Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability.

The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1ß that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability.

Identification of an HLA-A*11:01-restricted neoepitope of mutant PIK3CA and its specific T cell receptors for cancer immunotherapy targeting hotspot driver mutations.

Hotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy.

A chitosan-based antibacterial hydrogel with injectable and self-healing capabilities.

The presence of bacteria directly affects wound healing. Chitosan-based hydrogel biomaterials are a solution as they offer advantages for wound-healing applications due to their strong antimicrobial properties. Here, a double-cross-linking chitosan-based hydrogel with antibacterial, self-healing, and injectable properties is reported. Thiolated chitosan was successfully prepared, and the thiolated chitosan molecules were cross-linked by Ag-S coordination to form a supramolecular hydrogel. Subsequently, the amine groups in the thiolated chitosan covalently cross-linked with genipin to further promote hydrogel formation. In vitro experimental results indicate that hydrogel can release Ag+ over an extended time, achieving an antibacterial rate of over 99% against Escherichia coli and Staphylococcus aureus. Due to the reversible and dynamic feature of Ag-S coordination, an antibacterial hydrogel exhibited injectable and self-healing capabilities. Additionally, the hydrogel showed excellent biocompatibility and biodegradability. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00211-z.

Changes in the bacterial communities of Harmonia axyridis (Coleoptera: Coccinellidae) in response to long-term cold storage and progressive loss of egg viability in cold-stored beetles.

Bacteria have a profound influence on life history and reproduction of numerous insects, while the associations between hosts and bacteria are substantially influenced by environmental pressures. Cold storage is crucial for extending the shelf life of insects used as tools for biological control, but mostly causes detrimental effects. In this study, we observed a great decrease in egg hatch rate of cold-stored Harmonia axyridis during the later oviposition periods. Furthermore, most eggs produced by their F1 offspring exhibited complete loss of hatchability. We hypothesized that long-term exposure to cold may greatly alter the bacterial community within the reproductive tracts of H. axyridis, which may be an important factor contributing to the loss of egg viability. Through sequencing of the 16S rRNA gene, we discovered considerable changes in the bacterial structure within the reproductive tracts of female cold-stored beetles (LCS_F) compared to non-stored beetles (Control_F), with a notable increase in unclassified_f_Enterobacteriaceae in LCS_F. Furthermore, in accordance with the change of egg hatchability, we observed a slight variation in the microbial community of eggs produced by cold-stored beetles in early (Egg_E) and later (Egg_L) oviposition periods as well as in eggs produced by their F1 offspring (Egg_F1). Functional predictions of the microbial communities revealed a significant decrease in the relative abundance of substance dependence pathway in LCS_F. Moreover, this pathway exhibited relatively lower abundance levels in both Egg_L and Egg_F1 compared to Egg_E. These findings validate that long-term cold storage can greatly modify the bacterial composition within H. axyridis, thereby expanding our understanding of the intricate bacteria-insect host interactions.

Microbial production of branched chain amino acids: Advances and perspectives.

Branched-chain amino acids (BCAAs) such as L-valine, L-leucine, and L-isoleucine are widely used in food and feed. To comply with sustainable development goals, commercial production of BCAAs has been completely replaced with microbial fermentation. However, the efficient production of BCAAs by microorganisms remains a serious challenge due to their staggered metabolic networks and cell growth. To overcome these difficulties, systemic metabolic engineering has emerged as an effective and feasible strategy for the biosynthesis of BCAA. This review firstly summarizes the research advances in the microbial synthesis of BCAAs and representative engineering strategies. Second, systematic methods, such as high-throughput screening, adaptive laboratory evolution, and omics analysis, can be used to analyses the synthesis of BCAAs at the whole-cell level and further improve the titer of target chemicals. Finally, new tools and engineering strategies that may increase the production output and development direction of the microbial production of BCAAs are discussed.

Integrated analysis of single-cell and bulk RNA sequencing data reveals the association between hypoxic tumor cells and exhausted T cells in predicting immune therapy response.

