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Meng Chen,1,2 Yang Li,1,2 Wen-Xiu Hou,3 Da-Yong Peng,1,2 Jing-Kun Li,1,2 Hao-Xuan Zhang1,2 1Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong Province, 250014, People’s Republic of China; 2Department of Orthopedic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, 250014, People’s Republic of China; 3Department of Spine Surgery, Shandong University Qilu Hospital, Jinan, Shandong, 250000, People’s Republic of ChinaCorrespondence: Hao-Xuan Zhang, Department of Orthopedics, The First Affiliated Hospital of Shandong First Medical University, No. 16766, Lixia District, Jingshi Road, Jinan, Shandong Province, 250014, People’s Republic of China, Tel/Fax +86531-89268540, Email hoho0605@126.comPurpose: The repair and treatment of infected bone defects (IBD) is a common challenge faced by orthopedic clinics, medical materials science, and tissue engineering.Methods: Based on the treatment requirements of IBD, we utilized multidisciplinary knowledge from clinical medicine, medical materials science, and tissue engineering to construct a high-efficiency vancomycin sustained-release system with nanodiamond (ND) and prepare a composite scaffold. Its effect on IBD treatment was assessed from materials, cytology, bacteriology, and zoology perspectives.Results: The results demonstrated that the Van-ND-45S5 scaffold exhibited an excellent antibacterial effect, biocompatibility, and osteogenesis in vitro. Moreover, an efficient animal model of IBD was established, and a Van-ND-45S5 scaffold was implanted into the IBD. Radiographic and histological analyses and bone repair-related protein expression, confirmed that the Van-ND-45S5 scaffold had good biocompatibility and osteogenic and anti-infective activities in vivo.Conclusion: Collectively, our findings support that the Van-ND-45S5 scaffold is a promising new material and approach for treating IBD with good antibacterial effects, biocompatibility, and osteogenesis.Graphical Abstract: Keywords: antibacterial effect, nanodiamond, scaffold, infected bone defects

The aggressive nature of lung cancer is frequently accompanied by a high incidence of bone metastasis; however, proximal femoral metastasis from lung cancer is comparatively uncommon when compared to other malignancies. In this report, we present the case of a 53-year-old Asian male who presented with pain in the left thigh and back. Magnetic resonance imaging revealed severe bone destruction with involvement of adjacent soft tissue mass at the left thigh, exhibiting imaging findings that mimic osteosarcoma. Subsequent bone biopsy confirmed the diagnosis of epidermal growth factor receptor ( EGFR )-mutated lung adenocarcinoma with bone metastasis. The patient achieved survival following administration of osimertinib and underwent surgery for femoral metastases without palliative surgery for lung cancer. Therefore, proximal femoral metastasis from EGFR -mutated lung adenocarcinoma should be considered as a differential diagnosis in patients suspected to have osteosarcoma. The imaging findings of proximal femoral metastasis from EGFR -mutated lung adenocarcinoma were presented, and their therapeutic management was discussed., Competing Interests: The authors declared no conflict of interest., (Copyright 2024, Chen et al.)

To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P < 0.05 were considered statistically significant. Beta diversity analysis showed that there was a significant difference between groups (P = 0.046). LEfSe detected four kinds of characteristic microorganisms in the EPS of patients with IIIB prostatitis before and after LIPUS treatment. After multiple comparisons among groups by DESeq2 method, six different microorganisms were found. LIPUS may improve patients' clinical symptoms by changing the flora structure of EPS, stabilizing and affecting resident bacteria or opportunistic pathogens., (© 2024. The Author(s).)

The chemical composition of Ganoderma lucidum ethanol extracts was systematically analyzed and identified by ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Orbitrap-HRMS). The fragmentation pattern of the representative chemical compounds was summarized, and the potential anti-liver fibrosis active compounds of G. lucidum acting on the farnesoid X receptor(FXR) target were studied to elucidate its pharmacodynamic substance basis. Preliminarily, 95 chemical constituents of G. lucidum ethanol extracts were identified, including 24 ganoderic acids, 9 ganoderenic acids, 13 lucidenic acids, 3 ganolucidic acids, 1 ganoderma lactone, 40 other triterpenoids, 4 fatty acids, and 1 other constituent. In addition, the fragmentation patterns of the representative compounds were also analyzed. The structural characteristics of ganoderic acids and ganoderenic acids were the C30 skeleton, containing free-COOH and-OH groups, which could easily lose H&#95;2O and CO&#95;2 to form fragment ions. The D-ring was mostly a five-membered ring, which was prone to breakage. Lucidenic acids were the lanosterolane-type of the C27 skeleton, and the side-chain structure became shorter and contained the same free-COOH and-OH compared with ganoderic acids, which had been reduced from 8 to 5 cartons and prone to lose H&#95;2O and CO&#95;2. Then, six reported FXR receptor agonists were selected to form a training set for establishing a pharmacophore model based on FXR ligands. The 95 identified chemical constituents of G. lucidum were matched with the pharmacophore, and the optimal pharmacophore model 02(sensitivity=0.750 00, specificity=0.555 56, ROC=0.750) was selected for the virtual screening of the G. lucidum compound library through the validation of the test set. Finally, 31 potential G. lucidum active constituents were screened and chosen to activate the FXRs. The ADMET results showed that ganoderic acid H and lucidenic acid J had less than 90% plasma protein binding rate and no hepatotoxicity, which could be used as FXR activators for developing clinical drugs for the treatment of liver fibrosis, either alone or in combination.

Nonalcoholic fatty liver disease (NAFLD) is marked by hepatic steatosis accompanied by an inflammatory response. At present, there are no approved therapeutic agents for NAFLD. Dendrobium Huoshanense polysaccharide (DHP), an active ingredient extracted from the stems of Dendrobium Huoshanense , and exerts a protective effect against liver injury. However, the therapeutic effects and mechanisms of action DHP against NAFLD remain unclear. DHP was extracted, characterized, and administered to mice in which NAFLD had been induced with a high-fat and high-fructose drinking (HFHF) diet. Our results showed that DHP used in this research exhibits the characteristic polysaccharide peak with a molecular weight of 179.935 kDa and is composed primarily of Man and Glc in a molar ratio of 68.97:31.03. DHP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFHF-induced NAFLD mice, as evidenced by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG). Furthermore, DHP administration reduced hepatic steatosis, as shown by H&E and Oil red O staining. DHP also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway expression, thereby reducing levels of hepatic proinflammatory cytokines. Besides, untargeted metabolomics further indicated that 49 metabolites were affected by DHP. These metabolites are strongly associated the metabolism of glycine, serine, threonine, nicotinate and nicotinamide, and arachidonic acid. In conclusion, DHP has a therapeutic effect against NAFLD, whose underlying mechanism may involve the modulation of TLR4/NF-κB, reduction of inflammation, and regulation of the metabolism of glycine, serine, threonine, nicotinate and nicotinamide metabolism, and arachidonic acid metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Deng, Zhao, Cai, Zhang, Ma, Lv, Jiang, Peng, Wang, Xing and Yu.)

