Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

[Analysis of clinical research features and outcome indexes of traditional Chinese medicine intervention in septic kidney injury].

This study aims to systematically review the clinical features and outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) intervention in septic kidney injury and provide a reference for optimizing clinical study design and building the core outcome set(COS) of TCM treatment of septic kidney injury. Computer searches were conducted on PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed to find published RCT of TCM intervention in septic kidney injury in the past five years, extract the basic characteristics, intervention measures, outcome indicators, and other data of included studies, and conduct descriptive analysis. 53 RCTs were included, and the sample size was mostly concentrated in 60-80 cases, with abdominal infection being the most common(15 articles, 83.3%) and the TCM syndrome of blood stasis being the most frequent(9 articles, 50.0%). The frequency of intervention methods from high to low were TCM decoction(28 articles, 52.8%), Chinese patent medicine(22 articles, 41.5%), and combined TCM therapy(3 articles, 7.5%); the intervention time of the trial was more than 7 d(34 articles, 69.4%). The risk of bias in included studies was unclear. A total of 84 outcome indicators were involved, which were divided into 9 fields, including 63 physical and chemical tests(305 times, 72.2%), 4 kinds of disease degree(48 times, 11.6%), 4 kinds of clinical effective rate(15 times, 3.6%), 1 kind of quality of life(1 time, 0.2%), 2 kinds of economic evaluation(14 times, 3.3%), 1 kind of TCM disease(9 times, 2.1%), 2 kinds of long-term prognosis(16 times, 3.8%), 2 kinds of safety events(6 times, 1.4%), and 5 other indicators(8 times, 0.7%). The cumulative frequency was 422 times, among which the outcome indicators with higher frequency were inflammatory factors(42 articles, 79.2%) and markers of renal function and kidney injury(40 articles, 75.5%). Only 1(1.9%) of the included articles mentioned primary and secondary outcome indicators, and 6 articles(11.3%) mentioned safety events, 13 articles(24.5%) mentioned economic assessment. The RCT quality of TCM intervention in septic renal injury was generally low, and the reference standards for sepsis, kidney injury, and TCM syndrome diagnosis were not uniform. There are some problems in outcome indicators, such as unclear distinction between primary and secondary indicators, neglect of endpoint indicators, lack of application of TCM characteristic indicators, and insufficient attention to safety events and economic assessment. It is suggested that the quality of clinical research methodology should be improved in the future, and the COS should be constructed to provide high-level evidence-based evidence for TCM intervention in septic kidney injury.

Reduced graphene oxide promotes the biodegradation of sulfamethoxazole by white-rot fungus Phanerochaete chrysosporium under cadmium stress.

The biodegradation of antibiotics in aquatic environment is consistently impeded by the widespread presence of heavy metals, necessitating urgent measures to mitigate or eliminate this environmental stress. This work investigated the degradation of sulfamethoxazole (SMX) by the white-rot fungus Phanerochaete chrysosporium (WRF) under heavy metal cadmium ion (Cd2+) stress, with a focus on the protective effects of reduced graphene oxide (RGO). The pseudo-first-order rate constant and removal efficiency of 5 mg/L SMX in 48 h by WRF decrease from 0.208 h-1 and 55.6% to 0.08 h-1 and 28.6% at 16 mg/L of Cd2+, while these values recover to 0.297 h-1 and 72.8% by supplementing RGO. The results demonstrate that RGO, possessing excellent biocompatibility, effectively safeguard the mycelial structure of WRF against Cd2+ stress and provide protection against oxidative damage to WRF. Simultaneously, the production of manganese peroxidase (MnP) by WRF decreases to 38.285 U/L in the presence of 24 mg/L Cd2+, whereas it recovers to 328.51 U/L upon the supplement of RGO. RGO can induce oxidative stress in WRF, thereby stimulating the secretion of laccase (Lac) and MnP to enhance the SMX degradation. The mechanism discovered in this study provides a new strategy to mitigate heavy metal stress encountered by WRF during antibiotic degradation.

