Fasting-Mimicking Diet Facilitates Anti-tumor Therapeutic Effects by Nutrient-Sensitive Nanocomposites.

Cancer cells support their uncontrolled proliferation primarily by regulating energy metabolism. Inhibiting tumor growth by blocking the supply of nutrients is an effective treatment strategy. Fasting-mimicking diet (FMD), as a low-calorie, low-protein, low-sugar, high-fat diet, can effectively reduce the nutrient supply to tumor cells. However, the significant biological barrier presented by the tumor microenvironment imposes greater demands and challenges for drug design. This study constructs the multifunctional nanocomposite ZnFe2O4@TiO2@CHC@Orl-FA (ZTCOF), which has great potential to overcome the aforementioned drawbacks. ZnFe2O4@TiO2 could produce 1O2 with ultrasound, and stimulate the Fenton-like conversion of endogenous H2O2 to ·OH, achieving a combined therapeutic effect of sonodynamic therapy (SDT) and chemodynamic therapy (CDT). Orl (Orlistat) and CHC (α-cyano-4-hydroxycinnamic acid) not only block tumor cell energy metabolism but also increase sensitivity to reactive oxygen species, enhancing the cytotoxic effect on tumor cells. Furthermore, combining the treatment strategies with FMD condition control can further inhibit cancer cell energy metabolism, achieving significant synergistic anti-tumor therapy. Both in vitro and in vivo experiments confirm that ZTCOF with SDT/CDT/starvation can achieve effective tumor suppression and destruction. This work provides theoretical and technical support for anti-tumor multimodal synergistic therapy.

Biofilm microenvironment-activated multimodal therapy nanoplatform for effective anti-bacterial treatment and wound healing.

Antimicrobial drug development faces challenges from bacterial resistance, biofilms, and excessive inflammation. Here, we design an intelligent nanoplatform utilizing mesoporous silica nanoparticles doped with copper ions for loading copper sulfide (DM/Cu2+-CuS). The mesoporous silica doped with tetrasulfide bonds responds to the biofilm microenvironment (BME), releasing Cu2+ions, CuS along with hydrogen sulfide (H2S) gas. The release of hydrogen sulfide within 72 h reached 793.5 µM, significantly higher than that observed with conventional small molecule donors. H2S induces macrophages polarization towards the M2 phenotype, reducing inflammation and synergistically accelerating endothelial cell proliferation and migration with Cu2+ions. In addition, H2S disrupts extracellular DNA within biofilms, synergistically photothermal enhanced peroxidase-like activity of CuS to effectively eradicate biofilms. Remarkably, DM-mediated consumption of endogenous glutathione enhances the anti-biofilm activity of H2S and improves oxygen species (ROS) destruction efficiency. The combination of photothermal therapy (PTT), chemodynamic therapy (CDT), and gas treatment achieves sterilization rates of 99.3 % and 99.6 % against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro under 808 nm laser irradiation. Additionally, in vivo experiments demonstrate a significant biosafety and antibacterial potential. In summary, the H2S donor developed in this study exhibits enhanced biocompatibility and controlled release properties. By integrating BME-responsive gas therapy with antibacterial ions, PTT and CDT, a synergistic multimodal strategy is proposed to offer new therapeutic approaches for wound healing. STATEMENT OF SIGNIFICANCE: The advanced DMOS/Cu2+-CuS (DMCC) multimodal therapeutic nanoplatform has been developed for the treatment of drug-resistant bacterial wound infections and has exhibited enhanced therapeutic efficacy through the synergistic effects of photothermal therapy, chemodynamic therapy, Cu2+ions, and H2S. The DMCC exhibited exceptional biocompatibility and could release CuS, Cu2+, and H2S in response to elevated concentrations of glutathione within the biofilm microenvironment. H2S effectively disrupted the biofilm structure. Meanwhile, peroxidase activity of CuS combined with GSH-mediated reduction of Cu2+ to Cu+ generated abundant hydroxyl radicals under acidic conditions, leading to efficient eradication of pathogenic bacteria. Furthermore, both H2S and Cu2+ could modulate M2 macrophages polarization and regulate immune microenvironment dynamics. These strategies collectively provided a novel approach for developing antibacterial nanomedical platforms.

