Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve With Raphe Formation.

BACKGROUND: A better understanding of the molecular mechanism of aortic valve development and bicuspid aortic valve (BAV) formation would significantly improve and optimize the therapeutic strategy for BAV treatment. Over the past decade, the genes involved in aortic valve development and BAV formation have been increasingly recognized. On the other hand, ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family members have been reported to be able to modulate cardiovascular development and diseases. The present study aimed to further investigate the roles of ADAMTS family members in aortic valve development and BAV formation. METHODS: Morpholino-based ADAMTS family gene-targeted screening for zebrafish heart outflow tract phenotypes combined with DNA sequencing in a 304 cohort BAV patient registry study was initially carried out to identify potentially related genes. Both ADAMTS gene-specific fluorescence in situ hybridization assay and genetic tracing experiments were performed to evaluate the expression pattern in the aortic valve. Accordingly, related genetic mouse models (both knockout and knockin) were generated using the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) method to further study the roles of ADAMTS family genes. The lineage-tracing technique was used again to evaluate how the cellular activity of specific progenitor cells was regulated by ADAMTS genes. Bulk RNA sequencing was used to investigate the signaling pathways involved. Inducible pluripotent stem cells derived from both BAV patients and genetic mouse tissue were used to study the molecular mechanism of ADAMTS. Immunohistochemistry was performed to examine the phenotype of cardiac valve anomalies, especially in the extracellular matrix components. RESULTS: ADAMTS genes targeting and phenotype screening in zebrafish and targeted DNA sequencing on a cohort of patients with BAV identified ADAMTS16 (a disintegrin and metalloproteinase with thrombospondin motifs 16) as a BAV-causing gene and found the ADAMTS16 p. H357Q variant in an inherited BAV family. Both in situ hybridization and genetic tracing studies described a unique spatiotemporal pattern of ADAMTS16 expression during aortic valve development. Adamts16+/- and Adamts16+/H355Q mouse models both exhibited a right coronary cusp-noncoronary cusp fusion-type BAV phenotype, with progressive aortic valve thickening associated with raphe formation (fusion of the commissure). Further, ADAMTS16 deficiency in Tie2 lineage cells recapitulated the BAV phenotype. This was confirmed in lineage-tracing mouse models in which Adamts16 deficiency affected endothelial and second heart field cells, not the neural crest cells. Accordingly, the changes were mainly detected in the noncoronary and right coronary leaflets. Bulk RNA sequencing using inducible pluripotent stem cells-derived endothelial cells and genetic mouse embryonic heart tissue unveiled enhanced FAK (focal adhesion kinase) signaling, which was accompanied by elevated fibronectin levels. Both in vitro inducible pluripotent stem cells-derived endothelial cells culture and ex vivo embryonic outflow tract explant studies validated the altered FAK signaling. CONCLUSIONS: Our present study identified a novel BAV-causing ADAMTS16 p. H357Q variant. ADAMTS16 deficiency led to BAV formation.

Social anxiety and loneliness among older adults: a moderated mediation model.

BACKGROUND: Few studies have clarified the mechanisms linking social anxiety and loneliness in older populations. The study aimed to explore how social network mediate the relationship between social anxiety and loneliness in older adults, with perceived social support playing a moderating role. METHODS: A total of 454 older patients completed the Social Avoidance and Distress Scale, Lubben Social Network Scale-6, Chinese version of the Short Loneliness Scale and Perceived Social Support Scale. Bootstrap and simple slope methods were used to test the moderated mediation model. RESULTS: Social anxiety had a significant positive predictive effect on loneliness and social network partially mediated this relationship. The relationship between social anxiety and social network, as well as the relationship between social network and loneliness, was moderated by perceived social support. Specifically, perceived social support buffered the effects of social anxiety on social network, but the buffering effect diminished with increasing levels of social anxiety. On the social network and loneliness pathway, the social network of older persons with higher perceived social support has a stronger prediction of loneliness. CONCLUSIONS: The study found that social anxiety can contribute to loneliness by narrowing older adults' social network. High perceived social support can buffer this process, but do not overstate its protective effects. Thus, interventions to reduce social anxiety and improve social network and social support may help prevent and alleviate loneliness in older adults.

