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Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 μM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.

The box tree moth, Cydalima perspectalis, is native to East Asia (Inoue et al., 1982). It was first recorded in Europe in 2007, in southwest Germany and the Netherlands (Krüger, 2008; Straten and Muus, 2010). Since then it has been recorded in many other European countries, and climate models predict further spread of the species in Europe, invading most areas except for Northern Fenno-Scandinavia, Northern Scotland and high mountain regions (Nacambo et al., 2014). In the newly invaded regions, C. perspectalis larvae feed on the leaves of box trees, Buxus spp., resulting in defoliation, which can kill the trees. The most significant damage, however, can be from the larvae attacking the bark of box trees causing the trees to dry out and die. Besides cultural and economic effects, the most serious threat from C. perspectalis is on the natural Buxus populations (Kenis et al., 2013). The species is easily introduced accidentally with its host plant, which is extensively traded over Europe and therefore presents a serious threat (Leuthardt et al., 2010; Straten and Muus, 2010).

Background Widespread concern of the side effects and the broad-spectrum anticancer property of podophyllotoxin as an antitumor agent highlight the need for the development of new podophyllotoxin derivatives. Although some per-butyrylated glucosides of podophyllotoxin and 4β-triazolyl-podophyllotoxin glycosides show good anticancer activity, the per-acetylated/free of podophyllotoxin glucosides and their per-acetylated are not well studied. Methods A few glucoside derivatives of PPT were synthesized and evaluated for their in vitro cytotoxic activities against five human cancer cell lines, HL-60 (leukemia), SMMC-7721 (hepatoma), A-549 (lung cancer), MCF-7 (breast cancer), and SW480 (colon cancer), as well as the normal human pulmonary epithelial cell line (BEAS-2B). In addition, we investigated the structure-activity relationship and the physicochemical property-anticancer activity relationship of these compounds. Results Compound 6b shows the highest cytotoxic potency against all five cancer cell lines tested, with IC50 values ranging from 3.27±0.21 to 11.37±0.52 μM. We have also found that 6b displays higher selectivity than the etoposide except in the case of HL-60 cell line. The active compounds possess similar physicochemical properties: MSA > 900, %PSA 2, MW > 700 Da, and RB > 10. Conclusion We synthesized several glucoside derivatives of PPT and tested their cytotoxicity. Among them, compound 6b showed the highest cytotoxicity. Further studies including selectivity of active compounds have shown that the selectivity indexes of 6b are much greater than the etoposide except in the case of HL-60 cell line. The active compounds possessed similar physicochemical properties. This study indicates that active glucoside analogs of podophyllotoxin have potential as lead compounds for developing novel anticancer agents.

Punch shearing is used to form the part in the material process. Cryogenic treatment (CT) has active effect on local mechanical properties of steel, but it is still uncertain of the influence of CT on the properties of the magnesium alloy during punch shearing. In this work, the influence of AZ31 sheet treated by cryogenic on punch shearing was studied. Microstructures were observed with a ZEISS optical microscope, and mechanical properties, as well as shear properties were tested by tensile testing and punch shearing. The results show that the number of secondary phase increases and a large number of twins appear in the grains after CT. Meanwhile, the ultimate tensile strength (UTS), the ductility, and hardness of AZ31 are improved, while the yield strength (YS) decreases gradually during CT. During punch shearing, the shearing strength decreases, the rollover radius changes insignificantly, and the height of the burr on the edge of the cross section decreases. At the same time, a larger proportion of smooth zone on the cross section has been achieved.

This study aims to obtain satisfactory short-term traffic flow forecasting results in various traffic flow modes. Clustering analysis of traffic flow data is carried out using the Kohonen neural network. Then, different BP neural networks are trained using different classified traffic flow data. Different neural network models are combined with UKF to form multiple traffic estimators to realize the estimation function. Finally, the interactive method is used to fuse the prediction results of each estimator, and comprehensive traffic flow forecasting results are obtained. With the simulation example, a number of single estimators are obtained, and a joint estimator based on this method is constructed. The section flow of one given road is predicted to verify the performance of the estimator. Results show that the joint estimator has a higher prediction accuracy than the single estimator and has adaptive characteristics when traffic flow characteristics change.

In the ongoing investigation of bioactive compounds from the roots of Sophora flavescens, six prenylflavanones, including two new ones, sophoraflavanones M (1) and N (2), were isolated. The structures of the new compounds were elucidated on the basis of their spectroscopic data. In addition, compound 5 exhibited moderate anti-influenza virus activity, with EC50 value of 43.9 μM.

Honey is a complex and popular food product rich in sugars, vitamins, and minerals. Determination of antibiotic residues in honey is essential because the use of antibiotics has increased significantly in recent decades due to the growing need for food production. The concentration of antibiotic residues in honey is usually at trace levels, and thus liquid chromatography tandem mass spectrometry (LC/MS/MS) with its high sensitivity and selectivity has been increasingly applied for its quantitative analysis. In this review, common honey sample preparations and separation and detection methods appeared in the last ten years are summarized. Sugar-bound/protein-bound antibiotics are discussed in detail. We also summarized the representative matrix effect of antibiotics via LC/MS/MS. These are unseen in the chromatogram but can have deleterious effects on the method's accuracy and sensitivity for the determination of antibiotics in honey.

