Cilostazol Attenuates Hepatic Steatosis and Intestinal Disorders in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, which begins with liver lipid accumulation and is associated with metabolic syndrome. Also, the name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). We performed focused drug screening and found that Cilostazol effectively ameliorated hepatic steatosis and might offer potential for NAFLD treatment. Our aim was to investigate the therapeutic effects of Cilostazol on the glycolipid metabolism and intestinal flora in NAFLD mice and explore the specific mechanism. In this study, 7-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, and then treated with intragastric administration for 12 weeks. The results showed that Cilostazol inhibited liver lipid de novo synthesis by regulating the AMPK-ACC1/SCD1 pathway and inhibited liver gluconeogenesis by the AMPK-PGC1α-G6P/PEPCK pathway. Cilostazol improved the intestinal flora diversity and intestinal microbial composition in the NAFLD mice, and specifically regulated Desulfovibrio and Akkermansia. In addition, Cilostazol increased the level of short-chain fatty acids in the NAFLD mice to a level similar to that in the blank Control group. Cilostazol reduces liver lipid accumulation in NAFLD mice by improving glucose and lipid metabolism disorders and intestinal dysfunction, thereby achieving the purpose of treating NAFLD.

Comparison of protective effects of nicotinamide mononucleotide and nicotinamide riboside on DNA damage induced by cisplatin in HeLa cells.

Background: Previous studies have shown that the nicotinamide adenine dinucleotide (NAD+) precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), protect against endogenously or exogenously induced DNA damage. However, whether the two compounds have the same or different efficacy against DNA damage is not clear. In the current study, we systematically compared the effects of NMN and NR on cisplatin-induced DNA damage in HeLa cells. Methods: To evaluate the protective effects of NMN or NR, HeLa cells were pretreated with different doses of NMN or NR followed with 10 µM of cisplatin treatment. Cell viability was examined by Trypan blue staining assay. For observing the DNA damage repair process, HeLa cells were treated with 10 µM of cisplatin for 12 h, followed with 10 mM NMN or NR treatment for another 8, 16, 24, or 32 h, DNA damage levels were assessed for each time point by immunofluorescent staining against phosphor-H2AX (γH2AX) and alkaline comet assay. The effects of NMN and NR on intracellular NAD+ and reactive oxygen species (ROS) levels were also determined. Results: NMN and NR treatment alone did not have any significant effects on cell viability, however, both can protect HeLa cells from cisplatin-induced decrease of cell viability with similar efficacy in a dose-dependent manner. On the other hand, while both can reduce the DNA damage levels in cisplatin-treated cells, NR exhibited better protective effect. However, both appeared to boost the DNA damage repair process with similar efficacy. NMN or NR treatment alone could increase cellular NAD+ levels, and both can reverse cisplatin-induced decrease of NAD+ levels. Finally, while neither NMN nor NR affected cellular ROS levels, both inhibited cisplatin-induced increase of ROS with no significant difference between them. Conclusion: NR have a better protective effect against cisplatin-induced DNA damage than NMN.

Heterogeneity of Fish Taxonomic and Functional Diversity Evaluated by eDNA and Gillnet along a Mangrove-Seagrass-Coral Reef Continuum.

The effective and reliable monitoring of fish communities is important for the management and protection of marine ecosystems. Environmental DNA (eDNA) metabarcoding is a relatively new method that has been widely used in recent years, while traditional sampling via fish catching (i.e., gillnets) is one of the most common and reliable fish monitoring methods used to date. We compared the taxonomic and functional diversity of fish detected within a mangrove-seagrass-coral reef continuum using both survey methods. One liter seawater and gillnet samples were collected in August 2021 from mangrove forests, seagrass meadows and coral reef habitats (n = 3 each) in Hainan, China. Surveys using eDNA and gillnets identified 139 genera belonging to 66 families and 58 genera belonging to 42 families, respectively. Regardless of the survey method, fish detected in mangrove, seagrass and coral reef habitats were heterogeneous in their communities; however, the shared species between habitats suggest some degree of connectivity. There were no significant differences between habitats in terms of taxonomic and functional diversity, but a higher taxonomic diversity was detected using eDNA. Both methods were able to distinguish fish assemblages between different habitats; however, gillnet surveys performed better than eDNA surveys for distinguishing mangrove from seagrass assemblages. Therefore, the concurrent use of eDNA and gillnet survey methods provides a more comprehensive approach to understanding the heterogeneity of fish taxonomic and functional diversity along mangrove-seagrass-coral reef continuums.

