Clinical and Animal Studies of Waist and Knee Scraping Therapy for Knee Osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) is a degenerative condition with knee pain as the main clinical manifestation. Scraping is one of the commonly used traditional Chinese medicine treatment methods, which activates blood circulation, removes blood stasis, reduces inflammation, and so on. Although scholars have proposed that the synergistic treatment of the waist and knee for KOA is superior to simple knee treatment, there is no relevant reference literature on the application of scraping therapy. Therefore, this study aims to explore the effectiveness and potential mechanisms of waist and knee scraping therapy for treating KOA through clinical and animal studies in order to promote its clinical application. OBJECTIVE: To explore the clinical efficacy of waist and knee scraping therapy in the treatment of KOA from clinical study and increase animal study on this basis to preliminarily explore its mechanism, providing an objective basis for better treatment of KOA. METHODS: The clinical study recruited 90 KOA patients and divided them into a control group, a knee scraping group, and a waist and knee scraping group using a random number table method. All patients were evaluated for clinical efficacy, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), and Traditional Chinese Medicine Syndrome Score. The KOA rat model was established using the Hulth method. The rats were randomly divided into a control group, KOA group, waist scraping group, knee scraping group, and waist and knee scraping group. During the intervention process of rats, the pain sensitivity threshold was measured, and HE staining was performed on the synovium and cartilage. The protein and mRNA expression levels of TNF-α, IL- 1ß, IL-6, PGP9.5, SP and TRPA1, TRPV4, SP, and NGF were measured by Western blot and real-time PCR. RESULTS: In the clinical study, the clinical efficacy of the 2 scraping groups was significantly higher than that of the control group. The clinical efficacy of the waist and knee scraping group on the 60th day of treatment was significantly higher than that of the knee scraping group. In terms of improving WOMAC scores, all 3 groups had significance; The function and total score of the waist and knee scraping group on the 28th day of treatment, as well as the pain, function, and total score on the 60th day, were lower than those of the knee scraping group. In terms of improving pain while standing, pain when walking on flat ground, and total score, the scraping group had significant differences. The score of heavy limbs in the waist and knee scraping group was lower than that in the knee scraping group. In an animal study, during the 4th week after modeling, there were differences in the pain sensitivity threshold between the KOA group and the waist scraping group compared to the control group, while there were differences in the pain sensitivity threshold between the knee scraping group and the waist and knee scraping group compared to the KOA group. The expression levels of various proteins and genes in the KOA group and waist scraping group increased compared to the control group; The knee scraping group and the waist and knee scraping group were lower than those in the KOA group. CONCLUSION: Scraping therapy can significantly alleviate knee joint pain and stiffness, improve joint function, and improve clinical efficacy, and the short-term and long-term effects of waist and knee scraping therapy are more significant. The scraping therapy has a definite therapeutic effect on KOA rats, which can improve the threshold of cold hyperalgesia and mechanical hyperalgesia, and the waist and knee scraping therapy is more obvious. This may be related to reducing inflammatory reactions in synovial and ganglion tissues.

[Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond].

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Low-thermal-budget synthesis of monolayer molybdenum disulfide for silicon back-end-of-line integration on a 200 mm platform.

Two-dimensional (2D) materials are promising candidates for future electronics due to their excellent electrical and photonic properties. Although promising results on the wafer-scale synthesis (≤150 mm diameter) of monolayer molybdenum disulfide (MoS2) have already been reported, the high-quality synthesis of 2D materials on wafers of 200 mm or larger, which are typically used in commercial silicon foundries, remains difficult. The back-end-of-line (BEOL) integration of directly grown 2D materials on silicon complementary metal-oxide-semiconductor (CMOS) circuits is also unavailable due to the high thermal budget required, which far exceeds the limits of silicon BEOL integration (<400 °C). This high temperature forces the use of challenging transfer processes, which tend to introduce defects and contamination to both the 2D materials and the BEOL circuits. Here we report a low-thermal-budget synthesis method (growth temperature < 300 °C, growth time ≤ 60 min) for monolayer MoS2 films, which enables the 2D material to be synthesized at a temperature below the precursor decomposition temperature and grown directly on silicon CMOS circuits without requiring any transfer process. We designed a metal-organic chemical vapour deposition reactor to separate the low-temperature growth region from the high-temperature chalcogenide-precursor-decomposition region. We obtain monolayer MoS2 with electrical uniformity on 200 mm wafers, as well as a high material quality with an electron mobility of ~35.9 cm2 V-1 s-1. Finally, we demonstrate a silicon-CMOS-compatible BEOL fabrication process flow for MoS2 transistors; the performance of these silicon devices shows negligible degradation (current variation < 0.5%, threshold voltage shift < 20 mV). We believe that this is an important step towards monolithic 3D integration for future electronics.

