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Single-cell RNA sequencing (scRNA-seq) is a high-throughput transcriptomic approach with the power to identify rare cells, discover new cellular subclusters, and describe novel genes. scRNA-seq can simultaneously reveal dynamic shifts in cellular phenotypes and heterogeneities in cellular subtypes. Since the publication of the first protocol on scRNA-seq in 2009, this evolving technology has continued to improve, through the use of cell-specific barcodes, adoption of droplet-based systems, and development of advanced computational methods. Despite induction of the cellular stress response during the tissue dissociation process, scRNA-seq remains a popular technology, and commercially available scRNA-seq methods have been applied to the brain. Recent advances in spatial transcriptomics now allow the researcher to capture the positional context of transcriptional activity, strengthening our knowledge of cellular organization and cell-cell interactions in spatially intact tissues. A combination of spatial transcriptomic data with proteomic, metabolomic, or chromatin accessibility data is a promising direction for future research. Herein, we provide an overview of the workflow, data analyses methods, and pros and cons of scRNA-seq technology. We also summarize the latest achievements of scRNA-seq in stroke and acute traumatic brain injury, and describe future applications of scRNA-seq and spatial transcriptomics., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The widespread use of sub-therapeutic antibiotics may lead to treatment failures, increased resistance to antibiotics, and even the encouragement of the formation of superbugs. Fraudulent herbal medicines that actually contain unlabeled active ingredients are a global problem. Therefore, streamlined and accurate analytical techniques that can identify and quantify a variety of antimicrobials in suspected illegal products are required. In the present work, we developed a sensitive, robust, and accurate method that involves multi-step extraction, EMR-lipid-based pass-through cleanup, and UHPLC-Q/HRMS with an orbital ion trap instrument analysis for the simultaneous detection of ten illicit antifungal drugs (flucytosine, fluconazole, ketoconazole, naftifine hydrochloride, griseofulvin, bifonazole, econazole nitrate, elubiol, clotrimazole, and miconazole nitrate) in herbal disinfection products. This validated method was then applied to 210 authentic samples, resulting in 25% of the samples being positive for the drugs. The results suggested the need to strengthen controls in this field to detect illicit antifungal drugs in herbal bacteriostatic products, which represents a potential health risk for the consumer. On a global scale, more and more frequent routine monitoring is being carried out in this area. This study provides valuable insights into large-scale complex sample chemical profiling, and the method developed appears to be promising and applicable for high-throughput routine multiple antibiotic analysis in a complex sample matrix., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: To describe vascular anomalies and nonperfusion areas (NPAs) of stage 4 familial exudative vitreoretinopathy (FEVR) with radial retinal folds (RFs) and analyze their potential clinical significance., Methods: Retinal detachment (RD) could exceed the RFs due to exudative, rhegmatogenous, or tractional factors, which we could call secondary RD. Fluorescein fundus angiography (FFA) and risk factors for progression to secondary RD of pediatric stage 4 FEVR patients with radial RFs were respectively explored., Results: Fifty-eight eyes with RFs from 49 stage 4 pediatric FEVR patients were studied. Various angiographic changes were noted, including peripheral NPAs (93.1%), thinning retinal arteries (48.3%), straightened retinal vessels (34.5%), supernumerary vascular branching (32.8%), arteriovenous shunt (20.7%), aberrant circumferential vessels (13.8%), bulbous vascular endings (10.3%) and peripheral vascular dilation (6.9%). Nineteen (35.2%), 21(38.2%), and 14 (25.9%) of 58 eyes showed severe, moderate, and mild peripheral NPAs, respectively. The rate of secondary RDwas higher in eyes with severe peripheral NPAs (p = 0.004). The severity of the nonperfusion area (p = 0.040) was higher in eyes with exudation. Eight eyes (42.1%) with exudation and 12 eyes (30.8%) without exudation on color fundus pictures exhibited fluorescein leakage (p = 0.394). The rate of secondary RD was 26.3% in eyes with exudation, and 2.6% in eyes without exudation (p = 0.012)., Conclusions: The majority of stage 4 FEVR eyes with RFs have severe peripheral NPAs. Exudation is related to more severe peripheral NPAs. Exudation and NPAs are predictive factors for secondary RD., Key Messages: What is known • Radial retinal folds are a typical clinical sign of FEVR, observed in 50.9% of FEVR patients, but little is known about the angiographic characteristics of these individuals. What is new • The severity of the nonperfusion area was graded into 3 levels. The severity of the nonperfusion area and hard exudation are risk factors for progression to total retinal detachment., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study. Conflict of interest: The authors declare that there are no conflict of interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel method for the quantitative analysis of 56 per- and polyfluoroalkyl substances (PFASs) in human plasma was established on the basis of ultrahigh performance liquid chromatography tandem quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS) in combination with accurate customized mass databases and isotopic internal standards. A streamlined, high-throughput, and high-recovery (RE) sample pretreatment method was developed. The method's performance was evaluated in terms of linearity, limit of quantification, RE, repeatability, reproducibility, and matrix effect. The proposed method was applied in the simultaneous analysis of 56 PFASs in human plasma, and its results demonstrated high sensitivity, accuracy, and precision. The optimized method was implemented to analyze PFASs in 135 plasma samples, and 12 components were detected. The comparative analysis of the results from 135 plasma samples with domestic and international studies revealed elevated contents of PFOA, PFOS, PFBA, and PFTrDA, the moderate amounts of PFHxS, PFUdA, PFBS, and PFHpS, and the low concentrations of PFNA and PFDA. Notably, GenX was detected in human plasma for the first time. This finding suggests that the study region is contaminated with this substance. Correlation analysis revealed a strong relationship among PFNA, PFDA, and PFUdA, implying that these substances may have similar exposure sources., 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.)

This study investigates the most probable trajectories of a birhythmic oscillator under stochastic perturbations. The distinctive feature of the birhythmic oscillator is the coexistence of two stable limit cycles with different amplitudes and frequencies, separated by an unstable limit cycle. The path integral method was utilized to compute the instantaneous probability density. Based on the theory of most probable dynamics, by maximizing the probability density function, we present the time series of the most probable trajectories starting from different initial states. Furthermore, we conducted a detailed analysis of the noise-induced transitions between the two stable limit cycles under different parameter conditions. This approach enables us to understand and track the most probable escape time and specific most probable trajectories as the system transitions from the basin of attraction of one stable limit cycle to another. This work visualizes the most probable trajectories in stochastic systems and provides an innovative solution to the complex problem of noise-induced transitions between two stable limit cycles. Our research aims to provide a new perspective for studying complex stochastic dynamical systems., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Objectives: To explore a novel model of mobile stroke units (MSUs) integrated with rural emergency medical stations for pre-hospital care of stroke patients in remote areas., Methods: We used MSUs + Ambulance mode, where both the MSUs and conventional ambulances are sent to the patient's location. The conventional ambulance coordinates with the MSUs to choose the fastest route to meet and transfer the patient at the point along the way. We collected data from 149 patients from March 2022 to April 2023, including National Institutes of Health Stroke Scale (NIHSS) scores (on admission, 24 hours, day 7), 90-day modified Rankin Scale (mRS) scores, and other clinical variables. We performed propensity score matching (PSM) to balance the potential confounding variables between groups., Results: We found that the MSUs + Ambulance mode (OR = 12.507, 95% confidence interval [CI] [3.633, 43.061], p  < 0.001) and admission NIHSS score (OR = 0.583, 95% CI [0.493, 0.690], p  < 0.001) were independent prognostic risk factors for stroke patients. The MSUs + Ambulance mode reduced NIHSS scores 7 days prior to admission (OR = 0.679, 95% CI [0.563, 0.819], p  < 0.001). After PSM, patients who received MSUs + Ambulance mode had a better prognosis (χ 2  = 9.573, p  = 0.004), as well as a lower mRS score at 90 days (Z = -3.371, p  = 0.001)., Conclusions: MSUs integrated with rural emergency medical stations show the feasibility and potential benefits of pre-hospital intravenous thrombolysis for stroke patients in geographically distant regions.

