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Abstract Background Adaptive immunity is an important disease mediator of pulmonary vascular remodeling during pulmonary hypertension (PH) development, especially T‐cells lymphocytes. However, data for bibliometric analysis of T cell immunity in PH is currently vacant. This aimed to provide a comprehensive and visualized view of T‐cells research in PH pathogenesis and to lay a solid foundation for further studies. Methods The data was acquired from the Web of Science Core Collection database. Web of Science analytic tool was used to analysis the publication years, authors, journals, countries, and organizations. CiteSpace 6.2.R3, VOSviewer 1.6.16, and Scimago Graphica 1.0.35.0 were applied to conduct a visualization bibliometric analysis about authors, countries, institutions, journals, references, and keywords. Results Nine hundred and eight publications from 1992 to 2022 were included in the analysis. The results showed that Humbert Marc was the most prolific author. American Journal of Physiology Lung Cellular and Molecular Physiology had the most related articles. The institution with the most articles was Udice French Research University. The United States was far ahead in the article output. Keywords analysis showed that “Pulmonary hypertension” was the most usually appeared keyword in the relevant literature, and included “T‐cells”, “Regulatory T cells”, and “Activated T cell.” “miRNA” of reference co‐citation clustering analysis demonstrated the possible T‐cell immunity activation mechanisms in PH. The most cited literature was published in the European Heart Journal by Galie N in 2016. The strongest citation burst of keyword is “gene expression” and terms such as “vascular remodeling,” “growth,” “proliferation,” and “fibrosis” are among the list, indicating that T‐cells interact with stromal vascular cells to induce pulmonary vascular remodeling. The strongest burst of cited reference is “Galie N, 2016.” Conclusions T‐cell immunity is an important pathogenesis mechanism for PH development, which may have interaction with miRNAs and stromal vascular cells, but the possible T‐cell immunity activation mechanisms in PH need to be investigated further.

Background & aimsAccumulating studies have demonstrated associations between single lifestyle exposures and metabolic dysfunction-associated fatty liver disease (MAFLD). However, the joint effects of lifestyle exposures remain unclear, hindering the development of targeted prevention and control strategies. We aimed to investigate the joint associations between lifestyle exposomes and MAFLD.MethodsThis study included 5,002 participants from NHANES 2017–2020. Lifestyle exposomes, including sleep duration, metabolic equivalent of task (MET), Healthy Eating Index (HEI)-2015 score, alcohol consumption, and smoke exposure, were identified from questionnaire data. MAFLD was diagnosed by vibration-controlled transient elastography measurements and laboratory data. A logistic regression model and the weighted quantile sum method were used to evaluate the associations of single and joint lifestyle exposomes, respectively, with MAFLD. The population attributable fractions (PAFs) were calculated to assess the population benefits of different intervention strategies.ResultsPer-quartile range increases in sleep duration (OR=0.883, 95% CI: 0.826–0.944), MET (0.916, 0.871–0.963), and HEI-2015 score (0.827, 0.756–0.904) were significantly associated with MAFLD. The joint exposure of sleep duration, MET, and HEI-2015 score was associated with MAFLD (0.772, 0.688–0.865), with the highest weight (importance) for MET (0.526). PAFs revealed greater intervention benefits for sleep and the HEI-2015 when the majority of the population (>5%) had a low MAFLD risk (weak intervention targets), whereas MET was the most efficient intervention strategy when minority populations (≤5%) had a low MAFLD risk (strong intervention targets).ConclusionThis study demonstrated significant associations between MAFLD and single and joint exposures to sleep duration, MET, and HEI-2015 and identified physical activity as the most important lifestyle factor. Further population benefit analyses may provide evidence and suggestions for population-level interventions.

The Department of Commerce (DOC) uses differential pricing analysis in order to detect whether a foreign exporter dumps goods in the U.S. market at prices lower than the exporter sells the goods for in its domestic market. A dumping duty is then levied on the exporter, the amount of which depends on the dumping margin. Several recent cases at the Federal Circuit Court of Appeals have challenged the DOC’s methodology on statistical grounds. In this article, the DOC’s procedure for calculating the dumping margin is described in detail, including the rules for the controversial zeroing policy. Several statistical issues with the DOC’s approach are identified and some potential improvements are proposed.

Triple-negative breast cancer (TNBC) is a challenging subtype with unclear biological mechanisms. Recently, the transcription factor androgen receptor (AR) and its regulation of the DLGAP5 gene have gained attention in TNBC pathogenesis. In this study, we found a positive correlation between high AR expression and TNBC cell proliferation and growth. Furthermore, we confirmed DLGAP5 as a critical downstream regulator of AR with high expression in TNBC tissues. Knockdown of DLGAP5 significantly inhibited TNBC cell proliferation, migration, and invasion. AR was observed to directly bind to the DLGAP5 promoter, enhancing its transcriptional activity and suppressing the activation of the p53 signaling pathway. In vivo experiments further validated that downregulation of AR or DLGAP5 inhibited tumor growth and enhanced CD8+ T cell infiltration. This study highlights the crucial roles of AR and DLGAP5 in TNBC growth and immune cell infiltration. Taken together, AR inhibits the p53 signaling pathway by promoting DLGAP5 expression, thereby impacting CD8+ T cell infiltration in TNBC.

Benign metastasizing leiomyoma (BML) is a rare disease that results from metastasis of uterine leiomyoma to distant sites with benign pathologic features. The lung is the most common metastatic site for BML. This report describes the case of a 49-year-old woman who presented with a mass in the abdominal wall with a surgical history of uterine myomectomy. Ultrasound and Magnetic resonance imaging (MRI) revealed multiple mass lesions. The histopathology of the mass specimen indicated BML. The imaging and clinical features of BML are discussed based on the characteristics of this case and related literature reports.

