Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application.

Pancreatic cancer is a highly aggressive malignant tumor, that is becoming increasingly common in recent years. Despite advances in intensive treatment modalities including surgery, radiotherapy, biological therapy, and targeted therapy, the overall survival rate has not significantly improved in patients with pancreatic cancer. This may be attributed to the insidious onset, unknown pathophysiology, and poor prognosis of the disease. It is therefore essential to identify and develop more effective and safer treatments for pancreatic cancer. Tumor immunotherapy is the new and fourth pillar of anti-tumor therapy after surgery, radiotherapy, and chemotherapy. Significant progress has made in the use of immunotherapy for a wide variety of malignant tumors in recent years; a breakthrough has also been made in the treatment of pancreatic cancer. This review describes the advances in immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, oncolytic virus, and matrix-depletion therapies for the treatment of pancreatic cancer. At the same time, some new potential biomarkers and potential immunotherapy combinations for pancreatic cancer are discussed. The molecular mechanisms of various immunotherapies have also been elucidated, and their clinical applications have been highlighted. The current challenges associated with immunotherapy and proposed strategies that hold promise in overcoming these limitations have also been discussed, with the aim of offering new insights into immunotherapy for pancreatic cancer.

Selenobacteria-mediated Se transformation and uptake involving the unique genetic code.

Selenium (Se) is a crucial micronutrient for human health. Plants are the primary source of Se for humans. Selenium in the soil serves as the primary source of Se for plants. The soil contains high total Se content in large areas in Guangxi, China. However, the available Se is low, hindering Se uptake by plants. Microorganisms play a pivotal role in the activation of Se in the soil, thereby enhancing its uptake by plants. In this study, selenobacteria were isolated from Se-rich soils in Guangxi. Then two selenobacteria strains, YLB1-6 and YLB2-1, representing the highest (30,000 µg/mL) and lowest (10,000 µg/mL) Se tolerance levels among the Se-tolerant bacteria, were selected for subsequent analysis. Although the two selenobacteria exhibited distinct effects, they can significantly transform Se species, resulting in a decrease in the soil residual Se (RES-Se) content while concurrently increasing the available Se (AVA-Se) content. Selenobacteria also enhance the transformation of Se valencies, with a significant increase observed in soluble Se6+ (SOL-Se6+). Additionally, selenobacteria can elevate the pH of acidic soil. Selenobacteria also promote the uptake of Se into plants. After treatment with YLB1-6 and YLB2-1, the Se content in the aboveground part of Chinese flowering cabbage increased by 1.96 times and 1.77 times, respectively, while the Se accumulation in the aboveground part of the plant significantly increased by 104.36% and 81.69%, respectively, compared to the control. Further whole-genome sequencing revealed the genetic difference between the two selenobacteria. Additionally, 46 and 38 candidate genes related to selenium utilization were identified from YLB1-6 and YLB2-1, respectively. This work accelerates our understanding of the potential molecular mechanism of Se biofortification by selenobacteria. It also provides microorganisms and gene targets for improving crop varieties or microorganisms to exploit the rich Se source in soil.

Saikosaponin D Inducing Apoptosis and Autophagy through the Activation of Endoplasmic Reticulum Stress in Glioblastoma.

Saikosaponin D (SSD), a saponin derivative, is extracted from Bupleurum falcatum. It exhibits an inhibitory effect on a number of tumor cells and is relatively safe when used at therapeutic doses. However, its effects on glioblastoma multiforme (GBM) have not been fully explored. This study is aimed at investigating the cytotoxic effects of SSD in GBM cell lines. SSD induces apoptosis and autophagy by activating endoplasmic reticulum (ER) stress in GBM cells. GBM cell proliferation activity and morphology were observed using the Cell Counting Kit-8 assay and hematoxylin and eosin staining. Hoechst 33258 fluorescence staining and flow cytometry were performed to assess apoptosis. Western blotting and immunocytochemical staining were used to detect protein expression and distribution. SSD significantly inhibited the proliferation of RG-2, U87-MG, and U251 cells in a dose-dependent manner, and the proportion of apoptotic cells increased significantly. Additionally, the expressions of ER-, apoptosis-, and autophagy-related proteins were significantly upregulated and distributed in the cytoplasm and nucleus. Therefore, SSD may be considered a novel treatment option for GBM. This study demonstrated the anti-GBM effect of SSD from the perspectives of cell apoptosis and autophagy.

