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Cataracts are the world's number one blinding eye disease. Cataracts can only be effectively treated surgically, although there is a chance of surgical complications. One of the pathogenic processes of cataracts is oxidative stress, which closely correlated with pyroptosis. SIRT1 is essential for the regulation of pyroptosis. Nevertheless, the role of SIRT1 in formation of cataracts is unclear. In this work, we developed an in vitro model of shortwave blue light (SWBL)-induced scotomization in human lens epithelial cells (HLECs) and an in vivo model of SWBL-induced cataracts in rats. The study aimed to understand how the SIRT1/NF-κB/NLRP3 pathway functions. Additionally, the evaluation included cell death and the release of lactate dehydrogenase (LDH), a cytotoxicity marker, from injured cells. First, we discovered that SWBL exposure resulted in lens clouding in Sprague- Dawley (SD) rats and that the degree of clouding was positively linked to the duration of irradiation. Second, we discovered that SIRT1 exhibited antioxidant properties and was connected to the NF-κB/NLRP3 pathway. SWBL irradiation inhibited SIRT1 expression, exacerbated oxidative stress, and promoted nuclear translocation of NF-κB and the activation of the NLRP3 inflammasome, which caused LEC pyroptosis and ultimately led to cataract formation. Transient transfection to increase the expression of SIRT1 decreased the protein expression levels of NF-κB, NLRP3, caspase-1, and GSDMD, inhibited HLEC pyroptosis, and reduced the release of LDH, providing a potential method for cataract prevention and treatment., Competing Interests: Declaration of competing interest There are no declared competing interests for the writers., (Copyright © 2024. Published by Elsevier Ltd.)

Plant-associated microorganisms can negatively influence plant growth, which makes them potential biocontrol agents for weeds. Two Gammaproteobacteria, Serratia plymuthica and Pseudomonas brassicacearum, isolated from roots of Jacobaea vulgaris, an invasive weed, negatively affect its root growth. We examined whether the effects of S. plymuthica and P. brassicacearum on J. vulgaris through root inoculation are concentration-dependent and investigated if these effects were mediated by metabolites in bacterial suspensions. We also tested whether the two bacteria negatively affected seed germination and seedling growth through volatile emissions. Lastly, we investigated the host specificity of these two bacteria on nine other plant species. Both bacteria significantly reduced J. vulgaris root growth after root inoculation, with S. plymuthica showing a concentration-dependent pattern in vitro. The cell-free supernatants of both bacteria did not affect J. vulgaris root growth. Both bacteria inhibited J. vulgaris seed germination and seedling growth via volatiles, displaying distinct volatile profiles. However, these negative effects were not specific to J. vulgaris. Both bacteria negatively affect J. vulgaris through root inoculation via the activity of bacterial cells, while also producing volatiles that hinder J. vulgaris germination and seedling growth. However, their negative effects extend to other plant species, limiting their potential for weed control., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Contact Electro-Catalysis (CEC) using commercial dielectric materials in contact-separation cycles with water triggers interfacial electron transfer, generating reactive oxygen species (ROS). However, the hydrophobicity of these materials limits reaction sites, and the generated ROS often combine to form hydrogen peroxide (H2O2), which does not decompose further, leading to suboptimal rates. Addressing H2O2 generation and activation is crucial for advancing CEC. Here, we synthesized a catalyst by loading polytetrafluoroethylene (PTFE) onto ZSM-5 (PZ), achieving uniform dispersion in water. Introducing an FeIII-initiated self-cycling Fenton system (SF-CEC), with synergistic O2 activation and FeIII-activated H2O2, enhanced ROS generation. This system enabled nearly 99% degradation of azo dyes within 10 minutes, a sixfold improvement over traditional CEC. It represents the fastest ultrasound-induced degradation rate of methyl orange dye to date. Without extra oxidants, it also achieved stable dissolution of precious metals in weakly acidic solutions at room temperature, with 80% gold dissolution within 2 hours-2.5 times faster than similar systems. This study corrects the perception of CEC under acidic conditions, offering new insights for dye degradation and precious metal recovery., (© 2024 Wiley‐VCH GmbH.)

With the swift evolution of multidrug-resistant bacteria resulting from the intense and inappropriate use of antibiotics, there is a pressing need for innovative solutions. In this study, a thermosensitive hydrogel was developed for efficient bacterial inhibition and promotion of wound healing. The antibacterial chitosan (CS) thermosensitive hydrogel, cross-linked with two-dimensional photothermal nanomaterial black phosphorus (BP) nanosheets through electrostatic interactions, effectively encapsulates and sustains the release of angiogenic drug deferoxamine mesylate (DFO). This facilitates the acceleration of re-epithelialization and neovascularization by enhancing cell migration and proliferation. Following near-infrared (NIR) treatment, this hydrogel demonstrates rapid eradication of the most common multidrug-resistant bacteria encountered in clinical settings, achieved through physical disruption of bacterial membranes and photothermal therapies. Noteworthy is the significant upregulation of IL-19 expression via STAT3 signaling pathways by the BP/CS-DFO hydrogel in a full-thickness wound model. This results in the polarization of the anti-inflammatory M2 macrophage phenotype, altering the microenvironment to a pro-healing state and enhancing extracellular matrix deposition and blood vessel formation. In conclusion, the BP/CS-DFO hydrogel shows immense promise as a potential clinical candidate for wound healing and antimicrobial therapy. Its innovative design and multifunctional capabilities position it as a valuable asset in combating antibiotic resistance and enhancing efficiency in wound healing.

Background: Tumor recurrence and mortality rates remain challenging in cancer patients despite comprehensive treatment. Neoadjuvant chemotherapy and immunotherapy aim to eliminate residual tumor cells, reducing the risk of recurrence. However, drug resistance during neoadjuvant therapy is a significant hurdle. Recent studies suggest a correlation between RNA methylation regulators (RMRs) and response to neoadjuvant therapy., Methods: Using a multi-center approach, we integrated advanced techniques such as single-cell transcriptomics, whole-genome sequencing, RNA sequencing, proteomics, machine learning, and in vivo/in vitro experiments. Analyzing pan-cancer cohorts, the association between neoadjuvant chemotherapy/immunotherapy effectiveness and RNA methylation using single-cell sequencing was investigated. Multi-omics analysis and machine learning algorithms identified genomic variations, transcriptional dysregulation, and prognostic relevance of RMRs, revealing distinct molecular subtypes guiding pan-cancer neoadjuvant therapy stratification., Results: Our analysis unveiled a strong link between neoadjuvant therapy efficacy and RNA methylation dynamics, supported by pan-cancer single-cell sequencing data. Integration of omics data and machine learning algorithms identified RMR genomic variations, transcriptional dysregulation, and prognostic implications in pan-cancer. High-RMR-expressing tumors displayed increased genomic alterations, an immunosuppressive microenvironment, poorer prognosis, and resistance to neoadjuvant therapy. Molecular investigations and in vivo/in vitro experiments have substantiated that the JAK inhibitor TG-101,209 exerts notable effects on the immune microenvironment of tumors, rendering high-RMR-expressing pan-cancer tumors, particularly in pancreatic cancer, more susceptible to chemotherapy and immunotherapy., Conclusions: This study emphasizes the pivotal role of RMRs in pan-cancer neoadjuvant therapy, serving as predictive biomarkers for monitoring the tumor microenvironment, patient prognosis, and therapeutic response. Distinct molecular subtypes of RMRs aid individualized stratification in neoadjuvant therapy. Combining TG-101,209 adjuvant therapy presents a promising strategy to enhance the sensitivity of high-RMR-expressing tumors to chemotherapy and immunotherapy. However, further validation studies are necessary to fully understand the clinical utility of RNA methylation regulators and their impact on patient outcomes., (© 2024. The Author(s).)