Based on以华佗的个人经历、师承授徒、著作及相近时代的古籍为线索，探讨华佗针刺感传技术的源流，并分析其失传的可能原因。这项技术的形成，受到了《内经》《难经》中“调气”“得气”“气至”等描述的影响，同时结合了临床上对针感传导方向和具体停留位置的总结。由于华佗本人的经历、针刺技术的传承特点以及当时的时代背景，这项技术可能失传了，但是仍然影响了后世“气至病所”的针刺理念和实践。.

It is the core of the development for Chinese patent medicine enterprises to cultivate large varieties of Chinese patent medicine, and the selection of potentialquot;seedquot; products is the prerequisite for the cultivation strategy. By constructing the evaluation model from multiple dimensions of value and risk, we can conduct specialized evaluation of Chinese patent medicines to effectively, professionally and objectively select thequot;seedquot; products with large variety cultivation potential. In this paper, the establishment of a multidimensional evaluation system would be discussed from the aspects of drug naming and prescription composition, safety risk and supply guarantee of raw materials and medicinal materials, competition situation, access to policy catalogue, scientific and technological support, clinical evidence and recognition, systematical and standardized collection of information on product instructions, quality standards, policy catalogue, scientific and technological literature, market competition and clinical application of Chinese patent medicines. Through the objective evaluation index and the range of objective index, the multi-dimensional evaluation model on values and risks of Chinese patent medicine products was discussed. Based on this model, a batch of Chinese patent medicine products can be quickly and comprehensively analyzed, and quantitative comparison can be formed among different types and fields of products. According to the evaluation results of the model and the comprehensive evaluation of experts, high-qualityquot;seedquot; products can be selec-ted, laying a solid foundation for the next step of large variety cultivation. With use of this model, we can further clarify the external competitive advantages and internal priority levels of each product, and provide support for enterprises to optimize product structure and improve product strategic layout.

By defining the inclusion criteria of the lost acupuncture technique and sorting out the content of lost acupuncture technique (possibly lost acupuncture technique), this article aimed to provide ideas and methods of the inheritance of acupuncture technique.The whole entries ofA total of 364 items of acupuncture technique were retrieved, including 17 items of lost acupuncture technique and 12 items of possibly lost acupuncture technique.The lost acupuncture technique is defined as the acupuncture technique recorded in ancient classics but can not be retrieved in modern literature of clinical application or expert's experience. The change of government or alternation of dynasty, the evolution of acupuncture-moxibustion theories and education are the related causes of lost acupuncture technique.

Three new matrine-type alkaloids, 8β-hydroxyoxysophoridine (1), 9β-hydroxysophoridine (2), 9β-hydroxyisosophocarpine (3), together with one known analog, 11,12-dehydromatrine (4), were isolated from the seeds of Sophora alopecuroides L. The structures of new compounds were elucidated using extensive spectroscopic techniques including the experimental and calculated ECD data. The anti-inflammatory activities of all the isolates on NO production in RAW 264.7 cells stimulated by lipopolysaccharide were evaluated. Among them, 8β-hydroxyoxysophoridine (1) showed a significant inhibitory effect with an IC50 value of 18.26 μM.

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 μM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 μM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.

Covering: up to 2020As a main bioactive component of the Chinese, Indian, and American Podophyllum species, the herbal medicine, podophyllotoxin (PTOX) exhibits broad spectrum pharmacological activity, such as superior antitumor activity and against multiple viruses. PTOX derivatives (PTOXs) could arrest the cell cycle, block the transitorily generated DNA/RNA breaks, and blunt the growth-stimulation by targeting topoisomerase II, tubulin, or insulin-like growth factor 1 receptor. Since 1983, etoposide (VP-16) is being used in frontline cancer therapy against various cancer types, such as small cell lung cancer and testicular cancer. Surprisingly, VP-16 (ClinicalTrials NTC04356690) was also redeveloped to treat the cytokine storm in coronavirus disease 2019 (COVID-19) in phase II in April 2020. The treatment aims at dampening the cytokine storm and is based on etoposide in the case of central nervous system. However, the initial version of PTOX was far from perfect. Almost all podophyllotoxin derivatives, including the FDA-approved drugs VP-16 and teniposide, were seriously limited in clinical therapy due to systemic toxicity, drug resistance, and low bioavailability. To meet this challenge, scientists have devoted continuous efforts to discover new candidate drugs and have developed drug strategies. This review focuses on the current clinical treatment of PTOXs and the prospective analysis for improving druggability in the rational design of new generation PTOX-derived drugs.

A new acylated iridoid, valejatadoid H (1), along with fourteen known compounds, were obtained from the n-BuOH extract of the roots and rhizomes of Valeriana jatamansi, and their structures were elucidated by various spectroscopic methods. Among them, compounds 8, 11 and 13 exhibited potent inhibition on NO production, with IC50 values of 4.21, 6.08 and 20.36 μM, respectively. In addition, compounds 14 and 15 showed anti-influenza virus activities, among which compound 14 exhibited significant effect with an IC50 value of 0.99 μM.

