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Natural killer (NK) cells are crucial innate immune cells that provide defense against viruses and tumors. However, aging is associated with alterations in NK cell composition and compromised cell functions. Melatonin, known for its anti-tumor effects, has been reported to improve NK cell function. However, the molecular mechanism underlying melatonin’s effect on senescent NK cells remains unclear. In this study, we aimed to elucidate the mechanism by which melatonin enhances the function of senescent NK cells. Our findings revealed that melatonin significantly increased the number and function of NK cells in aging mice. The results suggest that melatonin enhances NK cell proliferation, degranulation, and IFN-γ secretion. Further investigations demonstrated that melatonin promotes NK cell maturation and activation, mainly via the JAK3/STAT5 signaling pathway, leading to increased expression of T-bet. These discoveries provide a theoretical basis for potential immunotherapy strategies based on melatonin-mediated modulation of NK cell function in aging individuals.

Long‐term subjection to shift work increases the risk of cancer. The purpose of the present study was to explore the mechanism by which chronic circadian disruption impairs natural killer (NK) cell immunosurveillance. Mice were subjected to light‐dark reverse every 4 days for 12 weeks to disrupt normal circadian rhythm. NK cell development and function were evaluated by flow cytometry. The mRNA and protein levels of period 1 (per1) and per2 were suppressed, while circadian locomotor output cycle kaput (CLOCK) was increased in the shifted mice, indicating successful generation of the circadian rhythm disruption mouse model. Chronic shift‐lag promoted NK cell ageing, which is likely due to the reduction in Ly49 family receptor expression in shifted NK. We further studied the effects of circadian rhythm disruption on NK cell function. Chronic shift‐lag inhibited NK cell secretion of granular CD107a and interferon gamma. Moreover, chronic shift‐lag attenuated the clearance of MHC‐I–deficient tumour cells by NK cells in vivo and promoted lung metastasis of B16F10 melanomas. Furthermore, chronic shift‐lag reduced NK cell killing function, which may be due to the suppression of Eomes transcription factor expression, which inhibiting the transcription of CD122. In conclusion, our findings suggest that chronic circadian disruption attenuates NK cell cytolytic activity by decreasing the expression of CD122.

Due to the good biocompatibility, polyvinyl alcohol (PVA) hydrogels have attracted the attention of many biomaterial researchers. However, the low strength and poor toughness of pure PVA hydrogel prepared by freeze–thaw method limit the application. In this study, silica was used to enhance the performances of PVA hydrogel. Different from previous PVA/SiO 2 hydrogels, urea was used to regulate the formation and distribution of silica in PVA, which greatly improved the mechanical properties of hydrogels. The tensile stress and toughness of the obtained PVA(Urea)/SiO 2 hydrogels reached 8.10 MPa and 44.45 MJ/m 3 , which were 39 times and 212 times as that of pure PVA hydrogel, respectively. In PVA(Urea)/SiO 2 hydrogels, SiO 2 had both strengthening and toughening effects on hydrogels, which is very different from the ordinary composite hydrogels. In addition, PVA(Urea)/SiO 2 hydrogels showed unique self-reinforcing characteristics with increasing the number of tensile recoveries in cyclic stretching and recovery tests. Thus, PVA(Urea)/SiO 2 hydrogel with high strength and toughness, constructed by a simple strategy, is a potential candidate in cartilage repair.

Integrated hydrogel supercapacitors have attracted increasing attention owing to their low interfacial contact resistance and excellent electrochemical performance even under folding and bending. Herein, phosphomolybdic acid-doped polypyrrole (PPy) was deposited in situ on the surface of a hydroxypropyl cellulose/polyvinyl alcohol (HPC/PVA) hydrogel to fabricate integrated hydrogel supercapacitors. The negatively charged phosphomolybdic acid (PMo 12 ) was anchored onto the positively charged PPy chain to prevent its dissolution in the electrolyte thereby enhancing its pseudocapacitive performance. PMo 12 also can dope and modify PPy, providing additional pseudocapacitance and thereby improving the energy storage capacity of the supercapacitor. The supercapacitor achieved a high areal specific capacitance (350 mF cm −2 at 0.5 mA cm −2 ) and demonstrated a remarkable energy density (24.0 μ Wh cm −2 at 1000 μ W cm −2 ). After 1000 galvanostatic charge–discharge cycles at a high current density of 10 mA cm −2 , it retained 71.3% of its initial capacitance and maintained 98% Coulombic efficiency.

GPR35 is a G protein-coupled receptor with notable involvement in modulating inflammatory responses. Although the precise role of GPR35 in inflammation is not yet fully understood, studies have suggested that it may have both pro- and anti-inflammatory effects depending on the specific cellular environment. Some studies have shown that GPR35 activation can stimulate the production of pro-inflammatory cytokines and facilitate the movement of immune cells towards inflammatory tissues or infected areas. Conversely, other investigations have suggested that GPR35 may possess anti-inflammatory properties in the gastrointestinal tract, liver and certain other tissues by curbing the generation of inflammatory mediators and endorsing the differentiation of regulatory T cells. The intricate role of GPR35 in inflammation underscores the requirement for more in-depth research to thoroughly comprehend its functional mechanisms and its potential significance as a therapeutic target for inflammatory diseases. The purpose of this review is to concurrently investigate the pro-inflammatory and anti-inflammatory roles of GPR35, thus illuminating both facets of this complex issue.