Abstract Background Mechanical ventilation can cause acute atrophy and injury in the diaphragm, which are related to adverse clinical results. However, the underlying mechanisms of ventilation-induced diaphragm dysfunction (VIDD) have not been well elucidated. The current study aimed to explore the role of cellular senescence in VIDD. Methods A total of twelve New Zealand rabbits were randomly divided into 2 groups: (1) spontaneously breathing anaesthetized animals (the CON group) and (2) mechanically ventilated animals (for 48 h) in V-ACV mode (the MV group). Respiratory parameters were collected during ventilation. Diaphragm were collected for further analyses. Results Compared to those in the CON group, the percentage and density of sarcomere disruption in the MV group were much higher (p

Background The Masimo Total Hemoglobin SpHb® is a continuous and non-invasive handheld device to measure hemoglobin levels. Previous research has found that SpHb is able to accurately detect hemoglobin levels in adult patients with a similar degree of bias and standard deviation to point-of-care invasive method measurements. Generally, limited clinical evidence, lack of validation of Masimo at higher than and lower than hemoglobin threshold values, and scientific consensus supporting the use of Masimo for accurate hemoglobin testing for the diagnosis of anemia during pregnancy calls for further research. Methods and analysis The proposed prospective cohort will be nested within the ongoing Pregnancy Risk and Infant Surveillance and Measurement Alliance (PRISMA) Maternal and Newborn Health (MNH) study. Three study sites (located in Zambia, Kenya, and Pakistan) will participate and collect hemoglobin data at five time points (

To exploit aquatic animals’ feed resources and functional ingredients and additives, this experiment investigated the effects (a 2 × 2 factorial trial) and mechanism of woody plants and probiotics on Nile tilapia. Each treatment group was randomly assigned triplicate nets of 40 fish (initial body weight of 35.04 ± 0.01 g) in 12 tanks for 56 days. Fish were fed four diets, including a CON–CON diet (with no supplementation) and CON–Ba (basal diet + 1 × 107 CFU/g B. amyloliquefaciens), MO-CON (basal diet + 10% Moringa oleifera) and MO-Ba (basal diet + 1 × 107 CFU/g B. amyloliquefaciens + 10% Moringa oleifera) until apparent satiation (2 meals/day). The results showed that the MO diet had a lower feed conversion ratio than the non-MO diets (P

Abstract Objective The study aimed to conduct a bibliometric analysis of mucosal immunity in IgA nephropathy (IgAN) and indicate its current status, hot sopts, and direction of future studies. Methods The literature data was collected from the Web of Science Core Collection. CiteSpace 6.1.R3 was employed to conduct a visualization bibliometric analysis of mucosal immunity in IgA nephropathy, including authors, countries, journals, keywords, organizations, references, the bursts of keywords and references, and the timeline of keyword clusters and reference clusters. Results A total of 315 publications from 1990 to 2022 were included. The number of articles in this field has increased in recent years. Suzuki H, Coppo R, and Feehally J took the first place parallelly with 18 articles. Japan contributes the most articles, accounting for 27.3% of all the publications. The institutions with the most publications were Juntendo University and University of Alabama Birmingham. 453 keywords were concluded in the analysis, which mainly focus on the mucosal pathogenesis and therapy of the IgAN. The top five co‐cited reference cluster are “aberrantly glycosylated IgA,” “corticosteroids,” “animal models,” “o‐glycosylationm” and “microRNA‐630.” The most recently burst of keyword is “tonsillectomy” and “gut.” Conclusion This was the first bibliometric analysis to systematically analyze the mucosal immunity in IgAN, which obtained the current status and indicated the future research hotspots and development trends. The gut microbiota and the related therapy‐targeted mucosal immunity might be the future research hotspot.

Background: Particulate matter (PM) exposure has been linked with cardiovascular disease (CVD) and metabolic syndrome (MetS), the latter characterized by concurrent multiple metabolic disorders. As a result, the mechanisms assumption from PM to CVD through MetS have emerged, thus requiring further epidemiological evidence. This cohort study aimed to assess whether MetS mediates the associations of PM with CVD risk. Methods: This study included 14,195 participants from the Chengdu cohort of the China Multi-Ethnic Cohort (CMEC) study in 2018. The primary outcome of incident CVD diagnoses was identified using matched hospital records from the Health Information Center of Sichuan Province. Residence-specific levels of PM with aerodynamic diameters of ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10) were estimated by spatiotemporal models. Causal mediation analyses were applied to evaluate the indirect effect of MetS. Results: Increased exposure levels to PM were significantly associated with MetS and CVD. Mediation analyses indicated that the associations between PM exposure and CVD were mediated by MetS, with the proportion of multiple mediations being 19.3%, 12.1%, and 13.5% for PM1, PM2.5, and PM10, respectively. Further moderated mediation analyses suggested that male, overweight individuals, alcohol drinkers, and those suffering from indoor air pollution may experience more significant adverse effects from PM exposure on CVD via MetS than others. Conclusions: Our findings suggest that MetS partially mediates the association between long-term exposure to PM and CVD. These mediation effects appear to be amplified by demographic characteristics and unhealthy lifestyles.

Abstract Background Significant association between bullous pemphigoid (BP) and stroke has been reported. This study aimed to evaluate the level of anti-BP180 antibody in stroke patients to explore the relationship between BP and stroke in their pathogenesis. Methods We collected serum samples from stroke patients and matched controls between February 2019 and June 2020. The anti-BP180 antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Results A total of 1183 stroke patients including 970 with cerebral infarction (CI), 192 with intracerebral hemorrhage (ICH), 21 with CI and ICH, and 855 controls were enrolled in this study. Anti-BP180 autoantibody values were significantly higher in stroke patients than in controls (p < 0.001). Anti-BP180 autoantibody-positive rates were 12.51% (148) in stroke patients and 4.68% (40) in controls (p < 0.001, OR = 2.65). In anti-BP180 autoantibody-positive subjects, the values were significantly higher in stroke patients than in controls (p < 0.001). However, only 10 (6.76%) stroke patients and 3 (7.5%) controls had high values (> 100 RU/mL) (p = 0.87). Stratified analysis showed that anti-BP180 antibody positive rates were independent of age, sex, and stroke subtypes in the stroke group. Positive rates in patients with both CI and ICH were nearly two times higher than those in patients with either CI or ICH alone (p = 0.11, OR = 1.94). Study limitations This study had a limited sample size and lacked quantitative criteria for stroke severity. Conclusions Anti-BP180 antibody values and positive rates were higher in stroke patients than in controls, suggesting that stroke patients may have higher of developing BP.

Abstract South China belongs to the northern geographic branch of the Australasian strewn field (AASF) of tektites and microtektites, and this area is assumed to be part of the uprange region of the putative impactor trajectory that formed the yet undiscovered source crater. Ferromagnetic minerals in impact glass may record the magnetization process and thermal history of impact melt, but the possible identity of ferromagnetic minerals in AASF tektites from South China is elusive. Here, we perform a rock magnetism and crystallography study of iron‐sulfur spherules in Muong Nong‐type tektites from South China, revealing abundant single‐domain and pseudo single‐domain nano‐grains of magnetite within the spherules. This result is consistent with the detection of magnetic signals caused by single‐domain and pseudo single‐domain magnetite in these samples. Compared to the large value ranges of magnetic properties of tektites in the entire strewn field, individual specimens of both Muong Nong‐type and single splash‐form tektites have relatively homogeneous magnetic properties in terms of magnetic susceptibility, natural remanent magnetization (NRM), saturation isothermal remanent magnetization (SIRM) and NRM/SIRM ratio. The results indicate that the impact melt that formed each tektite specimen experienced similar thermal history, and most AASF tektites from South China were cooled in an ambient magnetic field that is the same order of magnitude as the Earth's magnetic field.