Differential responses of ecosystem stability to climatic and anthropogenic factors in connected and isolated lake basins on the Yangtze River.

Maintaining optimal ecological security in the Yangtze River-connected and isolated lake basins is of great significance to national projects involving Yangtze River protection. Ecosystem stability and associated factors are important components of ecological security in these basins. However, few studies have focused on ecosystem stability and its driving factors over long periods in the Yangtze River Basin. In this study, a remote sensing index was used to analyze the spatiotemporal variation in the ecosystem stability of the Dongting Lake Basin (DTL), Poyang Lake Basin (PYL), and the isolated Chaohu Lake Basin (CHL) and Taihu Lake Basin (THL) in the Yangtze River over the period 2000-2022 to determine the potential affecting factors. The results showed fluctuations in the ecosystem stability of the DTL and PYL, while a V-shape was observed for the CHL and THL during the same period; the closer to the lake, the weaker the stability of the ecosystem, especially in the DTL and PYL. Moreover, the ecosystem stability was greater in the DTL and PYL than in the CHL and THL. The spillover effect of anthropogenic activities on the ecosystem stability of the four basins and the direct effect of temperature have the greatest effect on the ecosystem stability. Specifically, the ecosystem stability index for the area around the DTL and PYL decreased with increasing human interference, whereas the opposite was observed in the CHL and THL. The effect of temperature was negative for the ecosystem stability of DTL and PYL and significantly positive for CHL and THL, at a level of 0.01 %. The findings of this study provide significant information for targeted ecological restoration of the Yangtze River Basin.

Low-carbon emitting university campus achieved via anaerobic digestion of canteen food wastes.

University campuses of China accommodate over 30 million students and consume a large amount of fossil fuel energy, leading to high carbon emission. Implementation of bioenergy (e.g. biomethane) is one of promising ways to mitigate emission and foster low-carbon emitting campus. Biomethane potential from anaerobic digestion (AD) of food waste (FW) in 2344 universities of 353 cities of mainland China have been estimated herein. Results have shown that 1.74 million tons of FW are discharged from campus canteens annually, that can generate 195.8 million m3 biomethane and reduce 0.77 million ton CO2-eq. Wuhan, Zhengzhou, and Guangzhou are the top three cities having the most biomethane potential from campus FW, accounting up to 8.92, 7.89, and 7.28 million m3 year-1, respectively. Technical challenges and solutions have been summarized and discussed such as FW purity, accumulation of ammonia and fatty acid, foaming, and plant site selection. Low-carbon campuses are supposed to be achieved by using bioenergy, like biomethane, in appropriate ways after resolving technical and management challenges.

Psychometric Properties of the Chinese Warwick-Edinburgh Mental Well-being Scale in Medical Staff: Cross-sectional Study.

BACKGROUND: Worldwide, mental well-being is a critical issue for public health, especially among medical staff; it affects professionalism, efficiency, quality of care delivery, and overall quality of life. Nevertheless, assessing mental well-being is a complex problem. OBJECTIVE: This study aimed to evaluate the psychometric properties of the Chinese-language version of the 14-item Warwick-Edinburgh Mental Well-being Scale (WEMWBS) in medical staff recruited mainly from 6 hospitals in China and provide a reliable measurement of positive mental well-being. METHODS: A cross-sectional online survey was conducted of medical staff from 15 provinces in China from May 15 to July 15, 2020. Confirmatory factor analysis (CFA) was conducted to test the structure of the Chinese WEMWBS. The Spearman correlations of the Chinese WEMWBS with the 5-item World Health Organization Well-Being Index (WHO-5) were used to evaluate convergent validity. The Cronbach α and split-half reliability (λ) represented internal consistency. A graded response model was adopted for an item response theory (IRT) analysis. We report discrimination, difficulty, item characteristic curves (ICCs), and item information curves (IICs). ICCs and IICs were used to estimate reliability and validity based on the IRT analysis. RESULTS: A total of 572 participants from 15 provinces in China finished the Chinese WEMWBS. The CFA showed that the 1D model was satisfactory and internal consistency reliability was excellent, with α=.965 and λ=0.947, while the item-scale correlation coefficients ranged from r=0.727 to r=0.900. The correlation coefficient between the Chinese WEMWBS and the WHO-5 was significant, at r=0.746. The average variance extraction value was 0.656, and the composite reliability value was 0.964, with good aggregation validity. The discrimination of the Chinese WEMWBS items ranged from 2.026 to 5.098. The ICCs illustrated that the orders of the category thresholds for the 14 items were satisfactory. CONCLUSIONS: The Chinese WEMWBS showed good psychometric properties and can measure well-being in medical staff.

