Appropriate Drought Training Induces Optimal Drought Tolerance by Inducing Stepwise H2O2 Homeostasis in Soybean.

Soybean is considered one of the most drought-sensitive crops, and ROS homeostasis can regulate drought tolerance in these plants. Understanding the mechanism of H2O2 homeostasis and its regulatory effect on drought stress is important for improving drought tolerance in soybean. We used different concentrations of polyethylene glycol (PEG) solutions to simulate the progression from weak drought stress (0.2%, 0.5%, and 1% PEG) to strong drought stress (5% PEG). We investigated the responses of the soybean plant phenotype, ROS level, injury severity, antioxidant system, etc., to different weak drought stresses and subsequent strong drought stresses. The results show that drought-treated plants accumulated H2O2 for signaling and exhibited drought tolerance under the following stronger drought stress, among which the 0.5% PEG treatment had the greatest effect. Under the optimal treatment, there was qualitatively describable H2O2 homeostasis, characterized by a consistent increasing amplitude in H2O2 content compared with CK. The H2O2 signal formed under the optimum treatment induced the capacity of the antioxidant system to remove excess H2O2 to form a primary H2O2 homeostasis. The primary H2O2 homeostasis further induced senior H2O2 homeostasis under the following strong drought and maximized the improvement of drought tolerance. These findings might suggest that gradual drought training could result in stepwise H2O2 homeostasis to continuously improve drought tolerance.

The Burden of Cardiovascular Diseases Attributed to Diet High in Sugar-Sweetened Beverages in 204 Countries and Territories From 1990 to 2019.

This study examines the impact of sugar-sweetened beverage (SSB) consumption on cardiovascular diseases (CVDs) and aims to provide evidence for preventive measures. The analysis involved a comprehensive scrutiny of CVD-related data from 1990 to 2019. Temporal trends of ASMR and ASDR were assessed using the Estimated Annual Percentage Change (EAPC). Globally, there was an increase in deaths and DALYs from 1990 to 2019, despite decreasing ASMR and ASDR. In 2019, SSB-related CVDs accounted for approximately 193.1 thousand deaths and 3973.2 thousand DALYs. China had the highest number of deaths, Tajikistan had the highest ASMR, and Yemen had the highest ASDR in 2019. ASMR and ASDR increased with age and were higher in males. Deaths and DALYs increased overall, except in high Socio-demographic Index (SDI) regions. ASMR and ASDR declined across SDI regions, with the steepest decline in high SDI regions (EAPC: -2.8 for ASMR, -2.36 for ASDR). ASDR increased in low SDI countries but decreased in high SDI countries. This study provides comprehensive insights into the global burden of SSB-related CVDs. Urgent interventions and policies are needed to reduce SSB consumption and mitigate the impact on cardiovascular health.

New Insights into Immune Cells and Immunotherapy for Thyroid Cancer.

Thyroid cancer (TC) is the most common endocrine malignancy worldwide, and the incidence of TC has gradually increased in recent decades. Differentiated thyroid cancer (DTC) is the most common subtype and has a good prognosis. However, advanced DTC patients with recurrence, metastasis and iodine refractoriness, as well as more aggressive subtypes such as poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), still pose a great challenge for clinical management. Therefore, it is necessary to continue to explore the inherent molecular heterogeneity of different TC subtypes and the global landscape of the tumor immune microenvironment (TIME) to find new potential therapeutic targets. Immunotherapy is a promising therapeutic strategy that can be used alone or in combination with drugs targeting tumor-driven genes. This article focuses on the genomic characteristics, tumor-associated immune cell infiltration and immune checkpoint expression of different subtypes of TC patients to provide guidance for immunotherapy.

Integrative single-cell transcriptome analysis reveals immune suppressive landscape in the anaplastic thyroid cancer.

