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The functions of the natural dsRNA sensors TLR3 (TRIF) and RIG-I (MAVS) are crucial during viral challenge and have not been accurately clarified in adaptive immune responses to rotavirus (RV) infection. In this study, we found that RV infection caused severe pathological damage to the small intestine of TLR3-/- and TRIF-/- mice. Our data found that dendritic cells from TLR3-/- and TRIF-/- mice had impaired Ag presentation to the RV and attenuated initiation of T cells upon viral infection. These attenuated functions resulted in impaired CD4+ T and CD8+ T function in mice lacking TLR3-TRIF signaling postinfection. Additionally, attenuated proliferative capacity of T cells from TLR3-/- and TRIF-/- mice was observed. Subsequently, we observed a significant reduction in the absolute number of memory T cells in the spleen and mesenteric lymph node (MLN) of TRIF-/- recipient mice following RV infection in a bone marrow chimeric model. Furthermore, there was reduced migration of type 2 classical dendritic cells from the intestine to MLNs after RV infection in TLR3-/- and TRIF-/- mice. Notably, RV infection resulted in attenuated killing of spleen and MLN tissues in TRIF-/- and MAVS-/- mice. Finally, we demonstrated that RV infection promoted apoptosis of CD8+ T cells in TRIF-/- and TLR3-/-MAVS-/- mice. Taken together, our findings highlight an important mechanism of TLR3 signaling through TRIF in mucosal T cell responses to RV and lay the foundation for the development of a novel vaccine., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Avian influenza virus (AIV) subtype H9N2 has significantly threatened the poultry business in recent years by having become the predominant subtype in flocks of chickens, ducks, and pigeons. In addition, the public health aspects of H9N2 AIV pose a significant threat to humans. Early and rapid diagnosis of H9N2 AIV is therefore of great importance. In this study, a new method for the detection of H9N2 AIV based on fluorescence intensity was successfully established using CRISPR/Cas13a technology. The Cas13a protein was first expressed in a prokaryotic system and purified using nickel ion affinity chromatography, resulting in a high-purity Cas13a protein. The best RPA (recombinase polymerase amplification) primer pairs and crRNA were designed and screened, successfully constructing the detection of H9N2 AIV based on CRISPR/Cas13a technology. Optimal concentration of Cas13a and crRNA was determined to optimize the constructed assay. The sensitivity of the optimized detection system is excellent, with a minimum detection limit of 10° copies/μL and didn't react with other avian susceptible viruses, with excellent specificity. The detection method provides the basis for the field detection of the H9N2 AIV., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The impacts of straw removal on rice Cd absorption, behaviour of Cd and microbial community in rhizosphere soil were investigated in paddy fields over two consecutive seasons. The results of the experiments in two fields revealed that straw removal promoted the transformation of soil Cd from acid-extractable and oxidisable fraction to residual fraction and reduced soil DTPA-Cd content with the reduction in DOC and Cd ions in soil porewater, thereby decreasing Cd content in rice. Specifically, the Cd content in brown rice was below 0.2 mg·kg -1 when all rice straw and roots were removed in the slightly Cd-contaminated soils. The α-diversity of soil microbial communities was less influenced by continuous straw removal, β-diversity was altered and the relative abundances of Anaeromyxobacter, Methylocystis and Mycobacterium microbes were increased. Redundancy analysis and network analysis exhibited that soil pH predominantly influenced the microbial community. Path analysis revealed that the Cd content in brown rice could be directly influenced by the soil Total-Cd and DTPA-Cd, as well as soil pH and OM. Straw removal, including roots removal, is an economical and effective technique to reduce Cd accumulation in rice plants., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jiao-Feng Gu reports financial support was provided by Department of Science and Technology of Hunan Province. Jiao-Feng Gu reports financial support was provided by Department of Science and Technology of Changsha City. Hang Zhou reports financial support was provided by Department of Science and Technology of Hunan Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Programmed cell death (PCD) is a fundamental biological process for maintaining cellular equilibrium and regulating development, health, and disease across all living organisms. Among the various types of PCD, apoptosis plays a pivotal role in numerous diseases, notably cancer. Cancer cells frequently develop mechanisms to evade apoptosis, increasing resistance to standard chemotherapy treatments. This resistance has prompted extensive research into alternative mechanisms of programmed cell death. One such pathway is oncosis, characterized by significant energy consumption, cell swelling, dilation of the endoplasmic reticulum, mitochondrial swelling, and nuclear chromatin aggregation. Recent research suggests that oncosis can impact conditions such as chemotherapeutic cardiotoxicity, myocardial ischemic injury, stroke, and cancer, mediated by specific oncosis-related proteins. In this review, we provide a detailed examination of the morphological and molecular features of oncosis and discuss various natural or small molecule compounds that can induce this type of cell death. Additionally, we summarize the current understanding of the molecular mechanisms underlying oncosis and its role in both normal physiology and pathological conditions. These insights aim to illuminate future research directions and propose innovative strategies for leveraging oncosis as a therapeutic tool against human diseases and cancer resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Yang, Mai, Liang, Luo, Zhou, Yu, Wang and Li.)

HER2-positive breast cancer is an aggressive subtype that accounts for 15-20% of all breast cancers. Recent studies have suggested that HER2-positive breast cancer is a group of heterogeneous diseases with different sensitivities to standard treatment regimens. Revealing the molecular heterogeneity of HER2-positive breast cancer could potentially enable more precise treatment strategies. Here, we performed multiomics profiling on a HER2-positive breast cancer cohort and identified four transcriptome-based subtypes. The classical HER2 (HER2-CLA) subtype comprised 28.3% of the samples and displayed high ERBB2 activation and significant benefit from anti-HER2 therapy. The immunomodulatory (HER2-IM) subtype (20%) featured an immune-activated microenvironment, potentially suitable for de-escalated treatment and immunotherapy. The luminal-like (HER2-LUM) subtype (30.6%) possessed similar molecular features of hormone receptor-positive HER2-negative breast cancer, suggesting endocrine therapy and CDK4/6 inhibitors as a potential therapeutic strategy. Lastly, the basal/mesenchymal-like (HER2-BM) subtype (21.1%), had a poor response to current anti-HER2 dual-targeted therapies and could potentially benefit from tyrosine kinase inhibitors. The molecular characteristics and clinical features of the subtypes were further explored across multiple cohorts, and the feasibility of the proposed treatment strategies was validated in patient-derived organoid and patient-derived tumor fragment models. This study elucidates the molecular heterogeneity of HER2-positive breast cancer and paves the way for a more tailored treatment.

The widespread utilization of polyethylene terephthalate (PET) has caused a variety of environmental and health problems. Compared with traditional thermomechanical or chemical PET cycling, the biodegradation of PET may offer a more feasible solution. Though the PETase from Ideonalla sakaiensis (IsPETase) displays interesting PET degrading performance under mild conditions; the relatively low thermal stability of IsPETase limits its practical application. In this study, enzyme-catalysed PET degradation was investigated with the promising IsPETase mutant HotPETase (HP). On this basis, a carbohydrate-binding module from Bacillus anthracis (BaCBM) was fused to the C-terminus of HP to construct the PETase mutant (HLCB) for increased PET degradation. Furthermore, to effectively improve PET accessibility and PET-degrading activity, the truncated outer membrane hybrid protein (FadL) was used to expose PETase and BaCBM on the surface of E. coli (BL21with) to develop regenerable whole-cell biocatalysts (D-HLCB). Results showed that, among the tested small-molecular weight ester compounds (p-nitrophenyl phosphate (pNPP), p-Nitrophenyl acetate (pNPA), 4-Nitrophenyl butyrate (pNPB)), PETase displayed the highest hydrolysing activity against pNPP. HP displayed the highest catalytic activity (1.94 μM(p-NP)/min) at 50 °C and increased longevity at 40 °C. The fused BaCBM could clearly improve the catalytic performance of PETase by increasing the optimal reaction temperature and improving the thermostability. When HLCB was used for PET degradation, the yield of monomeric products (255.7 μM) was ∼25.5 % greater than that obtained after 50 h of HP-catalysed PET degradation. Moreover, the highest yield of monomeric products from the D-HLCB-mediated system reached 1.03 mM. The whole-cell catalyst D-HLCB displayed good reusability and stability and could maintain more than 54.6 % of its initial activity for nine cycles. Finally, molecular docking simulations were utilized to investigate the binding mechanism and the reaction mechanism of HLCB, which may provide theoretical evidence to further increase the PET-degrading activities of PETases through rational design. The proposed strategy and developed variants show potential for achieving complete biodegradation of PET under mild conditions., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and the financial support for this work have been given in the manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To identify recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation in patients with isolated distal deep vein thrombosis based on its anatomic localization (axial or muscular veins)., Methods: Data were sourced from PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases in the time period up to October 2023. The study followed PRISMA guidelines using a registered protocol (CRD42023443029). Studies reporting recurrent VTE in patients with axial or muscular DVT were included in the analysis., Results: Five studies with a total of 1,403 participants were evaluated. The results showed a pooled odds ratio of 1.12 (95% confidence interval 0.77-1.63) between axial and muscular DVT. Heterogeneity was low (I 2  = 0%, p = 0.91) and there was no significant difference in the rate of recurrent VTE between axial and muscular DVT in each subgroup., Conclusions: Muscular and axial DVT showed comparable recurrent VTE rates after anticoagulation. However, uncertainties regarding the possibility of recurrence affecting the popliteal vein or resulting in pulmonary embolism following muscular DVT anticoagulation persisted. Randomized trials in patients with isolated distal DVT are still needed to clarify its prognosis for different anatomical thrombus locations., (© 2024. The Author(s).)