LncRNA LncHrt preserves cardiac metabolic homeostasis and heart function by modulating the LKB1-AMPK signaling pathway.

Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling of the ischemic heart. Because little is known about the involvement of long non-coding RNAs (lncRNAs) in regulating cardiac metabolism, we used unbiased transcriptome profiling in a mouse model of myocardial infarction (MI). We identified a novel cardiomyocyte-enriched lncRNA, called LncHrt, which regulates metabolism and the pathophysiological processes that lead to heart failure. AAV-based LncHrt overexpression protects the heart from MI as demonstrated by improved contractile function, preserved metabolic homeostasis, and attenuated maladaptive remodeling responses. RNA-pull down followed by mass spectrometry and RNA immunoprecipitation (RIP) identified SIRT2 as a LncHrt-interacting protein involved in cardiac metabolic regulation. Mechanistically, we established that LncHrt interacts with SIRT2 to preserve SIRT2 deacetylase activity by interfering with the CDK5 and SIRT2 interaction. This increases downstream LKB1-AMPK kinase signaling, which ameliorates functional and metabolic deficits. Importantly, we found the expression of the human homolog of mouse LncHrt was decreased in patients with dilated cardiomyopathy. Together, these studies identify LncHrt as a cardiac metabolic regulator that plays an essential role in preserving heart function by regulating downstream metabolic signaling pathways. Consequently, LncHrt is a potentially novel RNA-based therapeutic target for ischemic heart disease.

The characteristics of ginsenosides and oligosaccharides in mountain- and garden-cultivated ginseng.

BACKGROUND: The present study aimed to explore the chemical characteristics of mountainous forest cultivated ginseng (MFCG) and garden ginseng (GG) with respect to their ginsenosides and oligosaccharides. METHODS: A high-performance liquid chromatography with diode-array detection-evaporative light-scattering detection technique was adopted to investigate the ginseosides and oligosaccharides of GG and MFCG. RESULTS: The features of ginsenosides showed Rg1/Re in different parts of GG and MFCG: main root > lateral root > fibrous root, as well as Rg1/Re in the main root: MFCG > GG, indicating that the Rg1/Re is related to age of the ginseng. In most cases, Rg1/Re < 1 in entire GG and Rg1/Re > 1 in entire MFCG. In addition, the ratio of protopanaxadiol/protopanaxatriol in main root of GG is approximately 1 and, in the main roots of MFCG, the ratio is approximately 2 and, furthermore, Ro/Rb1 of MFCG is lower than that of GG. Analysis of oligosaccharides showed that GG mainly contained sucrose and MFCG mainly contained sucrose and maltose, and the ratio of sucrose to maltose was at least more than 4:1 in GG and less than 4:1 in MFCG in most cases, indicating the characteristics of oligosaccharides of MFCG are primarily affected by its growing environment. The results also showed that ginsenoside Re is most probably the biosynthetic precursor of ginsenoside Rg1 (i.e. Re was synthesized first and then transformed to Rg1 in vivo). CONCLUSION: The characteristics of Rg1/Re and higher maltose can be regarded as one of the characteristics of high quality MFCG, and these characteristics are related to a higher age and the cultivation environment of ginseng. The formation mechanism of these characteristics for GG and MFGG is also discussed. As far as we know, the present study is the first to determine the difference of Rg1/Re and oligosaccharides between MFCG and GG and this provides a reference for the quality control criterion of GG and MFCG. © 2020 Society of Chemical Industry.

