Licorice extract inhibits porcine epidemic diarrhea virus in vitro and in vivo.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and even death in piglets, resulting in significant economic losses to the pig industry. Because of the ongoing mutation of PEDV, there might be variations between the vaccine strain and the prevailing strain, causing the vaccine to not offer full protection against different PEDV variant strains. Therefore, it is necessary to develop anti-PEDV drugs to compensate for vaccines. This study confirmed the anti-PEDV effect of licorice extract (Le) in vitro and in vivo. Le inhibited PEDV replication in a dose-dependent manner in vitro. By exploring the effect of Le on the life cycle of PEDV, we found that Le inhibited the attachment, internalization, and replication stages of the virus. In vivo, all five piglets in the PEDV-infected group died within 72 h. In comparison, the Le-treated group had a survival rate of 80 % at the same time, with significant relief of clinical symptoms, pathological damage, and viral loads in the jejunum and ileum. Our results suggested that Le can exert anti-PEDV effects in vitro and in vivo. Le is effective and inexpensive; therefore it has the potential to be developed as a new anti-PEDV drug.

Cross-Combination Analyses of Random Forest Feature Selection and Decision Tree Model for Predicting Intraoperative Hypothermia in Total Joint Arthroplasty.

BACKGROUND: In total joint arthroplasty patients, intraoperative hypothermia (IOH) is associated with perioperative complications and an increased economic burden. Previous models have some limitations and mainly focus on regression modeling. Random forest (RF) algorithms and decision tree modeling are effective for eliminating irrelevant features and making predictions that aid in accelerating modeling and reducing application difficulty. METHODS: We conducted this prospective observational study using convenience sampling and collected data from 327 total joint arthroplasty patients in a tertiary hospital from March 4, 2023, to September 11, 2023. Of those, 229 patients were assigned to the training and 98 to the testing sets. The Chi-square, Mann-Whitney U, and t-tests were used for baseline analyses. The feature variables selection used the RF algorithms, and the decision tree model was trained on 299 examples and validated on 98. The sensitivity, specificity, recall, F1 score, and area under the curve were used to test the model's performance. RESULTS: The RF algorithms identified the preheating time, the volume of flushing fluids, the intraoperative infusion volume, the anesthesia time, the surgical time, and the core temperature after intubation as risk factors for IOH. The decision tree was grown to 5 levels with 9 terminal nodes. The overall incidence of IOH was 42.13%. The sensitivity, specificity, recall, F1 score, and area under the curve were 0.651, 0.907, 0.916, 0.761, and 0.810, respectively. The model indicated strong internal consistency and predictive ability. CONCLUSIONS: The preheating time, the volume of flushing fluids, the intraoperative infusion volume, the anesthesia time, the surgical time, and the core temperature after intubation could accurately predict IOH in total joint arthroplasty patients. By monitoring these factors, the clinical staff could achieve early detection and intervention of IOH in total joint arthroplasty patients.

Identification of linear B cell epitopes on the leukotoxin protein of Fusobacterium necrophorum.

OBJECTIVE: Fusobacterium necrophorum can casuse Lemierre's syndrome in humans and a range of illnesses, including foot rot and liver abscesses, in animals. The main virulence factor released by F. necrophorum is leukotoxin, which has been shown to have a strong correlation with the severity of the disease. Leukotoxin is commonly employed as the key antigen in the formulation of subunit vaccines. Therefore, identification of the B-cell epitope of F. necrophorum leukotoxin is necessary. METHODS: In this research, we utilized lymphocyte hybridoma technology to develop a monoclonal antibody (mAb), 3D7, targeting the F. necrophorum leukotoxin protein. Identification of B-cell epitopes recognized by 3D7 mAb was achieved through Western blot, ELISA and dot blots using leukotoxin-truncated recombinant proteins and peptides, and through SWISS-MODEL homology modeling and PyMOL visualization. RESULTS: The 3D7 mAb was identified as belonging to the IgG1 subclass with a κ-chain light chain. It demonstrated reactivity with the natural leukotoxin. The results showed that the 3D7 mAb recognizes a B-cell epitope of the F. necrophorum leukotoxin protein, I2168SSFGVGV2175 (EP-3D7). Sequence comparison analysis showed that EP-3D7 was highly conserved in F. necrophorum strains, but less conserved in other bacteria, indicating the specificity of EP-3D7. EP-3D7 is present on the surface of leukotoxin proteins in a ß-folded manner. CONCLUSIONS: In summary, these results establish EP-3D7 as a conserved antigenic epitope of F. necrophorum leukotoxin. It could be valuable in the development of vaccines and diagnostic reagents for F. necrophorum epitopes.