The tumor immune microenvironment (TIME) in ATC is a complex and diverse ecosystem. It is essential to have a comprehensive understanding to improve cancer treatment and prognosis. However, TIME of ATC and the dynamic changes with PTC has not been revealed at the single-cell level. Here, we performed an integrative single-cell analysis of PTC and ATC primary tumor samples. We found that immunosuppressive cells and molecules dominated the TIME in ATC. Specifically, the level of infiltration of exhausted CD8+ T cells, and M2 macrophages was increased, and that of NK cells, B cells, and M1 macrophages was decreased. The cytotoxicity of CD8+ T cells, γδT cells, and NK cells was decreased, and immune checkpoint molecules, such as LAG3, PD1, HAVCR2, and TIGIT were highly expressed in ATC. Our findings contribute to the comprehension of TIME in both PTC and ATC, offering insights into the immunosuppressive factors specifically associated with ATC. Targeting these immunosuppressive factors may activate the anti-tumor immune response in ATC.

Expanding the Chiral Monoterpene Pool: Enantioselective Diels-Alder Reactions of α-Acyloxy Enones.

An enantioselective Diels-Alder (DA) reaction of α-acyloxy enones has been developed to synthesize chiral oxidized cyclohexenes. Yttrium(III) triflate, in conjunction with a chiral pyridinebisimidazoline (PyBim) ligand, was found to catalyze the asymmetric [4 + 2] cycloaddition with a variety of dienes and α-acyloxy enone dienophiles. Using this method, terpinene-4-ol, a key intermediate in the synthesis of commercial herbicide cinmethylin, can be prepared in four steps from isoprene. A combination of kinetic data and NMR studies support a mechanism involving reversible binding of a dienophile to a yttrium catalyst followed by cycloaddition with a diene as the rate-determining step.

Synthesis of Complex Diterpenes: Strategies Guided by Oxidation Pattern Analysis.

With complex molecular architectures, intriguing oxidation patterns, and wide-ranging biological activities, diterpene natural products have greatly impacted research in organic chemistry and drug discovery. Our laboratory has completed total syntheses of several highly oxidized diterpenes, including the ent-kauranoids maoecrystal Z, trichorabdal A, and longikaurin E; the antibiotic pleuromutilin; and the insecticides ryanodol, ryanodine, and perseanol. In this Account, we show how analysis of oxidation patterns and inherent functional group relationships can inform key C-C bond disconnections that greatly simplify the complexity of polycyclic structures and streamline their total syntheses. In articulating these concepts, we draw heavily from the approaches to synthetic strategy that were codified by Evans, Corey, Seebach, and others, based on the formalism that heteroatoms impose an alternating acceptor and donor reactivity pattern upon a carbon skeleton. We find these ideas particularly useful when considering oxidized diterpenes as synthetic targets.In the first part of the Account, we describe the use of reductive cyclizations as strategic tactics for building polycyclic systems with γ-hydroxyketone motifs. We have leveraged Sm-ketyl radical cyclizations as "reactivity umpolungs" to generate γ-hydroxyketones in our total syntheses of the Isodon ent-kauranoid diterpenes (-)-maoecrystal Z, (-)-longikaurin E, and (-)-trichorabdal A. Following this work, we identified the same γ-hydroxyketone pattern in the diterpene antibiotic (+)-pleuromutilin, which again inspired the use of a SmI2-mediated reductive cyclization, this time to construct a bridging eight-membered ring. This collection of four total syntheses highlights how reductive cyclizations are particularly effective umpolung tactics when used to simultaneously form rings and introduce 1,4-dioxygenation patterns.In the second part of the Account, we detail the syntheses of the complex and highly oxidized ryanodane and isoryanodane diterpenes and present the oxidation pattern analysis that guided our synthetic designs. We first discuss our 15-step total synthesis of (+)-ryanodol, which incorporated five of the eight oxygen atoms in just two transformations: a dihydroxylation of (S)-pulegone and a SeO2-mediated trioxidation of the A-ring cyclopentenone. This latter transformation gave rise to an independent investigation of SeO2-mediated peroxidations of simple bicyclic cyclopent-2-en-1-ones. The syntheses of (+)-ryanodine and (+)-20-deoxyspiganthine are also presented, which required modified end-game strategies to selectively incorporate the key pyrrole-2-carboxylate ester. Finally, we describe our fragment coupling approach to prepare the isoryanodane diterpene (+)-perseanol. Using a similar oxidation pattern analysis to that developed in the synthesis of ryanodol, we again identified a two-stage strategy to install the five hydroxyl groups. This strategy was enabled by a Pd-mediated carbopalladation/carbonylation cascade and leveraged unexpected, emergent reactivity to sequence a series of late-stage oxidations.While each of the diterpene natural products discussed in this Account present unique synthetic questions, we hope that through their collective discussion, we provide a conceptual framework that condenses and summarizes the chemical knowledge we have learned and inspires future discourse and innovations in strategy design and methodology development.