The widespread transmission of SARS-CoV-2 in humans poses a serious threat to public health security, and a growing number of studies have discovered that SARS-CoV-2 infection in wildlife and mutate over time. This article mainly reports the first systematic review and meta-analysis of the prevalence of SARS-CoV-2 in wildlife. The pooled prevalence of the 29 included articles was calculated by us using a random effects model (22.9%) with a high heterogeneity (I 2  = 98.7%, p = 0.00). Subgroup analysis and univariate regression analysis found potential risk factors contributing to heterogeneity were country, wildlife species, sample type, longitude, and precipitation. In addition, the prevalence of SARS-CoV-2 in wildlife increased gradually over time. Consequently, it is necessary to comprehensively analyze the risk factors of SARS-CoV-2 infection in wildlife and develop effective control policies, as well as to monitor the mutation of SARS-CoV-2 in wildlife at all times to reduce the risk of SARS-CoV-2 transmission among different species., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Background: Previous observational studies have shown that the prevalence of gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) is associated with socioeconomic status. However, due to the methodological limitations of traditional observational studies, it is challenging to definitively establish causality., Aim: To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization (MR)., Methods: We initially screened single nucleotide polymorphisms (SNPs) to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis. The inverse variance weighted (IVW) method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE. We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR (MVMR) analyses based on the IVW MVMR model. Furthermore, a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index, major depressive disorder (MDD), smoking, alcohol consumption, and sleep duration., Results: The study identified three socioeconomic statuses that had a significant impact on GERD. These included household income [odds ratio (OR): 0.46; 95% confidence interval (95%CI): 0.31-0.70], education attainment (OR: 0.23; 95%CI: 0.18-0.29), and the Townsend Deprivation Index at recruitment (OR: 1.57; 95%CI: 1.04-2.37). These factors were found to independently and predominantly influence the genetic causal effect of GERD. Furthermore, the mediating effect of educational attainment on GERD was found to be mediated by MDD (proportion mediated: 10.83%). Similarly, the effect of educational attainment on BE was mediated by MDD (proportion mediated: 10.58%) and the number of cigarettes smoked per day (proportion mediated: 3.50%). Additionally, the mediating effect of household income on GERD was observed to be mediated by sleep duration (proportion mediated: 9.75%)., Conclusion: This MR study shed light on the link between socioeconomic status and GERD or BE, providing insights for the prevention of esophageal cancer and precancerous lesions., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To compare the predictive efficacy of the PADUA and Caprini models for pulmonary embolism (PE) in gynecological inpatients, analyze the risk factors for PE, and validate whether both models can effectively predict mortality rates., Methods: A total of 355 gynecological inpatients who underwent computed tomography pulmonary angiography (CTPA) were included in the retrospective analysis. The comparative assessment of the predictive capabilities for PE between the PADUA and Caprini was carried out using receiver operating characteristic (ROC) curves. Logistic regression analysis was used to identify risk factors associated with PE. Additionally, Kaplan-Meier survival analysis plots were generated to validate the predictive efficacy for mortality rates., Results: Among 355 patients, the PADUA and Caprini demonstrated the area under the curve (AUC) values of 0.757 and 0.756, respectively. There was no statistically significant difference in the AUC between the two models (P = 0.9542). Multivariate logistic analysis revealed immobility (P < 0.001), history of venous thromboembolism (VTE) (P = 0.002), thrombophilia (P < 0.001), hormonal treatment (P = 0.022), and obesity (P = 0.019) as independent risk factors for PE. Kaplan-Meier survival analysis demonstrated the reliable predictive efficacy of both the Caprini (P = 0.00051) and PADUA (P = 0.00031) for mortality. ROC for the three- and six-month follow-ups suggested that the Caprini model exhibited superior predictive efficacy for mortality., Conclusions: The PADUA model can serve as a simple and effective tool for stratifying high-risk gynecological inpatients before undergoing CTPA. The Caprini model demonstrated superior predictive efficacy for mortality rates., (© 2024. The Author(s).)

