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Abstract Amid the ongoing Global Plastics Treaty, high-quality circulation of halogen-containing plastics in an environmentally sound manner is a globally pressing issue. Current chemical dechlorination methods are limited by their inability to recycle PVC at the long-chain carbon level and the persistence of eco-toxic organochlorine byproducts. Herein, we propose a click dechlorination strategy for transforming waste PVC into valuable vitrimers via a one-step cascade thiol-ene click reaction and dynamic polymerization. Thermal activation of C-Cl bonds initiates β-elimination dechlorination, while disulfide bonds synchronously undergo homolytic cleavage, generating sulfur-centered radicals that drive precise sulfur-chlorine substitution and the formation of disulfide dynamic networks. This strategy achieves nearly complete chlorine extraction (93.88%) and produces vitrimers with tailorable mechanical and reprocessing properties, spanning from soft elastomers with 784% elongation to rigid plastics with a yield strength of 34 MPa. The significant advantage of this strategy is backbone protective precise dechlorination, enabling ecosystem toxicity reduced by 99.51% compared with widely adopted pyrolysis methods. This work introduces a sustainable pathway for upcycling PVC into valuable materials, marking significant progress in chlorinated plastic recycling.

Abstract Background Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely.

Abstract Background Conflicting findings regarding the impact of High protein intake during the early phase in critically ill patients have been reported. Therefore, we aimed to assess the influence of higher early protein intake on the prognosis of critically ill patients. Methods This randomized controlled trial involved 173 critically ill patients who stayed in the Intensive Care Unit/Emergency ICU (ICU/EICU) for at least 7 days. The Low group (n = 87) and High group (n = 86) received protein supplementation of 0.8 g/kg.d and 1.5 g/kg.d, respectively, within 1–3 days of enteral nutrition (EN) initiation, with both groups transitioning to 1.5 g/kg.d on the 4th day. The serum prealbumin (PA), blood urea nitrogen/creatinine, and rectus femoris muscle thickness and cross-sectional area of all patients was measured on the 1th, 3rd, 5th, 7th day, and the day of ICU/EICU discharge. Results Patients in both Low and High groups showed no significant differences in age, APACHE II scores, or other demographic and baseline characteristics. There were also no significant differences in the primary outcome (28-day mortality rate) and secondary outcomes (incidence rate of refeeding syndrome and EN tolerance score) between the two groups. However, the Low group exhibited a significantly higher 28-day mortality rate (HR = 2.462, 95% CI: 1.021–5.936, P = 0.045) compared to High group, as determined by Cox proportional hazards models incorporating the time factor. The High group exhibited significantly shorter durations of mechanical ventilation and ICU stay compared to the Low group. Serum PA levels were higher, and rectus femoris muscle atrophy rates were lower in the High group. Furthermore, for septic patients, high protein intake significantly reduced the 28-day mortality rate despite a small sample size (n = 34). Conclusions Our study indicates that increasing early protein intake to 1.5 g/kg.d may be safe and help improve the nutritional status and prognosis of critically ill patients. Trial registration This study was registered with the Chinese Clinical Trial Registry (ChiCTR2000039997, https://www.chictr.org.cn/ ).

Abstract Background Platelet is enriched with Circular RNAs (circRNAs), with circFAM13B rank among the 10 most abundant circRNAs in platelets. The aim of the present study was to evaluate the predictive value of platelet-derived circFAM13B for the antiplatelet responsiveness and efficacy of ticagrelor in patients with acute coronary syndrome (ACS). Methods Consecutive ACS patients treated with ticagrelor were enrolled, and the antiplatelet responsiveness of 3 days of ticagrelor maintenance treatment was assessed by measuring the adenosine diphosphate (ADP)-induced platelet inhibition rate (ADP%) using thromboelastography. The expression of circFAM13B in the patients’ platelets was analyzed by quantitative real-time polymerase chain reaction. The correlation between circFAM13B expression and ticagrelor antiplatelet responsiveness, as well as the independent contribution of circFAM13B to the composite of adverse ischemic events during a follow-up period of at least 12 months was evaluated. Results A total of 129 eligible ACS patients treated with ticagrelor were enrolled in the study. A negative correlation was found between the expression of circFAM13B and the ADP% value (r = -0.41, P 1.05 with clinical risk factors could effectively predict the risk of adverse ischemic events (AUC = 0.81, 95% CI: 0.69 to 0.92, P 1.05 had a significantly higher risk of adverse ischemic events compared to those with circFAM13B ≤ 1.05 (P = 0.003). Multivariate logistic hazard analysis identified circFAM13B > 1.05 as an independent risk factor for adverse ischemic events in in ticagrelor-treated ACS patients (adjusted OR: 5.60, 95% CI: 1.69–18.50; P = 0.005). Conclusions Platelet-derived circFAM13B could be utilized for predicting the antiplatelet responsiveness and efficacy of ticagrelor in patients with ACS.

Abstract The rapid advancement in attractive platforms such as biomedicine and human‐machine interaction has generated urgent demands for intelligent materials with high strength, flexibility, and self‐healing capabilities. However, existing self‐healing ability materials are challenged by a trade‐off between high strength, low elastic modulus, and healing ability due to the inherent low strength of noncovalent bonding. Here, drawing inspiration from human fibroblasts, a monomer trapping synthesis strategy is presented based on the dissociation and reconfiguration in amphiphilic ionic restrictors (7000‐times volume monomer trapping) to develop a eutectogel. Benefiting from the nanoconfinement and dynamic interfacial interactions, the molecular chain backbone of the formed confined domains is mechanically reinforced while preserving soft movement capabilities. The resulting eutectogels demonstrate superior mechanical properties (1799% and 2753% higher tensile strength and toughness than pure polymerized deep eutectic solvent), excellent self‐healing efficiency (>90%), low tangential modulus (0.367 MPa during the working stage), and the ability to sensitively monitor human activities. This strategy is poised to offer a new perspective for developing high strength, low modulus, and self‐healing wearable electronics tailored to human body motion.

Summary: Epstein-Barr virus (EBV), an oncogenic herpesvirus, is predominantly found in the latent infection form and is highly associated with many human malignancies, which mainly have poor prognoses and no effective treatments. Here, we obtained thirteen compounds from small-molecule libraries for specific inhibition of EBV-latently infected cell growth in vitro by high-throughput screening. Among them, cetrimonium bromide (CetB) was identified to selectively inhibit the growth of different EBV-infected B lymphoma cell lines. Importantly, CetB reduced EBNA1 protein stability, activated G1 arrest and early apoptosis of EBV-latently infected cells without viral lytic reactivation, which leads to dramatically inhibit colony formation and tumor growth of EBV-infected cells in vitro and in vivo, and significantly prolong the survival of tumor-bearing mice. Overall, these findings demonstrate that CetB acts as a highly selective inhibitor of the growth of EBV-infected cells and has the potential for further development of effective therapeutic strategies specific against EBV-associated cancers.