Perceived professional preparedness and identity among senior nursing students: a latent profile Analysis.

BACKGROUND: Senior nursing students' perceptions of their professional preparedness help them for expectations of their future nursing role with more confidence, and professional identity may contribute to cultivating nursing students' perceptions of professional preparedness. In this study we applied latent profile analysis to identify the latent profiles of perceived professional preparedness among senior nursing students and to examine their identity and predictors. METHODS: This was a cross-sectional descriptive study. A total of 319 senior nursing students from five universities in China were enrolled. Data were collected using the Perceived Professional Preparedness of Senior Nursing Students' Questionnaire and the Professional Identity Scale for Nursing Students. RESULTS: Three latent profiles were identified and labeled as "low perceived professional preparedness" (n = 90, 28.2%), "low clinical competency-low EBP (Evidence-Based Practice)" (n = 190, 59.5%), and "high perceived professional preparedness" (n = 39, 12.2%). Place of residence, average clinical practicum hours per day, part-time experience, good relationships with classmates, and feeling nobility toward nursing due to COVID-19 significantly predicted profile membership. The average professional identity score was also statistically different across the three profiles (F = 54.69, p < 0.001). CONCLUSIONS: Senior nursing students' perceptions of their professional preparedness were divided into three profiles, and out results show that promoting professional identity may effectively foster their perceived professional preparedness. This study therefore highlights the importance of targeted interventions by considering their distinct perceptions of professional preparedness patterns.

Terephthalic Acid Intercalated CoNi-LDH Materials for Improved Li-O2 Battery.

CoNi-LDH (layered CoNi double hydroxides) hollow nanocages with specific morphology are obtained by Ni ion etching of ZIF-67 (Zeolitic imidazolate framework-67). The structure of the layered materials is further modified by molecular intercalation. The original interlayer anions are replaced by the ion exchange effect of terephthalic acid, which helps to increase the interlayer distance of the material. The intercalated cage-like structures not only benefit for the storage of oxygen, and the discharge product reaction, but also have more support between the material layers. The experimental results show that the excessive use of intercalation agent will affect structural stability of the intercalated CoNi-LDH. By adjusting the amount of terephthalic acid, the intercalated CoNi-LDH-2 (with 0.02 mmol terephthalic acid intercalated) is not easy to collapse after 209 cycles and shows the best electrochemical performance in Li-O2 battery.

The outer membrane protein of Fusobacterium necrophorum, 43K OMP, stimulates inflammatory cytokine production through nuclear factor kappa B activation.

