Advancements in Research on Duck Tembusu Virus Infections.

Duck Tembusu Virus (DTMUV) is a pathogen of the Flaviviridae family that causes infections in poultry, leading to significant economic losses in the duck farming industry in recent years. Ducks infected with this virus exhibit clinical symptoms such as decreased egg production and neurological disorders, along with serious consequences such as ovarian hemorrhage, organ enlargement, and necrosis. Variations in morbidity and mortality rates exist across different age groups of ducks. It is worth noting that DTMUV is not limited to ducks alone; it can also spread to other poultry such as chickens and geese, and antibodies related to DTMUV have even been found in duck farm workers, suggesting a potential risk of zoonotic transmission. This article provides a detailed overview of DTMUV research, delving into its genomic characteristics, vaccines, and the interplay with host immune responses. These in-depth research findings contribute to a more comprehensive understanding of the virus's transmission mechanism and pathogenic process, offering crucial scientific support for epidemic prevention and control.

Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1.

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic. Here, we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain (RBD) scaffold protein (3R-NC) adjuvanted with a flagellin protein (KFD) (3R-NC + KFDi.n). In mice, the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year. This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG- and IgA-producing plasma cells, alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant. Based upon these preclinical findings, an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2 (IAV) vaccine. With a favorable safety profile, the 3R-NC + KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions. To meet the challenge of frequently emerged variants, we further designed an updated triple-RBD scaffold protein with mutated RBD combinations, which can induce adaptable antibody responses to neutralize the newly emerging variants, including JN.1. Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

Duck Tembusu virus infection activates the MKK3/6-p38 MAPK signaling pathway to promote virus replication.

Duck Tembusu virus (DTMUV) infection poses a serious threat to ducks, chickens, and geese, causing a range of detrimental effects, including reduced egg production, growth retardation, and even death. These consequences lead to substantial economic losses for the Chinese poultry industry. Although it is established that various viral infections can trigger activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway, the precise role and mechanisms underlying p38 MAPK activation in DTMUV infection remain poorly understood. To address this knowledge gap, we conducted a study to investigate whether the replication of DTMUV necessitates the activation of p38 MAPK. We found that DTMUV infection stimulates activation of the MKK3/6-p38 MAPK pathway, and the activation of p38 MAPK increases with viral titer. Subsequently, the use of the small molecule inhibitor SB203580 significantly reduced DTMUV replication by inhibiting p38 MAPK activity. Furthermore, downregulation of p38 MAPK protein expression by siRNA also inhibited DTMUV replication, whereas transient transfection of p38 MAPK protein promoted DTMUV replication. Interestingly, we found that the DTMUV capsid protein activates p38 MAPK, and there is interaction between DTMUV capsid and p38 MAPK. Finally, we found that DTMUV infection induces elevated mRNA expression of IFN-α, IFN-ß, IFN-γ, IL-1ß, IL-6, and IL-12, which is associated with p38 MAPK activity. These results indicated that virus hijacking of p38 activation is a crucial event for DTMUV replication, and that pharmacological blockade of p38 activation represents a potential anti-DTMUV strategy.

Single-cell analysis of the miRNA activities in tuberculous meningitis (TBM) model mice injected with the BCG vaccine.

BACKGROUND: Our previous study revealed the transcriptome atlas of specific cell types in tuberculous meningitis (TBM) model mice injected with the BCG vaccine via scRNA sequencing. However, the activities of miRNAs in TBM at single-cell resolution remain to be explored. METHOD: Cell type-specific miRNA activities were investigated by using motif enrichment analyses (miReact) on the transcriptome data of 15 cell types. The target mRNAs of miRNAs were predicted and subjected to enrichment analysis. Furthermore, miRNAs and their target mRNAs with opposite expression trends were chosen to construct functional networks. Besides, qRT-PCR and RNA scope were performed to verify the expression level of representative miRNA. RESULTS: The tSNE dimensionality reduction presented 15 cell types in TBM model mice, in which microglia and endothelial cells accounted for the majority. Target mRNAs of each cell type were predicted for verification or network construction. The immune and inflammation-related miRNA-mRNA networks of macrophages and microglia, oxidative phosphorylation-related miRNA-mRNA networks of neurons, ion and protein transport-related networks of epididymal cells, and angiogenesis-related miRNA-mRNA networks of VSMCs were constructed. The miRNA activity analysis revealed that miR-21a-3p activity was increased in microglia, macrophages, neurons and epididymal cells. The result of qRT-PCR and RNA scope indicate that miR-21a-3p was significantly higher-expressed in TBM brain tissue compared with normal brain tissue. CONCLUSION: In our study, an in-depth exploration of the mRNA expression and miRNA activity of macrophages, microglia, epididymal cells, neurons and vascular smooth muscle cells during TBM progression was conducted using scRNA-Seq, which provided novel insights into the immune cell engagement in TBM patients.