Assembling nanocelluloses into fibrous materials and their emerging applications.

Nanocelluloses, derived from various plants or specific bacteria, represent the renewable and sophisticated nano building blocks for emerging functional materials. Especially, the assembly of nanocelluloses as fibrous materials can mimic the structural organization of their natural counterparts to integrate various functions, thus holding great promise for potential applications in various fields, such as electrical device, fire retardance, sensing, medical antibiosis, and drug release. Due to the advantages of nanocelluloses, a variety of fibrous materials have been fabricated with the assistance of advanced techniques, and their applications have attracted great interest in the past decade. This review begins with an overview of nanocellulose properties followed by the historical development of assembling processes. There will be a focus on assembling techniques, including traditional methods (wet spinning, dry spinning, and electrostatic spinning) and advanced methods (self-assembly, microfluidic, and 3D printing). In particular, the design rules and various influencing factors of assembling processes related to the structure and function of fibrous materials are introduced and discussed in detail. Then, the emerging applications of these nanocellulose-based fibrous materials are highlighted. Finally, some perspectives, key opportunities, and critical challenges on future research trends within this field are proposed.

Neural basis of dysphagia in stroke: A systematic review and meta-analysis.

Objectives: Dysphagia is a major cause of stroke infection and death, and identification of structural and functional brain area changes associated with post-stroke dysphagia (PSD) can help in early screening and clinical intervention. Studies on PSD have reported numerous structural lesions and functional abnormalities in brain regions, and a systematic review is lacking. We aimed to integrate several neuroimaging studies to summarize the empirical evidence of neurological changes leading to PSD. Methods: We conducted a systematic review of studies that used structural neuroimaging and functional neuroimaging approaches to explore structural and functional brain regions associated with swallowing after stroke, with additional evidence using a live activation likelihood estimation (ALE) approach. Results: A total of 35 studies were included, including 20 studies with structural neuroimaging analysis, 14 studies with functional neuroimaging analysis and one study reporting results for both. The overall results suggest that structural lesions and functional abnormalities in the sensorimotor cortex, insula, cerebellum, cingulate gyrus, thalamus, basal ganglia, and associated white matter connections in individuals with stroke may contribute to dysphagia, and the ALE analysis provides additional evidence for structural lesions in the right lentiform nucleus and right thalamus and functional abnormalities in the left thalamus. Conclusion: Our findings suggest that PSD is associated with neurological changes in brain regions such as sensorimotor cortex, insula, cerebellum, cingulate gyrus, thalamus, basal ganglia, and associated white matter connections. Adequate understanding of the mechanisms of neural changes in the post-stroke swallowing network may assist in clinical diagnosis and provide ideas for the development of new interventions in clinical practice.

Aberrant dynamic Functional-Structural connectivity coupling of Large-scale brain networks in poststroke motor dysfunction.