OBJECTIVE: Fusobacterium necrophorum causes bovine hepatic abscess, foot rot, mastitis, and endometritis. The 43 kDa outer membrane protein (43 K OMP) of F. necrophorum is a porin protein that plays an important role in infections by this bacterium, but the biological function and the pathogenesis of this protein are largely unknown. METHODS: In this study, we investigated the role of the 43 K OMP in bacterial infection of bovine mammary epithelial cells (MAC-T cells) by Tandem Mass Tag proteomic analysis. The RAW264.7 cells were incubated with recombinant 43 K OMP (12.5 µg/mL) for 2 h, 4 h, 6 h, and 12 h, and then the inflammatory related protein and inflammatory cytokine production were measured by Western blot analysis and ELISA, the mRNA expression levels of inflammatory cytokine were measured by Real-Time PCR. RESULTS: Proteomic analysis results demonstrated there were 224 differentially expressed proteins in the MAC-T cells stimulated with the 43 K OMP compared with control, and 118 proteins were upregulated and 106 proteins were downregulated. These differentially expressed proteins were mainly involved in NF-kappa B signaling, bacterial invasion of epithelial cells, cell adhesion, complement and coagulation cascades. The top six differentially expressed proteins were; MMP9, PLAU, STOM, PSMD13, PLAUR, and ITGAV, which were involved in a protein-protein interaction network. Furthermore, TLR/MyD88/NF-κB pathway related proteins and inflammatory cytokines (IL-6, TNF-α, and IL-1ß) were assessed by Western blot analysis and ELISA. Results showed the 43 K OMP to enhance the expression of TLR4 protein at 2 h (P < 0.01) and the MyD88 protein at 4 h (P < 0.05) post-stimulation, and to decrease IκBα expression at 4 h, 6 h and 12 h (P < 0.05) post-infection, as well as induce phosphorylation at Ser536 (P < 0.01). Levels of IL-6, IL-1ß, and TNF-α in the supernatants of mouse macrophages were increased (P < 0.05), as were mRNA expression levels of IL-6, IL-1ß, and TNF-α (P < 0.05), while IL-4 mRNA expression was decreased (P < 0.05). CONCLUSIONS: Taken together, these results suggested the important role for 43 K OMP in F. necrophorum infection, promoting the production of pro-inflammatory cytokines (IL-6 and TNF-α) by activation of the TLR/MyD88/NF-κB pathway. These findings provided a theoretical basis for a better understanding of the pathogenesis of F. necrophorum infection.

Coronavirus Porcine Epidemic Diarrhea Virus Nucleocapsid Protein Interacts with p53 To Induce Cell Cycle Arrest in S-Phase and Promotes Viral Replication.

Subversion of the host cell cycle to facilitate viral replication is a common feature of coronavirus infections. Coronavirus nucleocapsid (N) protein can modulate the host cell cycle, but the mechanistic details remain largely unknown. Here, we investigated the effects of manipulation of porcine epidemic diarrhea virus (PEDV) N protein on the cell cycle and the influence on viral replication. Results indicated that PEDV N induced Vero E6 cell cycle arrest at S-phase, which promoted viral replication (P < 0.05). S-phase arrest was dependent on the N protein nuclear localization signal S71NWHFYYLGTGPHADLRYRT90 and the interaction between N protein and p53. In the nucleus, the binding of N protein to p53 maintained consistently high-level expression of p53, which activated the p53-DREAM pathway. The key domain of the N protein interacting with p53 was revealed to be S171RGNSQNRGNNQGRGASQNRGGNN194 (NS171-N194), in which G183RG185 are core residues. NS171-N194 and G183RG185 were essential for N-induced S-phase arrest. Moreover, small molecular drugs targeting the NS171-N194 domain of the PEDV N protein were screened through molecular docking. Hyperoside could antagonize N protein-induced S-phase arrest by interfering with interaction between N protein and p53 and inhibit viral replication (P < 0.05). The above-described experiments were also validated in porcine intestinal cells, and data were in line with results in Vero E6 cells. Therefore, these results reveal the PEDV N protein interacts with p53 to activate the p53-DREAM pathway, and subsequently induces S-phase arrest to create a favorable environment for virus replication. These findings provide new insight into the PEDV-host interaction and the design of novel antiviral strategies against PEDV. IMPORTANCE Many viruses subvert the host cell cycle to create a cellular environment that promotes viral growth. PEDV, an emerging and reemerging coronavirus, has led to substantial economic loss in the global swine industry. Our study is the first to demonstrate that PEDV N-induced cell cycle arrest during the S-phase promotes viral replication. We identified a novel mechanism of PEDV N-induced S-phase arrest, where the binding of PEDV N protein to p53 maintains consistently high levels of p53 expression in the nucleus to mediate S-phase arrest by activating the p53-DREAM pathway. Furthermore, a small molecular compound, hyperoside, targeted the PEDV N protein, interfering with the interaction between the N protein and p53 and, importantly, inhibited PEDV replication by antagonizing cell cycle arrest. This study reveals a new mechanism of PEDV-host interaction and also provides a novel antiviral strategy for PEDV. These data provide a foundation for further research into coronavirus-host interactions.