Macroautophagy involves the encapsulation of cellular components within double-membrane autophagosomes for subsequent degradation in vacuoles or lysosomes. Coat protein complex II (COPII) vesicles serve as a membrane source for autophagosome formation. However, the specific role of SEC24D, an isoform of the COPII coat protein SEC24, in the macroautophagy pathway remains unclear. In this study, we demonstrate that SEC24D is indispensable for macroautophagy and important for autophagosome closure. Depletion of SEC24D leads to the accumulation of unsealed isolation membranes. Furthermore, under conditions of starvation, SEC24D interacts with casein kinase1 delta (CK1δ), a member of the casein kinase 1 family, and autophagy-related 9A (ATG9A). Collectively, our findings unveil the indispensable role of SEC24D in starvation-induced autophagy in mammalian cells., (© 2024 Federation of European Biochemical Societies.)

Objective: To present the real-world status and explore the predictors of the efficacy and prognosis of first-line treatment for unresectable hepatocellular carcinoma (uHCC)., Methods: Real-world data of uHCC patients who underwent first-line treatment at 4 hospitals in Northern Anhui, China, from July 2019 to December 2022 were retrospectively collected. The clinicopathological features, haematological indicators, including superoxide dismutase (SOD) and vascular endothelial growth factor-A (VEGF-A), efficacy and safety data were analysed., Results: A total of 153 patients were enrolled and most of them treated with targeted therapy combined with immunotherapy (TI). Compared to patients treated with TI, patients who were administrated with TI plus locoregional therapy (TIL) showed longer median progression-free survival (mPFS) and median overall survival (mOS) times (both p  < 0.05), with manageable safety profiles. Moreover, compared to patients with low baseline serum levels of SOD, patients with high baseline serum SOD levels had a better treatment efficacy and had longer mPFS and mOS times (all p  < 0.05). Subgroup analyses indicated that patients with low SOD levels had longer mPFS times when receiving TIL than when receiving TI ( p =  0.005), but, among patients with high SOD levels, their prognoses were not substantially different between TIL and TI ( p  > 0.05). Additionally, patients in the low-VEGF-A group had a longer mOS time than patients in the high-VEGF-A group ( p  = 0.004). In comparison with TI, TIL can improve the survival time among patients with high VEGF-A levels but not among patients with low VEGF-A levels., Conclusions: TI was the most commonly first-line systemic therapy for uHCC patients, with better efficacy and outcomes when combined with locoregional therapy in a certain population. Baseline serum SOD and VEGF-A were found to be potential predictive biomarkers for decision-making, treatment response, and outcome in patients with uHCC in the primary care setting.

Body size of organisms is a key trait influencing nearly all aspects of their life history. Despite growing evidence of Bergmann's rule, there is considerably less known about the links between body size and the maximum capacity to thermoregulate of an animal in response to extreme cold or hot environment. Thermal characteristics such as resting metabolic rate (RMR) and non-shivering thermogenesis (NST), and the upper- and lower-critical temperatures of the thermal neutral zone (TNZ) were investigated in small and large body sized striped hamsters (Cricetulus barabensis). The maximum capacity to thermoregulate in response to extreme cold (-15 °C) or hot temperature (38 °C) was also examined, where both, different sized hamsters had similar RMR and NST regardless of temperature exposure. The large hamsters had 29.9% more body mass compared to small hamsters. The large hamsters showed a wider TNZ, with lower, lower-critical temperature, and showed considerable hyperthermia at the end of a 17-h hot exposure. In contrast, the small hamsters showed hypothermia following a 17-h cold exposure relative to large hamsters. In addition, the large hamsters showed 17.2% lower basal thermal conductance, and 14.9% lower maximum thermal conductance than the small hamsters after cold exposure, and 22.6% lower thermal conductance following heat exposure. Several molecular markers indicative of thermogenesis and oxidative stress did not differ significantly between the large and small hamsters. These findings suggest that individuals with larger body sizes have greater capacity to thermoregulate to cope with extreme cold, and a reduced capacity in response to extreme hot. In contrast, smaller individuals demonstrated the opposite trend. Body size may decide the capacity to thermoregulate to cope with extreme cold and heat, within which body heat dissipation is likely more important than heat production., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Natural killer (NK) cell-based immunotherapy has received much attention in recent years. However, its practical application is still suffering from the decreased function and inadequate infiltration of NK cells in the immunosuppressive microenvironment of solid tumors. Herein, we construct light-responsive porphyrin Fe array-armed NK cells (denoted as NK@p-Fe) for cell behavior modulation via bioorthogonal catalysis. By installing cholesterol-modified porphyrin Fe molecules on the NK cell surface, a catalytic array with light-harvesting capabilities is formed. This functionality transforms NK cells into cellular factories capable of catalyzing the production of active agents in a light-controlled manner. NK@p-Fe can generate the active antineoplastic drug doxorubicin through bioorthogonal reactions to enhance the cytotoxic function of NK cells. Beyond drug synthesis, NK@p-Fe can also bioorthogonally catalyze the production of the FDA-approved immune agonist imiquimod (IMQ). The activated immune agonist plays a dual role, inducing dendritic cell maturation for NK cell activation and reshaping the tumor immunosuppressive microenvironment for NK cell infiltration. This work represents a paradigm for the modulation of adoptive cell behaviors to boost cancer immunotherapy by bioorthogonal catalysis., (© 2024 Wiley-VCH GmbH.)

Background: Regional citrate anticoagulation-continuous renal replacement therapy (RCA-CRRT) has a wide range of applications in clinical practice, but unplanned downtime due to RCA-CRRT circuit coagulation is as high as 15.75%-66.70%., Aim: To build a nomogram model for predicting the lifespan circuits of RCA-CRRT., Study Design: A prospective observational cohort study was conducted in Sichuan, China. The collected clinical data from 404 RCA-CRRT sessions involving 135 patients were utilized. The patients' basic information, laboratory indicators and RCA-CRRT parameters were used as independent variables, and the survival status and survival time of RCA-CRRT circuits were used as dependent variables. A Cox multivariate analysis was performed to build the nomogram model for predicting the lifespan of RCA-CRRT circuits. The model was validated internally and externally., Results: The median lifespan of RCA-CRRT circuits was 28.0 (12.0-46.5) h, and the unplanned downtime rate was 23.76%. In the Cox multivariate analysis, venous pressure, haemoglobin, Sequential Organ Failure Assessment (SOFA), lactate, and blood transfusion were identified as statistically significant predictive factors for the lifespan of RCA-CRRT circuits (p < .05). Subsequently, a nomogram model for predicting the lifespan of RCA-CRRT circuits was developed. The AUC values for internal and external validation within the 12-72-h timeframe ranged from 0.648 to 0.816 and 0.613 to 0.956, respectively. Both the calibration curve and clinical decision curve demonstrated the model's good performance., Conclusion: The nomogram model developed in this study demonstrates its efficacy in accurately predicting the lifespan circuits of RCA-CRRT., Relevance to Clinical Practice: Clinical nurses can use the prediction model to assess the lifespan of RCA-CRRT circuits, so as to formulate a personalized RCA-CRRT treatment plan for patients, thus reducing the unplanned downtime of RCA-CRRT., (© 2024 The Author(s). Nursing in Critical Care published by John Wiley & Sons Ltd on behalf of British Association of Critical Care Nurses.)

