Silicon Vacancies Diamond/Silk/PVA Hierarchical Physical Unclonable Functions for Multi-Level Encryption.

Physical unclonable functions (PUFs) have emerged as a promising encryption technology, utilizing intrinsic physical identifiers that offer enhanced security and tamper resistance. Multi-level PUFs boost system complexity, thereby improving system reliability and fault tolerance. However, crosstalk-free multi-level PUFs remain a persistent challenge. In this study, a hierarchical PUF system that harnesses the spontaneous phase separation of silk fibroin /PVA blend and the random distribution of silicon-vacancy diamonds within the blend is presented. The thermodynamic instability of phase separation and inherent unpredictability of diamond dispersion gives rise to intricate random patterns at two distinct scales, enabling time-efficient hierarchical authentication for cryptographic keys. These patterns are complementary yet independent, inherently resistant to replication and damage thus affording robust security and reliability to the proposed system. Furthermore, customized authentication algorithms are constructed: visual PUFs authentication utilizes neural network combined structural similarity index measure, while spectral PUFs authentication employs Hamming distance and cross-correlation bit operation. This hierarchical PUF system attains a high recognition rate without interscale crosstalk. Additionally, the coding capacity is exponentially enhanced using M-ary encoding to reinforce multi-level encryption. Hierarchical PUFs hold significant potential for immediate application, offering unprecedented data protection and cryptographic key authentication capabilities.

Glutamine supplementation improves the activity and immunosuppressive action of induced regulatory T cells in vitro and in vivo.

BACKGROUND: Glutamine is crucial for the activation and efficacy of T cells, and may play a role in regulating the immune environment. This study aimed to investigate the potential role of glutamine in the activation and proliferation of induced regulatory T cells (iTregs). METHODS: CD4+CD45RA+T cells were sorted from peripheral blood mononuclear cells and cultured to analyze iTreg differentiation. Glutamine was then added to the culture system to evaluate the effects of glutamine on iTregs by determining oxidative phosphorylation (OXPHOS), apoptosis, and cytokine secretion. Additionally, a humanized murine graft-versus-host disease (GVHD) model was constructed to confirm the efficacy of glutamine-treated iTregs in vivo. RESULTS: After being cultured in vitro, glutamine significantly enhanced the levels of Foxp3, CTLA-4, CD39, CD69, IL-10, TGF-ß, and Ki67 (CTLA-4, IL-10, TGF-ß are immunosuppressive markers of iTregs) compared with that of the control iTregs (P < 0.05). Furthermore, the growth curve showed that the proliferative ability of glutamine-treated iTregs was better than that of the control iTregs (P < 0.01). Compared with the control iTregs, glutamine supplementation significantly increased oxygen consumption rates and ATP production (P < 0.05), significantly downregulated Annexin V and Caspase 3, and upregulated BCL2 (P < 0.05). However, GPNA significantly reversed the effects of glutamine (P < 0.05). Finally, a xeno-GVHD mouse model was successfully established to confirm that glutamine-treated iTregs increased the mice survival rate, delayed weight loss, and alleviated colon injury. CONCLUSION: Glutamine supplementation can improve the activity and immunosuppressive action of iTregs, and the possible mechanisms by which this occurs are related to cell proliferation, apoptosis, and OXPHOS.

The effects of vitamin C supplementation in the critically ill patients outcomes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin C has significant anti-inflammatory effects and is particularly important for critically ill patients. However due to inconsistent research findings in critically ill patients in meta-analysis. Therefore, the primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness by comprehensively incorporating articles from randomized controlled trials. METHODS: Articles included searching through PubMed, Embase, Medline, Cochrane Library, and Web of Science up to April 28, 2023, for articles on vitamin C and the critically ill. We calculated pooled standard relative risk (RR), mean difference (MD), and 95% confidence intervals (CIs). And the protocol for the review has been registered on PROSPERO (CRD42023425193). RESULTS: There are 2047 critically ill included in 19 articles. Compared with placebo, patients who underwent intravenous vitamin C (IVVC) have reduced duration of vasopressor used (SMD 0.26; CI 0.01-0.51; I2 = 87.0%, P = .044), mechanical ventilation (SMD -0.29; CI -0.55 to -0.03; I2 = 36.8%, P = .031). However, the administration of IVVC had no statistical difference in 28-d mortality (RR 0.95; CI 0.80-1.11; I2 = 12.2%, P = .337), mortality (RR 0.79; CI 0.55-1.12; I2 = 0%, P = .188), fluid intake (SMD -0.02; CI -0.25 to 0.20; I2 = 0%, P = .838), urine output (SMD 0.23; CI -0.03 to 0.49; I2 = 0%, P = .084), ICU days (SMD 0.10; CI -0.03 to 0.22; I2 = 0%, P = .127), hospital stay (SMD 0.10; CI -0.12 to 0.32; I2 = 0%, P = .375), and pneumonia (RR 0.85; CI 0.50-1.44; I2 = 0%, P = .552). CONCLUSION: This study comprehensively and systematically evaluated IVVC supplementation in the critically ill through a meta-analysis of RCT. There is no difference except for patients who had reduced duration of vasopressor use and mechanical ventilation by the administration of IVVC. Of course. More scientific and rigorous conclusions can be drawn from multi-center RCT research in the future.

