Cyanidin-3-O-Glucoside Alleviates Alcoholic Liver Injury via Modulating Gut Microbiota and Metabolites in Mice.

Alcoholic liver disease (ALD) is primarily caused by long-term excessive alcohol consumption. Cyanidin-3-O-glucoside (C3G) is a widely occurring natural anthocyanin with multiple biological activities. This study aims to investigate the effects of C3G isolated from black rice on ALD and explore the potential mechanism. C57BL/6J mice (male) were fed with standard diet (CON) and Lieber-DeCarli liquid-fed (Eth) or supplemented with a 100 mg/kg/d C3G Diet (Eth-C3G), respectively. Our results showed that C3G could effectively ameliorate the pathological structure and liver function, and also inhibited the accumulation of liver lipids. C3G supplementation could partially alleviate the injury of intestinal barrier in the alcohol-induced mice. C3G supplementation could increase the abundance of Norank_f_Muribaculaceae, meanwhile, the abundances of Bacteroides, Blautia, Collinsella, Escherichia-Shigella, Enterococcus, Prevotella, [Ruminococcus]_gnavus_group, Methylobacterium-Methylorubrum, Romboutsia, Streptococcus, Bilophila, were decreased. Spearman's correlation analysis showed that 12 distinct genera were correlated with blood lipid levels. Non-targeted metabolic analyses of cecal contents showed that C3G supplementation could affect the composition of intestinal metabolites, particularly bile acids. In conclusion, C3G can attenuate alcohol-induced liver injury by modulating the gut microbiota and metabolites, suggesting its potential as a functional food ingredient against alcoholic liver disease.

Identification of bZIP Transcription Factors That Regulate the Development of Leaf Epidermal Cells in Arabidopsis thaliana by Single-Cell RNA Sequencing.

Epidermal cells are the main avenue for signal and material exchange between plants and the environment. Leaf epidermal cells primarily include pavement cells, guard cells, and trichome cells. The development and distribution of different epidermal cells are tightly regulated by a complex transcriptional regulatory network mediated by phytohormones, including jasmonic acid, and transcription factors. How the fate of leaf epidermal cells is determined, however, is still largely unknown due to the diversity of cell types and the complexity of their regulation. Here, we characterized the transcriptional profiles of epidermal cells in 3-day-old true leaves of Arabidopsis thaliana using single-cell RNA sequencing. We identified two genes encoding BASIC LEUCINE-ZIPPER (bZIP) transcription factors, namely bZIP25 and bZIP53, which are highly expressed in pavement cells and early-stage meristemoid cells. Densities of pavement cells and trichome cells were found to increase and decrease, respectively, in bzip25 and bzip53 mutants, compared with wild-type plants. This trend was more pronounced in the presence of jasmonic acid, suggesting that these transcription factors regulate the development of trichome cells and pavement cells in response to jasmonic acid.

Whole grain germinated brown rice intake modulates the gut microbiota and alleviates hypertriglyceridemia and hypercholesterolemia in high fat diet-fed mice.

Hyperlipidemia is a common clinical disorder of lipid metabolism in modern society and is considered to be one of the major risk factors leading to cardiovascular-related diseases. Germinated brown rice (GBR) is a typical whole grain food. The lipid-lowering effect of GBR has received increasing attention, but its mechanism of action is not fully understood. The gut microbiota has been proposed as a novel target for the treatment of hyperlipidemia. The aim of this study was to investigate the effects of GBR on the gut microbiota and lipid metabolism in high-fat diet (HFD)-fed C57BL/6J mice. The effect of GBR on hyperlipidemia was evaluated by measuring blood lipid levels and by pathological examination. The gut microbiota was detected by 16S rRNA sequencing, and the protein and mRNA expression levels involved in cholesterol metabolism were detected by western blotting and RT-qPCR to find potential correlations. The results showed that GBR supplementation could effectively reduce the levels of TC, TG, LDL-C and HDL-C in the serum and alleviate the excessive accumulation of fat droplets caused by HFD. Moreover, GBR intervention improved HFD-fed gut microbiota disorder via increasing the diversity of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio, and improving gut barrier damage. In addition, GBR could inhibit endogenous cholesterol synthesis and promote cholesterol transport and excretion. These findings suggest that GBR may be a competitive candidate for the development of functional foods to prevent abnormal lipid metabolism.