Aim: The purpose of this retrospective patient chart review was to analyze the clinical data of 52 patients with benign parotid tumors who underwent modified buried vertical mattress sutures and to assess the postoperative complication rate and patient scarring., Methods: A total of 52 patients with benign parotid tumors underwent total parotidectomy and modified buried vertical mattress suture. Variables included general characteristics (age, gender, tumor diameter, and pathologic type), surgical indicators (suture time, wound healing time, operative time, hospital stay, bleeding volume, and drainage volume), complication rates, and Sunnybrook facial neurological function score, visual scar scale (VSS) score and patient and observer scar assessment scale (POSAS) score., Results: Most tumors were less than 3 cm in diameter, with pleomorphic adenomas being the most common. Suture time was 14.83 ± 1.61 min, operative time was 58.90 ± 15.76 min and hospital stay were 5.12 ± 0.96 days. Postoperatively, salivary fistulae developed in one patient, Frey's syndrome in two patients, temporary facial paralysis in six patients and temporary numbness in the incision area in six patients. At 6 months postoperatively, 86.5% of patients had a Sunnybrook score of more than 80, and VSS scores and POSAS scores were between one and two., Conclusion: The postoperative complication rate was 30.8%, and the scarring in the facial incision area was mild and close to normal skin at 3 years postoperatively., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Ovarian cancer, the eleventh most prevalent cancer among women and a significant cause of cancer-related mortality, poses considerable challenges. While the Myc oncogene is implicated in diverse cancers, its impact on tumours expressing Myc during immune therapy processes remains enigmatic. Our study investigated Myc overexpression in a murine ovarian cancer cell line, focusing on alterations in HIF1a function. Seahorse experiments were utilized to validate metabolic shifts post-Myc overexpression. Moreover, we explored macrophage polarization and immunosuppressive potential following coculture with Myc-overexpressing tumour cells by employing Gpr132 -/- mice to obtain mechanistic insights. In vivo experiments established an immune-competent tumour-bearing mouse model, and CD8 T cell, Treg, and macrophage infiltration post-Myc overexpression were evaluated via flow cytometry. Additionally, adoptive transfer of OTI CD8 T cells was conducted to investigate antigen-specific immune response variations after Myc overexpression. The findings revealed a noteworthy delay in HIF1a degradation, enhancing its functionality and promoting the classical Warburg effect upon Myc overexpression. Lactic acid secretion by Myc-overexpressing tumour cells promoted Gpr132-dependent M2 macrophage polarization, leading to the induction of macrophages capable of significantly suppressing CD8 T cell function. Remarkably, heightened macrophage infiltration in tumour microenvironments post-Myc overexpression was observed alongside impaired CD8 T cell infiltration and function. Interestingly, CD4 T-cell infiltration remained unaltered, and immune-suppressive effects were alleviated when Myc-overexpressing tumour cells were administered to Gpr132 -/- mice, shedding light on potential therapeutic avenues for ovarian cancer management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Exosomes have received considerable attention as potent reference markers for the diagnosis of various neoplasms due to their close and direct relationship with the proliferation, adhesion, and migration of tumor. The ultrasensitive detection of cancer-derived low-abundance exosomes is imperative, but still a great challenge. Herein, we report an electrochemiluminescence (ECL) biosensor based on the DNA-bio-bar-code and hybridization chain reaction (HCR)-mediated dual signal amplification for the ultrasensitive detection of cancer-derived exosomes. In this system, two types of aptamers were modified on the magnetic nanoprobe (MNPs) and gold nanoparticles (AuNPs) with numerous bio-bar-code DNA, respectively, which formed "sandwich" structures in the presence of specific target exosomes. The "sandwich" structures were separated under magnetic field, and the numerous bio-bar-code DNA were released by dissolving AuNPs. The released bio-bar-code DNA triggered the HCR procedure to produce a good deal of long DNA duplex structure for embedding in hemin, which generated strong ECL signal in the presence of coreactors for ultrasensitive detection of exosomes. Under the optimal conditions, it exhibited a good linearly of exosomes ranging from 10 to 10 4 exosomes particle μL -1 with limit of detection down to 5.01 exosome particle μL -1 . Furthermore, the high ratio of ECL signal and minor change of ECL intensity indicated the good specificity, stability, and repeatability of this ECL biosensor. Given the good performance for exosome analysis, this ultrasensitive ECL biosensor has a promising application in the clinical diagnosis of early cancers.

Multiple Endocrine Neoplasia 1 gene (MEN1), which is known to be a tumor suppressor gene in lung tissues, encodes a 610 amino acid protein menin. Previous research has proven that MEN1 deficiency promotes the malignant progression of lung cancer. However, the biological role of this gene in the immune microenvironment of lung cancer remains unclear. In this study, we found that programmed cell death-ligand 1 (PD-L1) is upregulated in lung-specific Kras G12D mutation-induced lung adenocarcinoma in mice, after Men1 deficiency. Simultaneously, CD8 + and CD3 + T cells are depleted, and their cytotoxic effects are suppressed. In vitro, PD-L1 is inhibited by the overexpression of menin. Mechanistically, we found that MEN1 inactivation promotes the deubiquitinating activity of COP9 signalosome subunit 5 (CSN5) and subsequently increases the level of PD-L1., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Boron nitride nanosheets (BNNSs) have garnered significant attention across diverse fields; however, accomplishing on-demand, large-scale, and highly efficient preparation of BNNSs remains a challenge. Here, an on-demand preparation (OdP) method combining high-pressure homogenization and short-time ultrasonication is presented; it enables a highly efficient and controllable preparation of BNNSs from bulk hexagonal boron nitride (h-BN). The homogenization pressure and number of cycles are adjusted, and the production efficiency and yield of BNNSs reach 0.95 g g -1 h -1 and 82.8%, respectively, which significantly exceed those attained by using existing methods. The universality of the OdP method is demonstrated on h-BN raw materials of various bulk sizes from various producers. Furthermore, this method allows the preparation of BNNSs having specific sizes based on the final requirements. Both simulation and experimental results indicate that large BNNSs are particularly suitable for enhancing the thermal conductivity and electrical insulation properties of dielectric polymer nanocomposites. Interestingly, the small BNNS-filled photonic nanocomposite films fabricated via the OdP method exhibit superior daytime radiative cooling properties. Additionally, the OdP method offers the benefits of low energy consumption and reduced greenhouse gas emissions and fossil energy use. These findings underscore the unique advantages of the OdP method over other techniques for a high-efficiency and controllable preparation of large BNNSs., (© 2024 Wiley‐VCH GmbH.)

Background and Aims: Burn and scald injuries are the fourth most common type of trauma. Pediatric burns account for a high proportion of the total number of burn patients and impose a high burden on public health. Understanding the epidemiology of pediatric burns can help improve science education and reduce the incidence of burn injuries., Methods: This study is a single-center retrospective study. One thousand five hundred and twenty-seven pediatric burn patients admitted to our burn center from January 2016 to December 2020 were included. Demographic and epidemiological data of included patients were extracted and analyzed. The correlations of categorical data were tested by the Chi-square tests, and differences of continuous data were tested by the Kruskal-Wallis tests. A p -value of less than 0.05 was considered to be statistically significant., Results: The results showed that children under 3 years of age were most susceptible to burn and scald injuries. Burn injuries were most likely to occur in the season of winter and at the place of home. 56.6% of included patients did receive first aid measures, while 1.8% received gold-standard first aid. Clinical variables related to the severity of injuries were statistically different between patients with and without cooling measures in first aid. Linear regression models showed that emergency treatment of burns in children and adolescents was associated with outcome indicators, including number of operations, total operation duration per total burn surface area (TBSA), cost per TBSA, and length of stay per TBSA., Conclusions: This study summarized the epidemiology and outcomes of pediatric burn patients admitted to a burn center in northern China. Adopting cooling measures in first aid can reduce the severity of injuries and reduce the burden on the medical system. Education on burn prevention and first aid measures to caregivers of children, especially preschool children, should be strengthened., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Development of subtype-selective drugs for G protein-coupled receptors poses a significant challenge due to high similarity between subtypes, as exemplified by the three β-adrenergic receptors (βARs). The β3AR agonists show promise for treating the overactive bladder or preterm birth, but their potential is hindered by off-target activation of β1AR and β2AR. Interestingly, several β-blockers, which are antagonists of the β1ARs and β2ARs, have been reported to exhibit agonist activity at the β3AR. However, the molecular mechanism remains elusive. Understanding the underlying mechanism should facilitate the development of β3AR agonist drugs with improved selectivity and reduced off-target effects. In this work, we determined the structures of human β3AR in complex with the endogenous agonist epinephrine or with a synthetic β3AR agonist carazolol, which is also a high-affinity β-blocker. Structure comparison, mutagenesis studies and molecular dynamics simulations revealed that the differences on the flexibility of D3.32 directly contribute to carazolol's distinct activities as an antagonist for the β2AR and an agonist for the β3AR. The process is also indirectly influenced by the extracellular loops (ECL), especially ECL1. Taken together, these results provide key guidance for development of selective β3AR agonists, paving the way for new therapeutic opportunities., (© 2024 Wiley‐VCH GmbH.)