Dracocephalum moldavica L.: An updated comprehensive review of its botany, traditional uses, phytochemistry, pharmacology, and application aspects.

Dracocephalum moldavica, known as Xiang-qing-lan (in Chinese), is a traditional folk medicine, which was commonly used by Mongolian and Xinjiang Uyghurs area. Dracocephalum moldavica has the effects of purging liver fire, clearing stomach heat, hemostasis. It is used for treating insufficient heart and blood, weakened brain function, weak feeling and spirit disease etc. This review aimed to summarize the botany, traditional uses, phytochemistry, pharmacology and application of Dracocephalum moldavica, which expected to provide theoretical support for future utilization and highlight the further investigation of this vital plant. In addition to the essential oil, approximately 154 compounds have been isolated and identified from aerial parts of the Dracocephalum moldavica, including flavonoids, terpenoids, lignans, phenylpropanoids, phenols, glycosides, polysaccharide and other compounds. Extensive pharmacological activities of the extracts or compounds of Dracocephalum moldavica in vivo and in vitro were confirmed including cardiovascular protection, antioxidative, antimicrobial, antifungal, anti-complementary and chronic mountain sickness. Moreover, Dracocephalum moldavica is used in a wide range of applications in food, biological pesticides and cosmetics. In the future, Dracocephalum moldavica needs further study, such as paying more attention to quality control, toxicity, pharmacological mechanism and pharmacokinetics.

A new labdane diterpenoid from Scoparia dulcis improving pancreatic function against islets cell apoptotic by Bax/Bcl-2/Caspase-3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Scoparia dulcis has been identified as a significant ethnopharmacological substance in the Li, Zhuang, and Dai ethnic groups of China. Traditional medicine use S. dulcis to treat numerous illnesses, most notably diabetes. The considerable antidiabetic properties of this herbal remedy have been established by several clinical investigations and animal experiments. The islet is the intended target of S. dulcis, although the cause of its activity and mechanism for diabetes treatment is unclear. The diterpenoids from S. dulcis have been shown in the literature to have significant hypoglycemic efficacy and to protect islet cells in vitro. Diterpenoids may be the components of this herbal remedy that preserve islets, but further research is needed. AIM OF THE STUDY: This study was projected to investigate the new diterpenoid scoparicol E from S. dulcis and examined its islet-protective effect and the potential mechanism both in vitro and in vivo. METHODS: The structure of the novel diterpenoid scoparicol E was clarified by employing a wide range of spectroscopic methods. Using CCK-8 tests, cytotoxicity and antiapoptotic activity of scoparicol E were detected. Serum biochemical analysis and pathologic examination were performed to study the protective effect of scoparicol E against islet damage. The specific mechanism of action of scoparicol E was investigated through the mitochondrial membrane potential, Annexin V-FITC flow cytometry, and western blotting. RESULTS: Scoparicol E reduced MLD-STZ-induced hyperglycemia in mice and increased insulin and islet apoptosis. Scoparicol E effectively suppressed the Bax/Bcl-2/Caspase-3 pathway, according to the in vivo western blot investigation. Scoparicol E showed significant antiapoptotic action in vitro. We also showed that scoparicol E might prevent islet cells from dying by inhibiting the Bax/Bcl-2/Caspase-3 pathway. The Annexin V-FITC flow cytometry results revealed that MIN6 cell apoptosis was considerably decreased following scoparicol E intervention, showing anti-islet cell apoptosis action. Furthermore, the Caspase-3-mediated apoptosis pathway depends on cytochrome c and the potential of the mitochondrial membrane. Scoparicol E prevented the release of cytochrome c, restored the mitochondrial membrane potential, and prevented MIN6 cell apoptosis. CONCLUSION: We demonstrated the new diterpenoid scoparicol E could protect islet cells apoptosis by modulating the Bax/Bcl-2/Caspase-3 pathway.

