Prophylactic nicotinamide mononucleotide (NMN) mitigates CSDS-induced depressive-like behaviors in mice via preserving of ATP level in the mPFC.

Depression is a prevalent psychiatric disorder with accumulating evidence implicating dysregulation of extracellular adenosine triphosphate (ATP) levels in the medial prefrontal cortex (mPFC). It remains unclear whether facilitating endogenous ATP production and subsequently increasing extracellular ATP level in the mPFC can exert a prophylactic effect against chronic social defeat stress (CSDS)-induced depressive-like behaviors and enhance stress resilience. Here, we found that nicotinamide mononucleotide (NMN) treatment effectively elevated nicotinamide adenine dinucleotide (NAD+) biosynthesis and extracellular ATP levels in the mPFC. Moreover, both the 2-week intraperitoneal (i.p.) injection and 3-week oral gavage of NMN prior to exposure to CSDS effectively prevented the development of depressive-like behavior in mice. These protective effects were accompanied with the preservation of both NAD+ biosynthesis and extracellular ATP level in the mPFC. Furthermore, catalyzing ATP hydrolysis by mPFC injection of the ATPase apyrase negated the prophylactic effects of NMN on CSDS-induced depressive-like behaviors. Prophylactic NMN treatment also prevented the reduction in GABAergic inhibition and the increase in excitability in mPFC neurons projecting to the lateral habenula (LHb). Collectively, these findings demonstrate that the prophylactic effects of NMN on depressive-like behaviors are mediated by preventing extracellular ATP loss in the mPFC, which highlights the potential of NMN supplementation as a novel approach for protecting and preventing stress-induced depression in susceptible individuals.

Halide Perovskite Inducing Anomalous Nonvolatile Polarization in Poly(vinylidene fluoride)-based Flexible Nanocomposites.

Ferroelectric materials have important applications in transduction, data storage, and nonlinear optics. Inorganic ferroelectrics such as lead zirconate titanate possess large polarization, though they are rigid and brittle. Ferroelectric polymers are light weight and flexible, yet their polarization is low, bottlenecked at 10 µC cm-2. Here we show poly(vinylidene fluoride) nanocomposite with only 0.94% of self-nucleated CH3NH3PbBr3 nanocrystals exhibits anomalously large polarization (~19.6 µC cm-2) while retaining superior stretchability and photoluminance, resulting in unprecedented electromechanical figures of merit among ferroelectrics. Comprehensive analysis suggests the enhancement is accomplished via delicate defect engineering, with field-induced Frenkel pairs in halide perovskite stabilized by the poled ferroelectric polymer through interfacial coupling. The strategy is general, working in poly(vinylidene fluoride-co-hexafluoropropylene) as well, and the nanocomposite is stable. The study thus presents a solution for overcoming the electromechanical dilemma of ferroelectrics while enabling additional optic-activity, ideal for multifunctional flexible electronics applications.

Naringin ameliorates liver fibrosis in zebrafish by modulating IDO1-mediated lipid metabolism and inflammatory infiltration.

Liver fibrosis (LF) is an important reparative process in response to acute or chronic hepatic injury, which has the potential to advance towards cirrhosis and hepatocellular carcinoma. Dietary naringin consumption contributes to protection against LF in animal studies, while the exact protective mechanism of naringin remains unclear. This study aimed to investigate the molecular mechanisms behind the potential protective effect of naringin against TAA-induced LF in zebrafish. In this study, we utilized zebrafish to create the LF model and investigate the therapeutic mechanism of naringin. Firstly, we evaluated the changes in hepatic fibrosis and lipid accumulation in the liver following naringin treatment with oil red O, Nile red, and Sirius red and immunohistochemistry. In addition, we employed an ROS probe to directly measure oxidative stress and monitor inflammatory cell migration in a zebrafish transgenic line. Morpholino was used in the knockdown of IDO1 in order to verify its vital role in LF. Our findings demonstrated that naringin exhibited anti-inflammatory and anti-fibrotic action in conjunction with a reversal in lipid accumulation, oxidative stress and suppression of macrophage infiltration and activation of hepatic stellate cells. Furthermore, the results showed that the antifibrotic effect of naringin was removed upon IDO1 knockdown, proving that naringin exerts a protective effect by regulating IDO1. Naringin demonstrates remarkable protective effects against LF, effectively counteracting inflammation and hepatic steatosis in zebrafish liver. These findings suggest that naringin may function as an effective IDO1 inhibitor, holding the potential for clinical translation as a therapeutic agent for the treatment of LF.