At present, phenolic acid derivatives and triazole derivatives have a good antifungal effect, which has attracted widespread attention. A series of novel phenolic acid triazole derivatives were synthesized, and their structures were characterized by IR, MS, NMR, and X-ray crystal diffraction. Compound methyl 4-(2-bromoethoxy)benzoate, methyl 4-(2-(1 H -1,2,4-triazol-1-yl) ethoxy)benzoate, 4-(2-(1 H -1,2,4-triazol-1-yl)ethoxy)benzoic acid and 4-(2-(1 H -1,2,4-triazol-1-yl) ethoxy)-3-methoxybenzoic acid crystallize in the monoclinic system with space group P2 1 /n , the monoclinic system with space group P2 1 , the monoclinic system with space group P2 1 and the orthorhombic system with space group Pca2 1 , respectively. At a concentration of 100 μg/mL and 200 μg/mL, the antifungal activity against seven plant pathogen fungi was determined. Compound methyl 4-(2-bromoethoxy)benzoate has the best inhibitory effect on Rhizoctonia solani AG1 , and the inhibitory rate reached 88.6% at 200 μg/mL. The inhibitory rates of compound methyl 4-(2-(1 H -1,2,4-triazol-1-yl) ethoxy)benzoate against Fusarium moniliforme and Sphaeropsis sapinea at a concentration of 200 μg/mL were 76.1% and 75.4%, respectively, which were better than that of carbendazim.

The potential anti-stroke active components in Taohong Siwu Decoction(THSWD) were identified by target cell trapping coupled with ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of active components in THSWD in the treatment of ischemic stroke(IS) was explored by network pharmacology, molecular docking, and experimental validation. The UPLC-Q-TOF-MS technology combined with the UNIFI data analysis platform was used to analyze the composition of the cellular fragmentation fluid after co-incubation of THSWD with target cells. The targets of potential active components and IS were collected by network pharmacology, and the common targets underwent protein-protein interaction(PPI), Gene Ontology(GO), and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analyses. The target cell trapping component-core target-signaling pathway network was constructed, and the active components were molecularly docked to the top targets in the PPI network, followed by pharmacodynamic validation in vitro. Fifteen active components were identified in the target cellular fragmentation fluid, including bicyclic monoterpenes, cyanoglycosides, flavonols, quinoid chalcones, phenylpropanoids, and tannins. As revealed by the analysis of network pharmacology, THSWD presumably regulated PI3K-AKT, FoxO, MAPK, Jak-STAT, VEGF, HIF-1, and other signaling pathways to affect inflammatory cascade reaction, angiogenesis, oxidative stress, pyroptosis, apoptosis, and other pathological processes via paeoniflorin, butylphthalide, dehydrated safflower yellow B, 3,4-dicaffeoylquinic acid, amygdalin, paeoniflorin, and ligusticolactone. Molecular docking and in vitro pharmacodynamic validation revealed that the target cell trapping active components could promote neovascularization in rat brain microvascular endothelial cells(rBMECs) in the oxygen-glucose deprivation/reoxygenation(OGD/R) model. The application of target cell trapping coupled with UPLC-Q-TOF-MS technology can rapidly screen out the potential active components in THSWD. The active components of THSWD can be predicted to intervene in the pathogenesis of IS through network pharmacology, and molecular docking combined with experimental validation can further clarify the efficacy, thus providing a theoretical basis for research ideas on the pharmacodynamic substance basis of traditional Chinese medicine compounds.

In this study, visual-near infrared(VNIR), short-wave infrared(SWIR), and VNIR + SWIR fusion hyperspectral data of Polygonatum cyrtonema from different geographical origins were collected and preprocessed by first derivative(FD), second derivative(SD), Savitzky-Golay smoothing(S-G), standard normalized variate(SNV), multiplicative scatter correction(MSC), FD+S-G, and SD+S-G. Three algorithms, namely random forest(RF), linear support vector classification(LinearSVC), and partial least squares discriminant analysis(PLS-DA), were used to establish the identification models of P. cyrtonema origin from three spatial scales, i.e., province, county, and township, respectively. Successive projection algorithm(SPA) and competitive adaptive reweighted sampling(CARS) were used to screen the characteristic bands, and the P. cyrtonema origin identification models were established according to the selected characteristic bands. The results showed that(1)after FD preprocessing of VNIR+SWIR fusion hyperspectral data, the accuracy of recognition models established using LinearSVC was the highest, reaching 99.97% and 99.82% in the province origin identification model, 100.00% and 99.46% in the county origin identification model, and 99.62% and 98.39% in the township origin identification model. The accuracy of province, county, and township origin identification models reached more than 98.00%.(2)Among the 26 characteristic bands selected by CARS, after FD pretreatment, the accuracy of origin identification models of different spatial scales was the highest using LinearSVC, reaching 98.59% and 97.05% in the province origin identification model, 97.79% and 94.75% in the county origin identification model, and 90.13% and 87.95% in the township origin identification model. The accuracy of identification models of different spatial scales established by 26 characteristic bands reached more than 87.00%. The results show that hyperspectral imaging technology can realize accurate identification of P. cyrtonema origin from different spatial scales.

To realize the non-destructive and rapid origin discrimination of Poria cocos in batches, this study established the P. cocos origin recognition model based on hyperspectral imaging combined with machine learning. P. cocos samples from Anhui, Fujian, Guangxi, Hubei, Hunan, Henan and Yunnan were used as the research objects. Hyperspectral data were collected in the visible and near infrared band(V-band, 410-990 nm) and shortwave infrared band(S-band, 950-2 500 nm). The original spectral data were divided into S-band, V-band and full-band. With the original data(RD) of different bands, multiplicative scatter correction(MSC), standard normal variation(SNV), S-G smoothing(SGS), first derivative(FD), second derivative(SD) and other pretreatments were carried out. Then the data were classified according to three different types of producing areas: province, county and batch. The origin identification model was established by partial least squares discriminant analysis(PLS-DA) and linear support vector machine(LinearSVC). Finally, confusion matrix was employed to evaluate the optimal model, with F1 score as the evaluation standard. The results revealed that the origin identification model established by FD combined with LinearSVC had the highest prediction accuracy in full-band range classified by province, V-band range by county and full-band range by batch, which were 99.28%, 98.55% and 97.45%, respectively, and the overall F1 scores of these three models were 99.16%, 98.59% and 97.58%, respectively, indicating excellent performance of these models. Therefore, hyperspectral imaging combined with LinearSVC can realize the non-destructive, accurate and rapid identification of P. cocos from different producing areas in batches, which is conducive to the directional research and production of P. cocos.