Biodegradable pyroptosis inducer with multienzyme-mimic activity kicks up reactive oxygen species storm for sensitizing immunotherapy.

Triggering pyroptosis is a major new weathervane for activating tumor immune response. However, biodegradable pyroptosis inducers for the safe and efficient treatment of tumors are still scarce. Herein, a novel tumor microenvironment (TME)-responsive activation nanoneedle for pyroptosis induction, copper-tannic acid (CuTA), was synthesized and combined with the sonosensitizer Chlorin e6 (Ce6) to form a pyroptosis amplifier (CuTA-Ce6) for dual activation and amplification of pyroptosis by exogenous ultrasound (US) and TME. It was demonstrated that Ce6-triggered sonodynamic therapy (SDT) further enhanced the cellular pyroptosis caused by CuTA, activating the body to develop a powerful anti-tumor immune response. Concretely, CuTA nanoneedles with quadruple mimetic enzyme activity could be activated to an "active" state in the TME, destroying the antioxidant defense system of the tumor cells through self-destructive degradation, breaking the "immunosilent" TME, and thus realizing the pyroptosis-mediated immunotherapy with fewer systemic side effects. Considering the outstanding oxygen-producing capacity of CuTA and the distinctive advantages of US, the sonosensitizer Ce6 was attached to CuTA via an amide reaction, which further amplified the pyroptosis and sensitized pyroptosis-induced immunotherapy with the two-pronged strategy of CuTA enzyme-catalyzed cascade and US-driven SDT pathway to generate a "reactive oxygen species (ROS) storm". Conclusively, this work provided a representative paradigm for achieving safe, reliable and efficient pyroptosis, which was further enhanced by SDT for more robust immunotherapy.

Ultra-small Janus nanoparticle-induced activation of ferroptosis for synergistic tumor immunotherapy.

Ferroptosis induced by lipid peroxide (LPO) accumulation is an effective cell death pathway for cancer therapy. However, how to effectively induce ferroptosis at tumor sites and improve its therapeutic effectiveness remains challenging. Here, MnFe2O4@NaGdF4@NLG919@HA (MGNH) nanocomplex with tumor-specific targeting and TME response is constructed to overcome immunosuppressive tumor microenvironment (TME) to potentiate the curative effect of ferroptosis by coupling the immune checkpoint indoleamine 2,3-dioxygenase (IDO) inhibitor, NLG919, and hyaluronic acid (HA) to novel ultra-small MnFe2O4@NaGdF4 (MG) nanoparticles with a Janus structure. Firstly, tumor site-precise delivery of MG and NLG919 is achieved with HA targeting. Secondly, MG acts as a magnetic resonance imaging contrast agent, which not only has a good photothermal effect to realize tumor photothermal therapy, but also depletes glutathione and catalyzes the production of reactive oxygen species from endogenous H2O2, which effectively promotes the accumulation of LPO and inhibits the expression of glutathione peroxidase 4, achieving enhanced ferroptosis. Thirdly, NLG919 inhibits the differentiation of Tregs by blocking the tryptophan/kynurenine immune escape pathway, thereby reversing immunosuppressive TME together with the Mn2+-activated cGAS-STING pathway. This work contributes new perspectives for the development of novel ultra-small Janus nanoparticles to reshape immunosuppressive TME and ferroptosis activation. STATEMENT OF SIGNIFICANCE: The Janus structured MnFe2O4@NaGdF4@NLG919@HA (MGNH) nanocomplex was synthesized, which can realize the precise delivery of T1/T2 contrast agents MnFe2O4@NaGdF4 (MG) and NLG919 at the tumor site under the ultra-small Janus structural characteristics and targeted molecule HA. The production of ROS, consumption of GSH, and photothermal properties of MGNH make it possible for CDT/PTT activated ferroptosis, and synergistically disrupt and reprogram tumor growth and immunosuppressive tumor microenvironment with NLG919 and Mn2+-mediated activation of cGAS-STING pathway, achieving CDT/PTT/immunotherapy activated by ferroptosis. Meanwhile, ultra-small structural properties of MGNH facilitate subsequent metabolic clearance by the body, allowing for the minimization of potential biotoxicity associated with its prolonged retention.

