The identification of material basis of Si Miao Formula effective for attenuating non-alcoholic fatty liver disease.

ETHNOPHARMACOLOGICAL RELEVANCE: The Si Miao Formula (SMF), a traditional Chinese medicine, originated from the "Cheng Fang Bian Du" during the Qing Dynasty and is commonly employed for the treatment of gout and hyperuricemia. We have demonstrated the anti-NAFLD effect of SMF by regulating hepatic lipid metabolism in high fat and high sucrose (HFHS) feeding mice in our previous report. However, the material basis of SMF for its anti-NAFLD effect remains unknown. AIM OF THE STUDY: To compare the effeciacy of different components of SMF and identify the material basis for its anti-NAFLD effect. MATERIALS AND METHODS: In the present study, a "Leave-one out" strategy was adopted by removing one herb from SMF each time, and the anti-NAFLD effects of four decomposed recipes containing three herbs were evaluated in C57BL/6J mice fed with an HFHS diet for 16 weeks. The chemical components of SMF and the absorbed entities in serum were assayed using UHPLC-Q-Exactive-Orbitrap HRMS. Finally, a new chemical combination with four compounds (berberine, betaine, caffeic acid, p-coumaric acid, 2:2:1:1) were generated (SMF component composition, SMF_CC), and its anti-NAFLD effect was evaluated by comparing with the original SMF in the mouse model. RESULTS: Varified effects on NAFLD mice were observed among the decomposed recipes of SMF, while the original SMF showed advantages over its decomposed recipes. A total of 111 chemicals were identified from SMF, and 21 of them were detected in serum after oral administration of SMF. Comparing to SMF, SMF_CC showed comparable anti-NAFLD effect in HFHS-diet-fed mice, which was associated with the inhibition of hepatic fatty acid synthesis and transport, as well as inflammation. CONCLUSION: Our current results suggested that the original SMF was better than its decomposed recipes in NAFLD management, and the derived SMF_CC was also effective in inhibiting NAFLD formation, highlighting its potential of being a novel natural agent for NAFLD therapy.

STING agonist-boosted mRNA immunization via intelligent design of nanovaccines for enhancing cancer immunotherapy.

Messenger RNA (mRNA) vaccine is revolutionizing the methodology of immunization in cancer. However, mRNA immunization is drastically limited by multistage biological barriers including poor lymphatic transport, rapid clearance, catalytic hydrolysis, insufficient cellular entry and endosome entrapment. Herein, we design a mRNA nanovaccine based on intelligent design to overcome these obstacles. Highly efficient nanovaccines are carried out with machine learning techniques from datasets of various nanocarriers, ensuring successful delivery of mRNA antigen and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) to targets. It activates stimulator of interferon genes (STING), promotes mRNA-encoded antigen presentation and boosts antitumour immunity in vivo, thus inhibiting tumour growth and ensuring long-term survival of tumour-bearing mice. This work provides a feasible and safe strategy to facilitate STING agonist-synergized mRNA immunization, with great translational potential for enhancing cancer immunotherapy.

Effects of blood flow restriction training on bone turnover markers, microstructure, and biomechanics in rats.