Background: Plant cell culture technology is a potential way to produce polyphenols, however, this way is still trapped in the dilemma of low content and yield. Elicitation is regarded as one of the most effective ways to improve the output of the secondary metabolites, and therefore has attracted extensive attention. Methods: Five elicitors including 5-aminolevulinic acid (5-ALA), salicylic acid (SA), methyl jasmonate (MeJA), sodium nitroprusside (SNP) and Rhizopus Oryzae Elicitor (ROE) were used to improve the content and yield of polyphenols in the cultured Cyclocarya paliurus (C. paliurus) cells, and a co-induction technology of 5-ALA and SA was developed as a result. Meanwhile, the integrated analysis of transcriptome and metabolome was adopted to interpret the stimulation mechanism of co-induction with 5-ALA and SA. Results: Under the co-induction of 50 μM 5-ALA and SA, the content and yield of total polyphenols of the cultured cells reached 8.0 mg/g and 147.12 mg/L, respectively. The yields of cyanidin-3-O-galactoside, procyanidin B1 and catechin reached 28.83, 4.33 and 2.88 times that of the control group, respectively. It was found that expressions of TFs such as CpERF105, CpMYB10 and CpWRKY28 increased significantly, while CpMYB44 and CpTGA2 decreased. These great changes might further make the expression of CpF3'H (flavonoid 3'-monooxygenase), CpFLS (flavonol synthase), CpLAR (leucoanthocyanidin reductase), CpANS (anthocyanidin synthase) and Cp4CL (4-coumarate coenzyme A ligase) increase while CpANR (anthocyanidin reductase) and CpF3'5'H (flavonoid 3', 5'-hydroxylase) reduce, ultimately enhancing the polyphenols accumulation Conclusion: The co-induction of 5-ALA and SA can significantly promote polyphenol biosynthesis in the cultured C. paliurus cells by regulating the expression of key transcription factors and structural genes associated with polyphenol synthesis, and thus has a promising application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ling, Wang, Pan, Tang, Yuan, Zhang, Chen, Peng and Yin.)

Background: In the present work, we aimed to explore the correlated factors of quality of life in patients receiving lumbar fusion for lumbar degenerative disc disease (DDD) in China., Methods: A total of 180 patients treated with lumbar fusion were included in the present study. Their general demographic characteristics, Visual Analog Scale (VAS) scores, Japanese Orthopedic Association (JOA) scores, Simplified Coping Style Questionnaire (SCSQ), Social Support Questionnaire (SSQ), and Medical Outcomes Study Short Form 36 (MOS SF-36) were collected and evaluated preoperatively and at 1 year postoperatively., Results: There were significant improvements in scores of VAS, JOA, and quality of life of patients from preoperation to 1-year postoperation after lumbar fusion. Marital status, with or without children, education level, economic pressure, and social support had significant predictive effects on the physical health of patients undergoing lumbar fusion. Marital status, education level, and economic pressure had significant predictive effects on the mental health of patients undergoing lumbar fusion., Conclusions: Factors correlated with the physical health of patients after lumbar fusion included positive coping style, negative coping style, social support, age, education level (high school college), disease duration (5-10), suffering from other diseases (combined with two or more other disease) and the number of surgical segments (double and three or more). Factors correlated with the mental health included negative coping style, social support, age, education level (middle school and high school college) and the number of surgical segments (double and three or more). The results verify that these factors were correlated to the patient's quality of life after lumbar fusion. Emphasizing and selectively intervening these correlated factors can further improve the quality of life in patients receiving lumbar fusion for lumbar degenerative disc disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Chen, Peng, Hou, Li, Li and Zhang.)

Heteroatom doping was recently regarded as an effective method to tune the band gap and improve the separation and transfer of photogenerated electron-hole pairs in semiconductor photocatalysts. Herein, a novel S,F-codoped Bi 2 WO 6 (S,F-Bi 2 WO 6 ) with suitable oxygen vacancies was synthesized via the hydrothermal-calcination and post-sulfurization, for efficient Cr(VI) reduction and methyl orange (MO) degradation under visible light. The amount of surface oxygen vacancies could be controlled by adjusting the S/F ratio during the doping process, which modulated the band structure and photogenerated charge behavior of Bi 2 WO 6 . The optimal S 0.10 F-Bi 2 WO 6 exhibited an excellent photooxidation-reduction performance, which Cr(VI) reduction and MO degradation efficiencies were 1.6 and 2.6 times than those of the pristine Bi 2 WO 6 without oxygen vacancy under visible-light, respectively. The enhanced photooxidation-reduction performance was because the right amount of oxygen vacancies could effectively narrow the bandgap and improve the separation efficiency of electron-hole pairs. Thus, this work offered a mild and simply approach for preparing heteroatom doped Bi 2 WO 6 and a potential to be extended to the synthesis of other doped materials for environmental remediation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods.

Reference-based scaffolding is an important process used in genomic sequencing to order and orient the contigs in a draft genome based on a reference genome. In this study, we utilize the concept of genome rearrangement to formulate this process as an exemplar breakpoint distance (EBD)-based scaffolding problem, whose aim is to scaffold the contigs of two given draft genomes, both containing duplicate genes (or sequence markers) and acting with each other as a reference, such that the EBD between the scaffolded genomes is minimized. The EBD-based scaffolding problem is difficult to solve because it is non-deterministic polynomial-time (NP)-hard. In this work, we design an integer linear programming (ILP)-based algorithm to exactly solve the EBD-based scaffolding problem. Our experimental results on both simulated and biological data sets show that our ILP-based scaffolding algorithm can accurately and efficiently use a reference genome to scaffold the contigs of a draft genome. Moreover, our ILP-based scaffolding algorithm with considering duplicate genes indeed has better accuracy performance than that without considering duplicate genes, suggesting that duplicate genes and their exemplars are helpful for the application of genome rearrangement in the study of the reference-based scaffolding problem. When compared with RaGOO, a current state-of-the-art alignment-based scaffolder, our ILP-based scaffolding algorithm still has better accuracy performance on the biological data sets.

Clinopodium chinense, a traditional folk medicinal herb, has been used to treat abnormal uterine bleeding(AUB) for many years. Saponins and flavonoids are the main active components in C. chinense. To study the pharmacokine-tics of multiple components from the total extract of C. chinense(TEC), we established a sensitive and rapid method of ultra-perfor-mance liquid chromatography coupled with tandem mass spectrometry(UPLC-MS/MS) for simultaneous determination of five compounds in the plasma of AUB rats. After validation, the AUB model was established with SD female rats which got pregnant on the same day by gavage with mifepristone(12.4 mg·kg~(-1)) and misoprostol(130 μg·kg~(-1)). The established method was applied to the detection of hesperidin, naringenin, apigenin, saikosaponin a, and buddlejasaponin Ⅳb in AUB rats after the administration of TEC. The pharmacokinetic parameters were calculated by DAS 2.0. The five compounds showed good linear relationship within the detection range. The specificity, accuracy, precision, recovery, matrix effect, and stability of the method all matched the requirements of biolo-gical sample detection. The above 5 compounds were detected in the plasma of AUB rats after the administration of TEC. The C&#95;(max) va-lues of hesperidin, naringenin, apigenin, saikosaponin a, and clinoposide A were 701.6, 429.5, 860.7, 75.1, and 304.1 ng·mL~(-1), respectively. All the compounds owned short half-life and quick elimination rate in vivo, and the large apparent volume of distribution indicated that they were widely distributed in tissues. Being rapid, accurate, and sensitive, this method is suitable for the pharmacokinetic study of extracts of Chinese herbal medicines and provides a reference for the study of pharmacodynamic material basis of C. chinense in treating AUB.

