Gp93 inhibits unfolded protein response-mediated c-Jun N-terminal kinase activation and cell invasion.

In eukaryotes, Hsp90B1 serves as a vital chaperonin, facilitating the accurate folding of proteins. Interestingly, Hsp90B1 exhibits contrasting roles in the development of various types of cancers, although the underlying reasons for this duality remain enigmatic. Through the utilization of the Drosophila model, this study unveils the functional significance of Gp93, the Drosophila ortholog of Hsp90B1, which hitherto had limited reported developmental functions. Employing the Drosophila cell invasion model, we elucidated the pivotal role of Gp93 in regulating cell invasion and modulating c-Jun N-terminal kinase (JNK) activation. Furthermore, our investigation highlights the involvement of the unfolded protein response-associated IRE1/XBP1 pathway in governing Gp93 depletion-induced, JNK-dependent cell invasion. Collectively, these findings not only uncover a novel molecular function of Gp93 in Drosophila, but also underscore a significant consideration pertaining to the testing of Hsp90B1 inhibitors in cancer therapy.

Antibody responses to respiratory syncytial virus: A population-based cross-sectional serological study in southern China, 2021.

OBJECTIVES: With remarkable progress in the field of RSV prophylaxis, it is critical to understand population immunity against RSV. We aim to describe the RSV pre-F immunoglobin G (IgG) antibodies across all age groups in southern China and evaluate the risk factors associated with lower antibody levels. METHODS: We conducted a community-based cross-sectional sero-epidemiological study in Anhua County, Hunan Province, southern China, from July to November 2021. Serum samples were tested for IgG antibodies against the RSV prefusion F (pre-F) protein using an enzyme-linked immunosorbent assay. We estimated the geometric mean titres (GMTs) and seropositivity rates across all age groups. Generalized linear models (GLMs) were built to identify factors associated with antibody levels. RESULTS: A total of 890 participants aged 4 months to >89 years were enrolled. The lowest RSV pre-F IgG GMTs were observed in infants and toddlers aged 4 months to <2 years (3.0, 95% confidence interval [CI]: 2.6-3.5). With increasing age, RSV pre-F IgG GMT increased to 4.3 (95% CI: 4.1-4.4) between the ages of 2 and <5 years and then stabilized at high levels throughout life. All the children had serological evidence of RSV infection by the age of 5 years. Age was associated with RSV pre-F antibody levels in children, with an estimated 1.8-fold (95% CI: 1.1-2.9) increase in titre per year before 5 years of age, while it was not significantly associated with antibody levels in adults aged >60 years. CONCLUSIONS: Our findings could provide a comprehensive understanding of the gaps in RSV immunity at the population level and inform the prioritization of immunization platforms.

Uncovering the differentiated impacts of carbon neutrality and clean air policies in multi-provinces of China.

Ambitious action plans have been launched to address climate change and air pollution. Through coupling the IMED|CGE, GAINS, and IMED|HEL models, this study investigate the impacts of implementing carbon neutrality and clean air policies on the energy-environment-health-economy chain in the Beijing-Tianjin-Hebei-Henan-Shandong-Shanxi region of China. Results show that Shandong holds the largest reduction in energy consumption and carbon emissions toward the 1.5°C target. Shandong, Henan, and Hebei are of particularly prominent pollutant reduction potential. Synergistic effects of carbon reduction on decreasing PM2.5 concentration will increase in the future, specifically in energy-intensive regions. Co-deployment of carbon reduction and end-of-pipe technologies are beneficial to decrease PM2.5-related mortalities and economic loss by 4.7-12.9% in 2050. Provincial carbon reduction cost will be higher than monetary health benefits after 2030, indicating that more zero-carbon technologies should be developed. Our findings provide scientific enlightenment on policymaking toward achieving carbon reduction and pollution mitigation from multiple perspectives.

Definition and analysis of gray matter atrophy subtypes in mild cognitive impairment based on data-driven methods.

