[Research progress on chemical constituents of Schisandra chinensis and its effect on nonalcoholic fatty liver disease].

Schisandra chinensis, a traditional Chinese medicinal herb, is rich in chemical constituents, including lignans, triterpenes, polysaccharides, and volatile oils. Clinically, it is commonly used to treat cardiovascular, cerebrovascular, liver, gastrointestinal, and respiratory diseases. Modern pharmacological studies have shown that S. chinensis extract and monomers have multiple pharmacological activities in lowering liver fat, alleviating insulin resistance, and resisting oxidative stress, and have good application prospects in alleviating nonalcoholic fatty liver disease(NAFLD). Therefore, this study reviewed the research progress on chemical constituents of S. chinensis and its effect on NAFLD in recent years to provide references for the research on S. chinensis in the treatment of NAFLD.

[Prediction of quality markers and medicinal value of sea buckthorn leaves based on network pharmacology, content determination, and activity evaluation].

The leaves of sea buckthorn(Hippophae rhamnoides), considered as common food raw materials, have records of medicinal use and diverse pharmacological activities, showing a potential medicinal value. However, the active substances in the sea buckthorn leaves and their mechanisms of action remain unclear. In addition, due to the extensive source and large variety variations, the quality evaluation criteria of sea buckthorn leaves remain to be developed. To solve the problems, this study predicted the main active components, core targets, key pathways, and potential pharmacological effects of sea buckthorn leaves by network pharmacology and molecular docking. Furthermore, ultra-performance liquid chromatography with diode-array detection(UPLC-DAD) was employed to determine the content of active components and establish the chemical fingerprint, on the basis of which the quality markers of sea buckthorn leaves were predicted and then verified by the enzyme activity inhibition method. The results indicated that sea buckthorn leaves had potential therapeutic effects on a variety of digestive tract diseases, metabolic diseases, tumors, and autoimmune diseases, which were consistent with the ancient records and the results of modern pharmacological studies. The core targets of sea buckthorn leaves included PTPN11, AKT1, PIK3R1, ESR1, and SRC, which were mainly involved in the PI3K-AKT, MAPK, and HIF-1 signaling pathways. In conclusion, the active components of sea buckthorn leaves are associated with the rich flavonoids and tannins, among which quercitrin, narcissoside, and ellagic acid can be used as the quality markers of sea buckthorn leaves. The findings provide a reference for the quality control and further development and utilization of sea buckthorn leaves as medicinal materials.

[Degradation kinetics of ß-nicotinamide mononucleotide based on reliable HPLC quantitative method].

To explore the stability characteristics of ß-nicotinamide mononucleotide(NMN) and provide data support for NMN production, preparation, and related product development, this study established a simple HPLC content determination method for NMN in simple substrate and investigated the degradation behavior, degradation products, and degradation kinetics of NMN under various chemical, physical, and biological conditions. The HPLC method employed a Welch Xtimate AQ-C_(18) column(4.6 mm×250 mm, 5 µm), a detection wavelength of 266 nm, a column temperature of 30 ℃, a flow rate of 1.0 mL·min~(-1), an injection volume of 5 µL, and a mobile phase consisting of methanol(A) and a 10 mmol·L~(-1) ammonium formate aqueous solution(B) with a gradient elution(0-6.7 min, 0-4% A; 6.7-13 min, 4%-18% A; 13-14.2 min, 18% A; 14.2-15 min, 18%-0 A; 15-22 min, 0 A). This method provided good separation between NMN and potential impurities and degradation products, and had a wide linear range, short analysis time, good durability, high accuracy, an average sample recovery rate of 98.71%, and an RSD of 1.2%. The instrument precision had an RSD of 0.26%, and the linearity within the examined range was excellent(R~2≥0.999 9). This method can be applied for NMN content determination in simple substrate. The degradation process of NMN in aqueous solution followed apparent first-order kinetics, with the degradation rate primarily influenced by high temperature and pH. NMN was more stable in low-temperature, neutral, or weakly acidic/alkaline environments. Strong acids or strong alkalis could accelerate its degradation, and its degradation rate was less affected by pepsin and trypsin. In an aqueous solution at room temperature, it followed the kinetic equation lg C_t=0.005 7t + 4.817 2, with t_(0.9) and t_(1/2) values of 95.58, 860.26 h, respectively. The results suggest that pH and temperature are the main factors affecting the stability of NMN in aqueous solution, and low temperature, moisture protection, and a weakly acidic environment are more conducive to the storage and application of NMN and its products.