The aerial part of ​ Rubia cordifolia  ​L. has been used as an herbal medicine for a long time with various pharmacological activities, including anti-inflammatory, anticancer, and antibacterial activities. The most notable usage of these was that this herbal medicine had good therapeutic effects on diarrhea caused by various factors. However, the mechanism for the ethanolic extract of ​ R. cordifolia  ​L. (RCEE) to treat Ulcerative colitis (UC) effectively is still unclear. In this study, DSS successfully induced UC mice and then intervene using different polar parts of RCEE. The results indicated that RCEE-treatment inhibited colonic combination NLRP3 inflammasome formation and IL-6/JAK2/STAT3 activation in vivo, significantly ameliorating the clinical symptoms, including alleviating colonic mucosal damage and infiltration of macrophages, suppressing the release of inflammatory cytokines, and reducing mortality. Taken together, this study suggests that dual inhibition of NLRP3 inflammasome and IL-6/JAK2/STAT3 pathways activation using RCEE may be a promising therapeutic strategy for preventing the progression of UC., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Wang, Chen, Duan, Sun, Huang, Peng, Yu, Wang and Zhang.)

A novel three-dimensional (3D) network rodlike Ag 2 S/Bi 2 SiO 5 photocatalyst with a p-n heterostructure composed of ultrafine Ag 2 S nanoparticles (NPs) and Bi 2 SiO 5 nanosheets was prepared using an anionic self-regulation strategy by a two-step hydrothermal process. The architecture facilitated the efficient transfer and separation of photogenerated electron-hole pairs. The optimal Ag 2 S/Bi 2 SiO 5 composite (ABSO 0.10 ) exhibited an excellent reduction activity (93.5% Cr(VI) removal in wastewater containing 50 mg·L -1 Cr(VI) within 90 min under visible light), which was about 11.2 and 25.6 times higher than that of the pristine Ag 2 S and virgin Bi 2 SiO 5 , respectively. Assisted by experiments and density functional theory (DFT) calculations, a possible photocatalytic mechanism for Cr(VI) reduction over the Ag 2 S/Bi 2 SiO 5 composite under visible-light irradiation was proposed.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ji, Shi, Li, Hou, Yang, Liu, Duan, Liu, Chen and Peng.)

This study aims to explore the anti-inflammatory and hemostatic effects of the total extract of Clinopodium chinense(TEC), total saponins of C. chinense(TSC), and total flavonoids of C. chinense(TFC) in female rats with abnormal uterine bleeding(AUB), and the possible mechanism. Mifepristone(i.g., 12.4 mg·kg~(-1)) and misoprostol(i.g., 130 μg·kg~(-1)) were used to induce AUB in SD female rats conceiving on the same day. Then the AUB rats were randomized into model group, TEC group, TSC group, TFC group, Yimucao Granules(LG) group, and estradiol valerate(EV) group, with 8 rats in each group. Another 8 non-pregnant female rats were selected as normal group. During the experiment, each group was given the corresponding drug by gavage once a day for 7 days. After the administration, blood and uterine tissue were collected. The uterine bleeding volume was measured by ultraviolet spectrophotometry and the pathological changes of endometrium were observed based on hematoxylin-eosin(HE) staining. In addition, the microvessel density of endometrium was determined by immunohistochemistry, and the content of thromboxane B2(TXB2), 6-keto-PGF&#95;(1α), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in plasma and levels of lutenizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E&#95;2), and progesterone in serum were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expression of estrogenreceptor α(ERα), progesterone receptor(PR), matrix metalloproteinase(MMP)-2, MMP-9, and vascular endothelial growth factor(VEGF) in uterine tissue was determined by Western blot. Compared with the model group, TEC, TSC, and TFC can reduce uterine bleeding volume, alleviate the pathological damage of endometrium, and increase the microvessel density in endometrium. Moreover, TEC and TSC can significantly raise plasma TXB2 level and ratio of TXB2 to 6-keto-PGF&#95;(1α), and TEC and TFC can significantly reduce the levels of IL-6 and TNF-α. In addition, TEC significantly elevated serum progesterone level and TFC significantly increased serum levels of E&#95;2, FSH, and LH. TSC can significantly raise serum progesterone and FSH levels. In addition, TEC can significantly down-regulate the protein expression of PR, MMP-2, and VEGF and TSC significantly reduced the expression of MMP-9. TFC significantly decreased the expression of PR, MMP-9, and VEGF, and up-regulated the expression of ERα. In conclusion, TEC, TSC, and TFC all show therapeutic effects on AUB, particularly TEC. TSC exerts the effects by enhancing the coagulation function and promoting endometrial repair, and TFC by regulating estrogen levels and reducing inflammatory response. This study reveals the mechanism of C. chinense against AUB and also explains the holistic characteristics of Chinese medicine.

Wuzi-Yanzong-Wan (WZYZW) is a classic prescription for male infertility. Our previous investigation has demonstrated that it can inhibit sperm apoptosis via affecting mitochondria, but the underlying mechanisms are unclear. The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore (mPTP) in mouse spermatocyte cell line (GC-2 cells) opened by atractyloside (ATR). At first, WZYZW-medicated serum was prepared from rats following oral administration of WZYZW for 7 days. GC-2 cells were divided into control group, model group, positive group, as well as 5%, 10%, 15% WZYZW-medicated serum group. Cyclosporine A (CsA) was used as a positive control. 50 μmol·L -1 ATR was added after drugs incubation. Cell viability was assessed using CCK-8. Apoptosis was detected using flow cytometry and TUNEL method. The opening of mPTP and mitochondrial membrane potential (MMP) were detected by Calcein AM and JC-1 fluorescent probe respectively. The mRNA and protein levels of voltage-dependent anion channel 1 (VDAC1), cyclophilin D (CypD), adenine nucleotide translocator (ANT), cytochrome C (Cyt C), caspase 3, 9 were detected by RT-PCR (real time quantity PCR) and Western blotting respectively. The results demonstrated that mPTP of GC-2 cells was opened after 24 hours of ATR treatment, resulting in decreased MMP and increased apoptosis. Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associated with increased MMP and decreased apoptosis. Moreover, the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDAC1 and CypD, Caspase-3, 9 and CytC, as well as a increased ratio of Bcl/Bax. However, ANT was not significantly affected. Therefore, these findings indicated that WZYZW inhibited mitochondrial mediated apoptosis by attenuating the opening of mPTP in GC-2 cells. WZYZW-medicated serum inhibited the expressions of VDAC1 and CypD and increased the expression of Bcl-2, which affected the opening of mPTP and exerted protective and anti-apoptotic effects on GC-2 cell induced by ATR., (Copyright © 2022 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Objective: To explore the mechanism of the action of the miR-576/ALK4 axis on the progression of prostate cancer (PCa)., Methods: PCa cells were transfected with miR-576 mimics/inhibitor, the proliferation and migration distance of the cells were detected by MTT and scratch wound healing assay, respectively. The targeted regulation effect of miR-576 on ALK4 was verified by dual-luciferase reporter assay. The effects of miR-576 on the mRNA and protein expressions and phosphorylation levels of the ALK4 and JAK/STAT signaling pathway factors JAK2 and STAT3 were determined by qPCR and Western blot, respectively. The C4-2 cells were co-treated with sh-ALK4 and Ruxolitinib for measurement of the proliferation and migration of the PCa cells., Results: Bioinformatics analysis and binding site prediction showed that miR-576 was up-regulated in the PCa cells, and dual-luciferase reporter assay revealed its targeted regulation effect on ALK4 and its impact on the phosphorylation levels of JAK2 and STAT3. Overexpressed miR-576 promoted while knocked-down miR-576 inhibited the proliferation and migration of the PCa cells. sh-ALK4 increased the proliferation and migration of the cells, while Ruxolitinib suppressed the promoting effect of sh-ALK4., Conclusion: The expression of miR-576 is up-regulated in PCa, inhibits the expression of ALK4, regulates the activity of the JAK and STAT signaling pathways, and promotes the proliferation and migration of PCa cells.