The Anxiolytic Effect of Polysaccharides from Stellariae Radix through Monoamine Neurotransmitters, HPA Axis, and ECS/ERK/CREB/BDNF Signaling Pathway in Stress-induced Male Rats.

BACKGROUND: Stellaria dichotoma L. var. lanceolata Bge. is renowned for its efficacy in "clearing deficiency heat" and represents a significant traditional Chinese medicine (TCM) resource. Modern pharmacology has demonstrated the anti-anxiety effects of Stellaria dichotoma L. var. lanceolata Bge. polysaccharides (SDPs). SDPs are one of the active constituents of Stellaria dichotoma L. var. lanceolata Bge. This study presents the first extraction of SDPs and investigates their potential molecular mechanisms and anxiolytic effects that are not previously reported. METHODS: First, SDPs were obtained by water extraction and alcohol precipitation and analyzed for their monosaccharide composition by high performance liquid chromatography (HPLC). Male SD rats were subjected to a two-week indeterminate empty bottle stress procedure and a three-day acute restraint stress procedure, during which diazepam (DZP) (1 mg/kg) and SDPs (50, 100 and 200 mg/kg, intragastrically) were administered. A number of behavioral tests, including the elevated plus maze test (EPM), the open field test (OFT) and the light/dark box test (LDB), were used to assess the anti-anxiety potential of SDPs. Serum levels of Corticosterone (CORT) and Adrenocorticotropic hormone (ACTH), as well as the levels of Dopamine (DA) and serotonin (5-HT) found in the hippocampus and frontal cortex, were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits. In addition, protein levels of key proteins cAMP-response element binding protein (CREB), phospho-CREB (p-CREB), brain-derived neurotrophic factor (BDNF), ERK½, p-ERK½, and GAPDH expression in rat hippocampus were measured by Western blot analysis, and modulation of the endocannabinoid system was assessed by immunohistochemistry. RESULTS: Following administration of SDPs (50, 100, 200 mg/kg) and diazepam 1 mg/kg, anxiolytic activity was exhibited through an increase in the percentage of arm opening times and arm opening time of rats in the elevated plus maze. Additionally, there was an increase in the number of times and time spent in the open field center, percentage of time spent in the open box, and shuttle times in the LDB. Furthermore, tissue levels of DA and 5-HT were increased in the hippocampus and frontal cortex of rats after treatment with SDPs. In addition, SDPs significantly decreased serum levels of CORT and ACTH in rats. SDPs also effectively regulated the phosphorylation of the extracellular regulated protein kinases (ERK) and CREB-BDNF pathway in the hippocampus. Moreover, the expression levels of CB1 and CB2 proteins were heightened due to SDPs treatment in rats. CONCLUSIONS: The study verified that SDPs alleviate anxiety in the EBS and ARS. The neuroregulatory behavior is accomplished by regulating the Monoamine neurotransmitter, HPA axis, and ECB-ERK-CREB-BDNF signaling pathway.

Regulation of intestinal micro ecology between raw and salt-processed Alpinia oxyphylla on renal injury rats.

Alpinia oxyphylla Fructus is one of the traditional Chinese medicine plants in the treatment of kidney injury. In clinical practice, crude Alpinia oxyphylla Fructus (CAOF) and salt-processed Alpinia oxyphylla Fructus (SAOF) are the two commonly used drugs specificated in the prevention and treatment of diabetic nephropathy (DN). However, the intestinal micro ecology regulation between CAOF and SAOF on DN has not been reported. In this paper, intestinal micro ecology regulation activities between CAOF and SAOF in DN rats were compared and analyzed by short-chain fatty acids (SCFAs) and intestinal flora analysis. The results showed that both SAOF and CAOF can regulate the intestinal flora metabolite SCFAs level in DN rats, reduce blood glucose concentration and improve inflammatory reaction. The intestinal flora analysis showed SAOF and CAOF could increase the intestinal bacterial diversity. The treatment of renal injury may be related to their increased intestinal bacterial diversity.

[Research summary of chemical constituents and pharmacological effects of Panax notoginseng and predictive analysis on its Q-markers].

