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Objective To evaluate the associations between serum level of trimethylamine oxide （TMAO） and vascular calcification and explore the risk factors of vascular calcification in patients with chronic kidney disease （CKD）. Methods A total of 118 CKD3-5 patients were assigned into two experimental groups of calcification and non-calcification according to whether or not there was calcification of abdominal aorta. And 60 healthy people with matching age and gender were selected as control group. Serum level of TMAO was determined by enzyme-linked immunosorbent assay （ELISA）. The clinical data of two groups were compared. Results TMAO（6.49 ± 0.76）μmol/L，serum phosphorus (1.73±0.62)μmol/L，calcium-phosphorus product(3.66±1.30)，parathyroid hormone （PTH）[232.90（96.90，521.60）ng/L]，alkaline phosphatase （ALP） [72.00（55.75，113.50）U/L]，serum creatinine （Scr）[684.50（511.25，921.00）μmol/L] and C-reactive protein （CRP）[5.00（1.28，21.88）mg/L] were higher in experimental group than those in control group （P＜0.05）. Serum calcium（Scr）(2.13±0.24)μmol/L，25-hydroxyvitamin D[23.67（16.84，30.06）μg/L]，albumin （Alb）(37.35±5.97)g/L and estimated glomerular filtration rate （eGFR）[6.02（4.70，8.50）mL·min-1·（1.73m2）-1] were lower in control group （P＜0.05）. TMAO(6.01±0.90)μmol/L，age(47.81±13.51)year，proportion of hemodialysis，serum calcium (2.07±0.21)μmol/L and CRP[4.70（0.80，19.44）mg/L] were higher in calcification group than that in non-calcification group （P＜0.05）. No statistically significant inter-group difference existed in gender，basic diseases （hypertension & diabetes mellitus），blood phosphorus，calcium-phosphorus product，PTH，ALP，Alb，total cholesterol （TC），triglyceride （TG），25 hydroxyvitamin D，Scr and eGFR （P＞0.05）. Vascular calcification was correlated positively with age （r = 0.446，P＜0.001），TMAO （r = 0.614，P＜0.001），serum calcium （r = 0.192，P = 0.038），CRP （r = 0.208，P = 0.024） and hemodialysis （r = 0.238，P = 0.009）. Logistic analysis revealed that age （OR = 1.069，95%CI: 1.025-1.115，P = 0.002） and TMAO （OR = 19.295，95%CI: 5.785-64.663，P＜0.001） were the independent risk factors for vascular calcification. ROC curve indicated that area under curve （AUC） of TMAO and serum calcium were 0.855 and 0.611 respectively for diagnosing vascular calcification. AUC of combination was 0.868 with a sensitivity of 85.2% and a specificity of 71.9%. Conclusion Serum level of TMAO is correlated with vascular calcification in CKD patients. And TMAO is expected to become an adjunct to diagnosing vascular calcification. Due to a low specificity，it should be combined with other risk factors for assessing vascular calcification. The common risk factors for vascular calcification include age，TMAO，serum calcium，CRP and hemodialysis. And age and serum level of TMAO are independent risk factors for vascular calcification in CKD patients.

A growing body of evidence indicates that the G protein-coupled bile acid receptor, TGR5, plays a critical role in multiple physiological processes ranging from metabolic disorders to cancers. However, the biological functions of TGR5 in cervical cancer (CC) have not been elucidated. Here, using TGR5 knockout mice, we found that a deficiency of TGR5 leads to greater sensitivity to the progression of cervical inflammation. Activation of TGR5 by its specific ligands significantly attenuated the malignant behavior of CC cells. In addition, we found that TGR5 can negatively modulate the expression of lncRNA HCP5 by blocking its transcription activation when mediated by p65. HCP5 was highly expressed in CC tissues, which was positively correlated with the poor prognosis of CC patients. HCP5 knockdown notably restrained CC cell proliferation, colony formation, and migration in vitro, and inhibited tumor growth in vivo. Furthermore, HCP5 can function as the molecular sponge for miR-139-5p to upregulate DNA damage-induced transcript 4 (DDIT4) in CC cells. Murine xenograft studies demonstrated that TGR5 suppressed the tumor formation of CC cells and downregulated HCP5 and DDIT4 while increasing miR-139-5p in the xenografts. Taken together, these findings, for the first time, indicate that TGR5 inhibits CC progression by regulating the HCP5/miR-139-5p/DDIT4 axis, suggesting that it may represent a novel and potent target for CC treatment.

Abstract Background Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and immunoprivileged matrix essential for blastocyst implantation and placental development. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure (RIF), and miscarriages. Despite the increasing number of genes reportedly associated with endometrial receptivity and decidualization, the cellular and molecular mechanisms triggering and underlying decidualization remain largely unknown. Here, we analyze single-cell transcriptional profiles of endometrial cells during the window of implantation and decidual cells of early pregnancy, to gains insights on the process of decidualization. Results We observed a unique IGF1+ stromal cell that may initiate decidualization by single-cell RNA sequencing. We found the IL1B+ stromal cells promote gland degeneration and decidua hemostasis. We defined a subset of NK cells for accelerating decidualization and extravillous trophoblast (EVT) invasion by AREG-IGF1 and AREG-CSF1 regulatory axe. Further analysis indicates that EVT promote decidualization possibly by multiply pathways. Additionally, a systematic repository of cell–cell communication for decidualization was developed. An aberrant ratio conversion of IGF1+ stromal cells to IGF1R+ stromal cells is observed in unexplained RIF patients. Conclusions Overall, a unique subpopulation of IGF1+ stromal cell is involved in initiating decidualization. Our observations provide deeper insights into the molecular and cellular characterizations of decidualization, and a platform for further development of evaluation of decidualization degree and treatment for decidualization disorder-related diseases.