BACKGROUND AND PURPOSE: Stroke may lead to widespread functional and structural reorganization in the brain. Several studies have reported a potential correlation between functional network changes and structural network changes after stroke. However, it is unclear how functional-structural relationships change dynamically over the course of one resting-state fMRI scan in patients following a stroke; furthermore, we know little about their relationships with the severity of motor dysfunction. Therefore, this study aimed to investigate dynamic functional and structural connectivity (FC-SC) coupling and its relationship with motor function in subcortical stroke from the perspective of network dynamics. METHODS: Resting-state functional magnetic resonance imaging and diffusion tensor imaging were obtained from 39 S patients (19 severe and 20 moderate) and 22 healthy controls (HCs). Brain structural networks were constructed by tracking fiber tracts in diffusion tensor imaging, and structural network topology metrics were calculated using a graph-theoretic approach. Independent component analysis, the sliding window method, and k-means clustering were used to calculate dynamic functional connectivity and to estimate different dynamic connectivity states. The temporal patterns and intergroup differences of FC-SC coupling were analyzed within each state. We also calculated dynamic FC-SC coupling and its relationship with functional network efficiency. In addition, the correlation between FC-SC coupling and the Fugl-Meyer assessment scale was analyzed. RESULTS: For SC, stroke patients showed lower global efficiency than HCs (all P < 0.05), and severely affected patients had a higher characteristic path length (P = 0.003). For FC and FC-SC coupling, stroke patients predominantly showed lower local efficiency and reduced FC-SC coupling than HCs in state 2 (all P < 0.05). Furthermore, severely affected patients also showed lower local efficiency (P = 0.031) and reduced FC-SC coupling (P = 0.043) in state 3, which was markedly linked to the severity of motor dysfunction after stroke. In addition, FC-SC coupling was correlated with functional network efficiency in state 2 in moderately affected patients (r = 0.631, P = 0.004) but not significantly in severely affected patients. CONCLUSIONS: Stroke patients show abnormal dynamic FC-SC coupling characteristics, especially in individuals with severe injuries. These findings may contribute to a better understanding of the anatomical functional interactions underlying motor deficits in stroke patients and provide useful information for personalized rehabilitation strategies.

Effects of preoperative carbohydrate loading on recovery after elective surgery: A systematic review and Bayesian network meta-analysis of randomized controlled trials.

Background: Preoperative carbohydrate loading is an important element of the enhanced recovery after surgery (ERAS) paradigm in adult patients undergoing elective surgery. However, preoperative carbohydrate loading remains controversial in terms of improvement in postoperative outcomes and safety. We conducted a Bayesian network meta-analysis to evaluate the effects and safety of different doses of preoperative carbohydrates administrated in adult patients after elective surgery. Methods: MEDLINE (PubMed), Web of Science, EMBASE, EBSCO, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure (CNKI) were searched to identify eligible trials until 16 September 2022. Outcomes included postoperative insulin resistance, residual gastric volume (RGV) during the surgery, insulin sensitivity, fasting plasma glucose (FPG), fasting serum insulin (Fin) level, the serum levels of C-reactive protein (CRP), postoperative scores of pain, patients' satisfaction, thirst, hunger, anxiety, nausea and vomit, fatigue, and weakness within the first 24 h after surgery and the occurrences of postoperative infection. The effect sizes were estimated using posterior mean difference (continuous variables) or odds ratios (dichotomous variables) and 95 credible intervals (CrIs) with the change from baseline in a Bayesian network meta-analysis with random effect. Results: Fifty-eight articles (N = 4936 patients) fulfilled the eligibility criteria and were included in the meta-analysis. Both preoperative oral low-dose carbohydrate loading (MD: -3.25, 95% CrI: -5.27 to -1.24) and oral high-dose carbohydrate loading (MD: -2.57, 95% CrI: -4.33 to -0.78) were associated with postoperative insulin resistance compared to placebo/water. When trials at high risk of bias were excluded, association with insulin resistance was found for oral low-dose carbohydrate loading compared with placebo/water (MD: -1.29, 95%CrI: -2.26 to -0.27) and overnight fasting (MD: -1.17, 95%CrI: -1.88 to -0.43). So, there was large uncertainty for all estimates vs. control groups. In terms of safety, oral low-dose carbohydrate administration was associated with the occurrences of postoperative infection compared with fasting by 0.42 (95%Crl: 0.20-0.81). In the other outcomes, there was no significant difference between the carbohydrate and control groups. Conclusion: Although preoperative carbohydrate loading was associated with postoperative insulin resistance and the occurrences of postoperative infection, there is no evidence that preoperative carbohydrate administration alleviates patients' discomfort. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022312944].

Lesions causing post-stroke spasticity localize to a common brain network.