Objective: The present study aimed to investigate the effects of blood flow restriction training on muscle strength, bone tissue structure material, and biomechanical properties in rats applying various exercise interventions and to analyze the process by identifying the bone turnover markers, it provides a theoretical basis for the application of BFRT in clinical rehabilitation. Methods: A total of 24, 3-month-old male SD (Sprague Dawley) rats were randomly divided into pressurized control group (CON, n=6), low-intensity training group (LIRT, n=6), high-intensity training group (HIRT, n=6), and blood flow restriction training group (LIBFR, n=6) for 8-week ladder-climbing exercises. The pressured control group were given only ischemia treatments and did not undertake any burden. The low-intensity training group was allowed to climb the ladder with 30% of the maximum voluntary carrying capacity (MVCC). The rats in the high-intensity training group were allowed to climb the ladder with 70% MVCC. The blood flow restriction training group climbed the ladder with 30% MVCC while imposing blood flow restriction. Before sampling, the final MVCC was measured using a ladder-climbing protocol with progressively increasing weight loading. The serum, muscle, and bone were removed for sampling. The concentrations of the bone turnover markers PINP, BGP, and CTX in the serum were measured using ELISA. The bone mineral density and microstructure of femur bones were measured using micro-CT. Three-point bending and torsion tests were performed by a universal testing machine to measure the material mechanics and structural mechanics indexes of the femur bone. Results: The results of maximum strength test showed that the MVCC in LIRT, HIRT, and LIBFR groups was significantly greater than in the CON group, while the MVCC in the HIRT group was significantly higher than that in the LIRT group (P<0.05). According to the results of the bone turnover marker test, the concentrations of bone formation indexes PINP (amino-terminal extension peptide of type I procollagen) and BGP (bone gla protein) were significantly lower in the CON group than in the HIRT group (P<0.01), while those were significantly higher in the LIRT group compared to the HIRT group (P<0.01). In terms of bone resorption indexes, significant differences were identified only between the HIRT and other groups (P<0.05). The micro-CT examination revealed that the HIRT group had significantly greater bone density index values than the CON and LIRT groups (P<0.05). The results of three-point bending and torsion test by the universal material testing machine showed that the elastic modulus and maximum load indexes of the HIRT group were significantly smaller than those of the LIBFR group (P<0.05). The fracture load indexes in the HIRT group were significantly smaller than in the LIBFR group (P<0.05). Conclusion: 1. LIRT, HIRT, LIBFR, and CON all have significant differences, and this training helps to improve maximum strength, with HIRT being the most effective. 2. Blood flow restriction training can improve the expression of bone turnover markers, such as PINP and BGP, which promote bone tissue formation. 3. Blood flow restriction training can improve muscle strength and increase the positive development of bone turnover markers, thereby improving bone biomechanical properties such as bone elastic modulus and maximum load.

Characterization of Agronomic and Seed Oil Features for Different Cultivars of Tree Peony.

Tree peony is a unique oil plant resource in China, and tree peony seed oil is one of the healthy edible oils with a very promising future. However, the main oil tree peony cultivars promoted in China are Paeonia ostii 'Fengdan' and Paeonia rockii. In order to explore new oil tree peony cultivars, 68 tree peony cultivars were investigated and cultivars with oil potential were selected by cluster analysis and grey relational analysis (GRA) in this study. The results demonstrated that the 68 cultivars varied significantly in terms of agronomic characteristics (p < 0.05), with the coefficient of variation in seed yield per plant reaching a high of 75.36%. The oil content of 46 cultivars was higher than 'Fengdan' (20.87 ± 0.26%) and 'Zibanbai' (21.24 ± 1.01%), while the alpha-linolenic acids and total unsaturated fatty acid contents of 26 cultivars were higher than 'Fengdan' (39.79 ± 1.13% and 88.99 ± 0.47%) and 'Zibanbai' (40.51 ± 0.09% and 93.59 ± 0.09%). Finally, three cultivars with better integrated traits were selected by cluster analysis and grey relational analysis (GRA), comprising of 'Changshoule', 'Xianchizhenghui', and 'Yupantuojin'. The contents of alpha-linolenic acids and total unsaturated fatty acids in 'Changshoule' (47.98 ± 0.17% and 93.60 ± 0.08%), 'Xianchizhenghui' (49.44 ± 0.63% and 93.80 ± 0.06%), and 'Yupantuojin' (40.46 ± 0.26% and 93.58 ± 0.06%) were higher than that of 'Fengdan' (39.79 ± 1.13% and 88.99 ± 0.47%). In general, these cultivars can be used as hybrid parental materials for breeding new excellent oil tree peony cultivars.

Effects of long-term tillage practices on the stability of soil aggregates and organic carbon in black soil farmland.