Genetic predisposition and disruption of host gut microbiota and immune system can result in inflammatory bowel disease (IBD). Here, we show that miRNA-149-5p (miR-149-5p) and miRNA-149-3p (miR-149-3p) play crucial roles in IBD. Mice lacking miR-149-3p were considerably more susceptible to dextran sulfate sodium (DSS)-induced colitis than wild-type (WT) mice, accompanied by more serious inflammatory symptoms and increased gene expression of certain inflammatory cytokines. Both miR-149-5p and miR-149-3p suppressed colon inflammatory response in vitro and in vivo. Furthermore, we found significant differences in the composition of the gut microbiota between WT and miR-149-3p−/− mice by 16S rRNA sequencing. Co-housing endowed susceptibility to WT mice against DSS-induced colitis compared with the WT control group. However, susceptibility of miR-149-3p−/− mice against DSS-induced colitis was still present after antibiotic treatment. These findings suggest that the deletion of miR-149-3p altered gut microbiota and influenced pathogenesis of intestinal inflammation, but sensitivity of miR-149-3p−/− mice to DSS-induced colitis is not conferred by microbiota. In addition, we identified the roles of miR-149-5p and miR-149-3p in colon inflammation, which may serve as an attractive therapeutic tool for colitis or IBD, and even colitis-associated carcinoma.

Cardiovascular diseases (CVDs) are the leading cause of death globally, with CVDs accounting for nearly 30% of deaths worldwide each year. G-protein-coupled receptors (GPCRs) are the most prominent family of receptors on the cell surface, and play an essential regulating cellular physiology and pathology. Some GPCR antagonists, such as β-blockers, are standard therapy for the treatment of CVDs. In addition, nearly one-third of the drugs used to treat CVDs target GPCRs. All the evidence demonstrates the crucial role of GPCRs in CVDs. Over the past decades, studies on the structure and function of GPCRs have identified many targets for the treatment of CVDs. In this review, we summarize and discuss the role of GPCRs in the function of the cardiovascular system from both vascular and heart perspectives, then analyze the complex ways in which multiple GPCRs exert regulatory functions in vascular and heart diseases. We hope to provide new ideas for the treatment of CVDs and the development of novel drugs.

This study focuses on the effect of lateral mass impact on ring-stiffened thin-walled cylindrical shell. Cylindrical shells were fabricated to validate the numerical modeling and analytical techniques, and drop tests were performed using a rigid spherical indenter. Next, stiffened-ring cylindrical shells with various structural size parameters were simulated using ABAQUS software. The relationships between the impact force, deformation displacement, and rebound velocity were established, on the basis of impact mechanics theory and simulation results. It derived fitting functions to analyse the relationship between the maximum load and maximum displacement of ring-stiffened cylindrical shell under dynamic mass impact. Based on the validation of the simulation model, the fitting function data were compared with the simulation results, and the functions showed a good accuracy. Besides, the parameters, mass ratio and stiffened-ring mass ratio were used to reflect the effect of the mass change in the ring-stiffened cylindrical shell. Furthermore, parametric studies on ring-stiffened cylindrical shell models were conducted to analyse the progressive impact responses.

Summary Systemic fungicides and antifungals are used as frontline treatments for fungal diseases in plants and humans. It is generally accepted that fungicides will bring significant negative side‐effects to the environment and result in fungicide resistance in the pathogenic fungi. Although previous research has focused on fungicide application rates and fungal resistance for a long time, little attention has been paid to fungicide residues after treatment, especially their potential role in fungal growth and sporulation. Here we investigated the effect of fungicides at sublethal concentrations on fungal sporulation. The results showed that two kinds of 14α‐demethylase inhibitors (DMIs) fungicides increased the number of isolates of Colletotrichum spp. to sporulate on PDA. Both on PDA medium and plant tissue, low concentration of DMI fungicides could promote spore production of Colletotrichum spp., whereas pyraclostrobin, a quinone outside inhibitor (QoIs), had no significant effects on sporulation of Colletotrichum spp. Transcriptomic analysis suggested that the DMIs fungicide stress signal may be transmitted to the central regulatory pathway through the FluG‐mediated signalling pathway, and further confirmed the morphological effect of DMI fungicide on promoting sporulation of Colletotrichum. To our knowledge, this is the first study to provide insights into the reproductive response of fungi in response to fungicide stress. Our findings indicate that fungicides have two‐way effects on the growth and reproduction of pathogenic fungi and provide a new basis for the scientific and rational use of fungicides.

