Chemodivergence in Fluorine Source-Controlled Cascade Reaction of Aryne Precursors to Synthesize Pyrrolo[3,4-b]indoles and 3-Arylated Maleimides.

Reactions allowing chemodivergence prove to be attractive strategies in synthetic organic chemistry. We herein described a highly practical, transition-metal-free, highly regioselective and chemodivergent cascade reaction controlled by fluorine sources, which involved a [3 + 2] cycloaddition or C-arylation process between aryne precursors and 3-aminomaleimides. These two pathways led to a wide scope of structurally diverse pyrrolo[3,4-b]indoles (19 examples) and 3-arylated maleimides (25 examples) in good-to-excellent yields. Furthermore, the reaction could be scaled up, and several synthetic transformations were accomplished for the preparation of functionalized molecules and might provide new opportunities for the discovery of N-heterocyclic drugs.

Base-Catalyzed Cascade Cyclization of 2-Nitrochalcones and Isocyanides to Access Pyrano[3,4-b]indol-1(9H)-one Frameworks.

An unexpected cascade reaction of 2-nitrochalcones with isocyanoacetates has been reported for the efficient synthesis of indole carboxylic esters and pyranoindoles. The conversion was achieved by KOH-catalyzed cyclization and elimination of the nitro group with final decarbonylation-aromatization. The method was used to synthesize a series of potentially biologically active indole derivatives (49 examples) in 67-85% yields under transition-metal-free catalytic conditions.

Lactate induces C2C12 myoblasts differentiation by mediating ROS/p38 MAPK signalling pathway.

Lactate serves not merely as an energy substrate for skeletal muscle but also regulates myogenic differentiation, leading to an elevation of reactive oxygen species (ROS) levels. The present study was focused on exploring the effects of lactate and ROS/p38 MAPK in promoting C2C12 myoblasts differentiation. Our results demonstrated that lactate increased C2C12 myoblasts differentiation at a range of physiological concentrations, accompanied by enhanced ROS contents. We used n-acetylcysteine (NAC, a ROS scavenger) pretreatment and found that it delayed lactate-induced C2C12 myoblast differentiation by upregulating Myf5 expression on days 5 and 7 and lowering MyoD and MyoG expression. The finding implies that lactate accompanies ROS-dependent manner to promote C2C12 myoblast differentiation. Additionally, lactate significantly increased p38 MAPK phosphorylation to promote C2C12 cell differentiation, but pretreatment with SB203580 (p38 MAPK inhibitor) reduced lactate-induced C2C12 myoblasts differentiation. whereas lactate pretreatment with NAC inhibited p38 MAPK phosphorylation in C2C12 cells, demonstrating that lactate mediated ROS and regulated the p38 MAPK signalling pathway to promote C2C12 cell differentiation. In conclusion, our results suggest that the promotion of C2C12 myoblasts differentiation by lactate is dependent on ROS and the p38 MAPK signalling pathway. These observations reveal a beneficial role for lactate in increasing myogenesis through ROS-sensitive mechanisms as well as providing new ideas regarding the positive impact of ROS in improving the function of skeletal muscle.

Lactate ameliorates palmitate-induced impairment of differentiative capacity in C2C12 cells through the activation of voltage-gated calcium channels.

Palmitic acid (PA), a saturated fatty acid enriched in high-fat diet, has been implicated in the development of skeletal muscle regeneration dysfunction. This study aimed to examine the effects and mechanisms of lactate (Lac) treatment on PA-induced impairment of C2C12 cell differentiation capacity. Furthermore, the involvement of voltage-gated calcium channels in this context was examined. In this study, Lac could improve the PA-induced impairment of differentiative capacity in C2C12 cells by affecting Myf5, MyoD and MyoG. In addition, Lac increases the inward flow of Ca2+, and promotes the depolarization of the cell membrane potential, thereby activating voltage-gated calcium channels during C2C12 cell differentiation. The enchancement of Lac on myoblast differentiative capacity was abolished after the addition of efonidipine (voltage-gated calcium channel inhibitors). Therefore, voltage-gated calcium channels play an important role in improving PA-induced skeletal muscle regeneration disorders by exercising blood Lac. Our study showed that Lac could rescue the PA-induced impairment of differentiative capacity in C2C12 cells by affecting Myf5, MyoD and MyoG through the activation of voltage-gated calcium channels.