Optogenetic Neuromodulation in Inflammatory Pain.

Inflammatory pain is one of the most prevalent forms of pain and negatively influences the quality of life. Neuromodulation has been an expanding field of pain medicine and is accepted by patients who have failed to respond to several conservative treatments. Despite its effectiveness, neuromodulation still lacks clinically robust evidence on inflammatory pain management. Optogenetics, which controls particular neurons or brain circuits with high spatiotemporal accuracy, has recently been an emerging area for inflammatory pain management and studying its mechanism. This review considers the fundamentals of optogenetics, including using opsins, targeting gene expression, and wavelength-specific light delivery techniques. The recent evidence on application and development of optogenetic neuromodulation in inflammatory pain is also summarised. The current limitations and challenges restricting the progression and clinical transformation of optogenetics in pain are addressed. Optogenetic neuromodulation in inflammatory pain has many potential targets, and developing strategies enabling clinical application is a desirable therapeutic approach and outcome.

Targeting gut-liver axis by dietary lignans ameliorate obesity: evidences and mechanisms.

An imbalance between energy consumption and energy expenditure causes obesity. It is characterized by increased adipose accumulation and accompanied by chronic low-grade inflammation. Many studies have suggested that the gut microbiota of the host mediates the relationship between high-fat diet consumption and the development of obesity. Diet and nutrition of the body are heavily influenced by gut microbiota. The alterations in the microbiota in the gut may have effects on the homeostasis of the host's energy levels, systemic inflammation, lipid metabolism, and insulin sensitivity. The liver is an important organ for fat metabolism and gut-liver axis play important role in the fat metabolism. Gut-liver axis is a bidirectional relationship between the gut and its microbiota and the liver. As essential plant components, lignans have been shown to have different biological functions. Accumulating evidences have suggested that lignans may have lipid-lowering properties. Lignans can regulate the level of the gut microbiota and their metabolites in the host, thereby affecting signaling pathways related to fat synthesis and metabolism. These signaling pathways can make a difference in inhibiting fat accumulation, accelerating energy metabolism, affecting appetite, and inhibiting chronic inflammation. It will provide the groundwork for future studies on the lipid-lowering impact of lignans and the creation of functional meals based on those findings.

Dietary Polysaccharides Exert Anti-Fatigue Functions via the Gut-Muscle Axis: Advances and Prospectives.

Due to today's fast-paced lifestyle, most people are in a state of sub-health and face "unexplained fatigue", which can seriously affect their health, work efficiency, and quality of life. Fatigue is also a common symptom of several serious diseases such as Parkinson's, Alzheimer's, cancer, etc. However, the contributing mechanisms are not clear, and there are currently no official recommendations for the treatment of fatigue. Some dietary polysaccharides are often used as health care supplements; these have been reported to have specific anti-fatigue effects, with minor side effects and rich pharmacological activities. Dietary polysaccharides can be activated during food processing or during gastrointestinal transit, exerting unique effects. This review aims to comprehensively summarize and evaluate the latest advances in the biological processes of exercise-induced fatigue, to understand dietary polysaccharides and their possible molecular mechanisms in alleviating exercise-induced fatigue, and to systematically elaborate the roles of gut microbiota and the gut-muscle axis in this process. From the perspective of the gut-muscle axis, investigating the relationship between polysaccharides and fatigue will enhance our understanding of fatigue and may lead to a significant breakthrough regarding the molecular mechanism of fatigue. This paper will provide new perspectives for further research into the use of polysaccharides in food science and food nutrition, which could help develop potential anti-fatigue agents and open up novel therapies for sub-health conditions.

A randomized controlled trial examining a Tranquil sitting intervention compatible with Confucian values.

