The complete chloroplast genomes of three Alismataceae species, including the medicinally important Alisma orientale.

Alismataceae is one of the early diverged families of monocotyledonous plants. We report the complete chloroplast genomes of three Alisma species, including Alisma orientale (Sam.) Juzep. 1934, A. subcordatum Raf. 1908, and A. triviale Pursh 1813, of which A. orientale is a traditional Chinese medical plant used widely to treat diuretics, diabetes, hepatitis, and inflammation. We sequenced the complete chloroplast genomes with the Illumina Nova-Seq 6000 platform using herbarium collections. The chloroplast genomes of A. orientale, A. subcordatum and A. triviale are 159,861 bp, 160,180 bp, and 159,727 bp in length, respectively. The three chloroplast genomes each contain 113 genes, including four rRNAs, 30 tRNAs genes, and 79 protein-coding genes, and the average GC content is 36.0%. Based on the whole chloroplast genomes of 19 species of Alismataceae and the close allies, the medicinally important A. orientale was found to be closely related to another medicinal plant Alisma plantago-aquatica L. 1753 in the phylogenetic analysis. The genus Alisma was supported to be monophyletic.

Subthalamic nucleus deep brain stimulation in primary Meige syndrome: motor and non-motor outcomes.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. METHODS: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. RESULTS: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. CONCLUSIONS: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.

AaLaeA targets AaFla1 to mediate the production of antitumor compound in Alternaria alstroemeria.

Endophytic fungi are an important source of novel antitumor substances. Previously, we isolated an endophytic fungus, Alternaria alstroemeria, from the medicinal plant Artemisia artemisia, whose crude extracts strongly inhibited A549 tumor cells. We obtained a transformant, namely AaLaeAOE26 , which completely loses its antitumor activity due to overexpression of the global regulator AaLaeA. Re-sequencing analysis of the genome revealed that the insertion site was in the noncoding region and did not destroy any other genes. Metabolomics analysis revealed that the level of secondary antitumor metabolic substances was significantly lower in AaLaeAOE26 compared with the wild strain, in particular flavonoids were more downregulated according to the metabolomics analysis. A further comparative transcriptome analysis revealed that a gene encoding FAD-binding domain protein (Fla1) was significantly downregulated. On the other hand, overexpression of AaFla1 led to significant enhancement of antitumor activity against A549 with a sevenfold higher inhibition ratio than the wild strain. At the same time, we also found a significant increase in the accumulation of antitumor metabolites including quercetin, gitogenin, rhodioloside, liensinine, ginsenoside Rg2 and cinobufagin. Our data suggest that the global regulator AaLaeA negatively affects the production of antitumor compounds via controlling the transcription of AaFla1 in endophytic A. alstroemeria.

Dietary supplementation of Ocimum gratissimum improves growth performance and immune response in broilers under high ambient temperature.

Ocimum gratissimum (OG) was found to have immunity boosting effect on Taiwan country chickens and broiler chickens raised in moderate ambient temperature in previous studies, and the current study investigates its potential on the growth performance, blood traits, intestinal traits, and immune responses in Ross 308 broilers raised in high ambient temperature which can induce mild heat-stress (26 to 33 ˚C, average 30 ˚C). Two hundred 1-d-old male/female chicks were randomly assigned to a control group, three OG (1 g/kg, 3 g/kg, and 5 g/kg)/basal diet groups, and one Amoxicillin group. Data collected during the experiment indicated that the weight gain increase of 1742 g/bird to 1815 g/bird comparing control to 5 g/kg OG supplementation was statistically significant. In addition, the production efficiency factor was also noticeably increased by OG, particularly in the 5 g/kg group, and the uric acid levels were decreased in the 3 and 5 g/kg OG groups (from 4.26 to 2.91 and 2.90 mg/dL, respectively), indicating heat-stress alleviation was observed. Several areas of the carcass saw desirable growth changes, including the increase of breast muscle ratio observed in the 5 g/kg OG group, an overall decrease in abdominal fat in all OG groups, as well as dimensional changes in several areas of the digestive system. Lastly, the hemaglutination, hemaglutination inhibition, and phytohemaglutinin tests indicated elevated immuno-response in all OG groups. In conclusion, OG has exhibited the ability to alleviate symptoms of mild heat-stress, leading to improvement of the digestive organ development and increase of carcass mass and mean weight gain for birds, and we find OG to be a potentially beneficial feed supplement for poultry raising in high ambient temperature conditions.