Electron leak from NDUFA13 within mitochondrial complex I attenuates ischemia-reperfusion injury via dimerized STAT3.

The causative relationship between specific mitochondrial molecular structure and reactive oxygen species (ROS) generation has attracted much attention. NDUFA13 is a newly identified accessory subunit of mitochondria complex I with a unique molecular structure and a location that is very close to the subunits of complex I of low electrochemical potentials. It has been reported that down-regulated NDUFA13 rendered tumor cells more resistant to apoptosis. Thus, this molecule might provide an ideal opportunity for us to investigate the profile of ROS generation and its role in cell protection against apoptosis. In the present study, we generated cardiac-specific tamoxifen-inducible NDUFA13 knockout mice and demonstrated that cardiac-specific heterozygous knockout (cHet) mice exhibited normal cardiac morphology and function in the basal state but were more resistant to apoptosis when exposed to ischemia-reperfusion (I/R) injury. cHet mice showed a preserved capacity of oxygen consumption rate by complex I and II, which can match the oxygen consumption driven by electron donors of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD)+ascorbate. Interestingly, at basal state, cHet mice exhibited a higher H2O2 level in the cytosol, but not in the mitochondria. Importantly, increased H2O2 served as a second messenger and led to the STAT3 dimerization and, hence, activation of antiapoptotic signaling, which eventually significantly suppressed the superoxide burst and decreased the infarct size during the I/R process in cHet mice.

Poria ameliorates the side effects of rhubarb in pair treatment.

To investigate the effect of Poria and effective constituents on gastrointestinal injury animals in the area of the side effects which caused by Rhubarb. Mice were administered i.g. with Rhubarb until the induction of diarrhea followed by gastrointestinal injury. The gastrointestinal injured mice were treated with high, medium and low doses of poria water extract and it's subfractions for 5 days. All indexes were determined to evaluate the action of poria in the pair treatment. The results showed that the higher dose of poria water decoction was discovered to be the most effective dose to treat gastrointestinal injury induced by rhubarb. Body weight, thymus and spleen indexes, the small intestinal propulsion rate and D-xylose absorption in mice with diarrhea and intestinal injury were analyzed to reveal the significant difference with the model group (P<0.01). EAF (Ethyl Acetate Fraction), PEF (Petroleum Ether Fraction) and CPF (Crude Polysaccharide Fraction) not only increase the levels of AMS, GAS and VIP significantly but also ameliorate diarrhea and intestinal injury situation compared with the model group (P<0.01). EAF, PEF and CPF were the most effective components to alleviate diarrhea and gastrointestinal injury induced by rhubarb.

TNFR2 Stimulation Promotes Mitochondrial Fusion via Stat3- and NF-kB-Dependent Activation of OPA1 Expression.

RATIONALE: Mitochondria are important cellular organelles and play essential roles in maintaining cell structure and function. Emerging evidence indicates that in addition to having proinflammatory and proapoptotic effects, TNFα (tumor necrosis factor α) can, under certain circumstances, promote improvements in mitochondrial integrity and function, phenomena that can be ascribed to the existence of TNFR2 (TNFα receptor 2). OBJECTIVE: The present study aimed to investigate whether and how TNFR2 activation mediates the effects of TNFα on mitochondria. METHODS AND RESULTS: Freshly isolated neonatal mouse cardiac myocytes treated with shRNA targeting TNFR1 were used to study the effects of TNFR2 activation on mitochondrial function. Neonatal mouse cardiac myocytes exhibited increases in mitochondrial fusion, a change that was associated with increases in mitochondrial membrane potential, intracellular ATP levels, and oxygen consumption capacity. Importantly, TNFR2 activation-induced increases in OPA1 (optic atrophy 1) protein expression were responsible for the above enhancements, and these changes could be attenuated using siRNA targeting OPA1. Moreover, both Stat3 and RelA bound to the promoter region of OPA1 and their interactions synergistically upregulated OPA1 expression at the transcriptional level. Stat3 acetylation at lysine 370 or lysine 383 played a key role in the ability of Stat3 to form a supercomplex with RelA. Meanwhile, p300 modulated Stat3 acetylation in HEK293T (human embryonic kidney 293T) cells, and p300-mediated Stat3/RelA interactions played an indispensable role in OPA1 upregulation. Finally, TNFR2 activation exerted beneficial effects on OPA1 expression in an in vivo transverse aortic constriction model, whereby TNFR1-knockout mice exhibited better outcomes than in mice with both TNFR1 and TNFR2 knocked out. CONCLUSIONS: TNFR2 activation protects cardiac myocytes against stress by upregulating OPA1 expression. This process was facilitated by p300-mediated Stat3 acetylation and Stat3/RelA interactions, leading to improvements in mitochondrial morphology and function.