Panax notoginseng contains triterpene saponins, flavonoids, amino acids, polysaccharides, volatile oil and other active components, which have the effects of promoting blood circulation, stopping bleeding, removing blood stasis, etc. This study summarized the herbal research, chemical constituents and main pharmacological activities of P. notoginseng, and based on the theory of Q-markers of traditional Chinese medicine, predicted and analyzed the Q-markers of P. notoginseng from the aspects of plant kinship, efficacy, drug properties, measurability of chemical components, etc. It was found that ginsenosides Rg_1, Re, and Rb_1 with specific content ratio, ginsenosides Rb_2, Rb_3, Rc, Rd, Rh_2, and Rg_3, notoginseng R_1, dencichine and quercetin could be used as potential Q-markers of P. notoginseng, which facilitated the formulation of quality standards reflecting the efficacy of P. notoginseng.

[Traditional Chinese medicine microbiomics and its research strategies].

The tight relationships between microbiome and traditional Chinese medicine(TCM)have been widely recognized. New technologies, results, and theories are emerging in the field of microbiomics in recent years with the advances in high-throughput sequencing and multi-omics technologies. Based on the previous research, the present study has proposed the concept of TCM microbiomics(TCMM), which is an interdisciplinary subject aiming at elucidating the functions and applications of microbiome in the areas of herb resources, herb processing, herb storage, and clinical effects by using modern technology of biology, ecology, and informatics. This subject essentially contains the structures, functions, interactions, molecular mechanisms, and application strategies of the microbiome associated with the quality, safety, and efficacy of TCM. Firstly, the development of the TCMM concept was summarized, with the profound understanding of TCMM on the complexity and entirety of microbiome being emphasized. Then, the research contents and applications of TCMM in promoting the sustainable development of herb resources, improving the standardization and diversification of herb fermentation, strengthening the safety of herb storage, and resolving the scientific connotation of theories and clinical efficacy of TCM are reviewed. Finally, the research strategies and methods of TCM microbiomics were elaborated from basic research, application research, and system research. TCMM is expected to promote the integrative development of TCM with frontier science and technology, thereby expanding the depth and scope of TCM study and facilitating TCM modernization.

New aphidicolane diterpenoids with glucose consumption promoting and cell viability enhancing activities from Scoparia dulcis.

Two new aphidicolane diterpenoids, termed Scopadulinol A (1) and B (2), were obtained from whole plants of Scoparia dulcis. Their structures were elucidated by applying various spectroscopic techniques, including 1D- and 2D-NMR and HR-ESI-MS. The absolute configurations of 1 and 2 were determined by applying the calculated electronic circular dichroism (ECD). In addition, both compounds were tested for their effects on glucose consumption in HL-7702 cells and on palmitic acid (PA) induced viability in MIN6 cells at different concentrations. The results showed that they significantly promoted glucose consumption and attenuated the PA-induced decrease of cell viability. Additionally, 2 was tested to determine whether it could activate AMP-activated protein kinase (AMPK), but it showed no such effect at the tested dosage. These results indicated that the new compounds might promote glucose consumption through other pathways but not by activating AMPK. Collectively, we highlighted the isolation of two new aphidicolane diterpenoids from S. dulcis and found that they could promote glucose consumption and attenuate PA-induced decrease of cell viability.

Atorvastatin attenuates allergic inflammation by blocking prostaglandin biosynthesis in rats with allergic rhinitis.

BACKGROUND: Prostaglandins (PGs) are bioactive lipid mediators derived from the nuclear and plasma membranes via the cyclooxygenase (COX) pathway of arachidonic acid (AA) metabolism. PGs bridge the interactions between various immunomodulatory cells in allergic rhinitis (AR) and are considered key players in regulating pro-inflammatory and anti-inflammatory responses. AA conversion to PGs involves rate-limiting enzymes that may be blocked by statins. The mechanisms by which statins regulate these enzymes in AR remain unclear. We investigated the effects of oral atorvastatin on PGs production in AR. METHODS: An ovalbumin-induced AR rat model was constructed and the changes in nasal symptom score and nasal mucosa histopathological characteristics of AR rats under different atorvastatin doses were assessed. qRT-PCR, western blotting, and immunofluorescence were used to detect the mRNA and protein expression levels of rate-limiting enzymes and downstream molecules of AA metabolism in the nasal mucosa and liver. RESULTS: Oral atorvastatin significantly alleviated symptoms and eosinophil infiltration in the nasal mucosa, inhibited goblet cell hyperplasia and mast cell recruitment, and decreased mucus secretion in AR rats. Increasing atorvastatin dose increased the anti-inflammatory effects. High-dose atorvastatin inhibited upregulation of the inflammatory mediator PGD2 in the nasal mucosa of AR rats. Compared to the control group, the mRNA and protein expression of the rate-limiting enzymes COX-2, PGDS, and PGES in AA metabolism in the AR group were upregulated but downregulated after the oral administration of high-dose atorvastatin. Atorvastatin also showed dose-dependent inhibition of ERK1/2 and downstream NF-κB phosphorylation in the nasal mucosa and liver of AR rats. CONCLUSIONS: Atorvastatin inhibited allergic inflammation and attenuated AR nasal symptoms by downregulating PGD2 and rate-limiting enzyme expression in PGD2 biosynthesis, possibly by blocking the RAS/ERK/NF-κB signaling pathway.