The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(P&lt;0.05), and potentiated activity of SOD(P&lt;0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.

Salviae Miltiorrhizae Radix et Rhizoma is a Chinese herbal medicine that promotes blood circulation to remove blood stasis, nourishes blood to tranquilize the mind, and cools blood to disperse carbuncles. Salviae Miltiorrhizae Radix et Rhizoma has microcirculation-improving, blood vessel-dilating, atherosclerosis-preventing, anti-inflammatory, anti-tumor, and blood pressure-and blood lipid-lowering activities. As research progresses, the chemical composition, pharmacological effect, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma have attracted much attention. We reviewed the research progress in this field. Based on the concept of quality marker(Q-marker) in traditional Chinese medicine, the Q-markers of Salviae Miltiorrhizae Radix et Rhizoma were predicted and analyzed from the aspects of quality transfer, traceability, ingredient specificity, association between ingredients and pharmacological effects, ingredient predictability, and compounding environment. This review provides a scientific basis for the quality control of Salviae Miltiorrhizae Radix et Rhizoma and its preparations.

To find the polysaccharide with hepatoprotective activity from Poria cocos and clarify its structure, a galactoglucan (PCP-1C) with a molecular weight of 17 kDa was purified from the Poria cocos sclerotium by column chromatography and activity evaluation in the present work. It was composed of galactose, glucose, mannose, and fucose in a molar percentage of 43.5: 24.4: 17.4: 14.6. Structural characterization showed that PCP-1C has a backbone consisted of 1,6-α-D-Galp, which branches composed of 1,3-β-D-Glcp, 1,4-β-D-Glcp, 1,6-β-D-Glcp, T-β-D-Glcp, T-α-D-Manp, T-α-L-Fucp and 1,3-α-L-Fucp. In vivo experiments found that PCP-1C can apparently improve the damage of liver tissue in CCl 4 -treated mice and relieve oxidative stress and inflammation. PCP-1C also reduced the expression of CAR and CYP2E1 in the liver. These findings indicated strong hepatoprotective effect of PCP-1C, which was attributed to the reduction of CCl 4 metabolism via inhibiting the CAR/CYP2E1 signal pathway., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Glycyrrhizae Radix et Rhizoma, a traditional Chinese herbal medicine, mainly contains triterpenoids, flavonoids, polysaccharides, coumarins and volatile oils with many pharmacological activities such as anti-tumor, anti-bacterial, anti-viral, anti-inflammatory, immune regulatory and anti-fibrotic effects. The widespread applications of Glycyrrhizae Radix et Rhizoma in food, medicine and chemical industries make its demand increase gradually. Therefore, the quality guarantee of the medicinal is of great value. Starting from the elaboration of chemical components and pharmacological effects of Glycyrrhizae Radix et Rhizoma and the introduction to the concept of quality marker(Q-marker), this study analyzed the Q-markers of Glycyrrhizae Radix et Rhizoma from the aspects of plant phylogene-tics, chemical component specificity, traditional efficacy, traditional medicinal properties, absorbed components, different processing methods and so on, which provides reference for quality evaluation, development and utilization of Glycyrrhizae Radix et Rhizoma.

The present study explored the beneficial effect of Dendrobium huoshanense stem polysaccharide (cDHPS) after oral administration on rheumatoid arthritis (RA) using type Ⅱ collagen-induced arthritis (CIA) mouse model. It was found that cDHPS effectively alleviated joint swelling, synovial hyperplasia, pannus formation, cartilage erosion and bone destruction in CIA mice. Concurrently, cDHPS remodeled the balance of Th17 and regulatory T cells, reduced the secretion of pro-inflammatory mediators related to fibroblast-like synoviocyte activation, angiogenesis, articular cartilage degradation and osteoclast differentiation, inhibited HIF-1α expression and promoted anti-inflammatory mediator release in the joint tissues and serum of CIA mice. Western blot of joint tissues showed that cDHPS significantly inhibited the phosphorylation of IκB, p65, JNK, p38, ERK1/2, AKT, PI3K, JAK1 and STAT3 in CIA mice. These results suggest that cDHPS possesses the potential of ameliorating RA and its anti-RA effect may be attributed to the inhibition of inflammatory signaling pathways., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Five new natural compounds ( 1 - 5 ) along with four known ones, involving dibenzo- α -pyrone derivatives, a benzo- γ -pyrone derivative and an amide-type compound were obtained from Alternaria alternata , an endophyte isolated from Paeonia lactiflora. The structures of these isolates were elucidated by intensive analysis of spectroscopic data including NMR, HRMS (ESI and EI), UV and IR spectra. Compounds ( 1 - 4 ) were evaluated for their cytotoxicities against five selected human tumourtumour cell lines (A-549, MDA-MB-231, MCF-7, KB and KB-VIN), and compound 3 exhibited activities against MDA-MB-231and MCF-7 with IC 50 values of 20.1  μ M and 32.2  μ M.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cai, Ni, Han, Chen and Peng.)