Ocimum gratissimum (OG) was found to have immunity boosting effect on Taiwan country chickens and broiler chickens raised in moderate ambient temperature in previous studies, and the current study investigates its potential on broilers raised in high ambient temperature. Data collected during the experiment indicated desirable changes in the physiology of the chickens, including overall increase in production efficiency factor, a significant weight gain in the 5 g/kg OG supplementation group, noticeable weight gain in several areas of the carcass especially the breast, an overall decrease in abdominal fat, dimensional changes in several areas of the digestive system, elevated immuno-response for all OG groups. In conclusion, OG has exhibited the ability to alleviate symptoms of mild heat-stress, leading to improvement of the digestive organ development and increase of carcass mass and mean weight gain for birds, and we find OG to be a potentially beneficial feed supplement for poultry raising in high ambient temperature conditions.

Endophytic fungus Biscogniauxia petrensis produces antibacterial substances.

Widespread drug resistance and limited antibiotics challenge the treatment of pathogenic bacteria, which leads to a focus on searching for new antimicrobial lead compounds. We found the endophytic fungus Biscogniauxia petrensis MFLUCC14-0151 from the medicinal plant Dendrobium harveyanum had antibacterial activity for the first time. This work aimed to reveal the capacity of Biscogniauxia petrensis MFLUCC14-0151 against foodborne pathogenic bacteria and identify its bioactive substances. Bioassay-guided isolation led to the discovery of six infrequent active monomers, including (10R)-Xylariterpenoid B (1), Xylariterpenoid C (2), Tricycloalternarene 1b (3), Tricycloalternarene 3b (4), Funicin (5) and Vinetorin (6) from MFLUCC14-0151 for the first time. The results of antibacterial tests showed that (10R)-Xylariterpenoid B and Xylariterpenoid C exhibited inhibitory activities against Streptococcus agalactiae with MIC values ranging from 99.21 to 100.00 µM, and against Streptococcus aureus with MIC values ranging from 49.60 to 50.00 µM. Tricycloalternarene 1b and Tricycloalternarene 3b showed inhibitory effects on Streptococcus agalactiae with MIC values ranging from 36.13 to 75.76 µM. Unexpectedly, Funicin and Vinetorin exhibited remarkable antagonistic activities against Streptococcus agalactiae with MIC values of 10.35 and 10.21 µM, respectively, and against Streptococcus aureus with MIC values of 5.17 and 20.42 µM, respectively. In conclusion, we suggest that the isolated compounds Funicin and Vinetorin may be promising lead compounds for natural antibacterial agents.

Curcuma Longa Induces the Transcription Factor FOXP3 to Downregulate Human Chemokine CCR5 Expression and Inhibit HIV-1 Infection.