Clinical evaluation of resorbable polylactic acid (PLA) intracanal posts for primary incisor restoration. Randomized controlled clinical trial.

This randomized, controlled clinical trial compares the clinical performance of glass-fibre and resorbable polylactic acid (PLA) intracanal posts used to restore carious primary incisors in young patients. The study sample includes 180 primary upper central incisors of 90 children aged 3 to 4 years. All patients were randomly divided into two equal groups of 45 children who received PLA and glass-fibre (GFP) intracanal posts. The clinical assessment of incisor restorations was carried out immediately upon completion and at months 3, 6 and 12 according to the following criteria: anatomical form, marginal adaptation, surface roughness, marginal pigmentation, colour match, secondary caries and contact point. The Gingival Index (GI), the Bleeding Index (Cowell modification; mBI), and bite force (BF) were measured. At the 3-month follow-up, the occlusal BF of patients who received PLA posts was higher than the baseline; the GI and mBI scores were lower, by contrast (p < 0.05). This tendency was even more pronounced 6 and 12 months after the restoration. The incidence of side effects or symptoms (apical inflammation, cervical fracture, loosening of the crown) after the PLA posts was significantly lower than after the GFP (p < 0.05). No statistically significant differences were present between the two groups with respect to colour matching, anatomical form, marginal adaptation, marginal pigmentation, surface roughness, occlusal contact and secondary caries. Based on the results, applying PLA intracanal posts and cyanoacrylate to residual anterior crowns in young children can improve their gingival health, reduce side effects, and increase the likelihood of successful restoration.

Ultrasound-enhanced covalent reaction of gliadin: the inhibition of antigenicity and its potential mechanisms.

BACKGROUND: Wheat proteins can be divided into water/salt-soluble protein (albumin/globulin) and water/salt-insoluble protein (gliadins and glutenins (Glu)) according to solubility. Gliadins (Glia) are one of the major allergens in wheat. The inhibition of Glia antigenicity by conventional processing techniques was not satisfactory. RESULTS: In this study, free radical oxidation was used to induce covalent reactions. The effects of covalent reactions by high-intensity ultrasound (HIU) of different powers was compared. The enhancement of covalent grafting effectiveness between gliadin and (-)-epigallo-catechin 3-gallate (EGCG) was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry and Folin-Ciocalteu tests. HIU caused protein deconvolution and disrupted the intrastrand disulfide bonds that maintain the tertiary structure, causing a shift in the side chain structure, as proved by Fourier, fluorescence and Raman spectroscopic analysis. Comparatively, the antigenic response of the conjugates formed in the sonication environment was significantly weaker, while these conjugates were more readily hydrolyzed and less antigenic during simulated gastrointestinal fluid digestion. CONCLUSION: HIU-enhanced free radical oxidation caused further transformation of the spatial structure of Glia, which hid or destroyed the antigenic epitope, effectively inhibiting protein antigenicity. This study widened the application of polyphenol modification in the inhibition of wheat allergens. © 2024 Society of Chemical Industry.

Modern methods and materials used to treat root perforation: effectiveness comparison.