Objective: The efficacy of clinical interventions for post-stroke spasticity (PSS) has been consistently unsatisfactory, probably because lesions causing PSS may occur at different locations in the brain, leaving the neuroanatomical substrates of spasticity unclear. Here, we investigated whether heterogeneous lesions causing PSS were localized to a common brain network and then identified the key nodes in this network. Methods: We used 32 cases of PSS and the Human Connectome dataset (n = 1,000), using a lesion network mapping method to identify the brain regions that were associated with each lesion in patients with PSS. Functional connectivity maps of all lesions were overlaid to identify common connectivity. Furthermore, a split-half replication method was used to evaluate reproducibility. Then, the lesion network mapping results were compared with those of patients with post-stroke non-spastic motor dysfunction (n = 29) to assess the specificity. Next, both sensitive and specific regions associated with PSS were identified using conjunction analyses, and the correlation between these regions and PSS was further explored by correlation analysis. Results: The lesions in all patients with PSS were located in different cortical and subcortical locations. However, at least 93% of these lesions (29/32) had functional connectivity with the bilateral putamen and globus pallidus. These connections were highly repeatable and specific, as compared to those in non-spastic patients. In addition, the functional connectivity between lesions and bilateral putamen and globus pallidus in patients with PSS was positively correlated with the degree of spasticity. Conclusion: We identified that lesions causing PSS were localized to a common functional connectivity network defined by connectivity to the bilateral putamen and globus pallidus. This network may best cover the locations of lesions causing PSS. The putamen and globus pallidus may be potential key regions in PSS. Our findings complement previous neuroimaging studies on PSS, contributing to identifying patients with stroke at high risk for spasticity at an early stage, and may point to PSS-specific brain stimulation targets.

A new perspective on NAFLD: Focusing on the crosstalk between peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR).

Nonalcoholic fatty liver disease (NAFLD) is primarily caused by abnormal lipid metabolism and the accumulation of triglycerides in the liver. NAFLD is also associated with hepatic steatosis and nutritional and energy imbalances and is a chronic liver disease associated with a number of factors. Nuclear receptors play a key role in balancing energy and nutrient metabolism, and the peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR) regulate lipid metabolism genes, controlling hepatocyte lipid utilization and regulating bile acid (BA) synthesis and transport. They play an important role in lipid metabolism and BA homeostasis. At present, PPARα and FXR are the most promising targets for the treatment of NAFLD among nuclear receptors. This review focuses on the crosstalk mechanisms and transcriptional regulation of PPARα and FXR in the pathogenesis of NAFLD and summarizes PPARα and FXR drugs in clinical trials, laying a theoretical foundation for the targeted treatment of NAFLD and the development of novel therapeutic strategies.

mTOR: A Potential New Target in Nonalcoholic Fatty Liver Disease.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) continues to rise, yet effective treatments are lacking due to the complex pathogenesis of this disease. Although recent research has provided evidence for the "multiple strikes" theory, the classic "two strikes" theory has not been overturned. Therefore, there is a crucial need to identify multiple targets in NAFLD pathogenesis for the development of diagnostic markers and targeted therapeutics. Since its discovery, the mechanistic target of rapamycin (mTOR) has been recognized as the central node of a network that regulates cell growth and development and is closely related to liver lipid metabolism and other processes. This paper will explore the mechanisms by which mTOR regulates lipid metabolism (SREBPs), insulin resistance (Foxo1, Lipin1), oxidative stress (PIG3, p53, JNK), intestinal microbiota (TLRs), autophagy, inflammation, genetic polymorphisms, and epigenetics in NAFLD. The specific influence of mTOR on NAFLD was hypothesized to be divided into micro regulation (the mechanism of mTOR's influence on NAFLD factors) and macro mediation (the relationship between various influencing factors) to summarize the influence of mTOR on the developmental process of NAFLD, and prove the importance of mTOR as an influencing factor of NAFLD regarding multiple aspects. The effects of crosstalk between mTOR and its upstream regulators, Notch, Hedgehog, and Hippo, on the occurrence and development of NAFLD-associated hepatocellular carcinoma are also summarized. This analysis will hopefully support the development of diagnostic markers and new therapeutic targets in NAFLD.

