Six copies of pucL (encoding urate oxidase) were detected. Of these, five pucL copies were in a tandem arrangement and shared 70.42%-99.70% amino acid identity. In vivo experiments revealed that 44XB T reduced serum uric acid levels and attenuated kidney damage in hyperuricemic mice through uric acid catalysis in the gut and gut microbiota remodeling. In conclusion, our findings discover a strain for studying bacterial uric acid metabolism and may provide valuable insights into ULT., Importance: The increasing disease burden of hyperuricemia highlights the need for new therapeutic drugs and treatment strategies. Our study describes the developmental and application values of natural uric acid-degrading bacteria found in the gut of birds and broadened the source of bacteria with potential therapeutic value. Furthermore, the special physiology characteristics and genomic features of strain 44XB T are valuable for further study., Competing Interests: The authors declare no conflict of interest.

BGT-002, a new type of ATP-citrate lyase inhibitor, is a promising therapeutic for treatment of hypercholesterolemia. After an oral administration of BGT-002 to subjects, it underwent extensive metabolism and an acyl monoglucuronide (ZM326E-M2) on 1- carboxylic acid group was the major circulating metabolite. In this study, an LC-MS/MS method was developed and validated for the simultaneous determination of BGT-002 and ZM326E-M2 in plasma and the evaluation of their pharmacokinetic characteristics in humans. After extraction from the plasma by acetonitrile-induced protein precipitation, the analytes were separated on a Waters ACQUITY UPLC® BEH C 18 column using acetonitrile and 2 mM ammonium acetate containing 0.1% formic acid as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) of m/z 501.3→325.4 for ZM326E-M2 and m/z 507.3→331.2 for D 6 -ZM326E-M2, and pseudo-MRM of m/z 325.3→325.3 for BGT-002 and m/z 331.3→331.3 for D 6 -ZM326E, respectively. The method was validated with respect to accuracy, precision, linearity, stability, selectivity, matrix effect, and recovery. The analytical range in human plasma was linear over a concentration range of 0.0500-50.0 μg/mL for BGT-002 and 0.0100-10.0 μg/mL for ZM326E-M2. The pharmacokinetic results showed that after a single oral administration of 100 mg BGT-002, the parent drug was rapidly absorbed with a mean time to peak concentration (t max ) of 1.13 h, compared with BGT-002, the t max (4.00 h) of ZM326E-M2 was significantly delayed. The peak concentration and plasma exposure of ZM326E-M2 were about 14.1% and 19.5% of the parent drug, suggesting that attention should be paid to the safety and efficacy of ZM326E-M2 in clinical research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nanozyme-based metabolic regulation triggered by tumor-specific endogenous stimuli has emerged as a promising therapeutic strategy for tumors. The current efficacy, however, is constrained by the limited concentration of endogenous substrates and the metabolic plasticity of tumors. Consequently, the implementation of efficient metabolic regulation in tumor therapy is urgently needed. Herein, a versatile nanozyme-based nicotinamide adenine dinucleotide (NADH) circulating oxidation nanoreactor is reported. First, the synthesized cobalt-doped hollow carbon spheres (Co-HCS) possess NADH oxidase (NOX)-mimicking activity for the NADH oxidation to disrupt oxidative phosphorylation (OXPHOS) pathway of tumor cells. Second, the substrate-cycle manner of Co-HCS can be used for NADH circulating oxidation to overcome the limitation of substrate deficiency. Finally, 2-Deoxy-D-glucose (2-DG) and 6-aminonicotinamide (6-AN) are introduced to block glycolysis and pentose phosphate pathway (PPP), thus creating a versatile nanozyme-based NADH circulating oxidation nanoreactor (Co-HCS/D/A) for tumor therapy through triple cellular metabolism disruption. In vitro and in vivo results demonstrate that the designed nanoreactor not only enhances the catalytic efficiency but also disrupts the tumor metabolic homeostasis, leading to efficient therapy outcome. This study develops a novel NADH circulating oxidation nanoreactor for tumor therapy through triple cellular metabolism disruption, which addresses the limitations of current nanozyme-based metabolism regulation for tumor therapy., (© 2024 Wiley‐VCH GmbH.)