Mycorrhizal symbiosis promotes the nutrient content accumulation and affects the root exudates in maize.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) are a group of important symbiotic microorganisms found in ecosystems. Maize is the second most produced food crop globally. To investigate the mechanisms by which mycorrhizal symbiosis improves maize yields, the effects of mycorrhizal symbiosis on root vigor, nutrient accumulation in various tissues, and root exudates were investigated. We propose the following hypothesis: The secretion of organic acids in root exudates has antagonistic or synergistic effects, which are related to the rhizosphere environment. AMF symbiosis will enhance this effect. RESULT: Rhizophagus aggreatus, Claroideoglomus etunicatum, and Funneliformis mosseae were used to inoculate maize plants separately; meanwhile, maize was inoculated with the above three fungi together for another processing. The plant tissues were sampled at five growth stages: V12 (twelve-leaf), VT (Tassel), R1 (Silking), R2 (Blister), and R4 (Dough stage). The root vigor, and nutrient content in different maize organs and organic acids in root exudates were determined in these stages. The results show that mycorrhizal symbiosis significantly improved the root vigor of maize, especially for plants inoculated with F. mosseae. AMF symbiosis significantly increased N, P, and K accumulation. Mixed inoculation with arbuscular mycorrhizal fungi significantly promoted the accumulation of N and K in maize. P accumulation was significantly promoted by C. etunicatum inoculation. Mycorrhizal symbiosis reduced the levels of protocatechuic, vanillic, citric, and ferulic acid in maize root exudates and increased the levels of p-hydroxybenzoic and caffeic acid. Except for syringic, chlorogenic and succinic acid, the levels of other organic acids in root exudates were higher in plants inoculated with F. mosseae than in other treatments. CONCLUSION: This study demonstrates that mycorrhizal symbiosis improves root vigor and promotes nutrient accumulation at various sites; in addition, mycorrhizal symbiosis affects the content of organic acids in root exudates.

Understanding Ozone Transport and Deposition within Indoor Surface Boundary Layers.

Ozone-initiated oxidation reactions on indoor surfaces meaningfully alter the chemical composition of indoor air and human exposure to air toxins. Ozone mass transport within the indoor surface boundary layer plays a key role in ozone-surface reaction kinetics. However, limited information is available on detailed ozone transport dynamics near realistic, irregular indoor surfaces. This paper presents a research framework to study the underlying mechanisms of ozone reactions with realistic indoor surfaces based on microscope scanning of surface material and detailed Computational Fluid Dynamics (CFD) simulation. The study results show that indoor surface topography can meaningfully affect ozone mass transport within a surface boundary layer, thereby modulating near-surface ozone concentration gradient and surface uptake. The results also reveal that the effective indoor surface area available for ozone reaction varies with indoor air speed and turbulent air mixing within the boundary layer. The detailed dynamic behaviors of ozone reactions with realistic indoor surfaces provide insights into the implications of pollutant-surface interactions on indoor chemistry and air quality.

A Global Analysis of Alternative Splicing of Dichocarpum Medicinal Plants, Ranunculales.