Introduction: During the COVID-19 pandemic in China, the silent management (Lockdown) policy has caused severe sleep problems for university students. Long-term isolation may further deteriorate sleep quality, and it requires practical interventions. Today in mental and sleep health, interventions based on Buddhist, Taoist and Confucian ethics have been proven effective in reducing cognition and sleep disorders. However, such interventions also have limitations. They tend to focus on peace of mind or some technical means with the main direction of symptom improvement but neglect the mundane activities of daily life. Methods: We conducted an innovative tranquil sitting intervention program based on the Chinese Confucian value of the "tranquility and reverence" method, integrating various intervention techniques traditionally recognized as effective for achieving more lasting mental health and sleep quality. This study aims to assess the effectiveness and feasibility of a tranquil sitting intervention in improving sleep problems in isolated university students. Using a randomized control trial (RCT), the participants in the intervention program (n = 35) practiced the tranquil sitting intervention program for ten weeks. They had their PSQI scores measured at the pre-experimental, post-test, and 1-month follow-up time points and compared to the control group (n = 35). Results: The participants who received the tranquil sitting intervention had significantly better sleep quality than the control group, with moderate to large effect sizes in the middle and late stages. The instructor may challenge the intervention group at the beginning of the tranquil sitting technique. However, the improvement in sleep quality was significant after fully mastering the method. Discussion: The intervention program in this study emphasized the importance of "tranquility" and showed the same sleep improvement as in other traditional interventions. In conclusion, this intervention is a feasible and promising new approach to improving sleep quality among youths.

FLS2-RBOHD module regulates changes in the metabolome of Arabidopsis in response to abiotic stress.

Through crosstalk, FLAGELLIN SENSITIVE 2 (FLS2) and RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) are involved in regulating the homeostasis of cellular reactive oxygen species (ROS) and are linked to the metabolic response of plants toward both biotic and abiotic stress. In the present study, we examined the metabolome of Arabidopsis seedlings under drought and salt conditions to better understand the potential role of FLS2 and RBOHD-dependent signaling in the regulation of abiotic stress response. We identified common metabolites and genes that are regulated by FLS2 and RBOHD, and are involved in the response to drought and salt stress. Under drought conditions, D-aspartic acid and the expression of associated genes, such as ASPARAGINE SYNTHASE 2 (ASN2), increased in both fls2 and robed/f double mutants. The accumulation of amino acids, carbohydrates, and hormones, such as L-proline, D-ribose, and indoleacetaldehyde increased in both fls2 and rbohd/f double mutants under salt conditions, as did the expression of related genes, such as PROLINE IMINOPEPTIDASE, PHOSPHORIBOSYL PYROPHOSPHATE SYNTHASE 5, and NITRILASE 3. Collectively, these results indicate that the FLS2-RBOHD module regulates plant response to drought and salt stress through ROS signaling by adjusting the accumulation of metabolites and expression of genes related to metabolite synthesis.

Targeting gut-brain axis by dietary flavonoids ameliorate aging-related cognition decline: Evidences and mechanisms.

Aging-related cognitive impairment, mainly Alzheimer's disease (AD), has been widely studied. However, effective prevention and treatment methods are still lacking. In recent years, researchers have observed beneficial effects of plant-based supplements, such as flavonoids, on cognitive protection. This provides a new clue for the prevention of cognitive dysfunction. Studies have shown that dietary flavonoids have neuroprotective effects, but the mechanism is not clear. In this review, we systematically reviewed the research progress on the effects of dietary flavonoids on gut microbes and their metabolites, and concluded that flavonoids could improve cognitive function through the gut-brain axis. Flavonoids can be absorbed through the intestine, cross the blood-brain barrier, and enter the brain tissue. Flavonoids can inhibit the expression and secretion of inflammatory factors in brain tissue, reduce the damage caused by oxidative stress, clear neural damage proteins and inhibit neuronal apoptosis, thereby ameliorating age-related cognitive disorders. Future work will continue to explore the gut-brain axis and target genes regulated by flavonoids. In addition, clinical research and its mechanisms need to be further explored to provide solutions or advise for patients with cognitive impairment.

A near-infrared and lysosome-targeted BODIPY photosensitizer for photodynamic and photothermal synergistic therapy.