HIV mutations occur frequently despite the substantial success of combination antiretroviral therapy, which significantly impairs HIV progression. Failure to develop specific vaccines, the occurrence of drug-resistant strains, and the high incidence of adverse effects due to combination antiviral therapy regimens call for novel and safer antivirals. Natural products are an important source of new anti-infective agents. For instance, curcumin inhibits HIV and inflammation in cell culture assays. Curcumin, the principal constituent of the dried rhizomes of Curcuma longa L. (turmeric), is known as a strong anti-oxidant and anti-inflammatory agent with different pharmacological effects. This work aims to assess curcumin's inhibitory effects on HIV in vitro and to explore the underpinning mechanism, focusing on CCR5 and the transcription factor forkhead box protein P3 (FOXP3). First, curcumin and the RT inhibitor zidovudine (AZT) were evaluated for their inhibitory properties. HIV-1 pseudovirus infectivity was determined by green fluorescence and luciferase activity measurements in HEK293T cells. AZT was used as a positive control that inhibited HIV-1 pseudoviruses dose-dependently, with IC50 values in the nanomolar range. Then, a molecular docking analysis was carried out to assess the binding affinities of curcumin for CCR5 and HIV-1 RNase H/RT. The anti-HIV activity assay showed that curcumin inhibited HIV-1 infection, and the molecular docking analysis revealed equilibrium dissociation constants of [Formula: see text]9.8[Formula: see text]kcal/mol and [Formula: see text]9.3[Formula: see text]kcal/mol between curcumin and CCR5 and HIV-1 RNase H/RT, respectively. To examine curcumin's anti-HIV effect and its mechanism in vitro, cell cytotoxicity, transcriptome sequencing, and CCR5 and FOXP3 amounts were assessed at different concentrations of curcumin. In addition, human CCR5 promoter deletion constructs and the FOXP3 expression plasmid pRP-FOXP3 (with an EGFP tag) were generated. Whether FOXP3 DNA binding to the CCR5 promoter was blunted by curcumin was examined using transfection assays employing truncated CCR5 gene promoter constructs, a luciferase reporter assay, and a chromatin immunoprecipitation (ChIP) assay. Furthermore, micromolar concentrations of curcumin inactivated the nuclear transcription factor FOXP3, which resulted in decreased expression of CCR5 in Jurkat cells. Moreover, curcumin inhibited PI3K-AKT activation and its downstream target FOXP3. These findings provide mechanistic evidence encouraging further assessment of curcumin as a dietary agent used to reduce the virulence of CCR5-tropic HIV-1. Curcumin-mediated FOXP3 degradation was also reflected in its functions, namely, CCR5 promoter transactivation and HIV-1 virion production. Furthermore, curcumin inhibition of CCR5 and HIV-1 might constitute a potential therapeutic strategy for reducing HIV progression.

[Evaluation methods of clinical efficacy of traditional Chinese medicine].

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.

[Problems and thoughts in clinical safety evaluation of traditional Chinese medicine].

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Tetramerization of STAT5 regulates monocyte differentiation and the dextran sulfate sodium-induced colitis in mice.

In response to external stimuli during immune responses, monocytes can have multifaceted roles such as pathogen clearance and tissue repair. However, aberrant control of monocyte activation can result in chronic inflammation and subsequent tissue damage. Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces monocyte differentiation into a heterogenous population of monocyte-derived dendritic cells (moDCs) and macrophages. However, the downstream molecular signals that dictate the differentiation of monocytes under pathological conditions is incompletely understood. We report here that the GM-CSF-induced STAT5 tetramerization is a critical determinate of monocyte fate and function. Monocytes require STAT5 tetramers to differentiate into moDCs. Conversely, the absence of STAT5 tetramers results in a switch to a functionally distinct monocyte-derived macrophage population. In the dextran sulfate sodium (DSS) model of colitis, STAT5 tetramer-deficient monocytes exacerbate disease severity. Mechanistically, GM-CSF signaling in STAT5 tetramer-deficient monocytes results in the overexpression of arginase I and a reduction in nitric oxide synthesis following stimulation with lipopolysaccharide. Correspondingly, the inhibition of arginase I activity and sustained supplementation of nitric oxide ameliorates the worsened colitis in STAT5 tetramer-deficient mice. This study suggests that STAT5 tetramers protect against severe intestinal inflammation through the regulation of arginine metabolism.

Molecular networking-assisted systematical profiling and the in vivo neuroprotective effect of ellagitannins from the Melastoma dodecandrum Lour.