Recent studies increasingly suggest that targeting brown/beige adipose tissues to enhance energy expenditure offers a novel therapeutic approach for treating metabolic diseases. Brown/beige adipocytes exhibit elevated expression of uncoupling protein 1 (UCP1), which is a thermogenic protein that efficiently converts energy into heat, particularly in response to cold stimulation. Polyphenols possess potential anti-obesity properties, but their pharmacological effects are limited by their bioavailability and distribution within tissue. This study discovered 18a , a polyphenol compound with a favorable distribution within adipose tissues, which transcriptionally activates UCP1, thereby promoting thermogenesis and enhancing mitochondrial respiration in brown adipocytes. Furthermore, in vivo studies demonstrated that 18a prevents high-fat-diet-induced weight gain and improves insulin sensitivity. Our research provides strong mechanistic evidence that UCP1 is a complex mediator of 18a -induced thermogenesis, which is a critical process in obesity mitigation. Brown adipose thermogenesis is triggered by 18a via the AMPK-PGC-1α pathway. As a result, our research highlights a thermogenic controlled polyphenol compound 18a and clarifies its underlying mechanisms, thus offering a potential strategy for the thermogenic targeting of adipose tissue to reduce the incidence of obesity and its related metabolic problems.

In this work, an attapulgite-graphene nanocomposite was prepared. The tribological properties of the prepared attapulgite-graphene nanocomposite as an additive for 200SN mineral lubricating oil were investigated using an SRV-IV tribometer through ball-on-disk contact mode for the first time. The characterization of the prepared nanocomposite indicated that attapulgite nanofibers are enveloped by the graphene nanosheets and present fine combination. The tribological test results show that the friction-reducing and antiwear properties of 200SN were obviously improved by adding the attapulgite-graphene nanocomposite. Through the characterization and analysis of the worn surface and cross-section, it was found that a tribofilm composed of Fe, Fe 3 O 4 , FeO, Fe 2 O 3 , FeOOH, graphite, graphene, SiO 2 and organic compounds was formed on the worn surface. Furthermore, the bonding between the tribofilm and steel matrix is tight. The tribofilm and lubricating oil achieve a solid-liquid coupling lubrication effect, which is responsible for the improvement of the friction-reducing and antiwear properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The incidence of autoimmune diseases has significantly increased over the past 20 years. Excessive host immunoreactions and disordered immunoregulation are at the core of the pathogenesis of autoimmune diseases. The traditional anti-tumor chemotherapy drug CPT-11 is associated with leukopenia. Considering that CPT-11 induces leukopenia, we believe that it is a promising drug for the control of autoimmune diseases. Here, we show that CPT-11 suppresses T cell proliferation and pro-inflammatory cytokine production in healthy C57BL/6 mice and in complete Freund's adjuvant-challenged mice. We found that CPT-11 effectively inhibited T cell proliferation and Th1 and Th17 cell differentiation by inhibiting glycolysis in T cells. We also assessed CPT-11 efficacy in treating autoimmune diseases in models of experimental autoimmune encephalomyelitis and psoriasis. Finally, we proved that treatment of autoimmune diseases with CPT-11 did not suppress long-term immune surveillance for cancer. Taken together, these results show that CPT-11 is a promising immunosuppressive drug for autoimmune disease treatment., (© 2024. The Author(s).)