Background: In observational studies, dietary intakes are associated with gastroesophageal reflux disease (GERD)., Aim: To conduct a two-sample mendelian randomization (MR) analysis to determine whether those associations are causal., Methods: To explore the relationship between dietary intake and the risk of GERD, we extracted appropriate single nucleotide polymorphisms from genome-wide association study data on 24 dietary intakes. Three methods were adopted for data analysis: Inverse variance weighting, weighted median methods, and MR-Egger's method. The odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the causal association between dietary intake and GERD., Results: Our univariate Mendelian randomization (UVMR) results showed significant evidence that pork intake (OR, 2.83; 95%CI: 1.76-4.55; P = 1.84 × 10 -5 ), beer intake (OR, 2.70, 95%CI: 2.00-3.64; P = 6.54 × 10 -11 ), non-oily fish intake (OR, 2.41; 95%CI: 1.49-3.91; P = 3.59 × 10 -4 ) have a protective effect on GERD. In addition, dried fruit intake (OR, 0.37; 95%CI: 0.27-0.50; 6.27 × 10 -11 ), red wine intake (OR, 0.34; 95%CI: 0.25-0.47; P = 1.90 × 10 -11 ), cheese intake (OR, 0.46; 95%CI: 0.39-0.55; P =3.73 × 10 -19 ), bread intake (OR, 0.72; 95%CI: 0.56-0.92; P = 0.0009) and cereal intake (OR, 0.45; 95%CI: 0.36-0.57; P = 2.07 × 10 -11 ) were negatively associated with the risk of GERD. There was a suggestive association for genetically predicted coffee intake (OR per one SD increase, 1.22, 95%CI: 1.03-1.44; P = 0.019). Multivariate Mendelian randomization further confirmed that dried fruit intake, red wine intake, cheese intake, and cereal intake directly affected GERD. In contrast, the impact of pork intake, beer intake, non-oily fish intake, and bread intake on GERD was partly driven by the common risk factors for GERD. However, after adjusting for all four elements, there was no longer a suggestive association between coffee intake and GERD., Conclusion: This study provides MR evidence to support the causal relationship between a broad range of dietary intake and GERD, providing new insights for the treatment and prevention of GERD., Competing Interests: Conflict-of-interest statement: All authors declare that they have no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Molecular profiling guides precision treatment of breast cancer; however, Asian patients are underrepresented in publicly available large-scale studies. We established a comprehensive multiomics cohort of 773 Chinese patients with breast cancer and systematically analyzed their genomic, transcriptomic, proteomic, metabolomic, radiomic and digital pathology characteristics. Here we show that compared to breast cancers in white individuals, Asian individuals had more targetable AKT1 mutations. Integrated analysis revealed a higher proportion of HER2-enriched subtype and correspondingly more frequent ERBB2 amplification and higher HER2 protein abundance in the Chinese HR + HER2 + cohort, stressing anti-HER2 therapy for these individuals. Furthermore, comprehensive metabolomic and proteomic analyses revealed ferroptosis as a potential therapeutic target for basal-like tumors. The integration of clinical, transcriptomic, metabolomic, radiomic and pathological features allowed for efficient stratification of patients into groups with varying recurrence risks. Our study provides a public resource and new insights into the biology and ancestry specificity of breast cancer in the Asian population, offering potential for further precision treatment approaches., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Influenza virus is a kind of virus that poses several hazards of animal and human health. Therefore, it is important to develop an effective vaccine to prevent influenza. To this end we successfully packaged recombinant adenovirus rAd-NP-M2e-GFP expressing multiple copies of influenza virus conserved antigens NP and M2e and packaged empty vector adenovirus rAd-GFP. The effect of rAd-NP-M2e-GFP on the activation of dendritic cell (DC) in vitro and in vivo was detected by intranasal immunization. The results showed that rAd-NP-M2e-GFP promoted the activation of DC in vitro and in vivo. After the primary immunization and booster immunization of mice through the nasal immune way, the results showed that rAd-NP-M2e-GFP induced enhanced local mucosal-specific T cell responses, increased the content of SIgA in broncho alveolar lavage fluids (BALF) and triggered the differentiation of B cells in the germinal center. It is proved that rAd-NP-M2e-GFP can significantly elicit mucosal immunity and systemic immune response. In addition, rAd-NP-M2e-GFP could effectively protect mice after H1N1 influenza virus challenge. To lay the foundation and provide reference for further development of influenza virus mucosal vaccine in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to compare the efficacy of customized graduated elastic compression stockings (c-GECSs) based on lower leg parameter models with standard GECSs (s-GECSs) in patients with chronic venous disease (CVD)., Methods: In this randomized, single-blind, controlled trial, 79 patients with stage C2 or C3 CVD were assigned to one of two groups: c-GECSs or s-GECSs. The primary outcome was change to Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) scores at months 1, 3, and 6 as compared with baseline. Secondary outcomes included compliance with wearing ECSs, interface pressure at the smallest circumference of the ankle (point B) and the largest circumference of the calf (point C), and calf volume (CV)., Results: There were 13 pairs of s-GECS and 2 pairs of c-GECS that showed pressure values higher than the standard at either point B or C. The c-GECSs were significantly superior to s-GECSs in terms of score improvement at all three time points (month 1, 8.47 [95% confidence interval (CI), 7.47-9.45] vs 5.89 [95% CI, 5.00-6.78]; month 3, 9.60 [95% CI, 8.47-10.72] vs 6.72 [95% CI, 5.62-7.83]; month 6, 7.09 [95% CI, 5.93-8.24] vs 3.92 [95% CI, 2.67-5.18]; P < .0001). Besides, at month 1, the mean daily use time of the c-GECS and s-GECS groups was 10.7 and 9.5 hours, respectively (P < .05). Correlation analysis indicated a negative relationship between local high pressure and daily duration in the s-GECS group (r pb = -0.388; n = 38; P < .05). Variances in pressure were greater in the s-GECSs group. The c-GECSs showed advantage in maintaining pressure. Both c-GECSs and s-GECSs effectively reduced CV (mL), with no significant differences between groups (month 1, 90.0 [95% CI, 71.4-108.5] vs 85.0 [95% CI, 65.6-104.2]; month 3, 93.8 [95% CI, 69.7-117.8] vs 85.9 [95% CI, 65.5-106.2]; month 6, 70.8 [95% CI, 46.5-95.2]) vs 60.8 [95% CI, 44.1-77.5])., Conclusions: The c-GECSs based on individual leg parameter models significantly improved VEINES-QOL scores and provided stable and enduring pressure as compared with s-GECSs for patients with stage C2 or C3 CVD. Although both c-GECSs and s-GECSs effectively reduced CV, the superior fit and comfort of c-GECSs improved patient compliance. Hence, c-GECSs are a viable alternative for patients who have difficulty tolerating s-GECSs., Competing Interests: Disclosures None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: Human epidermal growth factor receptor 2 (HER2)-positive patients with breast cancer may have different HER2/CEP17 ratios and HER2 copy numbers, with inconsistent responses to anti-HER2 neoadjuvant chemotherapy (NACT). Our study aimed to explore the relationship between different HER2 fluorescence in situ hybridisation (FISH) patterns in HER2-positive patients with breast cancer and responses to anti-HER2 NACT., Methods: 527 patients with HER2-positive invasive breast cancer who received anti-HER2 NACT from 2015 to 2022 were included and divided into three groups by FISH results, namely group A: HER2/CEP17<2.0 and HER2 copy numbers ≥6.0, HER2 immunohistochemistry 2/3+; group B: HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0; group C: HER2/CEP17≥2.0 and HER2 copy numbers ≥6.0. We compared clinicopathological characteristics and pathological complete response (pCR) rates of different groups., Results: According to HER2 FISH results, 12 patients (2.3%, 12/527) were in group A, 40 (7.6%, 40/527) were in group B and 475 (90.1%, 475/527) were in group C. The pCR rate was the lowest in group B (5.0%), while the pCR rates in group A and group C were 33.3% and 44.4%, respectively (p (group A vs. B) =0.021, p (group C vs. B) < 0.001). Both univariate and multivariate analyses revealed that HER2 FISH pattern was correlated with pCR rate (p (group C vs. B) < 0.001, p (group C vs. B) = 0.025)., Conclusions: Patients with HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0 do not benefit to the same extent from current anti-HER2 therapies as FISH-positive patients with other patterns., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics., Results: Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids' deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8 + CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8 + CTLs to exert antiviral effects., Conclusions: Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract., (© 2024. The Author(s).)

Purpose: Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODS AND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method., Results: The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46 years (mean, 48.1 years; range, 10-80 years). The tumor sizes ranged from 0.3 to 6.8 cm, with a mean of 3.5 cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients., Conclusion: Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improve diagnosis and management in this unique subtype of breast cancer., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Triple-negative breast cancers display heterogeneity in molecular drivers and immune traits. We previously classified triple-negative breast cancers into four subtypes: luminal androgen receptor (LAR), immunomodulatory, basal-like immune-suppressed (BLIS), and mesenchymal-like (MES). Here, we aimed to evaluate the efficacy and safety of subtyping-based therapy in the first-line treatment of triple-negative breast cancer., Methods: FUTURE-SUPER is an ongoing, open-label, randomised, controlled phase 2 trial being conducted at Fudan University Shanghai Cancer Center (FUSCC), Shanghai, China. Eligible participants were females aged 18-70 years, with an Eastern Cooperative Oncology Group performance status of 0-1, and histologically confirmed, untreated metastatic or recurrent triple-negative breast cancer. After categorising participants into five cohorts according to molecular subtype and genomic biomarkers, participants were randomly assigned (1:1) with a block size of 4, stratified by subtype, to receive, in 28-day cycles, nab-paclitaxel (100 mg/m 2 , intravenously on days 1, 8, and 15) alone (control group) or with a subtyping-based regimen (subtyping-based group): pyrotinib (400 mg orally daily) for the LAR-HER2 mut subtype, everolimus (10 mg orally daily) for the LAR-PI3K/AKT mut and MES-PI3K/AKT mut subtypes, camrelizumab (200 mg intravenously on days 1 and 15) and famitinib (20 mg orally daily) for the immunomodulatory subtype, and bevacizumab (10 mg/kg intravenously on days 1 and 15) for the BLIS/MES-PI3K/AKT WT subtype. The primary endpoint was investigator-assessed progression-free survival for the pooled subtyping-based group versus the control group in the intention-to-treat population (all randomly assigned participants). Safety was analysed in all patients with safety records who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT04395989)., Findings: Between July 28, 2020, and Oct 16, 2022, 139 female participants were enrolled and randomly assigned to the subtyping-based group (n=69) or control group (n=70). At the data cutoff (May 31, 2023), the median follow-up was 22·5 months (IQR 15·2-29·0). Median progression-free survival was significantly longer in the pooled subtyping-based group (11·3 months [95% CI 8·6-15·2]) than in the control group (5·8 months [4·0-6·7]; hazard ratio 0·44 [95% CI 0·30-0·65]; p<0·0001). The most common grade 3-4 treatment-related adverse events were neutropenia (21 [30%] of 69 in the pooled subtyping-based group vs 16 [23%] of 70 in the control group), anaemia (five [7%] vs none), and increased alanine aminotransferase (four [6%] vs one [1%]). Treatment-related serious adverse events were reported for seven (10%) of 69 patients in the subtyping-based group and none in the control group. No treatment-related deaths were reported in either group., Interpretation: These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway., Funding: National Natural Science Foundation of China, Natural Science Foundation of Shanghai, Shanghai Hospital Development Center, and Jiangsu Hengrui Pharmaceuticals., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests Y Xia and QL are employees of Jiangsu Hengrui Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the incidence of isolated distal deep venous thrombosis (IDDVT) concurrent with pulmonary embolism (PE) in gynecologic inpatients, analyze the risk factors for IDDVT with PE, and establish a nomogram model for IDDVT patients with PE., Methods: A total of 260 patients were diagnosed with IDDVT between December 2017 and November 2020. The incidence of PE in these patients was determined using computed tomography pulmonary angiography. Logistic regression analysis was used to identify the related risk factors. On this basis, nomogram risk prediction models were established., Results: Among 260 patients with IDDVT, 106 (40.8%) had concurrent PE, of whom 74 (28.5%) experienced silent PE. Univariate logistic analysis demonstrated statistical significance for body mass index (BMI; P = 0.044), glucocorticoid therapy (P = 0.009), hypertension (P < 0.001), and diabetes (P < 0.001). Multivariate logistic analysis revealed that these were independent risk factors for IDDVT with PE that retained statistical significance. A nomogram based on these factors was constructed to predict PE in patients with IDDVT. Its receiver operating characteristic (ROC) showed an area under the curve of 0.710 (95% confidence interval 0.642-0.779), with prediction sensitivity of 64.2% and prediction specificity of 76.6%., Conclusions: In the present study, a high prevalence of PE was found in gynecologic inpatients with IDDVT. Glucocorticoid therapy, hypertension, diabetes, and BMI were independent risk factors for IDDVT patients with PE. Taking these risk factors into account, a nomogram risk prediction model was developed to help facilitate early detection of concurrent PE., (© 2023 International Federation of Gynecology and Obstetrics.)