BACKGROUND: Ellagitannins (ETs) are a major classification of natural tannins, with relatively large and complex structures. ETs from medicinal plants are focused increasingly due to urolithins, a kind of intestinal metabolite of ETs, which showed promising anti-Alzheimer's disease (AD) effects. Melastoma dodecandrum (MD), a widely used traditional Chinese medicine is rich in ETs, but their chemistry and potential neuroprotective effects have not been investigated. PURPOSE: This study aimed to identify the chemical composition of ETs in the crude extract of MD and to investigate their neuroprotective effects in vivo. METHODS: UPLC-QTOF-MS-based molecular networking (MN) and structural characterization were applied to targeted profiling of the MD-ETs. Animal behavior experiments, including the novel object recognition test (NOR), open field test (OFT), and Morris water maze test (MWM), were conducted to assess the memory improvement effects of MD-ETs in AD model mice. RESULTS: A total of 70 ETs, ranging from monomers to tetramers, were tracked and characterized in the MD extract using MN-guided targeted profiling, with 59 of them reported for the first time in this species. MD-ETs significantly improved memory impairment in AD mice, as indicated by decreased escape latency, increased number of crossings and target quadrant distance in MWM, increased rearing number in OFT, and increased preference index in NOR. CONCLUSION: This study systematically characterized the composition and structural features of ETs in MD using targeted LC-MS profiling, expanding the chemical information of ETs in MD. Furthermore, the results demonstrate that MD-ETs have significant effects on improving impaired memory in AD mice, suggesting their potential as alternative natural medicines for the treatment of neurodegenerative diseases.

Jointly Depleting Glutathione Based on Self-Assembled Nanomicelles for Enhancing Photodynamic Therapy.

Photodynamic therapy (PDT) is one common ROS-generating therapeutic method with high tumor selectivity and low side effects. But the GSH-upregulation often alleviates its therapeutic efficiency. Here, we proposed a new strategy of jointly depleting GSH to enhance the therapeutic effect of PDT by preparing a nanomicelle by self-assembly method from GSH-activated photosensitizer DMT, curcumin, and amphiphilic polymer TPGS.

Mechanisms of action underlying the effect of Tongsaimai on wound healing based on experimental and network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongsaimai (TSM) is a traditional Chinese medicine that has several therapeutic qualities, including anti-inflammatory, anti-oxidative, and anti-vasculitis effects. However, its impacts and underlying mechanisms on wound healing remain unclear. AIM OF THE STUDY: The aim of our study was to evaluate TSM for its pro-healing effect and the relevant mechanisms using both experimental validation and network pharmacology analysis. MATERIALS AND METHODS: The components of TSM were detected by high-performance liquid chromatography combined with diode array detector (HPLC-DAD). Skin wounds with a diameter of 4 mm were created on the backs of mice, after which, topical treatments of 2.5-10% TSM were applied onto the lesions once daily for either 2 or 7 days. Then, the wound tissues were collected to determine the impacts of TSM on collagen deposition, epithelial cell proliferation, oxidative stress, inflammation, and angiogenesis. Moreover, the effects of TSM (0.5-2 mg/mL) on the cell viability of HUVECs and HaCaT cells were evaluated. RESULTS: A total of 11 components in TSM were identified by HPLC-DAD. TSM was found to enhance the rate of wound contraction and increase epithelial thickness and collagen deposition during the healing process. In addition, TSM increased SOD activity and downregulated MDA and IL-1ß levels in the wound tissues. Immunofluorescence analysis further indicated an increased expression of Ki67, CD31, and VEGF in wound tissues following TSM administration. Results of the network pharmacology analysis revealed that multiple pathways including VEGF, PI3K/Akt, and MAPK pathways were involved in the pharmacological actions of TSM on wound healing. Accordantly, in vitro experiments revealed that TSM promoted the proliferation of HUVECs and HaCaT cells while activating the PI3K/Akt pathway. CONCLUSIONS: Our results suggest that TSM may serve as a therapeutic medication to improve wound healing by employing multiple regulatory mechanisms that affect proliferation, angiogenesis, collagen deposition, oxidative stress, and inflammation.

[Effect of electroacupuncture at "Zusanli" (ST36) and "Tianshu" (ST25) on intestinal function and autonomic nerve balance in rats with irritable bowel syndrome].