Arbuscular Mycorrhizal Fungal Inoculation Increases Organic Selenium Accumulation in Soybean (Glycine max (Linn.) Merr.) Growing in Selenite-Spiked Soils.

Selenium (Se) is an essential trace element for humans. Arbuscular mycorrhizal fungi (AMF) play a crucial role in increasing plant micronutrient acquisition. Soybean (Glycine max (Linn.) Merr.) is a staple food for most people around the world and a source of Se. Therefore, it is necessary to study the mechanism of Se intake in soybean under the influence of AMF. In this study, the effects of fertilization with selenite and inoculation with different AMF strains (Claroideoglomus etunicatum (Ce), Funneliformis mosseae (Fm)) on the accumulation and speciation of Se in common soybean plants were discussed. We carried out a pot experiment at the soil for 90 days to investigate the impact of fertilization with selenite and inoculation with Ce and Fm on the Se fractions in soil, soybean biomass, accumulation and speciation of Se in common soybean plants. The daily dietary intake of the Se (DDI) formula was used to estimate the risk threshold of human intake of Se from soybean seeds. The results showed that combined use of both AMF and Se fertilizer could boost total Se and organic Se amounts in soyabean seeds than that of single Se application and that it could increase the proportion of available Se in soil. Soybean inoculated with Fm and grown in soil fertilized with selenite had the highest organic Se. The results suggest that AMF inoculation could promote root growth, more soil water-soluble Se and higher Se uptake. The maximum Se intake of soybean for adults was 93.15 µg/d when treated with Se fertilizer and Fm, which satisfies the needs of Se intake recommended by the WHO. Combined use of AMF inoculation and Se fertilizer increases the bioavailable Se in soil and promotes the total Se concentration and organic Se accumulation in soybean. In conclusion, AMF inoculation combined with Se fertilization can be a promising strategy for Se biofortification in soybean.

Selenium-Functionalized Corn Starch as a Biodegradable GPx Mimic with High Catalytic Performance.

Selenium-functionalized starch (Se-starch80) is one of the main functional foods used for selenium supplementation. In traditional agriculture, Se-starch has some deficiencies such as long growth cycle and unstable selenium content that prevent its antioxidant performance. In this study, Se-starch was prepared by the nucleophilic addition between NaSeH and carbon-carbon double bond of octenyl succinic anhydride waxy corn starch ester (OSA starch). Some techniques such as 1HNMR, XPS, SEM-EDS, XRD and FT-IR were used to characterize the relevant samples and the results showed that the modification did not destroy the starch framework significantly and the catalytic center (negative divalent selenium) was anchored on the starch framework. The intensive distribution of catalytic center on the starch surface and the hydrophobic microenvironments derived from the OSA chains furnished the Se-starch80 with a high GPx-like catalytic activity (initial reaction rate = 3.64 µM/min). This value was about 1.5 × 105 times higher than that of a typical small-molecule GPx mimic (PhSeSePh). In addition, the Se-starch80, without any cytotoxicity, showed a saturated kinetic catalytic behavior that is similar to a typical enzyme. This work exemplifies a biodegradable selenium-functionalized polymer platform for the high-performing GPx mimic.

Starch and mineral element accumulation during root tuber expansion period of Pueraria thomsonii Benth.

Pueraria is a medicine plant with rich starch, and thus can be a potential agricultural and industrial resource. In this study, we evaluated the root tuber yield of a cultivar of starch kudzu (Pueraria thomsonii) and the starch accumulation during expansion period of root tuber. Additionally, mineral elements were quantified in root tuber and starch. The results indicated that the starch kudzu cultivar owned high yield of root tuber (greater than42 tons/hm2), high starch content (greater than17% FW) in root tuber, and rich accumulation of beneficial mineral elements. Interestingly, the root tuber of P. thomsonii contained a high concentration of selenium (70 mg/kg FW) and strontium (40 mg/kg FW), and thus it can be utilized as a Se and Sr rich food. Furthermore, Se and Sr can be well preserved in starch through the optimized starch extraction method.