We examined the effects of different tillage practices on plough layer soil structure and organic carbon stabilization in black soil farmland with a long-term positioning platform. The wet-sieving method and infrared spectroscopy method were used to investigate the impacts of conventional tillage (CT), no-tillage (NT), sub-soiling tillage (ST), and moldboard plowing tillage (MP) on soil aggregates distribution and organic carbon characteristics in 0-40 cm soil layers. Compared to CT, both NT and ST treatments significantly increased the proportion of large macroaggregates (>2 mm) in the topsoil layer (0-20 cm)and that of small macroaggregates (0.25-2 mm) in the subsoil layer (20-40 cm) for NT, ST, and MP. NT, ST, and MP treatments resulted in higher mean weight dia-meter (MWD) and mean geometric diameter (GMD) of soil aggregates in both the topsoil and subsoil layers. NT treatment improved organic carbon contents in bulk soil and large macroaggregates in the topsoil layer, while ST and MP enhanced organic carbon contents in bulk soil and large macroaggregates in the subsoil layer. The contribution rate of small macroaggregates organic carbon content to the total was between 68.9% and 83.4%. Furthermore, the organic carbon chemical stabilization of soil body and aggregates increased in the topsoil and subsoil layers under NT treatment compared to others. The MWD had a positive correlation with the organic carbon content and chemical stability of soil body and small macroaggregates. These findings offered a theoretical basis for understanding the impacts of different tillage practices on the stability of soil aggregate and organic carbon in black soil region.

Approximating First Hitting Point Distribution in Milestoning for Rare Event Kinetics.

Milestoning is an efficient method for rare event kinetics calculation using short trajectory parallelization. Mean first passage time (MFPT) is the key kinetic output of Milestoning, whose accuracy crucially depends on the initial distribution of the short trajectory ensemble. The true initial distribution, i.e., the first hitting point distribution (FHPD), has no analytic expression in the general case. Here, we introduce two algorithms, local passage time weighted Milestoning (LPT-M) and Bayesian inference Milestoning (BI-M), to accurately and efficiently approximate FHPD for systems at equilibrium condition. Starting from sampling the Boltzmann distribution on milestones, we calculate the proper weighting factor for the short trajectory ensemble. The methods are tested on two model examples for illustration purpose. Both methods improve significantly over the widely used classical Milestoning (CM) method in terms of the accuracy of MFPT. In particular, BI-M covers the directional Milestoning method as a special case in deterministic Hamiltonian dynamics. LPT-M is especially advantageous in terms of computational costs and robustness with respect to the increasing number of intermediate milestones. Furthermore, a locally iterative correction algorithm for nonequilibrium stationary FHPD is developed for exact MFPT calculation, which can be combined with LPT-M/BI-M and is much cheaper than the exact Milestoning (ExM) method.

Amino acid-induced rapid gelation and mechanical reinforcement of hydrogels with low-hysteresis and self-recoverable and fatigue-resistant properties.

Hydrogels with rapid gelation ability and robust mechanical properties are highly desirable for nascent applications in biomedical, wearable electronic, industrial and agricultural fields. However, current rapid-gelation hydrogels are compromised by poor mechanical properties, complex design of precursor molecular structures and limited precursor species. Herein, we propose a facile and universal strategy to achieve rapid gelation, strengthening and toughening of free-radical polymerized hydrogels by introducing cheap and accessible amino acids. Amino acids not only activate persulfate to quickly produce free radicals and thus induce fast free radical polymerization, but also can form strong hydrogen bonds with the network chains to strengthen and toughen the hydrogels. For example, with the presence of L-serine, the acrylamide (AM) monomer shows rapid gelation within tens of seconds, and moreover the resulting hydrogel reaches a tensile strength of 0.45 MPa and a breaking strain of 2060%. More importantly, owing to the extremely dynamic feature of the hydrogen bonds between L-serine molecules and network chains, the hydrogel possesses the advantages of low hysteresis, rapid self-recovery capability and outstanding fatigue resistance. Furthermore, this strategy is general to a wide range of amino acids and monomers. We also demonstrate that this rapid, controllable and universal strategy for the fabrication of mechanically robust hydrogels holds tremendous potential for diverse practical applications, such as flexible electronic sensors and ultraviolet (UV)-blocking artificial skins.