Background: The Regional Network for Asian Schistosomiasis and other Helminth Zoonoses (RNAS+) launched in 1998, has close partnerships with countries where schistosomiasis and other helminthiasis are endemic. RNAS+ has provided an ideal regional platform for experts involved in policy-making, control, and research of parasitic diseases in Asian countries. China, one of the initiating countries, has provided significant technical and financial support to the regional network. Although Chinese institutions provided great technical and resource support toward the RNAS+ development along with other member countries, its role and Chinese scientists or institutions’ contributions have not been evaluated systematically. This study assessed the Chinese contributions in the support of RNAS+ development.Methods: An assessment research framework was planned to evaluate China’s contribution to RNAS+ based on four aspects, including capacity building, funding support, coordination, and cooperation. An anonymous web-based questionnaire was designed to acquire basic information of the respondents, China’s contributions, challenges, and recommendations for RNAS+ development. Each participant scored from 0 to 10 to assess China’s contribution: “0” no contribution, and “10” 100% contribution. Participants who included their e-mail address in the 2017 - 2019 RNAS+ annual workshops were invited to participate the assessment. Results: Of 71 participants enrolled, 41 responded to the survey, 37 (37/41, 90.2%) of whom were from RNAS+ member countries while the remaining 4 (4/41, 9.8%) were international observers. Most respondents (34/41, 82.93%) are familiar with RNAS+. Respondents reported that China’s contributions were mainly in improving of capacity building, providing funding support, responsible of the coordination, and joint application of the cooperation programmes in the development of RNAS+. The average scores of China’s contributions in the above four fields were 8.92, 8.64, 8.75, and 8.67, respectively, with an overall assessment score of 8.81. The challenges of RNAS+ include the lack of sustainable funding and skills, and most participants indicated their continual need of China’s support.Conclusions This survey showed that China plays an important role in the development of RNAS+. This network-type organization for disease control and research can yet be regarded as a great potential pattern for China to enhance regional cooperation. These findings can be used to promote future cooperation between China and other RNAS+ member countries.

A new norsesquiterpene, wilfordonol E (

Twenty-one new iridoids, jatamansidoids A-U (1-12, 21-26, 32, 35 and 36), two new natural ones, jatamansidoids V (37) and W (38), eighteen known ones (13-20, 27-31, 33 and 34), together with three patchoulol-type sesquiterpenoids (39-41), were isolated from the roots and rhizomes of Valeriana jatamansi. Structurally, compounds 1-7 were the first examples of iridoids from V. jatamansi with unique α, β, γ, δ-unsaturated aldehyde fragment between C-11, C-4, C-5, C-9 and C-8; compound 8 was an unprecedented iridoid derivative with a methyl group (Me-10) at C-1, rather than C-8, and its plausible biogenetic pathway was proposed in this paper; compounds 22 and 23 were the first examples of Δ

By detecting and processing the Magnetic Flux Leakage (MFL) signals to identify and estimate the defects in ferromagnetic materials or structures, for example, in the steel pipelines, the so called Magnetic Flux Leakage Testing (MFLT) technology has been widely used in industry. However, the existing MFLT technology is suitable for locating the defects and rough estimating their sizes based on enormous sample data, incapable to image their Three-Dimensional (3D) shapes and precise estimate their sizes, while the physical model associating the defect geometry details and the MFL signals were still unclear. In this study, (1) the effects of an actual 3D defect are taken into account by introducing a new concept, Depth Field over a surface, i.e., a matrix of loss of material on the testing surface of a structure; (2) the governing equations for the depth field and the MFL signals are derived; (3) an algorithm to reconstruct the 3D defect or the depth field based on the governing equations is developed. This new method does not require huge amount of pulling-test data for calibration purpose as the existing MFLT technology used in industry, and it has been verified via a series of tests with various defects of different shapes in pipelines, the results indicate it is valid for 3D defect reconstruction with high accuracy.

Forty-three quinolizidine alkaloids (1–43), including twelve new matrine-type ones, sophalodes A–L (1–7, 17, 19 and 28–30), were isolated from the seeds of Sophora alopecuroides. Structurally, compounds 1–4 were the first examples of C-11 oxidized matrine-type alkaloids from Sophora plants. The structures and absolute configurations of new compounds were elucidated by extensive spectroscopic techniques, X-ray diffraction analysis, and quantum chemical calculation. In addition, the NMR data and absolute configuration of compound 18 was reported for the first time. All the isolates were evaluated for their inhibition on nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophages, among them, compounds 29, 38 and 42 exhibited the most significant activity with IC50 values of 29.19, 25.86 and 33.30 μM, respectively. Further research about new compound 29 showed that it also suppressed the protein levels of iNOS and COX-2, which revealed its anti-inflammatory potential. Moreover, additional research showed that compound 16 exhibited marginal cytotoxicity against HeLa cell lines, with an IC50 value of 24.27 μM.

Seven undescribed (valejatadoids A−G) and 26 known iridoids were obtained from the roots and rhizomes of Valeriana jatamansi. Their structures were determined based on extensive spectroscopic data, especially 1D and 2D NMR, along with HRESIMS. Valejatadoid B is a monoene-type iridoid with a unique double bond between C-4 and C-5. Valejatadoids D−G, jatamanin U, jatamanin O, jatamanvaltrate E, valeriotetrate C, IVHD-valtrate, 10-isovaleroxy-valtrathydrin, jatamanvaltrate Q, valeriandoid F, jatamanvaltrate K, jatamanvaltrate W and isovaltrate were more potent than the positive control when evaluated for inhibition of NO production. Among them, valeriandoid F and jatamanvaltrate K exhibited the most significant inhibitory effects with IC50 values of 0.88 and 0.62 μM, respectively. In addition, valeriandoid F selectively inhibited the proliferation of human glioma stem cell lines, GSC-3# and GSC-18#, with IC50 values of 7.16 and 5.75 μM, respectively.