This study aims to experimentally compare the efficacy of different endodontic materials (iRoot BP Plus, Biodentine, MTA, Rootdent, and Trioxide) in the treatment of pulpitis and perforations on extracted tooth specimens. Additionally, the study aims to investigate the influence of iRoot BP Plus endodontic material on the regenerative processes following pulp amputation in laboratory animals. The secondary goal is to evaluate the effect of iRoot BP Plus on the restoration process in laboratory animals after pulp removal. The study presents a micropermeability analysis of the selected biomaterials performed on a sample of 50 single-rooted apical teeth in 2022. All teeth underwent endodontic treatment. Changes in molar morphology were investigated with eight laboratory animals (rabbits, 3 months old, all males) after simulated pulp removal and subsequent treatment with the iRoot BP Plus biomaterials. iRoot BP Plus appeared to be more effective in retrograde apical root filling than other biomaterials, as evidenced by its higher sealing effect. An experiment involving animal participants revealed the presence of protective adaptive mechanisms, which manifested in the form of an inflammatory process within 6 weeks after the dental pulp was removed. The connective tissue replaced the necrosis, and new capillaries began to form intensively. These dental outcomes suggest that iRoot BP Plus enables hermetical sealing in tooth restoration with good adhesion. Thus, it may have the ability to promote more active tissue regeneration after pulp removal.

UiO-66-NH2 Metal-Organic Framework for the Detection of Alzheimer's Biomarker Aß (1-42).

Neurodegenerative disorders pose a significant challenge to global healthcare, with Alzheimer's disease (AD) being one of the most prevalent forms. Early and accurate detection of amyloid-ß (Aß) (1-42) monomers, a key biomarker of AD pathology, is crucial for effective diagnosis and intervention of the disease. Current gold standard detection techniques for Aß include enzyme-linked immunosorbent assay and surface plasmon resonance. Although reliable, they are limited by their cost and time-consuming nature, thus restricting their point-of-care applicability. Here we present a sensitive and rapid colorimetric sensor for the detection of Aß (1-42) monomers within 5 min. This was achieved by harnessing the peroxidase-like activity of metal-loaded metal-organic frameworks (MOFs), specifically UiO-66-NH2, coupled with the strong affinity of Aß (1-42) to the MOFs. Various metal-loaded MOFs were synthesized and investigated, and platinum-loaded UiO-66-NH2 was identified as the optimal candidate for our purpose. The Pt-loaded UiO-66-NH2 sensor demonstrated detection limits of 2.76 and 4.65 nM Aß (1-42) monomers in water and cerebrospinal fluid, respectively, with a linear range from 0.75 to 25 nM (R2 = 0.9712), outperforming traditional detection techniques in terms of both detection time and complexity. Moreover, the assay was specific toward Aß (1-42) monomers when evaluated against interfering compounds. The rapid and cost-effective sensor may help circumvent the limitations of conventional detection methods, thus providing a promising avenue for early AD diagnosis and facilitating improved clinical outcomes.

Research on the psychological status of medical staff during the COVID-19 epidemic in China: A longitudinal study.

An online questionnaire, including the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), was used to assess the psychological status of medical staff in Wuhan during the COVID-19 epidemic. Lasso-Logistic regression analysis was performed to analyze the risk factors of abnormal psychological status (anxiety or depression). 36.6% of the study subjects experienced anxiety, and 41.5% experienced depression. Female (OR [odds ratio] = 7.22, 95% CI [confidence interval]: 0.58-89.33), basic diseases (OR = 17.95, 95% CI: 1.59-202.49), suspected exposure history (OR = 9.63, 95% CI: 1.40-66.29), smoking (OR = 6.07, 95% CI: 0.38-96.78) were risk factors for anxiety. Female (OR = 5.00, 95% CI: 0.45-55.91), basic diseases (OR = 37.19, 95% CI: 2.70-512.73), suspected exposure history (OR = 5.10, 95% CI: 0.78-33.10), drinking wine (OR = 6.27, 95% CI: 0.38-103.85) were risk factors for depression. The results of the re-sampling evaluation after 2 years showed that some medical staff still showed anxiety (42.4%) and depression (27.3%), and the proportion of females was higher. Early intervention should be carried out, and short-term and long-term intervention plans should be formulated.

Nomogram Model Based on Iodine Nutrition and Clinical Characteristics of Papillary Thyroid Carcinoma to Predict Lateral Lymph Node Metastasis.