The p-type doping process during the growth of AlGaN nanowires directly influences the optoelectronic properties of the related devices. However, research on the p-type ionization mechanism in AlxGa1-xN nanowires remains limited. In this work, we utilize first principles calculations to investigate p-type doping in AlxGa1-xN nanowires under different structural variables (Al component, doping element, doping site, and doping concentration). Our results demonstrate that p-type doping in AlxGa1-xN nanowires is an endothermic process, and increased dopant concentration leads to a decrease in system stability. Moreover, we found that dopant atoms are easier to substitute for Ga atoms than Al atoms. Among the three doping elements (Zn, Be and Mg), Zn exhibits the most challenging doping difficulty, while Be shows the easiest doping process, with Mg falling in between. Crystal Orbital Hamilton Population (COHP) and bond population calculations reveal the mechanism for the variation in doping structure stability. Doping induces a rearrangement of energy level orbitals, resulting in changes in the band gap. Specifically, the valence band exhibits an overall upward trend crossing the Fermi level, showing the p-type conductive properties. Notably, a significant decrease in electron density near Mg and Be leads to the formation of p-type conductive properties. The changes in hole density and effective mass further confirm the formation of p-type conductivity after doping. Additionally, structures with lower Al composition exhibit higher doping ionization degrees. This study is expected to provide a theoretical basis for the growth, preparation, and application of optoelectronic devices based on p-type AlGaN nanowires.

Abstract Probiotic and engineered microbe-based therapeutics are an emerging class of pharmaceutical agents. They represent a promising strategy for treating various chronic and inflammatory conditions by interacting with the host immune system and/or delivering therapeutic molecules. Here, we engineered a targeted probiotic yeast platform wherein Saccharomyces boulardii is designed to bind to abundant extracellular matrix proteins found within inflammatory lesions of the gastrointestinal tract through tunable antibody surface display. This approach enabled an additional 24–48 h of probiotic gut residence time compared to controls and 100-fold increased probiotic concentrations within the colon in preclinical models of ulcerative colitis in female mice. As a result, pharmacodynamic parameters including colon length, colonic cytokine expression profiles, and histological inflammation scores were robustly improved and restored back to healthy levels. Overall, these studies highlight the potential for targeted microbial therapeutics as a potential oral dosage form for the treatment of inflammatory bowel diseases.

Abstract Background There is a high prevalence of childhood maltreatment among Chinese children and adolescents, but little is known about its impact on alcohol and tobacco use trajectories and how positive school and neighborhood environments moderate the associations. The objective of this study was to assess the association between multiple forms of childhood maltreatment and longitudinal alcohol and tobacco use trajectories, and to assess the possibility that perceived connections to school and neighborhood moderate these associations. Methods This longitudinal cohort study included 2594 adolescents (9 to 13 years) from a low-income rural area in China. Childhood exposure to abuse and neglect was assessed using the Childhood Trauma Questionnaire. Participants reported past-month alcohol and tobacco use at three time points over 1 year. Results Growth curve models revealed that childhood sexual abuse was associated with a higher risk of past-month drinking (OR = 1.53, 95% CI 1.19–2.03, p

Abstract Background Helicobacter pylori (H pylori) infection is the primary cause of gastric cancer (GC). The role of Disabled-2 (DAB2) in GC remains largely unclear. This study aimed to investigate the role of DAB2 in H pylori-mediated gastric tumorigenesis. Methods We screened various datasets of GC to analyze DAB2 expression and cell signaling pathways. DAB2 expression was assessed in human GC tissue microarrays. H pylori infection in vivo and in vitro models were further explored. Immunostaining, immunofluorescence, chromatin immunoprecipitation, co-immunoprecipitation, Western blot, quantitative polymerase chain reaction, and luciferase reporter assays were performed in the current study. Results The bioinformatic analysis verified that DAB2 was 1 of the 8 genes contributed to tumorigenesis and associated with poor prognosis in GC. The median overall survival and disease-free survival rates in DAB2high group were significantly less than those in DAB2low group. These findings demonstrated that H pylori transcriptionally activated DAB2 expression via signal transducer and activator of transcription 3 (STAT3)-dependent pathway. By bioinformatics analysis and knockdown or overexpression of DAB2, we found that DAB2 upregulated Yes-associated protein 1 (YAP1) transcriptional activity. Mechanistically, DAB2 served as a scaffold protein for integrin beta 3 (ITGB3) and SRC proto-oncogene non-receptor tyrosine kinase (SRC), facilitated the phosphorylation of SRC, promoted the small GTPase ras homolog family member A (RHOA) activation and phosphorylation of YAP1, and ultimately enhanced the YAP1 transcriptional activity. Conclusions Altogether, these findings indicated that DAB2 is a key mediator in STAT3–regulated translation of YAP1 and plays crucial roles in H pylori-mediated GC development. DAB2 might serve as a novel therapeutic target for GC.

Benefiting from the advantageous features of low manufacturing cost, inherent safety and resource renewability, aqueous Zn-ion batteries (AZIBs) are considered as one of the most promising candidates for energy storage systems. Unfortunately, problems of AZIBs such as cathode dissolution, Zn dendrite growth, and irreversible electrochemical side reactions have restricted the implementation for practical applications. Vanadium-based are deemed as hopeful cathode materials for AZIBs owing to diverse crystal structures and multiple valence states. Therefore, it is necessary to comprehensively summarize the advance facing vanadium-based cathodes and the corresponding progress to create roadmaps for the development of high-stability AZIBs. This review starts with a discussion of the storage and failure mechanisms of AZIBs and their related affects. Then, enormous up-to-date achievements of vanadium-based cathode materials are highlighted, including vanadium-based oxides and metal vanadium-based oxides. The challenges associated with the application of vanadium-based compounds in AZIBs are also highlighted, and effective strategies to overcome them are proposed. Finally, perspectives and directions on further optimizing vanadium-based cathode materials to improve the performance of AZIBs are discussed.

Abstract Scalable, high-capacity, and low-power computing architecture is the primary assurance for increasingly manifold and large-scale machine learning tasks. Traditional electronic artificial agents by conventional power-hungry processors have faced the issues of energy and scaling walls, hindering them from the sustainable performance improvement and iterative multi-task learning. Referring to another modality of light, photonic computing has been progressively applied in high-efficient neuromorphic systems. Here, we innovate a reconfigurable lifelong-learning optical neural network (L2ONN), for highly-integrated tens-of-task machine intelligence with elaborated algorithm-hardware co-design. Benefiting from the inherent sparsity and parallelism in massive photonic connections, L2ONN learns each single task by adaptively activating sparse photonic neuron connections in the coherent light field, while incrementally acquiring expertise on various tasks by gradually enlarging the activation. The multi-task optical features are parallelly processed by multi-spectrum representations allocated with different wavelengths. Extensive evaluations on free-space and on-chip architectures confirm that for the first time, L2ONN avoided the catastrophic forgetting issue of photonic computing, owning versatile skills on challenging tens-of-tasks (vision classification, voice recognition, medical diagnosis, etc.) with a single model. Particularly, L2ONN achieves more than an order of magnitude higher efficiency than the representative electronic artificial neural networks, and 14× larger capacity than existing optical neural networks while maintaining competitive performance on each individual task. The proposed photonic neuromorphic architecture points out a new form of lifelong learning scheme, permitting terminal/edge AI systems with light-speed efficiency and unprecedented scalability.