Nicotine Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells.

OBJECTIVE: Cigarette smoking is an independent risk factor for atherosclerosis. Nicotine, the addictive component of cigarettes, induces mast cell (MC) release and contributes to atherogenesis. The purpose of this study was to determine whether nicotine accelerates atherosclerosis through MC-mediated mechanisms and whether MC stabilizer prevents this pathological process. APPROACH AND RESULTS: Nicotine administration increased the size of atherosclerotic lesions in apolipoprotein E-deficient (Apoe-/-) mice fed a fat-enriched diet. This was accompanied by enhanced intraplaque macrophage content and lipid deposition but reduced collagen and smooth muscle cell contents. MC deficiency in Apoe-/- mice (Apoe-/-KitW-sh/W-sh) diminished nicotine-induced atherosclerosis. Nicotine activated bone marrow-derived MCs in vitro, which was inhibited by a MC stabilizer disodium cromoglycate or a nonselective nicotinic acetylcholine receptor blocker mecamylamine. Further investigation revealed that α7 nicotinic acetylcholine receptor was a target for nicotine activation in MCs. Nicotine did not change atherosclerotic lesion size of Apoe-/-KitW-sh/W-sh mice reconstituted with MCs from Apoe-/-α7nAChR-/- animals. CONCLUSIONS: Activation of α7 nicotinic acetylcholine receptor on MCs is a mechanism by which nicotine enhances atherosclerosis.

The reliability and validity of Chinese version of SF36 v2 in aging patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF), a major public health problem worldwide, seriously limits health-related quality of life (HRQOL). How to evaluate HRQOL in older patients with CHF remains a problem. AIM: To evaluate the reliability and validity of the Chinese version of the Medical Outcomes Study Short Form version 2 (SF-36v2) in CHF patients. METHODS: From September 2012 to June 2014, we assessed QOL using the SF-36v2 in 171 aging participants with CHF in four cardiology departments. Convergent and discriminant validity, factorial validity, sensitivity among different NYHA classes and between different age groups, and reliability were determined using standard measurement methods. RESULTS: A total of 150 participants completed a structured questionnaire including general information and the Chinese SF-36v2; 132 questionnaires were considered valid, while 21 patients refused to take part. 25 of the 50 participants invited to complete the 2-week test-retest questionnaires returned completed questionnaires. The internal consistency reliability (Cronbach's α) of the total SF-36v2 was 0.92 (range 0.74-0.93). All hypothesized item-subscale correlations showed satisfactory convergent and discriminant validity. Sensitivity was measured in different NYHA classes and age groups. Comparison of different NYHA classes showed statistical significance, but there was no significant difference between age groups. DISCUSSION: We confirmed the SF-36v2 as a valid instrument for evaluating HRQOL Chinese CHF patients. Both reliability and validity were strongly satisfactory, but there was divergence in understanding subscales such as "social functioning" because of differing cultural background. CONCLUSIONS: The reliability, validity, and sensitivity of SF-36v2 in aging patients with CHF were acceptable.

Iron deficiency anemia: a critical review on iron absorption, supplementation and its influence on gut microbiota.

