Preparation of high-temperature and low-temperature-resistant solid microbial agent for cattle manure fermentation and effect on composting.

We used microbiology and molecular biology techniques to screen out high-temperature and low-temperature-resistant saprobiotics for compost and prepared a compound fermentation bacteria agent to rapidly ferment cattle manure into high-quality organic fertilizer in low-temperature season. Conventional composting and high-throughput techniques were used to analyze the changes of physical and chemical indexes and biodiversity in the process of composting, from which high and low-temperature-resistant strains were obtained, and high-temperature and low-temperature-resistant solid composite bactericides were prepared and added to composting to verify the effects of composite bactericides on composting. The conventional composting cycle took 22 days, and the diversity of microflora increased first and then decreased. Composting temperature and microbial population were the key factors for the success or failure of composting. Two strains of high-temperature-resistant bacteria and six strains of low-temperature-resistant bacteria were screened out, and they were efficient in degrading starch, cellulose, and protein. The high-temperature and low-temperature-resistant solid bacterial agent was successfully prepared with adjuvant. The preparation could make the compost temperature rise quickly at low temperature, the high temperature lasted for a long time, the water content, C/N, and organic matter fell quickly, the contents of total phosphorus and total potassium were increased, and the seed germination index was significantly improved. Improve the composting effect. The solid composite bacterial agent can shorten the composting time at low temperature and improve the composting efficiency and quality.

Geniposide from Gardeniae Fructus exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The desiccative ripe fruits of Gardenia (Gardenia jasminoides Ellis) (called Zhizi in China) are known with cold character and the effects of reducing fire except vexed, clearing away heat evil, and cooling blood and eliminating stasis. Zhizi is often clinical formulated to treat various types of fever. Fever is a sign of inflammation and, geniposide from Zhizi has been proved with anti-inflammatory in various inflammatory models. AIM OF STUDY: The aim of this study was to investigate the antipyretic role of geniposide with three classical inflammatory fever models and explore the underlying mechanisms. MATERIALS AND METHODS: Water extract (WE), high polar part (HP), iridoid glycoside part (IG), and gardenia yellow pigment part (GYP) from Gardeniae Fructus (GF) were obtained from Zhizi. The antipyretic activities of these composes were tested with dry yeast induced fever rats. Geniposide was further purified from IG and the antipyretic activity was evaluated by gavage, intraperitoneal injection, and caudal intravenous injection to rats of fever induced by dry yeast, lipopolysaccharide (LPS), and 2, 4-dinitrophenol (DNP) in rats. Then, the mechanism of geniposide by intragastric administration was studied. The contents of thermoregulatory mediators and inflammatory factors relating to TLR4/NF-κB pathway in serum were determined by ELISA and Western blot, and the pathological changes of the hypothalamus were observed by HE staining. RESULTS: The temperature was decreased by geniposide in the three fever model rats. Geniposide can not only inhibit the increase of inflammatory factors in serum but also protect the hypothalamus from fever pathological damage in the three fever models. Western blot showed that geniposide could inhibit the TLR4/NF-κB pathway. CONCLUSION: Geniposide exerts antipyretic effect in febrile rats through modulating the TLR4/NF-κB signaling pathway.

Icariin Regulates EMT and Stem Cell-Like Character in Breast Cancer through Modulating lncRNA NEAT1/TGFß/SMAD2 Signaling Pathway.

Metastases and drug resistance are the major risk factors associated with breast cancer (BC), which is the most common type of tumor affecting females. Icariin (ICA) is a traditional Chinese medicine compound that possesses significant anticancer properties. Long non-coding RNAs (lncRNAs) are involved in a wide variety of biological and pathological processes and have been shown to modulate the effectiveness of certain drugs in cancer. The purpose of this study was to examine the potential effect of ICA on epithelial mesenchymal transition (EMT) and stemness articulation in BC cells, as well as the possible relationship between its inhibitory action on EMT and stemness with the NEAT1/transforming growth factor ß (TGFß)/SMAD2 pathway. The effect of ICA on the proliferation (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony assays), EMT (Western blotting, immunofluorescence, and wound healing), and stemness (mammosphere formation assays, Western blotting) of BC cells were examined. According to the findings, ICA suppressed the proliferation, EMT, and stem cell-like in MDA-MB-231 cells, and exerted its inhibitory impact by downregulating the TGFß/SMAD2 signaling pathway. ICA could significantly downregulate the expression of lncRNA NEAT1, and silencing NEAT1 enhanced the effect of ICA in suppressing EMT and expression of different stem cell markers. In addition, silencing NEAT1 was found to attenuate the TGFß/SMAD2 signaling pathway, thereby improving the inhibitory impact of ICA on stemness and EMT in BC cells. In conclusion, ICA can potentially inhibit the metastasis of BC via affecting the NEAT1/TGFß/SMAD2 pathway, which provides a theoretical foundation for understanding the mechanisms involved in potential application of ICA for BC therapy.