The mechanism and experimental verification of Ixeris sonchifolia promoting apoptosis of hepatocellular carcinoma based on network pharmacology: Ixeris sonchifolia Induces Hepatocellular Carcinoma Apoptosis via the PI3K/AKT Pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance, a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. AIM OF THE STUDY: This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. MATERIALS AND METHODS: We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. RESULTS: A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. CONCLUSION: Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention.

Efficacy of traditional Chinese medicine on diabetic cardiomyopathy in animal models: a systematic review and meta-analysis.

Background: Diabetic cardiomyopathy (DCM) is a severe complication of diabetes that can diminish the quality of life in patients and is a leading cause of death. Research has demonstrated the effectiveness of Traditional Chinese Medicine (TCM) in reducing blood sugar levels and protecting cardiovascular function in both animal models and clinical research studies. Nevertheless, the efficacy of TCM in animal models of DCM has not been analyzed systematically. Method: We searched the following electronic bibliographic databases: Web of Science, PubMed, Cochrane Library, and CNKI(China National Knowledge Infrastructure). Studies that reported the efficacy of TCM in animals with DCM were included. The literature search was conducted using the terms. The data will be restricted from the year 2013 to 24 April 2023, 24 studies were included in the meta-analysis. Result: A total of 24 Traditional Chinese Medicine interventions and 2157 animals met the inclusion criteria. The pooled data revealed that TCM interventions resulted in significant improvements in body weight (BW), heart weight (HW) to body weight ratio (HW/BW), triglyceride (TG) and cholesterol (TC) levels, ejection fraction (EF), fractional shortening (FS) and E/A ratio. Subgroup analysis and meta-regression revealed that the type of TCM, duration of intervention, method of modeling, and animal species were potential sources of heterogeneity. Conclusion: TCM interventions were associated with significant improvements in body weight, heart weight to body weight ratio, triglyceride and cholesterol levels, left ventricular internal dimension in systole, ejection fraction, fractional shortening and E/A ratio. The heterogeneity in the results was found to be potentially due to the type of TCM, duration of intervention, method of modeling, and animal species, as shown in subgroup analysis and meta-regression. Systematic Review Registration: identifier CRD42023402908.

Selenium-binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non-small cell lung cancer.

BACKGROUND: Selenium is an essential trace element in the human body. In epidemiological and clinical studies, Se supplementation significantly reduced the incidence of lung cancer in individuals with low baseline Se levels. The significant action of selenium is based on the selenium-containing protein as a mediator. Of note, the previous studies reported that the expression of selenium-binding protein 1 (SELENBP1) was obviously decreased in many human cancer tissues including non-small cell lung cancer (NSCLC). However, its roles in the origin and development of NSCLC are still unclear. METHODS: The expression of SELENBP1 was measured by qRT-PCR, Western blotting and IHC in our collected clinical NSCLC tissues and cell lines. Next, the CCK-8, colony formation, wound-haeling, Millicell, Transwell, FCM assay, and in vivo xenograft model were performed to explore the function of SELENBP1 in NSCLC. The molecular mechanisms of SELENBP1 were investigated by Western blotting or IF assay. RESULTS: We further identified that the expression of SELENBP1 was significantly decreased in NSCLC tissues in TCGA database and 45 out of 59 collected clinical NSCLC tissues compared with adjacent nontumor tissues, as well as in four NSCLC cell lines compared with normal lung cells. Particularly, we unexpectedly discovered that SELENBP1 was obviously expressed in alveolar type 2 (AT-II) cells for the first time. Then, a series of in vitro experiments uncovered that overexpression of SELENBP1 inhibited the proliferation, migration, and invasion of NSCLC cells, and induced cell apoptosis. Moreover, overexpression of SELENBP1 also inhibited growth and induced apoptosis of NSCLC cells in vivo. Mechanistically, we demonstrated that overexpression of SELENBP1 inhibited the malignant characteristics of NSCLC cells in part via inactivating the PI3K/AKT/mTOR signal pathway. Meanwhile, we found that overexpression of SELENBP1 inducing the apoptosis of NSCLC cells was associated with the activation of caspase-3 signaling pathway under nonhigh level of oxidative stress, but overexpression of SELENBP1 facilitating the cell apoptosis might be related to its combining with GPX1 and colocalizing in the nucleus under high level of oxidative stress. CONCLUSIONS: Our findings highlighted that SELENBP1 was an important tumor suppressor during the origin and development of NSCLC. It may help to discover novel biomarkers or drug therapy targets for NSCLC.