Sucrose-tannin-nanosilica hybrid bio-adhesive based on dual dynamic Schiff base and disulfide bonds with enhanced toughness and cohesion.

Herein, a high-performance sucrose-tannin bio-based adhesive is developed based on consisting of oxidized sucrose (OS), tannin acid (TA), SiO2 nanoparticles and 2,2'-disulfanediylbis (ethan-1-amine) (DBA) by a facile chemical cross-linking strategy. The OS-TA and OS-TA@SiO2 bio-based adhesives are characterized by XPS, FTIR, and 13C NMR, while the bonding performance is also investigated using shear strength test. Results show that the optimal formulation of OS-TA bio-based adhesive is a 2:1:1 mass ratio for OS: TA: DBA. When the mass fraction of SiO2 is 15 % and the solid content of main components is 50 %, the OS-TA@SiO2 bio-based adhesive has excellent bonding strength. Relative to OS-TA, the wet bonding strength of the OS-TA@SiO2 enhanced from 1.16 MPa to 1.85 MPa, while the dry bonding strength improved from 1.90 MPa to 2.50 MPa. The wood failure rate of the plywood fabricated by using the OS-TA@SiO2 bio-based adhesive reaches 80 %. Therefore, relying on the high flexibility of dynamic disulfide bonds, adding SiO2 nanoparticles into the adhesive system can facilitate greatly the mechanical interlocking effect and make the chemical cross-linking network more compact through the synergistic chemical interactions. This work provides new insights into producing green and renewable bio-based wood adhesives using sucrose and tannin.

Renal Interstitial Fibrosis Detected on 18F-AlF-NOTA-FAPI-04 PET/CT in a Patient With Multiple Myeloma.

ABSTRACT: 18F-AlF-NOTA-FAPI-04 PET/CT was performed on a 58-year-old woman newly diagnosed with multiple myeloma and acute renal insufficiency. 18F-AlF-NOTA-FAPI-04 PET/CT showed increased FAPI uptake in multiple osteolytic lesions and both kidneys. Subsequent renal aspiration biopsy confirmed renal interstitial fibrosis due to subacute tubular interstitial injury. This case suggests that 18F-AlF-NOTA-FAPI-04 PET/CT may be valuable in the evaluation of renal interstitial fibrosis in patients with multiple myeloma.

Decoding the biological toxicity of phenanthrene on intestinal cells of Eisenia fetida: Effects, toxicity pathways and corresponding mechanisms.

Phenanthrene is frequently detected and exists extensively in the soil environment, and its residues inevitably impose a significant threat to soil organisms. Exposure to and toxicity of phenanthrene on earthworms has been extensively studied before, however, the possible mechanisms and related pathways associated with phenanthrene-triggered toxicity at the intestinal cell level remain unclear. Herein, primary intestinal cells isolated from Eisenia fetida (Annelida, Oligochaeta) intestine were used as targeted receptors to probe the molecular mechanisms involved in ROS-mediated damaging effects and the potential pathways of phenanthrene-induced toxicity at cellular and sub-cellular levels. Results indicated that phenanthrene exposure induced oxidative stress by activating intracellular ROS (elevated O2-, H2O2, and OH- content) bursts in E. fetida intestinal cells, causing various oxidative damage effects, including lipid peroxidation (increased MDA content), protein oxidation (enhanced PCO levels), and DNA damage (enhanced 8-OHdG levels). The enzymatic and non-enzymatic strategies in earthworm cells were activated to mitigate these detrimental effects by regulating ROS-mediated pathways involving defense regulation. Also, phenanthrene stress destroyed the cell membrane of E. fetida intestinal cells, resulting in cellular calcium homeostasis disruption and cellular energetic alteration, ultimately causing cytotoxicity and cell apoptosis/death. More importantly, the mitochondrial dysfunction in E. fetida cells was induced by phenanthrene-caused mitochondrial membrane depolarization, which in turn caused un-controlled ROS burst and induced apoptosis through mitochondria-mediated caspase-3 activation and ROS-mediated mitochondrial-dependent pathway. Furthermore, exposure to phenanthrene activated an abnormal mRNA expression profile associated with defense regulation (e.g., Hsp70, MT, CRT, SOD, CAT, and GST genes) in E. fetida intestinal cells, resulting in various cellular dysfunctions and pathological conditions, eventually, apoptotic cell death. Taken together, this study offers valuable insights for probing the toxic effects and underlying mechanisms posed by phenanthrene at the intestinal cell level, and is of great significance to estimate the detrimental side effects of phenanthrene on soil ecological health.