Screening of immune-related biological markers for aneurysmal subarachnoid hemorrhage based on machine learning approaches.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a common hemorrhagic condition frequently encountered in the emergency department, which is characterized by high mortality and disability rates. However, the precise molecular mechanisms underlying the rupture of an aneurysm are still not fully understood. The primary objective of this study is to elucidate the fundamental molecular mechanisms underlying aSAH and provide novel therapeutic targets for the treatment of aSAH. Methods: The gene expression matrix of aSAH was downloaded from the Gene Expression Omnibus (GEO) database. In this study, we employed weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis (DEGs) screening to identify crucial modules and genes associated with aSAH. Furthermore, the evaluation of immune cell infiltration was conducted through the utilization of the single-sample gene set enrichment analysis (ssGSEA) technique and the CIBERSORT algorithm. The study utilized Gene Set Variation Analysis (GSVA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to investigate and comprehend the fundamental biological pathways and mechanisms. Results: Using WGCNA, six gene co-expression modules were constructed. Among the identified modules, the yellow module, which encompasses 184 genes, demonstrated the most significant correlation with aSAH. Consequently, it was determined to be the central module responsible for governing the pathogenesis of aSAH. Additionally, the application of WGCNA, LASSO regression, and multiple factor logistic regression analysis revealed ARHGAP26 and SLMAP as the key genes associated with aSAH. Furthermore, the diagnostic efficacy of these pivotal genes in aSAH was confirmed through the use of receiver operating characteristic (ROC) curve analysis, validating their discriminative potential. Moreover, the utilization of GO and KEGG pathway analysis revealed a significant enrichment of inflammation-related signaling in aSAH. Conclusion: The genes ARHGAP26 and SLMAP were identified as significant predictors of aSAH. Accordingly, these genes demonstrate significant potential to function as novel biological markers and therapeutic targets for aSAH.

Zexie decoction reduce glucose-dependent lipid accumulation and oxidative stress in Caenorhabditis elegans.

BACKGROUND: Obesity has become a global public health problem. Zexie decoction (ZXT) is a classic formula from Synopsis of the Golden Chamber. However, the long-term effect of ZXT in lipid accumulation remain unclear. PURPOSE: This study aims to investigate the effect of ZXT on aging, lipid metabolism and oxidative stress. METHODS: Different concentration of ZXT was administered to Caenorhabditis elegans (C. elegans) cultured in NGM or the high glucose nematode growth media (GNGM). The lifespan, heat stress resistance, lipid accumulation and related mRNA expression of the worms were examined. Oil Red staining and triglyceride were used to evaluated the lipid accumulation. Nhr-49, fat-5/fat-7, fat-5/fat-6 or skn-1 knockout mutants were used to clarify the effect on lipid metabolism of ZXT. GFP-binding mutants were used to observe the changes in protein expression. RESULTS: ZXT improved the survival rate of C. elegans in lifespan test and heat stress test. ZXT also reduced lipid accumulation in C. elegans and significantly changed the expression of fatty acid synthesis related genes and lipid metabolism related genes. In addition, ZXT-treated C. elegans showed a higher expression of anti-oxidative protein, and reduced the expression of oxidative stress and mitochondrial dysfunction marker. However, when skn-1 was knockdown, ZXT no longer had the effect of maintaining the mitochondria membrane potential and lipid lowering but still effectively decreased the O2·- induced by high glucose. CONCLUSIONS: ZXT reduced fat accumulation by regulating lipid metabolism via multiple targets and enhanced stress resistance by its antioxidant effect in C. elegans.

Composition-Driven Polarization Distribution in Poly(vinylidene fluoride)-Based Copolymer Blends for High Power Density Capacitors.