Ultrathin Two-Dimensional Bimetal-Organic Framework Nanosheets as High-Performance Electrocatalysts for Benzyl Alcohol Oxidation.

Ultrathin two-dimensional metal-organic frameworks (2D MOFs) have the potential to improve the oxidation of benzyl alcohol (BA) with a large surface area and open catalytic active sites. To achieve high-efficiency electrocatalysts for the oxidation of benzyl alcohol, a moderate solvothermal method was evolved to synthesize a series of 2D MOFs on nickel foam (Ni-MOF/NF, NiCo-61-MOF/NF, NiCo-21-MOF/NF). As the electrocatalyst used for the oxidation of benzyl alcohol, NiCo-61-MOF/NF presented a lower overpotential and superior chemical durability than other electrocatalysts; it only required a potential of ∼1.52 V (vs RHE) to reach 338.16 mA cm-2, with an oxidation efficiency of more than 86%. Besides, after continuous electrocatalysis for 20 000 s at 1.42 V (vs RHE), the current density of NiCo-61-MOF/NF nanosheets was still 38.67 mA cm-2 with 77.34% retention. This demonstrated that NiCo-61-MOF/NF nanosheet electrocatalysts had great potential for benzyl alcohol oxidation. From both the experimental and theoretical studies, it was discovered that NiCo-61-MOF/NF nanosheets have the highest electrocatalytic activity due to their distinctive ultrathin 2D structure, optimized electron structure, and more accessible active sites. This finding would pave a brand-new thought for the design of electrocatalysts with electrocatalytic activity for benzyl alcohol oxidation (EBO).

An energy model for recognizing the prokaryotic promoters based on molecular structure.

Promoter is an important functional elements of DNA sequences, which is in charge of gene transcription initiation. Recognizing promoter have important help for understanding the relative life phenomena. Based on the concept that promoter is mainly determined by its sequence and structure, a novel statistical physics model for predicting promoter in Escherichia coli K-12 is proposed. The total energies of DNA local structure of sequence segments in the three benchmark promoter sequence datasets, the sole prediction parameter, are calculated by using principles from statistical physics and information theory. The better results are obtained. And a web-server PhysMPrePro for predicting promoter is established at http://202.207.14.87:8032/bioinformation/PhysMPrePro/index.asp, so that other scientists can easily get their desired results by our web-server.

Improvement of Molecular Diagnosis Using Domain-Level Single-Nucleotide Variants by Eliminating Unexpected Secondary Structures.

Identification of single-nucleotide variants (SNVs) is of great significance in molecular diagnosis. The problem that should not be ignored in the identification process is that the unexpected secondary structure of the target nucleic acid may greatly affect the detection accuracy. Herein, we proposed a conditional domain-level SNV diagnosis strategy, in which the subsequent SNV detection can only be carried out after eliminating the unexpected secondary structure of target DNA. Specifically, the target DNA is assembled into a rigid double strand, which makes folding the target DNA difficult and the unexpected secondary structure is eliminated. Based on this double-stranded structure, specially designed probes are used to detect double-stranded properties and report abundant domain-level oligonucleotide information to improve the effective information in the detection results and complete domain-level SNV diagnosis. If the unexpected secondary structure is not eliminated, the detector will first detect it and feed back to us, ensuring the accuracy of the subsequent detection results. With the occurrence (or not) of SNV and the change of the SNV site, in the proof-of-concept experiment, we successfully identified the four homologous sequences to be tested related to BRAF gene.