Abstract Background Positive end-expiratory airway pressure (PEEP) is a potent component of management for patients receiving mechanical ventilation (MV). However, PEEP may cause the development of diaphragm remodeling, making it difficult for patients to be weaned from MV. The current study aimed to explore the role of PEEP in VIDD. Methods Eighteen adult male New Zealand rabbits were divided into three groups at random: nonventilated animals (the CON group), animals with volume-assist/control mode without/ with PEEP 8 cmH2O (the MV group/ the MV + PEEP group) for 48 h with mechanical ventilation. Ventilator parameters and diaphragm were collected during the experiment for further analysis. Results There was no difference among the three groups in arterial blood gas and the diaphragmatic excursion during the experiment. The tidal volume, respiratory rate and minute ventilation were similar in MV + PEEP group and MV group. Airway peak pressure in MV + PEEP group was significantly higher than that in MV group (p

Background The neuroendocrine tumor (NET) is rare, accounting for about 0.5% of all tumors. NETs have the characteristics of metastasis, especially lymph nodes, liver, spleen, and bone. Case presentation We report a 30‐year‐old man diagnosed with a NET with bone metastasis and presented with waist and leg pain. The imaging findings of this case showed multiple osteosclerosis and no apparent bone destruction. We collected the patient's previous examinations, including laboratory, imaging, and pathological examination to get a precise diagnosis. Given this case, we carried out symptomatic support treatment to relieve the patients' pain symptoms. Conclusion Bone metastases from NETs of unknown primary site are rare in both clinical and imaging manifestations. The disease is mainly manifested as multiple osteosclerosis, accompanied by muscle soreness and pain. It is recommended to try chemotherapy for this disorder.

The study of gene therapies has been of particular interest in recent decades due to their promising potential to slow or even rescue the degeneration of the retina in inherited retinal dystrophies (IRDs). Here, we review the current approaches to gene therapy trials on IRDs, including the selection of animal models, therapeutic window, vectors and dosages. Mice are typically the first choice of animal models and recombinant adeno-associated virus (rAAV) of serotype 8 is the most common vector for loss-of-function IRDs. Furthermore, the therapeutic window should be considered to ensure efficacy before retinal degeneration occurs if possible, and dosages must be tailored to each approach.

In December 2020, Texas filed a motion to the U.S. Supreme Court claiming that the four battleground states: Pennsylvania, Georgia, Michigan, and Wisconsin did not conduct their 2020 presidential elections in compliance with the Constitution. Texas supported its motion with a statistical analysis purportedly demonstrating that it was highly improbable that Biden had more votes than Trump in the four battleground states. This article points out that Texas’s claim is logically flawed and the analysis submitted violated several fundamental principles of statistics.

Background: The Masimo Total Hemoglobin SpHb® is a continuous and non-invasive handheld device to measure hemoglobin levels. Previous research has found that SpHb is able to accurately detect hemoglobin levels in adult patients with a similar degree of bias and standard deviation to point-of-care invasive method measurements. Generally, limited clinical evidence, lack of validation of Masimo at higher than and lower than hemoglobin threshold values, and scientific consensus supporting the use of Masimo for accurate hemoglobin testing for the diagnosis of anemia during pregnancy calls for further research. Methods and analysis: The proposed prospective cohort will be nested within the ongoing Pregnancy Risk and Infant Surveillance and Measurement Alliance (PRISMA) Maternal and Newborn Health (MNH) study. Three study sites (located in Zambia, Kenya, and Pakistan) will participate and collect hemoglobin data at five time points (

Osteosarcoma often presents the low response to chemotherapy, which brings difficulties to the treatment. Recently, it has become a new idea to use photothermal effect and Fenton/Fenton-like reaction to treat tumors or enhance the killing effect of chemotherapy drugs. We developed an iron-containing nanomaterial SiO2@PDA/Fe3+-FA (PDA: polydopamine; FA: folate) to treat chemotherapy-insensitive osteosarcoma. The nanomaterial has been proven to have: (1) high drug delivery efficiency (doxorubicin and cisplatin: 21.25% and 23.80% respectively), (2) precise release of drugs in pH response, (3) good biocompatibility, (4) effective tumor targeting (8 h after injection), and (5) satisfactory photothermal efficiency (photothermal conversion efficiency: 57.63%). Of note, nanomaterial containing Fe3+ ions can activate the Fenton-like reaction to generate reactive oxygen species (ROS) and induce apoptosis of drug-insensitive osteosarcoma cells. In addition, nanomaterial can also enhance the killing effect of cisplatin on drug-insensitive osteosarcoma. The activation of Fenton-like reaction and the recovery of cisplatin function by nanomaterials are significantly enhanced under low temperature photothermal conditions. The in vitro and in vivo experiments showed that SiO2@PDA/Fe3+-FA could be loaded with appropriate chemotherapy drugs and could be used as an effective means of synergistic therapy for drug-resistant tumors in combination with near infrared ray (NIR) irradiation.

Cutaneous Mycobacterium marinum infection is an increasingly infectious disease presenting unique diagnostic and therapeutic challenges. The aim of this study was to evaluate the differences in time to treatment among patients with different types of skin lesions and who were treated with single or multidrug therapies. In addition, the clinical characteristics of M. marinum infection were explored and the mechanism of the host immune responses was investigated. The electronic medical records of 35 patients with M. marinum infection were reviewed. The clinical characteristics, histopathological and laboratory data, and treatment outcomes were analyzed. Immunohistochemical analysis was performed to clarify the immune mechanisms induced by M. marinum infection in 9 patients and 5 healthy controls. Of the 35 patients, 25 (71.4%) had lesions with sporotrichoid patterns. The duration of patients with sporotrichoid lesions or treatment with multiple drugs was longer, although differences were not significant, possibly due to the small cohort. However, this trend was also observed in previous studies, making it worthy of further attention. Expression levels of cytokines (IFN-γ, IL-4, IL-9, and FOXP3) were significantly upregulated in the patient specimens, whereas there were no significant differences in IL-17 and IL-22 expression levels between the patient and control groups.