Background: Imbalances in Th1/Th2 and Th17/Treg immune axes, coupled with disruptions in the gut microbiota (GM), play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). Cordycepin, a natural anti-inflammatory compound, holds promise in mitigating IBD by rebalancing these immune axes in conjunction with modulating the GM. The aim of this experiment is to investigate the potential of cordycepin in mitigating enteritis and elucidate the underlying mechanisms associated with its ameliorative effects on enteritis., Methods: On the day of inducing experimental colitis with Dextran Sulfate Sodium (DSS), mice in the DSS + Cordycepin and Cordycepin groups received 50 mg/kg/day Cordycepin via intra-gastric administration (i.g.) for seven consecutive days, respectively. Mice in the DSS and control groups were treated with equal volumes of saline. On day 8, all mice were euthanized under pentobarbital sodium anesthesia., Results: In a DSS-induced colitis mouse model, Cordycepin treatment led to a significant reduction in the disease activity index (DAI), splenic weight, and colonic pathological injury while simultaneously improving body weight and colonic length. Furthermore, it positively impacted GM composition, resulting in decreased Th1 and Th17 cells, alongside an increase in Th2 and Treg cells. The contents of the mouse colon were extracted for microbial community analysis. Mouse blood was prepared into a single-cell suspension, and flow cytometry was used to assess the expressio of Treg, Th17, Th1, and Th2 immune cells., Conclusions: These results underscored the effective intervention of cordycepin in ameliorating DSS-induced colitis by harmonizing the interplay between GM and immune homeostasis., Competing Interests: Declaration of Competing Interest I, Jingting Jiang, declare that there are no conflicts of interest in relation to the manuscript titled "Cordycepin Mitigates Dextran Sulfate Sodium-Induced Colitis through Improving Gut Microbiota Composition and Modulating Th1/Th2 and Th17/Treg Balance" submitted to Biomedicine Pharmacotherapy. I confirm that the results and interpretations reported in the manuscript are original and have not been plagiarized. I certify that I have read and understand the Biomedicine Pharmacotherapy conflict of interest policy, and I understand that failure to disclose a conflict of interest may result in the manuscript being rejected or retracted. I also certify that I have disclosed any financial or non-financial relationships that may be interpreted as constituting a conflict of interest in relation to this manuscript. I understand that this information will be subject to peer review, and I am willing to provide further information or clarification if required. I confirm that I have no known conflicts of interest that would influence the results or interpretation of the data presented in this manuscript, and I understand that failure to disclose a conflict of interest is unethical and may result in sanctions being imposed on me., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This paper investigates the stochastic response of a classical model of the birhythmic Van der Pol oscillator under Poisson white noise excitation. The improved path integration (PI) method is comprehensively derived in this paper and the probability density of the system is calculated using this method. Monte Carlo simulations are employed to validate the accuracy of the improved PI method. The findings reveal that the nonlinear parameters of the system significantly influence the mechanism by which Poisson white noise impacts the birhythmic oscillator. For the stationary response, we compare the effects of Gaussian white noise and Poisson white noise at equivalent intensities, and specifically analyze the mechanisms of two key parameters of Poisson white noise. This analysis offers general insights into the mechanisms by which Poisson noise impacts the birhythmic oscillator. For transient response, the occurrence time of birhythmicity, along with the system's probability distribution at different moments, are influenced by random perturbations, yet the nonlinear parameters of the system remain pivotal factors. This study provides a perspective for investigating the dynamic behavior of birhythmic oscillators under discontinuous stochastic disturbances.

Many everyday empathetic experiences arise within our social interactions and depend significantly on interpersonal closeness. However, the interbrain processes underlying social-oriented empathy by interpersonal closeness remain unclear. To address this gap, we conducted a dyadic social judgement task with dyads of friends and strangers, where targets received social evaluative feedback and empathizers observed the scenario in different experimental trials. Results showed that dyads of friends exhibited greater affect sharing than strangers when witnessing their partners being accepted or rejected. This was supported by the more pronounced event-related potential similarity in friends during the 340-840 ms post-feedback window, mediating the link between interpersonal closeness and affect sharing. Furthermore, witnessing emotional feedback elicited greater interbrain neural synchronization of brain α-oscillation between the empathizer's left prefrontal cortex and the target's left temporoparietal junction in dyads of friends compared with those of strangers. This empathy-related synchronization was associated with mutual affect sharing within dyads of friends but not within dyads of strangers. Our findings highlight the sensitivity of empathy to interpersonal closeness, which links to sustained attention and detailed evaluation in social scenarios, along with functional communication between brain regions for mentalizing and emotional regulation. These insights have therapeutic potential for improving social functioning and relationship satisfaction.

Bioorthogonal chemistry has provided an elaborate arsenal to manipulate native biological processes in living systems. As the great advancement of nanotechnology in recent years, bioorthogonal nanozymes are innovated to tackle the challenges that emerged in practical biomedical applications. Bioorthogonal nanozymes are uniquely positioned owing to their advantages of high customizability and tunability, as well as good adaptability to biological systems, which bring exciting opportunities for biomedical applications. More intriguingly, the great advancement in nanotechnology offers an exciting opportunity for innovating bioorthogonal catalytic materials. In this comprehensive review, the significant progresses of bioorthogonal nanozymes are discussed with both spatiotemporal controllability and high performance in living systems, and highlight their design principles and recent rapid applications. The remaining challenges and future perspectives are then outlined along this thriving field. It is expected that this review will inspire and promote the design of novel bioorthogonal nanozymes, and facilitate their clinical translation., (© 2024 Wiley‐VCH GmbH.)

Understanding the trade-offs between ecological benefits and cost of grain supply caused by ecosystem restoration is essential for decision-making. Nevertheless, due to climate change, the benefits of ecosystem restoration and cost of grain supply change across various spatial locations, thereby complicating the trade-offs. Taking one of China's largest scale ecosystem restorations, the Grain for Green Program (GGP), as an example, this study used the Three Gorges Reservoir (TGR) region as the case study area and combined the crop environment resource synthesis (CERES)-Crop model, future land-use simulation (FLUS), and the revised universal soil loss equation (RUSLE) to simulate future grain supply and soil erosion during 2021-2050 under three climate change and socioeconomic development scenarios (SSP1-2.6, SSP2-4.5, SSP5-8.5) in the TGR region. The results showed that: (1) Until 2050, the implementation of GGP would bring a large soil conservation benefit by reducing soil erosion of 2.47-5.68 million tons, at the cost of 130,277-660,279 tons decrease in grain production in the TGR region. (2) Under SSP5-8.5 climate change scenario with the highest rainfall in the future, the GGP would maintain the greatest soil conservation benefits, resulting in a total amount of soil erosion decrease by 2.55 to 5.68 million tons. (3) Trade-offs between benefit of reducing soil erosion and cost of grain supply vary considerably across income. Specifically, GGP benefits are greater under low-income and higher-emission scenarios, with significant gains in soil erosion control and less impact on grain supply. In contrast, in high-income and low-emission scenarios, the GGP results in less soil erosion control and greater impact on grain supply., 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.)

Strobilanthes sarcorrhiza, a folk medicine from China, is known to treat kidney deficiency and lumbago. However, its protective effects and mechanisms against diabetic nephropathy (DN) remain unclear. This study aimed to investigate the effects and mechanisms of Strobilanthes sarcorrhiza root phenolic extract (CTS) on streptozotocin (STZ)-induced DN in mice. Firstly, the constituents in CTS were characterized by UPLC-QTOF-MS. Thirty-three constituents were identified, including 12 phenylethanoid glycosides and their derivatives, 14 phenylpropanoid glycosides derivatives, 6 polyphenols derivatives, and 1 other constituent. Then, utilizing the identified constituents of CTS, network pharmacology was used to anticipate potential pathways against DN. Thirty-two out of thirty-three constituents showed anti-DN activity; their mechanism of action was significantly linked to tumor-, glycosylation-, metabolism-related pathways, etc. Furthermore, the effectiveness of CTS against DN and its in vivo mechanism was assessed by combining immunohistochemistry, untargeted metabolomics, biochemical evaluation, and histopathological examination. The findings showed that CTS improved blood glucose and lipid levels in diabetic mice, reduced serum levels of ALT, CREA, UREA, IL-1β, and IL-17, decreased pathological damage and fibrosis in kidney tissue, and lowered the protein expression of VEGF, Laminin, TNF-α, and NF-κB in kidney tissue. Metabolomics results indicated that CTS alleviated DN mainly by regulating glycerophospholipid metabolism. To the best of our knowledge, this study is the first to report that Strobilanthes sarcorrhiza attenuates DN, potentially through the inhibition of the NF-κB pathway, leading to a reduction in the inflammatory response and fibrosis of renal tissue. These findings suggest that Strobilanthes sarcorrhiza could be a promising therapeutic agent for DN., 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.)