Screening of BHK-21 cellular proteins that interact with outer membrane protein 43K OMP of Fusobacterium necrophorum.

Fusobacterium necrophorum is a Gram negative, spore-free, anaerobic bacterium that can cause pyogenic and necrotic infections in animals and humans. It is a major bovine pathogen and causes hepatic abscesses, foot rot, and necrotic laryngitis. The 43K OMP of F. necrophorum is an outer membrane protein with molecular weight of 43 kDa, exhibiting similarity to pore-forming proteins of other Fusobacterium species that plays an important role in bacterial infections. However, the role of 43K OMP in F. necrophorum adhesion remains unknown. In this study, we evaluated whether the 43K OMP of F. necrophorum mediates adhesion to BHK-21 cells and performed a preliminary screen of the proteins that interact with 43K OMP of F. necrophorum by immunoprecipitation-mass spectrometry. The results showed that the natural 43K OMP and recombinant 43K OMP could bind to BHK-21 cells, and preincubation of F. necrophorum with an antibody against the recombinant 43K OMP of F. necrophorum decreased binding to BHK-21 cells. Seventy differential interacting proteins were successfully screened by immunoprecipitation-mass spectrometry. Among these seventy differential interacting proteins, seven cell membrane proteins and four extracellular matrix proteins shown to be relevant to bacteria adhesion through subcellular localization and single-molecule function analysis. These data increase our understanding of the pathogenesis of F. necrophorum and provide a new theoretical basis for the design of antimicrobial drugs against F. necrophorum.

Cobalt Phosphides Nanocrystals Encapsulated by P-Doped Carbon and Married with P-Doped Graphene for Overall Water Splitting.

As one class of important functional materials, transition metal phosphides (TMPs) nanostructures show promising applications in catalysis and energy storage fields. Although great progress has been achieved, phase-controlled synthesis of cobalt phosphides nanocrystals or related nanohybrids remains a challenge, and their use in overall water splitting (OWS) is not systematically studied. Herein, three kinds of cobalt phosphides nanocrystals encapsulated by P-doped carbon (PC) and married with P-doped graphene (PG) nanohybrids, including CoP@PC/PG, CoP-Co2 P@PC/PG, and Co2 P@PC/PG, are obtained through controllable thermal conversion of presynthesized supramolecular gels that contain cobalt salt, phytic acid, and graphene oxides at proper temperature under Ar/H2 atmosphere. Among them, the mixed-phase CoP-Co2 P@PC/PG nanohybrids manifest high electrocatalytic activity toward both hydrogen and oxygen evolution in alkaline media. Remarkably, using them as bifunctional catalysts, the fabricated CoP-Co2 P@PC/PG||CoP-Co2 P@PC/PG electrolyzer only needs a cell voltage of 1.567 V for driving OWS to reach the current density at 10 mA cm-2 , superior to their pure-phase counterparts and recently reported bifunctional catalysts based devices. Also, such a CoP-Co2 P@PC/PG||CoP-Co2 P@PC/PG device exhibits outstanding stability for OWS. This work may shed some light on optimizing TMPs nanostructures based on phase engineering, and promote their applications in OWS or other renewable energy options.

LIF Aggravates Pulpitis by Promoting Inflammatory Response in Macrophages.