Background: The multiple isoforms are often generated from a single gene via Alternative Splicing (AS) in plants, and the functional diversity of the plant genome is significantly increased. Despite well-studied gene functions, the specific functions of isoforms are little known, therefore, the accurate prediction of isoform functions is exceedingly wanted. Methods: Here we perform the first global analysis of AS of Dichocarpum, a medicinal genus of Ranunculales, by utilizing full-length transcriptome datasets of five Chinese endemic Dichocarpum taxa. Multiple software were used to identify AS events, the gene function was annotated based on seven databases, and the protein-coding sequence of each AS isoform was translated into an amino acid sequence. The self-developed software DIFFUSE was used to predict the functions of AS isoforms. Results: Among 8,485 genes with AS events, the genes with two isoforms were the most (6,038), followed by those with three isoforms and four isoforms. Retained intron (RI, 551) was predominant among 1,037 AS events, and alternative 3' splice sites and alternative 5' splice sites were second. The software DIFFUSE was effective in predicting functions of Dichocarpum isoforms, which have not been unearthed. When compared with the sequence alignment-based database annotations, DIFFUSE performed better in differentiating isoform functions. The DIFFUSE predictions on the terms GO:0003677 (DNA binding) and GO: 0010333 (terpene synthase activity) agreed with the biological features of transcript isoforms. Conclusion: Numerous AS events were for the first time identified from full-length transcriptome datasets of five Dichocarpum taxa, and functions of AS isoforms were successfully predicted by the self-developed software DIFFUSE. The global analysis of Dichocarpum AS events and predicting isoform functions can help understand the metabolic regulations of medicinal taxa and their pharmaceutical explorations.

[Research progress in DIR gene of lignan biosynthesis in medicinal plants].

The active components, mainly derived from secondary metabolites of medicinal plants, are the material basis for the efficacy of medicinal plants. Lignans, the secondary metabolites in plants with high bioactivity, are widely distributed in a variety of plant species, and their antiviral, antitumor, antibacterial, and antioxidant activities have been proved in clinical practice. Generally, lignans are diverse in structures with many chiral centers, and most of them are optically active. The biosynthesis of lignans depends on the oxidative coupling reaction through site selection and stereo selection, which impedes synthesized lignans to form racemates, but makes them in a three-dimensional configuration. Dirigent protein(DIR) plays an important role in guiding location selection and stereo selection of lignans in biosynthesis. In vitro studies on lignan biosynthesis have shown that racemic end products are obtained in the absence of DIR proteins, while the products in a three-dimensional configuration can be yielded in the presence of DIR proteins, indicating that DIR proteins play an asymmetric role in the biosynthesis of plant secondary metabolites. The present study reviewed the biolo-gical significance of DIR protein, the cloning of DIR gene, gene structure, catalytic mechanism, and the research progress in Isatis indigotica, Eucommia ulmoides, Forsythia suspensa, Salvia miltiorrhiza, Panax pseudoginseng var. notoginseng, and Schisandra chinensis, which provides a reference for the follow-up research of DIR gene.

Repeated subarachnoid administrations of allogeneic human umbilical cord mesenchymal stem cells for spinal cord injury: a phase 1/2 pilot study.

BACKGROUND AIMS: Stem cell transplantation is a potential treatment for intractable spinal cord injury (SCI), and allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the advantages of immune privilege, paracrine effect, immunomodulatory function, convenient collection procedure and little ethical concern, and there is an urgent need to develop a safe and effective protocol regarding their clinical application. METHODS: A prospective, single-center, single-arm study in which subjects received four subarachnoid transplantations of hUC-MSCs (1 × 106 cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months after final administration) was conducted. At each scheduled time point, safety and efficacy indicators were collected and analyzed accordingly. Adverse events (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were determined as primary efficacy outcomes, whereas these two indicators at the remaining time points as well as scores of pinprick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was also performed. RESULTS: Safety and efficacy assessments were performed on 102 and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed following hUC-MSC transplantation and resolved thoroughly after conservative treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed statistical increases when compared with the baselines at different time points during the study, mainly reflected in the improvement of pinprick, light touch, motor and sphincter scores. Moreover, subjects showed a continuous and remarkable decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder and bowel functions, RUV and MRI, data/imaging at final follow-up showed significant improvements compared with those at first collection. Subgroup analysis found that hUC-MSC transplantation improved neurological functions regardless of injury characteristics, including level, severity and chronicity. CONCLUSIONS: The authors' present protocol demonstrates that intrathecal administration of' allogeneic hUC-MSCs at a dose of 106 cells/kg once a month for 4 months is safe and effective and leads to significant improvement in neurological dysfunction and recovery of quality of life.