Iron deficiency anemia (IDA) caused by micronutrient iron deficiency has attracted global attention due to its adverse health effects. The regulation of iron uptake and metabolism is finely controlled by various transporters and hormones in the body. Dietary iron intake and regulation are essential in maintaining human health and iron requirements. The review aims to investigate literature concerning dietary iron intake and systemic regulation. Besides, recent IDA treatment and dietary iron supplementation are discussed. Considering the importance of the gut microbiome, the interaction between bacteria and micronutrient iron in the gut is also a focus of this review. The iron absorption efficiency varies considerably according to iron type and dietary factors. Iron fortification remains the cost-effective strategy, although challenges exist in developing suitable iron fortificants and food vehicles regarding bioavailability and acceptability. Iron deficiency may alter the microbiome structure and promote the growth of pathogenic bacteria in the gut, affecting immune balance and human health.

Copper-loaded Milk-Protein Derived Microgel Preserves Cardiac Metabolic Homeostasis After Myocardial Infarction.

Myocardial Infarction (MI) is a leading cause of death worldwide. Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling after MI. However, whether material-derived cues can treat MI through metabolic regulation is mainly unexplored. Herein, a Cu2+ loaded casein microgel (CuCMG) aiming to rescue the pathological intramyocardial metabolism for MI amelioration is developed. Cu2+ is an important ion factor involved in metabolic pathways, and intracardiac copper drain is observed after MI. It is thus speculated that intramyocardial supplementation of Cu2+ can rescue myocardial metabolism. Casein, a milk-derived protein, is screened out as Cu2+ carrier through molecular-docking based on Cu2+ loading capacity and accessibility. CuCMGs notably attenuate MI-induced cardiac dysfunction and maladaptive remodeling, accompanied by increased angiogenesis. The results from unbiased transcriptome profiling and oxidative phosphorylation analyses support the hypothesis that CuCMG prominently rescued the metabolic homeostasis of myocardium after MI. These findings enhance the understanding of the design and application of metabolic-modulating biomaterials for ischemic cardiomyopathy therapy.

[Research progress on the effect of mitochondrial network remodeling on macrophages].

Remodeling of the mitochondrial network is an important process in the maintenance of cellular homeostasis and is closely related to mitochondrial function. Interactions between the biogenesis of new mitochondria and the clearance of damaged mitochondria (mitophagy) is an important manifestation of mitochondrial network remodeling. Mitochondrial fission and fusion act as a bridge between biogenesis and mitophagy. In recent years, the importance of these processes has been described in a variety of tissues and cell types and under a variety of conditions. For example, robust remodeling of the mitochondrial network has been reported during the polarization and effector function of macrophages. Previous studies have also revealed the important role of mitochondrial morphological structure and metabolic changes in regulating the function of macrophages. Therefore, the processes that regulate remodeling of the mitochondrial network also play a crucial role in the immune response of macrophages. In this paper, we focus on the molecular mechanisms of mitochondrial regeneration, fission, fusion, and mitophagy in the process of mitochondrial network remodeling, and integrate these mechanisms to investigate their biological roles in macrophage polarization, inflammasome activation, and efferocytosis.