Elucidation of the mechanism of Yiqi Tongluo Granule against cerebral ischemia/reperfusion injury based on a combined strategy of network pharmacology, multi-omics and molecular biology.

BACKGROUND: Ischemic stroke is caused by local lesions of the central nervous system and is a severe cerebrovascular disease. A traditional Chinese medicine, Yiqi Tongluo Granule (YQTL), shows valuable therapeutic effects. However, the substances and mechanisms remain unclear. PURPOSE: We combined network pharmacology, multi-omics, and molecular biology to elucidate the mechanisms by which YQTL protects against CIRI. STUDY DESIGN: We innovatively created a combined strategy of network pharmacology, transcriptomics, proteomics and molecular biology to study the active ingredients and mechanisms of YQTL. We performed a network pharmacology study of active ingredients absorbed by the brain to explore the targets, biological processes and pathways of YQTL against CIRI. We also conducted further mechanistic analyses at the gene and protein levels using transcriptomics, proteomics, and molecular biology techniques. RESULTS: YQTL significantly decreased the infarction volume percentage and improved the neurological function of mice with CIRI, inhibited hippocampal neuronal death, and suppressed apoptosis. Fifteen active ingredients of YQTL were detected in the brains of rats. Network pharmacology combined with multi-omics revealed that the 15 ingredients regulated 19 pathways via 82 targets. Further analysis suggested that YQTL protected against CIRI via the PI3K-Akt signaling pathway, MAPK signaling pathway, and cAMP signaling pathway. CONCLUSION: We confirmed that YQTL protected against CIRI by inhibiting nerve cell apoptosis enhanced by the PI3K-Akt signaling pathway.

Synthesis, Structure Revision, and Anti-inflammatory Activity Investigation of Putative Blumeatin.

Blumeatin, reported herein, bearing two hydroxyl groups at C3' and C5' of ring B, is isolated from the traditional Chinese medicine Blumea balsamifera. But the isolation procedure of blumeatin from plants has limitations of prolonged duration and high cost. A procedure featuring Lewis acid-catalyzed ring closure and chiral resolution via Schiff base intermediates is provided here to prepare optically pure blumeatin and its R-isomer efficiently. Furthermore, the structure revision of putative blumeatin based on a logically synthetic procedure and NMR spectroscopic analysis was conducted. The 1D and 2D NMR data analysis unambiguously confirmed our proposal that the reported blumeatin structure has been misassigned as it corresponds to sterubin, which contains two hydroxyl groups at C3' and C4' of ring B. Finally, the results of the ear-swelling test exhibited that synthetic (±)-blumeatin and (±)-sterubin had moderate anti-inflammatory activity which was less than that of (-)-sterubin.

Hybrid 2D-CMOS microchips for memristive applications.

Exploiting the excellent electronic properties of two-dimensional (2D) materials to fabricate advanced electronic circuits is a major goal for the semiconductor industry1,2. However, most studies in this field have been limited to the fabrication and characterization of isolated large (more than 1 µm2) devices on unfunctional SiO2-Si substrates. Some studies have integrated monolayer graphene on silicon microchips as a large-area (more than 500 µm2) interconnection3 and as a channel of large transistors (roughly 16.5 µm2) (refs. 4,5), but in all cases the integration density was low, no computation was demonstrated and manipulating monolayer 2D materials was challenging because native pinholes and cracks during transfer increase variability and reduce yield. Here, we present the fabrication of high-integration-density 2D-CMOS hybrid microchips for memristive applications-CMOS stands for complementary metal-oxide-semiconductor. We transfer a sheet of multilayer hexagonal boron nitride onto the back-end-of-line interconnections of silicon microchips containing CMOS transistors of the 180 nm node, and finalize the circuits by patterning the top electrodes and interconnections. The CMOS transistors provide outstanding control over the currents across the hexagonal boron nitride memristors, which allows us to achieve endurances of roughly 5 million cycles in memristors as small as 0.053 µm2. We demonstrate in-memory computation by constructing logic gates, and measure spike-timing dependent plasticity signals that are suitable for the implementation of spiking neural networks. The high performance and the relatively-high technology readiness level achieved represent a notable advance towards the integration of 2D materials in microelectronic products and memristive applications.