Single-cell analysis reveals changes in BCG vaccine-injected mice modeling tuberculous meningitis brain infection.

Tuberculous meningitis (TBM) is the most severe and deadly manifestation of tuberculosis. Neurological complications are observed in up to 50% of patients affected. Here, attenuated Mycobacterium bovis are injected into the cerebellum of mice, and histopathological images and cultured colonies confirm successful brain infection. Then, whole-brain tissue is dissected for 10X Genomics single-cell sequencing, and we acquire 15 cell types. Transcriptional changes of inflammation processes are found in multiple cell types. Specifically, Stat1 and IRF1 are shown to mediate inflammation in macrophages and microglia. For neurons, decreased oxidative phosphorylation activity in neurons is observed, which corresponds to TBM clinical symptoms of neurodegeneration. Finally, ependymal cells present prominent transcriptional changes, and decreased FERM domain containing 4A (Frmd4a) may contribute to TBM clinical symptoms of hydrocephalus and neurodegeneration. This study shows a single-cell transcriptome of M. bovis infection in mice and improves the understanding of brain infection and neurological complications in TBM.

Epidemiology of extrapulmonary tuberculosis in central Guangxi from 2016 to 2021.

The burden of extrapulmonary tuberculosis (EPTB) has gradually increased in recent years, but not enough epidemiological data is available from central Guangxi. To better understand the epidemiology of EPTB in central Guangxi and identify risk factors associated with them, we retrospectively investigated the epidemiology of tuberculosis (TB), especially EPTB, among patients admitted to the Chest Hospital of Guangxi Zhuang Autonomous Region between 2016 and 2021. We excluded those infected with both pulmonary tuberculosis (PTB) and EPTB, reported the proportion and incidence of PTB or EPTB, and compared the demographic characteristics and risk factors of EPTB and PTB cases using univariate and multivariate logistic regression models. Among 30,893 TB patients, 67.25% (20,774) had PTB and 32.75% (10,119) had EPTB. Among EPTB, pleural, skeletal, lymphatic, pericardial, meningeal, genitourinary, intestinal, and peritoneal TB accounted for 49.44%, 27.20%, 8.55%, 4.39%, 3.36%, 1.48%, 0.87%, and 0.79%, respectively. Patients who were younger (age < 25), from rural areas, Zhuang and other ethnic groups, and diagnosed with anemia and HIV infection were more likely to develop EPTB. However, patients with diabetes and COPD were less likely to have EPTB. From 2016 to 2021, the proportion of PTB cases decreased from 69.73 to 64.07%. The percentage of EPTB cases increased from 30.27 to 35.93%, with the largest increase in skeletal TB from 21.48 to 34.13%. The epidemiology and risk factors of EPTB in central Guangxi are different from those of PTB. The incidence of EPTB is increasing and further studies are needed to determine the reasons for it.

The CPNE Family and Their Role in Cancers.

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite significant advances in cancer research and treatment, the overall prognosis of lung cancer patients remains poor. Therefore, the identification for novel therapeutic targets is critical for the diagnosis and treatment of lung cancer. CPNEs (copines) are a family of membrane-bound proteins that are highly conserved, soluble, ubiquitous, calcium dependent in a variety of eukaryotes. Emerging evidences have also indicated CPNE family members are involved in cancer development and progression as well. However, the expression patterns and clinical roles in cancer have not yet been well understood. In this review, we summarize recent advances concerning CPNE family members and provide insights into new potential mechanism involved in cancer development.

Case report: histopathology and molecular pathology analysis on enteric tissue of a COVID-19 patient.

