Constructing Interfacial Charge Transfer Channels and Electric Field in Violet Phosphorus-Based van der Waals Heterojunction for Phototherapy of Periodontitis.

Periodontitis, a chronic oral disease instigated by bacteria, severely compromises human oral health. The prevailing clinical treatment for periodontitis involves mechanical scraping in conjunction with antibiotics. Phototherapy is employed to rapidly remove the bacteria and achieve periodontitis treatment, effectively circumventing the adverse effects associated with traditional therapies. Constructing 2D/2D van der Waals (VDW) heterojunctions is a key strategy for obtaining excellent photocatalytic activity. Herein, a 2D/2D violet phosphorus (VP)/Ti3C2 VDW heterojunction is designed using an interfacial engineering strategy. By constructing an electron transport "bridge" (P-Ti bond) at the heterogeneous interface as an effective transfer channel for photogenerated carriers, a compact monolithic structure between the VP and Ti3C2 phases is formed, and the spatial barrier for electron transfer at the interface is eliminated. Meanwhile, the strong directional built-in electric field induced by the intensive electron-coupling effect at the heterogeneous interface served as an internal driving force, which greatly accelerates the exciton dissociation and charge transfer in the photocatalytic process. These excited photogenerated electrons and holes are trapped by O2 and H2O on the surfaces of Ti3C2 and VP, respectively, and are subsequently catalytically converted to antibacterial reactive oxygen species (ROS). The VP/Ti3C2 VDW heterojunction eradicated 97.5% and 98.48% of Staphylococcus aureus and Escherichia coli, respectively, by photocatalytic and photothermal effects under visible light for 10 min. The VP/Ti3C2 nanoperiodontal dressing ointment effectively attenuated inflammatory response, reduced alveolar bone resorption, and promoted periodontal soft and hard tissue repair. Its periodontitis therapeutic effect outperforms the clinically used Periocline.

Analysis of bioactive components and synergistic action mechanism of ShuGan-QieZhi Capsule for treating non-alcoholic fatty liver disease.

BACKGROUND: ShuGan-QieZhi capsule (SGQZC) is a traditional Chinese preparation used to treat hyperlipidemia and obesity, even non-alcoholic fatty liver disease (NAFLD). However, its therapeutic effects, main bioactive ingredients, as well as potential mechanisms for NAFLD are still unclear. PURPOSE: To investigate the pharmacological effect, main active ingredients, and mechanisms of SGQZC against high-fat diet (HFD)-induced NAFLD in mice. METHODS: NAFLD models were established by feeding C57BL/6 J mice an HFD for 24 weeks. From the 12th week, HFD-fed mice received daily gavage of either SGQZC or silibinin for 12 weeks. Hepatic hypertrophy parameters, along with hepatic and systemic lipid metabolism changes in NAFLD mice, were assessed. Oil red O and histopathological staining techniques determined lipid accumulation and liver injury severity. qRT-PCR analysis measured the expression of genes tied to liver lipid metabolism and inflammation. HPLC-MS/MS identified the primary components of SGQZC in the serum. Human normal hepatocytes (LO2) and hepatic stellate cells (LX-2) were used to screen SGQZC's bioactive ingredients. Network pharmacological analysis, transcriptomics, and western blotting delved into SGQZC's synergistic mechanisms against NAFLD. RESULTS: SGQZC ameliorated abnormal lipid metabolism and liver hypertrophy in mice with HFD-induced NAFLD, consequently reducing hepatic lipid accumulation, inflammatory cell infiltration, and liver impairment. Eight crucial components of SGQZC were detected in serum using HPLC-MS/MS and were found to effectively attenuate lipid accumulation and inflammation in liver cells. Further investigation indicated that SGQZC modulates MAPK pathway and AKT/NF-κB pathway, subsequently improving lipid metabolism and inflammation. CONCLUSION: SGQZC alleviates NAFLD by synergistically modulating the MAPK-mediated lipid metabolism and inhibiting AKT/NF-κB pathways-mediated inflammation. Our findings reveal the enormous potential of SGQZC for the treatment of NAFLD, providing a possible new clinical therapeutic strategy.

Effect of moxibustion on knee joint stiffness characteristics in recreational athletes pre- and post-fatigue.