Background: The management of axillary lymph nodes in early-stage breast cancer patients has changed considerably, with the primary focus shifting from the examination of sentinel lymph nodes (SLNs) to toward the detection of all macro-metastases. However, current methods, such as touch imprint cytology (TIC) and frozen sections, are inadequate for clinical needs. To address this issue, we proposed a novel miniaturised epifluorescence widefield microscope (MEW-M) to assess SLN status intraoperatively for improved diagnostic efficiency., Methods: A prospective, side-by-side comparison of intraoperative SLN evaluation between MEW-M and TIC was performed., Results: A total of 73 patients with 319 SLNs consecutive enrolled in this study. MEW-M showed significantly superior image quality compared to TIC (median score 3.1 vs 2.1, p < 0.0001) and had a shorter time to issue results (10.3 vs 19.4 min, p < 0.0001). Likelihood ratio analysis illustrated that the positive likelihood ratio value of MEW-M compared with TIC was infinitely great vs 52.37 (95% CI, 21.96-124.90) in model 1 (classifying results into negative/positive), infinitely great vs 52.37 (95% CI, 21.96-124.90) in model 2 (classifying results into macro-metastasis/others, and TIC results followed the same classification as model 1), respectively. Similarly, the negative likelihood ratio values of MEW-M compared with TIC were 0.055 (95% CI, 0.018-0.160) and 0.074 (95% CI, 0.029-0.190) in model 1; and 0.019 (95% CI, 0.003-0.130) vs 0.020 (95% CI, 0.003-0.140) in model 2, respectively., Conclusions: MEW-M is a promising technique that can be utilised to provide a rapid and accurate intraoperative assessment of SLN in a clinical setting to help improve decision-making in axillary surgery., (© 2023 John Wiley & Sons Ltd.)

Background: Tumor-infiltrating lymphocytes (TILs) and programmed cell death 1 ligand 1 (PD-L1) remain imperfect in predicting clinical outcomes of triple-negative breast cancer because outcomes do not always correlate with the expression of these biomarkers. Genomic and transcriptomic alterations that may contribute to the expression of these biomarkers remain incompletely uncovered., Methods: We evaluated PD-L1 immunohistochemistry scores (SP142 and 28-8 assays) and TILs in our triple-negative breast cancer multiomics dataset and 2 immunotherapy clinical trial cohorts. Then, we analyzed genomic and transcriptomic alterations correlated with TILs, PD-L1 expression, and patient outcomes., Results: Despite TILs serving as a decent predictor for triple-negative breast cancer clinical outcomes, exceptions remained. Our study revealed that several genomic alterations were correlated with unexpected events. In particular, PD-L1 expression may cause a paradoxical relationship between TILs and prognosis in certain patients. Consequently, we classified triple-negative breast cancers into 4 groups based on PD-L1 and TIL levels. The TIL-negative PD-L1-positive and TIL-positive PD-L1-negative groups were not typical "hot" tumors; both were associated with worse prognoses and lower immunotherapy efficacy than TIL-positive PD-L1-positive tumors. Copy number variation of PD-L1 and oncogenic signaling activation were correlated with PD-L1 expression in the TIL-negative PD-L1-positive group, whereas GSK3B-induced degradation may cause undetectable PD-L1 expression in the TIL-positive PD-L1-negative group. These factors have the potential to affect the predictive function of both PD-L1 and TILs., Conclusions: Several genomic and transcriptomic alterations may cause paradoxical effects among TILs, PD-L1 expression, and prognosis in triple-negative breast cancer. Investigating and targeting these factors will advance precision immunotherapy for patients with this disease., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Digital pathology allows computerized analysis of tumor ecosystem using whole slide images (WSIs). Here, we present single-cell morphological and topological profiling (sc-MTOP) to characterize tumor ecosystem by extracting the features of nuclear morphology and intercellular spatial relationship for individual cells. We construct a single-cell atlas comprising 410 million cells from 637 breast cancer WSIs and dissect the phenotypic diversity within tumor, inflammatory and stroma cells respectively. Spatially-resolved analysis identifies recurrent micro-ecological modules representing locoregional multicellular structures and reveals four breast cancer ecotypes correlating with distinct molecular features and patient prognosis. Further analysis with multiomics data uncovers clinically relevant ecosystem features. High abundance of locally-aggregated inflammatory cells indicates immune-activated tumor microenvironment and favorable immunotherapy response in triple-negative breast cancers. Morphological intratumor heterogeneity of tumor nuclei correlates with cell cycle pathway activation and CDK inhibitors responsiveness in hormone receptor-positive cases. sc-MTOP enables using WSIs to characterize tumor ecosystems at the single-cell level., (© 2023. Springer Nature Limited.)

Objective: Compression therapy with the use of graduated compression stockings (GCSs) is a common treatment strategy for chronic venous disease (CVD). However, there is no uniform and objective standard to assess adherence to the use of GCSs. The aim of this study is to develop and validate a GCS Compliance Scale (GCSAS) to fill gaps in internationally recognized comprehensive scales and provide a useful tool for future research., Methods: The items included in the GCSAS were based on a review of the literature and open-ended interviews with experts, who screened the initial items using an item-level content validity index. Then, pilot tests were conducted three times with 50 participants. After exclusion of redundant and cross-loading items by exploratory factor analysis, 290 subjects were recruited to evaluate the reliability and validity of the proposed GCSAS. Analyses included internal consistency, test-retest reliability, split-half reliability, construct validity, criterion validity, convergent validity, and discriminant validity., Results: The final GCSAS consisted of 17 items and 5 dimensions. The results of the exploratory factor analysis indicated that the variances of each factor explained were 22.03%, 14.85%, 14.74%, 14.16%, and 13.35%, and all 5 factors explained 79.13% of the variance among the 17 items. The factor loadings of all items were >0.7. Confirmatory factor analysis indicated that the indices were adequate. A significant positive correlation was found between the GCSAS and the Venous Insufficiency Epidemiological and Economic Study - Quality of Life questionnaire scores (r = 0.76, p < 0.001). The Cronbach's alpha coefficient was 0.90, test-retest reliability was 0.81, and split-half reliability was 0.92., Conclusions: The GCSAS showed good validity and reliability to assess compliance with the use of GCSs among patients with CVD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The molecular heterogeneity and distinct features of HER2-low breast cancers, particularly in the Chinese population, are not well understood, limiting its precise management in the era of antibody‒drug conjugates. To address this issue, we established a cohort of 434 Chinese patients with HER2-low breast cancer (433 female and one male) and integrated genomic, transcriptomic, proteomic, and metabolomic profiling data. In this cohort, HER2-low tumors are more distinguished from HER2-0 tumors in the hormone receptor-negative subgroup. Within HER2-low tumors, significant interpatient heterogeneity also exists in the hormone receptor-negative subgroup: basal-like tumors resemble HER2-0 disease, and non-basal-like HER2-low tumors mimic HER2-positive disease. These non-basal-like HER2-low tumors are enriched in the HER2-enriched subtype and the luminal androgen receptor subtype and feature PIK3CA mutation, FGFR4/PTK6/ERBB4 overexpression and lipid metabolism activation. Among hormone receptor-positive tumors, HER2-low tumors show less loss/deletion in 17q peaks than HER2-0 tumors. In this work, we reveal the heterogeneity of HER2-low breast cancers and emphasize the need for more precise stratification regarding hormone receptor status and molecular subtype., (© 2023. Springer Nature Limited.)