Da-Cheng-Qi decoction improves severe acute pancreatitis-associated acute lung injury by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response in rats.

CONTEXT: Da-Cheng-Qi Decoction (DCQD) has a significant effect on Severe Acute Pancreatitis-Associated Acute Lung Injury (SAP-ALI). OBJECTIVE: To explore the mechanism of DCQD in the treatment of SAP-ALI based on intestinal barrier function and intestinal lymphatic pathway. MATERIALS AND METHODS: Forty-five Sprague-Dawley rats were divided into three groups: sham operation, model, and DCQD. The SAP model was induced by a retrograde infusion of 5.0% sodium taurocholate solution (1 mg/kg) at a constant rate of 12 mL/h using an infusion pump into the bile-pancreatic duct. Sham operation and model group were given 0.9% normal saline, while DCQD group was given DCQD (5.99 g/kg/d) by gavage 1 h before operation and 1, 11 and 23 h after operation. The levels of HMGB1, RAGE, TNF-α, IL-6, ICAM-1, d-LA, DAO in blood and MPO in lung were detected using ELISA. The expression of HMGB1, RAGE, NF-κB p65 in mesenteric lymph nodes and lung were determined. RESULTS: Compared with SAP group, DCQD significantly reduced the histopathological scoring of pancreatic tissue (SAP, 2.80 ± 0.42; DCQD, 2.58 ± 0.52), intestine (SAP, 3.30 ± 0.68; DCQD, 2.50 ± 0.80) and lung (SAP, 3.30 ± 0.68; DCQD, 2.42 ± 0.52). DCQD reduced serum HMGB1 level (SAP, 134.09 ± 19.79; DCQD, 88.05 ± 9.19), RAGE level (SAP, 5.05 ± 1.44; DCQD, 2.13 ± 0.54). WB and RT-PCR showed HMGB1-RAGE pathway was inhibited by DCQD (p < 0.01). DISCUSSION AND CONCLUSIONS: DCQD improves SAP-ALI in rats by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response.

Effect of replacing inorganic minerals with small peptide chelated minerals on production performance, some biochemical parameters and antioxidant status in broiler chickens.

Due to the low bio-availability of inorganic trace minerals, its application in poultry production has been causing many problems such as environment pollution and waste of resources. The current study was designed to evaluate if replacing inorganic trace minerals (ITM) with small peptide chelate trace minerals (SPM) affects production performance, some biochemical parameters and antioxidant status, tibia mineral deposition, and fecal mineral content in 817 white-feathered broilers. A total of 432 broilers (21-day-old) were randomly divided into four groups with six replicates of 18 chicks each. The four groups included inorganic trace minerals group (addition of 1,000 mg/kg ITM; common practice by commercial poultry farms), three organic trace minerals groups with supplementation of 150, 300, and 500 mg/kg SPM, respectively. The experiment lasted for 30 days. The results showed that there was no significant difference in growth performance and slaughter performance among the four groups (p > 0.05). Total cholesterol in the SPM group was significantly lower than those in the ITM groups (p < 0.01). Compared with the ITM group, the serum urea nitrogen in 150 and 300 mg/kg SPM groups decreased significantly (p < 0.01). Among all SPM treatments, 300 mg/kg SPM groups had the highest serum glutathione peroxidase (GSH-Px) activity (p < 0.01). The activity of copper and zinc superoxide dismutase (Cu/Zn SOD) of liver in ITM group was the lowest among the four groups (p < 0.01). The catalase (CAT) activity of liver in the 150 mg/kg SPM group was significantly higher than the ITM group and 300 mg/kg SPM group (p < 0.05). Compared to the ITM group, the iron content of the tibia was significantly increased in 300 mg/kg SPM group (p < 0.05) and 500 mg/kg SPM group (p < 0.01). Compared to the ITM group, dietary supplementation with SPM significantly reduced fecal content of zinc and manganese (p < 0.01). The 150 mg/kg SPM and 300 mg/kg SPM group had significantly reduced content of iron (p < 0.05). This study demonstrated that replacing inorganic minerals with low doses of SPM (300 and 500 mg/kg) did not negatively affect growth and slaughter performance, as well as the antioxidant status of broiler chickens. In addition, SPM can also promote mineral content in the tibia and reduce mineral content in the feces.