To examine the effects of different solvents on the molecular weight, yield, chemical composition, and bioactivity of pectins, four RG-I type pectins were separately extracted from sweet potato residue (SPR) using hot water extraction (HWSP), sodium hydroxide extraction (SHSP), hydrochloric acid extraction (HASP), and chelating agents (CASP). The results showed that the four pectin samples comprised GalUA, Gal, Rha, Ara, Glc, GlcUA, Man, and Xyl components. Among these components, GalA content was the highest in all four pectins. SHSP exhibited relatively higher yield (3.16 %, w/w). Additionally, SHSP exhibited a lower molecular weight (44.49 kDa) and the largest proportion of the RG-I region (75.42 %) compared with other extraction methods. On the contrary, HASP showed relatively lower yield (2.14 %, w/w), and its corresponding prepared pectin had relatively high molecular weight (69.81 kDa) and the minimum range of RG-I region (46.87 %) compared with HWSP, SHSP, and CASP. The anti-inflammation effect of the four SPR pectin samples was investigated using in vitro experiments. Results showed that all of SPR pectin significantly inhibited the levels of IL-1β, IL-6, and TNF-α in lipopolysaccharide (LPS)-treated iBMDM macrophage cells. The preliminary structure-activity relationship between pectin structure and anti-inflammatory activity was also analyzed. SPR pectin can be developed as a potential bioactive ingredient for applications in the food and medicine industries., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The mung bean peel polysaccharide (MBP) extracted by hot water was chemically modified. By changing the dosage of phosphorylation reagent and acetylation reagent, three kinds of phosphorylated MBP ( P-MBP-1, P-MBP-2, P-MBP-3 ) and acetylated MBP ( AC 0.6-MBP, AC 1-MBP, AC 1.4-MBP ) with different degrees of substitution were prepared. By measuring the sugar content and substitution degree of the modified products, it was found that the amount of reagent had a certain effect on both of them. The modified products were determined by infrared spectrum and nuclear magnetic resonance. The results showed that the chemical modification was successful. The in vitro antioxidant capacity (·OH scavenging ability, O 2 - ·clearing ability, reducing capacity, resistance to lipid peroxidation) of seven polysaccharide were measured, which manifested that chemical modification could enhance the antioxidant ability of MBP to varying degrees, and the DS also had a certain impact on their antioxidant activity. This promoted the development of mung bean peel polysaccharide functional products and the utilization of mung bean peel resources., (© 2024. The Author(s).)

Aims: Hyperglycemia is one of the adverse effects of tacrolimus (TAC), but the underlying mechanism is not fully identified. We used multi-omics analysis to evaluate the changes in the gut microbiota and metabolic profile of rats with TAC-induced diabetes., Methods: To establish a diabetic animal model, Sprague Dawley rats were divided randomly into two groups. Those in the TAC group received intraperitoneal injections of TAC (3 mg/kg) for 8 weeks, and those in the CON group served as the control. 16S rRNA sequencing was used to analyze fecal microbiota. The metabolites of the two groups were detected and analyzed by nontargeted and targeted metabolomics, including amino acids (AAs), bile acids (BAs), and short-chain fatty acids (SCFAs)., Results: The rats treated with TAC exhibited hyperglycemia as well as changes in the gut microbiota and metabolites. Specifically, their gut microbiota had significantly higher abundances of Escherichia-Shigella , Enterococcus , and Allobaculum , and significantly lower abundances of Ruminococcus , Akkermansia , and Roseburia . In addition, they had significantly reduced serum levels of AAs including asparagine, aspartic acid, glutamic acid, and methionine. With respect to BAs, they had significantly higher serum levels of taurocholic acid (TCA), and glycochenodeoxycholic acid (GCDCA), but significantly lower levels of taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA). There were no differences in the levels of SCFAs between the two groups. Correlations existed among glucose metabolism indexes (fasting blood glucose and fasting insulin), gut microbiota ( Ruminococcus and Akkermansia ), and metabolites (glutamic acid, hydroxyproline, GCDCA, TDCA, and TUDCA)., Conclusions: Both AAs and BAs may play crucial roles as signaling molecules in the regulation of TAC-induced diabetes., 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 Jiang, Qian, Zhen, Yang, Xu, Zuo, Jiang, Zhang and Hu.)

The pursuit of highly efficient electrocatalysts for the alkaline hydrogen evolution reaction (HER) is of paramount importance for water splitting. However, it is still a formidable task in Mo 2 C-based materials because of the agglomeration and strong Mo-H binding of Mo 2 C units. Herein, a novel CeOCl-CeO 2 /Mo 2 C heterostructure nesting within a three-dimensional porous nitrogen-doped carbon matrix has been designed and used for catalyzing HER via simultaneous morphology and heterointerface engineering. As expected, the optimal CeOCl-CeO 2 (0.2)/Mo 2 C@3DNC exhibits impressive HER activity, with a low overpotential of 156 mV at a current density of 10 mA cm -2 coupled with a slight Tafel slope of 62.20 mV dec -1 . Introducing a Ce promoter, that is CeOCl and CeO 2 , would endow the interface with an internal electric field and electron redistribution between CeOCl-CeO 2 and Mo 2 C induced by the heterogeneous work function difference. Moreover, experimental investigation and density functional calculations confirm that the CeOCl-CeO 2 /Mo 2 C heterointerface can downshift the d-band center of the active Mo center, weakening the strength of the Mo-H coupling. This proposed concept, engineering Ce-based promoters into active entities involved in the heterostructure to modulate intermediate adsorption, offers a great opportunity for the design of superior electrocatalysts for energy conversion.

Objectives: Colistin sulphate for injection (CSI) became clinically available in China in July 2019. To date, there is no published data regarding its usage in children. Our research group has been following data on the efficacy and safety of CSI in Chinese paediatric patients with carbapenem-resistant organism infections. The purpose of this short communication is to provide a brief overview of the findings to date., Methods: We reviewed the electronic medical records of paediatric patients (aged 9-17 y) who were administered CSI during their hospital stay at Tongji Hospital in Wuhan, China, between June 2021 and November 2023. Drug efficacy was evaluated based on clinical and microbiological outcomes, while drug safety was assessed using surveillance markers that reflect adverse reactions., Results: A total of 20 patients met the inclusion criteria. The predominant pathogens were Klebsiella pneumoniae (8 strains), followed by Acinetobacter baumannii (5 strains) and Pseudomonas aeruginosa (2 strains). The clinical response rate of CSI was 85%, with a bacterial clearance rate of 79%. None of the patients experienced colistin-related nephrotoxicity or neurotoxicity during the treatment., Conclusions: In this real-world setting, CSI demonstrated a high level of clinical response and was well tolerated for the treatment of carbapenem-resistant organism infections in Chinese children., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To report the anatomic outcomes and retinal structure changes from lens-sparing vitrectomy (LSV) for eyes with Stage 3 or 4 familial exudative vitreoretinopathy (FEVR)., Methods: Overall, 133 consecutive eyes of 119 patients with Stage 3 (51 eyes) or 4 (82 eyes) FEVR who underwent LSV between January 2012 and May 2023 were retrospectively reviewed., Results: One hundred twenty-nine eyes (97.0%) achieved traction relief through one LSV operation. The extent of retinal detachment improved in 98 eyes (73.7%), remained stable in 32 eyes (24.1%), and progressed in three eyes (2.3%). At long-term follow-up, 39 (29.3%) and 60 (45.1%) eyes had completely or partially reattached retina, respectively. The median change of venular angle was 3.6° (95% CI, 3.5-10.5; P < 0.001) and -9.9° (95% CI, -15.8 to -4.6; P < 0.001) for temporal and nasal vessels, respectively. The mean disk-fovea distance was 0.3 papillary diameter shorter (95% CI, -0.4 to -0.2; P < 0.001), and the mean temporal venular arcade distance was 0.02 papillary diameter larger (95% CI, -0.16 to 0.21; P = 0.361)., Conclusion: These results suggest that LSV can relieve vitreoretinal traction and reattach the retina in late-stage FEVR eyes. Improvements in temporal and nasal venular angle and disk-fovea distance reflect positive retinal structure changes for patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by antiplatelet autoantibodies, thrombocytopenia, and bleeding, however, its treatment options are limited. In this study, a kind of active component, chlorogenic acid compounds (CGAs) from sweetpotato leaves was extracted out to explore its medicinal value and provide novel therapeutic strategies for the treatment of ITP. CGAs was isolated by ionic liquids-ultrasound (IL-UAE), which contains six isomers of chlorogenic acid with total purity of 95.69%. The thrombopoietic effect and mechanism of CGAs were investigated using in silico prediction and experimental validation. The changes of HEL cells morphology in volume and the increase in the total cell percentage of polyploid cells indicated that CGAs could promote megakaryocyte differentiation. Meanwhile, CGAs could promote platelet formation in a murine model of ITP, which was established by injection of antiplatelet antibody. Further quantitative proteomics analysis and Western blot verification revealed that CGAs could activate PI3K/AKT signaling pathway, which confirmed the mechanism prediction. It suggested that CGAs may provide a novel therapeutic strategy that relies on the PI3K/AKT pathway to facilitate megakaryocyte differentiation and platelet production., 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 Zhang, Zhao, Wang, Yue, Zhu, Zhang, Sun, Zhang and Ma.)

