Mangiferin, a Potential Supplement to Improve Metabolic Syndrome: Current Status and Future Opportunities.

Metabolic syndrome (MetS) represents a considerable clinical and public health burden worldwide. Mangiferin (MF), a flavonoid compound present in diverse species such as mango (Mangifera indica L.), papaya (Pseudocydonia sinensis (Thouin) C. K. Schneid.), zhimu (Anemarrhena asphodeloides Bunge), and honeybush tea (Cyclopia genistoides), boasts a broad array of pharmacological effects. It holds promising uses in nutritionally and functionally targeted foods, particularly concerning MetS treatment. It is therefore pivotal to systematically investigate MF's therapeutic mechanism for MetS and its applications in food and pharmaceutical sectors. This review, with the aid of a network pharmacology approach complemented by this experimental studies, unravels possible mechanisms underlying MF's MetS treatment. Network pharmacology results suggest that MF treats MetS effectively through promoting insulin secretion, targeting obesity and inflammation, alleviating insulin resistance (IR), and mainly operating via the phosphatidylinositol 3 kinase (PI3K)/Akt, nuclear factor kappa-B (NF-[Formula: see text]B), microtubule-associated protein kinase (MAPK), and oxidative stress signaling pathways while repairing damaged insulin signaling. These insights provide a comprehensive framework to understand MF's potential mechanisms in treating MetS. These, however, warrant further experimental validation. Moreover, molecular docking techniques confirmed the plausibility of the predicted outcomes. Hereafter, these findings might form the theoretical bedrock for prospective research into MF's therapeutic potential in MetS therapy.

Comprehensive insight into the pharmacology, pharmacokinetics, toxicity, detoxification and extraction of hypaconitine from Aconitum plants.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypaconitine (HA), a diterpenoid alkaloid, mainly derived from Aconitum plants such as Acoitum carmichaeli Debx. And Aconitum nagarum Stapf., has recently piqued significant interest among the scientific community given its multifaceted attributes including anti-inflammatory, anticancer, analgesic, and cardio-protective properties. AIM OF THE STUDY: This review presents a comprehensive exploration of the research advancements regarding the traditional uses, pharmacology, pharmacokinetics, toxicity, and toxicity reduction of HA. It aims to provide a thorough understanding of HA's multifaceted properties and its potential applications in various fields. MATERIALS AND METHODS: A systematic literature search was conducted using several prominent databases including PubMed, Web of Science, NCBI, and CNKI. The search was performed using specific keywords such as "hypaconitine," "heart failure," "anti-inflammatory," "aconite decoction," "pharmacological," "pharmacokinetics," "toxicity," "detoxification or toxicity reduction," and "extraction and isolation." The inclusion of these keywords ensured a comprehensive exploration of relevant studies and enabled the retrieval of valuable information pertaining to the various aspects of HA. RESULTS: Existing research has firmly established that HA possesses a range of pharmacological effects, encompassing anti-cardiac failure, anti-inflammatory, analgesic, and anti-tumor properties. The therapeutic potential of HA is promising, with potential applications in heart failure, ulcerative colitis, cancer, and other diseases. Pharmacokinetic studies suggest that HA exhibits high absorption rates, broad distribution, and rapid metabolism. However, toxic effects of HA on the nerves, heart, and embryos have also been observed. To mitigate these risks, HA needs attenuation before use, with the most common detoxification methods being processing and combined use with other drugs. Extraction methods for HA most commonly include cold maceration, soxhlet reflux extraction, and ultrasonic-assisted extraction. Despite the potential therapeutic benefits of HA, further research is warranted to elucidate its anti-heart failure effects, particularly in vivo, exploring aspects such as in vivo metabolism, distribution, and metabolites. Additionally, the therapeutic effects of HA monomers on inflammation-induced diseases and tumors should be validated in a more diverse range of experimental models, while the mechanisms underlying the therapeutic effects of HA should be investigated in greater detail. CONCLUSION: This review serves to emphasize the therapeutic potential of HA and highlights the crucial need to address its toxicity concerns before considering clinical application. Further research is required to comprehensively investigate the pharmacological properties of HA, with particular emphasis on its anti-cardiac failure and anti-inflammatory activities. Such research endeavors have the potential to unveil novel treatment avenues for a broad spectrum of diseases.

TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/ß-catenin Signaling Pathway.

OBJECTIVE: To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) and celastrol combination treatment (TCCT) in glioblastoma cells. METHODS: Cell counting kit-8 was used to detect the effects of different concentrations of celastrol (0-16 µmol/L) and TRAIL (0-500 ng/mL) on the cell viability of glioblastoma cells. U87 cells were randomly divided into 4 groups, namely control, TRAIL (TRAIL 100 ng/mL), Cel (celastrol 0.5 µmol/L) and TCCT (TRAIL 100 ng/mL+ celastrol 0.5 µmol/L). Cell proliferation, migration, and invasion were detected by colony formation, wound healing, and Transwell assays, respectively. Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition (EMT) markers (zona occludens, N-cadherin, vimentin, zinc finger E-box-binding homeobox, Slug, and ß-catenin). Wnt pathway was activated by lithium chloride (LiCl, 20 mol/L) and the mechanism for action of TCCT was explored. RESULTS: Celastrol and TRAIL synergistically inhibited the proliferation, migration, invasion, and EMT of U87 cells (P<0.01). TCCT up-regulated the expression of GSK-3ß and down-regulated the expression of ß-catenin and its associated proteins (P<0.05 or P<0.01), including c-Myc, Cyclin-D1, and matrix metalloproteinase (MMP)-2. In addition, LiCl, an activator of the Wnt signaling pathway, restored the inhibitory effects of TCCT on the expression of ß-catenin and its downstream genes, as well as the migration and invasion of glioblastoma cells (P<0.05 or P<0.01). CONCLUSIONS: Celastrol and TRAIL can synergistically suppress glioblastoma cell migration, invasion, and EMT, potentially through inhibition of Wnt/ß-catenin pathway. This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

A Machine Learning-Based Preclinical Osteoporosis Screening Tool (POST): Model Development and Validation Study.

Background: Identifying persons with a high risk of developing osteoporosis and preventing the occurrence of the first fracture is a health care priority. Most existing osteoporosis screening tools have high sensitivity but relatively low specificity. Objective: We aimed to develop an easily accessible and high-performance preclinical risk screening tool for osteoporosis using a machine learning-based method among the Hong Kong Chinese population. Methods: Participants aged 45 years or older were enrolled from 6 clinics in the 3 major districts of Hong Kong. The potential risk factors for osteoporosis were collected through a validated, self-administered questionnaire and then filtered using a machine learning-based method. Bone mineral density was measured with dual-energy x-ray absorptiometry at the clinics; osteoporosis was defined as a t score of -2.5 or lower. We constructed machine learning models, including gradient boosting machines, support vector machines, and naive Bayes, as well as the commonly used logistic regression models, for the prediction of osteoporosis. The best-performing model was chosen as the final tool, named the Preclinical Osteoporosis Screening Tool (POST). Model performance was evaluated by the area under the receiver operating characteristic curve (AUC) and other metrics. Results: Among the 800 participants enrolled in this study, the prevalence of osteoporosis was 10.6% (n=85). The machine learning-based Boruta algorithm identified 15 significantly important predictors from the 113 potential risk factors. Seven variables were further selected based on their accessibility and convenience for daily self-assessment and health care practice, including age, gender, education level, decreased body height, BMI, number of teeth lost, and the intake of vitamin D supplements, to construct the POST. The AUC of the POST was 0.86 and the sensitivity, specificity, and accuracy were all 0.83. The positive predictive value, negative predictive value, and F1-score were 0.41, 0.98, and 0.56, respectively. Conclusions: The machine learning-based POST was conveniently accessible and exhibited accurate discriminative capabilities for the prediction of osteoporosis; it might be useful to guide population-based preclinical screening of osteoporosis and clinical decision-making.

Integrating UPLC-Q-Exactive Orbitrap/MS, network pharmacology and experimental validation to reveal the potential mechanism of Tibetan medicine Rhodiola granules in improving myocardial ischemia-reperfusion injury.