Evaluation of selenium bioavailability to Brassica juncea in representative Chinese soils based on diffusive gradients in thin-films (DGT) and chemical extraction methods.

Selenium (Se) is an essential micronutrient for humans but is toxic when consumed in excess through the food chain, such as vegetables. Therefore, it is imperative to understand the relationship between the bioavailability of Se in soil and its uptake in edible parts of vegetables. This study investigated Se bioavailability of Brassica juncea in six representative Chinese soils treated with different concentrations of exogenous selenate fertilizer (0-2 mg·kg-1) by comparing diffusive gradients in thin-films (DGT) and chemical extraction methods. The correlation coefficients between the Se uptake by Brassica juncea and soil available Se determined by different extraction methods was as follows: DGT > KCl > Water > EDTA > KH2PO4 > NaHCO3 extractions. In addition, soil properties were correlated between Brassica juncea and soil Se concentrations determined by chemical extraction methods, while the DGT method was independent of soil properties. DGT was more suitable for the measurement of Se thresholds for Udic Ferrisols, Mollisols, Stagnic Anthrosols, Fluviogenic Loamy Paddy soil, Silty Loam soil, and Calcaric Regosols with values of 373.34, 648.68, 436.29, 589.84, 295.35, and 464.95 µg·L-1, respectively. Thus, DGT may be an effective method for the prediction and evaluation of Se bioavailability to Brassica juncea in different soil types.

DOM derivations determine the distribution and bioavailability of DOM-Se in selenate applied soil and mechanisms.

Straw amendment and plant root exudates modify the quality and quantities of soil dissolved organic matter (DOM) and then manipulate the fractions of soil selenium (Se) and its bioavailability. Two typical soils with distinct pH were selected to investigate the effect of different contributors on DOM-Se in soil. The mechanisms relying on the variation in DOM characteristics (quality, quantity and composition) were explored by UV-Vis, ATR-FTIR and 3D-EEM. Straw amendment significantly (p < 0.05) suppressed the selenate bioavailability. The reduction in wheat Se content was greater in krasnozems than in Lou soil, as more HA fraction appeared in krasnozems. The root exudates of wheat mainly elevated the low molecular hydrophilic compounds (Hy) in soil, which contributed to the SOL-Hy-Se fractions and thus grain Se in soils (p < 0.01). However, straw amendment promoted DOM transforming from small molecules (Hy and FA) to aromatic large molecules (HA), when accompanied with the reduction and retention of Se associated with these molecules. As a result, selenium bioavailability and toxicity reduced with DOM amendment and DOM-Se transformation.

Impact of land use/land cover change on the topsoil selenium concentration and its potential bioavailability in a karst area of southwest China.

Selenium (Se) is an essential micronutrient for human health, and its abundance and potential bioavailability in the soil are of increasing concern worldwide. To date, how total soil Se and its bioavailability would respond to human disturbance or future environmental change is not yet clear, and associated controlling factors remain incompletely understood. Here, we collected soil samples (0-15 cm) from different land use/land cover types, including active cropland, grassland, shrubland, and secondary forest, in a Se-enriched area of Guangxi, southwest China. Total Se concentration and its potential bioavailability, as estimated by phosphate extractability, were investigated. Total soil Se concentration (Setotal) for all samples ranged from 220 to 1820 µg kg-1, with an arithmetic average value of 676 ± 24 µg kg-1 (Mean ± SE, the same below). The concentration of phosphate extractable Se (Sephosphate) varied between 1 and 257 µg kg-1, with an arithmetic mean value of 79 ± 5 µg kg-1, accounting for on average 13 ± 1% of the Setotal. Among the four land use/land cover types, Setotal and Sephosphate were generally more enriched in the secondary forest than those in the grassland and cropland. The content of soil organic carbon (SOC) was the overriding edaphic factor controlling the abundance and potential bioavailability of Se in topsoils. In addition, climatic variables such as mean annual precipitation and mean annual temperature were also key factors affecting the abundance and potential bioavailability of soil Se. Our results suggest that changes in land use/land cover types may deeply influence Se biogeochemistry likely via alterations in soil properties, particularly SOC content.