Continuous stimulation of tumor neoantigens and various cytokines in the tumor microenvironment leads to T cell dysfunction, but the specific mechanisms by which these key factors are distributed among different cell subpopulations and how they affect patient outcomes and treatment response are incompletely characterized. By integrating single-cell and bulk sequencing data of non-small cell lung cancer patients, we constructed a clinical outcome-associated T cell exhaustion signature. We discovered a significant association between the T cell exhaustion state and tumor cell hypoxia. Hypoxic malignant cells were significantly correlated with the proportion of exhausted T cells, and they co-occurred in patients at advanced stage. By analyzing the ligand-receptor interactions between these two cell states, we observed that T cells were recruited towards tumor cells through production of chemokines such as CXCL16-CXCR6 axis and CCL3/CCL4/CCL5-CCR5 axis. Based on 15 immune checkpoint blockade (ICB)-treatment cohorts, we constructed an interaction signature that can be used to predict the response to immune checkpoint blockade therapy. Among genes composed of the signature, CXCR6 alone has similarly high prediction efficacy (Area Under Curve (AUC) = 1, 0.89 and 0.73 for GSE126044, GSE135222 and GSE93157, respectively) with the signature and thus could serve as a potential biomarker for predicting immunotherapy response. Together, we have discovered and validated a significant association between exhausted T cells and hypoxic malignant cells, elucidating key interaction factors that significantly associated with response to immunotherapy.

Canola bee pollen is an effective artificial diet additive for improving larval development of predatory coccinellids: a lesson from Harmonia axyridis.

BACKGROUND: Pollen is a common plant-derived food source for predatory ladybird beetles under field conditions, yet the potential for pollen to improve the quality of artificial diets remains largely unexplored. In this study, we developed three pollen diets by incorporating varying proportions of canola bee pollen (7.5%, 15.0% and 22.5% with 2.5%, 5.0%, and 7.5% of water, respectively) into a conventional diet. The feeding efficiency of Harmonia axyridis, an omnivorous predator, was evaluated and compared on three pollen diets, a conventional nonpollen diet and pea aphids. RESULTS: The larvae fed a medium or high pollen diet exhibited significantly higher survival in the 4th instar, pupa and adult stages than those fed a nonpollen diet. These larvae also developed into significantly heavier adults, and their survival rates in adulthood were comparable to those fed pea aphids. Specifically, we revealed the underlying mechanisms through which a high pollen diet enhances pupal development. Consumption of high pollen diet versus nonpollen diet resulted not only in a significant decrease in pupal glycogen content, but also an increase in adult lipid content. Both diet treatments induced similar changes in carbohydrate and glycogen content compared to the aphid diet while exhibiting different alterations in pupal protein content and adult lipid content. Furthermore, the transcriptome analysis revealed that the nutrient metabolism, immune response, and cuticle development pathways were predominantly enriched among the differentially expressed genes (DEGs). CONCLUSION: Canola bee pollen offers diverse advantages in terms of rearing H. axyridis larvae with an artificial diet, which will advance the development of effective diets for predaceous coccinellids. © 2024 Society of Chemical Industry.

The Microscopic Morphology of Mouthparts and Their Sensilla in the Mycophagous Ladybeetle Illeis chinensis (Coleoptera: Coccinellidae).

The morphological diversity of insect mouthparts is closely related to changes in food sources and diets. Research into the structures of insect mouthparts may help to establish a fundamental basis for a better understanding of insect feeding mechanisms. In this study, we examined the fine morphology of the mouthparts of Illeis chinensis using scanning electron microscopy. We paid particular attention to the types, quantities, and distribution of sensilla on the mouthparts. Our results showed that the basic components of the mouthparts of I. chinensis are the same as those in other lady beetles, i.e., the labrum, mandible, maxillae, labium, and hypopharynx. We also found structural specialization indicating adaptation to fungal feeding. On the mouthparts, there are eight kinds of sensilla and two kinds of glandular structures, including sensilla chaetica, sensilla basiconica, sensilla styloconica, sensilla coeloconica, sensilla campaniformia, sensilla placodea, sensilla digitiformia, Böhm bristles, perforated plates, and cuticular pores. This is the first time that sensilla digitiformia has been reported in ladybirds. Finally, variations in mouthparts among ladybirds with differing diets, as well as the putative functions of each of the mouthparts and sensilla, were discussed. This research can provide a reference for understanding the functions of the mouthparts in ladybird feeding behavior and thereby contribute to the development of precise insect behavior regulation and management strategies.

Developmental potency of human ES cell-derived mesenchymal stem cells revealed in mouse embryos following blastocyst injection.