Phototherapy is a promising approach for the treatment of cancers and other diseases. So far, many photosensitizers have been developed for photodynamic therapy (PDT) or photothermal therapy (PTT). However, it remains a challenge to develop a system for synergistic PDT and PTT with specific targeting and real-time fluorescence tracking. Herein, we designed a multifunctional BODIPY derivative, Lyso-BDP, for synergistic PDT and PTT against tumors. Lyso-BDP was composed of three parts: (1) the BODIPY fluorophore was selected as a theranostic core, (2) a morpholine group modified on meso-BODIPY served as a lysosome-targeting unit for enhancing the antitumor effect, and (3) N,N-diethyl-4-vinylaniline was attached to the BODIPY core to extend its wavelength to the near-infrared region. Finally, Lyso-BDP shows near-infrared absorption and emission, photosensitizing activity, lysosomal targeting, and synergistic PDT and PTT effects, and effectively kills cancer cells both in vitro and in vivo. Therefore, our study demonstrates that Lyso-BDP can serve as a promising photosensitizer in the therapy of cancer with potential clinical application prospects.

Association between estimated pulse wave velocity and silent lacunar infarct in a Korean population.

Aims: Previous studies have proposed the estimated pulse wave velocity (ePWV) as a simple and cost-effective measure of arterial stiffness. Since arterial stiffness plays a role in the progression of silent lacunar infarct (SLI), our present work aims to evaluate the association between ePWV and the presence of SLI. Methods: The present work was based on a cross-section study. Our study included 1,011 neurologically healthy Korean participants. The SLI was evaluated using brain magnetic resonance images (MRI). The ePWV was derived from a published equation using age and mean blood pressure (MBP). Logistic regression analyses were performed to investigate the association between ePWV and SLI. The linear relationship and robustness were evaluated using smooth curve fitting and subgroup analyses, respectively. Results: The prevalence of SLI was 11.87%. After fully adjusting for covariates, per 1 m/s increase of ePWV casted 31% additional risk for SLI (P = 0.009). When dividing the ePWV into quartiles, the top quartile had 4.01 times risk compared with the bottom quartile. The increasing trend across the quartiles was statistically significant (P for trend < 0.001). Consistently, smooth curve fitting revealed that the risk of SLI elevated linearly with the increase of ePWV. Finally, subgroup analysis suggested that the association was robust in several sub-populations divided by age, sex, smoking, hypertension, diabetes mellitus (DM), coronary artery occlusive disease (CAOD), hyperlipidemia, and statin medication (all P for interaction > 0.05). Conclusion: The current study revealed an independent and positive association between ePWV and the presence of SLI in a neurologically healthy Korean population.

Polysaccharides from Phellinus linteus: A systematic review of their extractions, purifications, structures and functions.

Phellinus linteus (P. linteus) is a famous Chinese medicine and has a long history in China. In recent years, P. linteus polysaccharides (PLPs) have attracted extensive attention because of their biological activities such as anti-bacteria, anti-aging, anti-oxidation, anti-inflammation, anti-tumor, hepatoprotective effect and hypoglycemic effect. In this review, we systemically summarized the advances in extractions, purifications and structural characterizations of PLPs, and also analyzed their biological functions and molecular mechanisms. Meanwhile, the structure-activity relationships of PLPs are closely related to their anti-oxidation and anti-tumor activities. So far, the applications of PLPs are still very limited, further exploring structure-activity relationships, biological functions and their mechanisms of PLPs will promote to develop functional foods.

HSP90ß promotes osteoclastogenesis by dual-activation of cholesterol synthesis and NF-κB signaling.

Heat shock protein 90ß (Hsp90ß, encoded by Hsp90ab1 gene) is the most abundant proteins in the cells and contributes to variety of biological processes including metabolism, cell growth and neural functions. However, genetic evidences showing Hsp90ß in vivo functions using tissue specific knockout mice are still lacking. Here, we showed that Hsp90ß exerted paralogue-specific role in osteoclastogenesis. Using myeloid-specific Hsp90ab1 knockout mice, we provided the first genetic evidence showing the in vivo function of Hsp90ß. Hsp90ß binds to Ikkß and reduces its ubiquitylation and proteasomal degradation, thus leading to activated NF-κB signaling. Meanwhile, Hsp90ß increases cholesterol biosynthesis by activating Srebp2. Both pathways promote osteoclastogenic genes expression. Genetic deletion of Hsp90ab1 in osteoclast or pharmacological inhibition of Hsp90ß alleviates bone loss in ovariectomy-induced mice. Therefore, Hsp90ß is a promising druggable target for the treatment of osteoporosis.

Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor.

In response to stressful events, the hypothalamic-pituitary-adrenal (HPA) axis is activated, and consequently glucocorticoids are released by the adrenal gland into the blood circulation. A large body of research has illustrated that excessive glucocorticoids in the hippocampus exerts negative feedback regulation of the HPA axis through glucocorticoid receptor (GR), which is critical for the homeostasis of the HPA axis. Maternal prenatal stress causes dysfunction of the HPA axis feedback mechanism in their offspring in adulthood. Here we report that telomerase reverse transcriptase (TERT) gene knockout causes hyperactivity of the HPA axis without hippocampal GR deficiency. We found that the level of TERT in the dentate gyrus (DG) of the hippocampus during the developmental stage determines the responses of the HPA axis to stressful events in adulthood through modulating the excitability of the dentate granular cells (DGCs) rather than the expression of GR. Our study also suggests that the prenatal high level of glucocorticoids exposure-induced hypomethylation at Chr13:73764526 in the first exon of mouse Tert gene accounted for TERT deficiency in the DG and HPA axis abnormality in the adult offspring. This study reveals a novel GR-independent mechanism underlying prenatal stress-associated HPA axis impairment, providing a new angle for understanding the mechanisms for maintaining HPA axis homeostasis.

R-I subtype single right coronary artery with congenital absence of left coronary system: A case report.

BACKGROUND: Isolated single coronary artery is a rare congenital anomaly. R-I subtype single coronary artery is even rarer. In this subtype, a very large right coronary artery extends in the coronary sulcus to the anterior base of the heart where it produces the left anterior descending coronary artery. Currently, only a few case reports are available in the literature for this anomaly. CASE SUMMARY: Here, we report the case of a 62-year-old woman who presented to the cardiology clinic with decreased exercise tolerance and poor blood pressure control. The patient underwent coronary angiography (CAG) and emission computed tomography (ECT). CAG images revealed a single gigantic right coronary artery (R-I type) arising from the right coronary sinus with branches supplying the left coronary territory. The ECT results confirmed myocardial ischemia at the location of the absent left coronary artery. The ECT findings confirmed that ischemia was consistent with the vascular loss location in CAG images. In such anomalies, there is a compensatory widening of the coronary artery lumen. Medical treatment was administered, and the patient was discharged. CONCLUSION: Isolated single coronary arteries are associated with ischemia and potentially fatal acute coronary events. Hence, controlling risk factors is critical.

Cotton proteomics: Dissecting the stress response mechanisms in cotton.

The natural environment of plants comprises a complex set of biotic and abiotic stresses, and plant responses to these stresses are complex as well. Plant proteomics approaches have significantly revealed dynamic changes in plant proteome responses to stress and developmental processes. Thus, we reviewed the recent advances in cotton proteomics research under changing environmental conditions, considering the progress and challenging factors. Finally, we highlight how single-cell proteomics is revolutionizing plant research at the proteomics level. We envision that future cotton proteomics research at the single-cell level will provide a more complete understanding of cotton's response to stresses.

PIN1 regulates epidermal cells development under drought and salt stress using single-cell analysis.

Over the course of evolution, plants have developed plasticity to acclimate to environmental stresses such as drought and salt stress. These plant adaptation measures involve the activation of cascades of molecular networks involved in stress perception, signal transduction and the expression of stress related genes. Here, we investigated the role of the plasma membrane-localized transporter of auxin PINFORMED1 (PIN1) in the regulation of pavement cells (PCs) and guard cells (GCs) development under drought and salt stress conditions. The results showed that drought and salt stress treatment affected the development of PCs and GCs. Further analysis identified the different regulation mechanisms of PIN1 in regulating the developmental patterns of PCs and GCs under drought and salt stress conditions. Drought and salt stress also regulated the expression dynamics of PIN1 in pif1/3/4/5 quadruple mutants. Collectively, we revealed that PIN1 plays a crucial role in regulating plant epidermal cells development under drought and salt stress conditions, thus contributing to developmental rebustness and plasticity.