With the rapid development of micro/nanofabrication technologies, the concept of transformable kirigami has been applied for device fabrication in the microscopic world. However, most nano-kirigami structures and devices were typically fabricated or transformed at fixed positions and restricted to limited mechanical motion along a single axis due to their small sizes, which significantly limits their functionalities and applications. Here, we demonstrate the precise shaping and position control of nano-kirigami microrotors. Metallic microrotors with size of ~10 micrometers were deliberately released from the substrates and readily manipulated through the multimode actuation with controllable speed and direction using an advanced optoelectronic tweezers technique. The underlying mechanisms of versatile interactions between the microrotors and electric field are uncovered by theoretical modeling and systematic analysis. This work reports a novel methodology to fabricate and manipulate micro/nanorotors with well-designed and sophisticated kirigami morphologies, providing new solutions for future advanced optoelectronic micro/nanomachinery.

Ethnopharmacological Relevance: Jin-Gui-Shen-Qi Wan (JGSQW) is a traditional Chinese medicine formula that has been traditionally used to alleviate urinary system ailments such as frequent urination and polyuria. Clinical studies have indicated that when combined with hypoglycaemic drugs, JGSQW exhibits a synergistic effect and can improve diabetic nephropathy (DN), yet its underlying mechanism and targets remain unclear., Aim of the Study: This study aims to investigate the therapeutic efficacy of JGSQW and its underlying mechanisms using a DN db/db mouse model., Materials and Methods: Ultrahigh-performance liquid chromatography coupled with mass spectrometry was utilized to analyse the primary active compounds, blood levels, and pharmacokinetics of JGSQW. Additionally, the therapeutic effects of JGSQW and metformin on blood glucose levels, lipid levels, renal function, and renal pathology in diabetic nephropathy mice were investigated using a db/db mouse model. Proteomic analysis was carried out to identify the primary target of JGSQW in treating DN. The mechanism of action was verified by western blotting, immunohistochemistry, and immunofluorescence. Then, molecular docking and molecular dynamics, transfection, drug affinity responsive target stability (DARTS) assay and cell thermal migration assay (CETSA) further validated the targeted binding effect., Results: JGSQW combined with metformin significantly improved the blood glucose levels, blood lipids, renal function, and renal pathology of DN mice. JGSQW mainly exerted its therapeutic effect on DN by targeting major histocompatibility complex class II (MHC class II) molecules. Immunohistochemistry results showed that JGSQW inhibited the expression of collagen I, fibronectin, and alpha smooth muscle actin (α-SMA) expression. Immunofluorescence and Western blot results showed that JGSQW inhibited the expression of H2-Ab1 and H2-Aa, which are MHC class II molecules, thereby suppressing CD4 + T-cell infiltration and improving diabetic kidney fibrosis. The binding ability of paeoniflorin to H2-Aa was predicted and verified by molecular, DARTS, and CETSA assays. Treatment with 80 μM paeoniflorin effectively alleviated high glucose-induced injury in the MPC-5 injury model. H2-Aa was overexpressed at this model concentration, and Western blotting further confirmed that paeoniflorin reduced glomerular podocyte fibrosis by regulating H2-Aa., Conclusions: JGSQW combined with metformin may have a synergistic effect to alleviates renal fibrosis in diabetic nephropathy by downregulating immune complex MHC class II molecules and attenuating the antigen presentation effect of MHC class II on CD4., 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.)