Objective: Joint stiffness results from the coupling of the nervous system and joint mechanics, and thus stiffness is a comprehensive representation of joint stability. It has been reported that moxibustion can alleviate general weakness and fatigue symptoms and subsequently may influence joint stiffness. This study investigated whether moxibustion could enhance knee joint stiffness in recreational athletes pre- and post-fatigue. Methods: Eighteen participants were randomized into intervention (5 males: 20.6 ± 1.5 yr; 4 females: 20.8 ± 1.5 yr) and control groups (5 males: 19.4 ± 0.9 yr; 4 females: 20.5 ± 0.6 yr). The intervention group received indirect moxibustion applied to acupoints ST36 (bilateral) and CV4 for 30 min every other day for 4 consecutive weeks. The control group maintained regular exercise without moxibustion. Peak torque (PT) of right knee extensor, relaxed and contracted muscle stiffness (MS) of vastus lateralis, and knee extensor musculoarticular stiffness (MAS) was assessed with an isokinetic dynamometer (IsoMed 2000), myometer, and free oscillation technique, respectively. Measurements were taken at three time points: pre-intervention, post-intervention/pre-fatigue, and post-fatigue. Results: MAS (P = 0.006) and PT (P = 0.007) in the intervention group increased more from pre-to post-intervention compared with the control group. Post-fatigue MAS (P = 0.016) and PT (P = 0.031) increased more in the intervention group than in the control group. Conclusion: Moxibustion enhanced PT and knee MAS, suggesting that this intervention could be used in injury prevention and benefit fatigue resistance in young recreational athletes.

Correlation between MRI features and CSF inflammatory factor levels in patients with infarction or TIA, assessed by contrast-enhanced high-resolution MRI.

OBJECTIVE: To explore the correlation between the time course of CE-T1WI plaque and the level of CSF inflammatory factors in patients with cerebral infarction or TIA assessed by contrast-enhanced high-resolution MRI. METHODS: From August 2019 to December 2021, 136 patients with ischemic stroke-related neurological symptoms or suspected ischemic stroke in Gong'an County Hospital of Traditional Chinese Medicine were retrospectively analyzed, including 69 men and 67 women aged 45-80 years old, with an average age of 65.98±8.29. The study was divided into two groups: infarction group (patients with high DWI signal in the middle cerebral artery supply area, n=68) and TIA group (patients with ischemic neurologic symptoms but no relevant imaging findings, n=68). Patients with grade 1 or grade 2 image quality were included in the study after imaging with a 3.0T MRI device. Unenhanced MRI (T1WI and T2WI) and contrast-enhanced T1WI (CE+T1WI) plaque signals were compared between the two groups. The expression levels of TNF-α, IL-6, and IL-1ß in CSF of the two groups were detected by ELISA. VAMLN, LAMLN, PA, stenosis rate, and reconstruction index were compared between the two groups. The SNR and CNR values on T1WI and CE+T1WI were compared. The expression levels of TNF-α, IL-6, and IL-1ß detected by ELISA in cerebrospinal fluid of patients with CE-T1WI plaque enhancement were compared. RESULTS: The expression levels of TNF-α, IL-6, and IL-1ß in the cerebral infarction group were higher than those in the TIA group (P<0.05). Comparing the VAMLN, LAMLN, PA, stenosis rate and remodeling index of the two groups, the VAMLN, PA, and remodeling index of the cerebral infarction group were higher than in the TIA group (P>0.05), and there was no significant difference in VAMLN and stenosis rate between groups (P<0.05). Comparing the plaque SNR and CNR values on T1WI and CE+T1WI, the signal intensity, adjacent signal intensity, SNR, and CNR of carotid plaque on CE+T1WI were higher than those on T1WI (P>0.05). The expression levels of TNF-α, IL-6, and IL-1ß in the moderate enhancement group were higher than those in the non-enhancement group, and the expression levels of TNF-α, IL-6 and IL-1ß in the high enhancement group were higher than those in the moderate enhancement group (P<0.05). CONCLUSION: The temporal variation of CE-T1WI plaque was positively correlated with the level of cerebrospinal fluid inflammatory factors. High levels of inflammatory factors, positive remodeling, and significant enhancement were closely related to unstable plaque, which may increase the risk of stroke in patients with atherosclerosis.

Pitsubcosides A-L, highly esterified eudesmane sesquiterpenoid glycosides with antibacterial activity from Pittosporum subulisepalum and their mechanism.