Background: Abusive head trauma (AHT) is a severe form of physical abuse leading to significant morbidity and mortality in children, often presenting with complex brain injuries. Among the varied manifestations, ophthalmologic presentations are critical yet underexplored, which may provide essential clues for early diagnosis and management, improving long-term visual and neurological outcomes., Objective: This study aims to explore the manifestation, management, and outcomes of AHT cases within a single center in China over a five-year period, with a focus on the importance of ophthalmologic evaluation in enhancing the diagnosis, management, and outcome predictions of AHT., Methods: A retrospective case series was conducted at a single institution, involving infants diagnosed with AHT from 2019 to 2023. Data on demographics, medical histories, and clinical management were collected. Ophthalmologic examinations including fundus photography, ocular B-scan ultrasound and fundus fluorescein angiography (FFA), were performed to evaluate retinal vasculature and identify peripheral ischemic retina (PIR). Statistical analyses were performed using SPSS ver. 26.0., Results: Eight AHT patients (16 eyes) were included in the study. Bilateral ocular involvement was observed in all patients, with 81.25% exhibiting retinal hemorrhages (RH). Other manifestations included retinal detachment (31.25%) and optic nerve atrophy (18.75%). Clinical interventions varied, with 68.75% of patients undergoing treatments such as laser photocoagulation and anti-vascular endothelial growth factor (VEGF) injections. Among all eyes, 75% showed resolution of RH. Despite treatment, some patients progressed to severe conditions such as retinal detachment (RD) and iris neovascularization (INV)., Conclusion: This study emphasizes the importance of a multidisciplinary approach in the diagnosis and management of AHT, particularly by integrating ophthalmological perspectives into patient care. These findings contribute to the understanding of ophthalmologic presentations in AHT., 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 Yin, Peng, Zhang, Yang, Gu, Zhang, Liu, Xiao, Xu and Zhao.)

This study aims to assess the global prevalence of kinesiophobia and the potential influencing factors among patients with heart disease. A comprehensive search was conducted in PubMed, Embase, Web of Science, PsycINFO, and Scopus databases to identify studies reporting on the prevalence of kinesiophobia and its influencing factors in heart disease patients up to January 2024. A random-effects model was employed to aggregate prevalence rates. Heterogeneity sources were investigated through subgroup analysis, while differences in the prevalence of kinesiophobia across regions, types of heart disease, and gender were evaluated. Additionally, a qualitative analysis of the factors influencing kinesiophobia was performed. This research incorporated 15 studies from six countries, with 14 providing data on the prevalence of kinesiophobia and nine exploring its potential influencing factors. The findings indicated that the overall prevalence of kinesiophobia among heart disease patients was 61.0% (95% CI 49.4-72.6%). Subgroup analysis revealed that the prevalence in upper-middle-income countries was 71.8% (95% CI 66.2-77.4%), while it stands at 49.9% (95% CI 30.2-69.5%) in high-income countries. The prevalence rates among patients with coronary artery disease, heart failure, and atrial fibrillation were 63.2% (95% CI 45.2-81.3%), 69.2% (95% CI 57.6-80.8%), and 71.6% (95% CI 67.1-76.1%), respectively. Gender-wise, no significant difference was observed in the prevalence of kinesiophobia between men and women (52.2% vs. 51.8%). A total of 24 potential influencing factors of kinesiophobia were identified, with education level, monthly income, anxiety, and exercise self-efficacy being the most recognized. The prevalence of kinesiophobia in patients with heart disease is notably high and is influenced by a multitude of factors. Early implementation of targeted preventive measures is imperative to mitigate the incidence of kinesiophobia in this population., (© 2024. The Author(s).)

Background: Adalimumab has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult rheumatoid arthritis (RA), and subsequently approved for pediatric treatment of various autoimmune diseases in children of different ages. Due to genetic differences between children and adults in terms of physiology and immunity, there is a need to explore the safety of adalimumab in children in the real world. The aim of this study is to identify potential adverse event (AE) signals associated with the use of adalimumab in pediatric patients (<18 years old) using data from the FDA Adverse Event Reporting System (FAERS)., Methods: AEs associated with adalimumab in pediatric patients reported in the FAERS database from the first quarter (Q1) of 2017 to the third quarter (Q3) of 2022 were systematically gathered. Reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayes geometric mean (EBGM) were used to assess the relationship between adalimumab and AEs in children., Results: Out of 8,363,304 reports collected from the FAERS database during the study period, 3819 reports on children on adalimumab were identified. Adalimumab-related AEs reports were concentrated on 10 toxicity areas and a total of 202 positive signals were detected, of which injection site papule (ROR = 261.97) and intestinal fistula (ROR = 122.09) had the strongest signals. Unexpected significant AEs, including intestinal obstruction, immunodeficiency, abdominal abscess, and Takayasu's arteritis might also occur. In comparison with patients of all ages in the same time window, the median onset time of children was shorter (99 vs. 149 days). Most of the AE cases occurred in children within the first 1 (1.71%), 2 (8.12%), and 3 months (8.39%) and had early failure types after adalimumab initiation. Methotrexate, folic acid, prednisone, azathioprine, and mesalamine were the top five drugs used concomitantly for adalimumab-associated AEs., Conclusions: When adalimumab is used in children, especially in the first 3 months of treatment, in addition to the AEs recorded in the drug package insert, close attention should be paid to the new potential AEs off-label to ensure the safety of adalimumab in children.

Antibody drug conjugates are an exciting therapeutic modality that combines the targeting specificity of antibodies with potent cytotoxins to selectively kill cancer cells. The targeting component improves efficacy and protects non-target cells from the harmful effects of the payload. To date 15 ADCs have been approved by regulatory agencies for commercial use and shown to be valuable tools in the treatment of cancer.The assembly of an ADC requires the chemical ligation of a linker-payload to an antibody. Conventional conjugation methods targeting accessible lysines and cysteines have produced all the ADCs currently on the market. While successful, technologies aiming to improve the homogeneity and stability of ADCs are being developed and tested.Here we provide a review of developing methods for ADC construction. These include enzymatic methods, oligosaccharide remodelling, and technologies using genetic code expansion techniques. The virtues and limitations of each technology are discussed.Emerging conjugation technologies are being applied to produce new formats of ADCs with enhanced functionality including bispecific ADCs, dual-payload ADCs, and nanoparticles for targeted drug delivery. The benefits of these novel formats are highlighted.