Chestnut Shell Polyphenols Inhibit the Growth of Three Food-Spoilage Bacteria by Regulating Key Enzymes of Metabolism.

The microbial contamination of food poses a threat to human health. Chestnut shells, which are byproducts of chestnut processing, contain polyphenols that exert various physiological effects, and thus have the potential to be used in food preservation. This study investigates the bacteriostatic effect and mechanism(s) of the action of chestnut shell polyphenols (CSPs) on three food-spoilage bacteria, namely Bacillus subtilis, Pseudomonas fragi, and Escherichia coli. To this end, the effect of CSPs on the ultrastructure of each bacterium was determined using scanning electron microscopy and transmission electron microscopy. Moreover, gene expression was analyzed using RT-qPCR. Subsequent molecular docking analysis was employed to elucidate the mechanism of action employed by CSPs via the inhibition of key enzymes. Ultrastructure analysis showed that CSPs damaged the bacterial cell wall and increased permeability. At 0.313 mg/mL, CSPs significantly increased the activity of alkaline phosphatase and lactate dehydrogenase, as well as protein leakage (p < 0.05), whereas the activity of the tricarboxylic acid (TCA) cycle enzymes, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, were inhibited (p < 0.05). The expression levels of the TCA-related genes gltA, icd, sucA, atpA, citA, odhA, IS178_RS16090, and IS178_RS16290 are also significantly downregulated by CSP treatment (p < 0.05). Moreover, CSPs inhibit respiration and energy metabolism, including ATPase activity and adenosine triphosphate (ATP) synthesis (p < 0.05). Molecular docking determined that proanthocyanidins B1 and C1, the main components of CSPs, are responsible for the antibacterial activity. Therefore, as natural antibacterial substances, CSPs have considerable potential for development and application as natural food preservatives.

Study on myocardial toxicity induced by lead halide perovskites nanoparticles.

Lead halide perovskites (LHPs) are outstanding candidates for next-generation optoelectronic materials, with considerable prospects of use and commercial value. However, knowledge about their toxicity is scarce, which may limit their commercialization. Here, for the first time, we studied the cardiotoxicity and molecular mechanisms of representative CsPbBr3 nanoparticles in LHPs. After their intranasal administration to Institute of Cancer Research (ICR) mice, using advanced synchrotron radiation, mass spectrometry, and ultrasound imaging, we revealed that CsPbBr3 nanoparticles can severely affect cardiac systolic function by accumulating in the myocardial tissue. RNA sequencing and Western blotting demonstrated that CsPbBr3 nanoparticles induced excessive oxidative stress in cardiomyocytes, thereby provoking endoplasmic reticulum stress, disturbing calcium homeostasis, and ultimately leading to apoptosis. Our findings highlight the cardiotoxic effects of LHPs and provide crucial toxicological data for the product.

Effects analysis and probability forecast (EAPF) of real-time management on urban flooding: A novel bidirectional verification framework.