Mesenchymal stem cells (MSCs) are present in almost all the tissues in the body, critical for their homeostasis and regeneration. However, the stemness of MSCs is mainly an in vitro observation, and lacking exclusive markers for endogenous MSCs makes it difficult to study the multipotency of MSCs in vivo, especially for human MSCs. To address this hurdle, we injected GFP-tagged human embryonic stem cell (hESC)-derived MSCs (EMSCs) into mouse blastocysts. EMSCs survived well and penetrated both the inner cell mass and trophectoderm, correlating to the higher anti-apoptotic capability of EMSCs than hESCs. Injected EMSCs contributed to skeletal, dermal, and extraembryonic tissues in the resultant chimera and partially rescued skeletal defects in Sox9+/- mouse fetuses. Thus, this study provides evidence for the stemness and developmental capability of human MSCs through chimerization with the mouse blastocyst, serving as a model for studying human mesenchymal and skeletal development.

Effects of copy number variations on longevity in late-onset Alzheimer's disease patients: insights from a causality network analysis.

Alzheimer's disease (AD), particularly late-onset Alzheimer's disease (LOAD), is a prevalent form of dementia that significantly affects patients' cognitive and behavioral capacities and longevity. Although approximately 70 genetic risk factors linked with AD have been identified, their influence on patient longevity remains unclear. Further, recent studies have associated copy number variations (CNVs) with the longevity of healthy individuals and immune-related pathways in AD patients. This study aims to investigate the role of CNVs on the longevity of AD patients by integrating the Whole Genome Sequencing (WGS) and transcriptomics data from the Religious Orders Study/Memory and Aging Project (ROSMAP) cohort through causality network inference. Our comprehensive analysis led to the construction of a CNV-Gene-Age of Death (AOD) causality network. We successfully identified three key CNVs (DEL5006, mCNV14192, and DUP42180) and seven AD-longevity causal genes (PLGRKT, TLR1, PLAU, CALB2, SYTL2, OTOF, and NT5DC1) impacting AD patient longevity, independent of disease severity. This outcome emphasizes the potential role of plasminogen activation and chemotaxis in longevity. We propose several hypotheses regarding the role of identified CNVs and the plasminogen system on patient longevity. However, experimental validation is required to further corroborate these findings and uncover precise mechanisms. Despite these limitations, our study offers promising insights into the genetic influence on AD patient longevity and contributes to paving the way for potential therapeutic interventions.

Prediction factors and clinical significance of different types of hemorrhagic transformation after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) in acute ischemic stroke seriously affects the prognosis of patients. This study aimed to investigate the risk factors of different types of HT and their correlation with prognosis after IVT. METHODS: Based on the CASE II registry, we included patients with acute ischemic stroke who received IVT within 4.5 h of onset. HT was further divided into hemorrhagic infarction (HI) and parenchymal hemorrhage (PH). Poor outcome was defined as a modified Rankin Scale (mRS) score of 3-6 at 3 months. Multivariate logistic regression analysis was used to determine the independent influencing factors of HT subtypes and clinical outcome. RESULTS: Among 13108 included patients, 541 (4.1%) developed HI and 440 (3.4%) developed PH. In multivariate analysis, age (OR 1.038, 95% CI 1.028 to 1.049, p < 0.001), atrial fibrillation (OR 1.446, 95% CI 1.141 to 1.943, p = 0.002), baseline diastolic pressure (OR 1.012, 95% CI 1.004 to 1.020, p = 0.005), baseline NIHSS score (OR 1.060, 95% CI 1.049 to 1.071, p < 0.001) and onset to treatment time (OR 1.002, 95% CI 1.000 to 1.004, p = 0.020) independently predicted PH after IVT. In the patients with HT, PH (OR 3.611, 95% CI 2.540 to 5.134, p < 0.001) and remote hemorrhage (OR 1.579, 95% CI 1.115 to 2.235, p = 0.010) were independently related to poor outcome. CONCLUSIONS: Different types of HT after IVT had different risk factors and clinical significance. The occurrence of PH and remote hemorrhage independently increased the risk of poor outcome.

The Expression of LDL-R in CD8+ T Cells Serves as an Early Assessment Parameter for the Production of TCR-T Cells.