Two non-destructive detection methods for potato blight based on hyperspectral imaging were used: convolutional neural network (CNN) and support vector machine (SVM) to classify potato leaves. By comparing the classification results, the advantages and disadvantages of different methods are analyzed. In the experiment, normal potato leaves and early blight leaves were selected as research objects. Hyperspectral images of samples were obtained by hyperspectral imaging system, and then principal component images were extracted by principal component analysis method. It was found that the principal component images of normal leaves and blight leaves were significantly different, and finally two models of blight detection were established for convolutional neural network and support vector machine. The experimental results showed that the convolutional neural network was better than the support vector function in the detection of potato blight.

Heterocycle modification has been widely and successfully employed in the antitumor drugs. However, the different antitumor efficacy was corelated with the heterocycle substituted, and the genetic mechanism underlying these effects has not been elucidated. In this study, the intrinsic regularity between different types of heterocycle-substituted DMEP derivative compounds and the mechanisms of their antitumor activity was preliminarily disclosed. Triazole/thiadiazole substituted 4'-demethylepipodophyllotoxin derivatives induced more severe DNA damage and higher levels of 26S proteasomal Topo IIβ degradation, though inhibited the recruition of γH2AX to resist the DNA damage. The reduced DNA repair led to higher up-regulation of cell cycle arrest proteins, and ultimately DNA damage mediated-ATM/ATR apoptotic pathways and specifically activated DNA damage response gene TMEM133, which induced apoptosis through up-regulation of G2/M cell cycle arrest-related genes. Over-expression and knock-out of TMEM133 demonstrated that TMEM133 is essential for inhibition of the tumor cell growth during treatment with triazole/thiadiazole substituted 4'-demethylepipodophyllotoxin derivatives.

Seventeen quinolizidine alkaloids, including a new matrine-type one, sophcence A (

Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae) is a well-known aphid predator in its native Asian habitat. Currently, H. axyridis are predominantly released for aphid control in China; however, light traps and colored sticky cards also were widely used to control aphid pests, which results in population reduction of H. axyridis. This study used 15 monochromatic and whole-spectrum lights to investigate whether H. axyridis has a particular light intensity and spectral preference. Positive phototaxis was found in both H. axyridis adults and larvae to a broad specturm of light. The phototactic responses of adult H. axyridis showed significant similarity to that of larvae. Female H. axyridis had four sensitivity maxima at 414, 492, 504, and 568 nm, male H. axyridis had four maxima of sensitivity at 380, 492, 504, and 549 nm, and H. axyridis larvae also had four maxima of sensitivity at 414, 504, 549, and 568 nm. The phototactic responses of H. axyridis to various monochromatic lights did not significantly differ between sexes. The larval response to a broad spectrum of light was significantly less than that of adults. Furthermore, H. axyridis adults of both sexes showed an increased phototactic response at low intensities and a decreased response at high intensities for both blue light and green light. Moreover, the phototactic response of both female and male H. axyridis was strongest at 10 lux. The males of H. axyridis are more sensitive to light intensity than females; however, the H. axyridis light intensity experiments between sexes showed no significant differences. These behavioral differences could be exploited for the development of selected colored light traps used for insect pest management.

Background The Regional Network for Asian Schistosomiasis and Other Helminth Zoonoses (RNAS+) was established in 1998, which has developed close partnerships with Asian countries endemic for schistosomiasis and other helminthiasis in Asia. RNAS+ has provided an ideal regional platform for policy-makers, practitioners and researchers on the prevention, control and research of parasitic diseases in Asian countries. China, one of the initiating countries, has provided significant technical and financial support to the regional network. However, its roles and contributions have not been explored so far. The purpose of this study was to assess China's contributions on the supporting of RNAS+ development. Methods An assessment research framework was developed to evaluate China’s contributions to RNAS+ in four aspects, including capacity building, funding support, coordination, and cooperation. An anonymous web-based questionnaire was designed to acquire respondents’ basic information, and information on China’s contributions, challenges and recommendations for RNAS+development. Each participant scored from 0 to 10 to assess China’s contribution: “0” represents no contribution, and “10” represents 100% contribution. Participants who included their e-mail address in the 2017–2019 RNAS+ annual workshops were invited to participate in the assessment. Results Of 71 participants enrolled, 41 responded to the survey. 37 (37/41, 90.24%) of them were from RNAS+ member countries, while the other 4 (4/41, 9.76%) were international observers. Most of the respondents (38/41, 92.68%) were familiar with RNAS+. Respondents reported that China’s contributions mainly focused on improving capacity building, providing funding support, coordination responsibility, and joint application of cooperation programs on RNAS+ development. The average scores of China’s contributions in the above four fields were 8.92, 8.64, 8.75, and 8.67, respectively, with an overall assessment score of 8.81 (10 for a maximum score). The challenge of RNAS+ included the lack of sustainable funding, skills, etc. and most participants expressed their continual need of China’s support. Conclusions This survey showed that China has played an important role in the development of RNAS+ since its establishment. This network-type organization for disease control and research can yet be regarded as a great potential pattern for China to enhance regional cooperation. These findings can be used to promote future cooperation between China and other RNAS+ member countries.