From the fruits of Cordia dichotoma , 11 new phenolic compounds, dichotomins A-K, were isolated, together with 19 known compounds. Through the analysis of detailed NMR data and HRESIMS data, the planar structures of all compounds were confirmed. Using NMR calculations, the absolute configuration of dichotomins A-K was elucidated by comparing their observed and computed electronic circular dichroism (ECD) spectra. Dichotomin H ( 8 ) and dichotomin I ( 9 ) were determined as two pairs of enantiomers. The enantiomers of compounds 8 and 9 were separated using chiral-phase high-performance liquid chromatography (HPLC), and the stereostructure of each enantiomer was determined by similarly calculating the ECD. Compounds 3 , 5, 7 , 17 , 18 , 23 - 25 , and 27 - 30 increased glucose uptake by 1.04- to 2.85-folds at concentrations of 30 μg/mL. Further studies revealed that compounds 3 and 5 had a moderate effect on glucose transporter 4 (GLUT4) translocation activity in L6 cells. At 30 μg/mL, compound 3 significantly enhanced AMPK phosphorylation and GLUT4 expression. As a whole, compound 3 has the potential to be a drug candidate for the treatment of type 2 diabetes mellitus (T2DM).

Purpose: To observe the vascular development results of tertiary anti-vascular endothelial growth factor (anti-VEGF) therapy following spontaneous second reactivation of retinopathy of prematurity (ROP)., Methods: This retrospective study included 22 infants (42 eyes) with Type 1 or aggressive ROP (A-ROP) who received three anti-VEGF drug treatments for ROP from January 2018 to December 2022. The vascular growth, possible associated risk factors, and the retinal vascularization (DB/DF ratio) were assessed., Results: The mean follow-up was 17.6 months. After the 3 rd intravitreal injection, seven eyes showed complete vascularization (Group 1), while the remaining 35 eyes demonstrated persistent avascular retina (PAR) (Group 2). In Group 2, 17 eyes maintained a stable state and were classified in the regression subgroup. The other 18 eyes developed a 3 rd reactivation (reactivation subgroup) and were treated with laser photocoagulation (LPC).Birth weight (BW) was significantly lower in Group 2 than in Group 1 ( p  < 0.001). The decision tree analysis shows that only infants weighing more than 1,250 g (17.50%) had a chance to achieve complete retinal vascularization. The possibility of PAR was higher in patients with BW <1,250 g than ≥1,250 g (70.00% vs. 12.50%). In addition, most infants with BW ≥ 1,290 g and initial ROP disease in Zone I or posterior Zone II developed PAR., Conclusion: Tertiary IVR can successfully treat a second ROP reactivation and improve peripheral retinal vascularization. BW is the most significant factor related to complete retinal vascularization. Our decision tree model may be helpful in predicting the prognosis of anti-VEGF drugs in the event of a second ROP reactivation., 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 Zhang, Peng, Yang, Liu, Zhang, Gu, Liu, Xiao, Yin, Xu and Zhao.)

Objective: Cancer is a predominant cause of death globally. PHD-finger domain protein 5 A (PHF5A) has been reported to participate in various cancers; however, there has been no pan-cancer analysis of PHF5A. This study aims to present a novel prognostic biomarker and therapeutic target for cancer treatment., Methods: This study explored PHF5A expression and its impact on prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), functional status and tumor immunity across cancers using various public databases, and validated PHF5A expression and its correlation with survival, immune evasion, angiogenesis, and treatment response in hepatocellular carcinoma (HCC) using bioinformatics tools, qRT-PCR and immunohistochemistry (IHC)., Results: PHF5A was differentially expressed between tumor and corresponding normal tissues and was correlated with prognosis in diverse cancers. Its expression was also associated with TMB, MSI, functional status, tumor microenvironment, immune infiltration, immune checkpoint genes and tumor immune dysfunction and exclusion (TIDE) score in diverse malignancies. In HCC, PHF5A was confirmed to be upregulated by qRT-PCR and IHC, and elevated PHF5A expression may promote immune evasion and angiogenesis in HCC. Additionally, multiple canonical pathways were revealed to be involved in the biological activity of PHF5A in HCC. Moreover, immunotherapy and transcatheter arterial chemoembolization (TACE) worked better in the low PHF5A expression group, while sorafenib, chemotherapy and AKT inhibitor were more effective in the high expression group., Conclusions: This study provides a comprehensive understanding of the biological function of PHF5A in the carcinogenesis and progression of various cancers. PHF5A could serve as a tumor biomarker related to prognosis across cancers, especially HCC, and shed new light on the development of novel therapeutic targets., (© 2024. The Author(s).)

Alzheimer's disease (AD) is one of the most fatal and irreversible neurodegenerative diseases, which causes a huge emotional and financial burden on families and society. Despite the progress made with recent clinical use of inhibitors of acetylcholinesterase and amyloid-β (Aβ) antibodies, the curative effects of AD treatment remain unsatisfactory, which is probably due to the complexity of pathogenesis and the multiplicity of therapeutic targets. Thus, modulating complex pathological networks could be an alternative approach to treat AD. Here, a neutrophil membrane-coated MOF nanozyme (denoted as Neu-MOF/Fla) is biomimetically engineered to disturb the malignant Aβ deposition-inflammation cycle and ameliorate the pathological network for effective AD treatment. Neu-MOF/Fla could recognize the pathological inflammatory signals of AD, and deliver the photo-triggered anti-inflammatory CO and MOF based hydrolytic nanozymes to the lesion area of the brain in a spontaneous manner. Based on the in vitro and in vivo studies, Neu-MOF/Fla significantly suppresses neuroinflammation, mitigates the Aβ burden, beneficially modulates the pro-inflammatory microglial phenotypes and improves the cognitive defects of AD mice models. Our work presents a good example for developing biomimetic multifunctional nanotherapeutics against AD by means of amelioration of multiple symptoms and improvement of cognitive defects., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

Objective: This study aimed to explore the neurological adverse events of oxaliplatin through the Food and Drug Administration Adverse Event Reporting System (FAERS) database and to provide reference for safe clinical drug use., Methods: The adverse events report data of oxaliplatin from the first quarter of 2019 (1 January 2019) to the third quarter of 2023 (30 September 2023) were extracted from FAERS database, and the adverse events signal intensity was determined using the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean methods. Time-to-onset and univariate logistic regression analysis were performed to describe the characteristics and risk factors of oxaliplatin-associated neurological adverse events., Results: A total of 4,471 cases of oxaliplatin-associated neurological adverse events were identified, with 318 neurological adverse events being documented, among which 87 adverse events satisfied the thresholds of four methodologies. The median time-to-onset of oxaliplatin-associated neurological adverse events was 2 days (interquartile range 0-36 days). Among the factors significantly influencing oxaliplatin-related neurological adverse events, male sex and combination medication decreased the risk of neurological adverse events, while higher cumulative dose increased the risk., Conclusion: The real-world neurotoxicity spectrum of oxaliplatin and its characteristics and influencing factors were obtained through data mining of FAERS, providing valuable insights for healthcare professionals to effectively manage the risk of neurological adverse events associated with oxaliplatin in clinical practice., 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 Pan, Xiao, Ding, Shu, Zhang and Huang.)