White mold of pea caused by Sclerotinia sclerotiorum is a common disease in China. However, we discovered that the diverse Sclerotinia species could cause white mold on pea plants in Chongqing and Sichuan of China during recent disease surveys. Thus, the objective of this study was to confirm the causal agents from diseased pea plants. The obtained isolates of white mold from Chongqing and Sichuan were identified by morphological characters and molecular characterization to determine the pathogen species, and their pathogenicity was confirmed on pea through completing Koch's postulates. Fungal isolates of Sclerotinia-like were obtained from diseased plants or sclerotia. Based on morphological characteristics and molecular characterization, 30 isolates were identified to three species, six isolates as S. minor, seven as S. sclerotiorum, and 17 as S. trifoliorum. In pathogenicity tests on pea cultivars Zhongwan 4 and Longwan 1, all 30 isolates caused typical symptoms of white mold on the inoculated plants, and the inoculated pathogens were re-isolated from the diseased plants. This study confirmed that white mold of pea was caused by three Sclerotinia species, S. sclerotiorum, S. minor and S. trifoliorum in Chongqing and Sichuan. It is the first report that S. minor and S. trifoliorum cause white mold of pea in Southwest China.

Abstract Background The gut microbiome is the totality of microorganisms, bacteria, viruses, protozoa, and fungi within the gastrointestinal tract. The gut microbiome plays key roles in various physiological and pathological processes through regulating varieties of metabolic factors such as short-chain fatty acids, bile acids and amino acids. Nuclear receptors, as metabolic mediators, act as a series of intermediates between the microbiome and the host and help the microbiome regulate diverse processes in the host. Recently, nuclear receptors such as farnesoid X receptor, peroxisome proliferator-activated receptors, aryl hydrocarbon receptor and vitamin D receptor have been identified as key regulators of the microbiome-host crosstalk. These nuclear receptors regulate metabolic processes, immune activity, autophagy, non-alcoholic and alcoholic fatty liver disease, inflammatory bowel disease, cancer, obesity, and type-2 diabetes. Conclusion In this review, we have summarized the functions of the nuclear receptors in the gut microbiome-host axis in different physiological and pathological conditions, indicating that the nuclear receptors may be the good targets for treatment of different diseases through the crosstalk with the gut microbiome.

The global incidence rate of non-alcoholic fatty liver disease (NAFLD) is approximately 25%. With the global increase in obesity and its associated metabolic syndromes, NAFLD has become an important cause of chronic liver disease in many countries. Despite recent advances in pathogenesis, diagnosis, and therapeutics, there are still challenges in its treatment. In this review, we briefly describe diagnostic methods, therapeutic targets, and drugs related to NAFLD. In particular, we focus on evaluating carbohydrate and lipid metabolism, lipotoxicity, cell death, inflammation, and fibrosis as potential therapeutic targets for NAFLD. We also summarized the clinical research progress in terms of drug development and combination therapy, thereby providing references for NAFLD drug development.

The chemical components of Xin'an famous prescription Ershen Zhenwu Decoction (ESZWD) are still unclear. The results showed that ESZWD could significantly reduce left ventricular end diastolic diameter, decrease N-terminal pro-brain natriuretic peptide (NT-proBNP), angiotensinII, aldosterone, reactive oxygen species, and malondialdehyde, increase serum superoxide dismutase, while had no significant effect on inflammatory factors. Ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) analysis detected 30 prototype components in model rats' serum, mainly including alkaloids, saponins, terpenoids, tanshinones, phenols. UPLC-MS/MS successfully detected the pharmacokinetic parameters of four components, and correlation analysis shows that there are negative correlations between four compounds and serum NT-proBNP. Thirty components of ESZWD may play a therapeutic role in chronic heart failure with heart-kidney Yang deficiency (CHF-HKYd) by improving myocardial injury, reducing oxidative stress levels, and inhibiting activation of the RAAS system in rats. Salsolinol, aconitine, paeoniflorin, and miltrione are equipped with potential characteristics as pharmacodynamic substances for ESZWD in treating CHF-HKYd. Additionally, the constituents of ESZWD in CHF-HKYd rats are different from normal rats, which provided a reference for the selection of subjects for further study.

Alcoholic liver disease (ALD) is a major worldwide chronic liver disease accompanied by hepatic inflammation, gut leakiness, and abnormal oxidative stress. Our previous study demonstrated substantial hepatoprotective activity of the active Poria cocos polysaccharide (PCP-1C). The present study explored whether PCP-1C protects against ALD among hepatic inflammation, gut leakiness, and abnormal oxidative stress. The results showed that PCP-1C significantly improved alcohol-induced liver injury by decreasing serum biochemical parameters, alleviating hepatic steatosis, and reducing lipid accumulation caused by ALD. Moreover, PCP-1C treatment reduced hepatic inflammation by inhibiting the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and also improved hepatocyte apoptosis by inhibiting the cytochrome P450 2E1 (CYP2E1)/reactive oxygen species (ROS)/mitogen-activated protein kinases (MAPKs) signaling pathway. Regarding intestinal protection, PCP-1C could repair the intestinal barrier and reduce lipopolysaccharide (LPS) leakage. Generally, PCP-1C exerts a positive therapeutic effect on ALD, which may play a pivotal of decreasing inflammatory factor release, inhibiting oxidative stress and apoptosis, and improving intestinal barrier injury.