Background Dobutamine (DOB) has been recommended as the first-line inotrope for septic patients with low cardiac output, but its long-term impact on intrinsic myocardial dysfunction during sepsis remains unclear. This study investigated the long-term effect of DOB on intrinsic myocardial function and cardiomyocyte apoptosis in sepsis. Methods Male Sprague-Dawley rats were randomly divided into sham and cecal ligation and puncture (CLP) groups. The intrinsic myocardial function and other organ functions were measured at different time points, the inflammatory response and serum biomarkers of myocardial injury were also determined. In separate experiments, the effect of DOB (5 or 10 µg/kg) treatment on survival, intrinsic myocardial function, serum and myocardial cytokines and myocardial apoptosis were measured in septic rats. Results The mortality rate of septic rats was 70% on day 10 after CLP. At 6 h after CLP, the left ventricular ± dP/dt were significantly depressed, serum tumor necrosis factor (TNF) –α level, cardiac TNF-α, intercellular adhesion molecule and vascular cell adhesion molecule-1 (VCAM-1) mRNA, and VCAM-1 protein levels were increased, but not serum cTnI, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), creatinine and urea nitrogen concentrations as well as lung wet-dry weight ratios in CLP group compared with those in sham group. At 9 h after CLP, serum alanine aminotransferase and aspartate aminotransferase activities were higher in CLP rats than controls. At 6 h after CLP, treatment with DOB did not affect the left ventricular ± dP/dt, the levels of TNF-α, interleukin (IL) − 1β and IL-6 in the serum and myocardium as well as cardiomyocyte apoptosis at 20 h after CLP. However, administration of 10.0 µg/kg DOB at 6 h after CLP significantly increased serum IL-10 level and improved survival in septic rats. Conclusions The intrinsic myocardial depression occurs earlier than hepatic and renal dysfunction in severe sepsis and serum cTnI, NT-proBNP and H-FABP are not suitable as an early biomarker for this kind of cardiac dysfunction. For septic rats, DOB treatment in the presence of intrinsic myocardial dysfunction neither improves myocardial function nor attenuates myocardial inflammation and cardiomyocyte apoptosis at the later stage of sepsis.

Two new stilbenoids, stemobenoids A (

Previous research has demonstrated that Herba Lysimachiae (HL) exerts the dual effects on platelet aggregation in the synovium, which may contribute to its protection against synovial lesions under different situations. However, the mechanism is unclear. In the present experiment, a biolabel research based on metabonomics was used to mine the information about the intervention of HL on synovium at the metabolite level, which may help to analyze the regulation of HL on synovial platelet aggregation and its possible treatment in synovial diseases. Synovial metabolic profiling was analyzed using a Shimadzu Nexera UHPLC LC-30A system and an AB SCIEX Triple TOF 4600 mass spectrometer. Enzyme-linked immunosorbent assay (ELISA) was used to verify the biolabels analysis results in the healthy and osteoarthritis rats. Totally, thirteen common metabolites were differentially expressed after treating with HL, and implicated in 2 key pathways (arachidonic acid metabolism and glycerophospholipid metabolism). ELISA showed that HL regulated the expression of prostaglandins E1 and E2 in synovial tissues of the healthy and osteoarthritis rats. This study reveals that HL may regulate synovial platelet aggregation through prostaglandin E1/E2. Additionally, HL is suitable for treating synovial diseases, especially osteoarthritis, which may be associated with platelet aggregation, apoptosis, inflammation, angiogenesis, and carcinogenesis processes.

Oligonucleotide-based therapeutics have become a reality, and are set to transform management of many diseases. Nevertheless, the modulatory activities of these molecules on immune responses remain incompletely defined. Here, we show that gene targeting 2′-O-methyl (2′OMe) gapmer antisense oligonucleotides (ASOs) can have opposing activities on Toll-Like Receptors 7 and 8 (TLR7/8), leading to divergent suppression of TLR7 and activation of TLR8, in a sequence-dependent manner. Surprisingly, TLR8 potentiation by the gapmer ASOs was blunted by locked nucleic acid (LNA) and 2′-methoxyethyl (2′MOE) modifications. Through a screen of 192 2′OMe ASOs and sequence mutants, we characterized the structural and sequence determinants of these activities. Importantly, we identified core motifs preventing the immunosuppressive activities of 2′OMe ASOs on TLR7. Based on these observations, we designed oligonucleotides strongly potentiating TLR8 sensing of Resiquimod, which preserve TLR7 function, and promote strong activation of phagocytes and immune cells. We also provide proof-of-principle data that gene-targeting ASOs can be selected to synergize with TLR8 agonists currently under investigation as immunotherapies, and show that rational ASO selection can be used to prevent unintended immune suppression of TLR7. Taken together, our work characterizes the immumodulatory effects of ASOs to advance their therapeutic development.

TiNi alloy has shape memory and pseudo-elastic properties, excellent corrosion resistance and good biocompatibility, it provides...