Sulfonylureas use and fractures risk in elderly patients with type 2 diabetes mellitus: a meta-analysis study.

BACKGROUND AND AIMS: Sulfonylureas are widely used in patients with type 2 diabetes; meanwhile, the increasing fractures risks especially in the old are gradually taken into consideration. This meta-analysis aimed at investigating whether sulfonylureas could influence the risk of fractures in type 2 diabetes (T2DM) in the elder patients (≥ 65 years old). METHODS: We searched the PubMed and other databases to screen eligible studies. Two authors independently extracted data according to the selection criteria for each study. The Newcastle-Ottawa scale was used to evaluate the quality. Subgroups and sensitivity analyses were performed and publication bias was assessed. RESULT: A total of 7 studies involving 464,121 individuals were included in our meta-analysis. The pooled risk ratio for developing fracture in sulfonylurea users with type 2 diabetes (≥ 65 years old) was 1.26 (95% CI 1.15-1.39). Sensitivity analyses confirmed the stability of the results and there was no publication bias. CONCLUSIONS: Sulfonylureas could add the risk of fractures among the old with type 2 diabetes. Initial sulfonylureas therapy in both men and women should be done prudently.

Exercise intervention for post-treatment colorectal cancer survivors: a systematic review and meta-analysis.

PURPOSE: This study aimed to explore the effects of exercise on post-treatment colorectal cancer survivors through a systematic review and meta-analysis as the current information is limited and controversial. METHODS: We searched PubMed, Web of Science, Embase, and Cochrane Library databases for randomized controlled trials that focused on exercise intervention for adult colorectal cancer survivors who had completed primary cancer treatment. We extracted and pooled information regarding psychosocial outcomes, physical functions, body composition, metabolic growth factors, and/or tumor-related biomarkers. All data were assessed by two independent reviewers. The risk of bias was assessed using the Cochrane Collaboration's tool. RESULTS: A total of 20 studies, which presented data from 1223 post-treatment colorectal cancer survivors, matched the inclusion criteria. Compared with usual care or usual lifestyle, exercise intervention increased VO2peak (n = 107, SMD = 0.72, 95% CI = 0.32 to 1.11, I2 = 41%, P = 0.0004), reduced fasting insulin levels and insulin resistance (n = 150, SMD = - 0.55, 95% CI = - 0.88 to - 0.23, I2 = 0%, P = 0.0009; SMD = - 0.62, 95% CI = - 0.95 to - 0.29, I2 = 0%, P = 0.0002), and decreased levels of sICAM-1. Moderate-intensity exercise was associated with a more pro-inflammatory immune state, resulting in increased oxidative DNA damage. However, no evidence was found for effects of exercise on psychosocial outcomes or body composition. CONCLUSIONS: Our results revealed that exercise could be a feasible and effective option for improving cardiopulmonary fitness, metabolism, and tumor-related biomarkers in post-treatment colorectal cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Given the benefits of exercise for colorectal cancer survivors, they should be encouraged to become more physically active.

Sulfonylurea and fracture risk in patients with type 2 diabetes mellitus: A meta-analysis.

AIMS: This meta-analysis was conducted to investigate the fracture risk among patients with T2DM treated with sulfonylurea. METHODS: The PubMed and other databases were searched for eligible studies. Both randomized controlled trials and observational studies that compared the fracture risk of sulfonylurea to other hypoglycemic agents were included. Pooled risk ratios and 95% confidence intervals were calculated. Subgroup analysis and meta-regression analyses were conducted to explore the source of heterogeneity. RESULTS: A total of 11 studies involving 255,644 individuals were included in our meta-analysis. In comparing sulfonylurea users with patients who had not taken sulfonylurea, the pooled risk ratio for developing fracture was 1.14 (95% confifidence interval, 1.08-1.19). In subgroup analyses, the pooled risk ratio of bone fracture in patients receiving sulfonylurea versus thiazolidinedione, metformin and insulin was 0.90 (95% CI, 0.76-1.06), 1.25 (95% CI, 1.18-1.32) and 0.81 (95% CI, 0.74-0.89) respectively. Meta regression showed that age and gender were not related to the effect of sulfonylurea on fracture. CONCLUSIONS: Sulfonylurea use was associated with 14% increase in the risk of developing fracture in T2DM. The risk of fracture caused by sulfonylurea was similar to thiazolidinedione, higher than metformin and lower than insulin.