Abstract Background Many carcinomas have recurrent chromosomal aneuploidies specific to the tissue of tumor origin. The reason for this specificity is not completely understood. Methods In this study, we looked at the frequency of chromosomal arm gains and losses in different cancer types from the The Cancer Genome Atlas (TCGA) and compared them to the mean gene expression of each chromosome arm in corresponding normal tissues of origin from the Genotype-Tissue Expression (GTEx) database, in addition to the distribution of tissue-specific oncogenes and tumor suppressors on different chromosome arms. Results This analysis revealed a complex picture of factors driving tumor karyotype evolution in which some recurrent chromosomal copy number reflect the chromosome arm-wide gene expression levels of the their normal tissue of tumor origin. Conclusions We conclude that the cancer type-specific distribution of chromosomal arm gains and losses is potentially “hardwiring” gene expression levels characteristic of the normal tissue of tumor origin, in addition to broadly modulating the expression of tissue-specific tumor driver genes.

Objective: Globally, cerebral ischemia has been shown to be the second leading cause of death. Our previous studies have shown that Taohong Siwu Decoction (THSWD) exhibits obvious neuroprotective effects on cerebral ischemia/reperfusion (I/R) injury (CIRI). In this study, we further explored the modulatory effect of THSWD on mitochondrial autophagy in CIRI and the relationship between modulatory effect and NLRP3 inflammatory vesicle activation, so as to further explain the mechanism of neuroprotective effect of THSWD.Methods: Middle cerebral artery occlusion reperfusion (MCAO/R) model in rats was built to simulate I/R. Adult male SD rats (220–270 g) were randomly divided into the following four groups: the sham group, the MCAO/R group, the MCAO/R + THSWD group, and the MCAO/R + THSWD + Mitochondrial division inhibitor 1 (Mdivi-1) group. Neurological defect scores were used to evaluate neurological function. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was conducted to measure cerebral infarct volume. Nissl staining, H&E staining and TUNEL staining were executed to detect ischemic cortical neuronal cell viability and apoptosis. Electron microscopy was used to observe the ultrastructural changes of mitochondria. Total Reactive Oxygen Species (ROS) in tissue were measured by fluorescence spectrophotometry, and the activation status of microglia was evaluated by Iba-1/CD16 immunofluorescence staining. The levels of mitophagy-related proteins (LC3, Parkin, PINK1), NLRP3 inflammasome-related proteins (NLRP3, ASC, Pro-caspase-1, Cleaved-caspase-1), and inflammatory cytokines (Pro-IL-18, Pro-IL-1β, IL-18, IL-1β) were evaluated by western blotting.Results: The studies showed that THSWD treatment alleviated cerebral infarction and neurological deficiencies. THSWD upregulated the expressions of autophagy markers (LC3-II/LC3-I and Beclin1) mitochondrial autophagy markers (Parkin and PINK1) after CIRI. Furthermore, THSWD treatment attenuated microglia activation and damage to mitochondrial structures, thereby reducing ROS production and NLRP3 inflammasome activation. In contrast, the mitochondrial autophagy inhibitor Mdivi-1 inhibited the above beneficial effects of THSWD.Conclusions: THSWD exhibits neuroprotective effects against MCAO/R in rats by enhancing mitochondrial autophagy and reducing NLRP3 inflammasome activation.

Abstract The gut microbiota regulates the biological processes of organisms acting like ‘another’ genome, affecting the health and disease of the host. MicroRNAs, as important physiological regulators, have been found to be involved in health and disease. Recently, the gut microbiota has been reported to affect host health by regulating host miRNAs. For example, Fusobacterium nucleatum could aggravate chemoresistance of colorectal cancer by decreasing the expression of miR-18a* and miR-4802. What’s more, miRNAs can shape the gut microbiota composition, ultimately affecting the host's physiology and disease. miR-515-5p and miR-1226-5p could promote the growth of Fusobacterium nucleatum (Fn) and Escherichia coli (E.coli), which have been reported to drive colorectal cancer. Here, we will review current findings of the interactions between the gut microbiota and microRNAs and discuss how the gut microbiota–microRNA interactions affect host pathophysiology including intestinal, neurological, cardiovascular, and immune health and diseases.

Hepatocyte growth factor (HGF) is a peptide-containing multifunctional cytokine that acts on various epithelial cells to regulate cell growth, movement and morphogenesis, and tissue regeneration of injured organs. HGF is sequestered by heparin-like protein in its inactive form and is widespread in the extracellular matrix of most tissues. When the liver loses its average mass, volume, or physiological and biochemical functions due to various reasons, HGF binds to its specific receptor c-Met (cellular mesenchymal-epithelial transition) and transmits the signals into the cells, and triggers the intrinsic kinase activity of c-Met. The downstream cascades of HGF/c-Met include JAK/STAT3, PI3K/Akt/NF-κB, and Ras/Raf pathways, affecting cell proliferation, growth, and survival. HGF has important clinical significance for liver fibrosis, hepatocyte regeneration after inflammation, and liver regeneration after transplantation. And the development of HGF as a biological drug for regenerative therapy of diseases, that is, using recombinant human HGF protein to treat disorders in clinical trials, is underway. This review summarizes the recent findings of the HGF/c-Met signaling functions in liver regeneration.