Background On January 20, 2020, a new coronavirus epidemic with human-to-human transmission was officially declared by the Chinese government, which caused significant public panic in China. In light of the coronavirus disease 2019 outbreak, pregnant women may be particularly vulnerable and in special need for preventive mental health strategies. Thus far, no reports exist to investigate the mental health response of pregnant women to the coronavirus disease 2019 outbreak. Objective This study aimed to examine the impact of coronavirus disease 2019 outbreak on the prevalence of depressive and anxiety symptoms and the corresponding risk factors among pregnant women across China. Study Design A multicenter, cross-sectional study was initiated in early December 2019 to identify mental health concerns in pregnancy using the Edinburgh Postnatal Depression Scale. This study provided a unique opportunity to compare the mental status of pregnant women before and after the declaration of the coronavirus disease 2019 epidemic. A total of 4124 pregnant women during their third trimester from 25 hospitals in 10 provinces across China were examined in this cross-sectional study from January 1, 2020, to February 9, 2020. Of these women, 1285 were assessed after January 20, 2020, when the coronavirus epidemic was publicly declared and 2839 were assessed before this pivotal time point. The internationally recommended Edinburgh Postnatal Depression Scale was used to assess maternal depression and anxiety symptoms. Prevalence rates and risk factors were compared between the pre- and poststudy groups. Results Pregnant women assessed after the declaration of coronavirus disease 2019 epidemic had significantly higher rates of depressive symptoms (26.0% vs 29.6%, P=.02) than women assessed before the epidemic declaration. These women were also more likely to have thoughts of self-harm (P=.005). The depressive rates were positively associated with the number of newly confirmed cases of coronavirus disease 2019 (P=.003), suspected infections (P=.004), and deaths per day (P=.001). Pregnant women who were underweight before pregnancy, primiparous, younger than 35 years, employed full time, in middle income category, and had appropriate living space were at increased risk for developing depressive and anxiety symptoms during the outbreak. Conclusion Major life-threatening public health events such as the coronavirus disease 2019 outbreak may increase the risk for mental illness among pregnant women, including thoughts of self-harm. Strategies targeting maternal stress and isolation such as effective risk communication and the provision of psychological first aid may be particularly useful to prevent negative outcomes for women and their fetuses.

The outbreak caused by 2019 novel coronavirus(2019-nCoV) is still spreading, posing a great threat to the safety and health of general population. However, there have not been any effective drugs for treatment, with symptomatic treatment and prevention prevailing. The treatment plans of severe acute respiratory syndrome(SARS) and Middle East respiratory syndrome(MERS) are often used for reference in clinic. The advantages of traditional Chinese medicine(TCM) in treating SARS and MERS are that it can intervene and block the progression of disease in early stage, significantly reduce symptoms, shorten the treatment duration of patients, reduce complications and side effects caused by hormone therapy. The coronavirus disease 2019(COVID-19) belongs to the category of TCM epidemic diseases. Chinese patent medicines and prescriptions in medical observation and clinical treatment were recommended in thequot;pneumonia diagnosis and treatment plan for new coronavirus infectionquot;(trial version fifth) of the National Health Commission of the People's Republic of China. Qingfei Paidu Decotion was recommended for the treatment of COVID-19 by the National Health Commission of the People's Republic of China and National Administration of Traditional Chinese Medicine. TCM shows good clinical efficacy and great potential in the treatment of COVID-19. Previous studies of TCM have shown broad-spectrum antiviral activity, providing a variety of sources for the discovery of new antiviral drugs. In this paper, we reviewed traditional Chinese medicines and its active ingredients in the hope of bringing novel inspirations to the drug screening and clinical treatment for COVID-19.

A novel 17-allylamino-17-demethoxygeldanamycin (17-AAG) glucoside (1) was obtained from in vitro enzymatic glycosylation using a UDP-glycosyltransferase (YjiC). The water-solubility of compound 1 was approximately 10.5 times higher than that of the substrate, 17-AAG. Compound 1 showed potential anti-proliferative activities against five human cancer cell lines, with IC50 values ranging from 5.26 to 28.52 μM. Further studies also indicated that compound 1 could inhibit the growth of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (Akt, c-Raf, Bcl-2, and HIF-1α). In addition, compound 1 showed greater potential anti-tumor efficacy than 17-AAG in nude mice xenografted with CNE-2Z cells. Therefore, we suggest that in vitro enzymatic glycosylation is a powerful approach for the structural optimization of 17-AAG.

Recent studies suggest that extracellular cGAMP can be taken up by macrophages to engage STING through several mechanisms. Our work demonstrates that connexin-dependent communication between epithelial cells and macrophages plays a significant role in the amplification of antiviral responses mediated by cGAMP and suggests that pharmacological strategies aimed at modulating connexins may have therapeutic applications to control antiviral responses in humans., Activation of cyclic GMP-AMP (cGAMP) synthase (cGAS) plays a critical role in antiviral responses to many DNA viruses. Sensing of cytosolic DNA by cGAS results in synthesis of the endogenous second messenger cGAMP that activates stimulator of interferon genes (STING) in infected cells. Critically, cGAMP can also propagate antiviral responses to uninfected cells through intercellular transfer, although the modalities of this transfer between epithelial and immune cells remain poorly defined. We demonstrate here that cGAMP-producing epithelial cells can transactivate STING in cocultured macrophages through direct cGAMP transfer. cGAMP transfer was reliant upon connexin expression by epithelial cells and pharmacological inhibition of connexins blunted STING-dependent transactivation of the macrophage compartment. Macrophage transactivation by cGAMP contributed to a positive-feedback loop amplifying antiviral responses, significantly protecting uninfected epithelial cells against viral infection. Collectively, our findings constitute the first direct evidence of a connexin-dependent cGAMP transfer to macrophages by epithelial cells, to amplify antiviral responses.