Government departments usually prepare and implement contingency plans to address frequent urban flooding caused by short-term heavy rainfall. Previous studies focused on the evaluation of the static impact of the policies on urban floods, while there is a lack of research on the effect of off-design conditions, real-time feedback and treatments of the flood events on urban flood mitigation, which is detrimental to the optimization of management strategies of the cities. To quantify the effects of real-time management on flood mitigation in Fuzhou City, China, this study proposed a framework (EAPF) for evaluation and risk prediction. First, we collected data on the locations, rainfall intensity, inundation time, and the triggers of the waterlogging events from 2017 to 2021. Second, based on the vigilance analyses, a structural equation model (SEM) was constructed to quantitatively evaluate the mitigation effects of management on waterlogging. Finally, a probability prediction model of dynamic drainage capacity was proposed for flood simulation caused by the rainwater grate blockage. The results indicate that the environmental factors were the decisive triggers affecting the severity of waterlogging, and increasing the frequency of management events effectively reduced the probability of blocking. The correlation between the number of management events and blocking flood events was -0.42, while a decrease in vigilance increased the possibility of flooding caused by overdue treatment. The proposed hydrological waterlogging model, which considered blockages, exhibited a Nash-Sutcliffe efficiency (NSE) coefficient exceeding 0.9 under deterministic conditions. The probability prediction model verified the mitigating effect of management on the blockages and urban flooding, and its results were consistent with those of the SEM. Our study contributes to improving the reliability of waterlogging prediction and optimizing the management flow in the developing cities.

ß-Elemene induced ferroptosis via TFEB-mediated GPX4 degradation in EGFR wide-type non-small cell lung cancer.

INTRODUCTION: ß-Elemene (ß-ELE), derived from Curcuma wenyujin, has anticancer effect on non-small cell lung cancer (NSCLC). However, the potential target and detail mechanism were still not clear. TFEB is the master regulator of lysosome biogenesis. Ferroptosis, a promising strategy for cancer therapy could be triggered via suppression on glutathione peroxidase 4 (GPX4). Weather TFEB-mediated lysosome degradation contributes to GPX4 decline and how ß-ELE modulates on this process are not clear. OBJECTIVES: To observe the action of ß-ELE on TFEB, and the role of TFEB-mediated GPX4 degradation in ß-ELE induced ferroptosis. METHODS: Surface plasmon resonance (SPR) and molecular docking were applied to observe the binding affinity of ß-ELE on TFEB. Activation of TFEB and lysosome were observed by immunofluorescence, western blot, flow cytometry and qPCR. Ferroptosis induced by ß-ELE was observed via lipid ROS, a labile iron pool (LIP) assay and western blot. A549TFEB KO cells were established via CRISPR/Cas9. The regulation of TFEB on GPX4 and ferroptosis was observed in ß-ELE treated A549WT and A549TFEB KO cells, which was further studied in orthotopic NOD/SCID mouse model. RESULTS: ß-ELE can bind to TFEB, notably activate TFEB, lysosome and transcriptional increase on downstream gene GLA, MCOLN1, SLC26A11 involved in lysosome activity in EGFR wild-type NSCLC cells. ß-ELE increased GPX4 ubiquitination and lysosomal localization, with the increase on lysosome degradation of GPX4. Furthermore, ß-ELE induced ferroptosis, which could be promoted by TFEB overexpression or compromised by TFEB knockout. Genetic knockout or inactivation of TFEB compromised ß-ELE induced lysosome degradation of GPX4, which was further demonstrated in orthotopic NOD/SCID NSCLC mice model. CONCLUSION: This study firstly demonstrated that TFEB promoted GPX4 lysosome degradation contributes to ß-ELE induced ferroptosis in EGFR wild-type NSCLC, which gives a clue that TFEB mediated GPX4 degradation would be a novel strategy for ferroptosis induction and NSCLC therapy.

Optimization for Pipeline Corrosion Sensor Placement in Oil-Water Two-Phase Flow Using CFD Simulations and Genetic Algorithm.