Prediction of selenium uptake by pak choi in several agricultural soils based on diffusive gradients in thin-films technique and single extraction.

The accurate assessment of soil selenium (Se) bioavailability is crucial for Se biofortification in Se-deficient areas and risk assessment in selenosis areas. However, a universally accepted approach to evaluate Se bioavailability in soil is currently lacking. This research investigated Se bioavailability in six soils treated with selenite (Se(IV)) or selenate (Se(VI)) by comparing diffusive gradients in thin-films (DGT) technique and chemical extraction methods through pot experiments. A bioindicator method was used to evaluate Se concentrations in pak choi and compare the results with the Se concentration measured by other methods. Results showed that chemical extraction methods presented different extraction efficiencies for available Se over a range of soil types, and the same extraction method had various extraction efficiencies for different Se species in the same soil. DGT measured Se concentrations (CDGT-Se) for Se(VI) treatment were 2.3-34.1 times of those for Se(IV) treatment. KH2PO4-K2HPO4 and AB-DTPA extractable Se could predict the bioavailability of soil Se, but they were disturbed by soil properties. HAc extraction was unsuitable for evaluating Se bioavailability in different Se(IV)-treated soils. By contrast, DGT technique was preferable for predicting plant uptake of Se(IV) over chemical extraction methods. Although DGT technique was independent of soil properties, KH2PO4-K2HPO4 extraction provided the best fitting regression equation for Se(VI) when it was dependent on soil organic matter. Thus, KH2PO4-K2HPO4 extraction may be preferred to assess Se(VI) bioavailability in different soil types on a large scale.

Nitric oxide alleviates selenium toxicity in rice by regulating antioxidation, selenium uptake, speciation and gene expression.

In plants, excess selenium (Se) causes toxicity, while the beneficial effects of nitric oxide (NO) have verified in plants under various abiotic conditions. In order to ensure safely Se-enriched rice production, the objective of the research was to clarify how exogenous NO alleviated high Se toxicity in rice. Under high Se (25 µM) stress, the effects of exogenous NO (by applying sodium nitroprusside, an exogenous NO donor) on growth parameters, Se content, Se speciation, photosynthesis, antioxidant system, expressions of Se transport and metabolism-related genes (phosphate transporter, OsPT2; S-adenosylmethionine synthase 1, OsSAMS1; cysteine synthase, OsCS; Se-binding protein gene, OsSBP1) in rice seedlings were investigated by a hydroponic experiment. The results showed that exogenous NO alleviated high Se-induced irreversible damage to root morphology, growth, photosynthesis, antioxidant capacity and decreased the contents of MDA, H2O2 and proline significantly in rice seedlings. Compared with high Se treatment, application of exogenous NO reduced root Se content (10%), and the Se(VI) decreased by 100% in root and shoot. Besides, exogenous NO decreased the accumulation of inorganic Se speciation in rice roots and shoots. Also, the qRT-PCR analysis showed that down-regulated gene expressions of OsPT2, OsSAMS1 and OsCS affected significantly via exogenous NO. So, the exogenous NO could effectively decrease the toxicity of high Se treatment in rice.

Assessing the uptake of selenium from naturally enriched soils by maize (Zea mays L.) using diffusive gradients in thin-films technique (DGT) and traditional extractions.