OBJECTIVE: To study whether electroacupuncture (EA) of "Zusanli" (ST36) combined with "Tianshu" (ST25) has a synergistic effect in regulating the colonic function and autonomic nerve balance in rats with irritable bowel syndrome (IBS). METHODS: Male Wistar rats were randomly divided into control, model, EA-ST36, and EA-ST36+ST25 groups, with 14 rats in each group. The IBS model was established by using water avoidance stress method. The visceral hypersensitivity was measured using the abdominal wall retraction reflex (AWR). The rectus abdominis electromyogram (EMG), intestinal electrical activity, and electrocardiogram (ECG) were recorded using a PowerLab data acquisition and analysis system. The contents of serum cAMP and cGMP were determined by ELISA, the expression levels of colonic tyrosine hydroxylase (TH) and choline acetyl-transferase (ChAT) proteins were determined by immunofluorescence staining and Western blot, respectively. RESULTS: Compared with the control group, the model group had an evident increase in the levels of AWR, LF, LF/HF, ChAT protein expression, cAMP and cGMP contents and cAMP/cGMP ratio (P<0.001, P<0.05), and a marked decrease in the levels of HF, frequency of slow waves of intestinal EMG, visceral pain threshold (PT), immunoactivity and expression of TH protein (P<0.05, P<0.001). In contrast to the model group, the levels of AWR, LF, LF/HF, ChAT protein expression and immunoactivity, cAMP and cGMP contents and ratio of cAMP/cGMP were significantly reduced (P<0.001, P<0.05, P<0.01), whereas the levels of frequency of slow waves of intestinal EMG, PT, and the immunoactivity and expression of TH were considerably increased (P<0.001, P<0.05) in both EA-ST36 and EA-ST36+ST25 groups. CONCLUSION: EA of both ST36 and ST36+ST25 can relieve visceral pain, and reduce sympathetic activity to improve autonomic nerve balance, but without apparent synergistic effect between EA-ST36 and EA-ST25 in rats with IBS.

HPF Modulates the Differentiation of BMSCs into HLCs and Promotes the Recovery of Acute Liver Injury in Mice.

Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into hepatocyte-like cells (HLCs) to alleviate acute liver injury (ALI). Herpetfluorenone (HPF), as an active ingredient in the dried, mature seeds Herpetospermum caudigerum Wall, used in Tibetan medicine, has been proven to effectively alleviate ALI. Therefore, the purpose of this study was to determine whether HPF can promote the differentiation of BMSCs into HLCs and promote ALI recovery. Mouse BMSCs were isolated, and the BMSCs' differentiation into HLCs was induced by HPF and hepatocyte growth factor (HGF). Under the induction of HPF and HGF, the expression of hepatocellular specific markers and the accumulation of glycogen and lipids in the BMSCs increased, indicating that BMSCs successfully differentiated into HLCs. Then, the ALI mouse model was established, using carbon tetrachloride, followed by an intravenous injection of BMSCs. Then, only HPF was injected intraperitoneally, in order to verify the effect of HPF in vivo. In vivo imaging was used to detect the homing ability of HPF-BMSCs, and it was detected that HPF-BMSCs significantly increased the levels of serum AST, ALT and ALP in the liver of ALI mice, and alleviated liver cell necrosis, oxidative stress and liver pathology. In conclusion, HPF can promote the differentiation of BMSCs into HLCs and promote the recovery of ALI in mice.

Mechanism and Molecular Targets of a Water-Soluble Extract of Artemisia annua on the Treatment of Alzheimer's Disease Based on Network Pharmacology and Experimental Validation.

Oxidative stress is an important contributor to the pathogenesis of Alzheimer's disease (AD). The overproduction of reactive oxygen species observed in AD patients results in the loss of mitochondrial function, altered metal ion homeostasis, lipopolysaccharide metabolism disorder, reduced anti-oxidant defense, increased release of inflammatory factors, and the aggravation and accumulation of amyloid-beta and tau hyper-phosphorylation, which directly cause synaptic and neuronal loss and lead to cognitive dysfunction. Thus, oxidative stress proves to be a fundamental part of AD development and progression, suggesting the potential benefits of anti-oxidant-based therapies for AD. In this study, we found that a water-soluble extract of Artemisia annua (WSEAA), a traditional Chinese herbal medicine, has a strong anti-oxidant function. We also found that WSEAA is able to improve the cognitive function of 3xTg AD mice. However, the mechanisms and molecular targets underlying WSEAA action are still not known. In order to uncover the potential molecular mechanisms involved, we used a combination of network pharmacology and different experimental approaches. Obtained results revealed key genes (such as AKT1, BCL2, IL-6, TNF-[Formula: see text] and BAX) and signaling pathways (like PI3K-AKT and BCL2/BAX) are closely associated with the biological processes responding to oxidative stress. Further verification of the survival/anti-oxidant effects of WSEAA in vitro and in vivo showed that the extract has anti-oxidatant/neuronal survival action against H2O2-induced damage, and is thus able to prevent the cognitive decline and pathological changes of 3xTg transgenic (3xTg) mice via the regulation of key target-genes and pathways, such as PI3K-AKT and BCL2/BAX, related to survival/apoptosis. Our findings strongly indicate the potential of WSEAA for the prevention and treatment of AD.