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Microbial communities are pivotal in aquatic ecosystems, as they affect water quality, energy dynamics, nutrient cycling, and hydrological stability. This study explored the effects of rainfall on hydrological and photosynthetic parameters, microbial composition, and functional gene profiles in the Fen River. Our results demonstrated that rainfall-induced decreases in stream temperature, dissolved oxygen, pH, total phosphorus, chemical oxygen demand, and dissolved organic carbon concentrations. In contrast, rainfall increased total dissolved solids, salinity, and ammonia-nitrogen concentrations. A detailed microbial community structure analysis revealed that Cyanobacteria was the dominant microbial taxon in the Fen River, accounting for approximately 75% and 25% of the microalgal and bacterial communities, respectively. The abundance of Chlorophyta and Bacillariophyta increased by 47.66% and 29.92%, respectively, whereas the relative abundance of Bacteroidetes decreased by 37.55% under rainfall conditions. Stochastic processes predominantly affected the assembly of the bacterial community on rainy days. Functional gene analysis revealed variations in bacterial functions between sunny (Sun) and rainy (Rain) conditions, particularly in genes associated with the carbon cycle. The 3-oxoacyl-[acyl-carrier-protein] reductase gene was more abundant in the Fen River bacterial community. Particular genes involved in metabolism and environmental information processing, including the acetyl-CoA C-acetyltransferase (atoB), enoyl-CoA hydratase (paaF), and branched-chain amino acid transport system gene (livK), which are integral to environmental information processing, were more abundant in Sun than the Rain conditions. In contrast, the phosphate transport system gene, the galactose metabolic gene, and the pyruvate metabolic gene were more abundant in Rain. The excitation-emission matrix analysis with parallel factor analysis identified four fluorescence components (C1-C4) in the river, which were predominantly protein- (C1) and humic-like (C2-C4) substances. Rainfall affected organic matter production and transport, leading to changes in the degradation and stability of dissolved organic matter. Overall, this study offers insight into how rainfall affects aquatic 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.)

As a potential vectored vaccine, Newcastle disease virus (NDV) has been subject to various studies for vaccine development, while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation. To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells (DCs) and T cells, DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide (LPS) for further detection by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunoblotting, and quantitative real-time polymerase chain reaction (qRT-PCR). The results revealed that NDV infection resulted in the inhibition of interleukin (IL)-12p40 in DCs through a p38 mitogen-activated protein kinase (MAPK)‍-dependent manner, thus inhibiting the synthesis of IL-12p70, leading to the reduction in T cell proliferation and the secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-6 induced by DCs. Consequently, downregulated cytokines accelerated the infection and viral transmission from DCs to T cells. Furthermore, several other strains of NDV also exhibited inhibitory activity. The current study reveals that NDV can modulate the intensity of the innate‍‒‍adaptive immune cell crosstalk critically toward viral invasion improvement, highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balance to enhance anti-PD-1 therapy in various murine cancer models. In summary, these data not only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery., Competing Interests: Declaration of interests The authors declare no potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The pleiotropic effects of TGR5 make it an appealing target for intervention of metabolic and inflammatory disorders, but systemic activation of TGR5 faces challenges of on-target side effects, especially gallbladder filling. Gut-restricted agonists were proved to be sufficient to circumvent these side effects, but extremely low systemic exposure may not be effective in activating TGR5 since it is located on the basolateral membrane. Herein, to balance potency and physicochemical properties, a series of gut-restricted TGR5 agonists with diversified kinetophores had been designed and synthesized. Compound 22-Na exhibited significant antidiabetic effect, and showed favorable gallbladder safety after 7 days of oral administration in humanized TGR5 H88Y mice, confirming that gut-restricted agonism of TGR5 is a viable strategy to alleviate systemic target-related effects., 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.)

Although multiple factors are known to concur with Alzheimer's disease (AD), the relationship between human cytomegalovirus (HCMV) and AD-like disease is unclear. Here, we propose a hypothesis that HCMV immediate-early 2 (IE2) protein promotes microglia activation and thus leads to AD-like disease. We successfully constructed IE2 transgenic mice expressing IE2 in the hippocampus. Single-cell sequencing analysis revealed that IE2 promoted the activation of microglia and upregulated the expression of disease-associated microglia genes. Differentially expressed gene analysis and pathway enrichment revealed that IE2 upregulated immune and nervous system disease-related genes. Immunohistochemical analysis showed that the expressions of both amyloid precursor protein (APP) and p-Tau were significantly upregulated in the brains of IE2 mice and were markers of AD. Taken together, these findings provide useful insights into AD-like disease activated by HCMV IE2., (© 2023. The Author(s).)