A generally accepted method to predict selenium (Se) bioavailability of long-term contaminated soils has not yet been established, even if risk assessments in selenosis areas are crucial. In this study, a set of methods were tested to assess the bioavailability of Se to field maize. Fifty maize (Zea mays L.) samples and corresponding soils were collected from a selenosis area (Ziyang, China). The diffusive gradients in thin-films (DGT) technique and the traditional chemical extraction methods, including seven single-step extraction procedures and a five-step sequential extraction were used to predict the bioaccumulation of Se in plant. The result verified the presence of 50% of total Se in the form of residual Se fraction, followed by organic-bound and Fe-Mn oxide-bound Se fractions in soil. In addition, Se6+, Se4+, and Se2- were all detected in the solution extracted by H2O, KCl, phosphate-buffered solution (PBS), NaHCO3, ethylenediaminetetraacetic acid-2Na (EDTA-2Na) and ammonium bicarbonate-diethylenetriaminepentaacetic acid (AB-DTPA), but Se6+ was not extracted by NaOH. The Se extracted by single-step extraction methods was weakly correlated with the Se uptake by plants with relatively high Se concentration (>3 mg·kg-1). The abilities of the tested methods to predict Se bioavailability in naturally Se-enriched soils declined in the following order: DGT > soil solution > PBS > KCl > H2O > NaHCO3 > EDTA > DTPA > NaOH. The ratio of CDGT to soil solution Se (Csoln) totaled 0.13, indicating an extremely low Se supply from the soil solid phase to the soil solution. Se measured by DGT was mainly derived from the soluble and exchangeable Se fractions that can accurately reflect the plant-absorbed Se pool. Therefore, the DGT technique is highly applicable in the simultaneous prediction of Se bioavailability in naturally Se-enriched soils.

Hydrogen sulfide enhances rice tolerance to nickel through the prevention of chloroplast damage and the improvement of nitrogen metabolism under excessive nickel.

Hydrogen sulfide (H2S) modulates plant tolerance to abiotic stresses, but its regulatory effects on nitrogen metabolism and chloroplast protection under nickel (Ni) stress in crop plants remain elusive. Taking this into account, we investigated the potential roles of sodium hydrosulfide (NaHS), a H2S generator, in the improvement of growth performance of rice plants under Ni stress. Results showed that NaHS successfully reversed the adverse effects of Ni, as reflected in plant growth and biomass, and photosynthesis attributes including photosynthetic rates, stomatal conductance, transpiration rate, internal CO2 concentration and photosynthetic pigment contents. NaHS generated H2S plays a crucial role in controlling the photosynthetic machinery of rice as evidenced by the ultrastructure of chloroplast viewed under transmission electron microscope (TEM). The reduced content of Ni in roots and leaves of NaHS-supplemented Ni-stressed plants has revealed the restricted uptake and accumulation of Ni. A rescue of NaHS to the Ni-induced decline in nitrate (NO3-) content and the activities NO3- biosynthesizing enzymes nitrate reductase, nitrite reductase, glutamate synthase, glutamate oxaloacetate transaminase, glutamine synthetase, and glutamate pyruvate transaminase in leaves indicated a positive role of H2S on NO3- metabolism in rice under Ni stress. NaHS application also reverted Ni-mediated increases in ammonium (NH4+) content and glutamate dehydrogenase activity, implying H2S-induced alleviation of NH4+ toxicity. The regulatory effects of H2S on nitrogen metabolism was further confirmed by increased and decreased transcript abundance of NO3- and NH4+ metabolism associated genes, respectively. Our study suggests a decisive role of H2S in controlling Ni toxicity as elucidated by the novel findings such as enhanced gas exchanged parameters, Ni homeostasis and chloroplast protection. Moreover, this article highlights the significance of H2S in controlling chloroplast biogenesis and nitrogen metabolism in rice crop under Ni stress.

Spatial variations in soil selenium and residential dietary selenium intake in a selenium-rich county, Shitai, Anhui, China.