ETHNOPHARMACOLOGY RELEVANCE: Rhodiola granules (RG) is a traditional Tibetan medicine prescription that can be used to improve the symptoms of ischemia and hypoxia in cardiovascular and cerebrovascular diseases. However, there is no report on its use to improve myocardial ischemia/reperfusion (I/R) injury, and its potential active ingredients and mechanism against myocardial ischemia/reperfusion (I/R) injury remain unclear. AIM OF THE STUDY: This study aimed to reveal the potential bioactive components and underlying pharmacological mechanisms of RG in improving myocardial I/R injury through a comprehensive strategy. MATERIALS AND METHODS: UPLC-Q-Exactive Orbitrap/MS technology was used to analyze the chemical components of RG, the potential bioactive components and targets were tracked and predicted by the SwissADME and SwissTargetPrediction databases, and the core targets were predicted through the PPI network, as well the functions and pathways were determined by GO and KEGG analysis. In addition, the molecular docking and ligation of the anterior descending coronary artery-induced rat I/R models were experimentally validated. RESULTS: A total of 37 ingredients were detected from RG, including nine flavones, ten flavonoid glycosides, one glycoside, eight organic acids, four amides, two nucleosides, one amino acid, and two other components. Among them, 15 chemical components, such as salidroside, morin, diosmetin, and gallic acid were identified as key active compounds. Ten core targets, including AKT1, VEGF, PTGS2, and STAT3, were discovered through the analysis of the PPI network constructed from 124 common potential targets. These possible targets were involved in the regulation of oxidative stress and HIF-1/VEGF/PI3K-Akt signaling pathways. Furthermore, molecular docking confirmed that the potential bioactive compounds in RG have good potential binding abilities to AKT1, VEGFA, PTGS2, STAT3, and HIF-1α proteins. Then, the animal experiments showed that RG could significantly improve the cardiac function of I/R rats, reduce the size of myocardial infarction, improve the myocardial structure, and reduce the degree of myocardial fibrosis, inflammatory cell infiltration, and myocardial cell apoptosis rate in I/R rats. In addition, we also found that RG could decrease the concentration of AGE, Ox-LDL, MDA, MPO, XOD, SDH, Ca2+, and ROS, and increase the concentration of Trx, TrxR1, SOD, T-AOC, NO, ATP, Na+k+-ATPase, Ca2+-ATPase, and CCO. Moreover, RG could significantly down-regulate the expressions of Bax, Cleaved-caspase3, HIF-1α, and PTGS2, as well up-regulate the expressions of Bcl-2, VEGFA, p-AKT1, and p-STAT3. CONCLUSION: In summary, we revealed for the first time the potential active ingredients and mechanisms of RG for myocardial I/R injury therapy through a comprehensive research strategy. RG may synergistically improve myocardial I/R injury through anti-inflammatory, regulating energy metabolism, and oxidative stress, improving I/R-induced myocardial apoptosis, which may be related to the HIF-1/VEGF/PI3K-Akt signaling pathway. Our study provides new insights into the clinical application of RG and also provides a reference for the development and mechanism research of other Tibetan medicine compound preparations.

Effects of rotted corn straw on soil environment, yield, and quality of cucumber.