[Withania somnifera: a kind of food-medicine plant popular in world in recent years].

Withania somnifera, also known as Indian ginseng, is an important traditional medicine in the Ayurvedic medical system of India, which has a significant effect of adaptation. Modern studies have shown that the main chemical components of W. somnifera are withanolides, which have antioxidant, anti-tumor, enhancing immunity, cardiovascular protection, neuroprotection, anti-stress, anti-stress reaction and hypoglycemic activities. Studies on human, animal, mutagenesis, genotoxicity, reproductive toxicity and drug interaction showed that W. somnifera had good safety. Clinical trials have proved that W. somnifera is effective in treating a variety of human diseases. As a famous traditional medicine and modern dietary supplement, it has a high reputation and market in the international health product market, but in China, there is little scientific research, market development, product introduction and application. In this paper, the traditional application, chemical composition, pharmacological activity, safety evaluation and clinical study of the plant were introduced, so as to increase the understanding of the dual use of the plant, and to provide reference for the future introduction of the product, the service to the health of the Chinese people and the promotion of the "double cycle" of the trade of health products between China and the international community.

[Material basis and mechanism of Huangqin Tea in prevention of colorectal cancer based on network pharmacology and molecular docking].

Colorectal cancer is a malignancy with high mortality. Huangqin Tea(HQT) can exert potential preventive and therapeutic effects on colorectal cancer. Flavonoids are the main compounds in HQT, but the pharmacodynamic material basis and mechanism are unclear. Network pharmacology and molecular docking were used to predict and analyze the targets and signaling pathways of HQT in the prevention and treatment of colorectal cancer. The active components of flavonoids in HQT were searched and screened out by literature review and FAFDrugs4. The related targets of active components were predicted by SwissTargetPrediction, STITCH, and TCMSP. Colorectal cancer-related genes were collected from OMIM, TTD, and GeneCards. The common targets were obtained as the potential targets of HQT in the prevention and treatment of colorectal cancer. Metascape was used for GO function enrichment and KEGG pathway enrichment analyses. Cytoscape was used to construct the protein-protein interaction(PPI) network and "component-target-disease-pathway" network to obtained and analyze core targets and key components. AutoDock Vina was used for molecular docking verification of key components and core targets. The results showed that apigenin, luteolin, wogonin, and baicalein were presumedly the key active components in the prevention and treatment of colorectal cancer, and core targets included TP53, AKT1, VEGFA, PIK3 CA, and SRC. The key KEGG signaling pathways mainly involved PI3 K-AKT, AGE-RAGE, p53, NF-κB, Wnt, Hippo, and calcium signaling pathways. Further molecular docking results showed that four key components showed strong hydrogen bonding ability with the five core targets. This study preliminarily reveals the pharmacodynamic material basis and potential mechanism of HQT in the prevention and treatment of colorectal cancer and provides a theoretical and scientific basis for the application of HQT.

[Application and modern research progress of sea buckthorn leaves].

Sea buckthorn(Hippophae rhamnoides) is widely distributed, with abundant resources, a long history of application, and rich nutrition and high medicinal value. Therefore, it has attracted extensive attention from researchers at home and abroad. The focus of attention is mainly on sea buckthorn fruit, but with weak research and development of sea buckthorn leaves. In order to develop and utilize abundant resources of sea buckthorn leaves, this paper systematically reviewed domestic and foreign literatures and summarized the current application, harvesting and processing, chemical constituents and pharmacological activities of sea buckthorn leaves. Sea buckthorn leaves have a wide development and utilization value in food raw materials(like a substituting-for-tea plant), pharmaceutical raw materials and animal feed. Modern studies have shown that the leaves of sea buckthorn are rich in polysaccharides, flavonoids, polyphenols, triterpenes and steroids, as well as vitamins(especially vitamin C), proteins, amino acids and mineral elements. It has various pharmacological effects, such as anti-obesity, hypoglycemia, anti-oxidation, antibacterial, anti-inflammatory and anti-cardiovascular diseases. Domestic and foreign studies have showed that sea buckthorn leaves have important development and utilization prospects, and are worth further study and development.