Bone metastases, as one of the common types of metastatic tumors, have a great impact on the survival period and quality of life of patients. Bone metastases are usually characterized by bone destruction. Skeletal related events caused by bone destruction often lead to pain, pathological fractures and even paralysis. In this review, we provide a detailed explanation of bone metastases from the epidemiology, clinical features, pathogenesis, and recently developed clinical treatment viewpoints. We concluded that the incidence of bone metastases is increasing gradually, with serious clinical symptoms, complex pathogenesis and diverse clinical treatment. Tumor cells, immune cells, osteoblasts/osteoclasts and other cells as well as cytokines and enzymes all play a key role in the pathogenesis of bone metastases. We believe that the future treatment of bone metastases will be diversified and comprehensive. Some advanced technologies, such as nanomedicine, could be used for treatment, but this depends on understanding how disease occurs. With the development of treatment, the survival time and quality of life of patients will be improved.

This study is a first report on the identification of multidrug-resistant (MDR) Acinetobacter bereziniae among non-baumannii acinetobacters that had previously escaped automated laboratory detection, and characterize their clinical courses of infection at two tertiary-care hospitals in Shenzhen city, China (2015–2017). Herein, definitive identification by PCR was performed with universal and species-specific primers targeting 16S rDNA and rpoB genes, respectively, followed by Sanger sequencing and blast analysis. Antimicrobial susceptibility of A. bereziniae isolates was assessed accordingly. Three of the five identified A. bereziniae isolates exhibited carbapenem-resistance and were subjected to a multiplex PCR assay to detect drug-resistance genes. Sequences of the rpoB amplicon were aligned with curated sequences from global databases for phylogenetic analysis on evolutionary relations. Five clinical isolates of A. bereziniae were thereby re-identified, whose infections were primarily nosocomial. Automated identification and susceptibility testing systems (Phoenix-100 and VITEK 2) proved insufficient for discriminating A. bereziniae from other acinetobacters such as Acinetobacter baumannii and Acinetobacter guillouiae. Among these isolates, three exhibited carbapenem-resistant phenotypes indistinguishable from that of carbapenem-resistant A. baumannii. The carbapenem-resistant A. bereziniae isolates were subsequently confirmed to carry a blaNDM-1 (New Delhi metallo-β-lactamase-1) gene downstream of ISAba125. Phylogenetic analysis revealed that A. bereziniae isolates evolved slowly but independently in local habitats. A. bereziniae isolates are difficult to distinguish by traditional automated detection systems. PCR-based identification via amplification and sequencing of selected house-keeping genes provides sufficient resolution for discriminating the isolates.

Abstract Background The reported incidence of sexually transmitted infections (STIs) in China has been increasing over the last decades, especially among drug users, which has become one of the main burdens of public health in China. This study was conducted to estimate the prevalence and associated factors of STIs among non-injecting methamphetamine (MA) users in Eastern China. Methods A cross-sectional survey was conducted among 632 MA users in Eastern China in 2017. Demographic characteristics, sexual behaviors, behaviors of MA use and sexual health knowledge were collected through questionnaire. First pass urine specimens were collected and detected for deoxyribonucleic acid (DNA) of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) with Nucleic Acid Amplification Technology (NAAT), while blood specimens were collected and detected for antibodies of Human immunodeficiency virus (HIV), Herpes simplex virus type-2 (HSV-2), and syphilis with enzyme-linked immune sorbent assay (ELISA). Results Among the 632 MA users, 464 (73.42%) were males, 60.92% were

Plants can rapidly close stomata to restrict pathogen entry into leaves. Here the authors show that phosphorylation of villin3 by mitogen-activated protein kinases modulates actin remodeling to activate stomatal defense in Arabidopsis.

Abstract Background According to the differences of antigen and genetic composition, canine coronavirus (CCoV) consists of two genotypes, CCoV-I and CCoV-II. Since 2004, CCoVs with point mutations or deletions of NSPs are contributing to the changes in tropism and virulence in dogs. Results In this study, we isolated a CCoV, designated HLJ-071, from a dead 5-week-old female Welsh Corgi with severe diarrhea and vomit. Sequence analysis suggested that HLJ-071 bearing a complete ORF3abc compared with classic CCoV isolates (1-71, K378 and S378). In addition, a variable region was located between S gene and ORF 3a gene, in which a deletion with 104 nts for HLJ-071 when compared with classic CCoV strains 1-71, S378 and K378. Phylogenetic analysis based on the S gene and complete sequences showed that HLJ-071 was closely related to FCoV II. Recombination analysis suggested that HLJ-071 originated from the recombination of FCoV 79-1683, FCoV DF2 and CCoV A76. Finally, according to cell tropism experiments, it suggested that HLJ-071 could replicate in canine macrophages/monocytes cells. Conclusion The present study involved the isolation and genetic characterization of a variant CCoV strain and spike protein and ORF3abc of CCoV might play a key role in viral tropism, which could affect the replication in monocyte/macrophage cells. It will provide essential information for further understanding the evolution in China.

Paeonia lactiflora Pall. is an important ornamental plant with high economic and medicinal value, which has considerable development prospects worldwide. The lack of efficient tissue culture techniques and genetic transformation systems has become a master obstacle for P. lactiflora research. The purpose of the present study focuses on obtaining an efficient and stable genetic transformation method using callus as the receptor and exploring an efficient protocol for callus induction and proliferation associated with P. lactiflora. Callus induction and proliferation were performed using MS medium with various concentrations of 2,4-Dichlorophenoxyacetic acid (2,4-D), 1-Naphthaleneacetic acid (NAA), 6-Benzylaminopurine (6-BA) and thidiazuron (TDZ). The sensitivity of callus to kanamycin and cefotaxime was determined. Several parameters such as Agrobacterium cell density, infection time and co-culture duration were studied to optimize transformation efficiency. Agrobacterium strains EHA105 and pBI121 binary vector harboring the β-glucuronidase (GUS) gene were used for transformation. Expression of the GUS reporter gene was detected by GUS assay, polymerase chain reaction (PCR) and Quantitative Real-time PCR (RT-qPCR). The MS medium containing 1.0 mg·L-1 NAA, 0.5 mg·L-1 2,4-D and 0.5 mg·L-1 TDZ was optimal for callus induction and MS medium containing 0.5 mg·L-1 NAA, 1.0 mg·L-1 2,4-D and 0.5 mg·L-1 TDZ was the best for callus proliferation. The concentrations of kanamycin and cefotaxime used for screening positive callus were 125 mg·L-1 and 200 mg·L-1, respectively. Among various combinations analyzed, the best transformation result was obtained via the 25 min of infection of Agrobacterium at 0.6 OD600 and 3 d of co-culture. Overall, this study provided technical support and theoretical guidance for improving the callus induction and proliferation efficiency and the study of gene function in P. lactiflora.