OBJECTIVE: Preoperative evaluation of lateral lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC) has been one of the major clinical challenges. This study aims to develop and validate iodine nutrition-related nomogram models to predict lateral cervical lymph node metastasis in patients with PTC. METHODS: This is a retrospective study. Urinary iodine concentration (UIC) and serum iodine concentration (SIC) were measured in 187 LLNM patients and 289 non-LLNM (NLLNM) patients. All patients were randomized 3:1 into the training cohort (n = 355) and the validation cohort (n = 121). Using logistic regression analysis, we analyzed the influence of iodine nutrition-related factors and clinicopathological characteristics on LLNM in PTC patients. Lasso regression method was used to screen risk factors and construct a nomogram for predicting LLNM. The receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis (DCA) of the nomogram models were carried out for the training and validation cohorts. RESULTS: Gender, SIC, smoking history, drinking history, family history of PTC, multifocality, bilateral or unilateral tumors, TSH, Tg, and tumor size were included in the nomogram model predicting LLNM, with an area under the curve (AUC) of .795. The nomogram model showed good calibration and clinical benefit in both the training and validation cohorts. CONCLUSION: The nomogram model based on iodine nutrition and other clinicopathological features is effective for predicting the lateral lymph node metastasis in PTC patients.

Research on the anti-ageing mechanism of Prunella vulgaris L.

Prunella vulgaris L. (P. vulgaris) has long been considered to have antipyretic, analgesic and anti-inflammatory effects, lowering blood lipids and pressure. Many studies show that in addition to the traditional telomere attrition, DNA damage and epigenetic changes, immunosenescence is also a new possibility to explore the mechanism of ageing. Therefore, this herb may have potential anti-ageing effects. Typically, there are a series of markers that identify senescent cells, such as superoxide dismutase (SOD)2, an inhibitor of CDK4 (p16INK4A), tumor necrosis factor (TNF)-α, immune cells number, proliferation, and nuclear abnormalities. These changes rarely present in young tissues, while greatly increasing in response to ageing. Firstly, the ageing model of the Institute of Cancer Research (ICR) mouse was established by D-galactose subcutaneous injection. Then, SOD2, p16INK4A and TNF-α were detected by quantitative Real-time PCR (qPCR), Western Blot (WB) and Enzyme-Linked Immunosorbent Assay (ELISA). Simultaneously, senescent cells in livers were stained by hematoxylin and eosin (HE). The viability of splenocytes was detected by Cell Counting Kit-8(CCK-8). The difference in specific immune cells (NK cells, B lymphocytes and T lymphocytes) was detected by flow cytometry. Both low (100 mg/kg) and high (300 mg/kg) concentrations of P. vulgaris treated ageing ICR mice show anti-ageing alterations, such as p16INK4A decreased approximately 1/2 and SOD2 tripled in livers, TNF-α decreased from 1 to 0.6 in plasma, and T cells increased from 0.09 to 0.19%. Compared with the ageing group, the spleen cells in the Prunella-treated group had stronger proliferation ability. Thus, P. vulgaris could have an anti-ageing effect. This is the first study to demonstrate the anti-ageing effect of P. vulgaris. It may also be capable of preventing a variety of age-related diseases.

Influences of resolvin D1 and D2 on the risk of type 2 diabetes mellitus: a Chinese community-based cohort study.