[Sagittaria sagittifolia polysaccharides regulates Nrf2/HO-1 to relieve liver injury caused by multiple heavy metals in vivo and in vitro].

This study explored whether Sagittaria sagittifolia polysaccharides(SSP) activates the nuclear factor erythroid-2-related factor2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway to protect against liver damage jointly induced by multiple heavy metals. First, based on the proportion of dietary intake of six heavy metals in rice available in Beijing market, a heavy metal mixture was prepared for inducing mouse liver injury and HepG2 cell injury. Forty male Kunming mice were divided into five groups: control group, model group, glutathione positive control group, and low-and high-dose SSP groups, with eight mice in each group. After 30 days of intragastric administration, the liver injury in mice was observed by HE staining. In the in vitro experiment, MTT assay was conducted to detect the effects of SSP at 0.25, 0.5, 1, and 2 mg·mL~(-1) on HepG2 cell survival at different time points. The content of alanine transaminase(ALT) and aspartate aminotransferase(AST) in the 48-h cell culture fluid was measured using micro-plate cultivation method, followed by the detection of the change in reactive oxygen species(ROS) content by flow cytometry. The mRNA expression levels of Nrf2 and HO-1 in cells were determined by RT-PCR, and their protein expression by Western blot. HE staining results showed that compared with the model group, the SSP administration groups exhibited significantly alleviated inflammatory cell infiltration and fatty infiltration in the liver, with better outcomes observed in the high-dose SSP group. In the in vitro MTT assay, compared with the model group, SSP at four concentrations all significantly increased the cell survival rate, decreased the ALT, AST, and ROS content(P<0.05), and down-regulated Nrf2 and HO-1 mRNA and protein expression(P<0.05). SSP significantly improves inflammatory infiltration in the liver tissue of mice exposed to a variety of heavy metals and corrects the liver fat degeneration, which may be related to its regulation of the Nrf2/HO-1 signaling pathway, reduction of ROS, and alleviation of oxidative damage.

Acupuncture Treatment for Cough-Variant Asthma: A Meta-Analysis.

BACKGROUND: In recent years, there have been many clinical reports on acupuncture treatment of cough-variant asthma, but no researcher has objectively analysed and evaluated the efficacy and safety of acupuncture treatment of cough-variant asthma from the perspective of evidence-based medicine. OBJECTIVE: To systematically evaluate the clinical efficacy and safety of acupuncture in treating cough-variant asthma and to provide reference values for clinical decision-making. METHODS: The comprehensive computer retrieval Chinese journal full-text database (CNKI), Chinese science and technology periodical database (VIP), ten thousand data knowledge service platform (WanFang Data), PubMed, Embase, and the Cochrane Library were used to collect literature for relevant randomized controlled trials (RCT) of acupuncture treatment of cough-variant asthma, as well as to retrieve papers and add reference retrieval after literature review, in accordance with the standard of literature filtering, data extraction, and quality evaluation. The data were meta-analysed using ReviewManager5.3 software recommended by Cochrane. RESULTS: A total of 11 randomized controlled clinical studies were screened and included, comprising 929 patients. The results of the meta-analysis showed that, compared with the control group, acupuncture intervention on CVA could enhance the total clinical effectiveness rate, reduce the relapse rate of drug withdrawal, relieve symptoms of cough, phlegm, and diaphragmatic congestion, and improve lung function-related indicators and immune inflammation indicators. There were statistically significant differences in all efficacy evaluation criteria. CONCLUSION: The clinical curative effect of acupuncture treatment for cough-variant asthma is precise and has certain advantages in relieving symptoms and reducing the recurrence rate. However, the low quality of the evaluation in the RCT research literature is a problem, and more high-quality clinical randomized controlled trials are needed to further verify the comprehensive clinical efficacy and safety of this treatment. Registration number: PROSPERO (no. CRD42020155244) (https://www.crd.york.ac.uk/prospero/).