BackgroundPrognostic effect of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD) is not fully clear yet, this study was designed to elucidate baseline characteristics of CKD patients with different severities of PH, the association between kidney indicators and PH severity, and survival factors in CKD patients with PH.MethodsWe extracted clinical data from electronic medical records of all patients diagnosed with PH in CKD from Jan 2016 to Dec 2020, and those with comorbid conditions causing PH were excluded. CKD stages were defined by estimated glomerular filtration rate thresholds. PH was defined as a systolic pulmonary artery pressure (sPAP) >35 mmHg estimated using echocardiograms. Demographics, clinical data, and test results were analyzed, and all-cause mortality data were obtained.ResultsA total of 137 patients were included in the study. The mean age of the participants was 60 (42.5, 67) years, the mean sPAP was 58 (51, 69.5) mmHg, and 40.9% of the patients were women. Moderate PH group had more patients undergoing dialysis and higher frequency of coronary heart disease. Moderate-severe PH group had higher parathyroid hormone levels and lower low-density lipoprotein levels. Severe PH group had better kidney function parameters and lower serum phosphorus levels. PH severity had no direct relationship with CKD stages. In the univariate analysis, age and PH severity influenced survival. Multivariate analysis also showed independent prognostic effects for age and sPAP. Kaplan-Meyer curve intuitively displayed the survival differences among CKD patients with different PH severity. Predictor values of nomogram identified from survival analyses enabled calculation of death probabilities for CKD with PH patients. Nomogram was validated by ROC analysis.ConclusionsPH begins with early-stage CKD, and PH severity is not related to CKD progression. A higher pulmonary artery pressure and an older age are associated with an increased risk of death.

The importance of reactive oxygen species (ROS) in the occurrence and development of orthopaedic related diseases is becoming increasingly prominent. ROS regulation has become a new method to treat orthopaedic related diseases. In recent years, the application of nanomaterials has become a new hope for precision and efficient treatment. However, there is a lack of reviews on ROS-regulated nanomaterials for orthopaedic related diseases. Based on the key significance of nanomaterials for the treatment of orthopaedic related diseases, we searched the latest related studies and reviewed the nanomaterials that regulate ROS in the treatment of orthopaedic related diseases. According to the function of nanomaterials, we describe the scavenging of ROS related nanomaterials and the generation of ROS related nanomaterials. In this review, we closely integrated nanomaterials with the treatment of orthopaedic related diseases such as arthritis, osteoporosis, wound infection and osteosarcoma, etc., and highlighted the advantages and disadvantages of existing nanomaterials. We also looked forward to the design of ROS-regulated nanomaterials for the treatment of orthopaedic related diseases in the future.

Recently, atypical infectious bursal disease (IBD) caused by a novel variant infectious bursal disease virus (varIBDV) suddenly appeared in immunized chicken flocks in East Asia and led to serious economic losses. The epizootic varIBDV can partly circumvent the immune protection of the existing vaccines against the persistently circulating very virulent IBDV (vvIBDV), but its mechanism is still unknown. This study proved that the neutralizing titer of vvIBDV antiserum to the epizootic varIBDV reduced by 7.0 log2, and the neutralizing titer of the epizootic varIBDV antiserum to vvIBDV reduced by 3.2 log2. In addition, one monoclonal antibody (MAb) 2-5C-6F had good neutralizing activity against vvIBDV but could not well recognize the epizootic varIBDV. The epitope of the MAb 2-5C-6F was identified, and two mutations of G318D and D323Q of capsid protein VP2 occurred in the epizootic varIBDV compared to vvIBDV. Subsequently, the indirect immunofluorescence assay based on serial mutants of VP2 protein verified that residue mutations 318 and 323 influenced the recognition of the epizootic varIBDV and vvIBDV by the MAb 2-5C-6F, which was further confirmed by the serial rescued mutated virus. The following cross-neutralizing assay directed by MAb showed residue mutations 318 and 323 also affected the neutralization of the virus. Further data also showed that the mutations of residues 318 and 323 of VP2 significantly affected the neutralization of the IBDV by antiserum, which might be deeply involved in the immune circumvention of the epizootic varIBDV in the vaccinated flock. This study is significant for the comprehensive prevention and control of the emerging varIBDV.

Summary How bacteria adjust gene expression to cope with variable environments remains open to question. Here, we investigated the way global gene expression changes in E. coli correlated with the metabolism of seven carbon substrates chosen to trigger a large panel of metabolic pathways. Coarse‐grained analysis of gene co‐expression identified a novel regulation pattern: we established that the gene expression trend following immediately the reduction of growth rate (GR) was correlated to its initial expression level. Subsequent fine‐grained analysis of co‐expression demonstrated that the Crp regulator, coupled with a change in GR, governed the response of most GR‐dependent genes. By contrast, the Cra, Mlc and Fur regulators governed the expression of genes responding to non‐glycolytic substrates, glycolytic substrates or phosphotransferase system transported sugars following an idiosyncratic way. This work allowed us to expand additional genes in the panel of gene complement regulated by each regulator and to elucidate the regulatory functions of each regulator comprehensively. Interestingly, the bulk of genes controlled by Cra and Mlc were, respectively, co‐regulated by Crp‐ or GR‐related effect and our quantitative analysis showed that each factor took turns to work as the primary one or contributed equally depending on the conditions.

Infectious bursal disease (IBD) is caused by infectious bursal disease virus (IBDV), which has a genome consisting of two segments of double-stranded linear RNA. IBDVs have been traditionally divided into four phenotypes based on their pathogenicity and antigenicity, including classic, variant, very virulent, and attenuated IBDV. With the emergences of divergent molecular characteristics of novel strains produced by continuous mutations and recombination, it is increasingly difficult to define new IBDV strains using the traditional descriptive classification method. The most common classification scheme for IBDV with segmented genome is based solely on segment A, while the significance of segment B has been largely neglected. In this study, an improved scheme for IBDV genotype classification based on the molecular characteristics of both VP2 (a viral capsid protein encoded by segment A) and VP1 (an RNA-dependent RNA polymerase protein encoded by segment B) was proposed for the first time. In this scheme, IBDV was classified into nine genogroups of A and five genogroups of B, respectively; the genogroup A2 was further divided into four lineages. The commonly used phenotypic classifications of classic, variant, very virulent, and attenuated IBDVs correspond to the A1B1, A2B1, A3B2, and A8B1 genotypes of the proposed classification scheme. The novel variant IBDVs including the strains identified in this study were classified as belonging to genotype A2dB1. The flexibility and versatility of this improved classification scheme will allow the unambiguous identification of existing and emerging IBDV strains, which will greatly facilitate molecular epidemiology studies of IBDV.