Background: Although cellular and animal studies have reported that resolvin D1 (RvD1) and resolvin D2 (RvD2) are mechanisms involved in the development of type 2 diabetes mellitus (T2DM), the impact of RvD1 and RvD2 on the risk of T2DM at a population level remains unclear. Methods: We included 2755 non-diabetic adults from a community-based cohort in China and followed them for seven years. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of RvD1 and RvD2 with T2DM probability. Time-dependent receiver operator characteristics (ROC) curve was used to evaluate the predictive performance of RvD1 and RvD2 for the risk of T2DM based on the Chinese CDC T2DM prediction model (CDRS). Results: A total of 172 incident T2DM cases were identified. Multivariate-adjusted HRs (95% CI) for T2DM across quartiles of RvD1 levels (Q1, Q2, Q3 and Q4) were 1.00, 1.64 (1.03-2.63), 1.80 (1.13-2.86) and 1.61 (1.01-2.57), respectively. Additionally, body mass index (BMI) showed a significant effect modification in the association of RvD1 with incident T2DM (P interaction = 0.026). After multivariate adjustment, the HR (95% CI) for T2DM in the fourth compared with the first quartile of RvD2 was 1.94 (95% CI: 1.24-3.03). Time-dependent ROC analysis showed that the area under time-dependent ROC curves of the "CDRS+RvD1+RvD2" model for the 3-, 5- and 7-year risk of T2DM were 0.842, 0.835 and 0.828, respectively. Conclusions: Higher RvD1 and RvD2 levels are associated with a higher risk of T2DM at the population level.

Selenomethionine protects against Escherichia coli-induced endometritis by inhibiting inflammation and necroptosis via regulating the PPAR-γ/NF-κB pathway.

Endometritis, inflammation of the endometrium, is a major cause of subfertility in women. Selenomethionine (SeMet)is known to exert anti-inflammatory activity. We aimed to verify the protective roles of SeMet on Escherichia coli (E.coli)-induced endometritis. The extent of uterus damage was assessed by detecting histopathology and inflammatory mediators. The results revealed that SeMet significantly prevented E.coli-induced endometritis by attenuating uterine histopathology and inflammatory cytokine production. E.coli-induced MPO activity and MDA content were inhibited by SeMey. E.coli-induced ZO-1 and occludin were upregulated by SeMet. E.coli-induced necroptosis was also inhibited by SeMet. Additionally, E.coli-induced NF-κB activation was alleviated by SeMet. PPAR-γ expression was upregulated by SeMet. Notably, the protective effects of SeMet on endometritis were abolished by a PPAR-γ inhibitor. In conclusion, SeMet inhibits E.coli-induced endometritis by attenuating inflammation and necroptosis, which is mediated by the PPAR-γ/NF-κB signaling pathway.

The emerging role of neutrophil extracellular traps in endometritis.

Endometritis is a kind of common obstetric disease in women, usually caused by various pathogenic bacteria. Neutrophil infiltration is one of the most important pathological features of endometritis. Neutrophils can reach the uterine cavity through the endometrium, and make early response to the infection caused by the pathogen. Neutrophil extracellular traps (NETs), a meshwork of chromatin fibers extruded by neutrophils, have a role in entrapping microbial pathogens. It has been confirmed that NETs have a strong antibacterial effect and play crucial roles in the occurrence and development of various diseases. However, while killing pathogenic bacteria, excessive NETs formation may cause immune damage to the body. NETs are present in endometrium of female domestic animals in different physiological periods, especially post-mating, postpartum and in the presence of lesions, especially in endometritis. Meanwhile, NETs and its products might contribute to a reduction in physical clearance and persistent endometritis. In brief, NETs is a double-edged sword and it may play a different role in the development of endometritis, which may be beneficial or harmful, and its specific mechanism needs further study. Here we provide an overview of the role of NETs in the development of endometritis and the regulatory role of selenium on NETs formation and endometritis.

Citral protects against LPS-induced endometritis by inhibiting ferroptosis through activating Nrf2 signaling pathway.