Introduction: Mild cognitive impairment (MCI) is an important stage in Alzheimer's disease (AD) research, focusing on early pathogenic factors and mechanisms. Examining MCI patient subtypes and identifying their cognitive and neuropathological patterns as the disease progresses can enhance our understanding of the heterogeneous disease progression in the early stages of AD. However, few studies have thoroughly analyzed the subtypes of MCI, such as the cortical atrophy, and disease development characteristics of each subtype. Methods: In this study, 396 individuals with MCI, 228 cognitive normal (CN) participants, and 192 AD patients were selected from ADNI database, and a semi-supervised mixture expert algorithm (MOE) with multiple classification boundaries was constructed to define AD subtypes. Moreover, the subtypes of MCI were obtained by using the multivariate linear boundary mapping of support vector machine (SVM). Then, the gray matter atrophy regions and severity of each MCI subtype were analyzed and the features of each subtype in demography, pathology, cognition, and disease progression were explored combining the longitudinal data collected for 2 years and analyzed important factors that cause conversion of MCI were analyzed. Results: Three MCI subtypes were defined by MOE algorithm, and the three subtypes exhibited their own features in cortical atrophy. Nearly one-third of patients diagnosed with MCI have almost no significant difference in cerebral cortex from the normal aging population, and their conversion rate to AD are the lowest. The subtype characterized by severe atrophy in temporal lobe and frontal lobe have a faster decline rate in many cognitive manifestations than the subtype featured with diffuse atrophy in the whole cortex. APOE ε4 is an important factor that cause the conversion of MCI to AD. Conclusion: It was proved through the data-driven method that MCI collected by ADNI baseline presented different subtype features. The characteristics and disease development trajectories among subtypes can help to improve the prediction of clinical progress in the future and also provide necessary clues to solve the classification accuracy of MCI.

Advances in the isolation, cultivation, and identification of gut microbes.

The gut microbiome is closely associated with human health and the development of diseases. Isolating, characterizing, and identifying gut microbes are crucial for research on the gut microbiome and essential for advancing our understanding and utilization of it. Although culture-independent approaches have been developed, a pure culture is required for in-depth analysis of disease mechanisms and the development of biotherapy strategies. Currently, microbiome research faces the challenge of expanding the existing database of culturable gut microbiota and rapidly isolating target microorganisms. This review examines the advancements in gut microbe isolation and cultivation techniques, such as culturomics, droplet microfluidics, phenotypic and genomics selection, and membrane diffusion. Furthermore, we evaluate the progress made in technology for identifying gut microbes considering both non-targeted and targeted strategies. The focus of future research in gut microbial culturomics is expected to be on high-throughput, automation, and integration. Advancements in this field may facilitate strain-level investigation into the mechanisms underlying diseases related to gut microbiota.

One-Pot Two-Stage Biocatalytic Cascade to Produce l-Phosphinothricin by Two Enantioselective Complementary Aminotransferases at High Substrate Loading via a Deracemization Process.

The bioderacemization of racemic phosphinothricin (D, L-PPT) is a promising route for the synthesis of l-phosphinothricin (L-PPT). However, the low activity and tolerance of wild-type enzymes restrict their industrial applications. Two stereocomplementary aminotransferases with high activity and substrate tolerance were identified in a metagenomic library, and a one-pot, two-stage artificial cascade biocatalytic system was developed to produce L-PPT through kinetic resolution and asymmetric amination. We observed that 500 mM D, L-PPT (100 g/L) could be converted into L-PPT with 94% final conversion and >99.9% enantiomeric excess (e.e.) within 24 h, with only 0.02 eq amino acceptor pyruvate and 1.2 eq amino donor l-aspartate required. The process could be scaled up to 10 L under sufficient oxygen and stirring. The superior catalytic performance of this system provides an eco-friendly and sustainable approach to the industrial deracemization of D, L-PPT to L-PPT.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury.

Objective: To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. Method: The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results: 73 patients were enrolled. Age among five groups was statistically different ( P = 0.032). Alanine aminotransferase (ALT) ( P = 0.033) and aspartate aminotransferase (AST) ( P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT ( r = 0.697, P = 0.025), AST ( r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Conclusion: Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI.

Dependence of a Hydrogen Buffer Layer on the Properties of Top-Gate IGZO TFT.

In this paper, the effect of a buffer layer created using different hydrogen-containing ratios of reactive gas on the electrical properties of a top-gate In-Ga-Zn-O thin-film transistor was thoroughly investigated. The interface roughness between the buffer layer and active layer was characterized using atomic force microscopy and X-ray reflection. The results obtained using Fourier transform infrared spectroscopy show that the hydrogen content of the buffer layer increases with the increase in the hydrogen content of the reaction gas. With the increase in the hydrogen-containing materials in the reactive gas, field effect mobility and negative bias illumination stress stability improve nearly twofold. The reasons for these results are explained using technical computer-aided design simulations.

Development of a nomogram for predicting liver transplantation prognosis in hepatocellular carcinoma.

BACKGROUND: At present, liver transplantation (LT) is one of the best treatments for hepatocellular carcinoma (HCC). Accurately predicting the survival status after LT can significantly improve the survival rate after LT, and ensure the best way to make rational use of liver organs. AIM: To develop a model for predicting prognosis after LT in patients with HCC. METHODS: Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated. The expression levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, Golgi protein 73, cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer. The best cutoff value of biomarkers was determined using the Youden index. Cox regression analysis was used to identify the independent risk factors. A forest model was constructed using the random forest method. We evaluated the accuracy of the nomogram using the area under the curve, using the calibration curve to assess consistency. A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomograms. RESULTS: The total tumor diameter (TTD), vascular invasion (VI), AFP, and cytokeratin-18 epitopes M30 (CK18-M30) were identified as important risk factors for outcome after LT. The nomogram had a higher predictive accuracy than the Milan, University of California, San Francisco, and Hangzhou criteria. The calibration curve analyses indicated a good fit. The survival and recurrence-free survival (RFS) of high-risk groups were significantly lower than those of low- and middle-risk groups (P < 0.001). The DCA shows that the model has better clinical practicability. CONCLUSION: The study developed a predictive nomogram based on TTD, VI, AFP, and CK18-M30 that could accurately predict overall survival and RFS after LT. It can screen for patients with better postoperative prognosis, and improve long-term survival for LT patients.

Associations of neighborhood sociodemographic environment with mortality and circulating metabolites among low-income black and white adults living in the southeastern United States.

BACKGROUND: Residing in a disadvantaged neighborhood has been linked to increased mortality. However, the impact of residential segregation and social vulnerability on cause-specific mortality is understudied. Additionally, the circulating metabolic correlates of neighborhood sociodemographic environment remain unexplored. Therefore, we examined multiple neighborhood sociodemographic metrics, i.e., neighborhood deprivation index (NDI), residential segregation index (RSI), and social vulnerability index (SVI), with all-cause and cardiovascular disease (CVD) and cancer-specific mortality and circulating metabolites in the Southern Community Cohort Study (SCCS). METHODS: The SCCS is a prospective cohort of primarily low-income adults aged 40-79, enrolled from the southeastern United States during 2002-2009. This analysis included self-reported Black/African American or non-Hispanic White participants and excluded those who died or were lost to follow-up ≤ 1 year. Untargeted metabolite profiling was performed using baseline plasma samples in a subset of SCCS participants. RESULTS: Among 79,631 participants, 23,356 deaths (7214 from CVD and 5394 from cancer) were documented over a median 15-year follow-up. Higher NDI, RSI, and SVI were associated with increased all-cause, CVD, and cancer mortality, independent of standard clinical and sociodemographic risk factors and consistent between racial groups (standardized HRs among all participants were 1.07 to 1.20 in age/sex/race-adjusted model and 1.04 to 1.08 after comprehensive adjustment; all P < 0.05/3 except for cancer mortality after comprehensive adjustment). The standard risk factors explained < 40% of the variations in NDI/RSI/SVI and mediated < 70% of their associations with mortality. Among 1110 circulating metabolites measured in 1688 participants, 134 and 27 metabolites were associated with NDI and RSI (all FDR < 0.05) and mediated 61.7% and 21.2% of the NDI/RSI-mortality association, respectively. Adding those metabolites to standard risk factors increased the mediation proportion from 38.4 to 87.9% and 25.8 to 42.6% for the NDI/RSI-mortality association, respectively. CONCLUSIONS: Among low-income Black/African American adults and non-Hispanic White adults living in the southeastern United States, a disadvantaged neighborhood sociodemographic environment was associated with increased all-cause and CVD and cancer-specific mortality beyond standard risk factors. Circulating metabolites may unveil biological pathways underlying the health effect of neighborhood sociodemographic environment. More public health efforts should be devoted to reducing neighborhood environment-related health disparities, especially for low-income individuals.

Icosahedral supracrystal assembly from polymer-grafted nanoparticles via interplay of interfacial energy and confinement effect.

Self-assembly of nanoparticles (NPs) in drying emulsion droplets paves the way for intricate three-dimensional (3D) superstructures, given the myriad of control parameters for fine-tuning assembly conditions. With their substantial energetic dynamics that are acutely responsive to emulsion confinements, polymeric ligands incorporated into a system can enrich its structural diversity. Here, we demonstrate the assembly of soft polymer-grafted NPs into Mackay icosahedrons beyond spherical body-centered cubic (BCC) packing structures commonly observed for these soft spheres. This behavior is governed by the free energy minimization within emulsions through the interplay of the oil-water interfacial energy and confinement effect as demonstrated by the experimental observations of structural transitions between icosahedrons and BCC crystals and by corresponding free energy calculations. The anisotropic surface of the icosahedral supracrystals provides the capability of guiding the position of a secondary constituent, creating unique hybrid patchy icosahedrons with the potential to develop into multifunctional 3D clusters that combine the benefits of both polymers and conventional colloids.

Management for children and adolescents with overweight and obesity: a recommendations mapping.

BACKGROUND: Childhood obesity is a global public health issue, and the status of clinical practice guidelines (CPGs) as instruction manuals for the management of childhood obesity remains unclear. This study aims to identify and apprise the methodological and reporting quality of CPGs focused on childhood obesity and provide an overview of key recommendations. METHODS: Databases and websites reporting guidelines were searched from January, 2018 to September, 2023. The methodological quality was graded using the AGREE II, and RIGHT was used to assess the reporting completeness. RESULTS: Among the six included CPGs, two were rated as high quality and considered "Recommended" and three were reported no less than 80%. CPGs included 184 recommendations cover diagnosis, assessment and management of complications, interventions and prevention. The diagnostic criteria for children with obesity over 2 years of age are based on normative BMI percentiles, depending on sex and age. CPGs recommended the delivery of multi-component behavior-changed interventions included controlling diet and increasing physical activity. Pharmacological interventions and bariatric surgery are considered as complementary therapies. CONCLUSION: CPGs for childhood obesity should emphasize the impact of psychological factors and consider the provision of interventions from multiple settings, and could consider the role of complementary alternative therapies. IMPACT: Six guidelines have been published in the past 5 years focusing children obesity. Recommendations covered diagnosis, multiple intervention and prevention. Guidelines should focus on the role of complementary alternative therapies. Guidelines should emphasize the impact of psychological factors. Guidelines should consider the provision of interventions from multiple settings.

Urolithin A promotes atherosclerotic plaque stability by limiting inflammation and hypercholesteremia in Apolipoprotein E-deficient mice.

Urolithin A (UroA), a dietary phytochemical, is produced by gut bacteria from fruits rich in natural polyphenols ellagitannins (ETs). The efficiency of ETs metabolism to UroA in humans depends on gut microbiota. UroA has shown a variety of pharmacological activities. In this study we investigated the effects of UroA on atherosclerotic lesion development and stability. Apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-cholesterol diet for 3 months to establish atherosclerosis model. Meanwhile the mice were administered UroA (50 mg·kg-1·d-1, i.g.). We showed that UroA administration significantly decreased diet-induced atherosclerotic lesions in brachiocephalic arteries, macrophage content in plaques, expression of endothelial adhesion molecules, intraplaque hemorrhage and size of necrotic core, while increased the expression of smooth muscle actin and the thickness of fibrous cap, implying features of plaque stabilization. The underlying mechanisms were elucidated using TNF-α-stimulated human endothelial cells. Pretreatment with UroA (10, 25, 50 µM) dose-dependently inhibited TNF-α-induced endothelial cell activation and monocyte adhesion. However, the anti-inflammatory effects of UroA in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) were independent of NF-κB p65 pathway. We conducted RNA-sequencing profiling analysis to identify the differential expression of genes (DEGs) associated with vascular function, inflammatory responses, cell adhesion and thrombosis in UroA-pretreated HUVECs. Human disease enrichment analysis revealed that the DEGs were significantly correlated with cardiovascular diseases. We demonstrated that UroA pretreatment mitigated endothelial inflammation by promoting NO production and decreasing YAP/TAZ protein expression and TEAD transcriptional activity in TNF-α-stimulated HUVECs. On the other hand, we found that UroA administration modulated the transcription and cleavage of lipogenic transcription factors SREBP1/2 in the liver to ameliorate cholesterol metabolism in ApoE-/- mice. This study provides an experimental basis for new dietary therapeutic option to prevent atherosclerosis.

Transcriptomic Responses and Larval-Stage Growth of Protandrous Yellowfin Seabream (Acanthopagrus Latus) to Different Polyethylene Microplastics Exposure.

Polyethylene microplastics (PE-MPs) were widespread in the marine environment; thus, their influences on marine hermaphroditic fish cannot be ignored. This study intends to evaluate the adverse biological effects of two different sources of PE, identified by Raman spectroscopy, on protandrous yellowfin seabream (Acanthopagrus latus) larvae. Growth retardation, brain lesions, head/body length ratio increase, and neuroendocrine system disorders were found, and growth and neuroendocrine regulation-related genes such as sstr2, ghrb, irs1, UGT2B15, UGT2C1, drd4a, esr2b, hsd3b7, and hsd17b2 were identified. PE microbeads (100 µm) showed more severe tissue damage on fish, while environmental PE fibers (500-2500 µm) showed more imperceptible adverse effects. There were 218 DEGs up-regulated and 147 DEGs down-regulated in the environmental PE group, while 1284 (up) and 1267 (down) DEGs were identified in the virgin PE group. PE-MP stress influenced physiological processes like growth and neuroendocrine regulation and cholesterol-steroid metabolism, and caused tissue damage in the fish larvae. The study highlights the effects of environmental PE exposure on hermaphroditic protandrous fish.

Structure information analysis and relative content determination of protein and chitin from yellow mealworm larvae using Raman spectroscopy.

Insect protein extract is one of the high-quality protein sources and is frequently viewed as a potential nutrition alternative. However, a more precise method for protein measurement is still needed due to protein overestimation by the Kjeldahl method due to the presence of a large amount of chitin in insects. Therefore, we demonstrated the monitoring of chitin and protein extracted from yellow mealworm larvae through the information on molecular vibration obtained using Raman spectroscopy and infrared (IR) spectroscopy. The NH vibration at 3475 cm-1 is the characteristic peak of chitin in defatted product observed in the Raman spectra. The nitrogen-to-protein conversion factor in protein extracted from larvae by the Raman method was determined based on the NH vibration and found to be 5.66 ± 0.01. We also compared these experimental data to theoretical Raman and IR spectra and determined the possible reasons for why nitrogen elements in chitin affect the determination of protein content. The method of sequentially removing fat and protein could provide more accurate quantification of protein and chitin. Raman spectroscopy is feasible for various types of insects with high chitin content. Compared with the Kjeldahl method, the Raman method is a faster and more accurate measurement method. Moreover, it provides the content of impurities, purity, and structural information.

Exploiting Photoinduced Atom Transfer Radical Polymerizations with Boron-Dopant and Nitrogen-Defect Synergy in Carbon Nitride Nanosheets.

Graphitic carbon nitrides (g-C3N4) possess various benefits as heterogeneous photocatalysts, including tunable bandgaps, scalability, and chemical robustness. However, their efficacy and ongoing advancement are hindered by challenges like limited charge-carrier separation rates, insufficient driving force for photocatalysis, small specific surface area, and inadequate absorption of visible light. In this study, boron dopants and nitrogen defects synergy are introduced into bulk g-C3N4 through the calcination of a blend of nitrogen-defective g-C3N4 and NaBH4 under inert conditions, resulting in the formation of BCN nanosheets characterized by abundant porosity and increased specific surface area. These BCN nanosheets promote intermolecular single electron transfer to the radical initiator, maintaining radical intermediates at a low concentration for better control of photoinduced atom transfer radical polymerization (photo-ATRP). Consequently, this method yields polymers with low dispersity and tailorable molecular weights under mild blue light illumination, outperforming previous reports on bulk g-C3N4. The heterogeneity of BCN enables easy separation and efficient reuse in subsequent polymerization processes. This study effectively showcases a simple method to alter the electronic and band structures of g-C3N4 with simultaneously introducing dopants and defects, leading to high-performance photo-ATRP and providing valuable insights for designing efficient photocatalytic systems for solar energy harvesting.

Moringin alleviates DSS-induced ulcerative colitis in mice by regulating Nrf2/NF-κB pathway and PI3K/AKT/mTOR pathway.

Ulcerative colitis (UC) is a main form of inflammatory bowel disease (IBD), which is a chronic and immune-mediated inflammatory disease. Moringin (MOR) is an isothiocyanate isolated from Moringa oleifera Lam., and has been recognized as a promising potent drug for inflammatory diseases and antibacterial infections. The present study investigated the role of moringin in dextran sulfate sodium (DSS)-induced UC mice. Mouse colitis was induced by adding DSS to the drinking water for seven consecutive days. Our experimental results showed that MOR relieves DSS-induced UC in mice by increasing body weight and colonic length, and reducing the disease activity index and histological injury. Mechanistically, MOR improves intestinal barrier function by increasing the expression of tight junction proteins (TJPs) and enhancing the secretion of mucin in DSS-induced mice. MOR inhibits inflammatory response and intestinal damage by regulating Nrf2/NF-κB signaling pathway and modulating the PI3K/AKT/mTOR pathway. Furthermore, in Nrf2 knockout (Nrf2-/-) mice, the protective effects of MOR on DSS-induced UC were abolished. Meanwhile, treatment with MOR reduced inflammation and cell damage via regulating Nrf2/NF-κB pathway in a lipopolysaccharide (LPS)-induced inflammation model of Caco-2 cells. In contrast, ML385, an Nrf2 inhibitor, might eliminate the protection provided by MOR. Notably, treatment with MOR significantly up-regulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), suggesting that MOR may be a potential PPAR-γ activator. In conclusion, MOR exerts protective effect in UC by improving intestinal barrier function, regulating Nrf2/NF-κB and PI3K/AKT/mTOR signaling pathways, and another effect associated with the regulation of PPAR-γ expression.

Electrical Stimulations Generated by P(VDF-TrFE) Films Enhance Adhesion Forces and Odontogenic Differentiation of Dental Pulp Stem Cells (DPSCs).

Biophysical and biochemical cues of biomaterials can regulate cell behaviors. Dental pulp stem cells (DPSCs) in pulp tissues can differentiate to odontoblast-like cells and secrete reparative dentin to form a barrier to protect the underlying pulp tissues and enable complete pulp healing. Promotion of the odontogenic differentiation of DPSCs is essential for dentin regeneration. The effects of the surface potentials of biomaterials on the adhesion and odontogenic differentiation of DPSCs remain unclear. Here, poly(vinylidene fluoride-trifluoro ethylene) (P(VDF-TrFE)) films with different surface potentials were prepared by the spin-coating technique and the contact poling method. The cytoskeletal organization of DPSCs grown on P(VDF-TrFE) films was studied by immunofluorescence staining. Using atomic force microscopy (AFM), the lateral detachment forces of DPSCs from P(VDF-TrFE) films were quantified. The effects of electrical stimulation generated from P(VDF-TrFE) films on odontogenic differentiation of DPSCs were evaluated in vitro and in vivo. The unpolarized, positively polarized, and negatively polarized films had surface potentials of -52.9, +902.4, and -502.2 mV, respectively. DPSCs on both negatively and positively polarized P(VDF-TrFE) films had larger cell areas and length-to-width ratios than those on the unpolarized films (P < 0.05). During the detachment of DPSCs from P(VDF-TrFE) films, the average magnitudes of the maximum detachment forces were 29.4, 72.1, and 53.9 nN for unpolarized, positively polarized, and negatively polarized groups, respectively (P < 0.05). The polarized films enhanced the mineralization activities and increased the expression levels of the odontogenic-related proteins of DPSCs compared to the unpolarized films (P < 0.05). The extracellular signal-regulated kinase (ERK) signaling pathway was involved in the odontogenic differentiation of DPSCs as induced by surface charge. In vivo, the polarized P(VDF-TrFE) films enhanced adhesion of DPSCs and promoted the odontogenic differentiation of DPSCs by electrical stimulation, demonstrating a potential application of electroactive biomaterials for reparative dentin formation in direct pulp capping.