Volatile Organic Compounds (VOCs) are not only essential precursors for the formation of ozone and PM2.5, but also hazardous to human health and responsible for unpleasant odors. The pharmaceutical industry has become an important industrial source of VOCs due to China’s large emissions and complex emission chains. In total, 245 VOCs samples were collected and analyzed from 11 typical pharmaceutical companies in Zibo City of the North China Plain, in order to investigate the VOCs emission characteristics and odor impacts. The emission factor for the pharmaceutical industry was 7.97 ± 8.21 g/kg pharmaceuticals, while the main emission links were chimney emissions, equipment sealing leakage, and so on. Finally, considering both purifying efficiency and economic benefits, the multistage absorption (AB) method is most effective for VOCs concentrations below 100 mg/m3, while UV photo-oxygenation combined with adsorption (UVA) is more suitable for concentrations below 300 mg/m3. The Regenerative Thermal Oxidizer (RTO), Catalytic Oxidizer (CO), and Condensation + Adsorption (CA) technologies demonstrated greater stability and efficiency, particularly in the treatment of complex organic pollutants, highlighting their advantages in both VOCs and odor removal at higher concentrations.

Abstract Background As social networking sites (SNSs) with diverse functions gradually become an important social place for modern people, openness, as a personality trait that represents the willingness to consider diverse things, will be more likely to affect people’s cognitive and emotional experience (e.g., social anxiety) in social interactions. This study examined the relationship between openness and social anxiety and the underlying psychological mechanism in the internet age based on the cognitive-behavioral model of social anxiety. Methods This cross‑sectional survey study conducted a questionnaire survey of 522 college students from two provinces in China (191 male; age range 18–25; M = 20.76, SD = 1.34). Results The results showed that openness is negatively related to social anxiety. Self-evaluation and passive SNS use independently mediate the relationship between openness and social anxiety, respectively. Moreover, openness is associated with social anxiety both through the chain mediating roles of active SNS use and self-evaluation and through the chain mediating roles of passive SNS use and self-evaluation. Conclusions Openness is negatively associated with social anxiety, and the different ways of SNS use and self-evaluation are the underlying mechanisms. These results provide insights into the clinical treatment of social anxiety and how to benefit from online interactions.

Abstract Background Recent studies have shown that mesenchymal stem cell (MSC) therapy has potential therapeutic effects for patients with end-stage liver diseases. However, a consensus on the efficacy and safety of MSCs has not been reached. Methods A systemic literature review was conducted by searching the Cochrane Library and PubMed databases for articles that evaluated the impact of MSC therapy on the outcomes among patients with end-stage liver disease. Various parameters, including pre- and post-treatment model of end-stage liver disease (MELD) score, serum albumin (ALB), total bilirubin (TB), coagulation function, aminotransferase, and survival rate, were evaluated. Results This meta-analysis included a final total of 13 studies and 854 patients. The results indicated improved liver parameters following MSC therapy at different time points, including in terms of MELD score, TB level, and ALB level, compared with conventional treatment. Furthermore, the MSC treatment increased the overall survival rate among patients with liver cirrhosis and acute-on-chronic liver failure (ACLF). The changes in transaminase level and coagulation function differed between the different therapies at various post-treatment time points, indicating that MSC therapy provided no significant benefits in this regard. The further subgroup analysis stratified by liver background revealed that patients with ACLF benefit more from MSC therapy at most time points with improved liver function, including in terms of MELD score, TB level, and ALB level. In addition, no serious side effects or adverse events were reported following MSC therapy. Conclusions The meta-analysis results suggest that MSC therapy is safe and results in improved liver function and survival rates among patients with end-stage liver disease. The subgroup analysis stratified by liver background indicated that patients with ACLF benefit more from MSC therapy than patients with liver cirrhosis at most time points.

Difenoconazole-loaded (CS-DIF) microcapsules were synthesized by encapsulating difenoconazole into biocompatible chitosan. The physical and chemical properties indicated that the encapsulation and chemical loading rates were 85.58% and 61.98%, respectively. The microcapsules exhibited prominent controlled-release and surface stability performance. The cumulative release rate was only 33.6% in 168 h, and the contact angle decreased by 11.73° at 120 s compared with difenoconazole. The antifungal activity of the CS-DIF microcapsules against Curvularia lunata was confirmed through observations of colony growth, in vitro and in vivo inoculation, mycelium morphology, as well as DNA and protein leakage. The antioxidant enzyme activity of superoxide dismutase, peroxidase, and catalase decreased by 65.1%, 84.9%, and 69.7%, respectively, when Curvularia lunata was treated with 200 μg/mL microcapsules, compared with the control in 24 h. The enzymatic activity of polyphenol oxidase decreased by 323.8%. The reactive oxygen species contents of hydrogen peroxide and superoxide anions increased by 204.6% and 164%, respectively. Additionally, the soluble sugar and soluble protein contents decreased by 65.5% and 69.6%, respectively. These findings provided a novel approach to control the growth of C. lunata efficiently, laying a foundation for reducing the quantity and enhancing the efficiency of chemical pesticides. The CS-DIF microcapsules exhibited a strong inhibitory effect on fungus, effectively preventing and controlling leaf spot disease and showing potential for field applications. This study might be of great significance in ensuring plant protection strategies.

Abstract Background Human papillomavirus (HPV) has been proposed as a potential pathogenetic organism involved in prostate cancer (PCa), but the association between HPV infection and relevant genomic changes in PCa is poorly understood. Methods To evaluate the relationship between HPV genotypes and genomic alterations in PCa, HPV capture sequencing of DNA isolated from 59 Han Chinese PCa patients was performed using an Illumina HiSeq2500. Additionally, whole-exome sequencing of DNA from these 59 PCa tissue samples and matched normal tissues was carried out using the BGI DNBSEQ platform. HPV infection status and genotyping were determined, and the genetic disparities between HPV-positive and HPV-negative PCa were evaluated. Results The presence of the high-risk HPV genome was identified in 16.9% of our cohort, and HPV16 was the most frequent genotype detected. The overall mutational burden in HPV-positive and HPV-negative PCa was similar, with an average of 2.68/Mb versus 2.58/Mb, respectively, in the targeted whole-exome region. HPV-negative tumors showed a mutational spectrum concordant with published PCa analyses with enrichment for mutations in SPOP, FOXA1, and MED12. HPV-positive tumors showed more mutations in KMT2C, KMT2D and ERCC2. Copy number alterations per sample were comparable between the two groups. However, the significantly amplified or deleted regions of the two groups only partially overlapped. We identified amplifications in oncogenes, including FCGR2B and CCND1, and deletions of tumor suppressors, such as CCNC and RB1, only in HPV-negative tumors. HPV-positive tumors showed unique deletions of tumor suppressors such as NTRK1 and JAK1. Conclusions The genomic mutational landscape of PCa differs based on HPV infection status. This work adds evidence for the direct involvement of HPV in PCa etiology. Different genomic features render HPV-positive PCa a unique subpopulation that might benefit from virus-targeted therapy.