Tetramethylpyrazine: A Review of Its Antitumor Potential and Mechanisms.

Cancer remains a major public health threat. The mitigation of the associated morbidity and mortality remains a major research focus. From a molecular biological perspective, cancer is defined as uncontrolled cell division and abnormal cell growth caused by various gene mutations. Therefore, there remains an urgent need to develop safe and effective antitumor drugs. The antitumor effect of plant extracts, which are characterized by relatively low toxicity and adverse effect, has attracted significant attention. For example, increasing attention has been paid to the antitumor effects of tetramethylpyrazine (TMP), the active component of the Chinese medicine Chuanqiong, which can affect tumor cell proliferation, apoptosis, invasion, metastasis, and angiogenesis, as well as reverse chemotherapeutic resistance in neoplasms, thereby triggering antitumor effects. Moreover, TMP can be used in combination with chemotherapeutic agents to enhance their effects and reduce the side effect associated with chemotherapy. Herein, we review the antitumor effects of TMP to provide a theoretical basis and foundation for the further exploration of its underlying antitumor mechanisms and promoting its clinical application.

Allium tuberosum alleviates pulmonary inflammation by inhibiting activation of innate lymphoid cells and modulating intestinal microbiota in asthmatic mice.

OBJECTIVE: This study tests whether long-term intake of Allium tuberosum (AT) can alleviate pulmonary inflammation in ovalbumin (OVA)-induced asthmatic mice and evaluates its effect on the intestinal microbiota and innate lymphoid cells (ILCs). METHODS: BALB/c mice were divided into three groups: phosphate buffer saline, OVA and OVA + AT. The asthmatic murine model was established by sensitization and challenge of OVA in the OVA and OVA + AT groups. AT was given to the OVA + AT group by oral gavage from day 0 to day 27. On day 28, mice were sacrificed. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin, and periodic acid-Schiff staining. The levels of IgE in serum, interleukin-5 (IL-5) and IL-13 from bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The ILCs from the lung and gut were detected by flow cytometry. 16S ribosomal DNA sequencing was used to analyze the differences in colon microbiota among treatment groups. RESULTS: We found that long-term intake of AT decreased the number of inflammatory cells from BALF, reduced the levels of IL-5 and IL-13 in BALF, and IgE level in serum, and rescued pulmonary histopathology with less mucus secretion in asthmatic mice. 16S ribosomal DNA sequencing results showed that AT strongly affected the colonic bacteria community structure in asthmatic mice, although it had no significant effect on the abundance and diversity of the microbiota. Ruminococcaceae and Desulfovibrionaceae were identified as two biomarkers of the treatment effect of AT. Moreover, AT decreased the numbers of ILCs in both the lung and gut of asthmatic mice. CONCLUSION: The results indicate that AT inhibits pulmonary inflammation, possibly by impeding the activation of ILCs and adjusting the homeostasis of gut microbiota in asthmatic mice.

Unconventional ferroelectricity in moiré heterostructures.

The constituent particles of matter can arrange themselves in various ways, giving rise to emergent phenomena that can be surprisingly rich and often cannot be understood by studying only the individual constituents. Discovering and understanding the emergence of such phenomena in quantum materials-especially those in which multiple degrees of freedom or energy scales are delicately balanced-is of fundamental interest to condensed-matter research1,2. Here we report on the surprising observation of emergent ferroelectricity in graphene-based moiré heterostructures. Ferroelectric materials show electrically switchable electric dipoles, which are usually formed by spatial separation between the average centres of positive and negative charge within the unit cell. On this basis, it is difficult to imagine graphene-a material composed of only carbon atoms-exhibiting ferroelectricity3. However, in this work we realize switchable ferroelectricity in Bernal-stacked bilayer graphene sandwiched between two hexagonal boron nitride layers. By introducing a moiré superlattice potential (via aligning bilayer graphene with the top and/or bottom boron nitride crystals), we observe prominent and robust hysteretic behaviour of the graphene resistance with an externally applied out-of-plane displacement field. Our systematic transport measurements reveal a rich and striking response as a function of displacement field and electron filling, and beyond the framework of conventional ferroelectrics. We further directly probe the ferroelectric polarization through a non-local monolayer graphene sensor. Our results suggest an unconventional, odd-parity electronic ordering in the bilayer graphene/boron nitride moiré system. This emergent moiré ferroelectricity may enable ultrafast, programmable and atomically thin carbon-based memory devices.