Branched-Long-Chain Monomethyl Fatty Acids: Are They Hidden Gems?

Branched-long-chain monomethyl fatty acids (BLCFA) are consumed daily in significant amounts by humans in all stages of life. BLCFA are absorbed and metabolized in human intestinal epithelial cells and are not only oxidized for energy. Thus far, BLCFA have been revealed to possess versatile beneficial bioactivities, including cytotoxicity to cancer cells, anti-inflammation, lipid-lowering, reducing the risk of metabolic disorders, maintaining normal ß cell function and insulin sensitivity, regulation of development, and mitigating cerebral ischemia/reperfusion injury. However, compared to other well-studied dietary fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), BLCFA has received disproportionate attention despite their potential importance. Here we outlined the major food sources, estimated intake, absorption, and metabolism in human cells, and bioactive properties of BLCFA with a focus on the bioactive mechanisms to advocate for an increased commitment to BLCFA investigations. Humans were estimated to absorb 6-5000 mg of dietary BLCFA daily from fetus to adult. Notably, iso-15:0 inhibited the growth of prostate cancer, liver cancer and T-cell non-Hodgkin lymphomas in rodent models at the effective doses of 35-105 mg/kg/day, 70 mg/kg/day, and 70 mg/kg/day, respectively. Feeding formula prepared with 20% w/w BLCFA mixture to neonatal rats with enterocolitis mitigated the intestine inflammation. Iso-15:0 at doses of 10, 40, and 80 mg/kg relieved brain ischemia/reperfusion injury in rats. In the future, it is crucial to conduct research to establish the epidemiology of BLCFA intake and their impacts on health outcomes in humans as well as to fully uncover the underlying mechanisms for their bioactivities.

[Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats].

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

Efficacy and safety of self-expandable metal stent placement for treatment of primary and metastatic gastric outlet obstruction.

BACKGROUND AND GOALS: Gastric outlet obstruction (GOO) usually occurs at the pylorus or the duodenum through primary gastric, duodenal, or pancreatic tumors. However, metastatic GOO is relatively rare. Although self-expandable metal stent (SEMS) placement is often performed as an alternative and practical palliative approach for primary GOO, there are few reports of metastatic GOO treatment with SEMS. This study aimed to investigate the efficacy, safety, stent patency, and complications of SEMS for treating primary and metastatic GOO. METHODS: The data of 42 patients with GOO who received SEMS from November 2016 to April 2022 were reviewed retrospectively. Patients were divided into primary group (n = 25) and metastatic group (n = 17) according to the cause of GOO. The rates of technical and clinical success, stent patency, and complications were compared between the two groups. RESULTS: The overall technical and clinical success rates were 97.9% and 93.5%, respectively. The total SEMS implantation time was 48.2 ± 33.5 (10.0-140.0) minutes. The primary technical success rate was 100.0% in both primary and metastatic groups, and the primary clinical success rate was 96.0% (24/25) in the primary group vs 88.2% (15/17) in the metastatic group (P = 0.350). After reintervention, the secondary technical success rate was 100.0% (27/27) in the primary group vs 95.0% (19/20) in the metastatic group (P = 0.330); and the secondary clinical success rate was 96.3% (26/27) in the primary group vs 89.5% (17/19) in the metastatic group (P = 0.367). No serious complications, such as gastrointestinal perforation, stent migration, bleeding, or aspiration pneumonia, were observed in these patients. CONCLUSIONS: SEMS under fluoroscopic guidance is an effective and safe treatment for primary and metastatic GOO. The etiology of obstruction did not influence stent patency or complications. Therefore, stent implantation is recommended for patients with metastatic GOO caused by multiple peritoneal metastases to improve their quality of life.

Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats / 中国中药杂志

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy.

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

Aqueous Solution-Grown Crystalline Phosphorus Doped Indium Oxide for Thin-Film Transistors Applications.

Solution-grown indium oxide (In2O3) based thin-film transistors (TFTs) hold good prospects for emerging advanced electronics due to their excellent mobility, prominent transparency, and possibility of low-cost and scalable manufacturing; however, pristine In2O3 TFTs suffer from poor switching characteristics due to intrinsic oxygen-vacancy-related defects and require external doping. According to Shanmugam's theory, among potential dopants, phosphorus (P) has a large dopant-oxygen bonding strength (EM-O) and high Lewis acid strength (L) that would suppress oxygen-vacancy related defects and mitigate dopant-induced carrier scattering; however, P-doped In2O3 (IPO) TFTs have not yet been demonstrated. Here, we report aqueous solution-grown crystalline IPO TFTs for the first time. It is suggested that the incorporation of P could effectively inhibit oxygen-vacancy-related defects while maintaining high mobility. This work experimentally demonstrates that dopant with high EM-O and L is promising for emerging oxide TFTs.

Effect of Pulmonary Function Training with a Respirator on Functional Recovery and Quality of Life of Patients with Stroke.

A stroke is a sudden onset cerebral blood circulation disorder. It occurs in patients with cerebrovascular disease due to various predisposing factors causing stenosis, occlusion, or rupture of intracerebral arteries, which, in turn, causes acute cerebral blood circulation disturbance and clinically manifests as symptoms and signs of excessive or permanent cerebral dysfunction. It can cause serious harm to patients' physical and mental health. This study aimed to evaluate the effect of Breathe-Link breathing trainers on lung function and the ability to perform activities of daily living in patients with stroke. Sixty patients with stroke were randomly divided into two groups. One group was set as the control group and received routine breathing training. The experimental group received a Breathe-Link trainer based on regular training, with rehabilitation training for 12 weeks as the time node. Respiratory muscle strength, respiratory velocity, respiratory capacity, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and rate in the first second (FEV1/FVC) were used to evaluate the respiratory function of patients, and the Barthel index was used to evaluate the ability to perform activities of daily living. Improvements in respiratory function and daily living ability were compared between the two groups. After 12 weeks of training, respiratory muscle strength, respiratory velocity, respiratory volume, FVC, FEV1, FEV1/FVC, and Barthel index of patients in the two groups improved compared with those before training (P < 0.05), and the improvement in the treatment group was better than that in the control group (P < 0.05). Breathe-Link breathing trainers can improve lung function and the ability to perform activities of daily living in patients with stroke, and its effect is acceptable. It can be recommended for clinical use.

Efficacy and safety of AnluoHuaxian pills on chronic hepatitis B with normal or minimally elevated alanine transaminase and early liver fibrosis: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: The AnluoHuaxian pill (AHP) is a widely used patented medicine for chronic hepatitis B (CHB) patients with advanced fibrosis or cirrhosis that has been used in China for more than 15 years. However, data are lacking on whether monotherapy with AHP can be effective in CHB patients with alanine aminotransferase (ALT) levels less than 2 times the upper limit of normal (ALT<2ULN) and early liver fibrosis (F ≤ 2). AIM OF THE STUDY: We aimed to investigate whether monotherapy with AHP improves liver histology in these patients. MATERIALS AND METHODS: In this double-blind, randomized, placebo-controlled trial, 270 CHB patients with ALT<2ULN and F ≤ 2 were treated in 12 hospitals in China. The patients were randomly assigned to an intervention (AHP) group and a placebo group at a ratio of 2:1. Of these 270 enrolled patients, 147 had paired liver biopsies. The primary end point was histological change after 48 weeks of treatment. RESULTS: Per-protocol analysis revealed that the rate of histologic improvement in liver fibrosis patients in the AHP group was significantly higher than that in the placebo group (37.7% vs. 19.5%, P = 0.035) after 48 weeks of treatment, which was consistent with results from intention-to-treat and sensitivity analyses. Moreover, after adjusting for baseline characteristics, AHP was superior to placebo with respect to improving liver fibrosis (odds ratio [OR] = 2.58, 95% confidence interval [CI]: (1.01, 6.63),P = 0.049) and liver histology (OR = 3.62, 95% CI: (1.42, 9.20),P = 0.007). In noninvasive measurement of liver fibrosis (FibroScan®), the level of liver stiffness measurement (LSM) had decreased significantly at 48 weeks (5.1 kPa) compared with that at baseline (5.7 kPa) (P = 0.008) in the AHP group, whereas it did not decrease significantly in the placebo group. Cirrhosis developed in one patient in the placebo group but in no patients in the AHP group. No serious side effects occurred in the AHP-treated patients. CONCLUSIONS: Treatment of CHB patients who had ALT<2ULN and F ≤ 2 with the traditional Chinese medicine AHP for 48 weeks improves liver fibrosis. However, due to the short duration of treatment and the limited sample size of liver pathology, the long-term benefits of AHP in reducing fibrosis and the risk of cirrhosis and hepatocellular carcinoma in these patients need to be further studied in the future.