Pantoea dispersa is a Gram-negative bacterium that exists in a variety of environments and has potential in many commercial and agricultural applications, such as biotechnology, environmental protection, soil bioremediation, and plant growth stimulation. However, P. dispersa is also a harmful pathogen to both humans and plants. This "double-edged sword" phenomenon is not uncommon in nature. To ensure survival, microorganisms respond to both environmental and biological stimuli, which could be beneficial or detrimental to other species. Therefore, to harness the full potential of P. dispersa, while minimizing potential harm, it is imperative to unravel its genetic makeup, understand its ecological interactions and underlying mechanisms. This review aims to provide a comprehensive and up-to-date overview of the genetic and biological characteristics of P. dispersa, in addition to potential impacts on plants and humans, as well as to provide insights into potential applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Only a small proportion of patients with triple-negative breast cancer benefit from immune checkpoint inhibitor (ICI) targeting PD-1/PD-L1 signaling in combination with chemotherapy. Here, we discovered that therapeutic response to ICI plus paclitaxel was associated with subcellular redistribution of PD-L1. In our immunotherapy cohort of ICI in combination with nab-paclitaxel, tumor samples from responders showed significant distribution of PD-L1 at mitochondria, while non-responders showed increased accumulation of PD-L1 on tumor cell membrane instead of mitochondria. Our results also revealed that the distribution pattern of PD-L1 was regulated by an ATAD3A-PINK1 axis. Mechanistically, PINK1 recruited PD-L1 to mitochondria for degradation via a mitophagy pathway. Importantly, paclitaxel increased ATAD3A expression to disrupt proteostasis of PD-L1 by restraining PINK1-dependent mitophagy. Clinically, patients with tumors exhibiting high expression of ATAD3A detected before the treatment with ICI in combination with paclitaxel had markedly shorter progression-free survival compared with those with ATAD3A-low tumors. Preclinical results further demonstrated that targeting ATAD3A reset a favorable antitumor immune microenvironment and increased the efficacy of combination therapy of ICI plus paclitaxel. In summary, our results indicate that ATAD3A serves not only as a resistant factor for the combination therapy of ICI plus paclitaxel through preventing PD-L1 mitochondrial distribution, but also as a promising target for increasing the therapeutic responses to chemoimmunotherapy., (© 2023. The Author(s).)

The zoonotic pathogen avian influenza A H5N8 causes enormous economic losses in the poultry industry and poses a serious threat to the public health. Here, we report the first systematic review and meta-analysis of the worldwide prevalence of birds. We filtered 45 eligible articles from seven databases. A random-effects model was used to analyze the prevalence of H5N8 in birds. The pooled prevalence of H5N8 in birds was 1.6%. In the regions, Africa has the highest prevalence (8.0%). Based on the source, village (8.3%) was the highest. In the sample type, the highest prevalence was organs (79.7%). In seasons, the highest prevalence was autumn (28.1%). The largest prevalence in the sampling time was during 2019 or later (7.0%). Furthermore, geographical factors also were associated with the prevalence. Therefore, we recommend site-specific prevention and control tools for this strain in birds and enhance the surveillance to reduce the spread of H5N8., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Measurement of lower limb volume in patients with chronic venous disease (CVD) is necessary for assessing severity at the time of diagnosis and evaluating response to therapy administered. Existing methods have some limitations in clinical application and accuracy. The study aimed to investigate the reliability and validity of a three-dimensional laser scanner (3DLS) in measuring the lower limb volume of patients with CVD., Methods: A total of 30 patients with CVD (mean age, 55.6 ± 8.07 years; mean body mass index, 24.61 ± 1.87) were recruited in a vascular surgery clinic. The lower limb volumes of all participants were measured using the 3DLS and circumferential method (CM). Statistical analysis was conducted to compare the 3DLS and CM., Results: There was a strong correlation between the CM and 3DLS method (r 2  = 0.9065). The 3DLS had a high intraoperator and interoperator reliability. A Bland-Altman plot showed satisfactory agreement between the two methods. The 3DLS demonstrated greater bilateral limb differences than CM., Conclusions: There was satisfactory agreement between the two investigated methods. The 3DLS method was confirmed to be accurate, repeatable, and rapid in measuring the lower limb volume in patients with CVD and is, therefore, suitable for clinical use., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Piglet diarrhea caused by the porcine epidemic diarrhea virus (PEDV) is a common problem on pig farms in China associated with high morbidity and mortality rates. In this study, three PEDV isolates were successfully detected after the fourth blind passage in Vero cells. The samples were obtained from infected piglet farms in Jilin (Changchun), and Shandong (Qingdao) Provinces of China and were designated as CH/CC-1/2018, CH/CC-2/2018, and CH/QD/2018. According to the analysis of the complete S protein gene sequence, the CH/CC-1/2018 and CH/CC-2/2018 were allocated to the G2b branch, while CH/QD/2018 was located in the G1a interval and was closer to the vaccine strain CV777. Successful detection and identification of the isolated strains were carried out using electron microscopy and indirect immunofluorescence. Meanwhile, animal challenge experiments and viral RNA copies determination were used to compare the pathogenicity. The results showed that CH/CC-1/2018 in Changchun was more pathogenic than CH/QD/2018 in Qingdao. In conclusion, the discovery of these new strains is conducive to the development of vaccines to prevent the pandemic of PEDV, especially that the CH/CC-1/2018, and CH/CC-2/2018 were not related to the classical vaccine strain CV777., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Avian influenza virus (AIV)is easy to cause diseases in birds and humans.It causes great economic losses to the poultry farms and leads to public health problems. Using vaccines is the main approach to control the prevalence of AIV. In our previously published article, a recombinant Lactobacillus plantarum (L. plantarum) expressing the NP-M2 peptide ofH9N2 AIV was generated, and its protective effect was evaluated in a chicken model. In this study, the protective effect was estimated in mice model. Humoral and cellular immune response parameters were measured using flow cytometry adding to body weight loss, survival rate, virus load, and histopathological changes in the lung. The obtained results elucidated that, the recombinant L. plantarum can promote the activation of dendritic cells (DC), proliferation of T and B cells adding to eliciting protective secretory IgA (sIgA) and humeral IgG level in mice model. Accordingly, it could be used as a patent vaccine to control the AIV infection., Competing Interests: Declaration of Competing Interest The author declares that there is no competitive interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

An extensive investigation of heavy metal (Cd, Hg, As, Pb, and Cr) levels in 137 pairs of soil-maize/rice samples was conducted in cultivated land from a typical karst mountain area in the Northwest of Guizhou Province. A health risk assessment model was used to assess the health risks of those areas, and the environmental benchmarks of heavy metals in soils were evaluated using the species sensitivity distribution (SSD) model. The results showed that the soils of maize and rice were polluted by heavy metals. Cd was the primary pollutant, with an exceeding rate ranging from 87% to 445%. The contaminated level of maize fields was higher than those of rice fields. In contrast, only 3.51% and 13.4% of Cd content in maize kernels and rice grains exceeded the national threshold, and the Cd heavy metal accumulation ability of rice was higher than that of maize. The carcinogenic and non-carcinogenic risks of heavy metals for adults and children in the study area were at a low level. The carcinogenic risk of rice consumption was slightly higher than that of maize, and the health risk to children was higher than that to adults. The results derived from the SSD method showed that the 95% and 5% hazardous concentrations (HC 5 and HC 95 ) of maize fields were 0.67 for Cd, 771.99 for As, 40.85 for Pb and 609.88 for Cr mg·kg -1 , and HC 95 were 48.47 for Cd, 159.67 for As, 1735.68 for Pb and 1671.74 for Cr mg·kg -1 , respectively. The HC 5 values of rice fields were 2.42 for Cd, 8.88 for As, 41.41 for Pb and 27.84 for Cr mg·kg -1 , and the HC 95 values were 48.47 for Cd, 159.67 for As, 1735.68 for Pb and 1671.74 for Cr mg·kg -1 , respectively. The HC 5 values of Cd, As, and Cr in maize fields and Cd in rice fields were significantly higher than the soil risk screening values in the current standard, and the HC 95 values of the two fields were higher than the soil risk intervened values. The results indicated that the current standard would be too strict to evaluate the actual pollution level of soil heavy metals in this area.

Purpose: Camrelizumab, an mAb against programmed cell death protein 1 (PD-1), plus nab-paclitaxel exhibited promising antitumor activity in refractory metastatic immunomodulatory triple-negative breast cancer (TNBC). Famitinib is a tyrosine kinase inhibitor targeting VEGFR2, PDGFR, and c-kit. We aimed to assess the efficacy and safety of a novel combination of famitinib, camrelizumab, and nab-paclitaxel in advanced immunomodulatory TNBC., Patients and Methods: This open-label, single-arm, phase II study enrolled patients with previously untreated, advanced, immunomodulatory TNBC (CD8 IHC staining ≥10%). Eligible patients received 20 mg of oral famitinib on days 1 to 28, 200 mg of i.v. camrelizumab on days 1 and 15, and i.v. nab-paclitaxel 100 mg/m2 on days 1, 8, and 15 in 4-week cycles. The primary endpoint was objective response rate (ORR), as assessed by investigators per RECIST v1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR), safety, and exploratory biomarkers., Results: Forty-eight patients were enrolled and treated. Median follow-up was 17.0 months (range, 8.7-24.3). Confirmed ORR was 81.3% [95% confidence interval (CI), 70.2-92.3], with five complete and 34 partial responses. Median PFS was 13.6 months (95% CI, 8.4-18.8), and median DOR was 14.9 months [95% CI, not estimable (NE)-NE]. Median OS was not reached. No treatment-related deaths were reported. Among 30 patients with IHC, 13 (43.3%) were programmed death-ligand 1 (PD-L1)-negative, and PD-L1 was associated with favorable response. PKD1 and KAT6A somatic mutations were associated with therapy response., Conclusions: The triplet regimen was efficacious and well tolerated in previously untreated, advanced, immunomodulatory TNBC. The randomized controlled FUTURE-SUPER trial is under way to validate our findings. See related commentary by Salgado and Loi, p. 2728., (©2022 The Authors; Published by the American Association for Cancer Research.)