BACKGROUND/AIM: The quantity and the phenotypes of desired T cell receptor engineered T (TCR-T) cells in the final cell product determine their in vivo anti-tumor efficacy. Optimization of key steps in the TCR-T cell production process, such as T cell activation, has been shown to improve cell quality. MATERIALS AND METHODS: Using a modified TCR (mTCR) derived from mice transducing PBMCs, we assessed the proportions of low-density lipoprotein receptor (LDL-R) and mTCR expressing cells under the various activation conditions of CD3/CD28-Dynabeads or OKT3 via flow cytometry. RESULTS: We demonstrate that the proportion of T cells expressing LDL-R post activation is positively correlated with the percentage of mTCR+CD8+ T cells with their less differentiated subtypes in the final product. In addition, we show that shifting the CD3/CD28-Dynabeads activation duration from a typical 48 h to 24 h can significantly increase the production of the desired mTCR+CD8+ T cells. Importantly, the percentages of TCR-T cells with less-differentiated phenotypes, namely mTCR central memory T cells (TCM), were found to be preserved with markedly higher efficiency when T cell activation was optimized. CONCLUSION: Our findings suggest that the proportion of LDL-R+ T cells may serve as an early assessment parameter for evaluating TCR-T cell quality, possibly facilitating the functional and economical improvement of current adoptive therapy.

A Systematic Stereo Camera Calibration Strategy: Leveraging Latin Hypercube Sampling and 2k Full-Factorial Design of Experiment Methods.

This research aimed to optimize the camera calibration process by identifying the optimal distance and angle for capturing checkered board images, with a specific focus on understanding the factors that influence the reprojection error (ϵRP). The objective was to improve calibration efficiency by exploring the impacts of distance and orientation factors and the feasibility of independently manipulating these factors. The study employed Zhang's camera calibration method, along with the 2k full-factorial analysis method and the Latin Hypercube Sampling (LHS) method, to identify the optimal calibration parameters. Three calibration methods were devised: calibration with distance factors (D, H, V), orientation factors (R, P, Y), and the combined two influential factors from both sets of factors. The calibration study was carried out with three different stereo cameras. The results indicate that D is the most influential factor, while H and V are nearly equally influential for method A; P and R are the two most influential orientation factors for method B. Compared to Zhang's method alone, on average, methods A, B, and C reduce ϵRP by 25%, 24%, and 34%, respectively. However, method C requires about 10% more calibration images than methods A and B combined. For applications where lower value of ϵRP is required, method C is recommended. This study provides valuable insights into the factors affecting ϵRP in calibration processes. The proposed methods can be used to improve the calibration accuracy for stereo cameras for the applications in object detection and ranging. The findings expand our understanding of camera calibration, particularly the influence of distance and orientation factors, making significant contributions to camera calibration procedures.

Investigation on Awareness of Cognitive Impairment Diseases Among Surgical Practitioners.

Objective: In this study, we assessed the awareness of cognitive dysfunction and the reasons for the lack of awareness among surgical practitioners in Jiaxing. Methods: Questionnaires were distributed to surgical practitioners covering all Class III and Class II hospitals in Jiaxing. Respondents were asked to make selections regarding the demographic data, clinical attitudes and practices of cognitive dysfunction based on Alzheimer's Disease Assessment Scale (ADKS) of the Chinese version. Results: A total of 180 questionnaires were distributed, 12 of which were incomplete, with 168 being included for analysis. The respondents were generally under 50 years of age (150, 89.3%), predominantly males (146, 86.9%), and surgeons (153, 91.1%). They generally had a bachelor's or master's degrees (165, 98.2%), and served in Class III hospitals (127, 75.6%). The title of the practitioner was found to impact their attention toward their patients' cognitive status during preoperative preparation (P<0.05). Titles and hospital levels were found to influence decisions of surgical practitioners to invite specialist physicians for consultation and assessment when a patient was identified to have cognitive dysfunction (P<0.05). Most surgical practitioners had little knowledge or training about Alzheimer's disease and cognitive dysfunction. Among the 168 respondents, the mean ADKS score was 20.14±2.40, and the awareness rate was 67.1%, indicating that the surgical practitioner's title influenced ADKS score (P<0.001). Conclusion: Surgical practitioners, especially young physicians and those in Class II hospitals, had lower awareness of cognitive dysfunction, with low ADKS scores; therefore, they needed to be further trained to recognize cognitive dysfunction.