Family Socioeconomic Status and Adolescent Mental Health Problems during the COVID-19 Pandemic: The Mediating Roles of Trait Mindfulness and Perceived Stress.

The present study was conducted twice over one year during the COVID-19 pandemic with Chinese adolescents (n = 1582) to investigate the relationships among family socioeconomic status (SES), adolescent mental health problems, trait mindfulness, and perceived stress using self-reported measures. We administered the Mindful Attention Awareness Scale (MAAS), the Perceived Stress Scale (PPS), the Self-rating Anxiety Scale (SAS), the Epidemiologic Studies Depression Scale (CES-D), and Conduct Problem Tendency Inventory (CPTDI) to a sample of Chinese adolescents. The results prove that (1) there were significant correlations among socioeconomic status, trait mindfulness, perceived stress, and adolescent mental health problems, and the (2) serial mediation analysis indicated that trait mindfulness and perceived stress performed as mediators on the path from SES to anxiety, depression, and externalizing problems. Our findings provide a contribution by showing the connection between socioeconomic position and adolescent mental health problems and by offering a reference for the treatment of psychological issues affecting adolescents.

A new anti-vitiligo unsaturated fatty glycoside from Euphorbia humifusa Willd.

A new unsaturated fatty glycoside Humionoactosides A, together with four known compounds were isolated from the whole plant of Euphorbia humifusa Willd. Their structures were identified by MS/MS, NMR and ECD spectroscopic analyses, and comparison with the literature data. All compounds were evaluated for the effect on melanogenesis and tyrosinase activity use B16 cells in vitro, and the results showed that compound 1 could significantly improve the formation of melanin (138.7%, 50 µM) and tyrosinase activity (137.2%, 50 µM) compared with the positive control 8-MOP (125.2%, 138.9%, 50 µM) in a dose-dependent manner. This is the first time that those compounds reported from Euphorbia humifusa Willd. with potential anti-vitiligo activity.

Effects and mechanisms of an online short-term audio-based mindfulness program on positive affect: A randomized controlled trial including exploratory moderator analyses.

This study investigated the effects and mechanisms of an online short-term audio-based mindfulness (SAM) intervention program on positive affect and explored how well-being and negative affect influenced these effects and mechanisms. Participants (N = 100) were randomized into an intervention group (n = 50) and a control group (n = 50). Those in the mindfulness group underwent 3 weeks of an online SAM program and completed the online measures four times, while those in the control group completed the measures twice. Participants completed measures including the World Health Organization Well-Being Index, the Freiburg Mindfulness Inventory, and the Positive and Negative Affect Schedule. The effects of measures in both groups were compared. Parallel process latent growth curve modeling analysis was used to explore the longitudinal moderated mediation effects. The results showed that SAM was effective at improving positive affect, mindfulness, well-being, and reducing negative affect. Mindfulness growth speed during the intervention period mediated the relationship between SAM and positive affect improvement speed. The moderation effects of baseline well-being and negative effect on mediation effects were found to be significant. The SAM program was effective for the general public and was more beneficial for those with medium/high well-being and low/medium negative affect.

Effectiveness of an online short-term audio-based mindfulness program on negative emotions during the COVID-19 pandemic: Latent growth curve analyses of anxiety and moderated mediation effects of anxiety between mindfulness and negative affect.