Nitrogen cycling in terrestrial ecosystems is critical for biodiversity, vegetation productivity and biogeochemical cycling. However, little is known about the response of functional nitrogen cycle genes to global change factors in soils under different land uses. Here, we conducted a multiple hierarchical mixed effects meta-analyses of global change factors (GCFs) including warming (W+), mean altered precipitation (MAP+/-), elevated carbon dioxide concentrations (eCO 2 ), and nitrogen addition (N+), using 2706 observations extracted from 200 peer-reviewed publications. The results showed that GCFs had significant and different effects on soil microbial communities under different types of land use. Under different land use types, such as Wetland, Tundra, Grassland, Forest, Desert and Agriculture, the richness and diversity of soil microbial communities will change accordingly due to differences in vegetation cover, soil management practices and environmental conditions. Notably, soil bacterial diversity is positively correlated with richness, but soil fungal diversity is negatively correlated with richness, when differences are driven by GCFs. For functional genes involved in nitrification, eCO 2 in agricultural soils and the interaction of N+ with other GCFs in grassland soils stimulate an increase in the abundance of the AOA-amoA gene. In agricultural soil, MAP+ increases the abundance of nifH. W+ in agricultural soils and N+ in grassland soils decreased the abundance of nifH. The abundance of the genes nirS and nirK, involved in denitrification, was mainly negatively affected by W+ and positively affected by eCO 2 in agricultural soil, but negatively affected by N+ in grassland soil. This meta-analysis was important for subsequent research related to global climate change. Considering data limitations, it is recommended to conduct multiple long-term integrated observational experiments to establish a scientific basis for addressing global changes in this context., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Natural estrogens, including estrone (E1), 17β-estradiol (E2), and estriol (E3), are potentially carcinogenic pollutants commonly found in water and soil environments. Bacterial metabolic pathway of E2 has been studied; however, the catabolic products of E3 have not been discovered thus far. In this study, Novosphingobium sp. ES2-1 was used as the target strain to investigate its catabolic pathway of E3. The metabolites of E3 were identified by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) combined with stable 13 C 3 -labeling. Strain ES2-1 could almost completely degrade 20 mg∙L -1 of E3 within 72 h under the optimal conditions of 30°C and pH 7.0. When inoculated with strain ES2-1, E3 was initially converted to E1 and then to 4-hydroxyestrone (4-OH-E1), which was then cleaved to HIP (metabolite A6) via the 4, 5-seco pathway or cleaved to the B loop via the 9,10-seco pathway to produce metabolite with a long-chain ketone structure (metabolite B4). Although the ring-opening sequence of the above two metabolic pathways was different, the metabolism of E3 was achieved especially through continuous oxidation reactions. This study reveals that, E3 could be firstly converted to E1 and then to 4-OH-E1, and finally degraded into small molecule metabolites through two alternative pathways, thereby reducing E3 pollution in water and soil environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Metastable binding sites (MBS) have been observed in a multitude of molecular dynamics simulations and can be considered low affinity allosteric binding sites (ABS) that function as stepping stones as the ligand moves toward the orthosteric binding site (OBS). Herein, we show that MBS can be utilized as ABS in ligand design, resulting in ligands with improved binding kinetics. Four homobivalent bitopic ligands ( 1 - 4 ) were designed by molecular docking of ( S )-alprenolol (( S )-ALP) in the cocrystal structure of the β 2 adrenergic receptor (β 2 AR) bound to the antagonist ALP. Ligand 4 displayed a potency and affinity similar to ( S )-ALP, but with a >4-fold increase in residence time. The proposed binding mode was confirmed by X-ray crystallography of ligand 4 in complex with the β 2 AR. This ligand design principle can find applications beyond the β 2 AR and G protein-coupled receptors (GPCRs) as a general approach for improving the pharmacological profile of orthosteric ligands by targeting the OBS and an MBS simultaneously.

Background and Aims: Endothelial-to-mesenchymal transition (EndMT) is an important reason for restenosis but the underlying mechanisms need to be further explored. Therefore, the purpose of this study is to screen significantly different microRNAs (miRNAs) and assess their functions and downstream pathways., Methods: This study screened several miRNAs with significant differences between human arterial segments from restenosis patients and healthy volunteers using whole transcriptome resequencing and real-time quantitative reverse transcription PCR (qRT-PCR). We explored the correlation between miR-1290 and EndMT using Western blot, qRT-PCR, Pearson correlation analysis and further functional gain and loss experiments. Subsequently, we identified the direct downstream target of miR-1290 by bioinformatics analysis, RNA pull-down, double Luciferase reporter gene and other functional experiments. Finally, rat carotid artery balloon injury model demonstrated the therapeutic potential of miR-1290 regulator., Results: We screened 129 differentially expressed miRNAs. Among them, miR-1290 levels were significantly higher in restenosis arteries than in healthy arteries, and as expected, EndMT was functionally enhanced with miR-1290 overexpression and comparatively weakened when miR-1290 was knocked down. In addition, fibroblast growth factor-2 (FGF2) was established as the downstream target of miR-1290. Finally, we utilized an animal model and found that low miR-1290 levels could alleviate EndMT and the progression of restenosis., Conclusions: Our study demonstrated the strong regulatory effects of miR-1290 on EndMT, endometrial hyperplasia and restenosis, which could be useful as biomarker and therapeutic target for stent implantation in patients with arterial occlusive disease of the lower extremities., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Synergistic control of nitrogen oxides (NO x ) and nitrogen-containing volatile organic compounds (NVOCs) from industrial furnaces is necessary. Generally, the elimination of n -butylamine ( n -B), a typical pollutant of NVOCs, requires a catalyst with sufficient redox ability. This process induces the production of nitrogen-containing byproducts (NO, NO 2 , N 2 O), leading to lower N 2 selectivity of NH 3 selective catalytic reduction of NO x (NH 3 -SCR). Here, synergistic catalytic removal of NO x and n -B via spatially separated cooperative sites was originally demonstrated. Specifically, titania nanotubes supported CuO x -CeO 2 (CuCe-TiO 2 NTs) catalysts with spatially separated cooperative sites were creatively developed, which showed a broader active temperature window from 180 to 340 °C, with over 90% NO x conversion, 85% n -B conversion, and 90% N 2 selectivity. A synergistic effect of the Cu and Ce sites was found. The catalytic oxidation of n -B mainly occurred at the Cu sites inside the tube, which ensured the regular occurrence of the NH 3 -SCR reaction on the outer Ce sites under the matching temperature window. In addition, the n -B oxidation would produce abundant intermediate NH 2 *, which could act as an extra reductant to promote NH 3 -SCR. Meanwhile, NH 3 -SCR could simultaneously remove the possible NO x byproducts of n -B decomposition. This novel strategy of constructing cooperative sites provides a distinct pathway for promoting the synergistic removal of n -B and NO x .