Multispecies transcriptomics identifies SIKE as a MAPK repressor that prevents NASH progression.

Nonalcoholic fatty liver (NAFL) remains relatively benign, but high-risk to end-stage liver diseases become highly prevalent when it progresses into nonalcoholic steatohepatitis (NASH). Our current understanding of the development of NAFL to NASH remains insufficient. In this study, we revealed MAP kinase (MAPK) activation as the most notable molecular signature associated with NASH progression across multiple species. Furthermore, we identified suppressor of IKKε (SIKE) as a conserved and potent negative controller of MAPK activation. Hepatocyte-specific overexpression of Sike prevented NASH progression in diet- and toxin-induced mouse NASH models. Mechanistically, SIKE directly interacted with TGF-ß-activated kinase 1 (TAK1) and TAK1-binding protein 2 (TAB2) to interrupt their binding and subsequent TAK1-MAPK signaling activation. We found that indobufen markedly up-regulated SIKE expression and effectively improved NASH features in mice and macaques. These findings identify SIKE as a MAPK suppressor that prevents NASH progression and provide proof-of-concept evidence for targeting the SIKE-TAK1 axis as a potential NASH therapy.

Association between transition patterns of sleep problems and suicidal ideation in Chinese female nurses: A prospective study.

OBJECTIVE: Suicidal ideation and sleep problems are both common in nurses. However, few longitudinal studies are available to examine the temporal association between sleep and suicidal ideation in nurses. METHOD: Data from the Health Longitudinal Survey of Nurses in Shandong Province was analyzed, involving 623 female nurses who had completed data of concern in 2018 (T1) and 2019 (T2). Sleep problem was assessed by the Pittsburgh Sleep Quality Index, in which the transition patterns for global and specific sleep component and the cumulative number of sleep component problems were defined. Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire. Binary logistic regression was used to explore the association between sleep and suicidal ideation. RESULTS: Chronic and deteriorated global sleep problems is associated with a greater risk of suicidal ideation. For the specific component of sleep, sleep disturbance and short sleep duration are associated with a higher risk of suicidal ideation. The higher number of cumulative sleep component problems is associated with a higher risk of suicidal ideation. CONCLUSION: Findings indicate sleep disturbance and short sleep duration may be pathways to suicidal ideation. Initiatives that target at sleep problems may be important to reduce suicidal ideation in nurses.

Mutational spectrum and clinical features of GBA1 variants in a Chinese cohort with Parkinson's disease.

GBA1 variants are important risk factors for Parkinson's disease (PD). Most studies assessing GBA1-related PD risk have been performed in European-derived populations. Although the coding region of the GBA1 gene in the Chinese population has been analyzed, the sample sizes were not adequate. In this study, we aimed to investigate GBA1 variants in a large Chinese cohort of patients with PD and healthy control and explore the associated clinical characteristics. GBA1 variants in 4034 patients and 2931 control participants were investigated using whole-exome and whole-genome sequencing. The clinical features of patients were evaluated using several scales. Regression analysis, chi-square, and Fisher exact tests were used to analyze GBA1 variants and the clinical symptoms of different groups. We identified 104 variants, including 8 novel variants, expanding the spectrum of GBA1 variants. The frequency of GBA1 variants in patients with PD was 7.46%, higher than that in the control (1.81%) (P < 0.001, odds ratio [OR] = 4.38, 95% confidence interval [CI]: 3.26-5.89). Among patients, 176 (4.36%) had severe variants, 34 (0.84%) carried mild variants, three (0.07%) had risk variants, and 88 (2.18%) carried unknown variants. Our study, for the first time, found that p.G241R (P = 0.007, OR = 15.3, 95% CI: 1.25-261.1) and p.S310G (P = 0.005, OR = 4.86, 95% CI: 1.52-28.04) variants increased the risk of PD. Patients with GBA1 variants exhibited an earlier onset age and higher risk of probable rapid-eye-movement sleep behavior disorder, olfactory dysfunction, depression, and autonomic dysfunction than patients without GBA1 variants.

Human forebrain organoid-based multi-omics analyses of PCCB as a schizophrenia associated gene linked to GABAergic pathways.

Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS, gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB's contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNPs rs6791142 and rs35874192, two eQTL SNPs for PCCB, showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA sequencing analysis revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse. The metabolomic and mitochondrial function analyses confirmed the decreased GABA levels resulted from inhibited tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics analyses and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic pathways, highlighting the mitochondrial function in SCZ.

Expression of expanded GGC repeats within NOTCH2NLC causes cardiac dysfunction in mouse models.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder characterized by widespread intranuclear inclusions in the nervous system as well as multiple visceral organs. In 2019, expanded GGC repeats within the 5' untranslated region of the NOTCH2NLC gene was identified as the causative factor. NIID is a heterogeneous disorder with variable clinical manifestations including cognitive impairment, cerebellar ataxia, parkinsonism, paroxysmal symptoms, autonomic dysfunction, and muscle weakness. Although NIID primarily affects the central and peripheral nervous systems, growing evidence suggests potential cardiac abnormalities in NIID. However, the link between expanded GGC repeats within NOTCH2NLC and cardiac dysfunction remains uncertain. RESULTS: In this study, we utilized two transgenic mouse models, expressing NOTCH2NLC-(GGC)98 ubiquitously or specifically in cardiomyocytes, and identified p62 (also known as sequestosome 1, SQSTM1)-positive intranuclear NOTCH2NLC-polyG inclusions in cardiomyocytes in two mouse models. We observed that both models exhibited cardiac-related pathological and echocardiographic changes, albeit exhibiting varying degrees of severity. Transcriptomic analysis revealed shared downregulation of genes related to ion channels and mitochondria in both models, with the cardiomyocyte-specific mice showing a more pronounced downregulation of mitochondria and energy metabolism-related pathways. Further investigations revealed decreased expression of mitochondria-related genes and electron transport chain activity. At last, we conducted a retrospective review of cardiac-related examination results from NIID patients at our hospital and also identified some cardiac abnormalities in NIID patients. CONCLUSIONS: Our study provided the first in vivo evidence linking GGC repeat expansions within NOTCH2NLC to cardiac abnormalities and highlighted the contribution of mitochondrial dysfunction in the development of cardiac abnormalities.

[Biological Evaluation and Key Stress Factor Diagnosis of Compound Contaminated Soil Based on Environmental DNA].

Healthy biological community composition and diversity are the basis for soil ecosystems to provide complete ecological functions and services. The current technical bottleneck in soil pollution control is the lack of systematic and comprehensive biodiversity indicators. In this study, the compound-polluted soil in an industrial park was taken as the object, and environmental DNA (eDNA)technology was used to monitor and analyze the composition of the biological community in the polluted soil. The environmental DNA-species sensitivity distribution (eDNA-SSD) method was constructed to diagnose the key stress factors and their ecological threshold. The results showed that:① compound pollution did not have a significant impact on the α-diversity of soil organisms in the park but led to changes in the composition of biological communities and dominant species with high relative abundance. The dominant groups in the polluted soil were Proteobacteria (25.54%), Ascomycota (15.65%), Actinobacteria (8.75%), and Chloroflexi (7.64%). ② Environmental factors accounted for 51.27% of the differences in soil biodistribution, and aniline, sulfate, petroleum hydrocarbon, and lead were the key stress factors for soil biomes. Among them, aniline had the most significant effect on the community distribution of bacteria (P=0.030), sulfate on fungi (P=0.025), and metazoans (P=0.032). ③ The ecological risk threshold (hazardous concentration for 5% of species, HC5) of pollutants with 95% species as the protection target showed a gradient decreasing trend of sulfate (470.00 mg·kg-1), petroleum hydrocarbon (17.00 mg·kg-1), lead (13.00 mg·kg-1), arsenic (6.20 mg·kg-1), 4-chloroaniline (0.16 mg·kg-1), and aniline (0.11 mg·kg-1). Nevertheless, the existing soil risk control value was significantly higher than the ecological risk value, indicating that the existing control standards targeting human health were not suitable for protecting soil health. The comprehensive pollution index showed that the soil pollution in the park was mostly mild pollution accompanied by heavy pollution at individual points. The biological evaluation method based on eDNA-SSD could achieve the comprehensive evaluation of composite pollution in the absence of the benchmark value of pollutants and at the same time better distinguish the differences in soil biological community structure and composition under different pollution levels (P=0.053). In conclusion, the environmental DNA soil biomonitoring and assessment method developed in this study has guiding significance and application value for soil ecosystem restoration assessment.