Protective role of antioxidant supplementation for depression and anxiety: A meta-analysis of randomized clinical trials.

BACKGROUND: New research supports an integrated approach to treating depression, and lifestyle modifications should be a regular component of both preventative and treatment programs. Therefore, in order to investigate the relationship between various antioxidant supplements and depressive status, we carried out a meta-analysis of randomized controlled trials (RCT). METHODS: We thoroughly searched PubMed, Medline, Scopus, and Web of Science databases to screen publications focusing on the effects of antioxidant supplements on depression status. The meta-analysis mainly compared depression scores between groups that received antioxidant supplements and controls. We also pooled studies reporting changes in anxiety status as a secondary outcome. RESULTS: 52 studies with 4049 participants were eventually identified. The meta-analysis found that the positive effect of antioxidant supplementation, such as magnesium (SMD = 0.16, p = 0.03), zinc (SMD = 0.59, p = 0.01), selenium (SMD = 0.33, p = 0.009), CoQ10 (SMD = 0.97, p = 0.05), tea and coffee (SMD = 1.15, p = 0.001) and crocin (MD = 6.04, p < 0.00001), on depressive status were all significant. And antioxidant supplementation also showed significant improvement in anxiety (SMD = 0.40, p < 0.00001). Subgroup analysis by scale types and countries were performed, and antioxidant supplementation's positive effects on depressive and anxiety states remained significant. LIMITATIONS: This study did not limit the characteristics of the included population, and the diversity of scales also contributed to the heterogeneity. CONCLUSION: Intake of antioxidant supplements is associated with improved depression and anxiety states, further affirms the therapeutic potential of antioxidant supplements as adjunctive therapy to conventional antidepressants.

Recurrence Rates and Pharmacological Treatment for Hemorrhoidal Disease: A Systematic Review.

INTRODUCTION: Hemorrhoidal disease (HD) is characterized by prolapse of the inflamed and bleeding vascular tissues of the anal canal. Although HD is associated with a high recurrence rate, there is a lack of understanding around interventions that can reduce recurrence and improve outcomes for patients. As such, a systematic literature review (SLR) was conducted to summarize evidence on epidemiology, recurrence, and efficacy of interventions in HD. METHODS: Real-world evidence (RWE) studies evaluating the incidence, prevalence, or recurrence of HD, as well as SLRs including a meta-analytic component reporting on the efficacy of systemic or topical pharmacological treatments for adults with HD, were included. Systematic searches were conducted in MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Database of Systematic Reviews. RESULTS: The SLR identified 44 eligible publications. Consistent data were limited on the epidemiology of HD or HD recurrence. Specifically, incidence and prevalence reported across geographies were impacted by differences in data collection. Reported risk factors for HD were sedentary behavior, constipation, male gender, and age. Twenty-three RWE studies and one meta-analysis reported HD recurrence rates ranging from 0 to 56.5% following surgery or phlebotonics, with most (n = 19) reporting rates of 20% or less. In addition to time since treatment, risk factors for recurring disease were similar to those for HD in general. With respect to treatment, micronized purified flavonoid fractions significantly improved the main symptoms of HD compared to other pharmacological treatments. CONCLUSION: The SLRs did not identify any RWE studies reporting recurrence in patients receiving systemic or topical treatments, highlighting the need for future research in this area. Further, more studies are needed to understand the optimum duration of medical treatment to prevent recurrence.