ZiBuPiYin recipe ameliorates diabetes-associated cognitive decline by improving neuronal mitochondrial function in chronic psychologically stressed zucker diabetic fatty rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Zibu Piyin Recipe (ZBPYR) is a traditional Chinese medicine compound composed of 12 kinds of Chinese herbal medicines including red ginseng and yam. Long-term basic and clinical applications have proved that ZBPYR can prevent and treat cognitive dysfunction. Previous studies showed that chronic psychological stress can increase the risk of type 2 diabetes mellitus (T2DM), and lead to cognitive decline. Mitochondrial dysfunction plays a key role in chronic psychological stress-induced diabetes mellitus. While the mechanism of mitochondrial dysfunction and insulin resistance in diabetes-associated cognitive decline (DACD) is unclear. AIM OF THE STUDY: Our previous research found that a ZiBuPiYin recipe (ZBPYR) has significant pharmacological effects against DACD. The present study investigated changes in mitochondrial dysfunction in the brain and the mechanism of insulin resistance and mitochondrial damage to explore the relationship between neuronal mitochondrial dysfunction and insulin resistance in chronic psychologically stressed DACD rats. MATERIALS AND METHODS: Zucker diabetic fatty (ZDF) rats with spontaneous T2DM and rats with diabetic cognitive impairment that was induced by chronic psychological stress were used in in vivo experiments. PC12 cells that were damaged by rotenone were used for the in vitro experiment. RESULTS: The findings indicated that the number of mitochondria decreased, morphology and membrane potential were damaged, and reactive oxygen species increased in the cortex and hippocampus in psychologically stressed DACD rats. Protein kinase Cß2 (PKCß2) activation and insulin resistance were markedly induced by chronic psychological stress, together with decreases in peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial fusion protein 2 (Mfn2). Furthermore, ZBPYR exerted protective effects both in in vivo and in vitro. CONCLUSION: Mitochondrial damage and insulin resistance were observed in the brain in chronic psychologically stressed DACD rats. The ZBPYR significantly improved brain mitochondrial damage and insulin resistance in chronic psychologically stressed DACD rats. These results provide novel insights for the development of ZBPYR as a traditional Chinese medicine for the treatment of chronic psychological stress and DACD.

Exogenous microbial antagonism affects the bioaugmentation of humus formation under different inoculation using Trichoderma reesei and Phanerochaete chrysosporium.

This study was aimed at exploring the effect of antagonism of Trichoderma reesei (T.r) and Phanerochaete chrysosporium (P.c) on humification during fermentation of rice (RS) and canola straw (CS). Results showed that exogeneous fungi accelerated straw degradation and enzyme activities of CMCase, xylanase and LiP. P.c inhibited the activity of LiP when co-existing with T.r beginning, it promoted the degradation of lignin and further increased the production of humus-like substances (HLS) and humic-like acid (HLA) in later fermentation when nutrients were insufficient. The HLS of RTP was 54.9 g/kg RS, higher than the other treatments, and displayed more complex structure and higher thermostability. Brucella and Bacillus were the main HLA bacterial producers. P.c was the HLA fungal producer, while T.r assisted FLA and polyphenol transformation. Therefore, RTP was recommended to advance technologies converting crop straw into humus resources.

Erchen Decoction alleviates obesity-related hepatic steatosis via modulating gut microbiota-drived butyric acid contents and promoting fatty acid ß-oxidation.

ETHNOPHARMACOLOGICAL RELEVANCE: Erchen decoction (ECD) is a traditional Chinese medicine formula comprising six distinct herbs and has been documented to possess a protective effect against obesity. The study conducted previously demonstrated that ECD has the potential to effectively modulate the composition of gut microbiota and levels of short-chain fatty acids (SCFAs) in obese rat. However, the regulatory mechanism of ECD on gut microbiota and SCFAs and further improvement of obesity have not been thoroughly explained. AIM OF THE STUDY: The objective of this study was to examine the therapeutic effect and molecular mechanism of ECD in a rat model of high-fat diet (HFD) feeding. MATERIALS AND METHODS: Rats with HFD-induced obesity were treated with ECD. Upon completion of the study, serum and liver samples were procured to conduct biochemical, pathological, and Western blotting analyses. The investigation of alterations in the gut microbiota subsequent to ECD treatment was conducted through the utilization of 16S rRNA sequencing. The metabolic alterations in the cecal contents were examined through the utilization of mass spectrometry-ultraperformance liquid chromatography. RESULTS: ECD treatment improved lipid metabolic disorders and reduced hepatic steatosis in HFD-induced obese rats. Obese rat treated with ECD showed a higher abundance of SCFA-producing bacteria, including Lactobacillus, Bifidobacterium, and Butyricicoccus, and lower abundance of disease-related bacteria, such as Bacteroides, Parabacteroides, and Sediminibacterium. Additionally, ECD caused an increase in total SCFAs levels; in particular, butyric acid was dramatically increased in the HFD group. Rats treated with ECD also exhibited significantly increased butyric acid concentrations in the serum and liver. The subsequent reduction in histone deacetylase 1 expression and increase in acetyl-histone 3-lysine 9 (H3K9ac) levels contributed to the promotion of fatty acid ß-oxidation (FAO) in liver by ECD. CONCLUSION: This study demonstrates that ECD regulates the gut microbiota and promotes butyric acid production to ameliorate obesity-related hepatic steatosis. The mechanism might be related to the promotion of FAO via a butyric acid-mediated increase in H3K9ac levels in the liver.