There are some limitations of traditional influenza vaccines concerning novel mutant strains. Therefore, it is particularly important to develop preventive means for antigen-unrelated types of influenza viruses. Recent studies have shown that probiotics can modulate the immune system and reduce the severity of viral infections. In this study, we investigated the potential of Lactiplantibacillus plantarum 0111 against influenza virus H9N2. Challenge experiments showed that L. plantarum 0111 pretreatments could effectively improve mice's survival rate and weight loss and reduce the inflammatory cytokines IL-6 and TNF-α in the lungs and bronchoalveolar lavage fluid (BALF) along with the degree of lung and intestinal injury. FMT experiment demonstrates that the protective effect produced by L. plantarum 0111 is associated with gut microorganisms. In addition, 16S high-throughput sequencing of the mouse intestinal microbiota showed that L. plantarum 0111 remodeled the intestinal microbiota after H9N2 infection and maintained the gut microbiota balance. In a mouse model, the oral administration of L. plantarum 0111 increased IFN-β expression in the serum and BALF. At the same time, the transcript levels of IFN-β and related ISGs in the intestine and lungs of mice were also increased. In addition, the activation and polarization of T cells in mesenteric lymph nodes (MLNs) and the spleen were detected by flow cytometry, and the results showed that L. plantarum 0111 modulated cytokines in T cells and increased IgA expression in B cells in the MLNs and spleen. Thus, L. plantarum 0111 may improve gut microbiota-mediated immune responses and thus, resist infection by the influenza virus, and it could be used as an effective preventive measure against the influenza virus., Competing Interests: WG was employed by Shandong BaoLai-LeeLai Bioengineering Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xing, Shi, Sun, Gu, Zhang, Chen, Li, Wang, Li, Niu, Huang, Qian, Huang, Jiang, Wang, Cao, Wang, Zeng, Yang, Yang and Wang.)

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype. Molecular stratification and target therapy bring clinical benefit for TNBC patients, but it is difficult to implement comprehensive molecular testing in clinical practice. Here, using our multi-omics TNBC cohort ( N = 425), a deep learning-based framework was devised and validated for comprehensive predictions of molecular features, subtypes and prognosis from pathological whole slide images. The framework first incorporated a neural network to decompose the tissue on WSIs, followed by a second one which was trained based on certain tissue types for predicting different targets. Multi-omics molecular features were analyzed including somatic mutations, copy number alterations, germline mutations, biological pathway activities, metabolomics features and immunotherapy biomarkers. It was shown that the molecular features with therapeutic implications can be predicted including the somatic PIK3CA mutation, germline BRCA2 mutation and PD-L1 protein expression (area under the curve [AUC]: 0.78, 0.79 and 0.74 respectively). The molecular subtypes of TNBC can be identified (AUC: 0.84, 0.85, 0.93 and 0.73 for the basal-like immune-suppressed, immunomodulatory, luminal androgen receptor, and mesenchymal-like subtypes respectively) and their distinctive morphological patterns were revealed, which provided novel insights into the heterogeneity of TNBC. A neural network integrating image features and clinical covariates stratified patients into groups with different survival outcomes (log-rank P < 0.001). Our prediction framework and neural network models were externally validated on the TNBC cases from TCGA ( N = 143) and appeared robust to the changes in patient population. For potential clinical translation, we built a novel online platform, where we modularized and deployed our framework along with the validated models. It can realize real-time one-stop prediction for new cases. In summary, using only pathological WSIs, our proposed framework can enable comprehensive stratifications of TNBC patients and provide valuable information for therapeutic decision-making. It had the potential to be clinically implemented and promote the personalized management of TNBC., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2022 The Authors. Publishing Services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Influenza is a serious respiratory disease that continues to threaten global health. Mucosa-associated invariant T (MAIT) cells use T-cell receptors (TCRs) that recognize microbial riboflavin derived intermediates presented by the major histocompatibility complex (MHC) class I-like protein MR1. Riboflavin synthesis is broadly conserved, but the roles or mechanisms of riboflavin in MR1 -/- mouse influenza infection are not well understood. In our study, immunofluorescence techniques were applied to analyze the number and distribution of viruses in lung tissue. The amount of cytokine expression was assessed by flow cytometry (FCM), ELISA, and qPCR. The changes in the fecal flora of mice were evaluated based on amplicon sequencing of the 16S V3-V4 region. Our study showed that MAIT cell deficiency increased mortality and that riboflavin altered these effects in microbiota-depleted mice. The oral administration of riboflavin inhibited IL-1β, IL-17A, and IL-18 production but significantly increased the expression of IFN-γ, TNF-α, CCL2, CCL3, and CCL4 in a mouse model. The analysis of the mouse flora revealed that riboflavin treatment significantly increased the relative abundance of Akkermansia and Lactobacillus ( p < 0.05) and decreased that of Bacteroides . In contrast, MR1 -/- mice exhibited a concentrated aggregation of Bacteroides ( p < 0.01), which indicated that MAIT cell deficiency reduced the diversity of the bacterial population. Our results define the functions of MAIT cells and riboflavin in resistance to influenza virus and suggest a potential role for riboflavin in enhancing MAIT cell immunity and the intestinal flora diversity. Gut populations can be expanded to enhance host resistance to influenza, and the results indicate novel interactions among viruses, MAIT cells, and the gut microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Shi, Zhang, Huang, Jiang, Wang, Cao, Wang, Zeng, Yang, Yang and Wang.)

African swine fever (ASF) is a severe disease affecting pigs with high economic losses and endemicity in various parts of the world. So, it represents a serious threat to the global food safety. The disease was discovered in sub-Saharan Africa where still endemic, and first case was recorded in Kenya in 1921. It is now found all over the world; in Africa, Europe, Asia, and the Pacific it already affects more than 50 countries including Republic of Korea, China, Malaysia, Germany, Bhutan, and India. The P72 protein encoded by the B646L gene is the major protein that reveals high reactogenicity and antigenicity. While the P54 plays a significant role in virus pathogenesis especially cell apoptosis. Multiple virus proteins can suppress the apoptosis of the infected cell at an early stage. The disease spreads through contact with the diseased cases, contaminated fomites, and tick bites. Meanwhile, contaminated water sources might be an essential source of infection. The recovered animals have a significant role in disease persistence as silent carriers. Multiple factors might lead to the observed disease seasonality. Route of exposure, infectious dose, and herd immunity are the main determinants of disease severity and clinical signs. The several types of PCR are well-accepted standard tests for early diagnosis. Although commercial ELISAs were stipulated by OIE, it should be combined with some other virology inspections or serological assays. The ASFV-free countries should be protected against the virus entrance especially that all developed vaccines failed to provoke enough immunity status against the challenged virus. Moreover, it accelerates the speed of revealing clinical symptoms., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Gut bacterial community plays a key role in maintaining host health. The Tibetan pig ( Sus scrofa ), an ancient breed in China, has been known for its high adaptability to harsh environments and for its meat quality. To understand the underlying mechanisms facilitating to shape these unique features, in this study, 16S rRNA sequencing using pigs feces and subsequent bacterial functional prediction were performed. Also, the gut bacteria of two other breeds of pigs, Barkshire and Landrace, were examined for comparison. It was revealed that the structure of bacterial community in Tibetan pigs appeared to be more complex; the relative abundances of dominant bacterial families varied inversely with those of the other pigs, and the proportion of Firmicutes in Tibetan pigs was lower, but Bacteroides, Fibrobacterota , Lachnospiraceae , Oscillospiraceae , and Ruminococcaceae were higher. Bacterial functional prediction revealed that the dominant flora in the Tibetan pigs was more correlated with functions regulating the hosts' immune and inflammatory responses, such as NOD-like&#95;receptor&#95;signaling&#95;pathway and vitamin metabolism. In addition, in Tibetan pigs, the taxonomic relationships in the gut bacteria on day 350 were closer than those on earlier stages. Furthermore, gender played a role in the composition and function of bacterial inhabitants in the gut; for boars, they were more correlated to drug resistance and xenobiotics metabolism of the host compared to the sows. In sum, our preliminary study on the gut bacterial composition of the Tibetan pigs provided an insight into the underlying host-microorganism interactions, emphasizing the role of intestinal bacteria in the context of modulating the host's immune system and host development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Niu, Feng, Shi, Zhang, Chen, Huang, Jiang, Wang, Cao, Wang, Zeng, Yang, Yang and Wang.)