[A preliminary pharmacophylogenetic study of Solanaceae medicinal plants containing tropane alkaloids].

The Solanaceae plants distributed in China belong to 105 species and 35 varietas of 24 genera. Some medicinal plants of Solanaceae are rich in tropane alkaloids(TAs), which have significant pharmacological activities. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, pharmacological activities, and biosynthetic pathways of TAs in Solanaceous plants were summarized. Besides, the phylogeny of medicinal plants belonging to Solanaceae was visualized by network diagram. Fourteen genera of Solanaceae plants in China contain TAs and have medical records. TAs mainly exist in Datura, Anisodus, Atropa, Physochlaina, and Hyoscyamus. The TAs-containing species were mainly concentrated in Southwest China, and the content of TAs was closely related to plant distribution area and altitude. The Solanaceae plants containing TAs mainly have antispasmodic, analgesic, antiasthmatic, and antitussive effects. Modern pharmacological studies have proved the central sedative, pupil dilating, glandular secretion-inhibiting, and anti-asthma activities of TAs. These pharmacological activities provide a reasonable explanation for the traditional therapeutic efficacy of tropane drugs. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, and modern pharmacological activities of TAs-containing species in Solanaceae were analyzed for the first time. Based on these data, the genetic relationship of TAs-containing Solanaceae species was preliminarily discussed, which provided a scientific basis for the basic research on TAs-containing solanaceous species and was of great significance for the development of natural medicinal plant resources containing TAs.

Newly identified peptide hormone inhibits intestinal fat absorption and improves NAFLD through its receptor GPRC6A.

BACKGROUND & AIMS: Circulating peptides and G protein-coupled receptors (GPCRs) have gained much attention because of their biofunctions in metabolic disorders including obesity and non-alcoholic fatty liver disease (NAFLD). Herein, we aimed to characterize the role and therapeutic potential of a newly identified peptide hormone in NAFLD. METHODS: Using bioinformatics, we identified a murine circulating pentadecapeptide flanked by potential convertase cleavage sites of osteocalcin (OCN), which we named 'metabolitin (MTL)'. We used ligand-receptor binding, receptor internalization, bioluminescence resonance energy transfer and Nano isothermal titration calorimetry assays to study the binding relationship between MTL and GPRC6A. For in vivo biological studies, wild-type mice kept on a high-fat diet (HFD) were injected or gavaged with MTL to study its function in NAFLD. RESULTS: We confirmed that MTL binds to GPRC6A and OCN interacts with GPRC6A using in vitro biological studies. Both intraperitoneal and oral administration of MTL greatly improved NAFLD and insulin resistance in a mouse model. Interacting with GPRC6A expressed in intestines, MTL can significantly inhibit intestinal neurotensin secretion, which in turn inhibits triglyceride but not cholesterol gut absorption, mediated by the 5'AMP-activated protein kinase pathway. In addition, glucagon like peptide-1 secretion was induced by MTL treatment. CONCLUSIONS: Oral or intraperitoneal MTL significantly improves the symptoms of NAFLD by inhibiting lipid absorption and insulin resistance. MTL could be a potential therapeutic candidate for the treatment of NAFLD. LAY SUMMARY: A novel murine peptide hormone, herein named 'metabolitin', inhibits fatty acid absorption and improves systemic insulin resistance in a murine model of obesity and non-alcoholic fatty liver disease. Thus, metabolitin has therapeutic potential for the treatment of patients with non-alcoholic fatty liver disease.

Chemokine-like receptor 1 deficiency leads to lower bone mass in male mice.