Aiming at solving the problems of soil environment deterioration and the decline of both yield and quality caused by excessive application of chemical fertilizer, we investigated the effects of rotted corn straw on the soil environment of root zone, yield and quality of cucumber with 'Jinyou 35' cucumber as the experimental material. There were three treatments, namely, combined application of rotted corn straw and chemical fertilizer (T1, the total nitrogen fertilizer application were 450 kg N·hm-2, of which 9000 kg·hm-2 rotted corn straw was used as the subsoil fertilizer, and the rest was supplemented with chemical fertilizer), pure chemical fertilizer (T2, the total nitrogen fertilizer application was the same as T1) and no fertilization (control). The results showed that the content of soil organic matter in root zone soil in T1 treatment was much higher, but no difference between T2 treatment and the control, after two continuous plantings in one year. The concentrations of soil alkaline nitrogen, available phosphorus, available potassium of T1 and T2 in cucumber root zone were higher than that in the control. T1 treatment had lower bulk density, but markedly higher porosity and respiratory rate than T2 treatment and the control in root zone soil. The electric conductivity of T1 treatment was higher than that of the control, but significantly lower than T2 treatment. There was no significant difference in pH among the three treatments. The quantity of bacteria and actinomycetes in cucumber rhizosphere soil were the highest in T1, and the lowest in the control. However, the highest quantity of fungi was found in T2. The enzyme activities of rhizosphere soil in T1 treatment were markedly higher than those of the control, whereas those of T2 treatment were significantly lower or had no significant difference relative to the control. The cucumber root dry weight and root activity of T1 were significantly higher than that of the control. The yield of T1 treatment increased by 10.1%, and fruit quality improved obviously. The root activity of T2 treatment was also significantly higher than that in the control. There was no significant difference in root dry weight and yield between T2 treatment and the control. Furthermore, T2 treatment revealed a decrease in fruit quality relative to T1 treatment. These results suggested that the combined application of rotted corn straw and chemical fertilizer could improve soil environment, promote root growth, enhance root activity and improve yield and quality of cucumber in solar-greenhouse, which could be popularized and applied in protected cucumber production.

Swertia L.: A comprehensive review of its genetic relationship, chemical compositions, pharmacological effects, toxicities, and applications.

Swertia L., as a commonly used ethnic medicine, is widely distributed in Sichuan, Yunnan, and Xizang in China. Moreover, the medicinal plants of Swertia L. have been widely used and constitute one of the most important sources of various traditional medicines in China due to their prominent activities. In this review, the information on the classification, distribution, genetic relationship, chemical composition, pharmacological effects, toxicities, and applications of the medicinal plants in Swertia L. was summarized based on the scientific literature. The results indicated that the medicinal plants of Swertia L. mainly contained chemical components including triterpenes, xanthones, and iridoids. These compounds exert pharmacological effects including ameliorating diseases related to the liver and gallbladder. They also exert antiviral and antibacterial effects and can alleviate the increase in blood glucose levels. Especially, prescriptions related to Swertia L. have been widely adopted in preclinical and clinical studies to protect against diseases affecting the liver and the gallbladder, including hepatitis, cirrhosis, and cholecystitis. In addition, it also discusses toxicity studies and future perspectives and provides a reference for their clinical development and utilization.

Metabonomics and 16S rRNA gene sequencing to study the therapeutic mechanism of Danggui Sini decoction on collagen-induced rheumatoid arthritis rats with Cold Bi syndrome.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent joint inflammation. The development of rheumatoid arthritis is directly correlated with the disturbance of gut microbiome and its metabolites. RA can be effectively treated with the Danggui Sini decoction (DSD), a Traditional Chinese medicine (TCM) prescription from the Treatise on Febrile Diseases. Further research is needed to clarify the precise mechanism of DSD in the treatment of RA. In this study, 1H NMR metabonomics and 16 S rRNA gene sequencing techniques were used to clarify the intervention of DSD on CIA-induced RA. The results of 1H NMR metabolomics of feces revealed that five metabolites (alanine, glucose, taurine, betaine, and xylose) were disturbed, which could be regarded as potential biomarkers of RA. The intestinal microbiome of RA rats had changed, according to the results of 16 S rRNA gene sequencing; eight microbes (g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_group, g_Dubosiell, g_Lactobacillus, g_norank_f_Desulfovibrionaceae, g_Bacteroides, g_Oscillibacter, and g_Romboutsia) occurred significantly at the genus level, and DSD significantly impacted six of them (g_Dubosiell, g_Lactobacillus, g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_grou, g_Bacteroides, and g_Romboutsia). Three of them (g_norank_f_Eubacterium_ coprostanoligenes_group, g_Romboutsia, and g_Lactobacillus) were regarded as key microbiomes for DSD to treat RA, and three common metabolic pathways (taurine and hypotaurine metabolism; alanine, aspartate, and glutamate metabolism; primary bile acid biosynthesis) were discovered based on the 1H NMR metabonomics and PICRUST2 prediction of 16 S rRNA gene sequencing. Six SCFAs in feces (acetic acid, butyric acid, propionic acid, caproic acid, isobutyric acid, and valeric acid) increased significantly in RA, according to the outcomes of targeting SCFAs, while five SCFAs (acetic acid, butyric acid, propionic acid, caproic acid, and valeric acid) had decreased significantly due to DSD treatment. In conclusion, our study indicated that DSD could regulate RA's metabolic disorder by affecting intestinal microbiome and its metabolites. It also establishes a framework for future research into exploiting gut microbes therapeutic to treat RA.

[Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology].

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

Efficacy and feasibility of a 12-week Tai Chi training for the prophylaxis of episodic migraine in Hong Kong Chinese women: A randomized controlled trial.

Background: Tai Chi has been broadly applied as alternative treatment for many neurological and psychological disorders. Whereas no study using Tai Chi as prophylactic treatment for migraine. The purpose of this study was to preliminarily examine the efficacy and feasibility of a 12-week Tai Chi training on migraine attack prevention in a sample of Chinese women. Methods: A two-arm randomized controlled trial was designed. Women aged 18 to 65 years and diagnosed with episodic migraine were randomized to either Tai Chi group (TC group) or the waiting list control group. A modified 33-short form Yang-style Tai Chi training with 1 h per day, 5 days per week for 12 weeks was implemented in the TC group, with a 12-week follow up period. The control group received a "delayed" Tai Chi training at the end of the trial. The primary outcome was the differences in attack frequency between 4 weeks before baseline and at the 9-12 weeks after randomization. The intensity and duration of headache were also measured. The feasibility was evaluated by the maintenance of Tai Chi practice and satisfactory level of the participants toward training. Results: Eighty-two women were randomized, finally 40 in TC group and 33 in control group were involved in the analysis. On average, women in TC group had 3.0 times (95% CI: -4.0 to -2.0, P < 0.01) and 3.6 days (95% CI: -4.7 to -2.5, P < 0.01) reduction of migraine attack per month. Compared with the control group, the differences were statistically significant (-3.7 attacks/month, 95% CI: -5.4 to -1.9; and -3.0 migraine days/month, 95% CI: -4.5 to -1.5; both P < 0.001). The intensity and duration of headache had 0.6 (95% CI: -1.2 to -0.0, P < 0.05) units and 1.2 (IQR: -5.0 to 1.1, P < 0.05) hours reduction in TC group, respectively. Most of the participants (69.2%-97.4%) were satisfied with the training. At the end of 24 weeks, on average, the participants maintained 1.5 times of practice per week and 20 min for each practice. Conclusion: The 12-week Tai Chi training significantly decreased the frequency of migraine attack. It was acceptable and practicable among female migraineurs. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT03015753.

The effect of PO43--P concentration on sludge settleability and nutrients removal performance.

In order to explore the effect of influent PO43--P concentration on the relationship of phosphorus remove performance and sludge settleability, three sequencing batch reactors (SBRs) operated as anaerobic/aerobic mode were used to treat wastewater with different PO43--P concentrations (same COD), and the organic loading rate (OLR) was changed through adjusting the anaerobic (aerobic) duration. The sludge settleability, nutrients removal, and microorganism species were investigated. The results showed that when the influent PO43--P were 4.3 mg·L-1 and 8.6 mg·L-1, increasing the OLR through decreasing aerobic duration could significantly improve sludge settleability, while decreasing anaerobic duration could not. It was found that increase the OLR could promote the denitrification compete for carbon sources with phosphorus release process by inhibiting the accumulation of NO2--N, leading to the decrease of phosphorus removal ability. When the influent PO43--P was 17.2 mg·L-1, sufficient nitrification was beneficial to enrich denitrifying phosphorus accumulating bacteria (DPAO), and the activities of Thauera and Flavobacterium (DPAO) were stronger. Therefore, increasing influent PO43--P concentration and reducing aerobic duration could help phosphorus accumulating bacteria (PAO) compete with denitrification for COD and enrich DPAO, thus reducing carbon source consumption.

Intratumoral PD-1+CD8+ T cells associate poor clinical outcomes and adjuvant chemotherapeutic benefit in gastric cancer.