Fowl adenovirus (FAdV) was first reported in Angara Goth, Pakistan, in 1987. For this reason, it is also known as “Angara disease.” It was later reported in China, Japan, South Korea, India, the United States, Canada, and other countries and regions, causing huge economic losses in the poultry industry worldwide. Notably, since June 2015, a natural outbreak of severe hydropericardium hepatitis syndrome (HHS), associated with a hypervirulent novel genotype FAdV-4 infection, has emerged in most provinces of China. The novel virus FAdV-4 spread rapidly and induced a 30-100% mortality rate, causing huge economic losses and threatening the green and healthy poultry breeding industry. Vaccines against FAdV-4, especially the emerging novel genotype, play a critical role and will be the most efficient tool for preventing and controlling HHS. Various types of FAdV-4 vaccines have been developed and evaluated, such as inactivated, live-attenuated, subunit, and combined vaccines. They have made great contributions to the control of HHS, but the details of cross-protection within FAdVs and the immunogenicity of different vaccines require further investigation. This review highlights the recent advances in developing the FAdV-4 vaccine and promising new vaccines for future research.

Abstract The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE2, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.

Abstract Background Severe hand-foot-and-mouth disease (HFMD) is a life-threatening contagious disease among young children and infants. Although enterovirus A71 has been well acknowledged to be the dominant cause of severe HFMD, there still remain other unidentified risk factors for severe HFMD. Previous studies mainly focused on identifying the individual-level risk factors from a clinical perspective, while rare studies aimed to clarify the association between regional-level risk factors and severe HFMD, which may be more important from a public health perspective. Methods We retrieved the clinical HFMD counts between 2008 and 2014 from the Chinese Center for Disease Control and Prevention, which were used to calculated the case-severity rate in 143 prefectural-level cities in mainland China. For each of those 143 cities, we further obtained city-specific characteristics from the China City Statistical Yearbook (social and economic variables) and the national meteorological monitoring system (meteorological variables). A Poisson regression model was then used to estimate the associations between city-specific characteristics (reduced by the principal component analysis to avoid multicollinearity) and the case-severity rate of HFMD. The above analysis was further stratified by age and gender to examine potential modifying effects and vulnerable sub-populations. Results We found that the case-severity rate of HFMD varied dramatically between cities, ranging from 0 to 8.09%. Cities with high case-severity rates were mainly clustered in Central China. By relating the case-severity rate to city-specific characteristics, we found that both the principal component characterized by a high level of social and economic development (RR = 0.823, 95%CI 0.739, 0.916) and another that characterized by warm and humid climate (RR = 0.771, 95%CI 0.619, 0.960) were negatively associated with the case-severity rate of HFMD. These estimations were consistent across age and gender sub-populations. Conclusion Except for the type of infected pathogen, the case-severity rate of HFMD was closely related to city development and meteorological factor. These findings suggest that social and environmental factors may also play an important role in the progress of severe HFMD.

The initial interaction mechanism is very important for the design and safety of nano-scale composite energetic materials composed of ammonium dinitramide (ADN) and nitrocellulose (NC). The thermal behaviors of ADN, NC and an NC/ADN mixture under different conditions were studied by using differential scanning calorimetry (DSC) with sealed crucibles, an accelerating rate calorimeter (ARC), a self-developed gas pressure measurement instrument and a DSC-thermogravimetry (TG)—quadrupole mass spectroscopy (MS)—Fourier transform infrared spectroscopy (FTIR) combined technique. The results show that the exothermic peak temperature of the NC/ADN mixture shifted forward greatly in both open and closed circumstances compared to those of NC or ADN. After 585.5 min under quasi-adiabatic conditions, the NC/ADN mixture stepped into the self-heating stage at 106.4 °C, which was much less than the initial temperatures of NC or ADN. The significant reduction in net pressure increment of NC, ADN and the NC/ADN mixture under vacuum indicates that ADN initiated the interaction of NC with ADN. Compared to gas products of NC or ADN, two new kinds of oxidative gases O2 and HNO2 appeared for the NC/ADN mixture, while NH3 and aldehyde disappeared. The mixing of NC with ADN did not change the initial decomposition pathway of either, but NC made ADN more inclined to decompose into N2O, which resulted in the formation of oxidative gases O2 and HNO2. The thermal decomposition of ADN dominated the initial thermal decomposition stage of the NC/ADN mixture, followed by the oxidation of NC and the cation of ADN.

Newcastle disease (ND) is one of the most important avian diseases that seriously threaten the poultry industry worldwide. Sometimes vaccination might not effectively reduce ND occurrence in some poultry farms for unclear reasons. Infectious bursal disease (IBD) is one of the most important immunosuppressive diseases, and the novel variant IBD virus (IBDV) is threatening chicken farms in China. This study evaluated the influence of the novel variant IBDV (SHG19 strain) on immunization of ND vaccine (LaSota strain) in broiler and layer chickens. In commercial broilers, the hemagglutination inhibition antibody titers against LaSota strain were decreased by the prior infection of the novel variant IBDV. Pathological examination revealed that the novel variant IBDV severely damaged the key immune organs of the bursa and spleen, and the B lymphocytes in the bursa were severely destroyed, which was the primary reason involved in the immunosuppression on ND vaccination. Moreover, the novel variant IBDV dramatically reduced the BW of infected broilers by about 16% compared to that of control, which indicated huge economic losses. Furthermore, this study confirmed the immunosuppression induced by the novel variant IBDV in specific pathogen–free layer chickens. In this study, it was discovered that the novel variant IBDV could interfere with ND vaccination in both broilers and layers, which was one important factor involved in immune failure in poultry farms. This study therefore suggests the urgency to control the novel variant IBDV infection for healthy breeding.