Shitai, a selenium (Se)-rich county in Anhui, China, has been reported for its resident longevity in the last 20 years. A recent survey by the Anhui Bureau of Geological Survey showed that soil Se contents in the Shitai area ranged from 0.05 to 51.20 mg/kg, with an average of 0.56 mg/kg. To explore the potential relationship between longevity and natural-occurring Se contents in Shitai county, Se concentrations were determined in Shitai's food chain (including soils and foods) and the daily Se intakes and hair Se contents were calculated for the residents. In the present study, 33 soil samples, 66 food samples and 82 hair samples were randomly collected from field sites, local food markets and male and female residents in downtown Shitai and in four nearby villages (Dashan, Xianyu, Yongfu and Yuantou). The total Se contents in all samples and the levels of water soluble, exchangeable, acid soluble, organic bound and residual Se in soil samples were determined with hydride generation - atomic fluorescence spectrometry. The total Se contents in soils ranged from 227 to 2603 µg/kg, with the averages of 1607 ±â€¯242 µg/kg in Dashan, 1149 ±â€¯118 µg/kg in Xianyu, 521 ±â€¯157 µg/kg in Yongfu, and 363 ±â€¯140 µg/kg in Yuantou. The soil bioavailable Se content (soluble and exchangeable Se) in Dashan was highest (14.98%), followed by Xianyu (13.69%), Yongfu (13.18%) and Yuantou (9.38%). For food samples, the highest Se concentration of grains was 468.5 µg/kg in Dashan, while lowest was observed in downtown (41.7 µg/kg). The estimated daily Se intake of residents in Dashan reached 298.4 µg/d/adult, which is about 5 times higher than the recommend nutrient intake in China (60 µg/d/adult), and 6-10 times higher than the levels observed in Xianyu (47.6 µg/d/adult), Yuantou (46.1 µg/d/adult), Yongfu (40.0 µg/d/adult), and downtown (30.0 µg/d/adult). Although hair Se contents in Dashan (male: 709.2 µg/kg; female: 589.2 µg/kg) were significantly higher than those at the other study sites, no significant relationships between daily Se intakes and hair Se contents were observed. The present study demonstrated that Se levels in soils, foods, resident dietary intake and human hairs in Shitai County varied significantly; therefore, the region could be a unique field site to study the direct relationship between Se and human health.

Selenium Accumulation, Antioxidant Enzyme Levels, and Amino Acids Composition in Chinese Mitten Crab (Eriocheir sinensis) Fed Selenium-Biofortified Corn.

The effects of selenium (Se)-biofortified corn on the total Se contents, the antioxidant enzyme levels, and the amino acids composition in Chinese mitten crab (Eriocheir sinensis) during the stage of the fifth shelling to maturity were investigated in the present study. The culture density of crabs was 600 per 667 m², and they were continuously fed 120.4 mg Se from Se-biofortified corn per 667 m² every two days for 90 days. The results showed that the total muscle Se levels in the crabs were significantly increased (p < 0.05). Activities of hemolymph supernatant enzymes including alkaline phosphatase (AKP), lysozyme (LZM), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were also enhanced (p < 0.05). The protein and crude fat levels at maturity were higher than those at the fourth molt. The levels of total essential amino acids (∑EAAs) and total delicious amino acids (∑DAAs) were significantly increased (p < 0.05). We demonstrate that the feeding of Se-biofortified corn could significantly improve total muscle Se concentrations and hemolymph supernatant antioxidant enzyme activities in Chinese mitten crab, and slow down the rapid decline of ∑EAAs and ∑DAAs at maturity, thus improving the nutritional quality of Chinese mitten crab.

Expanding indole diversity: direct 1-step synthesis of 1,2-fused indoles and spiroindolines from 2-halo anilines for fast SAR antiviral elucidation against tobacco mosaic virus (TMV).

To systematically investigate the influence of the variation of the original skeletons and spatial configuration of 2,3-fused indole natural products on antiviral activities, two types of structurally novel and potent pseudo-indole natural product derivatives, 1,2-fused indole and spiroindoline, with different substituents were direct synthesized from 2-halo anilines, and their antiviral activities against tobacco mosaic virus (TMV) were evaluated. The results showed that these compounds exhibited good anti-TMV activity, especially 3f, 3g, 3i, 5e, 5h, and 5l, which were more potent than the commercial anti-virus agent ribavirin. An SAR investigation demonstrates that the original ring size, arrangement, and planarity are not optimal; their anti-TMV activities can be improved by skeleton modification and spatial configuration variation. Both of the structurally novel skeletons provide a new template for antiviral studies, which may also provide some useful information for antiviral mechanism elucidation.

Assessing the feasibility and quality of shared decision making in China: evaluating a clinical encounter intervention for Chinese patients.