Cordycepin inhibits myogenesis via activating the ERK1/2 MAPK signalling pathway in C2C12 cells.

Cordycepin (with a molecular formula of C10H13N5O3), a natural adenosine isolated from Cordyceps militaris, has an important regulatory effect on skeletal muscle remodelling and quality maintenance. The aim of this study was to investigate the effect of cordycepin on myoblast differentiation and explore the underlying molecular mechanisms of this effect. Our results showed that cordycepin inhibited myogenesis by downregulating myogenic differentiation (MyoD) and myogenin (MyoG), preserved undifferentiated reserve cell pools by upregulating myogenic factor 5 (Myf5) and retinoblastoma-like protein p130 (p130), and enhanced energy reserves by decreasing intracellular reactive oxygen species (ROS) and enhancing mitochondrial membrane potential, mitochondrial mass, and ATP content. The effect of cordycepin on myogenesis was associated with increased phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2). PD98059 (a specific inhibitor of p-ERK1/2) attenuated the inhibitory effect of cordycepin on C2C12 differentiation. The present study reveals that cordycepin inhibits myogenesis through ERK1/2 MAPK signalling activation accompanied by an increase in skeletal muscle energy reserves and improving skeletal muscle oxidative stress, which may have implications for its further application for the prevention and treatment of degenerative muscle diseases caused by the depletion of depleted muscle stem cells.

Base-Promoted [5 + 1 + 3] Cascade Cyclization of o-Nitrochalcones, Elemental Sulfur, and Guanidine to Benzo[4,5]thieno[3,2-d]pyrimidine Frameworks.

An unexpected [5 + 1 + 3] cascade cyclization to the preparation of benzo[4,5]thieno[3,2-d]pyrimidine derivatives has been disclosed. In the new protocol, o-nitrochalcones reacted with elemental sulfur and guanidine promoted by NaOH, which reacted in EtOH for 20 min, providing structurally diverse benzo[4,5]thieno[3,2-d]pyrimidines with good yields (77-89%) and wide substrate compatibility (33 examples).

Plasma metabolomics identifies metabolic alterations associated with the growth and development of cat.

BACKGROUND: The purpose of our study was to study the composition and content of the feline plasma metabolome revealing the critical metabolites and metabolic pathways associated with age during growth and development. METHODS: Blood samples were collected from juvenile and adult groups for blood routine tests and serum biochemistry tests. Non-targeted metabolomics analyses of plasma were also performed to investigate changes in metabolites and metabolic pathways. RESULTS: In this study, we found that the red blood cell counts, liver function indexes (albumin and gamma-glutamyl transpeptidase), and the concentration of triglyceride and glucose changed significant with growth and development. The metabolomics results revealed that 1427 metabolites were identified in the plasma of young and adult cats. Most of these metabolites belong to major classes of lipids and lipid-like molecules. The most obvious age-related metabolites include reduced levels of chenodeoxycholate, taurocholate, cholate, and taurochenodeoxycholate but increased levels of L-cysteine and taurocyamine in the adult cat's serum. These metabolites are mainly involved in the primary bile acid biosynthesis pathway, the bile secretion pathway, and the taurine and hypotaurine metabolism pathway. CONCLUSION: This study revealed many age-related metabolite alterations in the feline plasma. These age-varying metabolites, especially in the bile acid biosynthesis and secretion metabolism pathways, indicate that the regulation of these pathways is involved in the growth and development of cats. This study promotes our understanding of the mechanism of feline growth and provides new insights into nutrition and medicine for cats of different ages.

Cu(II)-Catalyzed Cascade of N-Phenyl-o-phenylenediamine with Benzaldehyde: One-Step Direct Construction of 2-(1-Phenyl-1H-benzo[d]imidazol-2-yl)phenols.