Objective: We sought to examine high-risk factors for severe tetanus, construct a nomogram model, and predict the risk probability of severe tetanus in adult patients to provide a theoretical basis for clinical intervention. Methods: A retrospective analysis was employed in this study, which enrolled 65 adult patients with tetanus diagnosed at the Second Affiliated Hospital of Hainan Medical University from January 2017 to September 2022. Study participants were divided into severe and mild groups based on the Ablett classification. The general data and laboratory markers of both groups were compared, and logistic regression analysis was used to screen for independent risk factors for severe tetanus. A nomogram prediction model was constructed, and receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA) were constructed and used to assess discrimination, calibration, and net benefit. Results: Of the 65 adults patients with tetanus, 28 were placed in the severe group and 37 were placed in the mild group. Univariate logistic regression analysis showed that there were statistically significant differences in the incubation period, time from disease onset to treatment, white blood cell count (WBC), neutrophil count (NEU), lymphocyte count (LYM), platelet count (PLT), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase level (LDH), myoglobin level (Mb), and aspartate aminotransferase (AST) level between the two groups (P 0.05). Multivariate analysis showed that NLR (odds ratio [OR] = 4.998, 95 % confidence interval [CI] = 1.154–21.649, P = 0.031), AST (OR = 1.074, 95 % CI = 1.007–1.146, P = 0.031), PLT (OR = 1.055, 95 % CI = 1.006–1.106, P = 0.027), and incubation period (OR = 0.597, 95 % CI = 0.423–0.843, P = 0.003) are independent risk factor for severe tetanus. A Nomogram for predicting Severe Tetanus (N-ST) prediction model was constructed based on variables in the multivariate analysis with P

Summary: Here, we present a protocol for generating LtCas12a protein recognizing distinct TTNA (N represented A, T, C, G) protospacer adjacent motif sequence. We describe steps for transforming and harvesting bacterial cells and protein purification including nickel affinity chromatography and dialysis. We then detail procedures for verification of LtCas12a with cis- and trans-cleavage activities.For complete details on the use and execution of this protocol, please refer to Chen et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

AbstractOf the 12 medicinal ginseng species, three species (Panax ginseng, P. quinquefolium, and P. notoginseng) are significant given their biological activities and hence are widely used around the world. These species have cardiovascular protection, improved immunomodulatory ability, antioxidant, anti-tumor, cholesterol-lowering, anti-inflammatory and other effects. Hence, such ginseng is used in various products (foods, health foods, daily necessities, cosmetics, etc.). However, ginseng cultivation causes replanting problems due to its allelopathic effects. This review provides a comprehensive insight into the allelopathic ginseng plant and analyzes the allelopathic effects on soil diseases and soil microorganisms for ginseng researchers. More in-depth research is needed to reveal the mechanisms of ginseng allelopathy.

Hepatic fibrosis is an important pathological manifestation of chronic schistosome infection. Patients with advanced schistosomiasis show varying degrees of abnormalities in liver fibrosis indicators and bilirubin metabolism. However, the relationship between hepatic fibrosis in schistosomiasis and dysregulated bilirubin metabolism remains unclear. In this study, we observed a positive correlation between total bilirubin levels and the levels of ALT, AST, LN, and CIV in patients with advanced schistosomiasis. Additionally, we established mouse models at different time points following S. japonicum infection. As the infection time increased, liver fibrosis escalated, while liver UGT1A1 consistently exhibited a low expression, indicating impaired glucuronidation of bilirubin metabolism in mice. In vitro experiments suggested that SEA may be a key inhibitor of hepatic UGT1A1 expression after schistosome infection. Furthermore, a high concentration of bilirubin activated the NF-κB signaling pathway in L-O2 cells in vitro. These findings suggested that the dysregulated glucuronidation of bilirubin caused by S. japonicum infection may play a significant role in schistosomiasis liver fibrosis through the NF-κB signaling pathway.

Surface decoration with cesium on the photocathode is an effective method to reduce surface barriers and promote electron emission. In this study, we investigated the changes in surface properties of AlGaN nanowire coated with Cs atoms using first-principle calculations. The N bridge site is the most stable site for a single atom deposition. As more Cs atoms are deposited on the surface, the average adsorption energy increases along with the weakened ionization of Cs adatoms. The Bader charge of surface Al and Ga atoms undertake significant changes in comparison with tiny alteration of N atoms, especially for Al atom with a decrease of 0.41 |e|/atom. The variation in surface work function reaches a maximum of 2.3 ∼ 2.5 eV at Cs coverage of 0.5 ∼ 0.75 ML, which can be attributed to the synergistic effect of dipole length and charge redistribution. The donor states underneath CBM induced by the orbital overlap of Al-p, Ga-p and Cs-d electrons accompanied by the downward band bending in the band structures. This work provides theoretical insight into the surface evolution of Cs-decorated AlGaN nanowires and offers guidance for the development of state-of-the-art nanostructured vacuum devices.

Abstract It is increasingly important to study the impact of environmental inhalation exposures on human health in natural or man-made disasters in civilian populations. The members of the World Trade Center Environmental Health Center (WTC EHC; WTC Survivors) had complex exposures to environmental disaster from the destruction of WTC towers and can serve to reveal the effects of WTC exposure on the entire spectrum of lung functions. We aimed to investigate the associations between complex WTC exposures and measures of spirometry and oscillometry in WTC Survivors and included 3605 patients enrolled between Oct 1, 2009 and Mar 31, 2018. We performed latent class analysis and identified five latent exposure groups. We applied linear and quantile regressions to estimate the exposure effects on the means and various quantiles of pre-bronchodilator (BD) % predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio, as well as the resistance at an oscillating frequency of 5 Hz (R5), frequency dependence of resistance R5–20, and reactance area (AX). Compared with Group 5, which had low or unknown exposure and was treated as the reference group, Group 1, the local workers with both acute and chronic exposures, had a lower median of % predicted FVC (−3.6; 95% CI: −5.4, −1.7) and higher (more abnormal) measures of AX at 10th quantile (0.77 cmH2O L–1 s; 95% CI: 0.41, 1.13) and 25th quantile (0.80 cmH2O L−1 s; 95% CI: 0.41, 1.20). Results suggested heterogeneous exposures to the WTC disaster had differential effects on the distributions of lung functions in the WTC Survivors. These findings could provide insights for future investigation of environmental disaster exposures.