Effect of arsenic trioxide on cervical cancer and its mechanisms.

Cervical cancer is one of the most common types of gynecological tumor, and thus identifying complementary or substitute treatment methods to treat cervical cancer is important. The present study aimed to evaluate the effect of arsenic trioxide (ATO), a traditional Chinese medicine, on cervical cancer cells and its underlying mechanism. MTT, colony formation and Transwell assays were performed to investigate the effects of different concentrations of ATO on cell proliferation and invasion, respectively. Western blotting and reverse transcription-quantitative PCR were applied to measure hypoxia-inducible factor-1α expression (HIF-1α) expression following ATO treatment. Finally, the effects of HIF-1α knockdown on cervical cancer cell proliferation, apoptosis and invasion were evaluated. The results demonstrated that ATO could inhibit cell proliferation and invasion. Moreover, ATO could induce reactive oxygen species production in a time- and dose-dependent manner. ATO could also promote the apoptosis of cervical cancer cells via HIF-1α. Therefore, the present study may provide a theoretical basis for identifying effective molecular targets for the prevention and treatment of cervical cancer.

Isoforskolin and Cucurbitacin IIa promote the expression of anti-inflammatory regulatory factor SIGIRR in human macrophages stimulated with Borrelia burgdorferi basic membrane protein A.

Certain natural products, derived from medicinal plants, exhibit anti-inflammatory properties, but the mechanism of action of many remains unclear. Borrelia burgdorferi spirochetes are responsible for causing Lyme arthritis through activation of the Toll-like receptor (TLR) signaling pathway. In this study, we investigated the mechanisms by which Isoforskolin (ISOF) and Cucurbitacin IIa (CuIIa), compounds derived from Chinese herbs, can exert anti-inflammatory effects by modulating single immunoglobulin interleukin-1 receptor-related receptor (SIGIRR; also known as Toll/interleukin-1 receptor 8, TIR8) and thereby inhibiting B. burgdorferi basic membrane protein A (BmpA)-induced TLR signaling in human macrophages, specifically the THP-1 human monocytic cell line. After THP-1 cells were exposed in vitro to: i) recombinant (r)BmpA, ii) rBmpA and ISOF or iii) rBmpA and CuIIa, Cytotoxicity assay (Cell Counting Kit-8, CCK-8) are used to measure the effects of ISOF and CuIIa on cell viability. Meanwhile, real-time polymerase chain reaction and Western blotting were used to quantify SIGIRR mRNA and protein levels, respectively, at 6, 12, 24 and 48 h time points post-stimulation. In addition, proinflammatory cytokine tumor necrosis factor-α (TNF-α) was determined by ELISA analysis. Our study showed that rBmpA stimulation of THP-1 cells resulted in a drop in SIGIRR levels in THP-1 cells. More importantly, SIGIRR levels increased significantly in rBmpA-stimulated THP-1 cells following ISOF or CuIIa administration, and the results of ELISA analysis suggested that ISOF or CuIIa reduced the secretion of the proinflammatory cytokine TNF-α. In conclusion, These results reveal new possibilities for the treatment of Lyme arthritis.

Effectiveness and safety of acupuncture and moxibustion for defecation dysfunction after sphincter-preserving surgery for rectal cancer: protocol for systematic review and meta-analysis.

INTRODUCTION: Defecation dysfunction (DD) is one of the most common complications following sphincter-preserving surgery for rectal cancer. And there is no effective treatment of DD after sphincter-preserving surgery for rectal cancer. Although some studies suggested that acupuncture and moxibustion (AM) is effective and safe for DD after sphincter-preserving surgery for rectal cancer, lacking strong evidence, for instance, the relevant systematic review, meta-analysis and randomised controlled trial (RCT) of a large, multicentre sample, makes the effects and safety remain uncertain. The present protocol is described for a systematic review and meta-analysis to investigate the effectiveness and safety of AM for DD after sphincter-preserving surgery for rectal cancer. METHODS AND ANALYSIS: We will search nine online databases from inception to 1 October 2019; the language of included trials will not be restricted. This study will include RCTs that performed AM as the main method of the experimental group for patients with DD after sphincter-preserving surgery for rectal cancer. Two of the researchers will independently select the studies, conduct risk of bias assessment and extract the data. We will use the fixed-effects model or random-effects model of RevMan V.5.2 software to analyse data synthesis. The risk ratios with 95% CIs and weighted mean differences or standardised mean differences with 95% CIs will be used to present the data synthesis outcome of dichotomous data respectively and the continuous data. Evidence quality of outcome will be assessed by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. ETHICS AND DISSEMINATION: Ethical approval is not required in this secondary research evidence, and we will publish the results of this study in a journal or concerned conferences. TRIAL REGISTRATION NUMBER: CRD42019140097.