Ethnopharmacological Relevance: Wu-Zi-Yan-Zong-Wan (WZYZW) is a commonly used Chinese medicinal recipe for oligozoospermia. Oligozoospermia is a common disease that harms human fertility, there is no effective therapeutic medicine at present. However, the underlying pharmacological mechanism remains unclear., Methods: Oligozoospermia rats model induced by Tripterygium glycosides (TG) was established to inspect the efficiency of WZYZW in the treatment of oligozoospermia by traditional pharmacodynamics combined with NMR-based metabolomics. Multivariate statistics were used to extracted the underlying biomarkers and metabolic pathways of WZYZW in the treatment of oligozoospermia., Results: The results showed that TG disturbed many metabolites and metabolic pathways such as oxidative stress (choline, O-phosphocholine, betaine and ascorbate), energy metabolism in mitochondria (glucose, lactate, succinate, fumarate, 3-hydroxybutyrate and alanine), mitochondrial apoptosis markers (Bax and Bcl-2) and amino acids metabolisms (arginine, branched-chain amino acids, taurine and myo-inositol)., Conclusions: WZYZW could significantly reverse the disturbed metabolites to their normal status by their abilities of anti-oxidation, anti-apoptosis, balancing the osmotic pressure regulatory molecules and regulating the amino acids metabolism. This study provides pharmacological basis and guidance for the clinical usage of WZYZW., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A series of novel N -alkyl-1-deoxynojirimycin derivatives 25 ∼ 44 were synthesised and evaluated for their in vitro α-glucosidase inhibitory activity to develop α-glucosidase inhibitors with high activity. All twenty compounds exhibited α-glucosidase inhibitory activity with IC 50 values ranging from 30.0 ± 0.6 µM to 2000 µM as compared to standard acarbose (IC 50 = 822.0 ± 1.5 µM). The most active compound 43 was ∼27-fold more active than acarbose. Kinetic study revealed that compounds 43 , 40 , and 34 were all competitive inhibitors on α-glucosidase with K i of 10 µM, 52 µM, and 150 µM, respectively. Molecular docking demonstrated that the high active inhibitors interacted with α-glucosidase by four types of interactions, including hydrogen bonds, π-π stacking interactions, hydrophobic interactions, and electrostatic interaction. Among all the interactions, the π-π stacking interaction and hydrogen bond played a significant role in a various range of activities of the compounds.

This study is to improve the quality standard and supply the scientific basis for Anemarrhenae Rhizoma and its raw processed products. Steroidal saponin including timosaponin BⅡ, timosaponin AⅢ and flavonoids including neomangiferin and mangiferin were selected as the indicative components. Silica gel G thin layer chromatography(TLC) and polyamide TLC were used to detect the two types of compounds, respectively. The contents of timosaponin BⅡ and timosaponin AⅢ were determined by HPLC-ELSD and the content of neomangiferin, mangiferin and isomangiferin were determined by HPLC-UV. Moisture, total ash and acid insoluble ash were determined according to Chinese Pharmacopoeia(2015 edition). And 80% ethanol was selected as the solvent and the content determination of total extract were determined. The fingerprints of Anemarrhenae Rhizoma and its raw processed products were established by HPLC-UV and HPLC-ELSD. The results showed that the methods of TLC and HPLC have been successfully stablished. There are 2 and 3 peaks which have been identified by HPLC-ELSD and HPLC-UV, respectively. The HPLC fingerprint methods are specific and can be used to identify and quality control for Anemarrhenae Rhizoma and its raw processed products in the mass. Comparing to Chinese Pharmacopoeia(2015 edition), the TLC identification and content determination were revised and the total extract determination and HPLC fingerprints were added in the present study. Our results can be used as the scientific basis of quqlity control for Anemarrhenae Rhizoma and its raw processed products.

Platelet microparticles (PMPs) are membrane particles derived from the platelet membrane that enter into the blood circulation. We sought to explore the therapeutic effects of Tao-Hong-Si-Wu Decoction (THSWD) on angiogenesis in a rat model of cerebral ischaemia-reperfusion (I/R). The protective effect of THSWD on I/R rats was observed morphologically by immunohistochemical expression of VEGF and CD34, along with immunofluorescence results of co-expression of BrdU and vWF. Then, PMPs from different groups of rats were extracted, and cytokine array analysis was used to screen for angiogenesis associated proteins. The results showed that THSWD can promote the expression of VEGF, CD34, BrdU and vWF. Cytokine array analysis revealed the changes in the expression of 29 related angiogenic proteins in the total protein of PMPs, which involved the Notch signalling pathway. Compared with model group, the expression levels of NICD and Hes-1 in the THSWD group were significantly increased. In the context of I/R, the angiogenesis-related proteins of PMPs are different. THSWD may involve the promotion of activation of the Notch signalling pathway to achieve therapeutic effects on cerebral ischaemia., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

By using multivariate statistical analysis to evaluate essential quality, and provide scientific basis for their comprehensive utilization, we established an UHPLC-QTRAP-MS/MS method for the fast, precise, efficient determination of 21 kinds of amino acids and 10 kinds of nucleosides in different species of Dendrobium. The analysis was performed on a Waters XBridge Amide column(2.1 mm×100 mm,3.5 μm) with elution by mobile phase of 0.2% formic acid in water-0.2% formic acid in acetonitrile at a flow rate of 0.2 mL·min~(-1) with the column temperature at 30 ℃. The target compounds were analyzed by the positive ion multiple reaction monitoring(MRM) mode. The comprehensive evaluation of different species of Dendrobium was carried out by PCA and TOPSIS analysis. All 21 kinds of amino acids and 10 nucleosides showed good linearity among certain concentration range(r&gt;0.999), the RSDs of the stability, precision, and repeatability tests were less than 3.0%. The recovery rate was in the range from 93.31% to 107.5%, and RSD was in the range of 1.1%-3.7%. The comprehensive evaluation index obtained with PCA showed that D. huoshanense was significantly higher than others regarding amino acids and D. officinale has higher nucleosides than other species. The biggest C&#95;i difference of TOPSIS was 68.7%, and comprehensive evaluation showed that D. huoshanense produced the highest comprehensive quality. The method is precise, fast and efficient and can provide reliable basis for further researches and intrinsic quality control of Dendrobium.

Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury. In recent years, low-intensity pulsed ultrasound (LIPUS) has been studied as a potential method of stimulating peripheral nerve regeneration. In this review, the physiology of peripheral nerve regeneration is reviewed, and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed. Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms. These include an increase of neurotrophic factors, Schwann cell (SC) activation, cellular signaling activations, and induction of mitosis. We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models. We found numerous studies, suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes. Based on these findings, LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction., Competing Interests: None

Using the 260 geographical distribution records of Polygonatum cyrtonema in China, combined with 53 environmental factors, the maximum entropy modeling(MaxEnt) was used to study the ecological factors affecting the suitability distribution of P. cyrtonema. The ArcGIS software was used to predict the potential distribution of the population of P. cyrtonema. The dominant factors were chosen by using the Jackknife test and the Receiver Operating Characteristic(ROC) curve was used to evaluate the simulation. The results showed that high value of area under curve(AUC) denoted good results, which significantly differed from random predictions. Based on the evaluation criterion, the accuracies of the predictions of P. cyrtonema potential distribution in the current periods were excellent. The main environmental factors affecting the suitable growth of P. cyrtonema were the monthly precipitation, the wettest monthly precipitation, the annual average temperature range and the precipitation of November, March, February, April, May and October. There are 9 environmental factors in soil type. The potential fitness of P. cyrtonema in China is high, mainly concentra-ted in Hunan, western Hubei, Guangdong, northeastern Guangxi, southeastern Guizhou, Jiangxi, southwestern Anhui, Fujian, Zhejiang, Shaanxi, southwestern Henan and Chongqing. The growth distribution of the potential distribution area of P. cyrtonema was divided, and the zoning map of the growth suitability of P. cyrtonema was formed. Through the comparative analysis of the potential distribution range based on MaxEnt and the distribution range of literature records, the understanding of the distribution range of P. cyrtonema was expanded.

