Effects of short-term exposure to ferrous sulfate on bioaccumulation, oxidative stress biomarkers, immunity, and intestinal microbiota in Litopenaeus vannamei.

Fasciola gigantica: Ultrastructure and cytochemistry of tegumental secretory activity and extracellular vesicle formation in juvenile flukes migrating in mouse liver.

Antimicrobial peptides (AMPs) are key effectors of innate immunity that, beyond their canonical activity, exhibit promising therapeutic potential against cancer and cellular senescence. Their efficacy relies on selective membrane disruption driven by specific lipid signatures, yet quantifying these interactions in complex bilayer systems remains challenging. Lipid monolayers serve as powerful reductionist models to isolate the physicochemical determinants of this selectivity, effectively mimicking the outer leaflet of bacterial, cancerous, or senescent membranes. This review provides a critical analysis of how lipid composition, packing density, and phase behavior modulate AMP adsorption and insertion. We systematically integrate thermodynamic profiling (surface pressure, compressibility, mixing energy) with advanced structural and morphological characterization. Special emphasis is placed on how spectroscopic techniques (IRRAS, GIXD, SFG) and real-time microscopy (BAM, fluorescence, AFM) resolve peptide orientation, secondary structure induction, and lipid domain remodeling at the mesoscale. These experimental observables are bridged with Molecular Dynamics (MD) simulations, establishing a feedback loop between macroscopic measurements and atomistic resolution. By defining the advantages and limitations of monolayer models relative to vesicles and bilayers, we outline a rational framework for leveraging interfacial insights in the design of next-generation peptide therapeutics and nanobiotechnological applications.

Dendritic cells targeted CEA tumor antigen through DEC205 in combination with oncolytic reovirus stimulate strong immune response in colorectal cancer model.

Recurrent pneumonia in the elderly can repeatedly damage lung function and reduce quality of life, posing certain challenges to clinical treatment. To analyze the synergistic immune regulatory effects of Cistanche deserticola, Schisandra chinensis and Cornus officinalis on elderly patients with recurrent pneumonia. A total of 165 patients with recurrent pneumonia from Chengde Medical University from January 2024 to January 2025 were recruited, 158 were enrolled after exclusions, 8 lost to follow-up, and 150 finally analyzed. The 150 patients were divided into MC group (n=75) and MA group (n=75). Both groups were treated with Ma Xing Shi Gan Tang and Azithromycin, while the MC group was additionally treated with Cistanche deserticola, Schisandra chinensis and Cornus officinalis. The main evaluation includes the Traditional Chinese Medicine Syndrome Score (TCMSS), lung function indicators, inflammation indicators, immune indicator levels and clinical efficacy of two groups. Secondary outcomes include quality of life scores, incidence of complications and adverse reactions. After treatment, the lung function indicators, immune indicators and clinical efficacy in MC group were higher than in the CC group; the TCMSS and inflammatory indicators were lower in the CC group (P>0.05). No significant difference in quality of life score, incidence of complications and adverse reactions between the two groups (P<0.05). This method has a good immunomodulatory effect on elderly patients with recurrent pneumonia and is worthy of further promotion and application.

Evaluated the immune efficacy of a bivalent inactivated vaccine against post-weaning multisystemic wasting syndrome and mycoplasmal pneumonia of swine.

A review of targeting microRNAs as potential therapeutic strategies against respiratory viruses: Current insights and future directions.

Immune and protective effects of recombinant multi-epitopes vaccine against infectious spleen and kidney necrosis virus in pearl gentian grouper (♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatus).

Ginsenosides remodel tumor immune microenvironment through metabolic reprogramming: Targets and mechanisms.

Potential immunomodulatory and antitumor properties of hydatid cysts components.

Growth and immune effects of standardized Ashwagandha extract in whiteleg shrimp, Litopenaeus vannamei, post-larvae

Proteins are essential components in biotechnological and biopharmaceutical applications; however, their structural instability under alkaline conditions presents significant limitations. High-pH environments, such as chromatographic clean-in-place (CIP) protocols, frequently cause protein degradation and loss of biological activity. Current strategies for engineering alkali-stable proteins include rational design approaches targeting deamidation-susceptible residues, surface charge optimization, and enzyme extraction from alkaliphilic organisms. However, the fundamental principles governing alkaline stability remain poorly understood. In this study, we investigated alkaline stability mechanisms in Fc gamma receptor IIIa, a critical immune effector protein with applications in antibody purification and glycoform analysis. Systematic mutagenesis identified a tyrosine-to-phenylalanine substitution at position 59 that significantly enhanced protein stability during alkaline CIP exposure while retaining substantial IgG binding activity. Structural and biophysical characterizations revealed that this substitution prevents the deprotonation of tyrosine that occurs at alkaline pH, thereby mitigating destabilizing electrostatic repulsion within the protein structure. Our findings support a model in which targeted aromatic substitution enhances alkaline stability without severely compromising protein function and provide mechanistic insight into the contribution of buried tyrosine ionization to alkaline instability in FcγRIIIa.