Avian leukosis virus subgroup J (ALV-J) was first isolated from broiler chickens in China in 1999; subsequently, it was rapidly introduced into layer chickens and Chinese local chickens. Recently, the incidence of ALV-J in broiler and layer chickens has significantly decreased. However, it has caused substantial damage to Chinese local chickens, resulting in immense challenges to their production performance and breeding safety. To systematically analyze the molecular characteristics and the epidemic trend of ALV-J in Chinese local chickens, 260 clinical samples were collected for the period of 2013–2018; 18 ALV-J local chicken isolates were identified by antigen-capture enzyme-linked immunosorbent assay and subgroup A-, B-, and J-specific multiplex PCR. The whole genomic sequences of 18 isolates were amplified with PCR and submitted to GenBank. Approximately, 55.5% (10/18) of the 18 isolates demonstrated a relatively high homology (92.3–95.4%) with 20 ALV-J early-isolated local strains (genome sequences obtained from GenBank) in gp85 genes clustering in a separated branch. The 3ʹ untranslated region (3ʹ UTR) of the 18 isolates showed a 195–210 and 16–28 base pair deletion in the redundant transmembrane region and in direct repeat 1, respectively; 55.5% (10/18) of the 18 isolates retained the 147 residue E element. The U3 gene of 61.1% (11/18) of the 18 isolates shared high identity (94.6–97.3%) with ALV-J early-isolated local strains. These results implied that the gp85 and U3 of ALV-J local chicken isolates have rapidly evolved and formed a unique local chicken branch. In addition, it was determined that the gene deletion in the 3′UTR region currently serves as a unique molecular characteristic of ALV-J in China. Hence, the obtained results built on the existing ALV-J molecular epidemiological data and further elucidated the genetic evolution trend of ALV-J in Chinese local chickens.

Abstract Reticuloendotheliosis is an important immunosuppressive disease, associated with avian reticuloendotheliosis virus (REV) infection, and causes notable economic losses worldwide. Glycoprotein gp90 is an important structural protein of REV, and considered to be the most important immunogenic antigen, which can induce neutralizing antibodies against REV. In this study, an optimized suspension culture system was developed and applied to secretory express the immunogenic surface antigen gp90. To achieve an optimal glycosylation, the gp90 was designed to secretory expressed into the supernatant of the cell culture, which also occurs in the natural protein maturation procedure of REV. Serum-free culture medium was introduced to simplify the purification process and reduce the production costs. Based on the purified glycosylated gp90, an oil-emulsion subunit REV vaccine candidate was developed and evaluated in chickens. The subunit gp90-based vaccine induced fast immune responses, high levels of antibodies (REV-specific antibody, gp90-specific antibody, and neutralizing antibody against REV), and preferential T helper 2 (Th2) (interleukin-4 secretion) not Th1 (interferon-γ secretion) response. Furthermore, the viremia induced by REV infection was significantly reduced in chickens immunized with the glycosylated gp90. Overall, an optimized secretory expression system for glycosylated gp90 was developed, and the glycosylated gp90 obtained in this study retained good immunogenicity and could be an attractive vaccine candidate to protect chickens against REV horizonal infection.

Abstract Background Hydrogen sulphide (H2S) is involved in regulating physiological processes in plants. We investigated how H2S ameliorates iron (Fe) deficiency in soybean (Glycine max L.) seedlings. Multidisciplinary approaches including physiological, biochemical and molecular, and transcriptome methods were used to investigate the H2S role in regulating Fe availability in soybean seedlings. Results Our results showed that H2S completely prevented leaf interveinal chlorosis and caused an increase in soybean seedling biomass under Fe deficiency conditions. Moreover, H2S decreased the amount of root-bound apoplastic Fe and increased the Fe content in leaves and roots by regulating the ferric-chelate reductase (FCR) activities and Fe homeostasis- and sulphur metabolism-related gene expression levels, thereby promoting photosynthesis in soybean seedlings. In addition, H2S changed the plant hormone concentrations by modulating plant hormone-related gene expression abundances in soybean seedlings grown in Fe-deficient solution. Furthermore, organic acid biosynthesis and related genes expression also played a vital role in modulating the H2S-mediated alleviation of Fe deficiency in soybean seedlings. Conclusion Our results indicated that Fe deficiency was alleviated by H2S through enhancement of Fe acquisition and assimilation, thereby regulating plant hormones and organic acid synthesis in plants.

Infectious bursal disease (IBD), caused by IBD virus (IBDV), is one of the most devastating and immunosuppressive diseases of the poultry and has been a constraint on the sustainable poultry production around the globe including Pakistan. While the disease is threatening the poultry industry, the nature of predominant strains of IBDV in Pakistan remained ill-defined. In this study, an epidemiology survey was conducted in the main chicken-farming regions of Pakistan. The batch of Pakistan IBDVs genes simultaneously covering both VP1 and VP2 were amplified, sequenced, and analyzed. The unique segment-reassortant IBDVs (vv-A/Uniq-B), carrying segment A from vvIBDV and segment B from one unique ancestor, were identified as one important type of circulating strains in Pakistan. The data also discovered the characteristic molecular features of Pakistan IBDVs, which will contribute to scientific vaccine selection and effective prevention of the disease.

Abstract The correct folding is a key process for a protein to acquire its functional structure and conformation. Prefoldin is a well-known chaperone protein that regulates the correct folding of proteins. Prefoldin plays a crucial role in the pathogenesis of common neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease). The important role of prefoldin in emerging fields (such as nanoparticles, biomaterials) and tumors has attracted widespread attention. Also, each of the prefoldin subunits has different and independent functions from the prefoldin complex. It has abnormal expression in different tumors and plays an important role in tumorigenesis and development, especially c-Myc binding protein MM-1. MM-1 can inhibit the activity of c-Myc through various mechanisms to regulate tumor growth. Therefore, an in-depth analysis of the complex functions of prefoldin and their subunits is helpful to understand the mechanisms of protein misfolding and the pathogenesis of diseases caused by misfolded aggregation.

Abstract The article reviews the recent progress of electrochemical techniques on synthesizing nano-/microstructures as supercapacitor electrodes. With a history of more than a century, electrochemical techniques have evolved from metal plating since their inception to versatile synthesis tools for electrochemically active materials of diverse morphologies, compositions, and functions. The review begins with tutorials on the operating mechanisms of five commonly used electrochemical techniques, including cyclic voltammetry, potentiostatic deposition, galvanostatic deposition, pulse deposition, and electrophoretic deposition, followed by thorough surveys of the nano-/microstructured materials synthesized electrochemically. Specifically, representative synthesis mechanisms and the state-of-the-art electrochemical performances of exfoliated graphene, conducting polymers, metal oxides, metal sulfides, and their composites are surveyed. The article concludes with summaries of the unique merits, potential challenges, and associated opportunities of electrochemical synthesis techniques for electrode materials in supercapacitors.

Abstract Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, such as exosomes and cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, such as proteins, lipids and nucleic acids. Exosomes carry biologically active miRNAs to shuttle between tumor cells and TME, thereby affecting tumor development. Tumor-derived exosomal miRNAs induce matrix reprogramming in TME, creating a microenvironment that is conducive to tumor growth, metastasis, immune escape and chemotherapy resistance. In this review, we updated the role of exosomal miRNAs in the process of TME reshaping.

ABSTRACTSince 2015, the prevalence of severe hepatitis-hydropericardium syndrome, which is caused by the novel genotype fowl adenovirus serotype 4 (FAdV-4), has increased in China and led to considerable economic losses. The replication cycle of FAdV-4, especially the emerging highly pathogenic novel genotype FAdV-4, remains largely unknown. The adenovirus fibre interacts with the cellular receptor as the initial step in adenovirus (AdV) infection. In our previous studies, the complete genome sequence showed that the fibre patterns of FAdV-4 were distinct from all other AdVs. Here, protein-blockage and antibody-neutralization assays were performed to confirm that the novel FAdV-4 short fibre was critical for binding to susceptible leghorn male hepatocellular (LMH) cells. Subsequently, fibre 1 was used as bait to investigate the receptor on LMH cells via mass spectrometry. The chicken coxsackie and adenovirus receptor (CAR) protein was confirmed as the novel FAdV-4 receptor in competition assays. We further identified the D2 domain of CAR (D2-CAR) as the active domain responsible for binding to the short fibre of the novel FAdV-4. Taken together, these findings demonstrate for the first time that the chicken CAR homolog is a cellular receptor for the novel FAdV-4, which facilitates viral entry by interacting with the viral short fibre through the D2 domain. Collectively, these findings provide an in-depth understanding of the mechanisms of the emerging novel genotype FAdV-4 invasion and pathogenesis.

In the 1980s, reports from Congress and the Government Accountability Office (GAO) presented statistical evidence showing that employees in the Foreign Service were overwhelmingly White male, especially in the higher positions. To remedy this historical discrimination, the State Department instituted an affirmative action plan during 1990–1992 that allowed females and race-ethnic minorities to apply directly for mid-level positions. A White male employee claimed that he had been disadvantaged by the plan. The appellate court unanimously held that the manifest statistical imbalance supported the Department’s instituting the plan. One judge identified two statistical issues in the analysis of the data that neither party brought up. This article provides an empirical guideline for sample size and a one-sided Hotelling’s T2 test to answer these problems. First, an approximate rule is developed for the minimum number of expected minority appointments needed for a meaningful statistical analysis of under-representation. To avoid the multiple comparison issue when several protected groups are involved, a modification of Hotelling’s T2 test is developed for testing the null hypothesis of fair representation against a one-sided alternative of under-representation in at least one minority group. The test yields p-values less than 1 in 10,000 indicating that minorities were substantially under-represented. Excluding secretarial and clerical jobs led to even larger disparities. Supplemental materials for this article are available online.

The hippocampus plays an important role in the memory and cognition abilities of humans. Precise three-dimensional (3D) segmentation of the hippocampus from magnetic resonance imaging scans is of great importance in the diagnosis of neurological diseases. Conventional automatic segmentation methods poorly achieve satisfactory performance because of the irregular shape and small volume of the hippocampus. We propose a novel two-stage segmentation method, which includes a localization stage and a segmentation stage, to handle the task of the 3D segmentation of the hippocampus. In the localization stage, a novel strategy for localizing multi-size candidate regions was developed to improve the sample balance for the 3D segmentation task. In the segmentation stage, a method which fuses the multi-size candidate regions was proposed to improve the accuracy in predicting the hippocampal boundary, after which we aggregated the segmentation results from three orthogonal views to further improve the performance. Quantitative evaluation was performed on the Alzheimer's Disease Neuroimaging Initiative dataset. The experimental results achieved Dice similarity coefficients of 92.48 ± 0.61% and 92.90 ± 0.51% for the left and right hippocampus, respectively, outperforming state-of-the-art studies in hippocampus segmentation tasks.

Infectious bursal disease (IBD) is an acute and highly contagious immunosuppressive disease caused by the infectious bursal disease virus (IBDV), which seriously threatens the healthy development of the poultry industry. Since its spread to China in the early 1990s, the very virulent IBDV (vvIBDV) characterized by high lethality, has been the focus of prevention and control. However, the novel variant IBDV (nVarIBDV), which has been widely prevalent in China since 2017, has brought a new threat to the poultry industry. In this study, the prevalence of IBDV in the important poultry-raising areas of China from 2019 to 2020 was detected. Of these, 45.1% (101/224) of the samples and 61.9% (26/42) of the chicken flocks were shown to be positive for IBDV. For 50 IBDVs, the sequences of the hypervariable region of the VP2 gene in segment A and of the B-marker of the VP1 gene in segment B were analyzed. The results revealed the coexistence of a number of different IBDV genotypes, including A2dB1 (nVar, 26/50, 52.0%), A3B3 (HLJ0504-like, 15/50, 30.0%), A1B1 (classical, 1/50, 2.0%), and A8B1 (attenuated, 1/50, 2.0%). This indicated that the newly emerging nVarIBDV of A2dB1 and the persistently circulating HLJ0504-like vvIBDV of A3B3 are the two important epidemic strains. Furthermore, we established that segment reassortment has occurred among these circulating strains. This study is the first to reveal the novel epidemic characteristics of IBDV since the report of the emerging nVarIBDV of A2dB1 in China.

Severe hepatitis-hydropericardium syndrome (HHS) associated with a novel viral genotype, fowl adenovirus 4 (FAdV-4), has emerged and widely spread in China since 2015, causing severe economic losses to the poultry industry. We previously reported that the hexon gene is responsible for pathogenicity and obtained a non-pathogenic hexon-replacement rHN20 strain; however, the lack of information about the non-essential regions for virus replication limits the development of a FAdV-4 vector. This study first established an enhanced green fluorescent protein (EGFP)-indicator virus based on the FAdV-4 reverse genetic technique, effective for batch operations in the virus genome. Based on this, 10 open reading frames (ORFs) at the left end and 13 ORFs at the right end of the novel FAdV-4 genome were deleted separately and identified as non-essential genes for viral replication, providing preliminary insertion sites for foreign genes. To further improve its feasibility as a vaccine vector, seven combinations of ORFs were successfully replaced with EGFP without affecting the immunogenicity of the vector backbone. Finally, a recombinant rHN20-vvIBDV-VP2 strain, expressing the VP2 protein of very virulent infectious bursa disease virus (vvIBDV), was rescued and showed complete protection against FAdV-4 and vvIBDV. Thus, the novel FAdV-4 vector could provide sufficient protection for HHS and efficient exogenous gene delivery. Overall, our findings systemically identified 23 non-essential ORFs for FAdV-4 replication and seven foreign gene insertion regions, providing valuable information for an in-depth understanding of the novel FAdV-4 pathogenesis and development of multivalent vaccines.