COVID-19 has been a global concern for 3 years, however, consecutive plasma protein changes in the disease course are currently unclear. Setting the mortality within 28 days of admission as the main clinical outcome, plasma samples were collected from patients in discovery and independent validation groups at different time points during the disease course. The whole patients were divided into death and survival groups according to their clinical outcomes. Proteomics and pathway/network analyses were used to find the differentially expressed proteins and pathways. Then, we used machine learning to develop a protein classifier which can predict the clinical outcomes of the patients with COVID-19 and help identify the high-risk patients. Finally, a classifier including C-reactive protein, extracellular matrix protein 1, insulin-like growth factor-binding protein complex acid labile subunit, E3 ubiquitin-protein ligase HECW1 and phosphatidylcholine-sterol acyltransferase was determined. The prediction value of the model was verified with an independent patient cohort. This novel model can realize early prediction of 28-day mortality of patients with COVID-19, with the area under curve 0.88 in discovery group and 0.80 in validation group, superior to 4C mortality and E-CURB65 scores. In total, this work revealed a potential protein classifier which can assist in predicting the outcomes of COVID-19 patients and providing new diagnostic directions., (© 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

To reduce the preparation cost of high-purity hydrogen, it is necessary to search suitable non-precious metal catalysts with high activity and robust stability. Herein, two means (heteroatom-doping and the heterostructure construction) were adopted together to improve the dual-function activity of NiFe LDH which was widely used in water electrolysis. Mo doped NiFe LDH nanoflowers were firstly generated by hydrothermal reaction, and then NiS x was modified on the petals via electrodeposition. Finally, the obtained NF/Mo-NiFe LDH/NiS x with large electrochemical active area exhibits the expected electrochemical performance with the overpotential at 100 mA cm -2 of 169 and 249 mV for hydrogen evolution (HER) and oxygen evolution reaction (OER) respectively. Assembling NF/Mo-NiFe LDH/NiS x into a two-electrode device for the integral water electrolysis, it just requires a cell voltage of 1.69 V to drive a current density of 100 mA cm -2 , and keeps stable after 50-hour continuous operation in 1.0 M KOH. Mo-doping not only regulates the electronic structure of the transition metals and reduces the energy barrier of HER intermediates, but also facilitates the generation of reactive sites for OER. Meanwhile, the construction of heterointerface ensures the synergism between NiS x and Mo-NiFe LDH and accelerates the electron transfer across interfaces, thus enhancing the bifunctional performance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wei Hu reports financial support was provided by National Natural Science Foundation of China. Dan Zhou reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Cluster of differentiation 38 (CD38) has been found to be highly expressed in various solid tumours, and its expression level may be associated with patient prognosis and survival. This study aimed to evaluate the prognostic value of CD38 expression for patients with epithelial ovarian cancer (EOC) and construct two computed tomography (CT)-based radiomics models for predicting CD38 expression., Methods: A total of 333 cases of EOC were enrolled from The Cancer Genome Atlas (TCGA) database for CD38-related bioinformatics and survival analysis. A total of 56 intersection cases from TCGA and The Cancer Imaging Archive (TCIA) databases were selected for radiomics feature extraction and model construction. Logistic regression (LR) and support vector machine (SVM) models were constructed and internally validated using 5-fold cross-validation to assess the performance of the models for CD38 expression levels., Results: High CD38 expression was an independent protective factor (HR = 0.540) for overall survival (OS) in EOC patients. Five radiomics features based on CT images were selected to build models for the prediction of CD38 expression. In the training and internal validation sets, for the receiver operating characteristic (ROC) curve, the LR model reached an area under the curve (AUC) of 0.739 and 0.732, while the SVM model achieved AUC values of 0.741 and 0.700, respectively. For the precision-recall (PR) curve, the LR and SVM models demonstrated an AUC of 0.760 and 0.721. The calibration curves and decision curve analysis (DCA) provided evidence supporting the fitness and net benefit of the models., Conclusions: High levels of CD38 expression can improve OS in EOC patients. CT-based radiomics models can be a new predictive tool for CD38 expression, offering possibilities for individualised survival assessment for patients with EOC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Wurfbainia villosa var. villosa is a traditional Chinese herbal medicine under the family Zingiberaceae, and its ripe fruits (called Fructus Amomi) are widely used clinically for the treatment of gastrointestinal disorders (Yang et al. 2023; Chen et al. 2023). In September 2023, plants of W. villosa var. villosa exhibited anthracnose-like symptoms on leaf with a disease incidence of 35% (n = 100 investigated plants) in an approximately 90 m2 field in Guangning, China (N23°42'51.70″, E112°26'35.75″). Light yellowish-green spots (~2 mm diameter) initially appeared on the infected leaves, gradually formed sub-circular or irregular spots, then fused and expanded, resulting in wilting of the leaves. To identify the causal agent, 10 symptomatic leaves were collected and transferred to the laboratory. The symptomatic leaf samples were surface sterilized in 0.5% NaClO for 2 min, and in 70% ethanol for 30 s, then washed three times with sterile water and air-dried on sterile filter paper. The leaf tissues were placed on potato dextrose agar (PDA) medium containing 100 μg mL-1 of ampicillin (Sigma-Aldrich, St. Louis, MO) and incubated for 7 days at 28°C in darkness. Nine isolates with similar colony morphology were isolated from the 10 plated leaves. Three representative isolates (GNAF03, GNAF06, GNAF09 with approximately 3.5 cm in diameter after 3 days of incubation) appeared gray to dark brown with dense aerial hyphae at the front and gray to black colonies on the reverse of the plates. Conidia were cylindrical and measured 21.2 to 29.3 μm long × 7.1 to 9.6 μm wide (n = 50). Appressoria were formed by the tips of germ tubes or hyphae and were brown, ellipsoid, thick-walled, and smooth-margined, measuring 10.2 to 12.3 μm long × 6.4 to 8.2 μm wide (n = 50). Morphologically, the fungal isolates resembled Colletotrichum sp. (Weir et al. 2012). For molecular analysis, genomic DNA was extracted from fresh mycelia of the three isolates, and the primers ACT-512F/ACT-783R, CL1/CL2A, GDF/GDR, and ITS1/ITS4 were used to amplify partial regions of rDNA-ITS, actin (ACT), calmodulin (CAL), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) regions, respectively (Weir et al. 2012). The resulting sequences with more than 99% nucleotide identity to C. gloeosporioides were submitted to GenBank (accession numbers PP552725, PP552726, and OR827444 for ACT; PP552727, PP552728, and OR827443 for CAL; PP552729, PP552730, and OR827445 for GAPDH; PP549996, PP549999, and OR841394 for ITS). A phylogenetic tree was generated by the maximum likelihood method using the concatenated sequences of ACT, CAL, GADPH, and ITS by Polysuite software (Damm et al. 2020). Based on morphological and molecular analysis, the three isolates were characterized as C. gloeosporioides. The pathogenicity of the GNAF09 isolate was assessed on W. villosa var. villosa seedling leaves inoculated by spraying with 40 μL of conidial suspension at 106 conidia mL-1 or wounded with a sterile toothpick then inoculated with mycelial agar plugs (5 mm diameter). Control leaves were inoculated with 40 μL of sterile distilled water or agar plugs without mycelia. The inoculated plants were placed in a humid chamber at 28°C with 80% humidity and a 12 h light-dark photoperiod. Symptoms similar to those seen on naturally infected leaves were observed on all inoculated leaves after 7 days inoculation. Re-isolation was performed from 80% of the inoculated leaves and isolates were confirmed as C. gloeosporioides morphologically, confirming Koch's postulates, and by sequencing the ACT, CAL, GADPH, and ITS regions. The control groups remained asymptomatic. In previous studies, C. gloeosporioides has also caused anthracnose on Chinese medicinal plants, including Baishao (Radix paeoniae alba) (Zhang et al. 2017) and Rubia cordifolia L. (Tang et al. 2020). To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on W. villosa var. villosa in China. The results of our report serve as valuable references for further research on this disease.

The industrialization of animal agriculture has undoubtedly contributed to the improvement of human well-being by increasing the efficiency of food animal production. At the same time, it has also drastically impacted the natural environment and human society. The One Health initiative emphasizes the interdependency of the health of ecosystems, animals, and humans. In this paper, we discuss some of the most profound consequences of animal agriculture practices from a One Health perspective. More specifically, we focus on impacts to host-microbe interactions by elaborating on how modern animal agriculture affects zoonotic infections, specifically those of bacterial origin, and the concomitant emergence of antimicrobial resistance (AMR). A key question underlying these deeply interconnected issues is how to better prevent, monitor, and manage infections in animal agriculture. To address this, we outline approaches to mitigate the impacts of agricultural bacterial zoonoses and AMR, including the development of novel treatments as well as non-drug approaches comprising integrated surveillance programs and policy and education regarding agricultural practices and antimicrobial stewardship. Finally, we touch upon additional major environmental and health factors impacted by animal agriculture within the One Health context, including animal welfare, food security, food safety, and climate change. Charting how these issues are interwoven to comprise the complex web of animal agriculture's broad impacts on One Health will allow for the development of concerted, multidisciplinary interventions which are truly necessary to tackle these issues from a One Health perspective., Competing Interests: None., (© 2024 The Author(s).)