Internal corrosion is a major concern in ensuring the safety of transmission and gathering pipelines in Structural Health Monitoring (SHM). It usually requires numerous sensors deployed inside the piping system to comprehensively cover the locations with high corrosion rates. This study presents a hybrid modeling strategy using Computational Fluid Dynamics (CFD) and Genetic Algorithm (GA) to improve the sensor placement scheme for corrosion detection and monitoring. The essence of the proposed strategy harnesses the well-validated physical modeling capability of the CFD to simulate the oil-water two-phase flow and the stochastic searching ability of the GA to explore better solutions on a global level. The CFD-based corrosion rate prediction was validated through experimental results and further used to form the initial population for GA optimization. Importantly, fitness was defined by considering both sensing effectiveness and cost of sensor coverage. The hybrid modeling strategy was implemented through case studies, where three typical pipe fittings were used to demonstrate the applicability of the sensor layout design for corrosion detection in pipelines. The GA optimization results show high accuracy for sensor placement inside the pipelines. The best fitness of the U-shaped, upward-inclined, and downward-inclined pipes were 0.9415, 0.9064, and 0.9183, respectively. Upon this, the hybrid modeling strategy can provide a promising tool for the pipeline industry to design the practical placement.

Family function and emotional behavior problems in Chinese children and adolescents: A moderated mediation model.

BACKGROUND: Studies have shown that family function is associated with emotional behavior problems. However, the underlying relationship mechanisms between family function and emotional behavior problems in children and adolescents is not fully understood. Therefore, the purpose of this study is to explore the mediating effect of resilience and the moderating effect of sleep quality using a moderated mediation model. METHODS: 6363 children and adolescents in grades four to nine were surveyed in some areas of Anhui Province, China. Family function, resilience, sleep quality, and emotional behavior problems were measured through a self-administered questionnaire. All data analysis was by performed by SPSS 23.0. RESULTS: The results showed that family function was negatively associated with emotional behavior problems (r = -0.307, p < 0.01). Resilience partially mediated the relationship between family function and emotional behavior problems (indirect effect = -0.108, accounted for 38.4 %). Sleep quality moderated the relationship between family function and resilience (ß = -0.039, P < 0.001). CONCLUSION: Resilience and sleep quality respectively played a mediating and moderating effect in the relationship between family function and emotional behavior problems. These findings suggest that we should pay attention to the family function of children and adolescents in time, improve their resilience and sleep quality, so as to effectively reduce the occurrence of emotional behavior problems.

Enhancing stability of liposomes using high molecular weight chitosan to promote antioxidative stress effects and lipid-lowering activity of encapsulated lutein in vivo and in vitro.

Lutein is an antioxidant with multiple beneficial functions. However, its therapeutic potential is hampered by its low water solubility and bioavailability. The goal of this study is to compare the stability of lutein-loaded liposomes (Lu-lip) and low (LC)/high molecular weight (HC) chitosan-coated Lu-lip, along with their antioxidant capacity using H2O2-induced HepG2 cells and their lipid-lowering activity using high-fat diet mice. Both LC and HC reduced the lutein degradation rate by 17.5 % and 26.72 % in a challenging environment at pH 6 and T = 4 °C. Compared to LC, the HC coating improved the size- and zeta-potential-stability of Lu-lip at 5 < pH < 7, with the best performance at pH 6. The HC coating prolonged the lutein release profile, increased the cellular uptake of Lu-lip, and reduced the reactive oxygen species (ROS) levels and the H2O2-induced necrotic cell ratios by increasing the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Animal experiments have shown that oral administration of LC and HC coated Lu-lip can significantly reduce body weight levels, total triglycerides (TG), total cholesterol (TC), and non-high-density lipoprotein (n-HDL-C) in high-fat diet mice while significantly increasing the levels of CAT, SOD and GSH-Px in the liver of mice. LC and HC coated Lu-lip can reduce fat accumulation in the liver and epididymal adipose tissue.

D-pinitol ameliorated H2O2-induced oxidative damage in PC12 cells and prolonged the lifespan by IIS pathway in Caenorhabditis elegans.