The adipokine Chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), are associated with osteoblastogenic differentiation of mesenchymal stem cells (MSCs) and osteoclastogenic differentiation of osteoclast precursors in vitro, suggesting that CMKLR1 would affect the bone mineral density (BMD). However, the role of CMKLR1 on BMD in vivo remains unknown. Here, using CMKLR1 knockout mouse model, we unveiled that CMKLR1 effected the amount of Leydig cells in testis and regulated androgen-dependent bone maintenance in male mice, which exhibited lower serum testosterone levels, thereby reducing the trabecular bone mass. Correspondingly, the mRNA expression of testosterone synthesis enzymes in testis decreased. The bone tissue also showed decreased mRNAs expression of osteogenic markers and increased mRNA levels for osteoclast markers. Furthermore, by in vitro differentiation models, we found CMKLR1-deficiency could break the balance between osteoblastogenesis and osteoclastogenesis that caused a shift from osteogenic to adipogenic differentiation in MSCs and enhanced osteoclast formation. In addition, bone mass increase in CMKLR1 KO male mice can be promoted by treatment with 5α-dihydrotestosterone (DHT), and the inactivation of CMKLR1 in male wild-type (WT) mice with antagonist treatment can lead to low bone mass. Taken together, these data indicate that CMKLR1 positively regulates bone metabolism through mediating testosterone production and the balance between osteoblast and osteoclast formation.

[Simultaneous rapid detection of ten stilbenes in serum of mice by UPLC-MS/MS].

Stilbenes is a class of natural polyphenols with 1,2-diphenylethylene as the skeleton structure which have structural and active diversity. However, there are fewer studies on their metabolic process, which limits the in-depth research and development of such components. An UPLC-MS/MS method simultaneously determining contents of ten stilbenes was firstly established in this study and applied to study the ten stilbenes of peony seed coats in the serum of C57 mice.Piceatannol was the internal standard, and methanol was used for protein precipitation, UPLC-MS/MS with negative ion mode was used for analysis, and the method was validated.The serum samples were collected and detected after mice being oral administered with 800 mg·kg~(-1) peony seed coat extracts for 8 weeks. The results showed that suffruticosol A, suffruticosol B, suffruticosol C, trans-ε-viniferin, cis-gnetin H, trans-suffruticosol D and trans-gnetin H were detected in serum samples, and the highest is suffruticosol A. The method is simple and quick with high specificity and sensitivity, and it is suitable for quantitative determination of ten stilbenes in the serum of mice.

[Research methods and applications progress on spectrum-effect relationships in study of traditional Chinese medicine].

The application of chemical fingerprint to evaluate the quality of traditional Chinese medicine has been widely accepted and used in many countries. However,only by analyzing the type and content of its chemical components to evaluate the quality of traditional Chinese medicines,the gold standard of quality evaluation by evaluating pharmacodynamic effects is ignored. The study of Chinese medicinal spectrum-effect relationships combining the chemical composition with the pharmacodynamic activity of traditional Chinese medicine,which can evaluate the quality of traditional Chinese medicine from more comprehensive and different angles,has been applied in many fields of traditional Chinese medicine research. This paper mainly summarizes the research methods of the Chinese medicinal spectrum-effect relationships and its application in the field of traditional Chinese medicine study,and provides reference for the research,development and application of the Chinese medicinal spectrum-effect relationships.

Deficiency of Gpr1 improves steroid hormone abnormality in hyperandrogenized mice.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex genetic disease with multifarious phenotypes. Many researches use dehydroepiandrosterone (DHEA) to induce PCOS in pubertal mouse models. The aim of this study was to investigate the role of GPR1 in dehydroepiandrosterone (DHEA)-induced hyperandrogenized mice. METHODS: Prepubertal C57BL/6 mice (25 days of age) and Gpr1-deficient mice were each divided into two groups and injected daily with sesame oil with or without DHEA (6 mg/100 g) for 21 consecutive days. Hematoxylin and eosin (H&E) staining was performed to determine the characteristics of the DHEA-treated ovaries. Real-time PCR was used to examine steroid synthesis enzymes gene expression. Granulosa cell was cultured to explore the mechanism of DHEA-induced, GPR1-mediated estradiol secretion. RESULTS: DHEA treatment induced some aspects of PCOS in wild-type mice, such as increased body weight, elevated serum testosterone, increased number of small, cystic, atretic follicles, and absence of corpus luteum in ovaries. However, Gpr1 deficiency significantly attenuated the DHEA-induced weight gain and ovarian phenotype, improving steroidogenesis in ovaries and estradiol synthesis in cultured granulosa cells, partially through mTOR signaling. CONCLUSIONS: In conclusion, Gpr1 deficiency leads to the improvement of steroid synthesis in mice hyperandrogenized with DHEA, indicating that GPR1 may be a therapeutic target for DHEA-induced hyperandrogenism.