AIMS: Patients with COVID-19 can also have enteric symptoms. Here we analyzed the histopathology of intestinal detachment tissue from a patient with COVID-19. METHODS: The enteric tissue was examined by hematoxylin & eosin stain, PAS (Periodic acid-Schiff) staining, Gram staining, Ziehl-Neelsen stain and Grocott's Methenamine Silver (GMS) Stain. The distribution of CD3, CD4, CK20 and CD68, cytomegalovirus (CMV) and Herpes Simplex Virus (HSV) antigen were determined by immunohistochemistry. In situ hybridization (ISH) of SARS-CoV-2 and Epstein-Barr virus-encoded small RNA (EBER) were also performed. RESULTS: We observed mucosal epithelium shedding, intestinal mucosal erosion, focal inflammatory necrosis with hemorrhage, massive neutrophil infiltration, macrophage proliferation accompanied by minor lymphocyte infiltration. Fungal spores and gram positive cocci but not mycobacteria tuberculosis were identified. Immunohistochemistry staining showed abundant CD68+ macrophages but few lymphocytes infiltration. HSV, CMV and EBV were negative. ISH of SARS-CoV-2 RNA showed positive signal which mostly overlapped with CD68 positivity. CONCLUSIONS: The in situ detection of SARS-CoV-2 RNA in intestinal macrophages implicates a possible route for gastrointestinal infection. Further study is needed to further characterize the susceptibility of enteric cells to SARS-CoV-2 infection.

Analysis of pathogens and risk factors of secondary pulmonary infection in patients with COVID-19.

To investigate the distribution and risk factors of pathogens in secondary pulmonary infection in patients with COVID-19.142 patients with confirmed COVID-19 from Shanghai Public Health Clinical Center were collected, and 32 patients with pulmonary infection were taken as the infection group. The distribution of pathogens in the sputum specimens was applied for retrospective analysis. Meanwhile, 110 patients diagnosed with COVID-19, but without pulmonary infection were regarded as the asymptomatic group. The risk factors of pulmonary infection were analyzed with generalized linear models and logistic regression. The pathogens in the lung infection group were mainly gram-negative bacteria (22, 68.8%), especially Klebsiella pneumoniae. Gram-positive bacteria and fungi accounted for 13 (40.6%), mainly Staphylococcus aureus, and 11 (34.4%), mainly Candida albicans. There were 14 cases (43.8%) infected with two or more pathogens. The comparison between the two groups found that, patients with elder age, underlying diseases, more lung lesions and low protein contents, were more likely to develop lung infections. At last, univariate analysis showed that 6 factors, including indwelling gastric catheter, the number of deep vein catheters, tracheal intubation tracheotomy, invasive mechanical ventilation, hormonal application, and the use of more than three antibacterial drugs, are risk factors for COVID-19 secondary pulmonary infection. Generalized linear models and logistic regression analysis showed antimicrobial use as an independent risk factor for COVID-19 secondary lung infection. There are many risk factors for secondary lung infection in severe COVID-19 patients, and it is recommended to use antibiotics reasonably.

Pre-optimized phage therapy on secondary Acinetobacter baumannii infection in four critical COVID-19 patients.

Phage therapy is recognized as a promising alternative to antibiotics in treating pulmonary bacterial infections, however, its use has not been reported for treating secondary bacterial infections during virus pandemics such as coronavirus disease 2019 (COVID-19). We enrolled 4 patients hospitalized with critical COVID-19 and pulmonary carbapenem-resistant Acinetobacter baumannii (CRAB) infections to compassionate phage therapy (at 2 successive doses of 109 plaque-forming unit phages). All patients in our COVID-19-specific intensive care unit (ICU) with CRAB positive in bronchoalveolar lavage fluid or sputum samples were eligible for study inclusion if antibiotic treatment failed to eradicate their CRAB infections. While phage susceptibility testing revealed an identical profile of CRAB strains from these patients, treatment with a pre-optimized 2-phage cocktail was associated with reduced CRAB burdens. Our results suggest the potential of phages on rapid responses to secondary CRAB outbreak in COVID-19 patients.

Integrated analyses reveal hsa_circ_0028883 as a diagnostic biomarker in active tuberculosis.

Circular RNAs (circRNAs) are known to be closely involved in various diseases progression. Nevertheless, their function and underlying mechanisms in tuberculosis (TB) remain largely unknown. The aim of the present study was to explore their potential diagnostic values in TB. We downloaded the gene expression datasets of circRNA (GSE117563 and GSE106953), microRNA (miRNA, dataset GSE29190) and mRNA (GSE54992) from Gene Expression Omnibus (GEO) database. A competing endogenous RNAs (ceRNA) network was constructed based on circRNA-miRNA-mRNA potential interaction. We also constructed a circRNA-miRNA-hub gene regulatory module by using the Cytohubba. Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict their biological functions. By further validation, the expression level of hsa_circ_0028883 and hsa-miR-409-5p were detected by qRT-PCR in 20 active TB patients and 20 healthy donors. Then, Receiver Operating Characteristic (ROC) was constructed to evaluate the diagnostic values of hsa_circ_0028883. 1 differentially expressed circRNA (DE-circRNA), 1 differentially expressed miRNA (DE-miRNA), and 44 differentially expressed mRNAs (DE-mRNAs) were selected for the construction of ceRNA network in TB. A circRNA-miRNA-hub gene (mRNA) sub-network was constructed based on 1 DE-circRNA, 1 DE-miRNA, and 8 DE-mRNAs. Hsa_circ_0028883/hsa-miR-409-5p/mRNA interactions may provide some novel mechanisms for active TB. GO and KEGG pathway analysis indicated the possible function of hsa_circ_0028883 with TB. ROC analysis revealed that hsa_circ_0028883 had potential value for TB diagnosis. Hsa_circ_0028883 is a potentially reliable biomarker to diagnose active TB, but there remains a need to further study the mechanism in TB.