Patients with hemorrhoidal disease (HD) can experience recurring disease following a period of improvement or remission. It is not well established how often this might happen, who is at greatest risk, or which treatments can reduce this risk. In this study, a systematic literature review (SLR) was conducted to summarize evidence on the occurrence and recurrence of HD, as well as treatment effectiveness. Several literature databases were searched for articles that described real-world evidence (RWE) studies reporting the epidemiology or recurrence of HD as well as published SLRs that combined the results of multiple studies (meta-analyses) on treatment for adults with HD. Forty of 2037 articles identified by the search were considered relevant, and four others identified by clinicians were also included (total = 44; 39 RWE, 5 meta-analyses). Review of the RWE articles revealed that HD epidemiology was determined differently between studies. Only 23 reported recurrence rates (up to 56.5%) after surgery or treatment with phlebotonic drugs (drugs that improve blood flow in veins). Most (19/23) reported recurrence rates of 20% or less. Risk factors for recurrence were similar to usual HD risk factors (e.g., constipation, male gender, age) in addition to time since treatment. Phlebotonic agents, including those made from plant extracts (micronized purified flavonoid fractions, MPFFs) improved hemorrhoidal symptoms compared with placebo or no treatment. In one meta-analysis, MPFF was the only phlebotonic to significantly reduce recurrence risk versus no treatment or placebo. Overall, more research is needed to compare treatments and determine optimal treatment duration to prevent recurrence. Author-narrated video abstract.

Clinical application of acupuncture-moxibustion for the treatment of spirit based on approximate entropy of electrooculogram signal / 中国针灸

According to the theory of acupuncture-moxibustion for the treatment of spirit, starting from the relationship between eye movement and spirit, the application of electrooculogram (EOG) signal acquisition and analysis technology for the clinical treatment of spirit by acupuncture-moxibustion is discussed. Based on the nonlinear dynamic characteristics of EOG signals, it is proposed to apply the approximate entropy algorithm to extract the EOG signal characteristics in autism spectrum disorder children under different behavior states, which could realize the preliminary exploration of the correlation between EOG signals and cognitive activities. This could provide a possibility to objectively reflect the patient' s current mental state, and could be used as a potential method to grasp spirit in clinical acupuncture- moxibustion treatment. Furthermore, considering the characteristics of acupoint stimulation on the body surface, the EOG signal acquisition and analysis technology could further be combined with biofeedback technology, and a new idea for clinical acupuncture-moxibustion to treat spirit guided by biofeedback of EOG is proposed.

Transcutaneous electrical acupoint stimulation based on electro-oculogram signal regulation for children with mental retardation: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) at Changqiang (GV 1) based on the modulation of electro-oculogram (EOG) signal for children with mental retardation, and explore the evaluation effect of the goal attainment scale (GAS) in children with mental retardation.@*METHODS@#Sixty children with mental retardation were randomly divided into a treatment group and a control group, with 30 cases in each one. The children in the control group were treated with conventional rehabilitation, 5 times a week. On the basis of the control group, TEAS at Changqiang (GV 1) under the modulation of EOG signal was adopted in the treatment group. When the similarity between the collected EOG signal and the template was within the range of EOG threshold, one electric stimulation was triggered at Changqiang (GV 1) for 20 s (continuous wave, 70-100 Hz in frequency, 0.1-0.2 ms in pulse width), lasting 30 min in each treatment, the intervention was given twice a week. One course of treatment was composed of 4 weeks, and 3 courses were required in total in the two groups. The infant-junior high school student's social living ability scale (S-M) and GAS were scored and compared before and after treatment in the two groups.@*RESULTS@#After treatment, the scores of self-living ability in the treatment group and communication ability in the control group were higher than those before treatment (P<0.01, P<0.05). The scores of collective activity and motor ability in the treatment group were higher than those in the control group (P<0.05). After treatment, GAS scores were higher than before treatment in both groups (P<0.001), and the score in the treatment group was higher than the control group (P<0.05).@*CONCLUSION@#TEAS under the modulation of EOG signal is conductive to improving the collective, motor and self-living abilities of the children with mental retardation and promoting children's individual goals. Compared with the standard score of S-M, the T value of GAS can better reflect the subtle progress of individual.

Exploring the mechanism of Tengli Kangliu Decoction in the prevention and treatment of colorectal cancer precancerous based on network pharmacology.