Abstract Background Early diagnosis of lung adenocarcinoma (LUAD), one of the most common types of lung cancer, is very important to improve the prognosis of patients. The current methods can’t meet the requirements of early diagnosis. There is a pressing need to identify novel diagnostic biomarkers. Secretory proteins are the richest source for biomarker research. This study aimed to identify candidate secretory protein biomarkers for early diagnosis of LUAD by integrated bioinformatics analysis and clinical validation. Methods Differentially expressed genes (DEGs) of GSE31210, gene expression data of early stage of LUAD, were analyzed by GEO2R. Upregulated DEGs predicted to encode secreted proteins were obtained by taking the intersection of the DEGs list with the list of genes encoding secreted proteins predicted by the majority decision-based method (MDSEC). The expressions of the identified secreted proteins in the lung tissues of early-stage LUAD patients were further compared with the healthy control group in mRNA and protein levels by using the UALCAN database (TCGA and CPTAC). The selected proteins expressed in plasma were further validated by using Luminex technology. The diagnostic value of the screened proteins was evaluated by receiver operating characteristic (ROC) analysis. Cell counting kit-8 assay was carried out to investigate the proliferative effects of these screened proteins. Results A total of 2183 DEGs, including 1240 downregulated genes and 943 upregulated genes, were identified in the GSE31210. Of the upregulated genes, 199 genes were predicted to encode secreted proteins. After analysis using the UALCAN database, 16 molecules were selected for further clinical validation. Plasma concentrations of three proteins, Midkine (MDK), WAP four-disulfide core domain 2 (WFDC2), and C-X-C motif chemokine ligand 14 (CXCL14), were significantly higher in LUAD patients than in healthy donors. The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them. Overexpression of the three proteins enhanced the proliferation activity of A549 cells. Conclusions MDK, WFDC2, and CXCL14 were identified as candidate diagnostic biomarkers for early-stage LUAD and might also play vital roles in tumorigenesis.

Abstract Background This study aimed to evaluate the efficacy and safety of oral anticoagulants (OACs) in real-world elderly patients with comorbidities of stable coronary artery disease (SCAD) and atrial fibrillation (AF). Methods Elderly patients (aged ≥ 65 years old) diagnosed with SCAD and AF were consecutively recruited and grouped into patients with or without oral anticoagulant (OAC) treatment. Follow-up was performed for 5 years. Major adverse cardiac events (MACEs) were defined as a composite of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and systemic embolism. Major bleeding outcomes were defined as events that were type ≥ 3 based on the Bleeding Academic Research Consortium (BARC) criteria. The net clinical outcomes were defined as the combination of MACEs and bleeding of BARC type ≥ 3. Results A cohort of 832 eligible patients (78 ± 6.70 years) was included. Compared to the patients without OAC treatment (n = 531, 63.82%), the patients treated with OAC (n = 301, 36.18%) were much younger, had higher body mass index (BMI), and had lower prevalence of heart failure, chronic obstructive pulmonary disease (COPD), renal insufficiency, and previous myocardial infarction. During the follow-up of 5 years, compared to the patients without OAC treatment, patients with OAC had a significantly lower risk of MACEs (20.60% vs. 58.95%, adjusted HR: 0.21, 95% CI: 0.15–0.30, p

Abstract Objective Kirsten rat sarcoma viral oncogene homolog (KRAS) is an important driver gene of non‐small cell lung cancer (NSCLC). Despite a rapid progress achieved in the targeted therapy, chemotherapy remains the standard treatment option for patients with KRAS‐mutant NSCLC. This study aimed to assess real‐world data of Chinese patients with KRAS‐mutant NSCLC undergoing chemotherapy and/or immunotherapy. Methods KRAS mutational status was analyzed using next‐generation sequencing of 150,327 NSCLC patients from the Lung Cancer Big Data Precise Treatment Collaboration Group (LANDSCAPE) project (Cohort I). Treatment data were collected and analyzed retrospectively from 4348 NSCLC patients who were admitted to the Peking University Cancer Hospital and Institute between January 2009 and October 2020 (Cohort II). Results In Cohort I, 18,224 patients were detected with KRAS mutations (12.1%) of whom G12C (29.6%) was the most frequent subtype, followed by G12D (18.1%) and G12V (17.5%). In case of concomitant mutations, TP53 had the highest incidence of 33.6%, followed by EGFR (11.6%), STK11 (10.4%), KEAP1(6.2%), and CDKN2A (6.0%). Cohort II included 497 patients (11.4%) with KRAS mutations. In the first‐line chemotherapeutic analysis of Cohort II, patients benefited more from the pemetrexed/platinum (PP) regimen than the gemcitabine/platinum (GP) or taxanes/platinum (TP) regimen (median progression‐free survival [PFS], 6.4 vs. 4.9 vs. 5.6 months, hazard ratio [HR] = 0.65, 95% confidence interval [CI] 0.48–0.88, p = 0.033 and HR = 0.69, 95% CI 0.47–1.00, p = 0.05, respectively), with no significant difference when combined with bevacizumab. Regarding patients who received immune checkpoint inhibitors (ICIs), the objective response rate was 26% for a median PFS of 9.6 months (95% CI 6.16–13.03). Patients who received ICIs combined with chemotherapy had a significantly longer survival than monotherapy (median PFS, 13.9 vs. 5.2 months, HR = 0.59, 95% CI 0.35–0.99, p = 0.049). Conclusion KRAS is an important driver gene in NSCLC, compromising 12.1% in this study, and G12C was noted as the most common subtype. Patients with KRAS‐mutant NSCLC could benefit from pemetrexed‐based chemotherapy and ICIs.

Abstract Flexible stress sensors that can convert different forces into electrical signals show great potential for applications in wearable electronics and electronic skin. The integration of self‐healing capacity into stress‐sensing materials can boost their reliability, stability, and long‐term performance. There have been many reviews describing the progress of research on self‐healing stress sensors. However, most have typically investigated the self‐healing design separately from the sensing mechanism. The review focuses on how the latest advances in coupling stress‐sensing performance with dynamic chemistry balance self‐healing and sensing performance. Then, based on sensing structures and self‐healing dynamic bonds, the design strategies, and preparation methods of self‐healing sensors and their advantages and disadvantages in recent years are summarized in detail. It is anticipated that this work will provide insights and guidance for the future development of sensors with synergistically enhanced self‐healing and sensing properties and their application designs.