Introduction: This proof-of-concept, open-label phase 1b study evaluated the safety and efficacy of cilofexor, a potent selective farnesoid X receptor agonist, in patients with compensated cirrhosis due to primary sclerosing cholangitis., Methods: Escalating doses of cilofexor (30 mg [weeks 1-4], 60 mg [weeks 5-8], 100 mg [weeks 9-12]) were administered orally once daily over 12 weeks. The primary endpoint was safety. Exploratory measures included cholestasis and fibrosis markers and pharmacodynamic biomarkers of bile acid homeostasis., Results: Eleven patients were enrolled (median age: 48 years; 55% men). The most common treatment-emergent adverse events (TEAEs) were pruritus (8/11 [72.7%]), fatigue, headache, nausea, and upper respiratory tract infection (2/11 [18.2%] each). Seven patients experienced a pruritus TEAE (one grade 3) considered drug-related. One patient temporarily discontinued cilofexor owing to peripheral edema. There were no deaths, serious TEAEs, or TEAEs leading to permanent discontinuation. Median changes (interquartile ranges) from baseline to week 12 (predose, fasting) were -24.8% (-35.7 to -7.4) for alanine transaminase, -13.0% (-21.9 to -8.6) for alkaline phosphatase, -43.5% (-52.1 to -30.8) for γ-glutamyl transferase, -12.7% (-25.0 to 0.0) for total bilirubin, and -21.2% (-40.0 to 0.0) for direct bilirubin. Least-squares mean percentage change (95% confidence interval) from baseline to week 12 at trough was -55.3% (-70.8 to -31.6) for C4 and -60.5% (-81.8 to -14.2) for cholic acid. Fasting fibroblast growth factor 19 levels transiently increased after cilofexor administration., Discussion: Escalating doses of cilofexor over 12 weeks were well tolerated and improved cholestasis markers in patients with compensated cirrhosis due to primary sclerosing cholangitis (NCT04060147)., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Electrokinetic-Permeable Reaction Barrier (EK-PRB) coupled remediation technology can effectively treat heavy metal-contaminated soil near coal mines. This study was conducted on cadmium (Cd), a widely present element in the soil of the mining area. To investigate the impact of the voltage gradient on the remediation effect of EK-PRB, the changes in current, power consumption, pH, and Cd concentration content during the macroscopic experiment were analyzed. A three-dimensional visualized kaolinite-heavy metal-water simulation system was constructed and combined with the Molecular Dynamics (MD) simulations to elucidate the migration mechanism and binding active sites of Cd on the kaolinite (001) crystalline surface at the microscopic scale. The results showed that the voltage gradient positively correlates with the current, power consumption, and Cd concentration during EK-PRB remediation, and the average removal efficiency increases non-linearly with increasing voltage gradient. Considering power consumption, average removal efficiency, and cost-effectiveness, the voltage range is between 1.5 and 3.0 V/cm, with 2.5 V/cm being the optimal value. The results of MD simulations and experiments correspond to each other. Cd 2+ formed a highly stable adsorption structure in contrast to the Al-O sheet on the kaolinite (001) crystalline surface. The mean square displacement (MSD) curve of Cd 2+ under the electric field exhibits anisotropy, the total diffusion coefficient D Total increases and the Cd 2+ migration rate accelerates. The electric field influences the microstructure of Cd 2+ complexes. With the enhancement of the voltage gradient, the complexation between Cd 2+ and water molecules is enhanced, and the interaction between Cd 2+ and Cl - in solution is weakened., 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.)

Objective: The present study evaluated the effect of flaxseed meal degraded by a protease, Lactobacillus plantarum, or both on the growth performance, nutrient digestibility, and health status of broilers., Methods: There were four diets containing flaxseed meals in its non-degraded form (control, CON), degraded with 3,000 U/kg of protease (enzymatic, ELM), 1.0×109 CFU/kg of Lactobacillus plantarum (fermented, FLM), or both (dual-degraded, DLM). Each form of flaxseed meals was added at 15% of diet. A total of 480 yellow-feathered broilers at 22 d of age were distributed into 4 groups with 6 replicates of 20 chickens each. The feeding trial lasted for 42 d. Growth performance, apparent fecal digestibility (dry matter, energy, crude protein, and ash), and serum immunoglobins and antioxidases were determined at 42 and 63 d of age., Results: Results showed that ELM, FLM, and DLM increased (p<0.001) the contents of peptides and decreased (p<0.001) cyanogenic glycosides, compared to CON. The diets with degraded flaxseed meals increased (p<0.05) feed intake and body weight gain throughout the feeding trial, and the digestibility of energy, crude protein, and ash at the end of feeding trial. Furthermore, all degraded groups enhanced (p<0.05) broiler health status by increasing serum immunoglobulins A and G. Additinally, DLM showed more pronounced effects (p<0.05) on these parameters than ELM or FLM., Conclusion: Flaxseed meals degraded by enzymolysis, fermentation, or both had improved nutrition and application in broilers.

G-protein-coupled receptors (GPCRs) activate heterotrimeric G proteins by promoting guanine nucleotide exchange. Here, we investigate the coupling of G proteins with GPCRs and describe the events that ultimately lead to the ejection of GDP from its binding pocket in the Gα subunit, the rate-limiting step during G-protein activation. Using molecular dynamics simulations, we investigate the temporal progression of structural rearrangements of GDP-bound G s protein (G s ·GDP; hereafter G s GDP ) upon coupling to the β 2 -adrenergic receptor (β 2 AR) in atomic detail. The binding of G s GDP to the β 2 AR is followed by long-range allosteric effects that significantly reduce the energy needed for GDP release: the opening of α1-αF helices, the displacement of the αG helix and the opening of the α-helical domain. Signal propagation to the G s occurs through an extended receptor interface, including a lysine-rich motif at the intracellular end of a kinked transmembrane helix 6, which was confirmed by site-directed mutagenesis and functional assays. From this β 2 AR-G s GDP intermediate, G s undergoes an in-plane rotation along the receptor axis to approach the β 2 AR-G s empty state. The simulations shed light on how the structural elements at the receptor-G-protein interface may interact to transmit the signal over 30 Å to the nucleotide-binding site. Our analysis extends the current limited view of nucleotide-free snapshots to include additional states and structural features responsible for signaling and G-protein coupling specificity., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Pear black spot (PBS) is caused by Alternaria alternata and causes severe damage worldwide. It is particularly important to screen for synergistic fungicide combinations to address issues associated with the low efficacy of biocontrol agents, high dosage requirements and poor sustained effectiveness of chemical fungicides., Methods: In vitro and in vivo studies were performed to determine the efficacy of a treatment for this important disease. Additionally, transcriptomic and metabolomic analyses were performed to determine the main molecular and biochemical mechanisms involved in the interaction., Results: Bacillus tequilensis 2&#95;2a has a significant synergistic effect with difenoconazole, causing hyphal entanglement and spore lysis and inhibiting the formation of PBS lesions in vitro . In the field, the control effect of the combination was greater than 95%. The pathways associated with the synergistic effect on the mycelia of A. alternata were divided into two main types: one included glycolysis, oxidative phosphorylation, and MAPK signal transduction, while the other included glycolysis, the TCA cycle, coenzyme A biosynthesis, sterol synthesis, and fatty acid degradation. Both types of pathways jointly affect the cell cycle. The main functions of the key genes and metabolites that have been verified as being affected are glucose synthesis and oxidative respiration, as well as citric acid synthesis, acetyl-CoA synthesis, and sterol synthesis. Both functions involve intracellular pyridine nucleotide metabolism and adenine nucleotide transformation., Conclusion: This study helps to reveal the synergistic mechanisms underlying the combined efficacy of biological and chemical agents, providing a scientific basis for field applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 Bi, Lu, Wu, Liu, Han, Wang and Zhao.)

Reasonably designing highly active, environmentally friendly, and cost-effective catalysts for efficient elimination of pollutants from water is desirable but challenging. Herein, an efficient heterogeneous photo-Fenton catalyst tourmaline (TM)/tungsten oxide (WO 3-x ) (named TW10) containing tungsten/boron/iron (W/B/Fe) synergistic active centers and 90% of cheap natural tourmaline (TM) mineral rich in Fe and B elements. The TW10 catalyst can quickly activate peroxymonosulfate (PMS) to generate massive active free radicals, which may induce the rapid and efficient degradation of tetracycline (TC). The TW10/PMS/Visible light system can effectively degrade up to 98.7% of tetracycline (TC) in actual waters (i.e. seawater, Yellow River, and Yangtze River water), and the catalytic degradation rates reach 1.65, 5.569, and 2.38 times higher than those of TM, WO 3-x , and commercial P25 (Degussa, Germany), respectively. In addition, the catalyst can be recycled and reused multiple times. Electron spin resonance spectroscopy (EPR), X-ray photoelectron spectroscopy (XPS), and liquid chromatograph-mass spectrometer (LC-MS) analyses confirm that the synergistic catalytic effect of W/B/Fe sites on the TW10 catalyst accelerates the electron transfer between Fe(II) and Fe(III), as well as between W(V) and W(VI), and thus promotes the rapid degradation of TC. The catalytic reaction mechanism and degradation pathway of TC were explored. This work provides a feasible route for the design and development of new eco-friendly and efficient catalyst., 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. Published by Elsevier B.V.)