Aim: We aimed to establish a sensitive LC-MS/MS method to analyze the pharmacokinetics of Ani HBr tablets and injection. Methods: Around 10 mmNH 4 Ac containing 0.1% formic acid and acetonitrile were used as the mobile phase. Acute lung injury in septic and normal rats, respectively, were administered Ani HBr tablets at doses of 12.5, 25 and 50 mg/kg and injection at doses of 4, 8 and 16 mg/kg, followed by extraction of the drugs from plasma using ethyl acetate for subsequent analysis. Results & conclusion: The method met the requirements for biological analysis. Ani HBr tablets absorbed slowly in rats with disease, tail vein administration was a more promising approach for treating septic acute lung injury.

Although sodium alginate (SA) is frequently utilized because of its good gelling properties, the substance's dearth of adsorption active sites prevents it from effectively removing heavy metals. Herein, SA was used as the base material to form a cross-linked structure with Fe 3+ and Mg 2+ , and gel beads with a diameter of 2.0 ± 0.1 mm with specific adsorption on As(V) were synthesized as adsorbent (Fe/Mg-SA). Fe/Mg-SA was systematically characterized, and its adsorption properties were investigated by varying several conditions. Fe/Mg-SA had a wide pH application range. The adsorption kinetics revealed that a quasi-secondary kinetic model was followed. The adsorption process is linked to the complexation of hydroxyl and AsO 4 3- , chemisorption predominated the adsorption process. The maximal adsorption capacity of Fe/Mg-SA is determined by fitting the Langmuir model to be 37.4 mg/g. Compared to other adsorbents, it is simpler to synthesis, more effective and cheaper. Each treatment of 1 m 3 wastewater of Fe/Mg-SA only costs ¥ 38.612. The novel gel beads synthesized provides a better option for purifying groundwater contaminated with As(V)., 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 © 2023 Elsevier B.V. All rights reserved.)

Human cytomegalovirus (HCMV) infection is prevalent worldwide, and there is currently no licenced HCMV vaccine to control it. Therefore, developing an effective HCMV vaccine is a significant priority. Because of their excellent immunogenicity, the crucial components of HCMV, phosphoprotein 65 (pp65) and glycoproteins H (gH) are potential target proteins for HCMV vaccine design. In this study, we predicted and screened the dominant antigenic epitopes of B and T cells from pp65 and gH conjugated with the carrier protein cross-reacting material 197 (CRM197) to form three peptide-CRM197 vaccines (pp65-CRM197, gH-CRM197, and pp65-CRM197+gH-CRM197). Furthermore, the immunogenicity of the peptide-CRM197 vaccines and their effects on dendritic cells (DCs) were explored. The results showed that three peptide-CRM197 vaccines could induce maturation of DCs through the p38 MAPK signalling pathway and promote the release of proinflammatory factors, such as TNF-α and interleukin (IL) -6. Meanwhile, the peptide-CRM197 vaccines could effectively activate T cell and humoral immunity, which were far better than the inactivated HCMV vaccine. In conclusion, we constructed three peptide-CRM197 vaccines, which could induce multiple immune effects, providing a novel approach for HCMV vaccine design.