BACKGROUND: Plants from the genus Pittosporum are traditionally used as antibacterial, antifungal and antiviral agents. A bioassay evaluation of the extract of Pittosporum subulisepalum revealed antibacterial activity. This study focused on the discovery of the antibacterial metabolism in P. subulisepalum, as well as the modes of action of its active components. RESULTS: A chemical investigation of an ethyl acetate (EtOAc) extract of the aerial parts of P. subulisepalum led to the isolation of 12 previously undescribed eudesmane sesquiterpenoid glycoside esters (ESGEs), pitsubcosides A-L (1-12). Their structures were elucidated by extensive spectroscopic analysis, including one- and two-dimensional NMR, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism spectra and single-crystal X-ray crystallography analysis or by comparing with authentic samples. The new ESGEs were characterized by their highly esterified glycoside moieties. Among them, compounds 1-3, 5 and 8 showed a moderate inhibitory effect against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Bacillus cereus, Bacillus subtilis, Pseudomonas syringae pv. actinidiae (Psa) and Erwinia carotovora with minimum inhibitory concentrations (MICs) ranging from 3.13 to 100 µm. Among them, compounds 3 and 5 showed remarkable antibacterial activity against S. aureus and Psa with MIC values of 6.25 and 3.13 µm, respectively. Live bacterial mass and the biofilms of S. aureus and Psa were quantified using methyl tetrazolium and crystal violet assays. Fluorescence microscopy and scanning electron microscopy experiments revealed an antibacterial mechanism of cell membrane architectural disruption. CONCLUSION: The results suggest that ESGEs possess great potential for the development of antibacterial agents to control plant pathogens. © 2023 Society of Chemical Industry.

The Efficacy and Mechanism of Qinghua Jianpi Recipe in Inhibiting Canceration of Colorectal Adenoma Based on Inflammatory Cancer Transformation.

Objective: This study is aimed at exploring the effect of Qinghua Jianpi Recipe on preventing colon polyp recurrence and inhibiting the progress of "inflammatory cancer transformation." And another goal is to explore the changes of intestinal flora structure and intestinal inflammatory (immune) microenvironment of mice with colon polyps treated by Qinghua Jianpi Recipe and to clarify its mechanism. Methods: Clinical trials were conducted to confirm the therapeutic effect of Qinghua Jianpi Recipe on patients with inflammatory bowel disease. The inhibitory effect of Qinghua Jianpi Recipe on "inflammatory cancer transformation" of colon cancer was confirmed by an adenoma canceration mouse model. Histopathological examination was used to evaluate the effects of Qinghua Jianpi Recipe on intestinal inflammatory state, adenoma number, and pathological changes of adenoma model mice. The changes of inflammatory indexes in intestinal tissue were tested by ELISA. Intestinal flora was detected by 16S rRNA high-throughput sequencing. Short-chain fatty acid metabolism in the intestine was analyzed by targeted metabolomics. Network pharmacology analysis of possible mechanism of Qinghua Jianpi Recipe on colorectal cancer was performed. Western blot was used to detect the protein expression of the related signaling pathways. Results: Qinghua Jianpi Recipe can significantly improve intestinal inflammation status and function in patients with inflammatory bowel disease. Qinghua Jianpi Recipe could significantly improve the intestinal inflammatory activity and pathological damage of adenoma model mice and reduce the number of adenoma. Qinghua Jianpi Recipe significantly increased the levels of Peptostreptococcales_Tissierellales, NK4A214_group, Romboutsia, and other intestinal flora after intervention. Meanwhile, the treatment group of Qinghua Jianpi Recipe could reverse the changes of short-chain fatty acids. Network pharmacology analysis and experimental studies showed that Qinghua Jianpi Recipe inhibited the "inflammatory cancer transformation" of colon cancer by regulating intestinal barrier function-related proteins, inflammatory and immune-related signaling pathways, and free fatty acid receptor 2 (FFAR2). Conclusion: Qinghua Jianpi Recipe can improve the intestinal inflammatory activity and pathological damage of patient and adenoma cancer model mice. And its mechanism is related to the regulation of intestinal flora structure and abundance, short-chain fatty acid metabolism, intestinal barrier function, and inflammatory pathways.

Solid SiO2-Sealed Mesoporous Silica for Synergistically Combined Use of Inorganic and Organic Filters to Achieve Safe and Effective Skin Protection from All-Band UV Radiation.