The complete chloroplast genome of a karst-dwelling plant Primulina tenuituba (Gesneriaceae).

Primulina tenuituba is a species in the Gesneriaceae family that is widely distributed in China. It is a karst-dwelling species with an enormous tolerance for extreme drought and high temperatures. The species is also used in traditional Chinese medicine. In this study, the complete chloroplast genome of P. tenuituba was assembled and characterized for the first time. The complete chloroplast genome exhibited a typical quadripartite cycle of 153,236 bp in length, including a pair of inverted repeats (IRs) of 25,494 bp, which were separated by a large single-copy (LSC) region of 84,364 bp and a small single copy (SSC) region of 17,884 bp. The GC content was 37.6%. The complete chloroplast genome of P. tenuituba contains 114 genes, including 80 protein-coding genes, 30 tRNAs genes, and four rRNAs. The phylogenetic analysis showed that P. tenuituba is closely related to P. eburnea. The newly reported chloroplast genome of P. tenuituba would provide valuable data for further studies on its evolution and adaptation mechanism.

[Multiple components of Mahuang Shengma Decoction on prevention and treatment of acute lung injury based on RAGE/NF-κB signaling pathway].

To investigate the potential molecular markers and drug-compound-target mechanism of Mahuang Shengma Decoction(MHSM) in the intervention of acute lung injury(ALI) by network pharmacology and experimental verification. Databases such as TCMSP, TCMIO, and STITCH were used to predict the possible targets of MHSM components and OMIM and Gene Cards were employed to obtain ALI targets. The common differentially expressed genes(DEGs) were therefore obtained. The network diagram of DEGs of MHSM intervention in ALI was constructed by Cytoscape 3. 8. 0, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of target genes. The ALI model was induced by abdominal injection of lipopolysaccharide(LPS) in mice. Bronchoalveolar lavage fluid(BALF) was collected for the detection of inflammatory factors. Pathological sectioning and RT-PCR experiments were performed to verify the therapeutic efficacy of MHSM on ALI. A total of 494 common targets of MHSM and ALI were obtained. Among the top 20 key active compounds of MHSM, 14 from Ephedrae Herba were found to be reacted with pivotal genes of ALI [such as tumor necrosis factor(TNF), tumor protein 53(TP53), interleukin 6(IL6), Toll-like receptor 4(TLR4), and nuclear factor-κB(NF-κB)/p65(RELA)], causing an uncontrolled inflammatory response with activated cascade amplification. Pathway analysis revealed that the mechanism of MHSM in the treatment of ALI mainly involved AGE-RAGE, cancer pathways, PI3 K-AKT signaling pathway, and NF-κB signaling pathway. The findings demonstrated that MHSM could dwindle the content of s RAGE, IL-6, and TNF-α in the BALF of ALI mice, relieve the infiltration of inflammatory cells in the lungs, inhibit alveolar wall thickening, reduce the acute inflammation-induced pulmonary congestion and hemorrhage, and counteract transcriptional activities of Ager-RAGE and NF-κB p65. MHSM could also synergically act on the target DEGs of ALI and alleviate pulmonary pathological injury and inflammatory response, which might be achieved by inhibiting the expression of the key gene Ager-RAGE in RAGE/NF-κB signaling pathway and downstream signal NF-κB p65.