Background: We have previously reported that human cytomegalovirus (HCMV) infection could promote the progression of glioma. Here we discovered a stress-induced nuclear protein ZC3H11A (ZC3) through high-throughput sequencing after HCMV infection, which has been reported recently by our research group in regulating mRNA export under stress conditions. And also, a thorough analysis of ZC3 in pan-cancer and the omics data of ZC3 are yet to be conducted., Methods: The transcriptomes of glioma cells after HCMV infection were assessed by RNA sequencing. ZC3 mRNA and protein level following HCMV infection were validated and measured by qRT-PCR and Western-blot. The RNA sequencing and protein expression information of ZC3 across pan-cancer were analyzed and visualized by R packages. The localization of ZC3 protein was assessed by IHC images from HPA. The ZC3 proteomics and transcriptomics data in different cancers were extracted through the CPTAC data portal, and comparisons were conducted with a Python script. The genetic alteration, survival prognosis, immune infiltration analysis of ZC3 in pan-cancer were analyzed by cBioPortal, TCGA, and TIMER2 databases. The protein interaction networks were revealed by STRING, GEPIA2 and TCGA., Results: Genes in mRNA processing pathways were upregulated after HCMV infection and ZC3 expression in mRNA and protein level was validated. We also discovered that the status of ZC3 were generally at high levels in cancers, although varied among different cancer types. ZC3 protein in tumor cells localized to the nuclear whereas in normal cells it was mainly found in cytoplasmic/membranous. However, from ZC3 proteomics and transcriptomics data in some cancer types, the increase in ZC3 protein was not accompanied by a significant elevation in mRNA level. Additionally, our analysis indicated that elevated ZC3 expression was primarily linked to a negative prognosis in majority cancers but still varied depending on the cancer types. Our annotation analysis suggested that ZC3-related proteins are mainly involved in mRNA processing clusters., Conclusion: We demonstrated that ZC3 significantly impacted by HCMV infection in gliomas. Furthermore, we identified a set of genes exhibiting analogous expression patterns to ZC3H11A in TCGA pan-cancer cohorts, implying a potential functional role for ZC3H11A in mRNA processing. Our study provided valuable insights into the role of a new mRNA export protein ZC3 in HCMV infection and pan-cancer progression. These results lay the foundation for our next research on the regulatory mechanism of ZC3 in virus-infected tumors., 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 © 2023 Li, Song, Liu, Nan, Wang, Qian and Hu.)

Converting CO 2 into value-added chemicals to solve the issues caused by carbon emission is promising but challenging. Herein, by embedding metal ions (Co 2+ , Ni 2+ , Cu 2+ , and Zn 2+ ) into an imidazole-linked robust photosensitive covalent organic framework (PyPor-COF), effective photocatalysts for CO 2 conversion are rationally designed and constructed. Characterizations display that all of the metallized PyPor-COFs (M-PyPor-COFs) display remarkably high enhancement in their photochemical properties. Photocatalysis reactions reveal that the Co-metallized PyPor-COF (Co-PyPor-COF) achieves a CO production rate as high as up to 9645 µmol g -1 h -1 with a selectivity of 96.7% under light irradiation, which is more than 45 times higher than that of the metal-free PyPor-COF, while Ni-metallized PyPor-COF (Ni-PyPor-COF) can further tandem catalyze the generated CO to CH 4 with a production rate of 463.2 µmol g -1 h -1 . Experimental analyses and theory calculations reveal that their remarkable performance enhancement on CO 2 photoreduction should be attributed to the incorporated metal sites in the COF skeleton, which promotes the adsorption and activation of CO 2 and the desorption of generated CO and even reduces the reaction energy barrier for the formation of different intermediates. This work demonstrates that by metallizing photoactive COFs, effective photocatalysts for CO 2 conversion can be achieved., (© 2023 Wiley-VCH GmbH.)

Aims: Few treatments are available in the subacute phase of traumatic brain injury (TBI) except rehabilitation training. We previously reported that transient CO 2 inhalation applied within minutes after reperfusion has neuroprotective effects against cerebral ischemia/reperfusion injury. In this study, it was hypothesized that delayed CO 2 postconditioning (DCPC) starting at the subacute phase may promote neurological recovery of TBI., Methods: Using a cryogenic TBI (cTBI) model, mice received DCPC daily by inhaling 5%/10%/20% CO 2 for various time-courses (one/two/three cycles of 10-min inhalation/10-min break) at Days 3-7, 3-14 or 7-18 after cTBI. Beam walking and gait tests were used to assess the effect of DCPC. Lesion size, expression of GAP-43 and synaptophysin, amoeboid microglia number and glia scar area were detected. Transcriptome and recombinant interferon regulatory factor 7 (Irf7) adeno-associated virus were applied to investigate the molecular mechanisms., Results: DCPC significantly promoted recovery of motor function in a concentration and time-course dependent manner with a wide therapeutic time window of at least 7 days after cTBI. The beneficial effects of DCPC were blocked by intracerebroventricular injection of NaHCO 3 . DCPC also increased puncta density of GAP-43 and synaptophysin, and reduced amoeboid microglia number and glial scar formation in the cortex surrounding the lesion. Transcriptome analysis showed many inflammation-related genes and pathways were altered by DCPC, and Irf7 was a hub gene, while overexpression of IRF7 blocked the motor function improvement of DCPC., Conclusions: We first showed that DCPC promoted functional recovery and brain tissue repair, which opens a new therapeutic time window of postconditioning for TBI. Inhibition of IRF7 is a key molecular mechanism for the beneficial effects of DCPC, and IRF7 may be a potential therapeutic target for rehabilitation after TBI., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP 2 ), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP 2 , and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2., (© 2023. Springer Nature Limited.)