GOS Ameliorates Nonalcoholic Fatty Liver Disease Induced by High Fat and High Sugar Diet through Lipid Metabolism and Intestinal Microbes.

The treatment of nonalcoholic fatty liver disease (NAFLD) remains very challenging. This study investigated the therapeutic effect of galactose oligosaccharide (GOS), an important prebiotic, on NAFLD through in vivo and in vitro experiments and preliminarily explored the mechanism by which GOS improves liver lipid metabolism and inflammation through liver and intestinal microbiological analysis. The results of mouse liver lipidomics showed that GOS could promote body thermogenesis in mice with high-fat and high-sugar diet (HFHSD)-induced NAFLD, regulate lipolysis in liver fat cells, and accelerate glycine and cholesterol metabolism. GOS dose-dependently reduced the contents of total cholesterol (TC) and triglyceride (TG) in cells and reduced the accumulation of lipid droplets in cells. GOS also reduced the Firmicutes/Bacteroidetes ratio and altered the composition of the intestinal microbiota in mice fed a HFHSD. GOS can improve liver lipid metabolism and intestinal structure of NAFLD. These results provide a theoretical and experimental basis supporting the use of GOS as a health food with anti-NAFLD functions.

The Therapeutic Effect of SCFA-Mediated Regulation of the Intestinal Environment on Obesity.

Intestinal environment disorder is a potential pathological mechanism of obesity. There is increasing evidence that disorders in the homeostasis of the intestinal environment can affect various metabolic organs, such as fat and liver, and lead to metabolic diseases. However, there are few therapeutic approaches for obesity targeting the intestinal environment. In this review, on the one hand, we discuss how intestinal microbial metabolites SCFA regulate intestinal function to improve obesity and the possible mechanisms and pathways related to obesity-related pathological processes (depending on SCFA-related receptors such as GPCRs, MCT and SMCT, and through epigenetic processes). On the other hand, we discuss dietary management strategies to enrich SCFA-producing bacteria and target specific SCFA-producing bacteria and whether fecal bacteria transplantation therapy to restore the composition of the gut microbiota to regulate SCFA can help prevent or improve obesity. Finally, we believe that it will be of great significance to establish a working model of gut- SCFA- metabolic disease development in the future for the improvement this human health concern.

Biodegradation and Prospect of Polysaccharide from Crustaceans.

Marine crustacean waste has not been fully utilized and is a rich source of chitin. Enzymatic degradation has attracted the wide attention of researchers due to its unique biocatalytic ability to protect the environment. Chitosan (CTS) and its derivative chitosan oligosaccharides (COSs) with various biological activities can be obtained by the enzymatic degradation of chitin. Many studies have shown that chitosan and its derivatives, chitosan oligosaccharides (COSs), have beneficial properties, including lipid-lowering, anti-inflammatory and antitumor activities, and have important application value in the medical treatment field, the food industry and agriculture. In this review, we describe the classification, biochemical characteristics and catalytic mechanisms of the major degrading enzymes: chitinases, chitin deacetylases (CDAs) and chitosanases. We also introduced the technology for enzymatic design and modification and proposed the current problems and development trends of enzymatic degradation of chitin polysaccharides. The discussion on the characteristics and catalytic mechanism of chitosan-degrading enzymes will help to develop new types of hydrolases by various biotechnology methods and promote their application in chitosan.

Covalent Fixing of MoS2 Nanosheets with SnS Nanoparticles Anchored on g-C3N4/Graphene Boosting Fast Charge/Ion Transport for Sodium-Ion Hybrid Capacitors.