Chimeric antigen receptor T (CAR-T) cell therapy is revolutionizing cancer treatment in hematological malignancies, but challenges related to the tumor microenvironment have hindered CAR-T success, especially in solid tumors. Myeloid cells in particular have been implicated in CAR-T efficacy. In this review, we discuss the roles of myeloid cells in CAR-T-associated toxicities including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, along with strategies to treat these toxicities by modulating myeloid cells. The review also explores myeloid cell-mediated suppression or enhancement of CAR-T function. Finally, strategies employed to target myeloid cells in combination with CAR-T cell therapy will be investigated.

In 2014, the first patient received a CD22 chimeric antigen receptor (CAR) T-cell product. As one of the earliest approaches targeting an antigen other than CD19, this trial addressed an unmet need while providing insights into CAR T-cell efficacy, impact of manufacturing changes, and management of inflammatory toxicities over its 10-year span. This final chapter provides a comprehensive review of the collective findings. Across 78 patients with B-cell acute lymphoblastic leukemia who received infusion, cytokine release syndrome was observed in 66 (84.6%) patients, whereas 28 (35.9%) had immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), and 18 (23.1%) had reversible neurotoxicity. Complete response was achieved in 54 (70.1%) patients by day 28, of whom 45 (83.3%) were measurable residual disease negative. Median overall survival was 13.6 months, and median relapse-free survival was 6.1 months. Pharmacokinetics revealed peak CAR T-cell expansion at a median of 14 days (range, 12-50), with no variation by dose. Interestingly, toxicities, CAR T-cell expansion, and disease response did not correlate with baseline disease burden. Additionally, although early intervention approaches to mitigate IEC-HS severity for this construct appeared promising, further study is needed. Given the critical importance of CD22 targeting, this experience serves as a foundation for new approaches targeting CD22 while providing ongoing support for dual-targeting approaches and insights into toxicity mitigation. This trial was registered at www.ClinicalTrials.gov as NCT02315612.

NK and NKT cells act as major effector subsets across multiple immune heterogeneous cell populations (HCPs), and their precise identification is essential for assessing product quality and predicting clinical efficacy. Here, we present a label-free identification strategy that couples Raman spectroscopy with a convolutional neural network (CNN) to achieve rapid and accurate classification of NKT and NK cells within diverse immune HCPs, including NK and CIK HCPs. In contrast to flow cytometry, this approach requires no antibody labeling, enables in situ measurement, and markedly shortens analysis time, while deep learning substantially improves classification speed and accuracy. By combining a visualization module with spectral analysis, we identified characteristic Raman peaks at 558 and 938 cm-1 in NKT cells, which serve as robust spectral biomarkers distinguishing NKT from NK cells. These findings are of considerable significance for immune cell identification and for advancing mechanistic studies. Overall, the study addresses limitations of traditional cell-typing technologies and provides a robust new pathway for quality monitoring of immune effector cell products, offering important implications for the development of immunotherapy.