In this study, a 3D porous poly(ε-caprolactone)/polyethylene glycol (PCL/PEG) composite artificial tubular bile duct was fabricated for extrahepatic bile duct regeneration. PCL/PEG composite scaffolds were fabricated by 3D printing, and the molecular structure, mechanical properties, thermal properties, morphology, and in vitro biocompatibility were characterized for further application as artificial bile ducts. A bile duct defect model was established in beagle dogs for in vivo implantation. The results demonstrated that the implanted PE1 ABD, serving as a supportive scaffold, effectively stimulated the regeneration of a new bile duct comprising CK19-positive and CK7-positive epithelial cells within 30 days. Remarkably, after 8 months, the newly formed bile duct exhibited an epithelial layer resembling the normal structure. Furthermore, the study revealed collagen deposition, biliary muscular formation, and the involvement of microvessels and fibroblasts in the regenerative process. In contrast, the anastomotic area without ABD implantation displayed only partial restoration of the epithelial layer, accompanied by fibroblast proliferation and subsequent bile duct fibrosis. These findings underscore the limited inherent repair capacity of the bile duct and underscore the beneficial role of the PE1 ABD artificial tubular bile duct in promoting biliary regeneration.

The concept of lateral optical force (LOF) is of general interest in optical manipulation as it releases the constraint of intensity gradient in tightly focused light, yet such a force is normally limited to exotic materials and/or complex light fields. Here, we report a general and controllable LOF in a nonchiral elongated nanoparticle illuminated by an obliquely incident plane wave. Through computational analysis, we reveal that the sign and magnitude of LOF can be tuned by multiple parameters of the particle (aspect ratio, material) and light (incident angle, direction of linear polarization, wavelength). The underlying physics is attributed to the multipolar interplay in the particle, leading to a reduction in symmetry. Direct experimental evidence of switchable LOF is captured by polarization-angle-controlled manipulation of single Ag nanowires using holographic optical tweezers. This work provides a minimalist paradigm to achieve interface-free LOF for optomechanical applications, such as optical sorting and light-driven micro/nanomotors., (© 2023. Springer Nature Limited.)