Frequency of Signs and Symptoms in Persons With Asthma.

BACKGROUND: Signs and symptoms of asthma are well established; however, no study has been performed to rank them. Therefore, we performed this systematic review and meta-analysis to determine the pooled frequencies of different signs and symptoms of asthma in subjects age ≥ 14 y to develop a patient-specific questionnaire. METHODS: Specific search queries were developed to include records published in Embase, PubMed, Cochrane Library, and Google Scholar, until November 2016. We planned to include randomized controlled trials (RCTs) and observational studies for determining the pooled proportions of signs and symptoms and association between combination of symptoms and asthma severity in subjects age ≥ 14 y. The quality assessment was performed using 3 parameters: reported number or percentage of subjects with asthma symptoms, respiratory disorder history, and method for data collection. RESULTS: Of the 4,939 records retrieved, 67 observational studies (N = 57,033 subjects; age ≥ 14 y) were considered eligible for inclusion in the analysis. A total of 10 symptoms were reported across the studies, with pooled proportions of nasal congestion, sleep disturbances, breathlessness, chest tightness, and wheezing being 61.57%, 56.56%, 50.31%, 50.41%, and 46.97%, respectively. In records of medical history, the pooled proportion of rhinitis was 76.37%, followed by allergy/atopy at 63.53%. The pooled proportion of asthma medication use was 83.27%. In terms of the symptom combinations, the combination of wheezing, breathlessness, chest tightness, and cough was reported in 71.26% of subjects from 4 studies (n = 12,014 subjects). Nasal congestion, sleep disturbance, and chest tightness were the most common symptoms of asthma, followed by wheezing and breathlessness with a combination of symptoms (ie, wheezing, breathlessness, chest tightness, and cough) affecting the highest proportion of subjects. CONCLUSIONS: Asthma severity was dependent on variety of symptoms, consisting mostly of wheezing, breathlessness, chest tightness, and cough. On the basis of our analysis, we recommend a combination of symptoms be included in diagnostic-based questionnaires to aid early diagnosis.

A meta-analysis of the relationship between vitamin D receptor gene ApaI polymorphisms and polycystic ovary syndrome.

BACKGROUND: Emerging evidence from pre-clinical and clinical studies has shown that vitamin D (VD) plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). Potentially functional ApaI polymorphism of vitamin D receptor (VDR) gene has been implicated in PCOS risk, but individually published studies have yielded inconclusive results. OBJECTIVES: Studies on the associations of VDR gene polymorphisms with PCOS susceptibility reported conflicting results. The objective of this study was to perform a systematic meta-analysis to clarify this issue. MATERIAL AND METHODS: We searched for all publications regarding the associations mentioned above in PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases updated up to April 2017. A meta-analysis of the overall odds ratios (ORs) with 95% confidence interval (CI) was calculated with the fixed or random effect model. RESULTS: A total of 7 studies fulfilling the inclusion criteria were included in this meta-analysis (1,350 cases and 960 controls). Pooled ORs showed a significant association between ApaI polymorphism and PCOS risk in all 4 genetic models. Subgroup analysis by ethnicity showed that ApaI polymorphism was associated with the risk of PCOS in Asians (aa vs AA: OR = 1.54, 95% CI = 1.04-2.28, p = 0.03). However, ApaI polymorphism (a vs A: OR = 1.34, 95% CI = 1.00-1.79, p = 0.02; aa+Aa vs AA: OR = 1.36, 95% CI = 1.04-1.79, p = 0.03) was associated with the risk of PCOS in Caucasians. CONCLUSIONS: Our meta-analysis demonstrated that PCOS risk was significantly associated with VDR gene ApaI polymorphism. However, due to the relatively small sample size in this meta-analysis, further studies with a larger sample size should be conducted to confirm the findings.

2-Aryl-indenylphosphine ligands: design, synthesis and application in Pd-catalyzed Suzuki-Miyaura coupling reactions.