BACKGROUND: Although PD-1 has been reported to be a marker of T-cell exhaustion in several malignancies, the biological role of PD-1+CD8+ T cells in gastric cancer (GC) remains unclear. Herein, we aimed to investigate the role of PD-1+CD8+ T cells in the tumour microenvironment and its clinical significance in GC. DESIGNS: This study included 441 tumour microarray specimens and 60 Flow cytometry specimens of GC patients from Zhongshan Hospital, and 250 GC patients from the Asian Cancer Research Group. RESULTS: Here, we demonstrated that PD-1+CD8+ T cells functioned as an independent adverse prognosticator in GC. In addition, an abundance of intratumoral PD-1+CD8+ T cells indicated worse chemotherapeutic responsiveness to fluorouracil in Stage III GC patients. Mechanistically, PD-1+CD8+ T cell high infiltration indicated an exhausted phenotype of global CD8+ T cells in GC tissues, which was characterised by elevated immune checkpoint expression including CTLA-4 and TIM-3, whereas decreased expression of perforin. Furthermore, PD-1+CD8+ T cell high-infiltration patients with Stage III GC held elevated activity of several therapeutic signal pathways. CONCLUSIONS: Our study highlighted that PD-1+CD8+ T cell abundance predicts inferior prognosis in GC, and may serve as a novel predictive biomarker to guide therapeutic option.

High-throughput sequencing-based analysis of the composition and diversity of endophytic bacteria community in tubers of Gastrodia elata f.glauca.

Gastrodia elata f.glauca (G. elata) is a commonly used Chinese Medicinal Materials with great medicinal value. The medicinal plant and its endophytic bacteria are a symbiotic whole, and the endophytic bacteria are rich in species, and their metabolites are a treasure trove of natural compounds. However, there is a relative lack of analysis on the diversity, flora composition and network interactions of the endophytic bacteria of G. elata. In this study, high-throughput sequencing technology based on the Illumina Miseq platform was used to reveal the core microbiota by examining the diversity and community structures of tuber endophytic bacteria in G. elata grown under different regions and exploring the effect of region on its endophytic bacteria. Here, 1,265 endophytic ASVs were found to coexist with G. elata tuber in Guizhou and Hubei. At the phylum level, the dominant phyla were Proteobacteria, Actinobacteria and Acdobacteriota. At the family level, the dominant family were Comamonadaceae, Nocardicaece, Xanthobacteraceae, and Burkholderiaceae. At the genus level, Delftia and Rhodococcus were represented the core microbiota in G. elata tuber, which served as the dominant genera that coexisted in all samples tested. Moreover, we found that the beta diversity of endophytic bacteria in G. elata tuber was higher level in the Guizhou region than Hubei region. Overall, this study results to provide a reference for screening active strains and interaction between plants and endophytic bacteria.

Mechanical Anisotropy in Two-Dimensional Selenium Atomic Layers.

Two-dimensional (2D) trigonal selenium (t-Se) has become a new member in 2D semiconducting nanomaterial families. It is composed of well-aligned one-dimensional Se atomic chains bonded via van der Waals (vdW) interaction. The contribution of this unique anisotropic nanostructure to its mechanical properties has not been explored. Here, for the first time, we combine experimental and theoretical analyses to study the anisotropic mechanical properties of individual 2D t-Se nanosheets. It was found that its fracture strength and Young's modulus parallel to the atomic chain direction are much higher than along the transverse direction, which was attributed to the weak vdW interaction between Se atomic chains as compared to the covalent bonding within individual chains. Additionally, two distinctive fracture modes along two orthogonal loading directions were identified. This work provides important insights into the understanding of anisotropic mechanical behaviors of 2D semiconducting t-Se and opens new possibilities for future applications.

Construction of a Mesoporous Ceria Hollow Sphere/Enzyme Nanoreactor for Enhanced Cascade Catalytic Antibacterial Therapy.