OBJECTIVE: This study aimed to predict the targets and signaling pathways affected by Tengli Kangliu Decoction (TKD) in the treatment of colorectal cancer (CRC) precursor lesions and to determine TKDs mechanism of action based on previous experimental results using network pharmacology techniques and methods. METHODS: Using the traditional Chinese medicine systems pharmacology database (TCMSP) and UniProt database, the active ingredients and potential targets of TKD were identified. Human colorectal adenoma (CRA) targets were analyzed using the GeneCards database, the Online mendelian inheritance in man (OMIM) database, and the NCBI database. The common targets of drug-disease interactions were input into the String database to construct a protein-protein interaction (PPI) network. These data were then used to construct the network diagram. Gene ontology (GO) function analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed on the target genes. Finally, the component-disease-pathway-target network file was imported into Cytoscape 3.8.0 and used to construct the pathway network diagram. RESULTS: Compounds with a drug-likeness (DL) score ≥ 0.18 and an oral bioavailability (OB) ≥ 30% were selected as the active constituents of TKD. Two hundred eighty eight chemical constituents were screened and 305 chemical drug targets were predicted. After further screening, 1942 disease-related targets, which are hypothesized to be the main chemical components of TKD, were obtained. When comparing the targets of action and CRA treatment targets, 172 common targets were identified. Using GO enrichment analysis of common targets of drug diseases, 2550 biological processes (BP) were predicted, 164 items of which were related to molecular functioning (MF), and 67 items related to cell composition. KEGG pathway analysis was performed on the common targets of drug diseases, and a total of 178 signaling pathways were enriched. CONCLUSION: Using network pharmacology research, this study reports on the synergistic effect of the multiple components of TKD on the multi-target, and multiple pathways of colorectal precancerous lesions. These findings lay a theoretical foundation for further colorectal precancerous lesions research.

The Gut Microbial Co-Abundance Gene Groups (CAGs) Differentially Respond to the Flavor (Yao-Wei) of Chinese Materia Medica.

The property theory is a unique principle instructing traditional Chinese doctors to prescribe proper medicines against diseases. As an essential part of it, the five-flavor theory catalogs various Chinese materia medicas (CMMs) into five flavors (sweet, bitter, sour, salty, and pungent) based on their taste and medical functions. Although CMM has been successfully applied in China for thousands of years, it is still a big challenge to interpret CMM flavor via modern biomarkers, further deepening its elusiveness. Herein, to identify the correlation between gut microbiota and CMM flavor, we selected 14 CMMs with different flavors to prepare their aqueous extracts, quantified the contained major chemical components, and then performed full-length 16S rRNA sequencing to analyze the gut microbiota of C57BL/6 mice administrated with CMM extracts. We found that flavones, alkaloids, and saponins were the richest components for sweet-, bitter-, and pungent-flavored CMMs, respectively. Medicines with merged flavors (bitter-pungent and sweet-pungent) displayed mixed profiles of components. According to gut microbial analysis, modulation of CMMs belonging to the same flavor on the taxonomic classification was inconsistent to an extent, while the functional sets of gut microbiota, co-abundance gene groups (CAGs), strongly and differentially responded to distinct flavors. Moreover, these correlations were in line with their pharmacological actions. Therefore, the gut microbial functional sets (CAGs) could act as the possible indicator to reflect CMM flavor, rather than the composition of microbial community.

Update on new trend and progress of the mechanism of polysaccharides in the intervention of Alzheimer's disease, based on the new understanding of relevant theories: A review.

Alzheimer's disease (AD), a neurodegenerative disease with insidious onset and progressive progression, is the main type of dementia. Currently, there is no specific cure for the disease. At the same time, a series of drug developments based on the classic theory, the Aß cascade hypothesis, have not completed phase III clinical trials, challenging the hypothesis. Polysaccharides obtained from natural products can be used in the treatment of AD, which has attracted academic attention due to its advantages of multi-target, multi-channel, no or modest side effects. The TCM syndrome type of AD is mainly "qi and blood deficiency, kidney essence deficiency", and the medicine is mainly used to replenish qi and blood, kidney and bone marrow. Thus, there has been extensive and in-depth research on polysaccharides obtained from tonic Chinese herbal medicine in China. Based on this background, this paper evaluated the effects and mechanisms of natural polysaccharides on AD by combing and screening English and related literature in recent 5 years and summarized the extraction process and structure-activity relationship of polysaccharides.

Biosynthesis of silver nanoparticle composites based on hesperidin and pectin and their synergistic antibacterial mechanism.