Risk factor of contralateral radiculopathy following microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion.

PURPOSE: Microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an advantageous method for treating lumbar degenerative disease; however, some patients show contralateral radiculopathy postoperatively. This study aims to investigate its risk factor. METHODS: A total of 130 cases who underwent microendoscopy-assisted MIS-TLIF at L4-5 level were divided into symptomatic and asymptomatic groups according to the presence of postoperative contralateral radiculopathy. Both preoperative and postoperative radiographic parameters, as well as their changes were compared between the two groups, including lumbar lordosis (LL), surgical segmental angle (SSA), disc height (DH), contralateral foramen area (CFA) and contralateral canal area (CCA). Screw breach on contralateral L4 pedicle and decompression method (ipsilateral or bilateral canal decompression through unilateral route) were also analyzed as potential risk factors. Receiver operating characteristic (ROC) curve was drawn for the risk factor to determine the optimal threshold for predicting postoperative contralateral radiculopathy. Besides, clinical outcome assessment, involving Visual Analog Score (VAS) for back and leg, Japanese Orthopaedics Association Score (JOA) and Oswestry Disability Index (ODI), was also compared between the two groups before surgery and at final follow-up (at least 3 months after the surgery for asymptomatic patients or final treatments of contralateral radiculopathy for symptomatic cases). RESULTS: Postoperative contralateral radiculopathy occurred in 11 (8.5%) of the 130 patients. Both preoperative and postoperative CFA as well as its change were significantly decreased in symptomatic group compared with asymptomatic group (all P < 0.05). For the remaining four parameters (LL, SSA, DH, CCA), their preoperative, postoperative and change values showed no statistical difference between the two groups (all P > 0.05). Neither screw breach nor decompression method revealed statistical association with this complication (both P > 0.05). Based on ROC curve, the optimal threshold of preoperative CFA was 0.76 cm2. At final follow-up, significant improvement in VAS (back and leg), JOA and ODI was observed in both groups compared with preoperative baseline (all P < 0.05), while no difference was found between the two groups (all P > 0.05). CONCLUSIONS: Preoperative contralateral foramen stenosis is the risk factor of contralateral radiculopathy following microendoscopy-assisted MIS-TLIF. If preoperative CFA at L4-5 level is not larger than 0.76 cm2, prophylactic measures, including both indirect and direct decompression of contralateral foramen, are recommended.

The first Taxus rhizosphere microbiome revealed by shotgun metagenomic sequencing.

In the present study, the shotgun high throughput metagenomic sequencing was implemented to globally capture the features of Taxus rhizosphere microbiome. Total reads could be assigned to 6925 species belonging to 113 bacteria phyla and 301 species of nine fungi phyla. For archaea and virus, 263 and 134 species were for the first time identified, respectively. More than 720,000 Unigenes were identified by clean reads assembly. The top five assigned phyla were Actinobacteria (363,941 Unigenes), Proteobacteria (182,053), Acidobacteria (44,527), Ascomycota (fungi; 18,267), and Chloroflexi (15,539). KEGG analysis predicted numerous functional genes; 7101 Unigenes belong to "Xenobiotics biodegradation and metabolism." A total of 12,040 Unigenes involved in defense mechanisms (e.g., xenobiotic metabolism) were annotated by eggNOG. Talaromyces addition could influence not only the diversity and structure of microbial communities of Taxus rhizosphere, but also the relative abundance of functional genes, including metabolic genes, antibiotic resistant genes, and genes involved in pathogen-host interaction, bacterial virulence, and bacterial secretion system. The structure and function of rhizosphere microbiome could be sensitive to non-native microbe addition, which could impact on the pollutant degradation. This study, complementary to the amplicon sequencing, more objectively reflects the native microbiome of Taxus rhizosphere and its response to environmental pressure, and lays a foundation for potential combination of phytoremediation and bioaugmentation.