High power density capacitors have been highly demanded in modern electronics and pulsed power systems. Yet the long-standing challenge that restricts achieving high power in capacitors lies in the inverse relationship between the breakdown strength and permittivity of dielectric materials. Here, we introduce poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) into the host poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) to produce PVDF-based copolymer blends, resulting in composition-driven 0-3 type microstructures, featuring nanospheres of P(VDF-TrFE) lamellar crystals dispersed homogeneously in a P(VDF-HFP) matrix together with crystalline phase evolution from the γ-phase to the α-phase. At the critical composition, the TrFE/HFP mole ratio is equal to 1, and the blend film achieves maximum energy storage performance with discharged energy density (Udis) ∼ 24.3 J/cm3 at 607 MV/m. Finite element analyses reveal the relationship between microstructures, compositions, and the distribution of local electric field and polarization, which provide an in-depth understanding of the microscopic mechanism of the enhancement in energy storage capability of the blend films. More importantly, in a practical charge/discharge circuit, the blend film could deliver an ultrahigh energy density of 20.4 J/cm3, i.e., 88.3% of the total stored energy to 20 kΩ load in 2.8 µs (τ0.9), resulting a high power density of 7.29 MW/cm3, outperforming the reported dielectric polymer-based composites and copolymer films in both energy and power densities. The study thus demonstrates a promising strategy to develop high-performance dielectrics for high power capacitors.

Nitrogen Self-Doping Carbon Derived from Functionalized Poly(Vinylidene Fluoride) (PVDF) for Supercapacitor and Adsorption Application.

A new synthetic strategy has been developed for the facile fabrication of a N-doped porous carbon (NC-800) material via a facile carbonization of functionalized poly(vinylidene fluoride) (PVDF). The prepared NC-800 exhibits good specific capacitance of 205 F/g at 1 A/g and cycle stability (95.2% retention after 5000 cycles at 1 A/g). The adsorption capacity of NC-800 on methylene blue and methyl orange was 780 mg/g and 800 mg/g, respectively. The facile and economical method and good performance (supercapacitor and adsorption) suggest that the NC-800 is a promising material for energy storage and adsorption.

Mango-Stone-Derived Nitrogen-Doped Porous Carbon for Supercapacitors.

The preparation of N-doped porous carbon (NC-800) is presented via facile mango stone carbonization at 800 °C. The NC-800 material exhibits good cycle stability (the capacity retention is 97.8% after 5000 cycles) and high specific capacitance of 280 F/g at 1 A/g. Furthermore, the assembled symmetric device of NC-800//NCs-800 exhibits about 31.1 Wh/kg of energy density at 800 W/kg in a voltage range of 0-1.6 V. The results of the study suggest that NC-800 may be a promising energy storage material for practical application.

Neuro-regenerative imidazole-functionalized GelMA hydrogel loaded with hAMSC and SDF-1α promote stem cell differentiation and repair focal brain injury.

Brain tissues that are severely damaged by traumatic brain injury (TBI) is hardly regenerated, which leads to a cavity or a repair with glial scarring. Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage, whose use is, whereas, limited by the low survival rate and differentiation efficiency of stem cells. To approach this problem, we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate (GelMA-imid). In addition, polydopamine (PDA) nanoparticles were used as carrier for stromal-cell derived factor-1 (SDF-1α). GelMA-imid hydrogel loaded with PDA@SDF-1α nanoparticles and human amniotic mesenchymal stromal cells (hAMSCs) were injected into the damaged area in an in-vivo cryogenic injury model in rats. The hydrogel had low module and its average pore size was 204.61 ± 41.41 nm, which were suitable for the migration, proliferation and differentiation of stem cells. In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1α could promote the migration of hAMSCs to injury site and their differentiation into nerve cells. The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model. Additionally, histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells. In summary, the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells, and showed great application potential for the physiological recovery of TBI.

[Irbesartan ameliorates cardiac inflammation in type 2 diabetic db/db mice].