Mountain-water-forest-farmland-lake-grassland-sandland holistic protection and restoration engineering and landscape ecology.

Theoretical researches and practices on the life community of mountain-water-forest-farmland-lake-grassland-sandland mosaic and its protection and restoration have been gradually developed in China, which demands the support of a systematic disciplinary theory. Landscape ecology, as an interdisciplinary science of geography and ecology, can meet such demand thanks to its macroscopic spatial theory and technical system. Here, landscape ecology is taken as the supporting discipline of holistic protection and restoration for mountain-water-forest-farmland-lake-grassland-sandland mosaic. Firstly, we clarified that life community of mountain-water-forest-farmland-lake-grassland-sandland is a heterogeneously mosaic landscape, which bears all the characteristics of landscape and thus follows the principles of landscape ecology. Secondly, we expounded how the basic principles of landscape-ecological construction could be applied to the planning and evaluation of holistic protection and restoration for mountain-water-forest-farmland-lake-grassland-sandland mosaic. Finally, we summarized the new trend of landscape-ecological construction research, listed the theoretical and practical problems to be solved, and discussed how the projects of holistic protection and restoration for the mountain-water-forest-farmland-lake-grassland-sandland mosaic can provide a variety of practices for seeking the solutions. The combination of landscape ecology and practical restoration projects would generate effective solutions to realize sustainable development in terms of ecology, economy, and society in China and even the whole world.

Rationale and design of the RESTORE trial: A multicenter, randomized, double-blinded, parallel-group, placebo-controlled trial to evaluate the effect of Shenfu injection on myocardial injury in STEMI patients after primary PCI.

BACKGROUND: The mortality following ST-segment elevation myocardial infarction (STEMI) remains substantial in the reperfusion era. Shenfu injection, as a traditional Chinese herbal formula, can alleviate ischemia-reperfusion injury through multiple pharmacologic effects. However, no robust data are available regarding the role of Shenfu injection in reducing infarct size for patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). METHODS/DESIGN: This RESTORE trial is a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial (NCT04493840). A total of 326 eligible patients with first-time anterior STEMI undergoing PPCI within 12 h of symptom onset will be enrolled from 10 centers in mainland China. Patients are randomized in a 1:1 fashion to receive either intravenous Shenfu injection (80mL Shenfu injection + 70mL 5% glucose injection) or placebo group (150mL 5% glucose injection) before reperfusion and followed by once a day until 5 days after PPCI. The primary end point is infarct size assessed by cardiac magnetic resonance (CMR) imaging 5±2 days after PPCI. The major secondary end points include enzymatic infarct size, microvascular obstruction, intramyocardial hemorrhage, left ventricular volume and ejection fraction assessed by CMR, as well as cardiovascular events at 30 days. CONCLUSIONS: The RESTORE trial is sufficiently powered to demonstrate the clinical effects of Shenfu injection on myocardial injury in STEMI patients undergoing PPCI in the contemporary era.

Effects of acupuncture and medical training therapy on depression, anxiety, and quality of life in patients with frequent tension-type headache: A randomized controlled study.