Nanozyme has been regarded as one of the antibacterial agents to kill bacteria via a Fenton-like reaction in the presence of H2O2. However, it still suffers drawbacks such as insufficient catalytic activity in near-neutral conditions and the requirement of high H2O2 levels, which would minimize the side effects to healthy tissues. Herein, a mesoporous ceria hollow sphere/enzyme nanoreactor is constructed by loading glucose oxidase in the mesoporous ceria hollow sphere nanozyme. Due to the mesoporous framework, large internal voids, and high specific surface area, the obtained nanoreactor can effectively convert the nontoxic glucose into highly toxic hydroxyl radicals via a cascade catalytic reaction. Moreover, the generated glucose acid can decrease the localized pH value, further boosting the peroxidase-like catalytic performance of mesoporous ceria. The generated hydroxyl radicals could damage severely the cell structure of the bacteria and prevent biofilm formation. Moreover, the in vivo experiments demonstrate that the nanoreactor can efficiently eliminate 99.9% of bacteria in the wound tissues and prevent persistent inflammation without damage to normal tissues in mice. This work provides a rational design of a nanoreactor with enhanced catalytic activity, which can covert glucose to hydroxyl radicals and exhibits potential applications in antibacterial therapy.

[Preparation and Evaluation of Intranasal in situ Gel of Bupleuri Radix Volatile Oil and Baicalin].

OBJECTIVE: To prepare and evaluate a new formulation of thermosensitive and ion-sensitive in situ gel for nasal administration, using the volatile oil of Bupleuri radix and baicalin, the effective component extracted from Scutellariae radix . METHODS: Formulation of in situ nasal gel of Bupleuri radix volatile oil and baicalin was prepared by using poloxamer 407 and deacetylated gellan gum as the gel base, 10% pharmasolve and 2% polysorbate 80 as the solubilizer, and 0.8% triethanolamine as the pH regulator. The physical appearance, phase transition temperature, and baicalin release performance of the prepared gel were examined. The pharmacodynamic evaluation was done with the rat fever model developed with dry yeast and the mouse auricle swelling inflammation model. RESULTS: The phase transition temperature of the gel was optimized to be 36 ℃. The release of baicalin from the gel showed obvious features of sustained release, which accorded well the zero-order kinetics equation. The results of experiments with the rat dry yeast fever model and the mouse xylene auricle swelling inflammation model showed that the gel had significant antipyretic and anti-inflammatory effects that were significantly better than those of the groups treated with the blank gel base and the Bupleuri radix and Scutellariae radix granule. Results from the cilia toxicity test showed that the gel did not have obvious toxic effect on toad palate mucosal cilia. CONCLUSION: The in situ nasal gel of Bupleuri radix volatile oil and baicalin prepared in the study had a rapid onset time, high efficiency, and prolonged release of active ingredients, thus showing promises for further applicational development.

New limonoids and quinolone alkaloids with cytotoxic and anti-platelet aggregation activities from Evodia rutaecarpa (Juss.) Benth.

One new limonoid, named 19-hydroxy methyl isoobacunoate diosphenol (1); one new degraded limonoid, named 9α-methoxyl dictamdiol (9); two new quinolone alkaloids, 1-methyl-3-[(7E,9E,12Z)-7,9,12-pentadecadienyl]-4(1H)-quinolone (11) and 1-methyl-3-[(7E,9E,11E)-7,9,11-pentadecadienyl]-4(1H)-quinolone (12), along with eight known compounds, evodol (2), 7ß-acetoxy-5-epilimonin (3), rutaevine (4), 6ß-acetoxy-5-epilimonin (5), limonin (6), obacunone (7), clauemargine L (8), hiiranlactone E (10) were isolated from the fruits of Evodia rutaecarpa (Juss.) Benth.. Structures of the four new compounds were elucidated on the basis of extensive spectroscopic techniques, including 1D and 2D NMR techniques. Compounds 3, 5, 9, 11 and 12 showed obviously cytotoxic activity against six human tumor lines, while compounds 11, 12 displayed anti-platelet aggregation induced by ADP at 50 µM and 100 µM.

Controllable synthesis of iron-polyphenol colloidal nanoparticles with composition-dependent photothermal performance.