OBJECTIVE: To investigate the protective effects of irbesartan against cardiac inflammation associated with diabetes and obesity in the db/db mouse model of type 2 diabetes and explore the underlying mechanisms. METHODS: Twenty- four 10-week-old diabetic db/db mice were equally randomized into irbesartan treatment (50 mg/kg per day) group and model group, using 12 nondiabetic littermates (db/+) as the controls, The mice were treated with irbesartan or saline vehicle for 16 consecutive weeks, after which the heart pathology was observed and the heart weight, body weight, and serum levels of fasting blood glucose (FBG), total cholesterol(TC), and triglycerides(TG) were measured. The expression of nuclear factor-kappaB (NF-κB) p65 in the myocardium was assessed with immunohistochemistry, the protein levels of P-IκBα ,IκBα and ß-actin were analyzed with Western blotting, and the pro-inflammatory cytokines IL-6 and TNF-α mRNA were detected using quantitative real-time PCR (qPCR). RESULTS: Compared with db/+ mice, the saline-treated db/db mice developed obesity, hyperglycemia and hyperlipidemia (P<0.01). Histopathological examination of the heart tissue revealed inflammatory cell infiltration, increased myocardial interstitium and disorders of myocardial fiber arrangement. The diabetic mice showed increased P-IαBα and decreased IκBα protein levels, enhanced activity and expression of NF-κB in the hearts, and increased mRNA expression of IL-6 and TNF-α in the myocardium. These abnormalities were all associated with increased inflammatory response. Treatment with irbesartan improved the heart architecture and attenuated high glucose-induced inflammation in the diabetic mice. CONCLUSION: Treatment with irbesartan attenuates cardiac inflammation in type 2 diabetic db/db mice, and this effect was probably associated with the suppression of cardiac angiotensin II and NF-κB signaling pathway.

[Lead impairs ability of learning and memory and affects expression of synaptosomal-associated protein-25 in hippocampus of offspring].

OBJECTIVE: To find the effects of lead taken by pregnant mice on learning and memory and the expression of synaptosomal-associated protein (SNAP)-25 mRNA and protein, in order to reveal the mechanism of neurotoxicity induced by lead. METHODS: Lead exposure was conducted through freely drinking the corresponding lead acetate solutions with dosages of 0.3, 1.0, 3.0 g/L respectively. Each group was composed of 10 mice. 7, 14 and 21 days after their birth. The lead contents in blood and hippocampus of the offspring were determined. At the 21st day the expression of SNAP-25 mRNA and protein in hippocampus of all the offspring in various dosages groups were determined by RT-PCR and immunohistochemistry assay. RESULTS: The lead contents in blood and hippocampus of various lead exposed groups were significantly higher than those of the control group (P < 0.05). The lead levels in blood and hippocampus changed accordingly to the days of growth. In Water Morris Maze experiment, the result of 0.3 g/L group was not significantly different from that of the control group (P > 0.05), however, the results of 1.0, 3.0 g/L groups (5.89 ± 0.54, 9.53 ± 1.03) were significantly different from those of the control group (1.73 ± 0.07) (P < 0.05, P < 0.01). The expression of SNAP-25 mRNA and protein was lower in lead exposed groups than that of the control group (P < 0.05). CONCLUSION: Maternal lead exposure may induce the damage in the ability of learning and memory of the offspring. The neurotoxicity of lead may be induced by decreasing the expression of SNAP-25 mRNA and protein so as to affect the release of neurotransmitter from presynaptic terminal resulted in nerve damages.

[Differences in the response to sepsis between C57BL/6 and BALB/c mice].

OBJECTIVE: To compare the responses to sepsis between C57BL/6 and BALB/c mice. METHODS: Thirty C57BL/6 mice and 30 BALB/c mice were randomized into sham-operated group and sepsis group (n=15). Sepsis model was established by cecal ligation puncture (CLP) in the mice, and 6 h after the operation, 5 mice from each group were selected randomly for cytokine detection including IL-1beta, IL-2, IL-4, IL-5, IL-10, GM-CSF, IFN-gamma and TNF-alpha by Bio-plex. The other 10 mice in each group were used for survival analysis. RESULTS: The survival rates of BALB/c and C57BL/6 mice were both 100% in one week after the sham operation, but lowered to 10% and 50% in one week after CLP, respectively. The survival rate of C57BL/6 mice was significantly lower than that of BALB/c mice (P<0.05). After CLP, C57BL/6 mice showed significantly greater IL-4, TNF-alpha and IL-10 production than the sham-operated mice, but the concentrations of the 8 cytokines in BALB/c mice after CLP showed no significant increment. CONCLUSION: Compared with BALB/c mice, C57BL/6 strain mouse is more sensitive to sepsis.