To effectively shield the full band of ultraviolet (UV) radiation and provide desirable protection, the combination of inorganic and organic filters was often used to protect human skin from the serious harm of UV exposure. However, the incompatibility of different filters and their mutual negative effect limit the production of multifilter sunscreen. In addition, the hazard of reactive oxygen species (ROS) produced by inorganic filters after UV exposure and the skin permeability of organic filters remain unresolved problems. In this study, titanium dioxide (TiO2) and diethylamino hydroxybenzoyl hexyl benzoate (DHHB), two kinds of common filters with complementary UV shielding range, were first encapsulated into large mesoporous silica nanoparticles (MSN, ∼300 nm) to obtain MSN-TiO2 and MSN-DHHB. Also, a SiO2 coating was then made to seal and stabilize the MSN-TiO2 and MSN-DHHB. The structure, UV screen function, and safety of the SiO2-coated filters, MSN-TiO2@SiO2 and MSN-DHHB@SiO2, were evaluated. The good mechanical stability exhibited by the solid SiO2 layer prevented the release and skin penetration of the sealed DHHB and the photocatalysis of TiO2. Furthermore, the combination of MSN-TiO2@SiO2 and MSN-DHHB@SiO2 in sunscreen cream showed excellent UV shielding performance on covering the whole UV radiation range without mutual interference. Therefore, coating SiO2 over MSN is a feasible strategy for entrapping various filters to improve their photostability, preventing skin penetration and ROS generation, and enhancing their compatibility with different sunscreen formulations.

Spatiotemporal and Transcriptional Characterization on Tanshinone Initial Synthesis in Salvia miltiorrhiza Roots.

Tanshinones are the bioactive constituents of Danshen (Salvia miltiorrhiza Bunge), which is used in Traditional Chinese Medicine to treat cardiovascular and other diseases, and they synthesize and accumulate in the root periderm of S. miltiorrhiza. However, there is no relevant report on the initial stage of tanshinone synthesis, as well as the root structure and gene expression characteristics. The present study aims to provide new insights into how these bioactive principles begin to synthesize by characterizing possible differences in their biosynthesis and accumulation during early root development from both spatial and temporal aspects. The morphological characteristics and the content of tanshinones in roots of S. miltiorrhiza were investigated in detail by monitoring the seedlings within 65 days after germination (DAGs). The ONT transcriptome sequencing was applied to investigate gene expression patterns. The periderm of the S. miltiorrhiza storage taproot initially synthesized tanshinone on about 30 DAGs. Three critical stages of tanshinone synthesis were preliminarily determined: preparation, the initial synthesis, and the continuous rapid synthesis. The difference of taproots in the first two stages was the smallest, and the differentially expressed genes (DEGs) were mainly enriched in terpene synthesis. Most genes involved in tanshinone synthesis were up regulated during the gradual formation of the red taproot. Plant hormone signal transduction and ABC transport pathways were widely involved in S. miltiorrhiza taproot development. Five candidate genes that may participate in or regulate tanshinone synthesis were screened according to the co-expression pattern. Moreover, photosynthetic ferredoxin (FD), cytochrome P450 reductase (CPR), and CCAAT binding transcription factor (CBF) were predicted to interact with the known downstream essential enzyme genes directly. The above results provide a necessary basis for analyzing the initial synthesis and regulation mechanism of Tanshinones.

Maternal supplementation with Artemisia annua L. ameliorates intestinal inflammation via inhibiting the TLR4/NF-κB and MAPK pathways and improves the oxidative stability of offspring.