D-pinitol (DP) has been extensively regarded as the main active component of legumes for anti-aging. In this study, we intended to explore the anti-aging mechanism of DP, utilizing computer modeling techniques. The results demonstrated that DP significantly delayed H2O2-induced cellular senescence. Model PC12 cells treated with DP exhibited increased cell viability, increased antioxidant enzyme activity (SOD, CAT), and reduced ROS and MDA levels. Furthermore, DP was discovered to have a positive effect on healthy longevity. In C. elegans, DP treatment enhanced lifespan, stress capacity, antioxidant capacity (T-SOD/CAT/GSH-Px/MDA/ROS), and altered aging-related indicators of lipofuscin accumulation, pharyngeal pump rate, motility, and reproduction. Moreover, DP could reduce the toxicity Aß in transgenic C. elegans CL4176, CL2355, and CL2331. Further mechanistic studies indicated DP increased transcription factor (daf-16, skn-1, hsf-1) expression of insulin/insulin-like growth factor-1 signaling (IIS) pathway. As expected, DP also extended the downstream target genes of the three transcription factors (sod-3, ctl-1, ctl-2, gst-4, hsp-16.1, and hsp-16.2). Further mutant lifespan experiments, network pharmacology, and molecular docking revealed that DP might be life-extending through the IIS pathway. DP deserves extensive investigation and development as a potential anti-aging drug in the future.

Depletion of mTOR ameliorates CD4+ T cell pyroptosis by promoting autophagy activity in septic mice.

A reduction in the number of CD4+ T cells is a central part of the immunosuppression phase of sepsis and leads to impaired immune defense ability and increased mortality. Pyroptosis, a newly discovered programmed cell death, was confirmed to be an important mechanism of lymphocytopenia in a lot of human diseases and is under the regulation of autophagy. The mammalian target of rapamycin (mTOR) pathway is closely related to CD4+ T-cell survival. Whether the mTOR pathway influences CD4+ T cell pyroptosis by regulating autophagy remains unknown. In this study, a septic mouse model was developed using cecal ligation and puncture (CLP) to explore the degree of pyroptosis and autophagy of CD4+ T cells. T-cell-specific mTOR/TSC1-knockout mice were used to investigate the role of mTOR pathway in the regulation of CD4+ T cell pyroptosis. Bafilomycin, a specific autophagy inhibitor, was used to verify the regulatory effect of autophagy on pyroptosis in septic mice. We observed aggravated pyroptosis in CD4+ T cells in CLP mice accompanied by impaired autophagy activity and an overactivated mTOR signaling pathway. Depletion of mTOR relieved autophagy deficiency and reduced the proportion of pyroptotic CD4+ T cells. In T-cell-specific mTOR-knockout mice treated with bafilomycin, the protective effect of mTOR depletion vanished. This indicated that autophagy negatively regulates CD4+ T cell pyroptosis, which is under the control of the mTOR pathway. Taken together, our findings emphasize the importance of pyroptosis in sepsis-induced lymphopenia and reveal the regulatory effects of the mTOR pathway and the role of autophagy in this regulation.

The mechanisms and functions of TGF-ß1 in tendon healing.

Tendon injury accounts for 30% of musculoskeletal diseases and often leads to disability, pain, healthcare cost, and lost productivity. Following injury to tendon, tendon healing proceeds via three overlapping healing processes. However, due to the structural defects of the tendon itself, the tendon healing process is characterized by the formation of excessive fibrotic scar tissue, and injured tendons rarely return to native tendons, which can easily contribute to tendon reinjury. Moreover, the resulting fibrous scar is considered to be a precipitating factor for subsequent degenerative tendinopathy. Despite this, therapies are almost limited because underlying molecular mechanisms during tendon healing are still unknown. Transforming Growth Factor-ß1 (TGF-ß1) is known as one of most potent profibrogenic factors during tendon healing process. However, blockage TGF-ß1 fails to effectively enhance tendon healing. A detailed understanding of real abilities of TGF-ß1 involved in tendon healing can bring promising perspectives for therapeutic value that improve the tendon healing process. Thus, in this review, we describe recent efforts to identify and characterize the roles and mechanisms of TGF-ß1 involved at each stage of the tendon healing and highlight potential roles of TGF-ß1 leading to the fibrotic response to tendon injury.