Postpartum women's views on human milk banking in a city in Southeast China: a cross-sectional survey.

BACKGROUND: Donor human milk is the best alternative for preterm infants when their mother's own milk is insufficient or unavailable. The development of human milk banks in China started late, and in most of these banks, the amount of donor human milk is insufficient for clinical demand. Moreover, many mothers are reluctant to use donor human milk due to safety concerns. It is important to understand the potential supply and demand of donor human milk before establishing a new human milk bank. This study aimed to understand women's acceptance of human milk banking in Wenzhou, southeastern China. METHODS: A cross-sectional study was conducted in three community health centers in Wenzhou, southeast China, in December 2020. Data were collected from 305 postpartum women selected through convenience sampling. Sociodemographic, perinatal and breastfeeding characteristics, awareness and knowledge of human milk banking and willingness to donate human milk, and to accept donor human milk were assessed. Multivariable logistic regression analysis was used to explore independent predictors of willingness to donate human milk and to accept donor human milk. RESULTS: Only 17% (52/305) of our participants had heard of human milk banking prior to this survey. The prevalence of willingness to donate human milk and use donor human milk in our study was 73.4% (224/305) and 44.6% (136/305), respectively. Employment (adjusted odds ratio [AOR] 2.30; 95% confidence interval [CI] 1.17, 4.50) and human milk banking knowledge (AOR 1.23; 95% CI 1.12, 1.35) were independent predictors of willingness to donate human milk. Monthly household income in the previous year (AOR 2.18; 95% CI 1.17, 4.06), awareness of human milk banking (AOR 2.41; 95% CI 1.24, 4.67) and knowledge of human milk banking (AOR 1.22; 95% CI 1.11, 1.35) were significantly associated with willingness to accept donor human milk. CONCLUSIONS: In our study, awareness of human milk banks among women in the first year postpartum was low. More mothers were willing to donate human milk than to use donor human milk to feed their children. In our study, knowledge of human milk banking was a predictor of both willingness to donate human milk and willingness to use donor human milk. Programs with detailed information on human milk banking are needed to help mothers improve their knowledge and increase acceptance of human milk banking.

Surface-Anchored Nanogel Coating Endows Stem Cells with Stress Resistance and Reparative Potency via Turning Down the Cytokine-Receptor Binding Pathways.

Stem cell-based therapy has great potential in regenerative medicine. However, the survival and engraftment rates of transplanted stem cells in disease regions are poor and limit the effectiveness of cell therapy due to the fragility of stem cells. Here, an approach involving a single-cell coating of surface-anchored nanogel to regulate stem cell fate with anti-apoptosis capacity in the hypoxic and ischemic environment of infarcted hearts is developed for the first time. A polysialic acid-based system is used to anchor microbial transglutaminase to the external surface of the cell membrane, where it catalyzes the crosslinking of gelatin. The single-cell coating with surface-anchored nanogel endows mesenchymal stem cells (MSCs) with stress resistance by blocking the activity of apoptotic cytokines including the binding of tumor necrosis factor α (TNFα) to tumor necrosis factor receptor, which in turn maintains mitochondrial integrity, function and protects MSCs from TNFα-induces apoptosis. The administration of surface engineered MSCs to hearts results in significant improvements in engraftment, cardiac function, infarct size, and vascularity compared with using uncoated MSCs in treating myocardial infarction. The surface-anchored, biocompatible cell surface engineering with nanogel armor provides a new way to produce robust therapeutic stem cells and may explore immense potentials in cell-based therapy.