Acupuncture for glucose and lipid metabolic disorders of polycystic ovarian syndrome: A systematic review protocol.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common gynecological disease that is often accompanied by some metabolic abnormality such as insulin resistance and dyslipidemia. As a non-pharmacological therapy, acupuncture is widely used for the treatment of PCOS, but the effectiveness for insulin resistance and lipid metabolic disorder remains controversial. OBJECTIVES: To assess the effectiveness and safety of acupuncture for insulin resistance and lipid metabolic disorder of women with PCOS. SEARCH METHODS: Eight databases will be searched from inception to June 2021, three clinical trial registration platforms will be searched for relevant trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) of acupuncture therapy for insulin resistance and lipid metabolic of PCOS will be included. DATA COLLECTION AND ANALYSIS: Study screening, data collection, and analysis will be performed by two or more reviewers independently. We will calculate mean difference (MD), standard mean difference (SMD) with 95% confidence intervals (CIs). Data synthesis will be performed with RevMan V.5.3 software and with Stata V.15.0 software when necessary. PROSPERO REGISTRATION NUMBER: CRD42020177846.

Endogenous FGF-2 levels impact FGF-2/BMP-2 growth factor delivery dosing in aged murine calvarial bone defects.

Bone repair in elderly mice has been shown to be improved or negatively impacted by supplementing the highly osteogenic bone morphogenetic protein-2 (BMP-2) with fibroblast growth factor-2 (FGF-2). To better predict the outcome of FGF-2 supplementation, we investigated whether endogenous levels of FGF-2 play a role in optimal dosing of FGF-2 for augmenting BMP-2 activity in elderly mice. In vivo calvarial bone defect studies in Fgf2 knockout mice with wildtype controls were conducted with the growth factors delivered in a highly localized manner from a biomimetic calcium phosphate/polyelectrolyte multilayer coating applied to a bone graft substitute. Endogenous FGF-2 levels were measured in old mice versus young and found to decrease with age. Optimal dosing for improving bone defect repair correlated with levels of endogenous FGF-2, with a larger dose of FGF-2 required to have a positive effect on bone healing in the Fgf2 knockout mice. The same dose in wildtype old mice, with higher levels of FGF-2, promoted chondrogenesis and increased osteoclast activity. The results suggest a personalized medicine approach, based on a knowledge of endogenous levels of FGF-2, should guide FGF-2 supplementation in order to avoid provoking excessive bone resorption and cartilage formation, both of which inhibited calvarial bone repair.

Puerarin improved growth performance and postmortem meat quality by regulating lipid metabolism of cattle under hot environment.

This study aims to evaluate the effect of puerarin on performance, meat quality, and serum indexes of beef cattle under hot environment. Thirty-two bulls were divided into four groups and fed diet supplemented with puerarin at 0, 200, 400, or 800 mg/kg. Results showed that heat stress was employed for 54 out of 60 days, 400 mg/kg group declined serum cortisol (COR) contents, all treatments increased the contents of total cholesterol, high density lipoprotein cholesterol, and total superoxide dismutase activity; in addition, glutathione peroxidase activity of 200 mg/kg group were enhanced, only 800 mg/kg group enhanced immunoglobulin (IgA, IgM, and IgG) and low density lipoprotein cholesterol contents compared with the control (p < .05). Moreover, 400-mg/kg puerarin increased serum growth hormone levels compared with 200 mg/kg group but declined COR concentrations compared with 200 mg/kg and 800 mg/kg groups (p < .05). More importantly, average daily gain and daily matter intake, and intramuscular fat contents of 400 mg/kg group were enhanced, but the shear force of beef in 400 mg/kg and 800 mg/kg groups were declined compared with the control (p < .05). These findings indicated that supplemental with puerarin enhanced immune and antioxidant, and 400 mg/kg of puerarin improved performance and meat quality by normalizing levels of stress hormones and increasing intramuscular fat deposition of beef cattle under hot environment.