Aicardi-Goutières syndrome 6 (AGS6) is a serious auto-immunization-associated acute neurologic decompensation. AGS6 manifests as acute onset of severe generalized dystonia of limbs and developmental regression secondary to febrile illness mostly. Dyschromatosis symmetrica hereditaria (DSH), as pigmentary genodermatosis, is a characterized mixture of hyperpigmented and hypopigmented macules. Both AGS6 and DSH are associated with ADAR1 pathogenic variants. To explore the etiology of a proband with developmental regression with mixture of hyperpigmentation and hypopigmentation macules, we used the trio-WES. Later, to clarify the association between variants and diseases, we used guidelines of ACMG for variants interpretation and quantitative Real-time PCR for verifying elevated expression levels of interferon-stimulated genes, separately. By WES, we detected 2 variants in ADAR1 and a variant in TSC2, respectively, were NM&#95;001111.5:c.1096&#95;1097del, NM&#95;001111.5:c.518A>G, and NM&#95;000548.5:c.1864C>T. Variants interpretation suggested that these 3 variants were both pathogenic. Expression levels of interferon-stimulated genes also elevated as expected. We verified the co-occurrence of pathogenic variants of ADAR1 and TSC2 in AGS6 patients with DSH. Our works contributed to the elucidation of ADAR1 pathogenic mechanism, given the specific pathogenic mechanism of ADAR1, and it is necessary to consider with caution when variants were found in ADAR1., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Death anxiety is thought to cause a range of mental disorders among cancer patients, which may affect their mental health and even quality of life. This study sought to investigate experiential avoidance, meaning in life, and death anxiety among Chinese cancer patients and then explore the relationship between these 3 variables., Methods: A total of 300 cancer patients recruited from a tertiary cancer hospital participated in this study from October to December 2021. A cross-sectional survey was conducted using a demographic and clinical characteristics questionnaire, the Acceptance and Action Questionnaire II, the Meaning in Life Questionnaire, and Templer's Death Anxiety Scale. Correlation analysis, hierarchical regression analysis, and mediating effect analysis were used to analyze the relationship among experiential avoidance, meaning in life (including 2 dimensions: presence of meaning and search for meaning), and death anxiety., Results: A total of 315 questionnaires were distributed, and 300 valid questionnaires were returned, resulting in a valid response rate of 95.2%. Experiential avoidance (r = 0.552, p < 0.01) was moderately positively correlated with death anxiety. Presence of meaning (r = - 0.400, p < 0.01) was moderately negatively correlated with death anxiety, while search for meaning (r = - 0.151, p < 0.01) was weakly negatively correlated with death anxiety. Regression analysis showed that experiential avoidance (β = 0.464) and presence of meaning (β = -0.228) were predictors of death anxiety. Mediating effect analysis revealed that presence of meaning either completely or partially mediated the effect of experiential avoidance and death anxiety, and the indirect effect accounted for 14.52% of the total effect., Conclusion: Overall, experiential avoidance predicts death anxiety in cancer patients, and meaning in life can mediate this effect. The results of this study provide a new path for studying the mechanism of death anxiety and suggest a more positive and promising strategy for its management., (© 2024. The Author(s).)

Hyaluronic acid (HA) is a new functional food additive which has the potential to ameliorate persistent inflammation, immunosuppression and catabolism syndrome (PICS), but the biological effects of HA with various molecular weights differ dramatically. To systematically investigate the efficacy of HA in altering PICS symptoms, medium-molecular-weight (MMW) HA was specifically selected to test its intervention effect on a PICS mouse model induced by CLP through oral administration, with high-molecular-weight (HMW) and low-molecular-weight (LMW) HA also participating in the experimental validation process. The results of pathological observations and gut flora showed that MMW HA rapidly alleviated lung lesions and intestinal structural changes in PICS mice in the short term. However, although long-term MMW HA administration significantly reduced the proportions of harmful bacteria in gut flora, inflammatory responses in the intestines and lungs of PICS mice were significantly higher in the MMW HA group than in the HMW HA and LMW HA groups. The use of HMW HA not only rapidly reduced the mortality rate of PICS mice but also improved their grip strength and the recovery of spleen and thymus indices. Furthermore, it consistently promoted the recovery of lung and intestinal tissues in PICS mice, and it also assisted in the sustained restoration of their gut microbiota. These effects were superior to those of LMW HA and MMW HA. The experimental results indicate that HMW weight HA has the greatest potential to be an adjunct in alleviating PICS as a food additive, while the safety of other HAs requires further attention.

This study utilized middle cerebral artery occlusion (MCAO) mouse models and HT-22 cell oxygen and glucose deprivation/reoxygenation (OGD/R) models to investigate the therapeutic effects of melatonin on ischemic brain injury. In the experiments, MCAO mice were treated with 5 and 10 mg/kg doses of melatonin, and H-T22 cells underwent OGD/R treatment and were administered different concentrations of melatonin. The results showed that melatonin significantly reduced ischemic brain area, neural damage, cerebral edema, and neuronal apoptosis in MCAO mice. In the HT-22 cell model, melatonin also improved cell proliferation ability, reduced apoptosis, and ROS production. Further mechanistic studies found that melatonin exerts protective effects by inhibiting ferroptosis, an iron-dependent form of regulated cell death, through regulation of the ACSL4/CYP1B1 pathway. In MCAO mice, melatonin decreased lipid peroxidation, ROS production, and ACSL4 protein expression. Overexpression of CYP1B1 increased ACSL4 ubiquitination and degradation, thereby increasing cell tolerance to ferroptosis, reducing ACSL4 protein levels, and decreasing ROS production. CYP1B1 knockdown obtained opposite results. The CYP1B1 metabolite 20-HETE induces expression of the E3 ubiquitin ligase FBXO10 by activating PKC signaling, which promotes ACSL4 degradation. In the OGD/R cell model, inhibition of CYP1B1 expression reversed the therapeutic effects of melatonin. In summary, this study demonstrates that melatonin protects the brain from ischemic injury by inhibiting ferroptosis through regulation of the ACSL4/CYP1B1 pathway, providing evidence for new therapeutic targets for ischemic brain injury., (© 2024 Wiley Periodicals LLC.)

Background: Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying immune mechanisms are unclear., Methods: We performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells isolated from children (n=6) with TBM using 10 xGenomics platform. We used unsupervised clustering of cells and cluster visualization based on the gene expression profiles, and validated the protein and cytokines by ELISA analysis., Results: We revealed for the first time 33 monocyte populations across the CSF cells and PBMCs of children with TBM. Within these populations, we saw that CD4&#95;C04 cells with Th17 and Th1 phenotypes and Macro&#95;C01 cells with a microglia phenotype, were enriched in the CSF. Lineage tracking analysis of monocyte populations revealed myeloid cell populations, as well as subsets of CD4 and CD8 T-cell populations with distinct effector functions. Importantly, we discovered that complement-activated microglial Macro&#95;C01 cells are associated with a neuroinflammatory response that leads to persistent meningitis. Consistently, we saw an increase in complement protein (C1Q), inflammatory markers (CRP) and inflammatory factor (TNF-α and IL-6) in CSF cells but not blood. Finally, we inferred that Macro&#95;C01 cells recruit CD4&#95;C04 cells through CXCL16/CXCR6., Discussion: We proposed that the microglial Macro&#95;C01 subset activates complement and interacts with the CD4&#95;C04 cell subset to amplify inflammatory signals, which could potentially contribute to augment inflammatory signals, resulting in hyperinflammation and an immune response elicited by Mtb -infected tissues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mo, Shi, Cai, Xu, Xu, Xu, Zhang, Zhang, Liu, Che, Liu, Xing, Long, Chen and Liu.)

Renewable, green, and safe natural biopolymer-derived materials are highly desired for the purification of pollutants, but significantly improving their performance without the introduction of additional harmful chemicals remains a huge challenge. Based on the concept of "structure optimization design", environment-friendly composite beads (named SA/PASP/RE) with excellent adsorption performance and recyclability were rationally constructed through a green ionic crosslinking route, using the completely green biopolymer sodium alginate (SA), sodium salt of polyaspartic acid (PASP), and the natural nanoclay rectorite (RE) as starting materials. The nano-layered RE was embedded in the polymer matrix to prevent the polymer chain from becoming over-entangled so that more adsorption sites inside the polymer network were exposed, which effectively improved the mass transfer efficiency of the adsorbent and the removal rate of contaminants. The composite beads embedded with 0.6% RE showed high adsorption capacities of 211.78, 197.13, and 195.69 mg/g for Pb(II) and 643.00, 577.80, and 567.10 mg/g for methylene blue (MB) in Yellow River water, Yangtze River water, and tap water, respectively. And the beads embedded with 43% RE could efficiently adsorb Pb(II) and MB with high capacities of 187.78 mg/g and 586.46 mg/g, respectively. This study provides a new route to design and develop a green, cost-effective, and efficient adsorbent for the decontamination of wastewater., Competing Interests: The authors declare no conflicts of interest.

In visible light communication (VLC), the precise latency evaluation of wireless access networks and the efficient forwarding strategy of core networks are the crux for end-to-end reliability provisioning. Leveraging martingale theory, an elegant latency-bounded reliability analysis framework is studied for the VLC network. Considering the characteristic that VLC links are easy to block, the martingale of the service process is constructed. Based on the time shift features, the martingale process related to latency is proposed for the VLC system, which models the influence of entanglement between aggregate arrivals and random service on latency. A stopping time event about latency is defined. Renting the stopping time theory, a tight upper bound of the unreliability with regard to latency is derived. In the core network, a dynamic forward backhaul framework is proposed, which uses the relay selection algorithm based on back-pressure theory to improve data transmission quality. The theoretical latency-bounded reliability matches the simulation results well, which verifies the effectiveness of the proposed analysis framework, and the proposed relay selection algorithm can also improve network performance under data-intensive transmission.

Artificial intelligence (AI) has made significant progress in the medical field in the last decade. The AI-powered analysis methods of medical images and clinical records can now match the abilities of clinical physicians. Due to the challenges posed by the unique group of fetuses and the dynamic organ of the heart, research into the application of AI in the prenatal diagnosis of congenital heart disease (CHD) is particularly active. In this review, we discuss the clinical questions and research methods involved in using AI to address prenatal diagnosis of CHD, including imaging, genetic diagnosis, and risk prediction. Representative examples are provided for each method discussed. Finally, we discuss the current limitations of AI in prenatal diagnosis of CHD, namely Volatility, Insufficiency and Independence (VII), and propose possible solutions., 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., (© 2024 Liu, Zhang, Zhu, Jia, Wang, He and Zhang.)

Trehalases (TREs) are pivotal enzymes involved in insect development and reproduction, making them prime targets for pest control. We investigated the inhibitory effect of three thiazolidinones with piperine skeletons (6a, 7b, and 7e) on TRE activity and assessed their impact on the growth and development of the fall armyworm (FAW), Spodoptera frugiperda . The compounds were injected into FAW larvae, while the control group was treated with 2% DMSO solvent. All three compounds effectively inhibited TRE activity, resulting in a significant extension of the pupal development stage. Moreover, the treated larvae exhibited significantly decreased survival rates and a higher incidence of abnormal phenotypes related to growth and development compared to the control group. These results suggest that these TRE inhibitors affect the molting of larvae by regulating the chitin metabolism pathway, ultimately reducing their survival rates. Consequently, these compounds hold potential as environmentally friendly insecticides.

Multi-functionalised nano-platforms based on persistent-luminescence nanoparticles (PLNPs) have attracted considerable attention for biomedical applications owing to their lack of background noise and suitability for in vivo imaging without the need for in situ excitation. However, nano-platforms based on PLNPs for continuous photodynamic therapy (PDT) are currently lacking. Herein, we report a nano-platform (LiGa 4.99 O 8 :Cr 0.01 /IrO 2 , LGO:Cr/IrO 2 ) prepared using PLNPs (LiGa 4.99 O 8 :Cr 0.01 , LGO:Cr) covalently bonded with iridium oxide nanoparticles (IrO 2 NPs), producing near-infrared (NIR) persistent luminescence, "afterglow" PDT and photo-thermal therapy (PTT) effects. The LGO:Cr/IrO 2 not only exhibits NIR-persistent luminescence at 719 nm and a PTT effect under 808 nm irradiation but also a continuous "afterglow" PDT effect without the need for in situ excitation owing to persistent energy transfer from LGO:Cr to the IrO 2 NPs, in turn generating reactive oxygen species (ROS). This multi-functional nano-platform is expected to further promote the application of PLNPs in tumour treatment.

This study introduces the UV/glucose-oxidase@Kaolin (GOD@Kaolin) coupled organic green rust (OGR) system (UV/OGR/GOD@Kaolin) to investigate the promotion of glucose oxidase activity by UV light and its synergistic degradation mechanism for photosensitive pollutants, specifically targeting the efficient degradation of 4-chlorophenol (4-CP). The enzyme system demonstrates its ability to overcome drawbacks associated with traditional Fenton systems, including a narrow pH range and high localized concentration of H 2 O 2 , by gradually releasing hydrogen peroxide in situ within a neutral environment. In the presence of UV radiation under specific conditions, enhanced enzyme activity is observed, resulting in increased efficiency in pollutant removal. The gradual release of hydrogen peroxide plays a crucial role in preventing unwanted reactions among active substances. These unique features facilitate the generation of highly reactive species, such as Fe(IV)O, •OH, and •O 2 - , tailored to efficiently target the organic components of interest. Additionally, the system establishes a positive iron cycle, ensuring a sustained reactive capability throughout the degradation process. The results highlight the UV/OGR/GOD@Kaolin system as an effective and environmentally friendly approach for the degradation of 4-CP, and the resilience of the enzyme extends the system's applicability to a broader range of scenarios., 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.)

Glioblastoma (GBM) is one of the most malignant tumors of the central nervous system. The pattern of immune checkpoint expression in GBM remains largely unknown. We performed snRNA-Seq and spatial transcriptomic (ST) analyses on untreated GBM samples. 8 major cell types were found in both tumor and adjacent normal tissues, with variations in infiltration grade. Neoplastic cells&#95;6 was identified in malignant cells with high expression of invasion and proliferator-related genes, and analyzed its interactions with microglia, MDM cells and T cells. Significant alterations in ligand-receptor interactions were observed, particularly between Neoplastic cells&#95;6 and microglia, and found prominent expression of VISTA/VSIG3, suggesting a potential mechanism for evading immune system attacks. High expression of TIM-3, VISTA, PSGL-1 and VSIG-3 with similar expression patterns in GBM, may have potential as therapeutic targets. The prognostic value of VISTA expression was cross-validated in 180 glioma patients, and it was observed that patients with high VISTA expression had a poorer prognosis. In addition, multimodal cross analysis integrated SnRNA-seq and ST, revealing complex intracellular communication and mapping the GBM tumor microenvironment. This study reveals novel molecular characteristics of GBM, co-expression of immune checkpoints, and potential therapeutic targets, contributing to improving the understanding and treatment of GBM., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Rapeseed is a critical cash crop globally, and understanding its distribution can assist in refined agricultural management, ensuring a sustainable vegetable oil supply, and informing government decisions. China is the leading consumer and third-largest producer of rapeseed. However, there is a lack of widely available, long-term, and large-scale remotely sensed maps on rapeseed cultivation in China. Here this study utilizes multi-source data such as satellite images, GLDAS environmental variables, land cover maps, and terrain data to create the China annual rapeseed maps at 30 m spatial resolution from 2000 to 2022 (CARM30). Our product was validated using independent samples and showed average F1 scores of 0.869 and 0.971 for winter and spring rapeseed. The CARM30 has high spatial consistency with existing 10 m and 20 m rapeseed maps. Additionally, the CARM30-derived rapeseed planted area was significantly correlated with agricultural statistics (R 2  = 0.65-0.86; p < 0.001). The obtained rapeseed distribution information can serve as a reference for stakeholders such as farmers, scientific communities, and decision-makers., (© 2024. The Author(s).)

In the pig farming industry, it is recommended to avoid groups when treating individuals to reduce adverse reactions in the group. However, can this eliminate the adverse effects effectively? Piglets were assigned to the Rewarding Group (RG), the Punishing Group (PG), and the Paired Control Group (PCG). There were six replicates in each group, with two paired piglets per replicate. One piglet of the RG and PG was randomly selected as the Treated pig (TP), treated with food rewards or electric shock, and the other as the Naive pig (NP). The NPs in the RG and PG were unaware of the treatment process, and piglets in the PCG were not treated. The behavior and heart rate changes of all piglets were recorded. Compared to the RG, the NPs in the PG showed longer proximity but less contact behavior, and the TPs in the PG showed more freezing behavior. The percentage change in heart rate of the NPs was synchronized with the TPs. This shows that after sensory avoidance, the untreated pigs could also feel the emotions of their peers and their emotional state was affected by their peers, and the negative emotions in the pigs lasted longer than the positive emotions. The avoidance process does not prevent the transfer of negative emotions to peers via emotional contagion from the stimulated pig.