Chemical Constituents and Pharmacological Activities of Family Flacourtiaceae: A Class of Important Phytomedicine.

Flacourtiaceae plants are widely used as folk medicines in traditional medicine systems for its chemical diversity and pharmacological activities. In many different areas, Flacourtiaceae plants are used as traditional medicines for the treatment of ulcers, malaria, rheumatism. The Flacourtiaceae plants contain a very plentiful chemical composition, and phytochemical studies show that the Flacourtiaceae plants contained terpenoids, aromatic glycosides, flavnoids, phenylpropanoids, alkaloids, fatty hydrocarbon, and other compounds. In pharmacological studies, various extract and isolated individual compounds exhibited antitumor, anti-oxidation, and anti-inflammatory activities. In this review, the literature data on the chemical constituents and pharmacological investigations of the Flacourtiaceae plants are summarized, to provide information about a more comprehensive chemical composition and detailed pharmacological activities of Flacourtiaceae plants, with a view of further development of clinical medication. However, research on quantitative analysis, toxicity, and drug safety in vitro and in vivo is still insufficient, and further research is required.

Synthesis and Biological Evaluation of Structurally Diverse Benzimidazole Scaffolds as Potential Chemotherapeutic Agents.

BACKGROUND AND OBJECTIVE: Drug resistance and adverse effects are immense healthcare challenges in cancer therapy. Benzimidazole ring-based small molecules have been effective anticancer agents in drug development. In an effort to develop novel chemotherapeutics, we synthesized and assessed the anticancer and antibacterial activities of a small library of structurally unique benzimidazoles. METHODS: The benzimidazoles were derived from indole, N-alkyl indole, fatty acid, and alpha-amino acid scaffolds providing a panel of diverse structures. The compounds were tested in three different cancer cell lines for cytotoxicity: HepG2 (human hepatocellular carcinoma), HeLa (human cervical carcinoma), and A549 (human lung carcinoma). Mechanism of cell death induced by benzimidazoles was evaluated using fluorescent dye-based apoptosis-necrosis assay, immunoblotting for active caspases, topoisomerase-II activity assay, and cell cycle assay. RESULTS: Cell viability testing revealed that indole- and fatty acid-based benzimidazoles were most potent followed by the amino acid derivatives. Many compounds induced cytotoxicity in a concentration-dependent manner with cellular cytotoxicity (CC50) <20µM in the cell lines tested. Most compounds exhibited cytotoxicity via apoptosis through the intrinsic pathway. Inhibition of topoisomerase activity and cell cycle alterations were not the primary mechanisms of cytotoxicity. In addition, several compounds showed promising activity against S. aureus and S. epidermidis (Minimum Inhibitory Concentration (MIC) of as low as 0.04µmol/mL). CONCLUSION: The reported benzimidazole derivatives possess promising anticancer and antibacterial properties. Additionally, we discovered apoptosis to be the primary mechanism for cancer cell death induced by the tested benzimidazoles. Our findings suggest that further development of these scaffolds could provide drug leads towards new chemotherapeutics.

A Newly Discovered Phenylethanoid Glycoside from Stevia rebaudiana Bertoni Affects Insulin Secretion in Rat INS-1 Islet ß Cells.

The tea-like beverage Stevia rebaudiana Bertoni (Stevia) is popular in China because it reduces blood glucose and has a sweet taste. In this work, a comprehensive quality assessment of Stevia led to the discovery of five phenylethanoid glycosides, namely steviophethanoside (1), cuchiloside (2), salidroside (3), icariside D (4), and tyrosol (5). Of them, compound 1 is a novel compound. Mass spectrometry and NMR spectroscopy were employed to confirm the absolute configuration. A hydrolytic step with 4 N TFA at 95 °C for 4 h was used to confirm the monosaccharides. In addition, Discovery Studio 4.0 was used to predict the ADME and toxicity activity of compound 1. The results suggested that compound 1 was biocompatible and had poor toxicity, which was verified by rat INS-1 islet ß cells through an MTT assay. Meanwhile, a significant stimulatory effect on INS-1 cells was observed, which indicated a hypoglycemic effect of compound 1. This is the first report that describes a natural, novel, and hypoglycemic phenylethanoid glycoside in Stevia.