Stereo cameras can capture the rich image textures of a scene, while LiDAR can obtain accurate 3D coordinates of point clouds of a scene. They complement each other and can achieve comprehensive and accurate environment perception through data fusion. The primary step in data fusion is to establish the relative positional relationship between the stereo cameras and the 3D LiDAR, known as extrinsic calibration. Existing methods establish the camera–LiDAR relationship by constraints of the correspondence between different planes in the images and point clouds. However, these methods depend on the planes and ignore the multipath-closure constraint among the camera–LiDAR–camera sensors, resulting in poor robustness and accuracy of the extrinsic calibration. This paper proposes a trihedron as the calibration object to effectively establish various coplanar and collinear constraints between stereo cameras and 3D LiDAR. With the various constraints, the multipath-closure constraint between the three sensors is further formulated for the extrinsic calibration. Firstly, the coplanar and collinear constraints between the camera–LiDAR–camera are built using the trihedron calibration object. Then, robust and accurate coplanar constraint information is extracted through iterative maximum a posteriori (MAP) estimation. Finally, a multipath-closure extrinsic calibration method for multi-sensor systems is developed with structurally mutual validation between the cameras and the LiDAR. Extensive experiments are conducted on simulation data with different noise levels and a large amount of real data to validate the accuracy and robustness of the proposed calibration algorithm.

Over the past decades, ecological restoration initiatives in China have made great progress in restoring degraded forests and increasing vegetation coverage, yet the carbon sequestration effects of these initiatives in the context of climate change are not clear. In this study, we assessed the effects of vegetation restoration on gross primary production (GPP) in China’s forestry engineering areas, where large-scale vegetation restoration programmes were launched, during 2001–2020 by disentangling the respective roles of land cover change (LCC), CO _2 fertilization, and climate changes using a two-leaf light use efficiency model. We found that LCC attributed by the vegetation restoration dominantly accelerated the increase of GPP in seven out of the eight areas, and CO _2 fertilization played a near-equivalent role in all areas. By contrast, the changes in different climate factors contributed to GPP variations diversely. The solar radiation variation greatly inhibited the vegetation GPP over time in seven out of these areas, and the changes in air temperature and vapor pressure deficit regulated GPP inter-annual variations without clear trends in all areas. This study advances our understanding of the contribution of China’s afforestation on its forest GPP in a changing climate, which may help to better manage forests to tackle the challenge of the climate crisis in the future.

In the extreme alpine climate of the Qinghai-Tibet Plateau (QTP), plant growth and reproduction are limited by extremely cold temperatures, low soil moisture, and scarce nutrient availability. The root-associated microbiome indirectly promotes plant growth and plays a role in the fitness of plants on the QTP, particularly in Tibetan medicinal plants. Despite the importance of the root-associated microbiome, little is known about the root zone. This study used high-throughput sequencing to investigate two medicinal Meconopsis plants, M. horridula and M. integrifolia, to determine whether habitat or plant identity had a more significant impact on the microbial composition of the roots. The fungal sequences were obtained using ITS-1 and ITS-2, and bacterial sequences were obtained using 16S rRNA. Different microbial patterns were observed in the microbial compositions of fungi and bacteria in the root zones of two Meconopsis plants. In contrast to bacteria, which were not significantly impacted by plant identity or habitat, the fungi in the root zone were significantly impacted by plant identity, but not habitat. In addition, the synergistic effect was more significant than the antagonistic effect in the correlation between fungi and bacteria in the root zone soil. The fungal structure was influenced by total nitrogen and pH, whereas the structure of bacterial communities was influenced by soil moisture and organic matter. Plant identity had a greater influence on fungal structure than habitat in two Meconopsis plants. The dissimilarity of fungal communities suggests that more attention should be paid to fungi-plant interactions.

This study developed and evaluated a tailored nomogram to predict the potential occurrence of early lower extremity deep vein thrombosis (LDVT) in patients receiving thrombolytic therapy. We performed several logistic analyses on the training cohort and created a corresponding nomogram to forecast early LDVT. The classification accuracy and the accuracy of predicted probabilities of the multiple logistic regression model were evaluated using area under the curve (AUC) and the calibration graph method. According to the multivariate logistic regression model homocysteine, previous history of hypertension and atrial fibrillation, indirect bilirubin, age, and sex was identified as independent determinants of early LDVT. The nomogram was constructed using these variables. The calibration plots showed a good agreement between the predicted and observed LDVT possibilities in the training and validation cohorts with AUCs being 0.833 (95% CI: 0.774-0.892) and 0.907 (95% CI: 0.801-1.000), respectively. Our nomogram offers clinicians a tool for predicting the individual risk of LDVT in the early stage of acute ischemic stroke in patients receiving thrombolytic therapy, which could lead to early intervention.

Background: Bisphenols and phthalates are high production volume chemicals used as additives in a variety of plastic consumer products leading to near ubiquitous human exposure. These chemicals have established endocrine disrupting properties and have been linked to a range of adverse reproductive and developmental outcomes. Here, we investigated exposure in relation to fetal growth. Methods: Participants included 855 mother-fetal pairs enrolled in the population-based New York University Children’s Health and Environment Study (NYU CHES). Bisphenols and phthalates were measured in maternal urine collected repeatedly during pregnancy. Analyses included 15 phthalate metabolites and 2 bisphenols that were detected in 50 % of participants or more. Fetal biometry data were extracted from electronic ultrasonography records and estimated fetal weight (EFW) was predicted for all fetuses at 20, 30, and 36 weeks gestation. We used quantile regression adjusted for covariates to model exposure-outcome relations across percentiles of fetal weight at each gestational timepoint. We examined sex differences using stratified models. Results: Few statistically significant associations were observed across chemicals, gestational time periods, percentiles, and sexes. However, within gestational timepoints, we found that among females, the molar sums of the phthalates DiNP and DnOP were generally associated with decreases in EFW among smaller babies and increases in EFW among larger babies. Among males, the opposite trend was observed. However, confidence intervals were generally wide at the tails of the distribution. Conclusion: In this sample, exposure to bisphenols and phthalates was associated with small sex-specific shifts in fetal growth; however, few associations were observed at the median of fetal weight and confidence intervals in the tails were wide. Findings were strongest for DiNP and DnOP, which are increasingly used as replacements for DEHP, supporting the need for future research on these contaminants.