Background Reprogramming lipid metabolism for tumor metastasis is essential in breast cancer, and NUCB2/Nesfatin-1 plays a crucial role in regulating energy metabolism. Its high expression is associated with poor prognosis in breast cancer. Here, we studied whether NUCB2/Nesfatin-1 promotes breast cancer metastasis through reprogramming cholesterol metabolism. Methods ELISA was employed to measure the concentration of Nesfatin-1 in the serum of breast cancer patients and the control group. Database analysis suggested that NUCB2/Nesfatin-1 might be acetylated in breast cancer, which was confirmed by treating the breast cancer cells with acetyltransferase inhibitors. Transwell migration and Matrigel invasion assays were conducted, and nude mouse lung metastasis models were established to examine the effect of NUCB2/Nesfatin-1 on breast cancer metastasis in vitro and in vivo. The Affymetrix gene expression chip results were analyzed using IPA software to identify the critical pathway induced by NUCB2/Nesfatin-1. We evaluated the effect of NUCB2/Nesfatin-1 on cholesterol biosynthesis through the mTORC1-SREBP2-HMGCR axis by utilizing mTORC1 inhibitor and rescue experiments. Results NUCB2/Nesfatin-1 was found to be overexpressed in the breast cancer patients, and its overexpression was positively correlated with poor prognosis. NUCB2 was potentially acetylated, leading to high expression in breast cancer. NUCB2/Nesfatin-1 promoted metastasis in vitro and in vivo, while Nesfatin-1 rescued impaired cell metastasis induced by NUCB2 depletion. Mechanistically, NUCB2/Nesfatin-1 upregulated cholesterol synthesis via the mTORC1 signal pathway, contributing to breast cancer migration and metastasis. Conclusions Our findings demonstrate that the NUCB2/Nesfatin-1/mTORC1/SREBP2 signal pathway is critical in regulating cholesterol synthesis, essential for breast cancer metastasis. Thus, NUCB2/Nesfatin-1 might be utilized as a diagnostic tool and also used in cancer therapy for breast cancer in the future.

Oxidative stress can adversely affect the health status of the body, more specifically by causing intestinal damage by disrupting the permeability of the intestinal barrier. This is closely related to intestinal epithelial cell apoptosis caused by the mass production of reactive oxygen species (ROS). Baicalin (Bai) is a major active ingredient in Chinese traditional herbal medicine that has antioxidant, anti-inflammatory, and anti-cancer properties. The purpose of this study was to explore the underlying mechanisms by which Bai protects against hydrogen peroxide (H2O2)-induced intestinal injury in vitro. Our results indicated that H2O2 treatment caused injury to IPEC-J2 cells, resulting in their apoptosis. However, Bai treatment attenuated H2O2-induced IPEC-J2 cell damage by up-regulating the mRNA and protein expression of ZO-1, Occludin, and Claudin1. Besides, Bai treatment prevented H2O2-induced ROS and MDA production and increased the activities of antioxidant enzymes (SOD, CAT, and GSH-PX). Moreover, Bai treatment also attenuated H2O2-induced apoptosis in IPEC-J2 cells by down-regulating the mRNA expression of Caspase-3 and Caspase-9 and up-regulating the mRNA expression of FAS and Bax, which are involved in the inhibition of mitochondrial pathways. The expression of Nrf2 increased after treatment with H2O2, and Bai can alleviate this phenomenon. Meanwhile, Bai down-regulated the ratio of phosphorylated AMPK to unphosphorylated AMPK, which is indicative of the mRNA abundance of antioxidant-related genes. In addition, knockdown of AMPK by short-hairpin RNA (shRNA) significantly reduced the protein levels of AMPK and Nrf2, increased the percentage of apoptotic cells, and abrogated Bai-mediated protection against oxidative stress. Collectively, our results indicated that Bai attenuated H2O2-induced cell injury and apoptosis in IPEC-J2 cells through improving the antioxidant capacity through the inhibition of the oxidative stress-mediated AMPK/Nrf2 signaling pathway.

Streptococcus suis infection represents a major challenge in pig farming and public health due to its zoonotic potential and diverse serotypes, while existing vaccines lack effective cross-protection. This study employed reverse vaccinology and immunoinformatics to identify 8 conserved proteins across 11 prevalent serotypes of S. suis . 16 candidate epitopes were selected to design three multi-epitope antigens against S. suis (designated as MEASs), which fused with a dendritic cell-targeting peptide to improve antigen presentation in host. Purified MEASs displayed favorable cross-reactogenicity against 29 serotype-specific antiserums. Robust humoral and cellular immune responses can be induced by MEAS 1 and MEAS 3 in a mouse model, which provided substantial protection against virulent strains from two different serotypes. In particular, their immune serums exhibited positive opsonization effects within bloodstream and macrophage phagocytosis. Taken together, we identified two promising MEASs with excellent cross-protection, offering potential in preventing S. suis infections in a mouse model.