Clonorchis sinensis infection is highly prevalent in Asia. Diverse hepatobiliary morbidity has been documented for C. sinensis infection. This study aimed to assess the association between C. sinensis infection and hepatobiliary morbidity, taking into consideration of the control, confounders and infection intensity. A cross-sectional community survey was implemented in Hengxian county, southeastern China. Helminth infections were detected by fecal examination. Physical examination and abdominal ultrasonography were then conducted. After excluding confounding effects from gender, age and alcohol drinking, quantitative association between C. sinensis infection and hepatobiliary morbidity was assessed, and the effect from infection intensity was also evaluated, through adjusted odds ratio (aOR) and 95% confidence intervals (95% CI). 696 villagers older than 10 years were enrolled. The prevalence and infection intensity of C. sinensis were higher in male, elder people and the individuals consuming alcohol. Light C. sinensis infection was associated with the increase of diarrhoea (aOR: 2.2, 95% CI: 1.1–4.5). C. sinensis infection was associated with the increase of fatty liver (aOR: 2.7, 95% CI: 1.4–5.2), and the effect was similar in different infection intensities. Moderate C. sinensis infection was associated with the increase of gallbladder stone (aOR: 3.0, 95% CI: 1.1–8.6), while moderate and heavy infections with the increase of intrahepatic bile duct dilatation (aOR: 2.2, 95% CI: 1.0–4.9 and aOR: 4.3, 95% CI: 1.9–9.9, respectively). C. sinensis infection had an effect on the development of periductal fibrosis (aOR: 3.2, 95% CI: 2.1–4.9), which showed increasing trend by infection intensity. The length and width of gallbladder in those with C. sinensis infection were enlarged, especially in those over 30 years old. C. sinensis infection is significantly associated with hepatobiliary morbidity. The occurrence of some morbidity was strongly related to the infection intensity. Awareness on harm of clonorchiasis should be raised both for policy-makers and villagers to adopt effective interventions., Author summary Clonorchiasis is caused by ingestion of raw freshwater fish, which carries the larvae of Clonorchis sinensis. In this study, we aimed to assess the damages associated with clonorchiasis. A cross-sectional field survey was carried out in Hengxian county, southeastern China. Stool samples were collected and examined for helminth infections. Then, physical examination and abdominal ultrasonography were conducted. In total, 696 villagers older than 10 years were included. The prevalence and infection intensity of C. sinensis were higher in male, elder people and those drinking alcohol. Excluding the impact from gender, age and alcohol drinking, it was demonstrated that light C. sinensis infection was associated with the increase of diarrhoea, moderate infection with gallbladder stone, and moderate and heavy infections with intrahepatic bile duct dilatation. C. sinensis infection was relevant to the increase of fatty liver, and the effect was similar in different infection intensities. C. sinensis infection was associated with the development of periductal fibrosis and the effect increased by infection intensity. The length and width of gallbladder in individuals with C. sinensis infection were enlarged, especially in those over 30 years old. Thus, our study demonstrates that C. sinensis infection is associated with severe hepatobiliary morbidity, and the effect is strongly related to infection intensity for some morbidity. Concerted efforts should be exerted to tackle the morbidity in clonorchiasis endemic areas.

Seventeen quinolizidine alkaloids, including a new matrine-type one, sophcence A (1), were isolated from the roots of Sophora flavescens Alt. The structure of compound 1 was elucidated by means of 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. The NMR data of (-)-Δ7-dehydrosophoramine (10) and oxy-N-methylcytisine (12) were reported for the first time. In addition, (+)-sophoranol (4) exhibited moderate inhibition on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 value of 22.14 μM, while lupanine (17) was found to inhibit the growth of human glioma stem cells GSC-3# at 20 μg/mL.

Background br On 20th Jan 2020, a new coronavirus epidemic with “human-to-human” transmission was officially announced, which inevitably caused public panic in

Glioblastoma is one of the most malignant tumors with very poor prognosis. Glioma stem cells (GSCs) occupy a small proportion in glioma, but they are closely associated with radiotherapy and chemotherapy resistance, promoting tumor angiogenesis, hypoxia response, invasion and recurrence. Therefore, GSCs have become a new target for tumor treatment and are used in drug screening. Rupesin E is a natural compound obtained from Valeriana jatamansi, and its antitumor activity has not been reported. In the present study, the antitumor activity of rupesin E was investigated, and the results demonstrated that it inhibited the proliferation of GSCs (GSC-3#, GSC-12#, GSC-18#) with the IC50 values of 7.13±1.41, 13.51±1.46 and 4.44±0.22 µg/ml, respectively. In addition, immunofluorescence cell staining and flow cytometry techniques demonstrated that rupesin E inhibited GSC proliferation and induced apoptosis. Furthermore, rupesin E inhibited the ability of GSC colony formation, indicating its antitumor activity against GSCs in vitro.

The anti-inflammatory effects of shikonofuran E from Onosma paniculatum on RAW 264.7 murine macrophage cells induced by lipopolysaccharide (LPS) were first time examined. A series of non-cytotoxic concentrations of shikonofuran E (

Selective monoarylation of naphthylpyrimidines with a variety of aryl chlorides through C–H bond activation in water was achieved by using a water-soluble [RuCl2-(η6-PhOCH2CH2OH)]2/phosphine catalytic system. The monoarylation occurred at the C-2 carbon of the naphthalene moiety, and selectively polysubstituted naphthylpyrimidines were obtained by a one-pot reaction involving a subsequent hetarylation with 2-pyridyl chlorides.