T-cell acute lymphoblastic leukemia (T-ALL) is a type of aggressive leukemia with inferior prognosis. Although activating mutations of NOTCH1 are observed in most T-ALL cases, these mutations alone are not sufficient to drive the full development of T-ALL. β-Arrestins (ARRB) are versatile and multifunctional adapter proteins that regulate diverse cellular functions, including promoting the development of cancer. However, the role of ARRBs in T-ALL has largely remained elusive. In this study, we showed that ARRB1 is expressed at low levels in assayed T-ALL clinical samples and cell lines. Exogenous ARRB1 expression inhibited T-ALL proliferation and improved the survival of T-ALL xenograft animals. ARRB1 facilitated NOTCH1 ubiquitination and degradation through interactions with NOTCH1 and DTX1. Mechanistically, the oncogenic miRNA (oncomiR) miR-223 targets the 3'-UTR of ARRB1 (BUTR) and inhibits its expression in T-ALL. Furthermore, overexpression of the ARRB1-derived miR-223 sponge suppressed T-ALL cell proliferation and induced apoptosis. Collectively, these results demonstrate that ARRB1 acts as a tumor suppressor in T-ALL by promoting NOTCH1 degradation, which is inhibited by elevated miR-223, suggesting that ARRB1 may serve as a valid drug target in the development of novel T-ALL therapeutics. Significance: These findings highlight a novel tumor suppressive function of the adaptor protein β-arrestin1 in T-ALL., (©2019 American Association for Cancer Research.)

The structure features and anti-gastric cancer activities in vitro of stem, root, leaf and flower polysaccharides from cultivated Dendrobium huoshanense were investigated systematically. Stem polysaccharide (cDHPS) was composed of →4)-β-D-Glcp-(1→, →4)-β-D-Manp-(1→, →4)-3-O-acetyl-β-D-Manp-(1→ with the molecular weight of 2.59 × 10 5  Da; root polysaccharide (cDHPR) was composed of →3,5)-α-L-Araf-(1→, →4)-β-D-Glcp-(1→, →4)-β-D-Manp-(1→, →4,6)-β-D-Manp-(1→, →6)-α-D-Galp-(1→ and terminal β-L-Araf with the molecular weight of 1.41 × 10 4  Da; leaf polysaccharide (cDHPL) was composed of →4)-β-D-Glcp-(1→, →4)-β-D-Manp-(1→, →4)-3-O-acetyl-β-D-Manp-(1→, →3,6)-β-D-Manp-(1→ and terminal α-D-Galp with the molecular weight of 2.09 × 10 5  Da; and flower polysaccharide (cDHPF) was composed of →4)-β-D-Glcp-(1→, →4)-β-D-Manp-(1→, →3,6)-β-D-Manp-(1→ and terminal α-D-Galp with the molecular weight of 4.78 × 10 5  Da. Among these four polysaccharides, cDHPS showed the best anti-gastric cancer activity evidenced by the inhibited growth and c-myc expression as well as the enhanced apoptosis and p53 expression of murine forestomach carcinoma (MFC) cells, suggesting their difference in anti-gastric cancer activity should be contributed to their difference in structure features., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Polygonatum cyrtonema belongs to the plant family Liliaceae, and its dried rhizome is one of the sources of Chinese traditional medicine of Polygonati Rhizoma. It possesses the dual function as both medicine and food. Its main chemical components are polysaccharides and saponins. In order to understand the biosynthesis pathway of polysaccharides and diosgenin in P. cyrtonema, the corresponding transcriptomic data were obtained by extracting and sequencing the RNA of four parts of P. cyrtonema, namely, leaves, stems, rhizomes and roots. By adopting BGISEQ-500 sequencing platform, 42.03 Gb data were retrieved. Subsequently, the de novo assembly was carried out by Trinity software to obtain 137 233 transcripts, of which 68.13% of unigenes were annotated in seven databases including KEGG, GO, NR, NT, SwissProt, Pfam and KOG. Transcripts that may be involved in the biosynthesis of polysaccharides and diosgenin were analyzed by data mining. With help of qPCR, we validated expression data of four genes that were possibly involved in the biosynthesis of target metabolites. This experiment provides data for the study of biosynthetic pathways of P. cyrtonema secondary metabolites and the clarification of related structural gene functions.

A chemical investigation of the fibrous roots of Anemarrhena asphodeloides Bge. led to the isolation of four benzophenones, including one new compound ( 1 ) and three known ones ( 2-4 ). Comprehensive 1 D, 2 D NMR and HRESIMS data established the structures of the isolated compounds. The absolute configurations were determined by comparison of the calculated optical rotation (OR) with experimental data. All the isolates were evaluated for their cytotoxicities on hepatocellular carcinoma cell lines (HepG2 and Hep3B). Compound 1 showed strong cytotoxicity against HepG2 and Hep3B cells, with IC 50 values at 153.1 and 180.6 nM. Through MTT assay, flow cytometry and Western blot analysis, compound 1 demonstrated the ability to stimulate apoptosis via the NF-κB signaling pathway in HepG2 cells. These benzophenones are potential lead compounds for the development of better treatments for hepatocellular carcinoma.

Books on Chinese herbal medicines have shown that Dendrobium has the effect of nourishing Yin and reinforcing Yin,usually used for constipation induced by spleen Yin deficiency in clinical application. D. huoshanense,as an independent species among many species of Dendrobium,has no experimental studies about its effects on spleen Yin deficiency-type constipation. The purpose of this experiment was to illustrate the therapeutic effect of D. huoshanense on the constipation of spleen Yin deficiency type in rats,investigate its preliminary mechanism,and compare it with the D. officinale and D. nobile contained in the Chinese Pharmacopoeia to clarify its characteristics. The spleen Yin deficiency model was replicated in 70 rats by the composite factor method,and then the model rats were randomly divided into 7 groups: model group,Liuwei Dihuang Pills group( LWDHP),D. huoshanense high( DHS-H),medium( DHS-M),low( DHS-L) dose groups,D. nobile group( DNS),and D. officinale group( DOS),and another 10 rats were used as normal group( Normal). After 7 continuous days of administration,the fecal water content and intestine propulsion rate of each group were detected. HE staining was used to observe the pathological damage of ileum and colon in each group. Immunohistochemistry and Western blot were used to detect aquaporin 3( AQP3) expressions,while the expression levels of the somatostatin( SS) and motilin( MTL) in the ileum of each group were detected by enzyme-linked immunosorbent assay. The results showed that as compared with the model group,the rats in each drug-administered group had increased number of fecal pellets,increased fecal water content,and the increased intestinal propulsion rate( P<0. 01),while the pathological damage of the ileum and colon was significantly reduced; the expression of AQP3 protein was significantly decreased( P<0. 01); the level of MTL was significantly increased and the level of SS was decreased( P<0. 01). All DHS groups showed a good dose-effect relationship,and the same dose treatment effect was equivalent to that of DOS,but it was superior to DNS. Therefore,DHS has a significant therapeutic effect on constipation of spleen Yin deficiency type,and its mechanism may be related to intestinal motility and water-liquid metabolism,with a good therapeutic effect.