Leishmania parasites are transmitted through the bite of infected female sand flies. The sand fly inoculum contains both the parasite and the salivary proteins, which can modulate the immune system's function. Some of these salivary proteins have the potential to be used as a vaccine candidate. Since there have been fewer studies investigating the salivary proteins of Phlebotomus (Ph.) sergenti, this prompted us to select among the three protein members of Ph. sergenti apyrase family (PsSP40, PsSP41, and PsSP42) and measure its effectiveness as vaccine candidate against Leishmania (L.) tropica. To select among the three family members as the candidate for immunization, different parameters including the physicochemical characters, three-dimensional structure, virtual immune stimulatory potential, and human leukocyte antigen (HLA) class II-binding epitope content were considered. To investigate the effect of immunization with the selected antigen through immunoinformatics analysis (PsSP42) against L. tropica infection, we immunized BALB/c mice with two distinct recombinant plasmids (conventional VR1020 and new-generation NTC9385R) two times at 3-week intervals followed by immediate electroporation. Eight weeks post-challenge, the parasite load in draining lymph nodes was measured by quantitative real-time polymerase chain reaction (PCR). The interferon (IFN)-γ and interleukin (IL)-4 cytokines before (against recombinant Leishmania tarentolae expressing PsSP42) and after (against parasite frozen/thawed antigens) L. tropica infection (2 × 107 parasite per footpad plus Ph. sergenti salivary gland homogenate (SGH)) were measured by enzyme-linked immunosorbent assay (ELISA). On the basis of immunoinformatics analysis of three apyrase salivary proteins from Ph. sergenti, PsSP42 demonstrated superior HLA class II-binding peptides compared with the other two proteins (PsSP40 and PsSP41) and was selected for immunization studies. Our findings indicated that NTC-PsSP42 and not VR1020-PsSP42 plasmid immunization relatively reduced the parasite load in the draining lymph nodes. This was assigned to a significant higher IFN-γ to IL-4 ratio induced by NTC-PsSP42 immunization in comparison with pertinent controls. In our study, although the expected protective response was not achieved by any of the recombinant plasmids, the NTC-PsSP42 platform induced a weak Th1-polarized immune response, which partially influenced the parasite load. Since the new generation of plasmids are worth evaluating owing to the lack of antibiotic resistance genes on the backbone, we recommend further assessment of NTC-PsSP42 potential adjuvnated with immunostimulatory sequences such as as CpG motifs or even in heterologous prime-boost regimens.

Immune-mediated side effects of cancer immunotherapies.

Human Schlafen proteins restrict viral replication by cleaving tRNA, thereby suppressing protein synthesis. Although the ribonuclease domain of Schlafen proteins is conserved across all domains of life, its function in prokaryotes has remained unclear. Here we demonstrate that prokaryotic Schlafen nucleases are widespread antiviral effectors that protect bacteria from bacteriophages and are fused to a diverse array of phage-sensing domains. We expressed seven Enterobacterales Schlafen systems in Escherichia coli, identifying two that confer defence against coliphages. We focused on a system where Schlafen nuclease is fused to a previously unknown immunoglobulin-like sensor domain and demonstrated that it recognizes tail assembly chaperones of T5-like phages. Upon activation, the Schlafen nuclease cleaves both E. coli and phage-encoded tRNAs and restricts T5 phage by reducing its burst size. Our findings redefine Schlafens as an ancient, mechanistically conserved family of immune effectors, revealing the deep evolutionary origin of tRNA-targeting antiviral immunity in humans.

Cyclophosphamide (CYP) may through its toxic metabolite, acrolein, induce hemorrhagic cystitis and bladder hyperactivity. Previous studies demonstrated intra-iliac arterial administration of adipose derived mesenchymal stem cells (ADSC)-derived microvesicles with less immune response and adverse effects than ADSC itself may confer anti-oxidative stress and anti-inflammatory potential to improve bladder dysfunction. We explored whether ADSC-derived microvesicles may prevent CYP-induced bladder cystitis and overactivity. Female Wistar rats were divided into control (Con), CYP (Cy), CYP+microvesicles (CyM), and microvesicles treated control (CoM) groups. Con rats were intraperitoneally treated with saline, while the Cy rats were induced by intraperitoneally administered CYP (100 mg/kg body weight). We injected ADSC-derived microvesicles at the dosage of 15 μg/ml via intra-iliac artery to the rats with or without CYP treatment. We measured the responses of transcystometrogram, pathology, expression of muscarinic receptors (M3) and purinergic receptors (P2X7), pyroptosis related Caspase 1 and IL-1β, xCT/Gpx4 related ferroptosis by western blot in CYP-treated bladders. Wire myography of the urinary bladder was determined. ADSC-derived microvesicles effectively decreased micturition frequency (overactivity), inflammation and fibrosis in CyM rats versus Cy rats. ADSC-derived microvesicles efficiently downregulated P2X7 and M3 receptor expression, Caspase 1/IL-1β mediated pyroptosis, xCT/Gpx4 regulated ferroptosis and restored Bcl-2/HO-1 mediated antioxidant defense mechanisms in CYP-induced cystitis. The pathologic results also displayed the effective reduction of bladder immune cell infiltration (inflammation) and fibrosis, and the preservation of the integrity in the urothelium by the treatment of ADSC-derived microvesicles. ADSC-derived microvesicles can ameliorate CYP-induced bladder overactivity, inflammation, fibrosis, ferroptosis and pyroptosis.

Maternal immunization and early-life immunity: Mechanisms shaping neonatal protection.