Construction of a plasmid-free L-leucine overproducing Escherichia coli strain through reprogramming of the metabolic flux.

BACKGROUND: L-Leucine is a high-value amino acid with promising applications in the medicine and feed industries. However, the complex metabolic network and intracellular redox imbalance in fermentative microbes limit their efficient biosynthesis of L-leucine. RESULTS: In this study, we applied rational metabolic engineering and a dynamic regulation strategy to construct a plasmid-free, non-auxotrophic Escherichia coli strain that overproduces L-leucine. First, the L-leucine biosynthesis pathway was strengthened through multi-step rational metabolic engineering. Then, a cooperative cofactor utilization strategy was designed to ensure redox balance for L-leucine production. Finally, to further improve the L-leucine yield, a toggle switch for dynamically controlling sucAB expression was applied to accurately regulate the tricarboxylic acid cycle and the carbon flux toward L-leucine biosynthesis. Strain LEU27 produced up to 55 g/L of L-leucine, with a yield of 0.23 g/g glucose. CONCLUSIONS: The combination of strategies can be applied to the development of microbial platforms that produce L-leucine and its derivatives.

MXene-Regulated Metal-Oxide Interfaces with Modified Intermediate Configurations Realizing Nearly 100% CO2 Electrocatalytic Conversion.

Electrocatalytic CO2 reduction via renewable electricity provides a sustainable way to produce valued chemicals, while it suffers from low activity and selectivity. Herein, we constructed a novel catalyst with unique Ti3 C2 Tx MXene-regulated Ag-ZnO interfaces, undercoordinated surface sites, as well as mesoporous nanostructures. The designed Ag-ZnO/Ti3 C2 Tx catalyst achieves an outstanding CO2 conversion performance of a nearly 100% CO Faraday efficiency with high partial current density of 22.59 mA cm-2 at -0.87 V versus reversible hydrogen electrode. The electronic donation of Ag and up-shifted d-band center relative to Fermi level within MXene-regulated Ag-ZnO interfaces contributes the high selectivity of CO. The CO2 conversion is highly correlated with the dominated linear-bonded CO intermediate confirmed by in situ infrared spectroscopy. This work enlightens the rational design of unique metal-oxide interfaces with the regulation of MXene for high-performance electrocatalysis beyond CO2 reduction.

Two-step model of paleohexaploidy, ancestral genome reshuffling and plasticity of heat shock response in Asteraceae.

An ancient hexaploidization event in the most but not all Asteraceae plants, may have been responsible for shaping the genomes of many horticultural, ornamental, and medicinal plants that promoting the prosperity of the largest angiosperm family on the earth. However, the duplication process of this hexaploidy, as well as the genomic and phenotypic diversity of extant Asteraceae plants caused by paleogenome reorganization, are still poorly understood. We analyzed 11 genomes from 10 genera in Asteraceae, and redated the Asteraceae common hexaploidization (ACH) event ~70.7-78.6 million years ago (Mya) and the Asteroideae specific tetraploidization (AST) event ~41.6-46.2 Mya. Moreover, we identified the genomic homologies generated from the ACH, AST and speciation events, and constructed a multiple genome alignment framework for Asteraceae. Subsequently, we revealed biased fractionations between the paleopolyploidization produced subgenomes, suggesting the ACH and AST both are allopolyplodization events. Interestingly, the paleochromosome reshuffling traces provided clear evidence for the two-step duplications of ACH event in Asteraceae. Furthermore, we reconstructed ancestral Asteraceae karyotype (AAK) that has 9 paleochromosomes, and revealed a highly flexible reshuffling of Asteraceae paleogenome. Of specific significance, we explored the genetic diversity of Heat Shock Transcription Factors (Hsfs) associated with recursive whole-genome polyploidizations, gene duplications, and paleogenome reshuffling, and revealed that the expansion of Hsfs gene families enable heat shock plasticity during the genome evolution of Asteraceae. Our study provides insights on polyploidy and paleogenome remodeling for the successful establishment of Asteraceae, and is helpful for further communication and exploration of the diversification of plant families and phenotypes.

[Association between airborne particulate matter（PM 2.5） concentration and the incidence of allergic rhinitis in Shanghai].