The dynamic response of a multi-cabin protective structure subjected to impact load directly affects the protective performance of materials; thus, studying the dynamic response and communication law of wave effect of the load plays an important role in the prediction of protective performance. In this study, the protection experiments of box-structure under air- and/or water-medium are conducted, the dynamic response of the structure subjected to low-impact load is analyzed, and the corresponding numerical simulations are analyzed using the theory of finite element method (FEM). Combined with experimental and FEM simulations, the shock strain distribution, acceleration attenuation, and signal energy in defensive materials are determined. Based on the results, the metal structure exhibits good absorption characteristics for shock vibration. Using the experimental data, we also show that the attenuation of shock wave in water medium should be significantly better than that in air medium, and the protective structure should be designed for a combination of water and air mediums. Meanwhile, the numerical simulation can provide a quantitative analysis process for dynamic analysis of defensive materials.

Abstract The aim of present study was to develop folic acid (FA)‐modified nonionic surfactant vesicles (NISVs, niosomes) as carrier systems for targeted delivery of gambogenic acid (GNA). The FA‐GNA‐NISVs exhibited a mean particle size of 180.77 ± 2.41 nm with a narrow poly dispersion index of 0.147 ± 0.08 determined by dynamic light scattering. Transmission electron microscopy also revealed that the FA‐GNA‐NISVs were spherical with double‐layer structure. Entrapment efficiency (EE%) and zeta potential of the optimal FA‐GNA‐NISVs were 87.84 ± 1.06% and −37.33 ± 0.33 mV, respectively. Differential scanning calorimetry demonstrated that the GNA was in a molecular or amorphous state inside the FA‐NISVs in vitro release profiles suggested that FA‐GNA‐NISVs could release GNA at a sustained manner, and less than 60% of GNA was released from the FA‐NISVs within 12 hours of dialysis. in vivo pharmacokinetic results illustrated that FA‐GNA‐NISVs had considerably higher Cmax, area under curve (AUC0 − t) and accumulation in lung. The cell proliferation study shown that the FA‐GNA‐NISVs significantly enhanced the in vitro cytotoxicity against A549 cells. Flow cytometry and fluorescence microscopy further demonstrated that the FA‐GNA‐NISVs increased apoptosis compared with nonmodified GNA‐NISVs and free GNA. Moreover, FA‐GNA‐NISVs induced A549 cell apoptosis in a dose‐dependent manner. In addition, cellular uptake assays showed a higher uptake of FA‐GNA‐NISVs than GNA‐NISVs as well as free GNA. Taken together, it could be concluded that FA‐GNA‐NISVs were proposed as a novel targeting carriers for efficient delivering of GNA to cancers cells.

Abstract In this study, a novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)‐poly(lactide) (mPEG‐PLA) and poly(ethylene glycol)‐poly(ɛ‐caprolactone) (mPEG‐PCL), used as a novel nanocarrier to encapsulate gambogenic acid (GNA). GNA‐loaded mixed polymeric micelles (GNA‐MMs) was prepared by cosolvent evaporation method. The mean average size of GNA‐MMs was (83.23 ± 1.06) nm (n = 3) and entrapment efficiency (EE%) of GNA‐MMs was (90.18 ± 2.59) % (n = 3) as well as (12.36 ± 0.64) % (n = 3) for drug loading (DL%). Transmission electron microscopy revealed that the GNA‐MMs were spherical with “core‐shell” structures. Compared with free GNA solution, in vitro release of GNA from GNA‐MMs showed a two‐phase sustained release profile: an initial relatively fast phase and followed by a slower release phase. Pharmacokinetic results also indicated that the GNA‐MMs have longer systemic circulation time and slower plasma elimination rate than free GNA solution. Moreover, the in vitro cytotoxicity assay showed that the IC50 values on HepG2 cells for GNA‐MMs and free GNA were (5.67 ± 0.02) μM and (9.02 ± 0.03) μM, respectively. In addition, GNA‐MMs significantly increased the HepG2 cellular apoptosis in a concentration‐dependent manner. In conclusion, the results showed that mPEG‐PLA/mPEG‐PCL mixed micelles may serve as an ideal drug delivery system for GNA to prolong drug circulation time in body, enhance bioavailability and retained its potent antitumor effect.

Rheumatoid arthritis (RA) acts as one of the most common, agnogenic and chronic inflammatory-autoimmune disorder which is characterized by persistent synovitis, cartilage destruction, and joint deformities, leads to a wide range of disabilities, and increased mortality, thus imposing enormous burdens. Several drugs with anti-inflammatory and immunomodulatory properties such as celecoxib, diclofenac and methotrexate are being selected as conventional drugs in the allopathic system of medicine for the treatment of RA in clinic. However, there are some serious side effects more or less when using these drugs because of their short poor bioavailability and biological half-life for a long time. These shortcomings greatly promote the exploration and application of new low- or no-toxicity drugs for treating the RA. Meanwhile, a growing number of studies demonstrate that several herbs present certain anti-inflammatory and anti-arthritic activities through different enzymes and their derivatives, which indicate that they are promising therapeutic strategies when targeting these mediators based on herbal medicinal products in RA research. This review article summarizes the roles of the main enzymes and their derivatives during the pathogenesis of RA, and clearly clarifies the explicit and potential targeted actions of herbal medicinal products that have anti-RA activity. Our review provides timely and critical reference for the scientific rationale use of herbal medicinal products, with the increasing basic research and clinical application of herbal medicinal products by patients with RA.