Silver nanoparticles (AgNPs) were widely used in the antibacterial field because of their excellent antibacterial properties. In this study, we used hesperidin and pectin as reductants and stabilizers, and prepared uniform and stable Hesperidin-Pectin AgNPs (HP-AgNPs) by a simple microwave-assisted process. Increasing the proportion of hesperidin, P-AgNPs, HP-AgNPs1, HP-AgNPs2 and H-AgNPs were obtained respectively. With the increase of hesperidin ratio, the mean particle size and zeta potential increased gradually. Fourier transform infrared spectroscopy (FTIR) analysis showed that Ag+ was reduced by hesperidin and pectin. Antibacterial tests showed that HP-AgNPs2 showed the MIC values of 66.7 µg/mL against E. coli. In addition, HP-AgNPs2 was selected to clarify its antibacterial mechanism against E. coli. Morphological experiments showed that HP-AgNPs2 stress caused damage to the cell wall of E. coli, as well as leakage of its contents and an increase in reactive oxygen species (ROS). On the other hand, the release of Ag+ during cell co-culture was studied and the results showed that most of the Ag+ released was taken up by E. coli. The synergistic effect of hesperidin and pectin resulted in a significant enhancement of the antibacterial properties of AgNPs. These preliminary data suggest that HP-AgNPs has good antibacterial activity and may be developed as an effective antibacterial nanomaterial.

A new discovery: Total Bupleurum saponin extracts can inhibit the proliferation and induce apoptosis of colon cancer cells by regulating the PI3K/Akt/mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense DC has a history of using herb in China for more than 2000 years, which can be traced back to the Classic of Shennong Materia Medica in the Han Dynasty. Although Saikosaponin, the main active ingredient of Bupleurum, has the effects of anti-tumor, yet we still do not know the mechanism by total Bupleurum saponin extracts (TBSE) produces this effect on colon cancer. AIM OF THE STUDY: It is predicted by network pharmacology that TBSE may play an anti-colon cancer role by regulating the PI3K-Akt-mTOR pathway. The purpose of this study is to investigate whether TBSE inhibits proliferation and promote apoptosis of colon cancer cells by regulating PI3K/Akt/mTOR pathway. MATERIALS AND METHODS: The effect of saikosaponins on the proliferation of SW480 and SW620 cells was detected by CCK-8, apoptosis was determined by flow cytometry, morphological changes of cells were observed by microscope, nuclear morphological changes were observed after immunofluorescence staining, the expression of apoptosis-related proteins Bax, Bcl2, Caspase3, Caspase9, Cleaved Caspase3 and Cleaved Caspase9 were detected by Western Blot, and the expression of apoptosis-related genes Bax, Bcl2, Caspase3 and Caspase9 were detected by RT-PCR. According to the theory of network pharmacology, the potential targets of saikosaponins and colon cancer were predicted by database Pharmmapper and Genecards database respectively. The intersection of saikosaponins and colon cancer was enriched and analyzed on the Metascape platform. Then, the expression of PI3K/Akt/mTOR pathway related protein PI3K, Akt, Mtor, p-PI3K, p-Akt, p-mTOR were detected by Western Blot, and the corresponding amount of RNA expressions in the pathway was confirmed by RT-PCR. RESULTS: The results of CCK-8 demonstrated that the survival rate of SW480 and SW620 cells decreased significantly when the concentration of TBSE was in the range of 25-200 µg/ml. The morphological observation showed that the cells lost normal cell morphology, cytoplasmic condensation, and partial loss of adhesion after treatment with TBSE. Flow cytometry indicated that the apoptosis rates of SW480 cells and SW620 cells treated with TBSE (50 µg/ml) were 48.47% ± 1.20% and 36.13% ± 1.76%, respectively. Western Blot firstly confirmed that TBSE significantly up-regulated the expression of pro-apoptotic proteins Bax, Caspase3, Caspase9, Cleaved Caspase3 and Cleaved Caspase9, and down-regulated the expression of anti-apoptotic protein Bcl2. And RT-PCR results implied that TBSE significantly up-regulated the gene expression of apoptotic factors Bax, Caspase3 and Caspase9, and significantly decreased the gene expression of Bcl2. It was predicted that the PI3K/Akt/mTOR pathway may be the main regulatory object of the antitumor effect of TBSE by network pharmacology. Subsequent WB experiment also revealed that TBSE could significantly down-regulate (P < 0.01) the expressions of PI3K, Akt, mTOR and phosphorylated proteins P-PI3K, P-Akt, P-MTOR. Meanwhile, RT-PCR results also indicated that TBSE could significantly down-regulate (P < 0.01) the gene expression levels of PI3K, Akt and mTOR. CONCLUSIONS: TBSE activated Bax/Bcl2 and caspase-9/caspase-3 cascade to induced apoptosis of human colon cancer SW480 and SW60 cells in a dose-dependent manner, which was obviously related to the inhibition of PI3K/Akt/mTOR signaling pathway.