Artemisia annua L. (A. annua) contains artemisinin, which attracts attention on account of its anti-inflammatory and anti-oxidant effects. Increased intestinal inflammation, oxidative stress, and hypoimmunity commonly occur in neonatal and early-weaning piglets. Abundant evidence suggests that maternal nutritional interventions during pregnancy modify the offspring's long-term gut development. The present study was conducted to investigate the effects of maternal A. annua extract (AAE) supplementation on the offspring's intestinal inflammation and redox status. A total of 90 pregnant sows were assigned randomly and equally into the control (CON) group (fed with a basal diet) and the 0.1% (AAE) group (basal diet with 1.0 g kg-1 AAE) during late gestation and lactation. The results showed that 0.1% AAE supplementation significantly decreased the contents and relative mRNA expressions of interleukin (IL)-1ß, IL-6, and IL-12, and tumor necrosis factor-α in the small intestine of the newborn and weaned piglets (offspring) (P < 0.05). There were higher activities of total antioxidant capacity and total superoxide dismutase, whereas a lower concentration of malondialdehyde in the small instestine of offspring in the 0.1% AAE group than that in the CON group (P < 0.05). Furthermore, the 0.1% AAE group decreased the mRNA and protein expressions of Toll-like receptor 4 (TLR4) and inhibited the activation of TLR4-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways (P < 0.05). The mRNA expression of peroxisome proliferator activated receptor γ (PPARγ), porcine beta-defensin (PBD)-1, PBD-2, PBD-3, mucin (MUC)-1, MUC-2 and MUC-4 was significantly enhanced in the small intestine of both neonatal and weanling piglets (P < 0.05). Together, these results showed that maternal 0.1% AAE supplementation improved the redox status and attenuated the neonatal and early-weaning associated inflammatory response in the offspring's small intestine, possibly by suppressing the activation of the TLR4/NF-κB and MAPK inflammatory pathways, and stimulated expressions of beta-defensins, mucins, and PPARγ to promote inflammation resolution and innate immunity response.

The Effects of Tai Chi Exercise for Patients with Type 2 Diabetes Mellitus: An Overview of Systematic Reviews and Meta-Analyses.

Objectives: Tai chi (TC) is a potential complementary treatment for type 2 diabetes mellitus (T2DM). This overview systematically summarizes and evaluates the existing evidence of TC in the treatment of T2DM. Methods: Systematic reviews (SRs)/meta-analyses (MAs) on TC interventions for T2DM were comprehensively searched in seven databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the list of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Eight published SRs/MAs were included in our study. Based on the methodology and quality of evidence assessment, all SRs/MAs are considered to be of very low quality, and only 1 SR/MA has been assessed as low risk of bias, and none of the SR/MA has been fully reported on the checklist. A total of 65 outcome indicators extracted from the included SRs/MAs were evaluated, and only 1 item was assessed as high quality. Conclusions: TC may be an effective and safe complementary treatment for T2DM. However, this conclusion must be treated with caution because the quality of the evidence provided by the included SRs/MAs is generally low.

Performance enhancement and population structure of denitrifying phosphorus removal system over redox mediator at low temperature.

The development of denitrifying polyphosphate accumulating organisms (DPAOs) presents a strategy to carbon competition between denitrifying bacteria and phosphorus removing bacteria. However, low temperature inhibits the rate of enzyme-catalyzed and substrate diffusion during denitrifying phosphorus removal (DPR). Therefore, the present study assessed the addition of NQS (100 µmol/L) for enhancing the removal of TP and TN in DPR reactors operated at alternating anaerobic and anoxic phases and different influent phosphate concentrations. The results showed that the removal efficiency of TP and TN in NQS-DPR system at 10 °C were 99.9% and 42.0%, respectively, which were 2.1 and 2.0 times higher than that of DPR system. Adding NQS significantly alleviated the increase of pH under anoxic condition and decreased the ORP value of the reactor, which in turn enhanced the PHAs accumulation process. The determination of functional genes (nirK, narG and phoD) showed that Dechloromonas, Lentimicrobium, and Terrimonas were the dominant functional bacteria in NQS-DPR system at 10 °C with the relative abundance of 3.09%, 2.99% and 2.28%, respectively. This study can provide valuable information for the effects of the addition of the redox mediator on denitrifying phosphorus removal technology.

K Value: An Indicator that can Characterize the Cold and Hot Properties of Traditional Chinese Medicines.

Aims: The cold and hot properties of Chinese medicines are an important concept to represent the function of drugs, and are also a unique classification method of traditional Chinese medicine (TCM). The method reflects an herb's therapeutic properties and guides reasonable clinical prescription. However, the present key problem is the lack of an objective and quantitative evaluation index for the cold and hot properties of Chinese herbs. Delayed luminescence (DL) is the long-term afterglow of biological systems after illumination with light, which can reflect differences in herbal materials prepared under different conditions. We aim to use S. obliquus as an indicator organism to characterize the differences between the cold and hot properties of Chinese herbs. Methods: Scenedesmus obliquus (S. obliquus) was used as an indicator organism to characterize the differences between the cold and hot properties of Chinese herbs. The decoction solution of different properties of Chinese herbs was added to S. obliquus culture medium; then, the delayed luminescence (DL) of S. obliquus after the addition of decoctions of different properties of Chinese herbs was measured to obtain information on the effect of different properties of Chinese herbs on S. obliquus. Many DL parameters were calculated, and ROC curve analysis was applied with the aim of finding a suitable parameter that can characterize the differences in cold and hot properties of Chinese herbs. Results: Our results show that the K value is a sensitive parameter that can reflect the differences of cold and hot properties of Chinese herbs, thus providing new insights into the cold and hot properties of Chinese herbs. Conclusions: DL measurement of S. obliquus after addition of different properties of Chinese herbs could be a novel and promising method to study the cold and hot properties of Chinese herbs.