Leukemia inhibitory factor (LIF) has been recognized as a novel inflammatory modulator in inflammation-associated diseases. This study aimed to investigate the modulation of LIF in dental pulp inflammation. Experimental pulpitis was established in wild-type (WT) and Lif-deficient (Lif-/-) mice. Histological and immunostaining analyses were conducted to assess the role of LIF in the progression of pulpitis. Mouse macrophage cell line (RAW264.7) was treated with LPS to simulate an inflammatory environment. Exogenous LIF was added to this system to examine its modulation in macrophage inflammatory response in vitro. Primary bone marrow-derived macrophages (BMDMs) from WT and Lif-/- mice were isolated and stimulated with LPS to confirm the effect of Lif deletion on macrophage inflammatory response. Supernatants from LIF and LPS-treated human dental pulp cells (hDPCs) were collected and added to macrophages. Macrophage chemotaxis was assessed using transwell assays. The results showed an increased expression of LIF and LIFR with the progression of pulpitis, and LIFR was highly expressed in macrophages. Lif deficiency alleviated experimental pulpitis with the reduction of pro-inflammatory cytokines and macrophage infiltration. Exogenous LIF promoted inflammatory response of LPS-induced macrophages through a STAT3/p65-dependent pathway. Consistently, Lif deletion inhibited macrophage inflammatory response in vitro. Supernatants of LIF-treated hDPCs enhanced macrophage migration in LPS-induced inflammatory environment. Our findings demonstrated that LIF aggravates pulpitis by promoting macrophage inflammatory response through a STAT3/p65-dependent pathway. Furthermore, LIF plays a crucial role in driving the recruitment of macrophages to inflamed pulp tissue by promoting chemokine secretion in DPCs.

Lif-deficiency promote systemic Iron metabolism disorders and increases the susceptibility of osteoblasts to ferroptosis.

Leukemia inhibitory factor (LIF) is a multifunctional cytokine that plays a crucial role in various biological processes. However, LIF involvement in iron metabolism remains almost unexplored. This study aimed to explore the impact of LIF on systemic iron transportation and its potential role in ferroptosis in osteoblasts. We observed that the Lif-deficient (Lif-/-) mice is characterized by a reduction in bone mass and a decrease in bone mineral density compared with wild-type (WT) mice. Energy-dispersive X-ray spectroscopy revealed a marked increase in iron content on the surface of femurs from Lif-/- mice. Meanwhile, iron stores test lower iron levels in the spleens and higher levels in the femurs of Lif-/- mice. Besides, Lif-/- mice display increased levels of serum iron, total iron-binding capacity, unsaturated iron-binding capacity, and transferrin saturation and serum ferritin relative to WT mice. Hepcidin mRNA expression reduction in the liver of Lif-/- mice. It also holds true in the AML-12 hepatocyte cell line after Lif-knockdown. Immunohistochemistry and RT-PCR revealed elevated ferroportin (FPN) in duodenal cells of Lif-/- mice. Lif-deficiency decreases SLC7A11 levels in osteoblasts. In addition, overexpression of LIF downregulates CD71, DCYTB, and DMT1, thereby reducing iron uptake in iron-overloaded cells. Femur immunohistochemistry (IHC) revealed increased ACSL4 and decreased GPX4 and SLC7A11, indicating an increase in ferroptosis of osteoblasts in Lif-/- mice. Whole-transcriptome sequencing showed gene expression changes after Lif-knockdown, exhibiting a negative correlation with genes involved in long-chain fatty acid transport, mitochondrial organization, and the p38 MAPK signaling pathway. These results demonstrate that Lif-deficiency alter systemic iron metabolism and increases the susceptibility of osteoblasts to ferroptosis.

Construction and immune effect evaluation of the S protein heptad repeat-based nanoparticle vaccine against porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV), a highly virulent enteropathogenic coronavirus, is a significant threat to the pig industry. High frequency mutations in the PEDV genome have limited the effectiveness of current vaccines in providing immune protection. Developing efficient vaccines that can quickly adapt to mutant strains is a challenging but crucial task. In this study, we chose the pivotal protein heptad repeat (HR) responsible for coronavirus entry into host cells, as the vaccine antigen. HR-Fer nanoparticles prepared using ferritin were evaluated them as PEDV vaccine candidates. Nanoparticle vaccines elicited stronger neutralizing antibody responses in mice compared to monomer vaccines. Additionally, HR protein delivered via nanoparticles increased antigen uptake by antigen-presenting cells in vitro by 2.75-fold. The collective results suggest that HR can be used as antigens for vaccines, and the HR vaccine based on ferritin nanoparticles significantly enhances immunogenicity.