INTRODUCTION: Endometritis is the inflammatory condition of the uterus. Citral, a component of lemongrass oil, is known to exhibit anti-inflammatory activity. AIM: The effects of citral on LPS-induced endometritis were tested and the mechanisms were investigated. METHODS: LPS-induced endometritis mice model was established and the effects of citral were detected using this model. Inflammatory cytokines were tested by ELISA. Ferroptosis was assessed by detecting GSH, ATP, MDA, and Fe2+ levels. Signaling pathway was tested by western blot analysis. RESULTS: Citral prevented LPS-induced endometritis through attenuating uterine pathological changes and inflammatory cytokine release. Meanwhile, citral prevents LPS-induced ferroptosis through attenuating MDA and Fe2+ levels, as well as increasing ATP and GSH levels. Furthermore, citral up-regulated Nrf2 and HO-1 expression and attenuated NF-κB activation. In addition, in Nrf2 knockdown mice, the inhibitory roles of citral on ferroptosis and endometritis were largely reversed. CONCLUSION: Taken together, citral inhibited LPS-induced endometritis through preventing ferroptosis, which were regulated by Nrf2 signaling pathway.

A new B cell epitope of pC129R protein of African swine fever virus identified by monoclonal antibodies.

African swine fever virus (ASFV) is a most important pathogen which causes huge damage in swine production in the world. pC129R protein is one of the most abundant ASFV proteins in infected Vero cells and WSL-HP cells, which consequently could be a target for ASF detection and surveillance. In this study, 5-6-week-old female BALB/c mice were immunized with rpC129R protein expressed by a prokaryotic system. And three hybridomas, 1B1, 1B4 and 4H4, steadily secreted anti-pC129R monoclonal antibodies were screened by an indirect enzyme linked immunosorbent assay (ELISA). Among them, 1B4 and 4H4 had IgG2a isotype with Kappa light chain, while 1B1 had IgG1 isotype with Kappa light chain. Western blot and indirect immunofluorescence assay showed that three monoclonal antibodies (mAbs) specifically reacted with ASFV. Epitope mapping was performed with truncated polypeptides. And a new B cell epitope, 18KHYVLIPK25 was identified by the mAbs, which was highly conserved in most genotypes of ASFV. These findings not only provide a monoclonal antibody tool for further study of the function of C129R, but also lay the foundation for serological diagnosis and vaccine development.

Deoxycholic acid inhibits Staphylococcus aureus-induced endometritis through regulating TGR5/PKA/NF-κB signaling pathway.

Endometritis, a common gynecological disease, is the most common cause of infertility. As a natural metabolite of gut microbiota, deoxycholic acid (DCA) has been reported to have anti-inflammatory function. In the current study, the protective role of DCA on Staphylococcus aureus (S.aureus)-induced endometritis was tested. In vivo, DCA inhibited uterine histological change, MPO activity, endometrial barrier disruption, and inflammatory cytokine production induced by S.aureus. In vitro, DCA suppressed S.aureus-induced TNF-α and IL-1ß production in mouse endometrial epithelial cells (mEECs). Also, DCA markedly suppressed S.aureus-induced NF-κB activation. Takeda G protein-coupled receptor 5 (TGR5)is a critical bile acid membranereceptor that mainly regulated the cyclic AMP (cAMP)/protein kinase A (PKA)signaling pathway to inhibit NF-κB activation. We found DCA significantly increased TGR5 and PKA expression and S.aureus-induced inflammatory cytokine production and NF-κB activation were prevented by TGR5 inhibitor and PKA inhibitor. In conclusion, DCA protected S.aureus-induced endometritis by regulating TGR5/PKA/NF-κB signaling pathway.

The protective effects of lipoxin A4 on type 2 diabetes mellitus: A Chinese prospective cohort study.

Background: Several cellular and animal studies have suggested that lipoxin A4 (LXA4) has a protective effect on type 2 diabetes mellitus (T2DM) development. However, little is known about whether LXA4 influences T2DM development at the population level. Methods: We included 2755 non-diabetic participants from a cohort study in China who were followed for about seven years. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for the association between LXA4 and incident T2DM. Mediation models were used to examine how serum lipids as mediators impact the association between LXA4 and T2DM. Results: In total, 172 newly diagnosed T2DM cases were identified. Multivariate-adjusted HR for T2DM in the fourth compared with the first quartile of LXA4 was 0.62 (95% CI: 0.40-0.96). When used the optimal cutoff value determined by the receiver operating characteristic curve, the results showed participants with LXA4 > 2.84 ng/mL had a decreased T2DM risk compared to those with LXA4 ≤ 2.84 ng/mL (HR: 0.63, 95% CI: 0.45-0.89). The effect of LXA4 on incident T2DM was significantly modified by gender (P -interaction = 0.024) and family history of diabetes (P -interaction = 0.025). Additionally, the association between LXA4 and incident T2DM was partially suppressed by the TyG and TG/HDL-c ratio, with a suppression proportion of 22.2% and 16.0%, respectively. Conclusions: Higher LXA4 levels are significantly associated with a lower risk of T2DM development. The present findings would be helpful in understanding the effect of LXA4 on T2DM development at the population level.