Colorectal cancer (CRC) is the fourth leading cause of cancer death worldwide, and constitutive activation of the Wnt signaling pathway is universal in most CRC cases. Wnt ligands (Wnts) are secreted glycoproteins and fundamentally essential for the transduction of Wnt signaling pathway. However, the 19 members of Wnts in humans imply a daunting complexity of Wnt signaling and biological effects, and our understanding of their roles in CRC tumorigenesis is still quite rudimentary. This review will give an overview of the structural characteristics and maturation process of Wnts. The expression pattern of all human Wnts in CRC tissues, including Wnt1, Wnt2, Wnt2b, Wnt3, Wnt3a, Wnt4, Wnt5a, Wnt5b, Wnt6, Wnt7a, Wnt7b, Wnt8a, Wnt8b, Wnt9a, Wnt9b, Wnt10a, Wnt10b, Wnt11, and Wnt16, and their relationship with the tumorigenesis and the progression of CRC will be specifically summarized separately. Despite certain challenges, Wnt-based therapeutics for CRC emerge continuously and some are now in clinical trials. In conclusion, a deep understanding of Wnts is very helpful for a better management of this disease.

Gut microbiota, an integral part of the human body, comprise bacteria, fungi, archaea, and protozoa. There is consensus that the disruption of the gut microbiota (termed “gut dysbiosis”) is influenced by host genetics, diet, antibiotics, and inflammation, and it is closely linked to the pathogenesis of inflammatory diseases, such as obesity and inflammatory bowel disease (IBD). Macrophages are the key players in the maintenance of tissue homeostasis by eliminating invading pathogens and exhibit extreme plasticity of their phenotypes, such as M1 or M2, which have been demonstrated to exert pro- and anti-inflammatory functions. Microbiota-derived metabolites, short-chain fatty acids (SCFAs) and Gram-negative bacterial lipopolysaccharides (LPS), exert anti-inflammatory or pro-inflammatory effects by acting on macrophages. Understanding the role of macrophages in gut microbiota-inflammation interactions might provide us a novel method for preventing and treating inflammatory diseases. In this review, we summarize the recent research on the relationship between gut microbiota and inflammation and discuss the important role of macrophages in this context.

Apelin, an endogenous neuropeptide, has been identified as the cognate ligand for the G-protein-coupled receptor APJ. Apelin, APJ messenger RNA, and protein are widely expressed in the central nervous system and peripheral tissues of humans and animals. The apelin/APJ system has been implicated in diverse physiological and pathological processes. The present article reviews the progress of the latest research investigating the apelin/APJ system in pain, depression, anxiety, memory, epilepsy, neuroprotection, stroke, and brain injury and protection, and highlights its promising potential as a therapeutic target for treatment of psychosis and neuropathy.

The output power of a photovoltaic system largely depends on the amount of solar radiation that can be received by the photovoltaic panel, and the solar radiation energy reaching the ground is affected by the radiation transmission process. However, in engineering practice, numerical simulation prediction schemes tend to adopt a kind of radiation scheme, and the prediction of solar radiation and photovoltaic power cannot always meet the prediction accuracy. In this paper, NCEP–NCAR reanalysis data are used as the initial field, and a variety of radiation parameterization schemes are used to produce simulations for the Xinjiang area. Through analysis of examples, it is found that the simulation results differ greatly depending on the radiation parameterization scheme employed, with the maximum absolute error of the total radiation and the predicted power being 106.67 W m−2 and 3.5 MW, respectively. Meanwhile, the mean absolute percentage error of the total radiation ranges from 8.6% to 17.3%, and that of the predicted power from 11.3% to 20.2%. Having analyzed the simulation results of the different radiation parameterization schemes, we conclude that the RRTM/Dudhia and CAM (Community Atmospheric Model) schemes are the most appropriate when under clear-weather conditions.

The aberrant expression of Wnt3 has linked to several types of human malignancies. However, it is not known for its role in tumorigenesis of colorectal cancer (CRC). Herein, we show that Wnt3 is upregulated in human CRC tissues and is essential for the CRC progression. Knockdown of Wnt3 in human CRC cells delayed tumor formation in nude mouse xenografts through silencing of canonical Wnt pathway and glycolysis. We further found that silencing of Wnt3 enhanced the sensitivity of CRC cells to cisplatin through inducing apoptotic cell death. Taken together, it demonstrates that Wnt3 is a novel clinical biomarker for the detection of CRC and plays an important role in colorectal tumorigenesis. Therefore, downregulation of Wnt3 will be a valuable strategy in CRC treatment.

Spexin (SPX), also called neuropeptide Q (NPQ), is a novel endogenous neuropeptide. Spexin gene and protein are widely expressed in central nervous system and peripheral tissues in humans, rodents, goldfish, etc. A few of physiological and pathological roles of spexin are gradually emerged recently. This article summarized the roles of spexin in feeding behavior, gastrointestinal motility, obesity, diabetes, energy metabolism, endocrine, mental diseases, and cardiovascular function. Given the broad roles of spexin, this neuropeptide has attracted much interest from investigators and will be as a promising future target for novel therapeutic research and drug design.

Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor and is associated with ethnicity, genetics, and dietary intake. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been reported as functional regulatory molecules involved in the development of many human cancers, including ESCC. Recently, several ncRNAs have been detected as oncogenes or tumor suppressors in ESCC progression. These ncRNAs influence the expression of specific genes or their associated signaling pathways. Moreover, interactions of ncRNAs are evident in ESCC, as miRNAs regulate the expression of lncRNAs, and further, lncRNAs and circRNAs function as miRNA sponges to compete with the endogenous RNAs. Here, we discuss and summarize the findings of recent investigations into the role of ncRNAs (miRNAs, lncRNAs, and circRNAs) in the development and progression of ESCC and how their interactions regulate ESCC development.

Hepatocellular carcinoma is one of the leading causes of cancer death worldwide and the activation of canonical Wnt signaling pathway is universal in hepatocellular carcinoma patients. MicroRNAs are found to participate in the pathogenesis of hepatocellular carcinoma by activating or inhibiting components in the canonical Wnt signaling pathway. Meanwhile, transcriptional activation of microRNAs by canonical Wnt signaling pathway also contributes to the occurrence and progression of hepatocellular carcinoma. Pharmacological inhibition of hepatocellular carcinoma pathogenesis and other cancers by microRNAs are now in clinical trials despite the challenges of identifying efficient microRNAs candidates and safe delivery vehicles. The focus of this review is on the interplay mechanisms between microRNAs and canonical Wnt signaling pathway in hepatocellular carcinoma, and a deep understanding of the crosstalk will promote to develop a better management of this disease.

The gut microbiota, as the main member in gut microecology, is an essential mediator in health and disease. The gut microbiota interacts with various organs and systems in the body, including brain, lung, liver, bone, cardiovascular system, and others. Microbiota-derived metabolites such as the short chain fatty acid (SCFA) butyrate are primary signals, which link the gut microbiota and physiology. Recently, the gut microbiota has been identified as the origin of a number of diseases by influencing the related cell signaling pathways such as WNT/beta-catenin pathway in colorectal cancer and T cell receptor signaling in the central nervous system. Moreover, several microRNAs participate in signaling networks through the intervention of the gut microbiota. The interaction between the gut microbiota and miRNAs plays a crucial role in vascular dysfunction and hepatocellular carcinoma (HCC). In this review, we will report and discuss recent findings about the crosstalk between the gut microbiota and physical organs and how the gut microbiota and miRNAs regulate each other while influencing the host via genes, proteins, or metabolites.

Aging is associated with age-related diseases and an increase susceptibility of cancer. Dissecting the molecular mechanisms that underlie aging and longevity would contribute to implications for preventing and treating the age-dependent diseases or cancers. Multiple signaling pathways such as the insulin/IGF-1 signaling pathway, TOR signaling, AMPK pathway, JNK pathway and germline signaling have been found to be involved in aging and longevity. And DAF-16/FOXO, as a key transcription factor, could integrate different signals from these pathways to modulate aging, and longevity via shuttling from cytoplasm to nucleus. Hence, understanding how DAF-16/FOXO functions will be pivotal to illustrate the processes of aging and longevity. Here, we summarized how DAF-16/FOXO receives signals from these pathways to affect aging and longevity. We also briefly discussed the transcriptional regulation and posttranslational modifications of DAF-16/FOXO, its co-factors as well as its potential downstream targets participating in lifespan according to the published data in C. elegans and in mammals, and in most cases, we may focus on the studies in C. elegans which has been considered to be a very good animal model for longevity research.

Apelin is an endogenous peptide that is a ligand for the APJ receptor (angiotensin II receptor like-1, AT-1). The apelin/APJ system is distributed in diverse periphery organ tissues. It has been shown that the apelin/APJ system plays various roles in physiology and pathophysiology of many organs. It regulates cardiovascular development or cardiac disease, glycometabolism and fat metabolism as well as metabolic disease. The apelin/APJ system participates in various cell activities such as proliferation, migration, apoptosis or inflammation. However, apelin/APJ function in the liver is still under investigation. In the liver, the apelin-APJ system could play an inhibitory role in liver regeneration and promote Fas-induced apoptosis. It may participate in the formation of hepatic fibrosis or cirrhosis, and even cancer. In this review, we summarize the role of the apelin/APJ system in liver disease.