Objective: To study the correlation of human cytomegalovirus infection (HCMV) with inflammatory factor secretion and myocardial cell injury in patients with acute myocardial infarction. Methods: A total of 80 patients with acute myocardial infarction who were treated in our hospital between September 2015 and September 2017 were selected as the acute myocardial infarction (AMI) group of the research, and 60 healthy volunteers who received physical examination in our hospital during the same period were selected as the control group of the research. The serum was collected to qualitatively determine HCMV, and quantitatively determine the inflammatory factors and myocardial injury indicators. Results: Serum IL- 10 and TGF-β1 levels of AMI group were significantly lower than those of control group whereas IL-1β, IL-6, CD62P, CCL21, CK-MB, cMyBP-C, sLOX-1, Caspase-3 and MDA levels were significantly higher than those of control group; serum IL-10 and TGF-β1 levels of AMI group of patients with HCMV infection were lower than those of patients with nonHCMV infection whereas IL-1β, IL-6, CD62P, CCL21, CK-MB, cMyBP-C, sLOX-1, Caspase-3 and MDA levels were higher than those of patients with non-HCMV infection. Conclusion: Cytomegalovirus infection can promote and aggravate the inflammatory factor secretion and myocardial cell injury in patients with acute myocardial infarction.

Phytochemical investigation on the twigs and leaves of Lyonia ovalifolia led to the isolation of thirty-four compounds, including six grayanane diterpenoids (1–6), sixteen ursane triterpenoids and their glycosides (7–22), and twelve phenolic components (23–34). This study is the first report of compounds 1, 4, 5 and 7–34 in L. ovalifolia, while compounds 1, 4, 5, 7–28 and 30–34 have not been recorded in the genus Lyonia previously. The structures of these compounds were elucidated using spectroscopic methods and by comparing their data to those reported in the literatures. The anti-HIV-1 and anti-influenza virus activities of compounds 1–7, 10–14, 16, 18–22, 24, 25, 30–34 were also evaluated. The chemotaxonomic significance of the isolates has been discussed.

Introduction We previously demonstrated that microRNAs (miRNA) play an important role in Hypothermic Circulatory Arrest (DHCA)-associated neural injury. However, the specific role of miRNAs in the pathogenesis of DHCA-induced neuron death is still unclear. Material and methods Thus, in the present study, we investigated miR-29 expression and roles in neuronal HT-22 cells with Oxygen-glucose Deprivation/reoxygenation (OGD/R). In this study, the model of OGD/R was established using an airtight culture container and the anaeropack. Measurement of Reactive Oxygen Species (ROS) production and Mitochondrial Membrane Potential (MMP) was done using the probes of JC-1 and H2DCFDA. The microRNA (miRNA) profile in hippocampal neurons from rat model of DHCA was determined by miRNA deep sequencing. Results We found that the expression of the miR-29 family (miR-29a/b/c) was significantly reduced in model of DHCA and OGD/R. Overexpression of the miR-29 family inhibited the OGD/R-induced elevation of ROS and reduction of MMP in HT-22 cells. In addition, administration of the miR-29 family suppressed proteins of Keap1, Bax and PUMA and increased Nrf2 expression. We further demonstrated that the miR-29 family targeted the PUMA by luciferase reporter assay and Western blot analysis. Conclusion In conclusion, our data suggest that by targeting a pro-apoptotic BCL2 family member PUMA, the miR-29 family might emerge as a strategy for protection against DHCA-mediated neural cell injury.

A new diterpenoid, 19-O-β-D-glucopyranosyl-labda-8(17),14-dien-13-ol (1), and nine known triterpenes (2–10) were isolated from the aerial parts of Tripterygium hypoglaucum. All structures were elucidated by NMR spectroscopic methods. Moreover, the inhibition of superoxide anion generation and elastase release were also examined.

A UDP-glycosyltransferase (YjiC) from Bacillus licheniformis was exploited for the glycosylation of bavachin. The in vitro glycosylation reaction generated three novel bavachin glucosides, which were structurally characterized as bavachin-4′-O-β- d -glucopyranoside (1), bavachin-7-O-β- d -glucopyranoside (2), and bavachin-4′,7-di-O-β- d -glucopyranoside (3) based on spectroscopic techniques. To enhance product yield, the reaction time, buffer pH, and UDP-glucose concentration were optimized. The water-solubility of compounds 1, 2, and 3 was approximately 5.18, 56.22, and 84.17 times higher than that of bavachin, respectively. In addition, compounds 1-3 displayed the highest stability at pH 8.8 and were stable up to 70 °C for 30 min. Furthermore, the biological activities of bavachin and compounds 1-3 were assayed. Bavachin showed moderate cytotoxicity against four human cancer cell lines while the three glycosylation products displayed weak activity. The results demonstrate that the UDP-glycosyltransferase (YjiC) has the capacity to synthesis bavachin glucosides and that glycosylation of bavachin enhances its water-solubility and stability.

The present article reports the feasibility of Nd:YAG laser welding of Ti alloy to stainless steel through composite layer Ta/V/Fe. The laser beam was focused on the centerline of Ta and Fe sheets respectively to ensure that V interlayer was not completely melted. Two pass welding was employed involving creation of a joint with two weld zones separated by remaining unmelted V. Composite interlayer Ta/V/Fe was used to prevent the formation of Ti-Fe intermetallics and improve microstructure and properties of the Ti alloy-SS joint. The joint fractured at the unmelted V with the tensile strength of 627 MPa.