The quality and safety of agricultural products are related to people's lives and health, economic development, and social stability, and have always been a hot issue of concern to the government and society. The rapid development of digital traceability technology in the digital environment has brought new opportunities for the supervision of agricultural product quality and safety, but the frequent occurrence of agricultural product safety incidents in recent years has exposed many problems such as the lack of governmental supervision, unstandardized production process of enterprises, and weak consumer awareness. To improve the cooperation efficiency of stakeholders and ensure the quality and safety of agricultural products, this paper proposes a dynamic model based on evolutionary game theory. The model incorporates the government, agricultural product producers, and farmers, and evaluates the stability and effectiveness of the system under different circumstances. The results of the study show that there are multiple evolutionary stabilization strategies in the tripartite evolutionary game model of agricultural product quality and safety supervision, and there are corresponding evolutionary stabilization conditions. There are several factors affecting the stability of the system, the most important of which are government regulation, severe penalties for agricultural product producers, and incentives. When these factors reach a certain threshold, the stakeholder cooperation mechanism can establish an evolutionarily stable strategy. This study contributes to the understanding of the operational mechanism of stakeholder cooperation in agricultural product quality and safety regulation in the digital environment and provides decision support and policy recommendations for stakeholders to promote the sustainable development and optimization of agricultural product quality and safety regulation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huo and Liu.)

Aim: To establish a supportive care framework for addressing unmet needs among breast cancer survivors, providing practical guidance for healthcare providers to assess and manage these needs, ultimately enhancing the health outcomes and quality of life of breast cancer survivors., Design: We conducted a two-round Delphi survey to gather expert opinions regarding the unmet needs supportive care framework for breast cancer survivors., Methods: Initial framework identification and inquiry questionnaire creation was achieved via literature search and expert group discussions, which included 15 experts from nursing practice, clinical medicine, nursing management and nursing education was conducted using a Delphi survey. To establish consensus, a two-round Delphi poll was done, using criteria based on the mean (≥4.0), coefficient of variation (CV < 0.25) and percentage for entire score (≥20%)., Results: Experts reached a consensus, leading to six care modules, and 28 care entries: Tumour Detection Support (three care entries), Management of Complications of Antitumor Therapy (seven care entries), Healthy Lifestyle Management (five care entries), Sexual and Fertility Support (four care entries), Psychosocial Support (four care entries) and Resource and Linkage Support (five care entries)., Conclusion: To address breast cancer survivors' unmet needs, a supportive framework was developed to actively enhance their health outcomes. However, further refinement and feasibility testing using mobile devices or artificial intelligence are required., Implications for the Profession and Patient Care: This pioneering framework prioritises addressing unmet needs and equips healthcare providers to assess and manage these needs effectively, facilitating the implementation of programs aimed at improving the well-being of breast cancer survivors., Reporting Method: This study was guided by a modified guideline for the Conducting and Reporting of Delphi Studies (CREDES) (Palliative Medicine, 31(8), 684, 2017)., Patient or Public Contribution: No Patient or Public Contribution., Trial and Protocol Registration: The Delphi study methodology does not require registration., (© 2024 John Wiley & Sons Ltd.)

Objective: To evaluate the effectiveness of percutaneous nephrolithotomy (PCNL) compared with open surgery for urinary stone removal., Methods: A total of 95 patients with urinary stones were screened for eligibility between October 2020 and December 2021. After excluding 5 patients who revoked their consent, 90 patients were randomized to receive either traditional open surgery (traditional group) or PCNL (PCNL group), with 45 patients in each group. In addition, the two groups received Shugan Qingre Tonglin decoction twice daily for 2 weeks. Outcome measures included intraoperative indexes, stone removal rate, postoperative healing, and quality of life., Results: PCNL resulted in significantly better intraoperative indexes (95% CI, 0.49-1.11; P < .001), lower creatinine concentration (95% CI, 0.59-1.61; P < .001), and higher glomerular filtration rate (95% CI, 2.43-2.91; P < .001) compared with traditional open surgery. Patients in the PCNL group had a significantly higher stone removal rate (95% CI, 1.09-2.51; P < .001) and a lower incidence of adverse events (95% CI, 0.69-1.87; P < .001) compared with those receiving traditional open surgery. Patients in the PCNL group had significantly higher quality of life (95% CI, 1.39-2.81; P < .001) and significantly higher maximum urinary flow rate (95% CI, 1.36-2.61; P < .001) than those in the traditional group at 1 month and 3 months after treatment., Conclusion: PCNL provides better postoperative renal function improvement, enhances the postoperative recovery of patients with urinary stones, and features manageable safety compared with traditional open surgery. The benefits of PCNL make it a promising technique for the clinical management of urinary stones. Its minimally invasive nature reduces patient discomfort, promotes faster recovery, and improves overall patient satisfaction. The superior outcomes of PCNL in terms of renal function improvement and postoperative recovery suggest that it is a viable alternative to traditional open surgery. Further research and clinical trials are warranted to validate these findings and establish PCNL as a widely adopted approach in the field of urology.

The human organic cation transporter 1 (hOCT1), also known as SLC22A1, is integral to hepatic uptake of structurally diversified endogenous and exogenous organic cations, influencing both metabolism and drug pharmacokinetics. hOCT1 has been implicated in the therapeutic dynamics of many drugs, making interactions with hOCT1 a key consideration in novel drug development and drug-drug interactions. Notably, metformin, the frontline medication for type 2 diabetes, is a prominent hOCT1 substrate. Conversely, hOCT1 can be inhibited by agents such as spironolactone, a steroid analog inhibitor of the aldosterone receptor, necessitating a deep understanding of hOCT1-drug interactions in the development of new pharmacological treatments. Despite extensive study, specifics of hOCT1 transport and inhibition mechanisms remain elusive at the molecular level. Here, we present cryo-electron microscopy structures of the hOCT1-metformin complex in three distinct conformational states - outward open, outward occluded, and inward occluded as well as substrate-free hOCT1 in both partially and fully open states. We also present hOCT1 in complex with spironolactone in both outward and inward facing conformations. These structures provide atomic-level insights into the dynamic metformin transfer process via hOCT1 and the mechanism by which spironolactone inhibits it. Additionally, we identify a 'YER' motif critical for the conformational flexibility of hOCT1 and likely other SLC22 family transporters. Our findings significantly advance the understanding of hOCT1 molecular function and offer a foundational framework for the design of new therapeutic agents targeting this transporter., (© 2024. The Author(s).)

Brain damage is a common tissue damage caused by trauma or diseases, which can be life-threatening. Stem cell implantation is an emerging strategy treating brain damage. The stem cell is commonly embedded in a matrix material for implantation, which protects stem cell and induces cell differentiation. Cell differentiation induction by this material is decisive in the effectiveness of this treatment strategy. In this work, we present an injectable fibroin/MXene conductive hydrogel as stem cell carrier, which further enables in-vivo electrical stimulation upon stem cells implanted into damaged brain tissue. Cell differentiation characterization of stem cell showed high effectiveness of electrical stimulation in this system, which is comparable to pure conductive membrane. Axon growth density of the newly differentiated neurons increased by 290% and axon length by 320%. In addition, unfavored astrocyte differentiation is minimized. The therapeutic effect of this system is proved through traumatic brain injury model on rats. Combined with in vivo electrical stimulation, cavities formation is reduced after traumatic brain injury, and rat motor function recovery is significantly promoted., (© 2024. The Author(s).)