Non-antibiotic strategies are desperately needed to treat post-traumatic osteomyelitis (PTO) due to the emergence of superbugs, complex inflammatory microenvironments, and greatly enriched biofilms. Previously, growing evidence indicated that quorum sensing (QS), a chemical communication signal among bacterial cells, can accelerate resistance under evolutionary pressure. This study aims to develop a medical dressing to treat PTO by inhibiting QS and regulating the inflammatory microenvironment, which includes severe oxidative stress and acid abscesses, through a reactive oxygen species (ROS)-responsive bond between N1- (4-borobenzoyl)-N3-(4-borobenzoyl)-the N1, the N1, N3, N3-tetramethylpropane-1,3-diamine (TSPBA) and polyvinyl alcohol (PVA), and the amino side chain of hyperbranched polylysine (HBPL). Physically enclosed QS inhibitors subsequently exerted the antibacterial effects. This hydrogel can scavenge hydrogen peroxide (H 2 O 2 ), superoxide anion free radical (·O 2 - ), hydroxyl radicals (·OH) and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH) to reduce oxidative stress and inhibit "bacteria-to-bacteria communication", thus clearing planktonic bacteria and biofilms, accelerating bacterial plasmolysis, reducing bacterial virulence and interfering with membrane transport. After in vivo treatment with hydrogel, nearly all bacteria are eliminated, inflammation is effectively inhibited, and osteogenesis and bone repair are promoted to facilitate recovery from PTO. The work demonstrates the clinical translational potential of the hydrogel in the treatment of drug-resistant bacteria induced PTO., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Bioorthogonal reactions provide a powerful tool to manipulate biological processes in their native environment. However, the transition-metal catalysts (TMCs) for bioorthogonal catalysis are limited to low atomic utilization and moderate catalytic efficiency, resulting in unsatisfactory performance in a complex physiological environment. Herein, sulfur-doped Fe single-atom catalysts with atomically dispersed and uniform active sites are fabricated to serve as potent bioorthogonal catalysts (denoted as Fe-SA), which provide a powerful tool for in situ manipulation of cellular biological processes. As a proof of concept, the N 6 -methyladensoine (m 6 A) methylation in macrophages is selectively regulated by the mannose-modified Fe-SA nanocatalysts (denoted as Fe-SA@Man NCs) for potent cancer immunotherapy. Particularly, the agonist prodrug of m 6 A writer METTL3/14 complex protein (pro-MPCH) can be activated in situ by tumor-associated macrophage (TAM)-targeting Fe-SA@Man, which can upregulate METTL3/14 complex protein expression and then reprogram TAMs for tumor killing by hypermethylation of m 6 A modification. Additionally, we find the NCs exhibit an oxidase (OXD)-like activity that further boosts the upregulation of m 6 A methylation and the polarization of macrophages via producing reactive oxygen species (ROS). Ultimately, the reprogrammed M1 macrophages can elicit immune responses and inhibit tumor proliferation. Our study not only sheds light on the design of single-atom catalysts for potent bioorthogonal catalysis but also provides new insights into the spatiotemporal modulation of m 6 A RNA methylation for the treatment of various diseases.

Biological studies on the endocannabinoid system (ECS) have suggested that monoacylglycerol lipase (MAGL), an essential enzyme responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), is a novel target for developing antidepressants. A decrease of 2-AG levels in the hippocampus of the brain has been observed in depressive-like models induced by chronic stress. Herein, employing a structure-based approach, we designed and synthesized a new class of (piperazine-1-carbonyl) quinolin-2(1H)-one derivatives as potent, reversible and selective MAGL inhibitors. And detailed structure-activity relationships (SAR) studies were discussed. Compound 27 (IC 50  = 10.3 nM) exhibited high bioavailability (92.7%) and 2-AG elevation effect in vivo. Additionally, compound 27 exerted rapid antidepressant effects caused by chronic restraint stress (CRS) and didn't show signs of addictive properties in the conditioned place preference (CPP) assays. Our study is the first to report that reversible MAGL inhibitors can treat chronic stress-induced depression effectively, which may provide a new potential therapeutic strategy for the discovery of an original class of safe, rapid antidepressant drugs., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of the manuscript., (Copyright © 2024. Published by Elsevier Masson SAS.)

The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective To prepare anti-human B7 homolog 4 (B7-H4) egg yolk immunoglobulins (IgY) polyclonal antibody and establish a double-antibody sandwich ELISA for the detection of soluble B7-H4 (sB7-H4) protein in human serum. Methods Bioinformatics was used to screen specific B cell epitope peptides of human sB7-H4. New Hyland Grey laying hens were immunized with these peptides, and the eggs from the immunized hens were collected to purify chicken anti-human B7-H4 IgY antibody. The purity, concentration and titer of the antibody were detected, and its specificity and function of the antibodies were verified by using ELISA, Western blot analysis and flow cytometry, respectively. A double-antibody sandwich ELISA was established to detect sB7-H4 in clinical samples by using the IgY antibody. Comparative detection was performed using a commercialized ELISA kit on the same set of clinical samples. Results The chicken anti-human B7-H4 IgY antibodies were successfully prepared and proven to be highly specific for the human B7-H4 protein. The ELISA established with the IgY polyclonal antibody detected significantly higher levels of soluble B7-H4 in the serum of patients with ovarian cancer and benign ovarian tumors compared to healthy controls. These results were consistent with the detection results obtained using a commercialized ELISA kit. However, the ELISA with IgY antibody exhibited higher sensitivity than the commercialized kit. Conclusion The chicken polyclonal antibody against human B7-H4 IgY is successfully prepared, and a double-antibody sandwich ELISA suitable for detecting sB7-H4 protein in human serum is established.

Salt stress significantly impedes plant growth and the crop yield. This study utilized de novo transcriptome assembly and ribosome profiling to explore mRNA translation's role in rice salt tolerance. We identified unrecognized translated open reading frames (ORFs), including 42 upstream transcripts and 86 unannotated transcripts. A noteworthy discovery was the role of a small ORF, Ospep5, in conferring salt tolerance. Overexpression of Ospep5 in plants increased salt tolerance, while its absence led to heightened sensitivity. This hypothesis was corroborated by the findings that exogenous application of the synthetic small peptide Ospep5 bolstered salt tolerance in both rice and Arabidopsis . We found that the mechanism underpinning the Ospep5-mediated salt tolerance involves the maintenance of intracellular Na + /K + homeostasis, facilitated by upregulation of high-affinity potassium transporters (HKT) and Na + /H + exchangers (SOS1). Furthermore, a comprehensive multiomics approach, particularly ribosome profiling, is instrumental in uncovering unannotated ORFs and elucidating their functions in plant stress responses.

Heavy pollution of particulate matter with an aerodynamic diameter of <2.5 μm (PM 2.5 ) poses increasing threats to the living environment worldwide. Urban agglomerations often lead to regional rather than local air pollution problems. This study explored the underlying global and local spatial driving mechanisms of PM 2.5 variations of the 195 county-level administrative units in the urban agglomeration in the middle reaches of the Yangtze River, China, in 2020, using the global spatial regression and geographically weighted regression methods. Results showed that (1) at the county level, there were spatial variations of PM 2.5 , fluctuating from 20.1263 μg/m 3 to 44.8416 μg/m 3 . (2) The concentrations of PM 2.5 presented a positive spatial autocorrelation with a remarkable direct spatial spillover effect. (3) Forestland, grassland, elevation and ecological restoration were negatively correlated with PM 2.5 concentrations, the indirect spatial spillover effect of elevation was noticeable. (4) The indirect reduction effects of ecological restoration on PM 2.5 concentrations were substantial in the Wuhan urban agglomeration. (5) The reduction effect of forestland, grassland, ecological restoration and elevation on PM 2.5 showed a noticeable spatial heterogeneity. In the future, it is suggested regional variability and the spatial spillover effect of air pollution be taken into account in environmental governance. Simultaneously, utilization of the mitigation effect of ecological restoration on PM 2.5 is anticipated for the concerted effort in air pollution governance., 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.)