Bladder cancer is one of the leading causes of cancer-related death in men, however, there was only limited effective treatment for invasive bladder cancer. DAPK1 has been shown to play important role in apoptosis and autophagy to suppress cancer progression. Previous results have shown that DAPK1 promoter was hypermethylated in the majority of bladder cancer specimens, however, the prognostic significance of DAPK1 in bladder cancer has yet to be demonstrated. In the present study, we found that DAPK1 expression was negatively associated with tumor stage and a low level expression of DAPK1 in bladder cancer specimens were associated with shorter survival in bladder cancer patients in 3 independent bladder cancer datasets (n = 462). Further investigation showed that FGFR3 knockdown resulted in downregulation of DAPK1 in bladder cancer cell line, suggesting that FGFR3 may be an upstream factor of DAPK1. Further analysis of the 3 independent bladder cancer datasets have identified ACOX1, UPK2, TRAK1, PLEKHG6 and MT1X genes had their expression significantly correlated with that of DAPK1. Knockdown of DAPK1 in bladder cancer T24 cells resulted in downregulation of ACOX1, UPK2 and TRAK1. Interestingly, TRAK1, by itself, was a favorable prognostic marker in the 3 independent bladder cancer datasets. Importantly, by using connectivity mapping with DAPK1-associated gene signature, we found that vemurafenib and trametinib could possibly reverse DAPK1-associated gene signature, suggesting that inhibition of Raf/MEK pathway may be a potential therapeutic approach for bladder cancer. Indeed, treatment of vemurafenib in T24 bladder cancer cells resulted in upregulation of DAPK1 confirming our connectivity mapping, while knockdown of DAPK1 resulted in reduced sensitivity towards inhibition of Braf signaling by vemurafenib. Together, our results suggest that DAPK1 is an important prognostic marker and therapeutic target for bladder cancer and have identified possible therapeutic agents for future testing in bladder cancer models with low DAPK1 expression.

The HGF/c-MET pathway is active in the development of digestive system cancers, indicating that inhibition of HGF/c-MET signaling may have therapeutic potential. Various HGF/c-MET signaling inhibitors, mainly c-MET inhibitors, have been tested in clinical trials. The observed efficacy and adverse events of some c-MET inhibitors were not very suitable for treating digestive system cancers. The development of new HGF/c-MET inhibitors in preclinical studies may bring promising treatments and synergistic combination (traditional anticancer drugs and c-MET inhibitors) strategies provided anacceptable safety and tolerability. Insights into miRNA biology and miRNA therapeutics have made miRNAs attractive tools to inhibit HGF/c-MET signaling. Recent reports show that several microRNAs participate in inhibiting HGF/c-MET signaling networks through antagonizing c-MET or HGF in digestive system cancers, and the miRNAs-HGF/c-MET axis plays crucial and novel roles for cancer treatment. In the current review, we will discuss recent findings about inhibitors of HGF/c-MET signaling in treating digestive system cancers, and how miRNAs regulate digestive system cancers via mediating HGF/c-MET pathway.

Objective To analyse the location of pathogenic genes of autosomal dominant Charcot⁃Marie⁃Tooth disease (CMT, peroneal atrophy) in a Chinese pedigree. Methods The pedigree of autosomal dominant Charcot ⁃ Marie ⁃ Tooth disease was confirmed by genetic pattern, clinical manifestation and neuromuscular electrophysiological and laboratory examinations. Linkage analysis was performed by using 37 microsatellite genetic markers for the autosomal dominant Charcot⁃Marie⁃Tooth disease pedigree. Thirty⁃ seven microsatellite genetic markers covering 16 genetic loci were linked to 20 kinds of known autosomal dominant Charcot ⁃ Marie ⁃ Tooth disease. The 16 genetic loci were 17p11.2 ⁃ p12 (D17S839, D17S122, D17S793), 1q22 (D1S426, D1S2771), 16p12.3⁃p13.1 (D16S764, D16S3137), 10q21.1 (D10S546, D10S561, D10S581), 1p36.2 (D1S2845, D1S2893, D1S2660), 3q21 (D3S1273, D3S1292), 12q23 (D12S1329, D12S105), 7p15 (D7S2562, D7S516), 8p21 (D8S552, D8S265), 7q11⁃q21 (D7S634, D7S669), 12q12⁃q13 (D12S1663, D12S368, D12S1632), 8q13 ⁃ q21 (D8S286, D8S548), 12q24.3 (D12S1679, D12S86), 10q24 (D10S554, D10S571, D10S1863), 19p12 ⁃ p13 (D19S916, D19S433) and 1p34 ⁃ p35 (D1S489, D1S432). Results All microsatellite genetic markers were amplified successfully, and polymorphisms were presented on every genetic loci. The examined pedigree of Charcot ⁃ Marie ⁃ Tooth disease was autosomal dominant inheritance. Three patients did not present the same allele on the 16 genetic loci. Linkage analysis indicated that the pathogenic genes in all the members of this pedigree did not link with the 16 known pathogenic genetic loci in autosomal dominant Charcot ⁃ Marie ⁃ Tooth disease. Conclusion The diagnosis of autosomal dominant Charcot ⁃ Marie⁃Tooth disease in this pedigree is confirmed, but do not coincide with the diagnostic criteria of the known types of this disease recommended by European Neuromuscular Center (ENMC). It is suggested that autosomal dominant Charcot⁃Marie⁃Tooth disease in this Chinese pedigree may be a new type caused by other pathogenic genes. DOI：10.3969/j.issn.1672-6731.2010.03.018

A dual-polarization substrate-integrated Fabry-Pérot cavity (SI-FPC) antenna is presented in this paper. The patch embedded in SI-FPC is excited with a near-field coupled feeding structure for V-polarization and with a slot-coupled feeding structure for H-polarization. The feeding structures are separated by a ground plane to improve the isolation between the ports. As a design example, an antenna operating at 10.0 GHz is fabricated and measured. A high degree of port isolation (25 dB) can be achieved.