The efficacy and safety of acupuncture combined with language training for motor aphasia after stroke: study protocol for a multicenter randomized sham-controlled trial.

BACKGROUND: Motor aphasia after stroke is a common and intractable complication of stroke. Acupuncture and language training may be an alternative and effective approach. However, the efficacy of acupuncture and language training for motor aphasia after stroke has not been confirmed. The main objectives of this trial are to evaluate the effectiveness and safety of acupuncture and low-intensity, low-dose language training in treating ischemic motor aphasia after stroke from 15 to 90 days. METHODS: This is a multicenter randomized sham-controlled clinical trial. We will allocate 252 subjects aged between 45 and 75 years diagnosed with motor aphasia after stroke with an onset time ranging from 15 to 90 days into two groups randomly in a 1:1 ratio. Patients in the experimental group will be treated with "Xing-Nao Kai-Qiao" acupuncture therapy plus language training, and those in the control group will be treated with sham-acupoint (1 cun next to the acupoints) acupuncture therapy plus language training. All the patients will be given acupuncture and language training for 6 weeks, with a follow-up evaluation 6 weeks after the end of the treatment and 6 months after the onset time. The patients will mainly be evaluated using the Western Aphasia Battery and Chinese Functional Communication Profile, and the incidence of treatment-related adverse events at the 2nd, 4th, and 6th weeks of treatment will be recorded. The baseline characteristics of the patients will be summarized by group, the chi-squared test will be used to compare categorical variables, and repeated measures of analysis of variance or a linear mixed model will be applied to analyze the changes measured at different time points. DISCUSSION: The present study is designed to investigate the effectiveness and safety of traditional acupuncture therapy and language training in ischemic motor aphasia after stroke and explore the correlation between the treatment time and clinical effect of acupuncture. We hope our results will help doctors understand and utilize acupuncture combined with language training. TRIAL REGISTRATION: ChiCTR ChiCTR1900026740 . Registered on 20 October 2019.

Danggui Buxue Decoction Ameliorates Idiopathic Pulmonary Fibrosis through MicroRNA and Messenger RNA Regulatory Network.

OBJECTIVE: To develop a putative microRNA (miRNA) and messenger RNA (mRNA) regulatory network of Danggui Buxue decoction's (DGBXD) amelioration of idiopathic pulmonary fibrosis (IPF). METHODS: The Gene Expression Omnibus (GEO) database was used to identify differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs). Using miRNet, the predicted target genes of identified DE-miRNAs were estimated, and then the target genes of DE-miRNAs in IPF were comprehensively examined. The Enrichr database was used to conduct functional enrichment and pathway enrichment. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was employed to obtain the target genes of DGBXD as well as active compounds. A putative miRNA-mRNA regulatory network of DGBXD acting on IPF was developed by intersecting the target genes of DGBXD with the DE-miRNA target genes in IPF. A bleomycin-induced mouse model was established and used to perform histopathology as well as real-time quantitative polymerase chain reaction (qRT-PCR) analyses of some miRNA-mRNA pairs. RESULTS: Fourteen upmodulated DE-miRNAs and six downmodulated DE-miRNAs were screened. The downstream target genes of upmodulated and downmodulated DE-miRNAs were predicted. Subsequently, 1160 upmodulated DE-mRNAs and 1427 downmodulated DE-mRNAs were identified. Then, target genes of DE-miRNAs comprising 49 downmodulated and 53 upmodulated target genes were further screened to perform functional enrichment and pathway enrichment analyses. Subsequently, 196 target genes of DGBXD were obtained from TCMSP, with six downregulated target genes and six upregulated target genes of DGBXD acting on IPF being identified. A promising miRNA-mRNA regulatory network of DGBXD acting on IPF was developed in this study. Moreover, mir-493 together with its target gene Olr1 and mir-338 together with Hif1a were further validated by qRT-PCR. CONCLUSION: This study proposed detailed possible processes of miRNA-mRNA modulatory axis in IPF and constructed a prospective IPF-related miRNA-mRNA modulatory network with the aim of alleviating IPF with DGBXD.