Tailoring nanoscale catalysts to targeted applications is a vital component in reducing the carbon footprint of industrial processes; however, understanding and controlling the nanostructure influence on catalysts is challenging. Molybdenum disulfide (MoS 2 ), a transition metal dichalcogenide (TMD) material, is a popular example of a nonplatinum-group-metal catalyst with tunable nanoscale properties. Doping with transition metal atoms, such as cobalt, is one method of enhancing its catalytic properties. However, the location and influence of dopant atoms on catalyst behavior are poorly understood. To investigate this knowledge gap, we studied the influence of Co dopants in MoS 2 nanosheets on catalytic hydrodesulfurization (HDS) through a well-controlled, ligand-directed, tunable colloidal doping approach. X-ray absorption spectroscopy and density functional theory calculations revealed the nonmonotonous relationship between dopant concentration, location, and activity in HDS. Catalyst activity peaked at 21% Co:Mo as Co saturates the edge sites and begins basal plane doping. While Co prefers to dope the edges over basal sites, basal Co atoms are demonstrably more catalytically active than edge Co. These findings provide insight into the hydrogenolysis behavior of doped TMDs and can be extended to other TMD materials., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In response to the stricter EU VII emission standards and the "150 ℃ challenge", selective catalytic reduction by ammonia (NH 3 -SCR) catalysts for motor vehicles are required to achieve high NO conversion below 200 °C. Compounding metal oxides with zeolites is an important strategy to design the low-temperature SCR catalysts. Here, we original prepared Cu-SSZ-13 @ MnGdO x (Cu-Z @ MGO), which achieved over 90% NO conversion and 95% N 2 selectivity at 150 ℃. It has been demonstrated that a uniform mesoporous loaded layer of MGO grows on Cu-Z, and a recrystallization zone appears at the MGO-Cu-Z interface. We discover that the excellent low-temperature SCR activity derives from the strong metal oxide-zeolite interaction (SMZI) effects. The SMZI effects cause the anchor and high dispersion of MGO on the surface of Cu-Z. Driven by the SMZI effects, the Mn 3+ /Mn 4+ redox cycle ensures the low and medium temperature-SCR activity and the Cu 2+ /Cu + redox cycle guarantees the medium and high temperature-SCR activity. The introduction of MGO improves the reaction activity of -NH 2 species adsorbed at Mn sites at 150 ℃, achieving a cycle of reduction and oxidation reactions at low temperatures. This strategy of inducing SMZI effects of metal oxides and zeolites paves a way for development of high-performance catalysts., Competing Interests: Declaration of Competing Interest All authors declare that there are no conflicts of interest, financial or otherwise in this work; and there are no other relationships or activities that can appear to have influenced the submitted work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Surface electromyography (sEMG)-based gesture recognition can achieve high intra-session performance. However, the inter-session performance of gesture recognition decreases sharply due to the shift in data distribution. Therefore, developing a robust model to minimize the data distribution difference is crucial to improving the user experience. In this work, based on the inter-session gesture recognition task, we propose a novel algorithm called locality preserving and maximum margin criterion (LPMM). The LPMM algorithm integrates three main modules, including domain alignment, pseudo-label selection, and iteration result selection. Domain alignment is designed to preserve the neighborhood structure of the feature and minimize the overlap of different classes. The pseudo-label selection and iteration result selection can avoid the decrease in accuracy caused by mislabeled samples. The proposed algorithm was evaluated on two of the most widely used EMG databases. It achieves a mean accuracy of 98.46% and 71.64%, respectively, which is superior to state-of-the-art domain adaptation methods.

Ovarian cancer is one of the most common gynaecological malignancies with poor prognosis and lack of effective treatment. The improvement of the situation of ovarian cancer urgently requires the exploration of its molecular mechanism to develop more effective molecular targeted drugs. In this study, the role of human ribosomal protein l35a (RPL35A) in ovarian cancer was explored in vitro and in vivo. Our data identified that RPL35A expression was abnormally elevated in ovarian cancer. Clinically, high expression of RPL35A predicted short survival and poor TNM staging in patients with ovarian cancer. Functionally, RPL35A knock down inhibited ovarian cancer cell proliferation and migration, enhanced apoptosis, while overexpression had the opposite effect. Mechanically, RPL35A promoted the direct binding of transcription factor YY1 to CTCF in ovarian cancer cells. Consistently, RPL35A regulated ovarian cancer progression depending on CTCF in vitro and in vivo. Furthermore, RPL35A affected the proliferation and apoptosis of ovarian cancer cells through PPAR signalling pathway. In conclusion, RPL35A drove ovarian cancer progression by promoting the binding of YY1 and CTCF promoter, and inhibiting this process may be an effective strategy for targeted therapy of this disease., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Progressive hemifacial atrophy (PHA) is a rare disease characterized by progressive atrophy of skin, soft tissue, muscles, and underlying bone structures. For severe PHA patients with obvious bone deformities, skeletal framework reconstruction is needed in addition to soft-tissue augmentation. The authors propose a new combinatorial surgical method using rib cartilage graft and free adipofascial flap for restoring facial symmetry. To improve the surgical accuracy, preoperative three-dimensional planning and printing was used., Methods: Twelve patients with severe facial atrophy were included in the authors' study. Three-dimensional facial image analyses were performed preoperatively to quantify the facial asymmetry. Rib cartilages were harvested and sculptured to the appropriate shape created by three-dimensional planning and fixed to the atrophic bone. The circumflex scapular artery-based adipofascial flap was transplanted to repair soft-tissue deficiency. A residual small monitor flap was left with the adipofascial flap. A revision surgery was performed to perfect the repair if the contour was suboptimal 6 months postoperatively., Results: The adipofascial flaps survived in all 12 patients. All patients achieved good healing without complications. At 1 more year after surgery, the rib cartilage was still in position and rarely absorbed. The morphologic and volumetric difference between the affected side and the unaffected side was improved significantly postoperatively. All patients were satisfied with the results, and no more additional operations were required., Conclusion: The combinatorial surgery of rib cartilage graft and free adipofascial flap in the setting of three-dimensional planning and printing can be a good choice in restoring facial symmetry in severe cases of PHA., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Tislelizumab, an anti-programmed cell death protein 1 monoclonal antibody, has demonstrated improved survival benefits over standard of care for multiple cancer indications. We present the clinical rationale and data supporting tislelizumab dose recommendation in patients with advanced tumors. The phase I, first-in-human, dose-finding BGB-A317-001 study (data cutoff [DCO]: August 2017) examined the following tislelizumab dosing regimens: 0.5-10 mg/kg every 2 weeks (q2w), 2-5 mg/kg q2w or q3w, and 200 mg q3w. Similar objective response rates (ORRs) were reported in the 2 and 5 mg/kg q2w or q3w cohorts. Safety outcomes (grade ≥3 adverse events [AEs], AEs leading to dose modification/discontinuation, immune-mediated AEs, and infusion-related reactions) were generally comparable across the dosing range examined. These results, alongside the convenience of a fixed q3w dose, formed the basis of choosing 200 mg q3w as the recommended dosing regimen for further clinical use. Pooled exposure-response (E-R) analyses by logistic regression using data from study BGB-A317-001 (DCO: August 2020) and three additional phase I/II studies (DCOs: 2018-2020) showed no statistically significant correlation between tislelizumab pharmacokinetic exposure and ORR across multiple solid tumor types or classical Hodgkin's lymphoma, nor was exposure associated with any of the safety end points evaluated over the dose range tested. Hence, tislelizumab showed a relatively flat E-R relationship. Overall, the totality of data, including efficacy, safety, and E-R analyses, together with the relative convenience of a fixed q3w dose, provided clinical rationale for the recommended dosing regimen of tislelizumab 200 mg q3w for multiple cancer indications., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

R-loops are three-stranded structures that can pose threats to genome stability. RNase H1 precisely recognizes R-loops to drive their resolution within the genome, but the underlying mechanism is unclear. Here, we report that ARID1A recognizes R-loops with high affinity in an ATM-dependent manner. ARID1A recruits METTL3 and METTL14 to the R-loop, leading to the m6A methylation of R-loop RNA. This m6A modification facilitates the recruitment of RNase H1 to the R-loop, driving its resolution and promoting DNA end resection at DSBs, thereby ensuring genome stability. Depletion of ARID1A, METTL3, or METTL14 leads to R-loop accumulation and reduced cell survival upon exposure to cytotoxic agents. Therefore, ARID1A, METTL3, and METTL14 function in a coordinated, temporal order at DSB sites to recruit RNase H1 and to ensure efficient R-loop resolution. Given the association of high ARID1A levels with resistance to genotoxic therapies in patients, these findings open avenues for exploring potential therapeutic strategies for cancers with ARID1A abnormalities., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)