Abstract Background Despite strong antiplatelet therapy with ticagrelor, serious ischemic events still occur in patients with acute coronary syndrome (ACS). The predictability of platelet reactivity to the residual risk of ischemic events during ticagrelor treatment remains uncertain. Objectives We aimed to investigate the predictability of the thromboelastography (TEG)-measured adenosine disphosphate (ADP)-induced platelet inhibition rate (ADP%) to the ischemic events in ticagrelor-treated patients with ACS. Methods A cohort of ticagrelor-treated patients with ACS were consecutively recruited. ADP% was measured by TEG after 3 days of ticagrelor maintenance treatment. The primary ischemic event was defined as rehospitalization for unstable angina (UA) within 1 year, and the secondary ischemic event was a composite of the primary ischemic event plus all-cause death, nonfatal myocardial infarction (MI), stent thrombosis, stroke, and unplanned revascularization within 1 year. Results A total of 751 eligible patients with ACS were included in the analysis, with 336 patients randomly assigned to the derivation group and 415 to the validation group. The overall rates of primary and secondary ischemic events were 14.51% (n = 109) and 16.91% (n = 127), respectively. Compared to the patients without ischemic events, those with ischemic events had a significantly lower ADP% both in the derivation group (for primary ischemic events: 66.05% vs. 92.80%, p

Yucca has abundant amounts of polyphenolics, steroidal saponins, and resveratrol and its extract can be used as a feed additive in the animal husbandry, which might contribute to the improvement in the growth and productivity in rabbit production. Hence, the current study aimed to examine the effects of yucca extract alone and in combination with Clostridium butyricum (C. butyricum) on growth performance, nutrient digestibility, muscle quality, and intestinal development of weaned rabbits. A total of 400 40-day-old male rabbits were randomly divided into 4 treatment groups for 40 days: (1) basal diet group, (2) basal diet contained 300 mg/kg of yucca extract, (3) basal diet supplemented with 0.4 × 1010 colony-forming units (CFU)/kg of C. butyricum, and (4) the blend of 0.4 × 1010/kg CFU of C. butyricum and 300 mg/kg of yucca extract. The supplementation of yucca extract or C. butyricum increased body weight (BW) of rabbits depending on the age, the combined addition of yucca extract and C. butyricum significantly increased BW, weight gain, and feed intake, companying with increased the digestibility of crud protein, fiber, phosphorous, and calcium as compared to control diet (P < 0.05). Furthermore, yucca extract and C. butyricum treatment alone and in combination notably increased the villus high and the ratio of villus high to crypt depth of rabbits (P < 0.05). The combined supplementation of yucca extract and C. butyricum altered the intestinal microbiota of rabbits, as demonstrated by increased the abundance of beneficial bacteria Ruminococcaceae and decreased the proportion of pathogenic bacteria such as Pseudomonadaceae and S24-7. In addition, the rabbits fed the diet with yucca extract and the blend of yucca extract and C. butyricum had significantly increased pH45min, decreased pressing loss, drip loss, and shears force when compared with rabbits received control diet (P < 0.05). Diet with C. butyricum or its mixture with yucca extract increased the fat content of meat, while the combined addition of yucca extract and C. butyricum declined the content of fiber in meat (P < 0.05). Collectively, the combined use of yucca extract and C. butyricum showed better results on growth performance and meat quality, which might be closely associated with the improved intestinal development and cecal microflora of the rabbits.

Abstract The emerging use of laser irradiation in synthesis smartly bridges “nanotechnology” and “light”, and has attracted enormous attention as an efficient synthetic methodology for versatile nanomaterials toward electrochemical energy storage and conversion devices (ESCDs). In this review, recent contributions and progress regarding the laser‐induced nanomaterials for ESCDs are comprehensively summarized, with a special focus on their practical utilization in rechargeable batteries, supercapacitors and electrocatalysis. The laser‐induced synthesis strategies and corresponding mechanisms involved in nanoarchitecture generation/regulation, including pulsed laser deposition and laser irradiation in liquid, are also discussed in detail. With the in‐depth insights into the mechanisms and revolutionary advancements of laser irradiation technology, the comprehensive performances of ESCDs have been strikingly optimized. Finally, the existing challenges and future directions in this booming research field are outlined. This review will exert the significant guidance for future design and purposeful fabrication of advanced laser‐induced nanomaterials with appealing properties for advanced ESCDs and beyond.

Background: Small cell lung cancer (SCLC) transformation had previously been reported mainly in epidermal growth factor receptor (EGFR) mutant adenocarcinoma. However, the underlying genomic profile remains unclear. Our study aimed to find the evolution and genotypic characteristic of SCLC transformation. Methods: Thirty-one SCLC transformation patients who were initially diagnosed as non-small cell lung cancer (NSCLC) patients were included. Whole exome sequencing (WES) of both primary and transformed re-biopsy lesions was conducted on 12 patients. Clinical characteristics were analyzed using R software (v.3.6.1). Results: Our study included 31 patients, of whom, three had lung squamous cell carcinoma, 6 patients did not carry EGFR mutations, and 30 patients received chemotherapy for SCLCs. The disease control rate (DCR) was 96.7%, and the median progression-free survival (PFS) was 4.03 months. The median time to transformation was 33.07 months, and the median overall survival (OS) was 62.08 months. Somatic mutation analysis showed that besides TP53, RB1, and EGFR, there was a high occurrence of mutations to CSMD3 and ADAMTS19, especially in the EGFR-wild type (EGFR-wt) group. Concerning mutational signature, the EGFR-mutant (EGFR-mut) transformed group favored an apolipoprotein B (APOBEC) mRNA editing catalytic polypeptide-like-associated mutation pattern (P = 0.16). DNA damage repair (DDR)-related signatures were significantly enriched in the EGFR-wt transformed group (P = 0.034). Additionally, clonal evolution analysis revealed that all patients had the same main trunk genes in the phylogenetic tree. Transformed SCLCs are not sensitive to immunotherapy, possibly due to increased tumor heterogeneity. Conclusions: Our results indicate that the EGFR-wt patients could also transform to SCLCs, but they have different genetic features with EGFR-mut patients. SCLC-transformed patients respond to classical chemotherapy and have a better prognosis than those with classical SCLCs.

Background Osteogenic differentiation of aortic valve interstitial cells (AVICs) plays a key role in the calcific aortic valve disease progression. Extracellular vesicles (EVs)-derived from M1-polarized macrophages (M1-EVs) orchestrated intercellular communication by delivering non-coding RNAs such as tRNA-derived small RNAs (tsRNAs) is crucial for cardiovascular disease. However, the role and mechanism of M1-EVs tsRNAs in osteogenic differentiation of AVICs remains largely unclear. Methods M1-EVs and PBS treated-RAW 264.7 cell-derived EVs (NC-EVs) were incubated with AVICs and subjected to small RNA sequencing. Candidate tsRNA in M1-EVs was silenced to explore their effects on AVIC osteogenic differentiation and mitophagy. Results DiI-labeled M1-EVs were internalized by AVICs, resulting in significantly increased calcium nodule formation and expression of osteogenesis-related genes in AVICs, including RUNX2, BMP2, osteopontin, and SPP1, compared with NC-EVs. Small RNA sequencing revealed that 17 tsRNAs were significantly up-regulated such as tsRNA-5006c, while 28 tsRNAs were significantly down-regulated in M1-EVs compared with NC-EVs. Intriguingly, tsRNA-5006c-deleted M1-EVs treatment significantly reduced calcium nodule formation and expression of osteogenesis-related genes in AVICs relative to control group. Moreover, target genes of tsRNA-5006c were mainly involved in autophagy-related signaling pathways, such as MAPK, Ras, Wnt, and Hippo signaling pathway. Hallmarks of mitophagy activation in AVICs including mitophagosome formation, TMRM fluorescence, expression of LC3-II, BINP3, and PGC1α, were significantly elevated in the M1-EVs group compared with NC-EVs group, whereas M1-EVs tsRNA-5006c inhibitor led to a significant reduction in these indicators. Conclusion M1-EVs carried tsRNA-5006c regulates AVIC osteogenic differentiation from the perspective of mitophagy, and we provide a new target for the prevention and treatment of aortic valve calcification.