MicroRNA sequencing (miRNA‑seq) was performed in the present study to investigate miRNA expression profiles in infarcted brain areas following focal cerebral ischemia induced by middle cerebral artery occlusion in rats. In total, 20 miRNAs were identified to be upregulated and 17 to be downregulated in the infarct area. The expression levels of six differentially expressed miRNAs (DEmiRs), miR‑211‑5p, miR‑183‑5p, miR‑10b‑3p, miR‑182, miR‑217‑5p and miR‑96‑5p, were examined by reverse transcription‑​quantitative polymerase chain reaction. Subsequently, a miRNA‑mRNA network was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to investigate the functions of the mRNAs targeted by these DEmiRs. The present study aimed to investigate the association between miRNAs and cerebral ischemia to provide potential insight into the molecular mechanisms underlying ischemic stroke.

In order to understand the function of GDP-mannose pyrophosphorylase(GMPP) function and its regulation in polysaccharide biosynthesis mechanism in Dendrobium. D. huoshanense was used to clone GMPP gene. GMPP gene expression in D. huoshanense,D. officinale and D. moniliforme was also determined by qPCR. The results showed that the length of D. huoshanense GMPP gene c DNA sequence is 1 867 bp,containing 1 245 bp open reading frame(ORF),encoding 415 amino acids. Phylogenetic tree analysis showed that D. huoshanense,D. officinale and D. moniliforme are closely related with GMPP taken into consideration. Bioinformatics analysis demonstrated that GMPP sequence similarity among the three species reached as high as 99%. qPCR results indicated that GMPP genes was highly expressed in stem of D. huoshanense compared with its leaf,flower and root. According to GMPP gene expression profile in D. huoshanense,D. officinale and D. moniliforme grown in Huoshan area,it was clear that GMPP in D. huoshanense showed the highest expression level. Furthermore,our findings of GMPP gene expression profile will facilitate future researches into its polysaccharide biosynthetic mechanism.

Relationships among Fallopia multiflora (Thunb.) Haraldson., F. multiflora var. angulata (S. Y. Liu) H. J. Yan, Z. J. Fang & Shi Xiao Yu., and F. multiflora var. ciliinervis (Nakai) Yonekura & H. Ohashi. were determined based on macroscopic and microscopic morphology, molecular phylogeny, and chemical analysis. The macroscopic and microscopic morphologies of root tubers or rhizomes, stems, and leaves were compared among the three taxa. The content of 11 chemical components (catechin, polydatin, stilbene glucoside, emodin, emodin-8-O-β-D-glucopyranoside, rhein, chrysophanol, aloe-emodin, quercetin, physcion, and resveratrol) in the three taxa was determined by HPLC, and the chemical diversity was further evaluated by principal component and hierarchical cluster analyses. Molecular phylogenies were mapped using two chloroplast markers (matK and the psbA-trnH intergenic region) and a nuclear ribosomal marker [internal transcribed spacer 2 (ITS2) region]. Analyses of macroscopic and microscopic morphological characteristics revealed that the subterranean organs of F. multiflora and F. multiflora var. angulata are root tubers, whereas those of F. multiflora var. ciliinervis are rhizomes. In the phylogenetic trees, F. multiflora and F. multiflora var. angulata were clustered into a clade based on the combine matK + psbA-trnH sequence, with neighbour-joining, maximum likelihood, and Bayesian inference bootstrap support values of 99, 85, and 0.99, respectively. In addition, there were obvious differences in the chemical compositions of F. multiflora, F. multiflora var. angulata and F. multiflora var. ciliinervis. The root tubers of F. multiflora contain higher levels of stilbene glucoside and catechin, but lower levels of polydatin and anthraquinone compounds. In contrast to F. multiflora, the rhizomes of F. multiflora var. ciliinervis contain higher levels of polydatin and anthraquinone compounds, but lack stilbene glucoside. The content of all 11 assessed components was lower in F. multiflora var. angulata than in F. multiflora and F. multiflora var. cillinervis. Principal component and hierarchical cluster analyses revealed that F. multiflora and F. multiflora var. angulata individuals were clustered into a single clade, whereas F. multiflora var. ciliinervis individuals were clustered into a single clade separate from that containing F. multiflora and F. multiflora var. angulata individuals. On the basis of the results of our morphological, molecular phylogeny, and chemical analyses, we tentatively conclude that F. multiflora var. ciliinervis is an independent species, whereas F. multiflora var. angulata should be considered as a variety of F. multiflora., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the ocean waveguide, the sediment sound speed has a simple relationship with the group speed of the highest order mode that propagates close to the critical angle. The paper shows that robust estimates of the sound speed are obtained from estimates of the "critical" mode group speed determined from analysis of the energy distribution of the time-warped spectrum of a broadband signal. The method is applied to experimental data collected in the Yellow Sea of China. Estimated sound speeds agreed closely with expected values for clayey slit (1531 m/s) and sandy silt (1593 m/s) sediment at the sites.

MicroRNAs (miRNAs) exhibit various roles in multiple biological processes and abnormal expression of miR-182-5p has been involved in many diseases. However, the role miR-182-5p in Atherosclerosis (AS) remains poorly understood. In our current investigation, an AS model was established by using oxidized low-density lipoprotein (ox-LDL) in RAW264.7 cells. miR-182-5p was markedly decreased in AS model dose-dependently and time-dependently. Additionally, CD36, oil-red staining levels, TC, and TG were inhibited by miR-182-5p mimics, meanwhile ROS levels, MDA, and cell apoptosis were also restrained with an enhancement of SOD activity. Consistently, opposite results were exhibited when miR-182-5p inhibitors were transfected into RAW264.7 cells. It is well known that toll-like receptor 4 (TLR4) is responsible for many inflammation diseases. By using bioinformatics analysis, TLR4 was indicated as a potential target of miR-182-5p. We observed TLR4 was activated in AS models and miR-182-5p could repress AS progression by targeting TLR4 in vitro. In conclusion, we uncovered that miR-182-5p played significant roles in AS through inhibiting oxidative stress and apoptosis via inactivating TLR4 expression., (© 2017 Wiley Periodicals, Inc.)