A practical protocol for the construction of hydroxylated 2-(1-phenyl-1H-benzo[d]imidazol-2-yl)phenols (PBIs) from N-phenyl-o-phenylenediamine with benzaldehydes was developed. The cascade reaction was enabled by heating a mixture of the two substrates in the presence of air as an oxidant and anhydrous Cu(OAc)2 as a catalyst in dimethyl sulfoxide, and a diverse series of PBIs were synthesized in moderate to good yields (69-81%). Furthermore, the synthesis of the PBIs was enabled via a one-pot cascade reaction that proceeded through subsequent dehydration condensation, intramolecular cyclization, and aromatic C-H hydroxylation. This protocol can be used for the synthesis of hydroxylated PBI via a one-pot annulation C-H hydroxylation reaction rather than through a series of multistep reactions, which provides the possibility of further modification.

A Meta-Analysis of the Association Between Genetic Polymorphisms in IL-12, IL-17, and IL-21 and Risk of Hepatitis B Virus Infection.

Cytokine imbalance is an important feature in the occurrence and outcome of hepatitis B virus (HBV). Single nucleotide polymorphisms (SNPs) within cytokine genes may affect the protein expression and eventually contribute to the susceptibility of HBV infection. The association between interleukin (IL)-12, IL-17, or IL-21 and the risk of HBV infection has been extensively studied, but yielding equivocal results. The aim of this meta-analysis was to determine the impact of SNPs in IL-12, IL-17, and IL-21 on the risk of HBV infection. We retrieved studies evaluating whether SNPs in IL-12, IL-17, and IL-21 influenced HBV infection from electronic databases, including PUBMED, Web of Science, EBOCO, OVID, and Embase. Summarized odds ratios (ORs) and confidence intervals (CIs) were calculated using STATA software. Under a homozygous comparison, the IL-12A rs568408 was associated with an increased risk of HBV infection in both overall analysis (OR = 1.68, 95% CI, 1.12-2.53) and Caucasians (OR = 1.80, 95% CI, 1.14-2.84). Under a dominant genetic model, the similarly higher risk was also observed in overall analysis (OR = 3.62, 95% CI, 3.08-4.24), Caucasians (OR = 3.29, 95% CI, 2.67-4.05), high-quality studies (OR = 3.29, 95% CI, 2.61-4.14), and low-quality studies (OR = 3.95, 95% CI, 3.17-4.93). Although no significant association was observed between IL-17A rs2275913 and the risk of HBV infection in overall comparison, subgroup analysis revealed that the IL-17A rs2275913 AA genotype was associated with a reduced risk in Asians (OR = 0.72, 95% CI, 0.57-0.91) and high-quality studies (OR = 0.71, 95% CI, 0.55-0.92). However, no significant association of IL12B rs3212227, IL-17A rs2275913, IL-21 rs2221903, and rs907715 with HBV infection was observed. In conclusion, we provide evidence that IL-12A rs568408 was associated with an increased risk of HBV infection and IL-17A rs2275913 AA genotype was a protective factor against HBV infection in Asians.

Network-based analysis identifies key regulatory transcription factors involved in skin aging.

Skin aging is a complex process involving intricate genetic and environmental factors. In this study, we performed a comprehensive analysis of the transcriptional regulatory landscape of skin aging in canines. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to identify aging-related gene modules. We subsequently validated the expression changes of these module genes in single-cell RNA sequencing (scRNA-seq) data of human aging skin. Notably, basal cell (BC), spinous cell (SC), mitotic cell (MC), and fibroblast (FB) were identified as the cell types with the most significant gene expression changes during aging. By integrating GENIE3 and RcisTarget, we constructed gene regulation networks (GRNs) for aging-related modules and identified core transcription factors (TFs) by intersecting significantly enriched TFs within the GRNs with hub TFs from WGCNA analysis, revealing key regulators of skin aging. Furthermore, we demonstrated the conserved role of CTCF and RAD21 in skin aging using an H2O2-stimulated cell aging model in HaCaT cells. Our findings provide new insights into the transcriptional regulatory landscape of skin aging and unveil potential targets for future intervention strategies against age-related skin disorders in both canines and humans.

Human forebrain organoids-based multi-omics analyses reveal PCCB's regulation on GABAergic system contributing to schizophrenia.

Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS (including FUSION, PrediXcan, summary-data-based Mendelian randomization (SMR), joint-tissue imputation approach with Mendelian randomization (MR-JTI)), gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta ( PCCB ), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB ’s contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNP rs35874192, an eQTL SNP for PCCB , showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA-seq revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse, as well as genes dysregulated in postmortem brains of SCZ patients or in cerebral organoids derived from SCZ patients. The metabolomic and mitochondrial function analyses confirmed the deceased GABA levels resulted from reduced tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics data and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic system, highlighting the mitochondrial function in SCZ.

Effects of habitat factors on the plant diversity on naturally-restored wind farm slopes.

This study investigated naturally-restored plant communities on wind farm slopes and analyzed the effects of various habitat factors on the plant diversity. The findings provide a technical support for the ecological restoration of mountainous slopes.Twenty-one slopes on five wind farms were selected and the characteristics of the habitat, including slope position, slope aspect, slope gradient, altitude, years since restoration, and plant communities, were recorded. The species richness of the plant communities and the vegetation diversity indexes of these wind farms were measured and calculated, including the Shannon-Wiener diversity index (H'), Pielou's species evenness index (J), and Margalef's richness index (R). The key factors influencing plant diversity were identified using a stepwise regression analysis. A total of 36 families, 54 genera, and 57 species of plants were identified in this study with the Gramineae, Compositae, Rosaceae, Liliaceae, and Juglandaceae families the mostly predominant. Cynodon dactylon, Rubus lambertianus Ser., and Lindera glauca were the dominant species of herbs, shrubs, and trees, respectively. The highest number of species were found on lower slopes, slopes with semi-sunny aspects, slopes with gradients 30-50°, elevation below 500 m, and on slopes with at least five years since restoration. The plant diversity H' and R tended to be higher on lower slopes than on upper slopes, and higher on slopes with semi-shady aspects than on slopes with semi-sunny aspects (P < 0.05). Vegetation diversity increased with the years since restoration. Slope position and slope aspect were identified as the primary influencing factors, and the H' and R indexes were major indicators of changes in plant diversity on mountainous slopes.

Study on the improvement of clay properties by xanthan gum and its application on ecological slope protection engineering.

Traditional substrate binder releases greenhouse gases during the production and application processes, and is detrimental to the vegetation restoration on slopes. To develop a new environmentally friendly soil substrate, this paper conducted a serial of experimental studies on the ecological function and mechanical properties of the xanthan gum (XG)-amended clay by plant growth tests and direct shear tests. The improvement mechanism of the xanthan gum (XG)-amended clay has also explored through microscopic examinations. Experimental results of plant growth tests show that the germination of ryegrass seeds and growth of seedlings can be effectively promoted by adding a proper content (≤2%) of XG into clay. Plants in substrates with 2% of XG grew best, while a high content (3-4%) of XG has an inhibitory effect on the plant growth. The results of direct shear tests illustrate that the shear strength and cohesion both increase with the increase of XG contents, while the internal friction has an opposite trend. The improve mechanism of the xanthan gum (XG)-amended clay were also explored by XRD tests and micro-scopic examinations. It is found that shows that XG does not react chemically to form new mineral components after mixing with clay. The mechanism of XG improving clay is mainly because the XG gel can fill the pores between clay particles, and enhance the cementation between clay particles. XG can enhance the mechanical properties of clay and offset the deficiencies of traditional binder. It can play an active role in the ecological slope protection project.

PPAR-γ signaling in nonalcoholic fatty liver disease: Pathogenesis and therapeutic targets.

Non-alcoholic fatty liver disease (NAFLD), currently the leading cause of global chronic liver disease, has emerged as a major public health problem, more efficient therapeutics of which are thus urgently needed. Peroxisome proliferator-activated receptor γ (PPAR-γ), ligand-activated transcription factors of the nuclear hormone receptor superfamily, is considered a crucial metabolic regulator of hepatic lipid metabolism and inflammation. The role of PPAR-γ in the pathogenesis of NAFLD is gradually being recognized. Here, we outline the involvement of PPAR-γ in the pathogenesis of NAFLD through adipogenesis, insulin resistance, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. In addition, the evidence for PPAR-γ- targeted therapy for NAFLD are summarized. Altogether, PPAR-γ is a promising therapeutic target for NAFLD, and the development of drugs that can balance the beneficial and undesirable effects of PPAR-γ will bring new light to NAFLD patients.