Abstract The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example, Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals, and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion. Furthermore, many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers. Therefore, it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs. In this review, we focus on research progress in the field of immune checkpoints based on three topics: (1) immune checkpoint targets and pathways, (2) development of novel immune checkpoint-based drugs, and (3) application of immune checkpoints in the development of TCMs.

Population growth and urban expansion have led to increased demand for buildings. Optimizing the building façade design, using integrated photovoltaic (PV) shading and vertical farming (VF) can reduce building energy consumption while ensuring a partial food supply. However, the importance and prevalence of productive façades have not received significant attention. Furthermore, few studies have focused on the impact of productive façades on both indoor and outdoor environmental qualities. Therefore, this study aimed to explore the potential of integrating productive façades with residential façades in high-density cities. A typical community in Guangzhou, China was investigated. Thermal comfort, light comfort, electricity production, and crop yield were considered, and the optimal façade configuration was chosen from the established 146-model library. The integrated module can effectively improve the indoor lighting and thermal comfort of residential buildings. The module also mitigates the outdoor thermal environment to a certain extent, meeting 6.3–10.3% and 7.6–9.6% of the annual electricity and vegetable demands, respectively, in residential communities. This study can guide other densely populated cities with subtropical climates to advance the research and construction of productive façades, improving occupant comfort, reducing energy consumption, and mitigating food security and urban climate change issues.

Si, as a highly competitive anode material for lithium‐ion batteries (LIBs), has gained enormous commercial interests due to its high theoretical capacity, low delithiation potential, and natural abundance. However, its poor cycling stability/electron conductivity seriously restrains its practical applications. To address this problem well, herein, a scalable spray‐drying method is explored to construct an ultrahigh stable 3D Si‐based composite (designed as Si@C‐MX) anode, where the Ti3C2Tx MXene nanosheets (NSs) crump the nano‐Si coated uniformly with an ultrathin carbon layer. Synergistically, the coating carbon layer and Ti3C2Tx NSs as the conductive elastomer constrain/buffer the volume expansion of nano‐Si, avoid direct contact with the electrolyte, build a continuous electronic network for rapid electron transport, and meanwhile improve mechanical properties of the electrodes. Thanks to the dual protection (i.e., carbon coating and Ti3C2Tx NSs) strategy, the resultant Si@C‐MX anode exhibits large reversible capacities, superior rate capability, and long‐duration cycle stability. Additionally, the Si@C‐MX‐based full batteries delivered an energy density of 371.8 Wh kg−1 based on the whole device at 123.9 W kg−1 and a desirable capacity retention with cycling, which convincingly highlights its promising application in advanced LIBs.

[This corrects the article DOI: 10.1371/journal.ppat.1007416.].

As we know, harmonic noises widely exist in industrial fields and have a crucial impact on the computational accuracy of the zeroing neural network (ZNN) model. For tackling this issue, by combining the dynamics of harmonic signals, two harmonic noise-tolerant ZNN (HNTZNN) models are designed for the dynamic matrix pseudoinversion. In the design of HNTZNN models, an adaptive compensation term is adopted to eliminate the influence of harmonic noises, and a Li activation function is introduced to further improve the convergence rate. The convergence and robustness to harmonic noises of the proposed HNTZNN models are proved through theoretical analyses. Besides, compared with the ZNN model without adaptive compensation term, the HNTZNN models are more effective for tacking the problem of dynamic matrix pseudoinverse under harmonic noises environments. Moreover, HNTZNN models are further applied to the kinematic control of a four-link planar robot manipulator under harmonic noises. In general, the experimental results verify the effectiveness, superiority, and broad application prospect of the models.

BackgroundThe efficacy and safety of antithrombotic treatment with oral anticoagulants (OACs) in elderly patients with comorbidities of acute coronary syndrome (ACS) and atrial fibrillation (AF) are unclear.MethodsA cohort of hospitalized elderly patients (≥65 years of age) diagnosed with ACS and AF and treated with oral antithrombotic agents were consecutively recruited. Follow-up was performed for at least 1 year. Major adverse cardiac events (MACEs) were defined as a composite of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and systemic embolism. The safety outcomes of bleeding were defined according to the Bleeding Academic Research Consortium (BARC) criteria.ResultsA cohort of 548 eligible patients (76 ± 6.6 years) was analyzed. Compared to the patients with OAC treatment (n = 184, 33.6%), patients treated without OAC (n = 364, 66.4%) were older, had a lower prevalence of persistent AF and unstable angina (UA), and more often presented with paroxysmal AF, acute myocardial infarction (AMI), stent implantation and dual antiplatelet therapy (DAPT). Compared to the patients without OAC treatment (n = 364, 66.4%), patients treated with OAC (n = 184, 33.6%) had a lower risk of MACEs at both the 1-year (4.3 vs. 15.1%, adjusted HR: 0.34, 95% CI: 0.15–0.80, p = 0.014) and 5-year (17.5 vs. 48.4%, adjusted HR: 0.36, 95% CI: 0.19–0.67, p = 0.001) follow-up. No significant difference was observed for bleeding events of BARC ≥2 between the groups (8.0 vs. 9.0%, adjusted HR: 1.17, 95% CI: 0.58–2.34, p = 0.667). Compared with warfarin-treated patients, the non-vitamin K antagonist oral anticoagulant-treated patients had lower risks of all-cause mortality (2.1 vs. 9.5%, HR: 0.18, 95% CI: 0.03–0.98, p = 0.047) and bleeding events of BARC ≥ 3 (2.1 vs. 4.8%, HR: 0.14, 95% CI: 0.02–1.10, p = 0.062).ConclusionsAntithrombotic therapy with OACs in elderly patients with ACS and AF was associated with a lower risk of ischemic events without an increase in bleeding events. In real-world practice, the clinical awareness of anticoagulation treatments in elderly patients with ACS and AF needs to be strengthened.

Strong self-healing materials with high healing efficiency are of great use in many fields but their fabrication is extremely challenging. Here, the authors present a robust self-healing material by incorporating high density noncovalent bonds at the interfaces between dentritic tannic acid-modified tungsten disulfide nanosheets and a polyurethane matrix to collectively produce a strong interfacial interaction.