Background: Immune checkpoint inhibitors had a great effect in triple-negative breast cancer (TNBC); however, they benefited only a subset of patients, underscoring the need to co-target alternative pathways and select optimal patients. Herein, we investigated patient subpopulations more likely to benefit from immunotherapy and inform more effective combination regimens for TNBC patients., Methods: We conducted exploratory analyses in the FUSCC cohort to characterize a novel patient selection method and actionable targets for TNBC immunotherapy. We investigated this in vivo and launched a phase 2 trial to assess the clinical value of such criteria and combination regimen. Furthermore, we collected clinicopathological and next-generation sequencing data to illustrate biomarkers for patient outcomes., Results: CD8-positivity could identify an immunomodulatory subpopulation of TNBCs with higher possibilities to benefit from immunotherapy, and angiogenesis was an actionable target to facilitate checkpoint blockade. We conducted the phase II FUTURE-C-Plus trial to assess the feasibility of combining famitinib (an angiogenesis inhibitor), camrelizumab (a PD-1 monoclonal antibody) and chemotherapy in advanced immunomodulatory TNBC patients. Within 48 enrolled patients, the objective response rate was 81.3% (95% CI, 70.2-92.3), and the median progression-free survival was 13.6 months (95% CI, 8.4-18.8). No treatment-related deaths were reported. Patients with CD8- and/or PD-L1- positive tumors benefit more from this regimen. PKD1 somatic mutation indicates worse progression-free and overall survival., Conclusion: This study confirms the efficacy and safety of the triplet regimen in immunomodulatory TNBC and reveals the potential of combining CD8, PD-L1 and somatic mutations to guide clinical decision-making and treatments., Trial Registration: ClinicalTrials.gov: NCT04129996 . Registered 11 October 2019., (© 2022. The Author(s).)

Avian influenza viruses can be efficiently transmitted through mucous membranes, and conventional vaccines are not effective in protecting against mucosal infection by influenza viruses. To induce multiple immune responses in an organism, we constructed a recombinant Lactobacillus plantarum expressing the influenza virus antigen HA1 with the adjuvant dendritic cell-targeting peptide (DCpep). The recombinant L. plantarum strains NC8Δ-pWCF-HA1 and NC8Δ-pWCF-HA1-DCpep were used to immunize mice via oral administration, and the humoral, cellular and mucosal immune responses were evaluated. In addition, the serum levels of specific antibodies and hemagglutination inhibition (HI) levels were also measured. Our results showed that recombinant L. plantarum activated dendritic cells in Peyer's patches (PPs), increased the numbers of CD4 + IFN-γ + and CD8 + IFN-γ + cells in the spleen and mesenteric lymph nodes (MLNs), and affected the ability of CD4 + and CD8 + cells to proliferate in the spleen and MLNs. Additionally, recombinant L. plantarum increased the number of B220 + IgA + cells in PPs and the level of IgA in the lungs and different intestinal segments. In addition, specific IgG, IgG1 and IgG2a antibodies were induced at high levels in the mice serum, specific IgA antibodies were induced at high levels in the mice feces, and HI potency was significantly increased. Thus, the recombinant L. plantarum strains NC8Δ-pWCF-HA1 and NC8Δ-pWCF-HA1-DCpep have potential as vaccine candidates for avian influenza virus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Niu, Xing, Zou, Shi, Huang, Jiang, Wang, Cao, Wang, Zeng, Yang, Yang and Wang.)

To explore a new method of in vitro culture and purification of rat corpus cavernosum endothelial cells (CCECs). Male Sprague-Dawley rats' penile tissue were digested with elastase or collagenase combined with mechanical extrusion to isolate and culture the CCECs. The fixed-point digestion method was used to purify the primary cells. High-purity CCECs were successfully isolated. Following the digestion of the primary CCECs by elastase or collagenase coupled with mechanical extrusion, the cells were paving stone- and cobblestone-shaped over 10 days. The cell purity yielded in the second generation (P2) CCECs after using the fixed-point digestion method was significantly high. Compared with primary CCECs extracted by elastase digestion combined with the mechanical extrusion method, CCECs cultured by collagenase digestion yielded higher purity and a more stable morphology after fixed-point digestion and purification. Immunofluorescence staining of the third generation CCECs and the expression results of endothelial cell-associated marker antibodies CD31 and VWF were positive, and flow cytometry showed the purity of CCECs was 96.9%. Enzymatic digestion combined with mechanical extrusion and fixed-point digestion is a simple, economical method for in vitro culture and purification of CCECs, which is conducive to studying the pathophysiological mechanisms of endothelial dysfunction and erectile dysfunction., (© 2021 Wiley-VCH GmbH.)

Background: The gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) has recently been recognized as one of the novel marker for adverse cardiovascular events and risk of death. However, data on the relationship between TMAO and atrial fibrillation (AF) is limited. The current study was performed to quantify and evaluate the relationship between circulating TMAO levels and AF occurrence., Methods: The electronic databases PubMed, Cochrane Library, and Embase were systematically searched to March 20, 2021. Research studies were considered that recorded or analyzed the prevalence of AF in individuals in specific populations as well as their circulating TMAO levels. A meta-analysis of two-class variables was used to obtain pooled effects. A dose-response meta-analysis was used to investigate the dose-response relationship between TMAO levels and the risk of AF., Results: Six studies with a total of 8,837 individuals and 1,668 AF cases were included in the present meta-analysis. Compared with a lower circulating TMAO level, a higher TMAO level was associated with a higher prevalence of AF [odds ratio (OR): 1.40; 95% confidence interval (CI): 1.23, 1.59; I2=19.8%]. The dose-response analysis revealed the risk of AF increased by 6% per 1-µmol/L increment (OR: 1.06; 95% CI: 1.00, 1.11), 32% per 5-µmol/L increment (OR: 1.32; 95% CI: 1.03, 1.70), and 73% per 10-µmol/L increment (OR: 1.73; 95% CI: 1.05, 2.86) of the circulating TMAO level., Discussion: This is the first systematic literature review and meta-analysis to demonstrate a significant dose-dependent relationship between increased AF risk and circulating TMAO levels.

H9N2 subtype, a low pathogenic avian influenza virus, is emerging as a major causative agent circulating poultry workplaces across China and other Asian countries. Increasing case number of interspecies transmissions to mammals reported recently provoked a great concern about its risks inducing global pandemics. In an attempt to understand the underlying mechanism of how the H9N2 virus disrupts the interspecies segregation to transmit to mammals. A mutant H9N2 strain was obtained by passaging the wildtype H9N2 A/chicken/Hong Kong/G9/1997 eight times from lung to lung in BALB/c mice. Our finding revealed that mice manifested severe clinical symptoms including losses of body weight, pathological damages in pulmonary sites and all died within two weeks after infected with the mutated H9N2, whereas all mice survived upon infected with wildtype strain in comparison, which suggested increased pathogenicity of the mutant strain. In addition, mice showed enhanced levels of proinflammatory cytokines in sera, including IL-6, TNF-α and IL-1β compared to those subjected to wildtype viral infections. Sequence analysis showed that five amino acid substitutions occurred at PB2 627 , HA 87, HA 234 , NP 387 and M 156 , and a deletion mutation happened in the M gene (M 157 ). Of these mutations, PB2 E627K played key roles in modulating lethality in mice. Taken together, the mutant H9N2 strain obtained by serial passaging of its wildtype in mice significantly increased its virulence leading to death of mice, which might be associated the accumulated mutations occurred on its genome., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Gut microbes play an important role in the development of host B cells. It has been controversial whether GALT is the development site of B cells in pigs. By investigating the relationship between gut microbes and the development of B cells in the GALT of piglets, we found, to our knowledge for the first time, that early B cells exist in the gut lamina propria (LP) in pigs at different ages. We further used Lactobacillus rhamnosus GG (LGG) to treat piglets. The results showed that LGG promotes the development of the early B lineage, affects the composition of the Ig CDR3 repertoires of B cells, and promotes the production of IgA in the intestinal LP. Additionally, we found that the p40 protein derived from LGG can activate the EGFR/AKT and NF-κB signaling pathways, inducing porcine intestinal epithelial cells (IPEC-J2) to secrete a proliferation-inducing ligand (APRIL), which promotes IgA production in B cells. Finally, we identified ARF4 and DIF3 as candidates for p40 receptors on IPEC-J2 by GST pull-down, liquid chromatography-mass spectrometry/mass spectrometry analysis, and coimmunoprecipitation. In conclusion, LGG could promote early B cell differentiation and development in the intestinal LP in piglets and might contribute to promoting IgA production via secretion of p40, which interacts with the membrane receptors on IPEC-J2 and induces them to secrete APRIL. Our study will provide insight to aid in better utilization of probiotics to increase human health., (Copyright © 2021 by The American Association of Immunologists, Inc.)