Association of maternal folate intake during pregnancy with infant asthma risk.

Several studies assessed the association of maternal folate intake with infant asthma risk, but the findings are controversial. We performed a meta-analysis to clarify the association between maternal folate intake and infant asthma risk. PubMed and SCOPUS databases were searched for related studies published until August 2018. Fixed-effects models were applied to pool relative risks (RRs) and their corresponding 95% confidence intervals (CIs) due to the low heterogeneity. We also adopted generalized least-squares trend (GLST) estimation for the dose-response analysis. In our study, a total of 10 studies with maternal folate intake and 5 studies with blood folate concentration were included. We found that maternal folate intake during pregnancy was significantly related to the risk of infant asthma (RR = 1.11; 95% CI = 1.06-1.17). Similar results were found for geographic region from Europe (RR = 1.08; 95% CI = 1.01-1.16) and North America (RR = 1.20; 95% CI = 1.11-1.30) in subgroup analyses. Meanwhile, the dose-response analysis showed a linear relationship between maternal folic acid intake during pregnancy and infant asthma risk. This meta-analysis indicates that maternal folate intake during pregnancy could increase infant asthma risk. Therefore, the adverse effect of folic acid on infant asthma should not be ignored when it is supplemented during pregnancy to prevent birth defects.

Rapid identification of urokinase plasminogen activator inhibitors from Traditional Chinese Medicines based on ultrafiltration, LC-MS and in silico docking.

The urokinase plasminogen activator (uPA) is regarded as the crucial trigger for plasmin generation, which is involved in several diseases especially for neoplasm metastasis. In this study, an efficient approach integrating ultrafiltration, LC/MS, bioassay and in silico docking, was proposed for rapidly detecting uPA ligands from Traditional Chinese Medicines (TCMs). Forty-two TCMs were initially assessed, and as illustrative case studies, Galla Chinensis and Sanguisorbae Radix, which appeared significant inhibitory activities on uPA, were chosen to develpe and verify the strategy. A total of seven uPA ligands were successfully detected and identified. Two of them, pentagalloylglucose and 28-O-ß-d-glucopyranosyl pomolic acid, were demonstrated to be potential inhibitors, with IC50 at 1.639 µM and 37.82 µM repectively. Furthermore, a combinatorial compound library screening combined with in silico docking assay, was revealed that ursolic acid (IC50 = 2.623 µM) was also speculated to be a potent parent structure for inhibition of uPA. This approach offers a multidimensional perspective to discover uPA-binding leading compounds from TCMs or other complex mixtures, which would provide an efficient route for drug discovery.

A MoTe2-based light-emitting diode and photodetector for silicon photonic integrated circuits.

One of the current challenges in photonics is developing high-speed, power-efficient, chip-integrated optical communications devices to address the interconnects bottleneck in high-speed computing systems. Silicon photonics has emerged as a leading architecture, in part because of the promise that many components, such as waveguides, couplers, interferometers and modulators, could be directly integrated on silicon-based processors. However, light sources and photodetectors present ongoing challenges. Common approaches for light sources include one or few off-chip or wafer-bonded lasers based on III-V materials, but recent system architecture studies show advantages for the use of many directly modulated light sources positioned at the transmitter location. The most advanced photodetectors in the silicon photonic process are based on germanium, but this requires additional germanium growth, which increases the system cost. The emerging two-dimensional transition-metal dichalcogenides (TMDs) offer a path for optical interconnect components that can be integrated with silicon photonics and complementary metal-oxide-semiconductors (CMOS) processing by back-end-of-the-line steps. Here, we demonstrate a silicon waveguide-integrated light source and photodetector based on a p-n junction of bilayer MoTe2, a TMD semiconductor with an infrared bandgap. This state-of-the-art fabrication technology provides new opportunities for integrated optoelectronic systems.