This pilot study aims to explore the effects and mechanisms of a mindfulness-based intervention on negative emotions in community settings during the COVID-19 pandemic. Participants (N = 100) were randomized into an intervention group (n = 50) and a waitlist control group (n = 50). Participants in the mindfulness group underwent 3 weeks (21 sessions) of an online audio-based mindfulness-based intervention program and completed the online measures four times whereas those in the waitlist control group needed to complete the measures twice. Participants completed measures of the Hospital Anxiety and Depression Scale and Positive and Negative Affect Schedule. The results of the measures of the two groups were compared. Moderated mediation analysis was used to analyze intervention outcomes on negative affect through anxiety. Unconditional quadratic latent growth analysis was used to test the growth trajectories of anxiety. The results showed that this intervention program was effective at improving positive affect and at reducing depression, anxiety, and negative affect. The baseline anxiety moderator was found to be significant, and indirect effects of anxiety post-intervention were found between the mindfulness-based intervention and negative affect. Anxiety levels of participants were not at the same starting point and had similar but non-quadratic growth trajectories. The mindfulness-based intervention program was effective at promoting mental wellbeing and reducing mental problems in community settings in China. Mindfulness practices were beneficial to people with different anxiety levels but had more obvious benefits on anxiety and a negative affect for participants with low anxiety levels. Clinical trial registration: ISRCTN16205138 on 26/02/2021.

The Anti-Sepsis Effect of Isocorydine Screened from Guizhou Ethnic Medicine is Closely Related to Upregulation of Vitamin D Receptor Expression and Inhibition of NFκB p65 Translocation into the Nucleus.

Background: The anti-inflammatory application of Guizhou ethnic medicine in the Karst area of China is mainly based on folk medicine experience, and there has been a lack of systematic research, leading to limited application of Guizhou ethnic medicine. Purpose: To evaluate the anti-inflammatory effects of compounds extracted from Guizhou ethnic medicine in the Karst area and investigate their molecular mechanisms. Methods and Results: Preliminarily, the anti-inflammatory effects of 181 compounds extracted from Guizhou ethnic medicine were screened in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and the 41 compounds with anti-inflammatory effects were selected. Then, these 41 compounds with anti-inflammatory effects were investigated for their druggability and 18 compounds were selected. Thirdly, compound Hx-150, named isocorydine, was selected as the candidate compound. In vitro and in vivo, isocorydine inhibited LPS-induced TNF-α and IL-6 release from LPS-treated mouse peritoneal macrophages. Isocorydine decreased TNF-α, IL-6, and IL-1ß levels in the blood, lung, and spleen, and ameliorated lung tissue damage. Mechanistically, isocorydine had no effect on the mRNA expressions and protein levels of Tlr4, Myd88, and Traf6. Isocorydine also had no effect on the expression of RelA (encoding NFκB p65) mRNA, but inhibited phosphorylation of IκBα and NFκB p65 in the TLR4-mediated signaling pathway. Furthermore, isocorydine increased the cytoplasmic level of NFκB p65 and decreased its nuclear level in LPS-treated macrophages. Importantly, isocorydine upregulated Vdr mRNA (encoding the vitamin D receptor) expression and increased the nuclear VDR protein level. Conclusion: Many compounds from Guizhou ethnic medicine had potential anti-inflammatory activities. Among them, isocorydine has a strong anti-sepsis effect, which is tightly related to its upregulation of VDR expression and inhibition of NFκB p65 translocation into the nucleus, leading to reduced pro-inflammatory cytokines release and protection for LPS-challenged mice.