Natural hyperoside extracted from hawthorn exhibits antiviral activity against porcine epidemic diarrhea virus in vitro and in vivo.

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and death in piglets, resulting in significant economic losses for the pork industry. There is an urgent need for new treatment strategies. Here, we focused on optimizing the process of purifying natural hyperoside (nHYP) from hawthorn and evaluating its effectiveness against PEDV both in vitro and in vivo. Our findings demonstrated that nHYP with a purity >98% was successfully isolated from hawthorn with an extraction rate of 0.42 mg/g. Furthermore, nHYP exhibited strong inhibitory effects on PEDV replication in cells, with a selection index of 9.72. nHYP significantly reduced the viral load in the intestines of piglets and protected three of four piglets from death caused by PEDV infection. Mechanistically, nHYP could intervene in the interaction of PEDV N protein and p53. The findings implicate nHYP as having promising therapeutic potential for combating PEDV infections.

Combination of S1-N-Terminal and S1-C-Terminal Domain Antigens Targeting Double Receptor-Binding Domains Bolsters Protective Immunity of a Nanoparticle Vaccine against Porcine Epidemic Diarrhea Virus.

Variants of coronavirus porcine epidemic diarrhea virus (PEDV) frequently emerge, causing an incomplete match between the vaccine and variant strains, which affects vaccine efficacy. Designing vaccines with rapidly replaceable antigens and high efficacy is a promising strategy for the prevention of infection with PEDV variant strains. In our study, three different types of self-assembled nanoparticles (nps) targeting receptor-binding N-terminal domain (NTD) and C-terminal domain (CTD) of S1 protein, named NTDnps, CTDnps, and NTD/CTDnps, were constructed and evaluated as vaccine candidates against PEDV. NTDnps and CTDnps vaccines mediated significantly higher neutralizing antibody (NAb) titers than NTD and CTD recombinant proteins in mice. The NTD/CTDnps in varying ratios elicited significantly higher NAb titers when compared with NTDnps and CTDnps alone. The NTD/CTDnps (3:1) elicited NAb with titers up to 92.92% of those induced by the commercial vaccine. Piglets immunized with NTD/CTDnps (3:1) achieved a passive immune protection rate of 83.33% of that induced by the commercial vaccine. NTD/CTDnps (3:1) enhanced the capacity of mononuclear macrophages and dendritic cells to take up and present antigens by activating major histocompatibility complex I and II molecules to stimulate humoral and cellular immunity. These data reveal that a combination of S1-NTD and S1-CTD antigens targeting double receptor-binding domains strengthens the protective immunity of nanoparticle vaccines against PEDV. Our findings will provide a promising vaccine candidate against PEDV.

A survey of fecal virome and bacterial community of the diarrhea-affected cattle in northeast China reveals novel disease-associated ecological risk factors.