Acupuncture for chronic pelvic pain in patients with SPID: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic pelvic pain (CPP) is one of the common sequela of pelvic inflammatory disease, the pathological factors are adhesions, scarring and pelvic congestion which caused by inflammation, often cause abdominal pain and lumbosacral soreness, and aggravated after fatigue, sexual intercourse and during menstruation. It is difficult to treat because special pathological changes. Although acupuncture has gained increased popularity for the management of CPP, evidence regarding its efficacy is lacking. Therefore, a systematic review of acupuncture for chronic pelvic pain in patients with SPID is required to provide available evidence for further study. METHODS AND ANALYSIS: We will conduct a systematic review of randomized controlled trials (RCTs) that investigate the effect and safety of acupuncture for the treatment of chronic pelvic pain patients with SPID. We will electronically search the literature in the databases of PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, the Web of Science, China National Knowledge Infrastructure (CNKI), Wan-fang Digital Periodicals, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP) and select eligible articles. Data extraction will be conducted by 2 researchers independently, and risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcomes will be total effective rate and VAS pain score, and the secondary outcomes include the recurrence rate and adverse reaction. All data analysis will be conducted by software Review Manager V.5.3. RESULTS: This study will provide the latest analysis of the currently available evidence for the efficacy of acupuncture for chronic pelvic pain in patients with SPID. PROSPERO REGISTRATION NUMBER: CRD42020193826.

Engineering a Reliable and Convenient SARS-CoV-2 Replicon System for Analysis of Viral RNA Synthesis and Screening of Antiviral Inhibitors.

The etiologic agent of COVID-19 is highly contagious and has caused a severe global pandemic. Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for SARS-CoV-2 virologic research and inhibitor screening. In this study, we reported a replicon system which consists of four plasmids expressing the required segments of SARS-CoV-2. Our study revealed that the features for viral RNA synthesis and responses to antivirus drugs of the replicon are similar to those of wild-type viruses. Further analysis indicated that ORF6 provided potent in trans stimulation of the viral replication. Some viral variations, such as 5'UTR-C241T and ORF8-(T28144C) L84S mutation, also exhibit their different impact upon viral replication. Besides, the screening of clinically used drugs identified that several tyrosine kinase inhibitors and DNA-Top II inhibitors potently inhibit the replicon, as well as authentic SARS-CoV-2 viruses. Collectively, this replicon system provides a biosafety-worry-free platform for studying SARS-CoV-2 virology, monitoring the functional impact of viral mutations, and developing viral inhibitors.IMPORTANCE COVID-19 has caused a severe global pandemic. Until now, there has been no simple and reliable system available in a lower-biosafety-grade laboratory for SARS-CoV-2 virologic research and inhibitor screening. We reported a replicon system which consists of four ordinary plasmids expressing the required segments of SARS-CoV-2. Using the replicon system, we developed three application scenarios: (i) to identify the effects of viral proteins on virus replication, (ii) to identify the effects of mutations on viral replication during viral epidemics, and (iii) to perform high-throughput screening of antiviral drugs. Collectively, this replicon system would be useful for virologists to study SARS-CoV-2 virology, for epidemiologists to monitor virus mutations, and for industry to develop antiviral drugs.

Network pharmacology and molecular docking reveal the mechanism of Scopoletin against non-small cell lung cancer.

AIMS: Scopoletin is a natural anticarcinogenic and antiviral coumarin component. Many studies have proved its anti-cancer effect, and after the preliminary screening of this study, Scopoletin had the best inhibitory effect on Non-small cell lung cancer (NSCLC). But its mechanism for treating NSCLC is still unclear. Therefore, network pharmacology and molecular docking technology were used to explore the potential anti-NSCLC targets and pathways of Scopoletin. The results were verified in vitro. MAIN METHODS: First, Scopoletin was isolated from Fennel and screened to conduct cell proliferation assay on Human lung cancer cell line A549, Human colon cancer cell line HCT-116 and Human hepatoma cell line HepG2 respectively, through the MTT test. Then, the key targets and related pathways were screened through Protein-protein Interaction (PPI) network and "component-target-pathway" (C-TP) network constructed by network pharmacology. And the key targets were selected to dock with Scopoletin via molecular docking. A549 and Human normal lung epithelial cell BEAS-2B were used to verify the results, finally. KEY FINDINGS: Through MTT, A549 was chosen as the test cancer cell. From network pharmacology, 16 targets, 27 signaling pathways and 16 GO items were obtained (P < 0.05). The results of PPI network and molecular docking showed that EGFR, BRAF and AKT1 were the key targets of Scopoletin against NSCLC, which were consistent with the western-blot results. SIGNIFICANCE: Through network pharmacology, molecular docking and experiments in vitro, Scopoletin was verified to against NSCLC through RAS-RAF-MEK-ERK pathway and PI3K/AKT pathway.

ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma.

Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was negatively associated with IC50 values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC.