Explore the vast range of titles available.

Apoptosis is a form of cell death by which the body maintains the homeostasis of the internal environment. Apoptosis is an initiative cell death process that is controlled by genes and is mainly divided into endogenous pathways (mitochondrial pathway), exogenous pathways (death receptor pathway), and apoptotic pathways induced by endoplasmic reticulum (ER) stress. The homeostasis imbalance in ER results in ER stress. Under specific conditions, ER stress can be beneficial to the body; however, if ER protein homeostasis is not restored, the prolonged activation of the unfolded protein response may initiate apoptotic cell death via the up-regulation of the C/EBP homologous protein (CHOP). CHOP plays an important role in ER stress-induced apoptosis and this review focuses on its multifunctional roles in that process, as well as its role in apoptosis during microbial infection. We summarize the upstream and downstream pathways of CHOP in ER stress induced apoptosis. We also focus on the newest discoveries in the functions of CHOP-induced apoptosis during microbial infection, including DNA and RNA viruses and some species of bacteria. Understanding how CHOP functions during microbial infection will assist with the development of antimicrobial therapies.

A PI control approach grounded in an optimized improved whale algorithm is devised to tackle the characteristics of multivariable, nonlinear, strong coupling, and uncertain and fluctuating wind speeds in electric variable pitch systems. In the improved whale algorithm optimization algorithm, the reverse learning mechanism is utilized within the population initialization stage, the nonlinear inertial weight coefficient is introduced in the global and local search processes of whale predation, and the convergence factor is updated by the exponential function, which effectively addresses the issue of sluggish convergence speed and low convergence efficiency of the whale optimization algorithm. The position control of the electric variable pitch system is implemented with the application of the improved whale optimization algorithm. According to the performance index of the position ring, the appropriate objective function is established, and the adaptive control of the position ring is realized through the adaptive adjustment of PI parameters. The simulation outcomes demonstrate that the PI control, which is founded on an improved whale optimization algorithm, is superior to the PI control based on the whale optimization algorithm in dynamic and steady performance. When the load torque changes, using PI control based on the improved whale optimization algorithm, the pitch angle reaches the steady-state value in 0.06 s without overshoot, while using PI control based on the whale optimization algorithm, the pitch angle reaches the steady-state value in 0.09 s with a maximum overshoot of 2.4°. When the load torque is constant, PI control based on the improved whale optimization algorithm can achieve pitch angle tracking in 0.16 s, while PI control based on the whale optimization algorithm can achieve pitch angle tracking in 0.48 s.

Power system inertia is receiving increasing attention because the inclusion of renewable energy generation equipment weakens the inertia of the regional equivalent system and affects the transient stability of the system. In this paper, the influence of variation of inertia constant on the transient stability of the system is studied analytically by adding short‐circuit faults, Equal Area Criterion, and derivation of equations. On the basis of theoretical analysis, multi‐machine system is established to simulate and verify the correctness of the analysis results.

Under the “dual carbon” goals, this study focuses on realizing energy exchange among multiple microgrids via shared energy storage to promote sustainable energy transition. Accordingly, a distributed robust optimwhichization strategy is proposed in this paper. Addressing the uncertainty of distributed renewable energy sources within microgrids, the scenario set generated by the Wasserstein generative adversarial network with gradient penalty and pruned by the K-means++ clustering algorithm serves as the initial renewable energy scenario for the distributed robust optimization set. Combining Nash theory, a cooperative game operation model is constructed. The benefit distribution model based on contribution factors ensures a fair benefit allocation scheme. The parallelizable column and constraint generation algorithm is employed to enhance computational efficiency. Case studies demonstrate that compared to scenes produced by other methods, the proposed model has the lowest alliance operating cost. It more effectively captures renewable energy uncertainty and lowers system operational costs. The respective efficiency improvement rates for each microgrid are as follows: 4.6%, 5.0%, and 4.1%, ensuring a fair profit distribution scheme. This study provides a technical reference for realizing the sustainable development of a multiple microgrid system, contributing to the global goal of low-carbon energy transition and sustainable development.

Brucella is an intracellular parasitic pathogen that causes the worldwide zoonotic disease brucellosis. The type IV secretion system (T4SS) is utilized to secrete various effectors to help Brucella form Brucella -containing vacuoles within the cell and accomplish intracellular trafficking and replication. Brucella has fewer recognized effector proteins than other intracellular parasites in the Proteobacteria , indicating that Brucella may contain a large number of unidentified effector proteins. In this study, the optimal conditions for inducing protein secretion from Brucella were screened, and the secreted proteins of 2308 and the T4SS-deficient mutant SV123 under optimal conditions were collected for comparative proteomics analysis. By label-free quantitative proteomics, we identified 15 differential proteins. Through the β-lactamase TEM1 assay and indirect immunofluorescence assay, we identified RS15060 and RS10635 as novel T4SS effectors. Furthermore, by constructing mutation strains and performing cell/mouse infection experiments, we found that deletion of the rs15060 gene reduced the capacity of Brucella to replicate in cells and cause chronic infection in mice. In conclusion, a novel Brucella T4SS effector protein, RS15060, was identified to be associated with virulence in this study, and the discovery of effector proteins is conducive to a more comprehensive elucidation of T4SS function as well as to uncovering the cryptic strategies of Brucella survival in cells.

Brucellosis, a globally significant zoonotic disease caused by  Brucella  infection, relies on the pathogen’s ability to invade and replicate within host cells. This intracellular replication is tightly regulated by transcriptional networks, including the LysR-family regulator VtlR, which is critical for  B. abortus  virulence but whose role in B. melitensis remains unclear. Here, we constructed  vtlR  mutant and complemented strains in B. melitensis M5 and demonstrated that VtlR is essential for virulence. Phenotypic assays revealed that vtlR deletion impaired bacterial growth on L-fucose, D-glucose, and meso-erythritol, increased sensitivity to hydrogen peroxide and sodium nitroprusside, and reduced intracellular survival in RAW264.7 macrophages while triggering reactive oxygen species (ROS) production. RNA-seq and RT-qPCR analysis indicated that VtlR positively regulates small RNA AbcR2 and three DUF1127-domain proteins (RS13565, RS04310, RS13280), mirroring its regulatory role in  B. abortus . However, overexpression of these targets failed to restore virulence in the  vtlR  mutant. Notably, the mutant strain elicited protective immunity in mice, suggesting its potential as a live-attenuated vaccine candidate. Collectively, this study elucidates the VtlR regulon in  B. melitensis , advancing our understanding of  Brucella  pathogenesis and vaccine development.

The inappropriate use of antibiotics has led to the emergence of multidrug-resistant strains. Bacteriophages (phages) have gained renewed attention as promising alternatives or supplements to antibiotics. In this study, a lytic avian pathogenic Escherichia coli (APEC) phage designated as PEC9 was isolated and purified from chicken farm feces samples. The morphology, genomic information, optimal multiplicity of infection (MOI), one-step growth curve, thermal stability, pH stability, in vitro antibacterial ability and biofilm formation inhibition ability of the phage were determined. Subsequently, the therapeutic effects of the phages were investigated in the mice model. The results showed that PEC9 was a member of the siphovirus-like by electron microscopy observation. Biological characterization revealed that it could lyse two serotypes of E. coli , including O1 (9/20) and O2 (6/20). The optimal multiplicity of infection (MOI) of phage PEC9 was 0.1. Phage PEC9 had a latent period of 20 min and a burst period of 40 min, with an average burst size of 68 plaque-forming units (PFUs)/cell. It maintained good lytic activity at pH 3-11 and 4-50°C and could efficiently inhibit the bacterial planktonic cell growth and biofilm formation, and reduce bacterial counts within the biofilm, when the MOI was 0.01, 0.1, and 1, respectively. Whole-genome sequencing showed that PEC9 was a dsDNA virus with a genome of 44379 bp and GC content of 54.39%. The genome contains 56 putative ORFs and no toxin, virulence, or resistance-related genes were detected. Phylogenetic tree analysis showed that PEC9 is closely related to E. coli phages vB_EcoS_Zar3M, vB_EcoS_PTXU06, SECphi18, ZCEC10, and ZCEC11, but most of these phages exhibit different gene arrangement. The phage PEC9 could successfully protect mice against APEC infection, including improved survival rate, reduced bacterial loads, and organ lesions. To conclude, our results suggest that phage PEC9 may be a promising candidate that can be used as an alternative to antibiotics in the control of APEC infection.

The widespread chronic enteritis known as Paratuberculosis (PTB) or Johne's disease (JD) is caused by Mycobacterium avium subspecies paratuberculosis (MAP), posing a significant threat to global public health. Given the challenges associated with PTB or JD, the development and application of vaccines are potentially important for disease control. The aim of this study was to design a multi-epitope vaccine against MAP. A total of 198 MAP genomes were analyzed using pan-genome and reverse vaccinology approaches. B-cell and T-cell epitope analysis was performed on the selected promising cross-protective antigens followed by selection of epitopes with high antigenicity, no allergenicity, and no toxicity for the design of the vaccine. The designed vaccine was evaluated through molecular dynamics simulations, molecular docking, and immunological simulations. The results revealed the identification of five promising cross-protective antigens. In total, 10 B-cell epitopes, 10 HTL epitopes, and 9 CTL epitopes were selected for the design of the vaccine. Both the vaccine candidate and the vaccine-TLR4 complex demonstrated considerable stability in molecular dynamics simulations. Molecular docking studies confirmed that the vaccine candidate successfully interacted with TLR4. Immunological simulations showed an increase in both B-cell and T-cell populations after vaccination. Additionally, the vaccine candidate exhibited a codon adaptability index of 1.0 and a GC content of 53.64%, indicating strong potential for successful expression in Escherichia coli . This research developed a multi-epitope vaccine targeting MAP through pan-genomes and reverse vaccinology methods, offering innovative strategies for creating effective vaccines against MAP.

Background: Brucellosis is a zoonotic bacterial disease primarily controlled through quarantine, culling, and vaccination. Live attenuated vaccines remain the most effective countermeasure, yet their application is limited by residual virulence and diagnostic interference. This study developed three rough-type attenuated Brucella melitensis mutants (G7, G8, G16) and evaluated their potential as DIVA (Differentiating Infected from Vaccinated Animals) vaccine candidates. Methods: Rough phenotypes were characterized through heat agglutination, acridine orange staining, and immunoblotting. Macrophage cytotoxicity was assessed via LDH release assays, while RT-qPCR analyzed macrophage activation capacity. Mouse infection and immunization-challenge experiments, complemented by histopathology, evaluated residual virulence and protective immunity. Antibody profiles were determined by ELISA, and DIVA capability was verified using LPS-coated ELISA. Results: G7 and G8 exhibited complete rough phenotypes, whereas G16 retained partial O-antigen (semi-rough). All rough mutants induced macrophage cytotoxicity and activation. The strains showed attenuated virulence with no viable bacteria recovered from spleens at 4 weeks post-inoculation. Histopathology revealed no liver lesions at 6 weeks post-inoculation. Immunized mice predominantly produced IgG2a-dominated Th1-type responses. The immune protection levels of G7 and G16 matched the reference vaccine M5–90Δ26, while G8 showed slightly lower efficacy. LPS-ELISA effectively differentiated vaccinated from infected animals via concurrent IgM/IgG detection. Conclusions: This study demonstrates that the rough-type B. melitensis mutants G7 and G16 serve as promising DIVA vaccine candidates, offering strong protection with low residual virulence while enabling serological differentiation between vaccinated and infected animals, highlighting their potential as effective vaccines for brucellosis control.

Background Mycoplasma synoviae (MS) is considered to be one of the main mycoplasma pathogens of poultry, causing arthritis, airsacculitis, eggshell apex abnormalities and production drops in chickens and turkeys. Infection by MS usually results in considerable economic losses to the poultry industry worldwide. Therefore, it is essential to develop a highly sensitive and accurate diagnostic method in the livestock production. Results The MSLP53 was predicted as a highly conserved and specific membrane associated lipoprotein of MS by bioinformatics analysis. The His-tagged MSLP53 (rMSLP53) protein was expressed and purified using E. coli expression system, and was confirmed by Western blotting to react with each MS-positive serum, but not react with positive sera against other avian pathogens, suggesting that the rMSLP53 had strong immunoreactivity and specificity. An rMSLP53-based indirect ELISA was developed, compared to IDEXX kit with a pool of 277 chicken sera samples, and showed high sensitivity (85.54%), specificity (89.19%) and coincidence rate (87.00%) within these two methods. When detecting the sera from experimentally infected chickens, the newly established rMSLP53-ELISA had certain advantages over the IDEXX kit, that is, it could identify the serum 3–18 weeks after infection as MS-positive serum, while IDEXX kit could only identify the serum 3–12 weeks after infection as positive serum. Conclusion The MSLP53 protein is a specific immunogenic lipoprotein of MS, which was confirmed to be a promising antigen target for the detection of serum antibodies of MS. A rMSLP53-based indirect ELISA assay was successfully established in this study, showed high sensitivity, specificity and consistency with the commercial IDEXX kit, and could recognize the serum as MS-positive in a longer period after MS infection than IDEXX kit. This newly established rMSLP53-ELISA may be used as an effective detection method for MS serological monitoring and epidemiological investigation.