A vaccine against Trichinella spiralis infection is urgently needed to interrupt its transmission from domestic animals to humans. However, no vaccine against T. spiralis is currently available. Our previous study demonstrated that the use of the 43-kDa glycoprotein present in excretory-secretory (ES) proteins of muscle larvae (ML) as an intramuscular DNA vaccine led to a 52.1% protection rate against T. spiralis infection. Attenuated Salmonella strains have the advantage of eliciting mucosal immunity, which is important for controlling T. spiralis infections at the intestinal stage and can be provided as vaccines via oral or intranasal routes. Therefore, in this study, complete 43-kDa glycoprotein (Ts43) sequences of T. spiralis were cloned into the vector pYA3681, and the recombinant plasmid pYA3681-Ts43 was transformed into the attenuated Salmonella typhimurium strain χ11802. The results showed that oral vaccination of mice with attenuated Salmonella carrying the recombinant plasmid pYA3681-Ts43 induced an evident elevation of the local intestinal mucosal sIgA and serum IgG antibody responses. The flow cytometry results showed that the percentages of CD4 + T cells and secreted IFN-γ, IL-4, and IL-17A in CD4 + T cells were significantly increased in the spleen and mesenteric lymph node (MLN) lymphocytes of the vaccinated groups. In addition, increased levels of the IFN-γ, IL-4, and IL-17A cytokines were also observed in the serum of the immunized groups. The above immune response results in the immunized groups demonstrated that protective immunity was elicited in this study. Finally, vaccinated mice demonstrated a significant 45.9% reduction in ML burden after infection with T. spiralis. This study demonstrated that oral vaccination with Ts43 delivered by attenuated Salmonella elicited local and systemic concurrent Th1/Th2/Th17 immune responses and provided partial protection against T. spiralis infection in BALB/c mice. This is a prospective strategy for the prevention and control of trichinellosis., (Copyright © 2021. Published by Elsevier B.V.)

African classical swine fever virus (ASFV) has spread seriously around the world and has dealt with a heavy blow to the pig breeding industry due to the lack of vaccines. In this study, we produced recombinant Lactobacillus plantarum (L. plantarum) expressing an ASFV p54 and porcine IL-21 (pIL-21) fusion protein and evaluated the immune effect of NC8-pSIP409-pgsA'-p54-pIL-21 in a mouse model. First, we verified that the ASFV p54 protein and p54-pIL-21 fusion protein were anchored on the surface of L. plantarum NC8 by flow cytometry, immunofluorescence and Western blotting. Then, the results were verified by flow cytometry, ELISA and MTT assays. Mouse-specific humoral immunity and mucosal and T cell-mediated immune responses were induced by recombinant L. plantarum. The results of feeding mice recombinant L. plantarum showed that the levels of serum IgG and mucosal secreted IgA (SIgA), the number of CD4 and CD8 T cells, and the expression of IFN-γ in CD4 and CD8 T cells increased significantly, and lymphocyte proliferation occurred under stimulation with the ASFV p54 protein. Our data lay a foundation for the development of oral vaccines against ASFV in the future., (© 2021. The Author(s).)

In the present study, we have designed and synthesized a series of 42 novel sulfonylurea compounds with ortho- alkoxy substitutions at the phenyl ring and evaluated their herbicidal activities. Some target compounds showed excellent herbicidal activity against monocotyledon weed species. When applied at 7.5 g ha -1 , 6-11 exhibited more potent herbicidal activity against barnyard grass ( Echinochloa crus-galli ) and crab grass ( Digitaria sanguinalis ) than commercial acetohydroxyacid synthase (AHAS; EC 2.2.1.6) inhibitors triasulfuron, penoxsulam, and nicosulfuron at both pre-emergence and postemergence conditions. 6-11 was safe for peanut for postemergence application at this ultralow dosage, suggesting that it could be considered a potential herbicide candidate for peanut fields. Although 6-11 and triasulfuron share similar chemical structures and have close K i values for plant AHAS, a significant difference has been observed between their LUMO maps from DFT calculations, which might be a possible factor that leads to their different behaviors toward monocotyledon weed species.

Trichinellosis is a significant food-borne zoonotic parasitic disease caused by parasite Trichinella. Given the side effects of anti-Trichinella drugs (e.g., Mebendazole) aroused in the course of treatments, an effective vaccine against the parasite is called for. The therapies available to date are in most instances targeting a single stage of Trichinella, resulting in an incomplete protective immunity against the parasite in terms of the complexity of its developmental stages. In this study, a recombinant dual-expression double anchor vector NC8-pLp-TsNd-S-pgsA'-gp43 was constructed carrying two antigen genes from Trichinella spiralis (T. spiralis), encoding the gp43 and T. spiralis Nudix hydrolase (TsNd) proteins which were mainly expressed in muscle larva (ML) and intestinal infective larva stages of the parasite respectively. These two proteins were to be expressed by Lactobacillus plantarum NC8 (L. plantarum NC8) which was designed to express the two anchored peptides, a truncated poly-γ-glutamic acid synthetase A (pgsA') and the surface layer protein of Lactobacillus acidophilus (SlpA), on its surface for attaching expressed foreign proteins. Oral immunization with the above recombinant vaccine induced higher levels of specific serum IgG and mucosal secretory IgA (SIgA) in BALB/c mice. In addition, cytokines, interferon-γ (IFN- γ), interleukin-4 (IL-4) and IL-17 released by lymphocytes, and CD4 + levels displayed on the surfaces of splenic and mesenteric lymph cells were significantly enhanced by the vaccination. Moreover, after larval challenges, a 75.67 % reduction of adult worms (AW) at 7 days post-infection (dpi) and 57.14 % reduction of ML at 42 dpi were observed in mice immunized with the recombinant vaccine. Furthermore, this oral vaccination reduced the counts of encysted larvae presented in tongue and masseter muscles after infected with T. spiralis in mice. The overall results demonstrated that the recombinant vaccine developed in this study could induce specific humoral, mucosal, and cellular immune responses, and provides protections against different stages (adult worms and muscle larva) of T. spiralis infections in BALB/c mice, which could make it a promising oral vaccine candidate against trichinellosis., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Acute pancreatitis (AP) is a sudden inflammatory process in the pancreas with variable involvement of nearby organs or other organ systems, and it is a common cause for hospitalization of gastrointestinal origin. Early prediction of the prognosis of patients with AP is important to help physicians triage the patients and decrease mortality. Red cell distribution width (RDW) and total serum calcium (TSC) have been reported to be useful predictors of the severity of AP, but if these parameters are associated with the prognosis of AP is unknown. The objective of the study was to evaluate whether RDW/TSC can be used to predict the prognosis of patients with AP at an early stage., Methods: We retrospectively enrolled AP patients admitted to the emergency department of West China Hospital of Sichuan University from January 1, 2016, to June 30, 2016. According to the prognosis, AP patients were divided into ICU group and non-ICU group, surgery group and nonsurgery group, and hospital survival group and hospital death group. Demographic information and clinical and laboratory parameters of all enrolled patients after being admitted to ED were compared between the groups. The receiver operator characteristic (ROC) curves were used to evaluate the prognostic values of RDW, TSC, and RDW/TSC in patients with AP., Results: A total of 666 AP patients were enrolled in this study, with an average age of 47.99 ± 14.11 years, including 633 patients who survived to discharge and 33 patients who died during hospitalization. The areas under the curve (AUC) of RDW and RDW/TSC predict that patients need to be admitted to ICU (0.773 vs. 0.824 vs. 0.723), patients need surgery treatment (0.744 vs. 0.768 vs. 0.690), and patients survived to hospital discharge (0.809 vs. 0.855 vs. 0.780) were greater than that of TSC, with RDW/TSC being the greatest., Conclusions: RDW/TSC may be a new method to identify the AP patients who need to be transferred to the ICU, accompanying complications which need surgery treatment, or may be died in hospital at an early stage, and we should pay more attention to RDW/TSC in patients with AP, for they may have a worse prognosis., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 Tian-Yong Han et al.)

Zinc finger and BTB domain containing 1(Zbtb1) is a transcriptional suppressor protein, and a member of the mammalian Zbtb gene family. Previous studies have shown that Zbtb1 is essential for T-cell development. However, the role of Zbtb1 in T-cell lymphoma is undetermined. In this study, an EL4 cell line with Zbtb1 deletion was constructed using the CRISPR-Cas9 technique. The expression profiles of microRNA and circRNA produced by the control and gene deletion groups were determined by RNA-seq. In general, 24 differentially expressed microRNA and 16 differentially expressed circRNA were found between normal group and gene deletion group. Through further analysis of differentially expressed genes, GO term histogram and KEGG scatter plot were drawn, and three pairs of miRNA and circRNA regulatory relationships were found. This study describes the differentially expressed microRNA and circRNA in normal and Zbtb1-deficient EL4 cell lines, thus providing potential targets for drug development and clinical treatment of T-cell lymphoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Shi, Lu, Zeng, Cheng, Wang, Sun, Jiang, Yang, Zhao, Huang, Ye, Cao, Yang and Wang.)