Due to the different physical and chemical properties such as surface charge and ion morphology between As(V) and Cd(II), it is challenging to remove As(V) and Cd(II), especially at low concentrations. This study constructed a novel three-dimension nanocomposite adsorbent Mg/Al/Fe-CLDH (CFMA) by "hydrothermal + calcination method". And different initial concentration ratios (Cd: As=1: 2, 1: 1, 2: 1) were used to investigate the removal performance of CFMA for Cd(II) and As(V). When the concentration ratio Cd: As=1: 2, the residual concentrations of As(V) and Cd(II) were 8.7 μg/L and 4.2 μg/L, respectively, which met the drinking water standard; In the co-adsorption system, As(V) and Cd(II) influence each other's adsorption behavior due to the anionic bridge and shielding effect of As(V) on Cd(II), As(V) gradually changed from monolayer adsorption to multi-layer adsorption dominant, while Cd(II) gradually changed from multi-layer adsorption to monolayer adsorption dominant. In this paper, the structure-activity relationship between material structure and synchronous removal of arsenic and cadmium was clarified, and the mechanism of synchronous removal was revealed, which provided technical guidance for synchronous removal of As(V) and Cd(II) from non-ferrous metal smelting wastewater., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Maize ( Zea mays L.) is one of the most important crops, influencing food production and even the whole industry. In recent years, global crop production has been facing great challenges from diseases. However, most of the traditional methods make it difficult to efficiently identify disease-related phenotypes in germplasm resources, especially in actual field environments. To overcome this limitation, our study aims to evaluate the potential of the multi-sensor synchronized RGB-D camera with depth information for maize leaf disease classification. We distinguished maize leaves from the background based on the RGB-D depth information to eliminate interference from complex field environments. Four deep learning models (i.e., Resnet50, MobilenetV2, Vgg16, and Efficientnet-B3) were used to classify three main types of maize diseases, i.e., the curvularia leaf spot [ Curvularia lunata (Wakker) Boedijn], the small spot [ Bipolaris maydis (Nishik.) Shoemaker], and the mixed spot diseases. We finally compared the pre-segmentation and post-segmentation results to test the robustness of the above models. Our main findings are: 1) The maize disease classification models based on the pre-segmentation image data performed slightly better than the ones based on the post-segmentation image data. 2) The pre-segmentation models overestimated the accuracy of disease classification due to the complexity of the background, but post-segmentation models focusing on leaf disease features provided more practical results with shorter prediction times. 3) Among the post-segmentation models, the Resnet50 and MobilenetV2 models showed similar accuracy and were better than the Vgg16 and Efficientnet-B3 models, and the MobilenetV2 model performed better than the other three models in terms of the size and the single image prediction time. Overall, this study provides a novel method for maize leaf disease classification using the post-segmentation image data from a multi-sensor synchronized RGB-D camera and offers the possibility of developing relevant portable devices., 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 © 2023 Nan, Song, Yu, Nie, Liu, Bai, Zou, Wang, Yin, Yang and Jin.)

Recently, photodynamic therapy (PDT) based on the generation of cytotoxic reactive oxygen species (ROS) has drawn great attention in tumor treatment. However, the hypoxia tumor microenvironment (TME) inhibits the generation efficacy of ROS, and the high glutathione (GSH) level in TME could neutralize the generated ROS, both of which strongly reduce the therapeutic efficiency of PDT. In this work, we first constructed the porphyrinic metal-organic framework PCN-224. Then Au nanoparticles were decorated on the PCN-224 to obtain the PCN-224@Au. The decorated Au nanoparticles could not only produce O 2 through the decomposition of H 2 O 2 in tumor sites for enhancing the generation of 1 O 2 in PDT but also deplete glutathione through the strong interactions between Au and sulfhydryl groups on glutathione to weaken the antioxidant ability of tumor cells, thus amplifying the 1 O 2 damage to cancer cells. The in vitro and in vivo experiments totally exhibited that the as-prepared PCN-224@Au nanoreactor can be used as an oxidative stress amplifier for enhanced PDT, which provides a promising candidate to conquer the limitation of intratumor hypoxia and high GSH level on PDT of cancer.

Infertility and menstrual abnormalities in endometriosis patients are frequently caused by aberrant follicular growth or a reduced ovarian reserve. Endometriosis typically does not directly harm the oocyte, but rather inhibits the function of granulosa cells, resulting in a decrease in oocyte quality. Granulosa cells, as oocyte nanny cells, can regulate meiosis, provide the most basic resources required for oocyte development, and influence ovulation. Endometriosis affects oocyte development and quality by causing granulosa cells apoptosis, inflammation, oxidative stress, steroid synthesis obstacle, and aberrant mitochondrial energy metabolism. These aberrant states frequently interact with one another, however there is currently relatively little research in this field to understand the mechanism of linkage between abnormal states., 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 © 2023 Fan, Yuan, Li, Zhang and Nan.)