BACKGROUND: The aim of this study was to evaluate the feasibility of using the Statin Choice decision aid to have discussions about starting a statin medication for cardiovascular risk reduction in Chinese patients with stable coronary artery diseases. METHODS: A prospective, pilot study of the Statin Choice decision aid in two teaching hospitals in Northern China was conducted. A total of seven clinicians were enrolled and underwent a 12-hour, group-based, in-person training on shared decision making (SDM) and the Statin Choice decision aid. Then, these clinicians used the Statin Choice decision aid in patients during a clinical encounter. A total of 86 patients aged 40-80 years, who had stable angina, were enrolled. All clinical encounters were video recorded. A team of three researchers viewed and scored all the encounter recordings to evaluate the SDM process and fidelity to the intervention using the OPTION scale and Fidelity scale, respectively. All the patients were followed up for 12 months to record adherence to statin and any major adverse cardiac events (MACEs). RESULTS: The average scores on the OPTION normalized score and Fidelity scale were 21 (range, 3-32; out of a possible, 48) and 10 (range, 6-10; out of a possible, 10), respectively. This suggested that Chinese clinicians who were using Statin Choice in their patients were able to exhibit behaviors consistent with SDM at a level that is similar to that reported in Western countries. After SDM, the statin adherence was 94.5% (69/73), and the proportion of MACEs was 2.9% (2/69). CONCLUSION: Using an encounter decision aid developed in the US, it was feasible to implement SDM in a referral cardiology practice in Mainland China. Further work to ensure that the encounter aid is pertinent to the Chinese population and that SDM is tested in at-risk patients could contribute to the implementation of SDM across Mainland China.

C ring may be dispensable for ß-carboline: Design, synthesis, and bioactivities evaluation of tryptophan analog derivatives based on the biosynthesis of ß-carboline alkaloids.

According to our previous work and the latest research on the biosynthesis of ß-carboline, and using the reverse thinking strategy, tryptophan, the biosynthesis precursor of ß-carboline alkaloids, and their derivatives were synthesized, and their biological activities and structure-activity relationships were studied. This bioassay showed that these compounds exhibited good inhibitory activities against tobacco mosaic virus (TMV); especially (S)-2-amino-3-(1H-indol-3-yl)-N-octylpropanamide (4) (63.3±2.1%, 67.1±1.9%, 68.7±1.3%, and 64.5±3.1%, 500µg/mL) exhibited the best antiviral activity both in vitro and in vivo. Compound 4 was chosen for the field trials and the acute oral toxicity test, the results showed that the compound exhibited good anti-TMV activity in the field and low acute oral toxicity. We also found that these compounds showed antifungal activities and insecticidal activities.

[The increased level of IL-17 in stomach and up-regulated splenic Th17 cell frequency and IL-17 mRNA level in rats infected with Helicobacter pylori].

OBJECTIVE: To investigate the variation of Th17 cell frequency and IL-17 level in rats infected with Helicobacter pylori (Hp). METHODS: A total of 30 rats were used to be infected with Hp by intragastric administration of bacterial suspension. Every 10 rats were sacrificed after 3, 6 and 9 weeks, respectively. The gastric tissues of rats were pathologically examined by HE staining. The level of IL-17 in the gastric tissues of rats was detected by ELISA. The flow cytometry was performed to determine Th17 cell frequency and reverse transcription PCR was to detect the level of IL-17 mRNA in single-cell suspensions of rat spleen. RESULTS: Hp infection induced the obvious pathological changes in the rat gastric mucosa. The level of IL-17 in the gastric tissues increased with the prolonging of the Hp infection. Both Th17 cell frequency and IL-17 mRNA level in rat spleen cells infected with Hp at 3, 6 and 9 weeks were significantly higher than those in control rats, and they were significantly different when compared among different time points. CONCLUSION: Hp infection could induce the damage of rat gastric mucosa and increase IL-17 level in the stomach. Furthermore, Hp infection could up-regulate the Th17 cell frequency and IL-17 mRNA level in rat spleen cells.

Regio- and chemoselective N-1 acylation of indoles: Pd-catalyzed domino cyclization to afford 1,2-fused tricyclic indole scaffolds.

A concise method for the synthesis of 1,2-fused tricyclic indole scaffolds by domino cyclization involving a Pd-catalyzed Sonogashira coupling, indole cyclization, regio- and chemoselective N-1 acylation, and 1,4-Michael addition is reported. This method provides straightforward access to tetrahydro[1,4]diazepino[1,2-a]indole and hexahydro[1,5]diazocino[1,2-a]indole scaffolds.