Laminarin ameliorates alcohol-induced liver damage and its molecular mechanism in mice.

Alcoholic liver disease (ALD) has become a health issue globally. Laminarin, a low molecular weight marine-derived ß-glucan, has been identified with multiple biological activities. In this study, the ameliorative effect on ALD of laminarin isolated from brown algae was investigated. Phenotypic, pathological alterations and biochemical characteristics indicated that laminarin administration (100 mg/kg/day) significantly alleviated liver injury and improved liver function in the alcohol-induced mice. Gene chip results indicated that laminarin treatment caused 52 up-regulated and 13 down-regulated genes in the hepatic tissues of alcohol-induced damage mice, and most of these genes are associated with regulation of oxidative stress (such as CYP450/glutathione-dependent antioxidation), Wnt signaling pathway, retinol metabolism, and cAMP pathway based on GO and KEGG analysis. PPI network analysis indicated that the downstream target genes lied in the hub of the net. Our experiments also confirmed the changed expressions of some target genes. Taken together, these results suggest that laminarin can ameliorate alcohol-induced damage in mice and its molecular mechanism lies in modulating anti-oxidation pathway, WNT pathway, and cAMP pathway, which regulate the expressions of downstream target genes and alleviate alcohol-induced damage. Our study provides new clue to prevent alcohol-induced damage and will be benefit to develop functional foods. PRACTICAL APPLICATIONS: This study verified the positive effect on alcoholic liver disease (ALD) of laminarin, a water-soluble brown algae-derived ß-glucan, linked by ß-(1,3) glycosidic bonds with ß-(1,6) branches. Laminarin significantly alleviated liver injury and improved liver function of ALD mice. Moreover, transcriptomics and bioinformatics analysis further revealed the gene expression patterns, hub targets, and signalings including CYP450/glutathione, Wnt, retinol metabolism, cAMP pathways regulated by laminarin. This research is the first evidence for hepatoprotective effect of laminarin against ALD and its molecular mechanism, which will be advantage to develop functional foods or adjuvant therapy of ALD.

Establishment of a PBMC-derived induced pluripotent stem cell (NJUCMi001-A) from a patient with LAMA2-related congenital muscular dystrophy (MDC1A) carrying frameshift deletion c.3367delA in LAMA2 gene.

LAMA2-related congenital muscular dystrophy (MDC1A), the most commonly recognized type of congenital muscular dystrophies, is a severe neonatal onset muscle disease caused by recessive mutations in the LAMA2 gene. Here, we established an induced pluripotent stem cell line from a MDC1A patient carrying a frameshift deletion c.3367delA in LAMA2 gene. The iPSC line expressed pluripotency markers, retained normal karyotype, showed capability of differentiating into three germ layers. The iPSC line will help to further elucidate the pathogenic mechanisms of LAMA2 mutation, and benefit treatment for congenital muscular dystrophies in the future.

Biological functions of active ingredients in quinoa bran: Advance and prospective.

Quinoa is known to be a rich source of nutrients and bioactive components. Quinoa bran, used mainly as animal feed in processing by-products, is also a potential source of bioactive ingredients being conducive to human health. The importance of nutrition and function of quinoa seed has been discussed in many studies, but the bioactive properties of quinoa bran often are overlooked. This review systemically summarized the progress in bioactive components, extraction, and functional investigations of quinoa bran. It suggests that chemically assisted electronic fractionation could be used to extract albumin from quinoa bran. Ultrasound-assisted extraction method is a very useful method for extracting phenolic acids, triterpene saponins, and flavonoids from quinoa bran. Based on in vitro and in vivo studies for biological activities, quinoa bran extract exhibits a wide range of beneficial properties, including anti-oxidant, anti-diabetes, anti-inflammation, anti-bacterial and anti-cancer functions. However, human experiments and action mechanisms need to investigate. Further exploring quinoa bran will promote its applications in functional foods, pharmaceuticals, and poultry feed in the future.