The sluggish layered structural sodium reaction kinetics and the easy restacking property are major obstacles hindering the practical application of MoS2-based electrodes for sodium storage. Herein, covalently assembled two-phase MoS2-SnS supported by a hierarchical graphitic carbon nitride/graphene (MoS2-SnS@g-C3N4/G) composite is constructed to improve cycling cyclability and rate performances for Na storage. The multiphase MoS2-SnS@g-C3N4/G is featured with a covalent assembly strategy and an interconnected network architecture. This unique structural design can not only enhance the conductivity and facilitate fast interfacial electron transport, which is confirmed by experiments and density functional theory, but also buffer the volumetric changes of MoS2-SnS. As a result, the as-obtained MoS2-SnS@g-C3N4/G anode delivers a high reversible capacity of 834 mA h g-1 at 0.1 A g-1, a high rate capability of 452 mA h g-1 at 5 A g-1, and a long-term cycling stability (320 mA h g-1 at 2 A g-1 with 54.7% retention after 500 cycles) for the Na half-cell. Coupling with activated carbon (AC), our MoS2-SnS@g-C3N4/G||AC sodium-ion hybrid capacitor delivers high energy/power densities (193.1 W h kg-1/90 W kg-1 and 41.5 W h kg-1/18,000 W kg-1) and a stable cycle life in the potential range of 0-4.0 V.

Synergistic Engineering of Defects and Heterostructures Enhance Lithium/Sodium Storage Properties of F-SnO2-x -SnS2-x Nanocrystals Supported on N,S-Graphene.

Phase engineering of the electrode materials in terms of designing heterostructures, introducing heteroatom and defects, improves great prospects in accelerating the charge storage kinetics during the repeated Li+ /Na+ insertion/deintercalation. Herein, a new design of Li/Na-ion battery anodes through phase regulating is reported consisting of F-doped SnO2 -SnS2 heterostructure nanocrystals with oxygen/sulfur vacancies (VO /VS ) anchored on a 2D sulfur/nitrogen-doped reduced graphene oxide matrix (F-SnO2-x -SnS2-x @N/S-RGO). Consequently, the F-SnO2-x -SnS2-x @N/S-RGO anode demonstrates superb high reversible capacity and long-term cycling stability. Moreover, it exhibits excellent great rate capability with 589 mAh g-1 for Li+ and 296 mAh g-1 at 5 A g-1 for Na+ . The enhanced Li/Na storage properties of the nanocomposites are not only attributed to the increase in conductivity caused by VO /VS and F doping (confirmed by DFT calculations) to accelerate their charge-transfer kinetics but also the increased interaction between F-SnO2-x -SnS2-x and Li/Na through heterostructure. Meanwhile, the hierarchical F-SnO2-x -SnS2-x @N/S-RGO network structure enables fast infiltration of electrolyte and improves electron/ion transportation in the electrode, and the corrosion resistance of F doping contributes to prolonged cycle stability.

Checklist of the coral fish fauna of Xisha Islands, China.

BACKGROUND: The Xisha Islands are composed of the Yongle Islands and the Xuande Islands in Hainan Province, China. It has one of the highest species diversity in the world and is also a typical oceanic distribution area of coral reefs globally. The ichthyofauna of the Xisha Islands were recorded by underwater visual census in May 2019 and July 2020. The survey data were combined with previous records of species into the checklist of the Xisha Islands presented herein. A total of 691 species, belonging to 24 orders and 97 families, was recorded. The major families were Labridae, Pomacentridae, Serranidae, Chaetodontidae, Hexanchidae, Lutjanidae, Scaridae, Gobiidae, Scorpaenidae and Carangidae. In this study, the Coral Fish iversity Index (CFDI) of six families (Chaetodontidae, Pomacanthidae, Pomacentridae, Labridae, Scaridae and Acanthuridae) was 229, indicating 756 coral fishes. In terms of the IUCN Red List, one species is Critically Endangered (Glyphis gangeticus), six species are Endangered (Stegostoma fasciatum, Aetomylaeus maculatus, Aetomylaeus vespertilio, Epinephelus akaara, Cheilinusundulatus sp. and Xiphias gladius), 16 species are Vulnerable, and 13 species are Near Threatened in the Xisha Archipelago, so conservation should be strengthened in this area in the future. NEW INFORMATION: One species is a new record for China (Dischistodus pseudochrysopoecilus) and 23 species are newly found in the Xisha Islands.