Limited information on the virome and bacterial community hampers our ability to discern systemic ecological risk factors that cause cattle diarrhea, which has become a pressing issue in the control of disease. A total of 110 viruses, 1,011 bacterial genera, and 322 complete viral genomes were identified from 70 sequencing samples mixed with 1,120 fecal samples from 58 farms in northeast China. For the diarrheic samples, the identified virome and bacterial community varied in terms of composition, abundance, diversity, and geographic distribution in relation to different disease-associated ecological factors; the abundance of identified viruses and bacteria was significantly correlated with the host factors of clinical status, cattle type, and age, and with environmental factors such as aquaculture model and geographical location (P < 0.05); a significant interaction occurred between viruses and viruses, bacteria and bacteria, as well as between bacteria and viruses (P < 0.05). The abundance of SMB53, Butyrivibrio, Facklamia, Trichococcus, and Turicibacter was significantly correlated with the health status of cattle (P < 0.05). The proportion of BRV, BCoV, BKV, BToV, BoNoV, BoNeV, BoAstV, BEV, BoPV, and BVDV in 1,120 fecal samples varied from 1.61% to 12.05%. A series of significant correlations were observed between the prevalence of individual viruses and the disease-associated ecological factors. A genome-based phylogenetic analysis revealed high variability of 10 bovine enteric viruses. The bovine hungarovirus was initially identified in both dairy and beef cattle in China. This study elucidates the fecal virome and bacterial community signatures of cattle affected by diarrhea, and reveals novel disease-associated ecological risk factors, including cattle type, cattle age, aquaculture model, and geographical location.IMPORTANCEThe lack of data on the virome and bacterial community restricts our capability to recognize ecological risk factors for bovine diarrhea disease, thereby hindering our overall comprehension of the disease's cause. In this study, we found that, for the diarrheal samples, the identified virome and bacterial community varied in terms of composition, abundance, diversity, configuration, and geographic distribution in relation to different disease-associated ecological factors. A series of significant correlations were observed between the prevalence of individual viruses and the disease-associated ecological factors. Our study aims to uncover novel ecological risk factors of bovine diarrheal disease by examining the pathogenic microorganism-host-environment disease ecology, thereby providing a new perspective on the control of bovine diarrheal diseases.

Efficacy and safety of belimumab therapy for patients with lupus nephritis: A meta-analysis and a propensity score-matched case-control study.

OBJECTIVE: In this study, we performed a meta-analysis and a propensity score-matched case-control study to evaluate the efficacy and safety of belimumab in patients with lupus nephritis (LN). METHODS: We analyzed the data from three randomized controlled trials (RCTs) to assess the effects of belimumab treatment on renal improvement and adverse effects. Our study included a total of six LN patients who received belimumab treatment and an additional six LN patients who received standard therapy. All participants were followed up for a duration exceeding 96 weeks to evaluate the outcomes of the treatments. RESULTS: Our meta-analysis incorporated data from three articles involving a total of 666 patients. The results of the analysis revealed that a higher proportion of patients who received belimumab treatment experienced renal improvement compared to those in the control group. The patients in belimumab group had a higher renal complete response rate and proteinuria improvement rate compared to the control group. However, belimumab treatment did not increase the renal partial response rate compared to the control group. The belimumab group also exhibited a higher proportion of patients who achieved normalization of antidouble-stranded DNA, as well as normalization of low C3 and C4 levels. In our case-control study, significant improvement in proteinuria was demonstrated with belimumab at Week 48 (p = 0.037) and at all subsequent time points (all p < 0.05). Over the course of 96 weeks, belimumab treatment was associated with renal function stabilization and an increase in C3 and C4 levels. Moreover, the use of belimumab resulted in a reduction in glucocorticoid dosage at Week 24 (p = 0.02). Additionally, patients receiving belimumab treatment had a lower risk of severe treatment-emergent adverse events, and no other significant adverse effects were observed between the two groups. CONCLUSIONS: In patients with LN, the utilization of belimumab therapy has demonstrated notable improvements in renal response rates. Additionally, it has shown a decreased likelihood of serious treatment-related adverse events and a diminished need for glucocorticoid dosage when compared to the active control group.

Positive outcomes with neoadjuvant chemotherapy in the management of colovesical fistula in cancer: a case report and literature review.

Colovesical fistula (CVF) is usually developed from colonic diverticulitis, followed by tumor. Traditional surgery is usually completed in one or more stages. For complex cancerous CVF, radical resection is more difficult. We report a 62-year-old male patient diagnosed with sigmoid colon cancer combined with sigmoid vesical fistula. In the course of treatment, in addition to conventional surgery, neoadjuvant chemotherapy (NAC) was innovatively used. The sigmoid tumor and fistula were significantly shrunken. Radical surgery achieved negative margins.