Efficacy and safety of acupuncture in the treatment of foot drop in post-stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Foot drop is a common complication in post-stroke. Patients with foot drop are at high risk for falls and fall-related injuries. Accordingly, it can reduce independence and quality of life in patients. Clinical studies have confirmed that acupuncture is effective in treating foot drop in post-stroke. However, there is a lack of systematic review exploring the efficacy and safety of acupuncture treatment. This study aims to assess the efficacy and safety of acupuncture in the treatment of foot drop in poststroke from the results of randomized controlled trials. METHODS: We will search articles in 8 electronic databases including the Cochrane Central Register of Controlled Trials, the Web of Science, PubMed, Embase, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Wanfang Data Database, and the Chinese Scientific Journal Database for RCTs of acupuncture treated foot drop in post-stroke from their inception to 10 August 2022. We will analyze the data meeting the inclusion criteria with the RevMan V.5.4 software. Two authors will assess the quality of the study with the Cochrane collaborative risk bias tool. We will evaluate the certainty of the estimated evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Data analysis will be performed using STATA 16.0. RESULTS: This study will review and evaluate the available evidence for the treatment of foot drop in post-stroke using acupuncture. CONCLUSION SUBSECTIONS: This study will determine the efficacy and safety of acupuncture applied to post-stroke individuals with foot drop.

A Candidate Drug Screen Strategy: The Discovery of Oroxylin A in Scutellariae Radix Against Sepsis via the Correlation Analysis Between Plant Metabolomics and Pharmacodynamics.

Sepsis is an acute systemic infectious disease with high mortality, which urgently needs more effective treatment. Scutellariae radix (SR), a commonly used traditional Chinese medicine (TCM) for clearing heat and detoxification, contains rich natural products possessing anti-inflammatory activity. In previous studies, it was found that the anti-inflammatory activities of SR extracts from different ecological conditions varied wildly. Based on this, in the present study, a screening strategy of antisepsis active components from SR based on correlation analysis between plant metabolomics and pharmacodynamics was established, and the mechanism was explored. First of all, a mass spectrum database of SR (above 240 components) was established to lay the foundation for the identification of plant metabolomics by liquid chromatography tandem mass spectrometry (LC-MS/MS). Through the correlation analysis between plant metabolomics and anti-inflammatory activity of SR from different ecology regions, 10 potential components with high correlation coefficients were preliminarily screened out. After the evaluation of anti-inflammatory activity and toxicity at the cellular level, the pharmacodynamic evaluation in vivo found that oroxylin A had the potentiality of antisepsis both in LPS- and CLP-induced endotoxemia mice. Network pharmacology and Western blot (WB) results indicated that oroxylin A significantly inhibited the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway, which was further confirmed by secreted embryonic alkaline phosphatase (SEAP) assay. Moreover, the molecular docking analysis indicated that oroxylin A might competitively inhibit LPS binding to myeloid differentiation 2 (MD-2) to block the activation of TLR4. The study provided a feasible research strategy for the screening and discovery of antisepsis candidate drugs from TCM.

[Analysis and prediction of quality markers of Lonicerae Japonicae Flos].

Lonicerae Japonicae Flos, as common Chinese medicine, has been used for thousands of years in the treatment of inflammation and infectious diseases with definite efficacies. The complex composition of Lonicerae Japonicae Flos results in its extensive pharmacological effects, so the assessment of its quality by only a few index components is not comprehensive. Guided by the quality marker(Q-marker), the present study comprehensively analyzed and predicted the quality connotation of Lonicerae Japonicae Flos based on the chemical composition and component transfer, the phylogenetic relationship, chemical composition effectiveness, measurability, and specificity. Chlorogenic acid, isochlorogenic acids A, B, and C, luteoloside, rutin, sweroside, and secoxyloganin were predicted as candidate Q-markers of Lonicerae Japonicae Flos.

The effectiveness of Salvianolate injection for in-stent restenosis after percutaneous coronary intervention: A protocol for systematic review and meta-analysis.

BACKGROUND: In-stent restenosis (ISR) caused by vascular remodeling after percutaneous coronary intervention limits the long-term efficacy of this method. Salvianolate injection is now widely used in the clinical treatment of ISR. However, there is no systematic review or meta-analysis to evaluate the effects of Salvianolate injection on ISR. METHODS: We will search articles in 8 electronic databases, including the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Wanfang Database, and the Chinese Scientific Journal Database for randomized controlled trials of ISR treated by Salvianolate injection from their inception to February 27, 2022. The primary outcome measure will be the restenosis rate. The data meeting the inclusion criteria were analyzed by RevMan V.5.4 software. Two authors evaluated the study using the Cochrane collaborative risk bias tool. We will use a scoring method to assess the overall evidence supporting the main results. RESULTS: This study will analyze the clinical effectiveness of Salvianolate injection in the treatment of ISR. CONCLUSION: The findings of this systematic review will provide evidence to evaluate the effectiveness of Salvianolate injection for the treatment of ISR. INPLASY REGISTRATION NUMBER: INPLASY202220117.