Overview of Current Herb-Drug Interaction Databases.

An HERB-Drug Interaction (HDI) database is a structured data collection method for HDI information extracted from scattered literatures for quick retrieval. Our review summarized the ten currently available HDI databases, including those databases comprising HDI on the market. A detailed comparison on the scope of monographs, including the nature of content extracted from the original literature and user interfaces of these databases, was performed, and the number of references of fifty popular herbs in each HDI database was counted and presented in a heatmap to give users an intuitive understanding of the focuses of different HDI databases. Since it is well known that the development and maintenance of databases need continuous investment of capital and manpower, the sustainability of these databases was also reviewed and compared. Recently, artificial intelligence (AI) technologies, especially Natural Language Processing (NLP), have been applied to screen specific topics from massive articles and automatically identify the names of drugs and herbs in the literature. However, its application on the labor-intensive extraction and evaluation of HDI-related experimental conditions and results from literature remains limited due to the scarcity of these HDI data and the lack of well-established annotated datasets for these specific NLP recognition tasks. In view of the difficulties faced by current HDI databases and potential expansion of AI application in HDI database development, we propose a standardized format for data reporting and use of Concept Unique Identifier (CUI) for medical terms in the literature to accelerate the structured data collection. SIGNIFICANCE STATEMENT: The worldwide popularity of botanical and/or traditional medicine products has raised safety concerns due to potential HDI. However, the publicly available HDI databases are mostly outdated or incomplete. Through our review of the currently available HDI databases, a clear understanding of the key issues could be obtained and possible solutions to overcome the labour-intensive extraction as well as professional evaluation of information in HDI database development are proposed.

Accumulation of the Major Components from Polygoni Multiflori Radix in Liver and Kidney after Its Long-Term Oral Administrations in Rats.

Although Polygoni Multiflori Radix (PMR) has been widely used as a tonic and an anti-aging remedy for centuries, the extensively reported hepatotoxicity and potential kidney toxicity hindered its safe use in clinical practice. To better understand its toxicokinetics, the current study was proposed, aiming to evaluate the biodistributions of the major PMR components including 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucopyranoside (TSG), emodin, emodin-8-O-ß-D-glucopyranoside (EMG) and physcion as well as their corresponding glucuronides following bolus and multiple oral administrations of PMR to rats. Male Sprague-Dawley rats received a bolus dose or 21 days of oral administrations of PMR concentrated granules at 4.12 g/kg (equivalent to 20.6 g/kg raw material). Fifteen minutes after bolus dose or the last dose on day 21, rats were sacrificed and the blood, liver, and kidney were collected for the concentration determination of both parent form and glucuronides of TSG, emodin, EMG, and physcion by HPLC-MS/MS. Among all the tested analytes, TSG, EMG, EMG glucuronides in liver and TSG, EMG, as well as all the glucuronides of these analytes in the kidney demonstrated the most significant accumulation after multiple doses. Moreover, the levels of the parent analytes were all significantly higher in liver and kidney in comparison to their plasma levels. Strong tissue binding of all four analytes and accumulation of TSG, EMG, and EMG glucuronides in the liver and TSG, EMG, as well as the glucuronides of all four analytes in the kidney after multiple dosing of PMR were considered to be associated with its toxicity.

Pharmacological mechanism of JiaWeiSiWu granule in the treatment of hypertension based on network pharmacology.

BACKGROUND: JiaWeiSiWu granule (JWSWG) has been applied clinically for more than a decade, and the preliminary results show that blood pressure can be reduced while protecting the target organ at the same time. The purpose of this research is to study the pharmacological mechanism of JWSWG in treating hypertension using network pharmacology. METHODS: The chief active components, relevant targets, and the target genes of JWSWG were retrieved by the databases TCMSP and UniProt. The GeneCards database was used to obtain target genes of hypertension. Then, the target genes of hypertension and active components were intersected to discover the potential targets by which JWSWG acts on hypertension. Cytoscape software was employed to construct the "medicine-compound-target-disease" network. The STRING database was used to construct the protein-protein interaction network in order to screen the key target genes. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed by RGUI and org.Hs.eg.db. RESULTS: By intersecting 102 compound target genes with 6,732 target genes of hypertension, 88 action target genes were obtained, thereby screening out the key compounds and key targets. The results of GO enrichment showed the main molecular functions, biological processes, and cellular components. The main pathways of JWSWG in treating hypertension were revealed by KEGG pathway enrichment. CONCLUSIONS: This research clarified the mechanism of JWSWG in the treatment of hypertension systematically, providing new potential ideas and a theoretical foundation for further experimental and clinical research.