Recent Advances in the Inhibition of Membrane Lipid Peroxidation by Food-Borne Plant Polyphenols via the Nrf2/GPx4 Pathway.

Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function and potentially triggering apoptosis or necrosis. This process is closely correlated with the onset of many diseases. Evidence suggests that the phenolic hydroxyl groups in food-borne plant polyphenols (FPPs) make them effective antioxidants capable of preventing diseases triggered by cell membrane LP. Proper dietary intake of FPPs can attenuate cellular oxidative stress, especially damage to cell membrane phospholipids, by activating the Nrf2/GPx4 pathway. Nuclear factor E2-related factor 2 (Nrf2) is an oxidative stress antagonist. The signaling pathway regulated by Nrf2 is a defense transduction pathway of the organism against external stimuli such as reactive oxygen species and exogenous chemicals. Glutathione peroxidase 4 (GPx4), under the regulation of Nrf2, is the only enzyme that reduces cell membrane lipid peroxides with specificity, thus playing a pivotal role in regulating cellular ferroptosis and counteracting oxidative stress. This study explored the Nrf2/GPx4 pathway mechanism, antioxidant activity of FPPs, and mechanism of LP. It also highlighted the bioprotective properties of FPPs against LP and its associated mechanisms, including (i) activation of the Nrf2/GPx4 pathway, with GPx4 potentially serving as a central target protein, (ii) regulation of antioxidant enzyme activities, leading to a reduction in the production of ROS and other peroxides, and (iii) antioxidant effects on LP and downstream phospholipid structure. In conclusion, FPPs play a crucial role as natural antioxidants in preventing LP. However, further in-depth analysis of FPPs coregulation of multiple signaling pathways is required, and the combined effects of these mechanisms need further evaluation in experimental models. Human trials could provide valuable insights into new directions for research and application.

Rutin prevents EqHV-8 induced infection and oxidative stress via Nrf2/HO-1 signaling pathway.

Introduction: The Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway has been extensively studied for its role in regulating antioxidant and antiviral responses. The Equid herpesvirus type 8 (EqHV-8) poses a significant threat to the equine industry, primarily manifesting as respiratory disease, abortions, and neurological disorders in horses and donkeys. Oxidative stress is considered a key factor associated with pathogenesis of EqHV-8 infection. Unfortunately, there is currently a dearth of therapeutic interventions available for the effective control of EqHV-8. Rutin has been well documented for its antioxidant and antiviral potential. In current study we focused on the evaluation of Rutin as a potential therapeutic agent against EqHV-8 infection. Methods: For this purpose, we encompassed both in-vitro and in-vivo investigations to assess the effectiveness of Rutin in combatting EqHV-8 infection. Results and Discussion: The results obtained from in vitro experiments demonstrated that Rutin exerted a pronounced inhibitory effect on EqHV-8 at multiple stages of the viral life cycle. Through meticulous experimentation, we elucidated that Rutin's antiviral action against EqHV-8 is intricately linked to the Nrf2/HO-1 signaling pathway-mediated antioxidant response. Activation of this pathway by Rutin was found to significantly impede EqHV-8 replication, thereby diminishing the viral load. This mechanistic insight not only enhances our understanding of the antiviral potential of Rutin but also highlights the significance of antioxidant stress responses in combating EqHV-8 infection. To complement our in vitro findings, we conducted in vivo studies employing a mouse model. These experiments revealed that Rutin administration resulted in a substantial reduction in EqHV-8 infection within the lungs of the mice, underscoring the compound's therapeutic promise in vivo. Conclusion: In summation, our finding showed that Rutin holds promise as a novel and effective therapeutic agent for the prevention and control of EqHV-8 infections.