Integrating metabolomics and network pharmacology to reveal the mechanisms of Delphinium brunonianum extract against nonalcoholic steatohepatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Delphinii Brunoniani, a Tibetan Material Medica, derived from the aerial parts of Delphinium brunonianum Royle, possesses efficacy of cooling blood to remove apthogentic heat, and dispelling wind to arrest itching, and has been used for the treatment for liver disease according to Tibetan Medicine Theories in Shel Gong Shel Phreng. However, the mechanisms of action remain unclear. AIM OF THE STUDY: This work aimed to investigate the efficacy mechanism of Delphinium brunonianum extract (DBE) on nonalcoholic steatohepatitis (NASH), a kind of liver disease by integrating serum metabolomics and network pharmacology analysis. MATERIALS AND METHODS: In this study, NASH model mice were established by a high-fat diet. The indexes of lipid accumulation, insulin resistance, and inflammatory reaction were used to evaluate the efficacy of DBE. A combination of UHPLC-QTOF-MS based metabolomics and network pharmacology was established to illustrate the serum biomarkers of NASH mice and to demonstrate the anti-NASH mechanisms of DBE. Serum metabolomics demonstrated potential metabolites and the corresponding metabolic pathways in the efficacy of DBE. Network pharmacology screened the targets of DBE against NASH. Finally, the mechanisms of DBE against NASH were verified by in-vivo pharmacology. RESULTS: Metabolomics revealed that DBE significantly regulated the abnormal levels of twenty-two metabolites, which involved the biosynthesis of unsaturated fatty acids and steroid hormone, linoleic acid metabolism, arachidonic acid metabolism, and alpha-Linolenic acid metabolism pathways. Network pharmacology showed that DBE exhibited anti-NASH effects through regulating the targets of PTGS2, PLA2, ALOX5, ALOX15, FASN, and CYP450. Finally, united pharmacological verification result, we found that the mechanisms of DBE against NASH may be related to the regulation of the unsaturated fatty acids biosynthesis and the arachidonic acid metabolism pathway. CONCLUSIONS: Integrating serum metabolomic and network analysis, we found that DBE might inhibit the pathological process of NASH by regulating the relative targets and the metabolic pathways, which may be a potential mechanism for the anti-NASH efficacy of DBE. This integrated strategy also provided a rational way for revealing the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine (TCM).

The effectiveness of acupoint herbal patching for constipation after stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Constipation is one of the common problems in stroke patients, which seriously affects the life quality of patients and even leads to the recurrence of cerebrovascular disease. The clinical trials of acupoint herbal patching (AHP) in the adjuvant treatment of constipation after stroke (CAS) is currently in progress. However, there is no systematic review or meta-analysis to evaluate the effects of AHP on CAS. METHODS: We will search articles in 8 electronic databases including the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Wanfang Database, and the Chinese Scientific Journal Database for randomized controlled trials of CAS treated by AHP from their inception to November 1, 2021. The primary outcome measures will be clinical effective rate, defecation frequency, improvement of clinical symptoms including complete spontaneous bowel movements. The data meeting the inclusion criteria were analyzed by RevMan V.5.4 software. Two authors evaluated the study using the Cochrane collaborative risk bias tool. We will use a scoring method to assess the overall quality of evidence supporting the main results. RESULTS: This study will analyze the clinical effective rate, defecation frequency, improvement of clinical symptoms including complete spontaneous bowel movements after stroke. CONCLUSION: The findings of this systematic review will provide evidence to evaluate the effectiveness and safety of AHP for CAS. INPLASY REGISTRATION NUMBER: INPLASY202210065.