Objective:To explore the impact of PM 2.5 concentration in Shanghai on the incidence of allergic rhinitis（AR） in the population, and provide strategies for early warning and prevention of AR. Methods:Collect daily average concentrations of atmospheric pollutants monitored in Shanghai from January 1, 2017 to December 31, 2019, and clinical data of AR patients from five hospitals in Shanghai during the same period. We used a time-series analysis additive Poisson regression model to analyze the correlation between PM 2.5 levels and outpatient attendance for AR patients. Results:During the study period, a total of 56 500 AR patients were included, and the daily average concentration of PM 2.5 was（35.28±23.07）µg/m³. There is a correlation between the concentration of PM 2.5 and the number of outpatient attendance for AR cases. There is a positive correlation between the daily average number of outpatient for AR and levels of PM 2.5 air pollution（（P<0.05）） . We found that every 10 µg/m³ increase in PM 2.5, the impact of on the number of AR visits was statistically significant on the same day, the first day behind, and the second day behind, with the strongest impact being the exposure on the same day. Every 10 µg/m³ increases in PM 2.5, the number of outpatient visits increased by 0.526% on the same day（95%CI 1.000 50-1.010 04）. Conclusion:The atmospheric PM 2.5 concentration in Shanghai is positively correlated with the number of outpatient for AR, and PM 2.5 exposure is an independent factor in the onset of AR. This provides an important theoretical basis for AR.

Alginate Oligosaccharides Repair Liver Injury by Improving Anti-Inflammatory Capacity in a Busulfan-Induced Mouse Model.

Liver diseases are associated with many factors, including medicines and alcoholics, which have become a global problem. It is crucial to overcome this problem. Liver diseases always come with inflammatory complications, which might be a potential target to deal with this issue. Alginate oligosaccharides (AOS) have been demonstrated to have many beneficial effects, especially anti-inflammation. In this study, 40 mg/kg body weight (BW) of busulfan was intraperitoneally injected once, and then the mice were dosed with ddH2O or AOS 10 mg/kg BW every day by oral gavage for five weeks. We investigated AOS as a potential no-side-effect and low-cost therapy for liver diseases. For the first time, we discovered that AOS 10 mg/kg recovered liver injury by decreasing the inflammation-related factors. Moreover, AOS 10 mg/kg could improve the blood metabolites related to immune and anti-tumor effects, and thus, ameliorated impaired liver function. The results indicate that AOS may be a potential therapy to deal with liver damage, especially in inflammatory conditions.

Neutralizing antibodies from the rare convalescent donors elicited antibody-dependent enhancement of SARS-CoV-2 variants infection.

Currently, neutralizing antibody and vaccine strategies have been developed by targeting the SARS-CoV-2 strain identified during the early phase of the pandemic. Early studies showed that the ability of SARS-CoV-2 RBD or NTD antibodies to elicit infection enhancement in vivo is still controversial. There are growing concerns that the plasma and neutralizing antibodies from convalescent patients or people receiving vaccines mediate ADE of SARS-CoV-2 variants infections in immune cells. Here, we constructed engineered double-mutant variants containing an RBD mutation and D614G in the spike (S) protein and natural epidemic variants to gain insights into the correlation between the mutations in S proteins and the ADE activities and tested whether convalescent plasma and TOP10 neutralizing antibodies in our laboratory mediated the ADE effects of these SARS-CoV-2 variants. We found that one out of 29 convalescent plasma samples caused the ADE effect of pandemic variant B.1.1.7 and that the ADE effect of wild-type SARS-CoV-2 was not detected for any of these plasma samples. Only one antibody, 55A8, from the same batch of convalescent patients mediated the ADE effects of multiple SARS-CoV-2 variants in vitro, including six double-mutant variants and four epidemic variants, suggesting that ADE activities may be closely related to the antibody itself and the SARS-CoV-2 variants' S proteins. Moreover, the ADE activity of 55A8 depended on FcγRII on immune cells, and the introduction of LALA mutations at the Fc end of 55A8 eliminated the ADE effects in vitro, indicating that 55A8LALA may be a clinical drug used to prevent SARS-CoV-2 variants. Altogether, ADE may occur in rare convalescent patients or vaccinees with ADE-active antibodies who are then exposed to a SARS-CoV-2 variant. These data suggested that potential neutralizing antibodies may need to undergo ADE screening tests for SARS-CoV-2 variants, which should aid in the future design of effective antibody-based therapies.