Iron-polyphenol nanoparticles are usually prepared with nontoxic plant polyphenols as a main building block, which are an emerging photothermal agent for photothermal therapy. However, till now, few works have been made on the controllable synthesis of iron-polyphenol nanoparticles with tunable composition, as well as investigation of the relationship between material composition and photothermal property. In the present study, iron-polyphenol colloidal nanoparticles with tunable diameter (21-303 nm) and ion content (9.2-97.6 mg/g), as well as high colloidal stability are successfully synthesized using different polyphenols (such as tannic acid, epigallocatechin gallate, gallic acid, epicatechin and proanthocyanidin) as a ligand. In addition, photothermal performance is highly dependent on the organic ligand, iron content and particle size. Higher iron content and smaller diameter can contribute to higher photothermal performance. The iron-polyphenol nanoparticles with the optimal iron content and particle size are selected as a photothermal agent. They can effectively inhibit the tumour growth in vivo. The current work demonstrates a general synthesis strategy for iron-polyphenol colloidal nanoparticles with tailorable composition and clarifies the relationship between material composition and photothermal performance. Moreover, it is conductive to the rational design of polyphenol-based photothermal agents for theranostic applications.

Feasibility, acceptability, and preliminary effectiveness of mindfulness-based interventions for people with recent-onset psychosis: A systematic review.

BACKGROUND: Early intervention for psychosis is recommended because the first 5 years beyond the first episode is considered the critical period within which individuals have the most potential to maximize their response to treatment and recovery. Mindfulness-based interventions (MBIs) have been studied extensively in diverse disease groups, but research in people with recent-onset psychosis is still immature. AIM: This review aims to explore the feasibility, acceptability and summarize any effectiveness data on of the MBIs for people with recent-onset psychosis reported by the study authors. METHODS: A systematic search of original intervention research studies relevant to the topic published between January 2000 and August 2019 was conducted with 10 databases. Articles published in English with accessible full text were included. RESULTS: A total of eight studies were included, which reported recruitment rates of between 62.5% and 100%, withdrawal rates between 0% and 37.5% and attendance rates of between 56% and 100%. Participants' qualitative feedback indicated high levels of satisfaction with the MBIs. The intervention approaches adopted in the reviewed studies include mindfulness-based interventions, acceptance and commitment therapy and compassion-based interventions. MBIs have produced promising positive effects on participants' psychiatric and psychosocial outcomes. CONCLUSION: This review confirms that MBIs are generally feasible and acceptable for people with recent-onset psychosis. The preliminary results suggested the potential effects of MBIs in this area. Fully powered randomized controlled trials are suggested to confirm the effectiveness and exploratory studies to gain greater insight into the active components and mechanism of actions of MBIs for recent-onset psychosis.

Intratumoral CD103+CD4+ T cell infiltration defines immunoevasive contexture and poor clinical outcomes in gastric cancer patients.

Our previous study has identified intratumoral CD103+CD8+ T cells as a favorable prognostic factor in gastric cancer. However, the significance of CD103+CD4+ T cells in gastric cancer hasn't yet been elucidated. Here, we aimed to investigate the clinical significance and phenotype characteristics of intratumoral CD103+CD4+ T cells in gastric cancer. In our study, 469 formalin-fixed and paraffin-embedded samples and 24 fresh tissue specimens of patients with gastric cancer from Zhongshan Hospital were included. We manifested that intratumoral CD103+CD4+ T cells in gastric cancer predicted poor overall survival and inferior responsiveness to fluorouracil-based ACT. The density and phenotypic characteristics of CD103+CD4+ T cells in gastric cancer were detected by immunohistochemistry and flow cytometry, which showed that CD103+CD4+ T cells exhibited an immunosuppressive phenotype and higher retention capacity in tumor tissues. Furthermore, increased CD103+CD4+ T cells contributed to CD8+T cell dysfunction with decreased granzyme B (GZMB), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and perforin (PRF-1) expression in gastric cancer. Overall, this study revealed that intratumoral CD103+CD4+T cell infiltration defined immunoevasive contexture and predicted poor prognosis and inferior responsiveness to fluorouracil-based ACT. Therefore, we recommended that CD103+CD4+ T cells might be a potential immunotherapeutic target for gastric cancer.