OBJECTIVES: To compare the effects of acupuncture and medical training therapy in combination or individually with usual care on quality of life, depression, and anxiety in patients with tension-type headache. METHODS: In this single-center, prospective, randomized, controlled, unblinded trial, 96 adults (38.7(+/-13.3) years of age; 75 females/20 males/one dropout) with frequent episodic or chronic tension-type headache were randomized to one of four treatment groups (n = 24). The treatment groups received six weeks of either acupuncture or medical training therapy as monotherapies or in combination (12 interventions each), or usual care. We assessed depressiveness (PHQ-9), anxiety (GAD-7), and health-related quality of life (SF-12) as secondary outcome parameters at baseline, six weeks, three months, and six months after initiation of treatment. Linear mixed models were calculated. RESULTS: Both, acupuncture (baseline to six-weeks change scores: mean: -2(standard deviation: 2.5 points), three months: -2.4(2.4), six-months -2.7(3.6)) and the combination of acupuncture and medical training therapy (-2.7(4.9), -2.2(4.0), -2.2(4.2)) (each within-group p < .05) significantly reduced depressiveness-scores (PHQ-9) to a greater extent than medical training therapy (-0.3(2.0), -0.5(1.6), -0.9(2.6)) or usual care alone (-0.8(2.9), 0.1(2.8), 0.2(3.6)). We found similar results with anxiety scores and the physical sum scores of the SF-12. No severe adverse events occurred. CONCLUSIONS: Acupuncture and the combination of acupuncture and medical training therapy elicit positive effects on depression, anxiety, quality of life, and symptom intensity in patients with episodic and chronic tension-type headache. Acupuncture appears to play a central role in mediating the therapeutic effects, underscoring the clinical relevance of this treatment. An additive benefit of the combination of both therapies does not appear to be relevant.Trial registration: Registered on 11 February 2019. German Clinical Trials Register, DRKS00016723.

Use of Ferulic Acid in the Management of Diabetes Mellitus and Its Complications.

Diabetes mellitus, a metabolic disease mainly characterized by hyperglycemia, is becoming a serious social health problem worldwide with growing prevalence. Many natural compounds have been found to be effective in the prevention and treatment of diabetes, with negligible toxic effects. Ferulic acid (FA), a phenolic compound commonly found in medicinal herbs and the daily diet, was proved to have several pharmacological effects such as antihyperglycemic, antihyperlipidemic and antioxidant actions, which are beneficial to the management of diabetes and its complications. Data from PubMed, EM-BASE, Web of Science and CNKI were searched with the keywords ferulic acid and diabetes mellitus. Finally, 28 articles were identified after literature screening, and the research progress of FA for the management of DM and its complications was summarized in the review, in order to provide references for further research and medical applications of FA.

Effects of Chlorella extracts on growth of Capsicum annuum L. seedlings.

The long-term application of chemical fertilizers has caused to the farmland soil compaction, water pollution, and reduced the quality of vegetable to some extent. So, its become a trend in agriculture to find new bio-fertilizers. Chlorella extract is rich in amino acids, peptides, nucleic acids, growth hormones, potassium, calcium, magnesium, iron, zinc ions, vitamin E, B1, B2, C, B6, folic acid, free biotin and chlorophyll. Chlorella extract can promote biological growth, mainly by stimulating the speed of cell division, thereby accelerating the proliferation rate of cells and playing a role in promoting plant growth. Whether Chlorella extract can be used to improve the growth of pepper (Capsicum annuum), needs to be verified. In current study, a pepper variety 'Chao Tian Jiao' was used as experiment material, by determining the changes of the related characteristics after spraying the seedlings with Chlorella extract, and its effect on growth of Capsicum annuum plants was investigated. The results showed that the Chlorella extract significantly increased plant height of pepper seedlings (treatment: 32.2 ± 0.3 cm; control: 24.2 ± 0.2 cm), stem diameter (treatment: 0.57 ± 0.02 cm; control: 0.41 ± 0.03 cm) and leaf area (treatment: 189.6 ± 3.2 cm2; control: 145.8 ± 2.5 cm2). Particularly, the pepper seedlings treated with Chlorella extract, developed the root system in better way, significantly increased the chlorophyll a, and the activities of SOD, POD and CAT enzymes were also improved significantly. Based on our results, we can speculate that it is possible to improve the growth of Capsicum annuum seedlings and reduce the application of chemical fertilizers in pepper production by using Chlorella extract.