A focused library of phosphine ligands was constructed for structural optimization. The catalyst can be used to perform the Suzuki-Miyaura cross-coupling reaction of aryl and heteroaryl chlorides.

An efficient indenyl-derived phosphine ligand for the Suzuki-Miyaura coupling of sterically hindered aryl halides.

An air-stable aryl substituted indenyl phosphine used in combination with Pd(OAc)2 provides a highly efficient catalyst for the Suzuki-Miyaura cross-coupling reaction of sterically hindered aryl halides with aryl boronic acids.

Dual-doping to suppress cracking in spinel LiMn2O4: a joint theoretical and experimental study.

Electrochemical cycling stabilities were compared for undoped and Al/Co dual-doped spinel LiMn2O4 synthesized by solid state reactions. We observed the suppression of particle fracture in Al/Co dual-doped LiMn2O4 during charge/discharge cycling and its distinguishable particle morphology with respect to the undoped material. Systematic first-principles calculations were performed on undoped, Al or Co single-doped, and Al/Co dual-doped LiMn2O4 to investigate their structural differences at the atomistic level. We reveal that while Jahn-Teller distortion associated with the Mn(3+)O6 octahedron is the origin of the lattice strain, the networking -i.e. the distribution of mixed valence Mn ions - is much more important to release the lattice strain, and thus to alleviating particle cracking. The calculations showed that the lattice mismatching between Li(+) intercalation and deintercalation of LiMn2O4 can be significantly reduced by dual-doping, and therefore also the volumetric shrinkage during delithiation. This may account for the near disappearance of cracks on the surface of Al/Co-LiMn2O4 after 350 cycles, while some obvious cracks have developed in undoped LiMn2O4 at similar particle size even after 50 cycles. Correspondingly, Al/Co dual-doped LiMn2O4 showed a good cycling stability with a capacity retention of 84.1% after 350 cycles at a rate of 1C, 8% higher than the undoped phase.

Pd-indenyl-diphosphine: an effective catalyst for the preparation of triarylamines.

A new Buchwald-type diphosphine ligand has been developed for applications in Pd-catalyzed amination reactions towards the preparation of triarylamines. The catalyst can be used to perform the amination of a diverse array of aryl and heteroaryl chlorides.

[LUTS in BPH patients with histological prostatitis before and after transurethral resection of the prostate].

OBJECTIVE: To investigate the effects of transurethral resection of the prostate (TURP) on lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) complicated by histological prostatitis. METHODS: This study included 432 cases of BPH pathologically confirmed after TURP. Excluding those with LUTS-related factors before and after surgery and based on the international prostatitis histological classification of diagnostic criteria, the remaining 144 cases were divided into groups A (pure BPH, n = 30), B (mild inflammation, n = 55), C (moderate inflammation, n = 31), and D (severe inflammation, n = 28). Each group was evaluated for LUTS by IPSS before and a month after surgery. RESULTS: A total of 399 cases (92.4%) were diagnosed as BPH with histological prostatitis, 269 (67.4%) mild, 86 (21.6%) moderate and 44 (11.0%) severe. The preoperative IPSS was 21.43 +/- 6.09 in group A, 21.75 +/- 5.97 in B, 27.84 +/- 4.18 in C and 31.00 +/- 2.92 in D, with statistically significant differences among different groups (P < 0.001) except between A and B (P = 1.000); the postoperative IPSS was 5.60 +/- 2.16 in A, 7.36 +/- 2.77 in B, 11.55 +/- 3.39 in C and 16.89 +/- 3.37 in D, with statistically significant differences among different groups (P < 0.01), and remarkably lower than the preoperative one (P < 0.001). Almost all the infiltrating inflammatory cells in BPH with histological prostatitis were lymphocytes. CONCLUSION: BPH is mostly complicated with histological chronic prostatitis. The severity of LUTS is higher in BPH patients with histological prostatitis than in those without before and after TURP, and positively correlated with the grade of inflammation. Those complicated with moderate or severe histological prostatitis should take medication for the management of LUTS.

Isomerism and Blue Electroluminescence of a Novel Organoboron Compound: BIII2 (O)(7-azain)2 Ph2.

Bright blue light with a maximum at 450 nm is emitted by both structural isomers of the novel, stable BIII2 (O)(7-azain)2 Ph2 (7-azain=7-azaindole anion) on irradiation with UV light. The isomer shown in the picture has approximate C2 symmetry (the other isomer approximate Cs symmetry) and electroluminesces when used as the emitting layer in an electroluminescent device.