Self-assembled aggregations in Coptidis Rhizoma decoction dynamically regulate intestinal tissue permeability through Peyer's patch-associated immunity.

Objective: To investigate the dynamic regulation of self-assembled aggregations (SAA) in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying. Methods: The effects of SAA on berberine (Ber) absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer's patches (PPs). The expression levels of ZO-1, Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction (TJ) between intestinal epithelium cells. The expression levels of T-box-containing protein expressed in T cells, signal transducers and activators of tranion-6, retinoic acid receptor-related orphan receptor γt and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-ß (TGF-ß) in PPs were evaluated by immunohistochemistry, to reflect the differentiation of T lymphocyte in PPs to helper T (Th) cell 1, Th2, Th17 and regulatory T (Treg) cell. To confirm the correlation between SAA in Coptidis Rhizoma decoction, PPs-associated immunity and intestinal epithelium permeability, SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression. Results: SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment, with the participation of PPs. The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs. The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation, inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression. Conclusion: SAA can improve the Ber absorption in small intestine, through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression. These findings might enlighten the research of traditional Chinese medicine decoction.

Are mindful people more risk-averse? Effects of trait and state mindfulness on risk preference in decision-making.

The current research investigated whether various aspects of mindfulness were differentially associated with risk preference in decision-making. In Studies 1 and 2, attention and present-focus aspects of trait mindfulness were associated with lower risk preference in making monetary gains. In Study 3, participants completed either a mindfulness training or listened to a comparable control recording. Compared to the control condition, subjects in the mindfulness condition were more risk-averse in making choices for monetary gains. The attention and present-focus aspects of state mindfulness mediated this connection. Study 4 introduced a loss framing, where attention and present-focus no longer associated with lower risk preference, but awareness and acceptance aspects of trait mindfulness associated with higher risk preference in avoiding monetary losses. The results suggest that different aspects of mindfulness have potential for mitigating risk preference, but such potential is limited depending on the framing of a decision context.

Novel Angiotensin-Converting Enzyme Inhibitory Peptides Identified from Walnut Glutelin-1 Hydrolysates: Molecular Interaction, Stability, and Antihypertensive Effects.

In recent years, angiotensin-converting enzyme (ACE) inhibitory peptide has become a research hotspot because of its essential role in maintaining human blood pressure balance. In this study, two novel ACE inhibitory peptides of Val-Glu-Arg-Gly-Arg-Arg-lle-Thr-Ser-Val (Valine-Glutamate-Arginine-Glycine-Arginine-Arginine-Isoleucine-Threonine-Serine-Valine, VERGRRITSV) and Phe-Val-Ile-Glu-Pro-Asn-Ile-Thr-Pro-Ala (Phenylalanine-Valine-Isoleucine-Glutamate-Proline-Asparagine-Isoleucine-Threonine-Proline-Alanine, FVIEPNITPA) were isolated and purified from defatted walnut meal hydrolysates through a series of preparation processes including ultrafiltration, Sephadex G-15 gel chromatography, and reverse high performance liquid chromatography (RP-HPLC). Both peptides showed high ACE inhibitory activities. The molecular docking study revealed that VERGRRITSV and FVIEPNITPA were primarily attributed to the formation of strong hydrogen bonds with the active pockets of ACE. The binding free energies of VERGRRITSV and FVIEPNITPA with ACE were -14.99 and -14.69 kcal/mol, respectively. Moreover, these ACE inhibitory peptides showed good stability against gastrointestinal enzymes digestion and common food processing conditions (e.g., temperature and pH, sugar, and salt treatments). Furthermore, animal experiment results indicated that the administration of VERGRRITSV or FVIEPNITPA exhibited antihypertensive effects in spontaneously hypertensive rats. Our results demonstrated that walnut could be a potential source of bioactive peptides with ACE inhibitory activity.