Plant Growth Promotion and Biocontrol of Leaf Blight Caused by Nigrospora sphaerica on Passion Fruit by Endophytic Bacillus subtilis Strain GUCC4.

Passion fruit (Passiflora edulis Sims) is widely cultivated in tropic and sub-tropic regions for the production of fruit, flowers, cosmetics, and for pharmacological applications. Its high economic, nutritional, and medical values elicit the market demand, and the growing areas are rapidly increasing. Leaf blight caused by Nigrospora sphaerica is a new and emerging disease of passion fruit in Guizhou, in southwest China, where the unique karst mountainous landscape and climate conditions are considered potential areas of expansion for passion fruit production. Bacillus species are the most common biocontrol and plant-growth-promotion bacteria (PGPB) resources in agricultural systems. However, little is known about the endophytic existence of Bacillus spp. in the passion fruit phyllosphere as well as their potential as biocontrol agents and PGPB. In this study, 44 endophytic strains were isolated from 15 healthy passion fruit leaves, obtained from Guangxi province, China. Through purification and molecular identification, 42 of the isolates were ascribed to Bacillus species. Their inhibitory activity against N. sphaerica was tested in vitro. Eleven endophytic Bacillus spp. strains inhibited the pathogen by >65%. All of them produced biocontrol- and plant-growth-promotion-related metabolites, including indole-3-acetic acid (IAA), protease, cellulase, phosphatase, and solubilized phosphate. Furthermore, the plant growth promotion traits of the above 11 endophytic Bacillus strains were tested on passion fruit seedlings. One isolate, coded B. subtilis GUCC4, significantly increased passion fruit stem diameter, plant height, leaf length, leaf surface, fresh weight, and dry weight. In addition, B. subtilis GUCC4 reduced the proline content, which indicated its potential to positively regulate passion fruit biochemical properties and resulted in plant growth promotion effects. Finally, the biocontrol efficiencies of B. subtilis GUCC4 against N. sphaerica were determined in vivo under greenhouse conditions. Similarly to the fungicide mancozeb and to a commercial B. subtilis-based biofungicide, B. subtilis GUCC4 significantly reduced disease severity. These results suggest that B. subtilis GUCC4 has great potential as a biological control agent and as PGPB on passion fruit.

Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma.

Head and neck cancer is a malignant tumour with a high mortality rate characterized by late diagnosis, high recurrence and metastasis rates, and poor prognosis. Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer. Various factors are involved in the occurrence and development of HNSCC, including external inflammatory stimuli and oncogenic viral infections. In recent years, studies on the regulation of cell death have provided new insights into the biology and therapeutic response of HNSCC, such as apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, and recently the newly discovered cuproptosis. We explored how various cell deaths act as a unique defence mechanism against cancer emergence and how they can be exploited to inhibit tumorigenesis and progression, thus introducing regulatory cell death (RCD) as a novel strategy for tumour therapy. In contrast to accidental cell death, RCD is controlled by specific signal transduction pathways, including TP53 signalling, KRAS signalling, NOTCH signalling, hypoxia signalling, and metabolic reprogramming. In this review, we describe the molecular mechanisms of nonapoptotic RCD and its relationship to HNSCC and discuss the crosstalk between relevant signalling pathways in HNSCC cells. We also highlight novel approaches to tumour elimination through RCD.