A 16-step synthesis of the isoryanodane diterpene (+)-perseanol.

(+)-Perseanol is an isoryanodane diterpene that is isolated from the tropical shrub Persea indica1 and has potent antifeedant and insecticidal properties. It is structurally related to (+)-ryanodine, which is a high-affinity ligand for and modulator of ryanodine receptors-ligand-gated ion channels that are critical for intracellular Ca2+ signalling in most multicellular organisms2. Ryanodine itself modulates ryanodine-receptor-dependent Ca2+ release in many organisms, including mammals; however, preliminary data indicate that ryanodane and isoryanodane congeners that lack the pyrrole-2-carboxylate ester-such as perseanol-may have selective activity in insects3. Here we report a chemical synthesis of (+)-perseanol, which proceeds in 16 steps from commercially available (R)-pulegone. The synthesis involves a two-step annulation process that rapidly assembles the tetracyclic core from readily accessible cyclopentyl building blocks. This work demonstrates how convergent fragment coupling, when combined with strategic oxidation tactics, can enable the concise synthesis of complex and highly oxidized diterpene natural products.

Allylative Approaches to the Synthesis of Complex Guaianolide Sesquiterpenes from Apiaceae and Asteraceae.

With hundreds of unique members isolated to date, guaianolide lactones represent a particularly prolific class of terpene natural products. Given their extensive documented therapeutic properties and fascinating chemical structures, these metabolites have captivated the synthetic chemistry community for many decades. As a result of divergent biosynthetic pathways, which produce a wide array of stereochemical and oxidative permutations, a unifying synthetic pathway to this broad family of natural products is challenging. Herein we document the evolution of a chiral-pool-based synthetic program aimed at accessing an assortment of guaianolides, particularly those from the plant family Apiaceae as well as Asteraceae, members of which possess distinct chemical substructures and necessitate deviating synthetic platforms. An initial route employing the linear monoterpene linalool generated a lower oxidation state guaianolide but was not compatible with the majority of family members. A double-allylation disconnection using a carvone-derived fragment was then developed to access first an Asteraceae-type guaianolide and then various Apiaceae congeners. Finally, using these findings in conjunction with a tandem polyoxygenation cascade, we developed a pathway to highly oxygenated nortrilobolide. A variety of interesting observations in metal-mediated aldehyde allylation and alkene polyoxygenation are reported and discussed.

Exercise therapy in patients with constipation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Exercise therapy has shown significant efficacy as a means of treating various intestinal diseases, but its role in the treatment of constipation is still unclear. The purpose of this study was thus to analyze the effects of exercise on constipation by means of a systematic review and meta-analysis. METHODS: PubMed, Web of Science, EMBASE, Cochrane Library and three Chinese databases [Wanfang Database, Chinese Biomedical Literature (CBM) and China National Knowledge Infrastructure (CNKI)] were searched for relevant studies published through June 2018. Eligible studies were selected in accordance with the PRISMA statement. The main results of interest were changes in gastrointestinal symptoms. RESULTS: A total of nine randomized controlled trials involving 680 participants were included. Eight studies involved aerobic exercise and only one study involved anaerobic exercise. The aerobic exercises included were Qigong, walking and physical movement. The results of this systematic review and meta-analysis indicated that exercise had significant benefits as a means of improving the symptoms of constipation patients [relative risk (RR) = 1.97; 95% CI: 1.19, 3.27; p = .009; I2=91.3%]. Subgroup analyses showed that aerobic exercise (RR = 2.42; 95% CI: 1.34, 4.36; p = .000; I2=88%) similarly had a positive effect on constipation. However, these results were associated with a high risk of bias. CONCLUSION: Our results suggest that exercise may be a feasible and effective treatment option for patients with constipation. However, due to methodological shortcomings, the real effect of this intervention cannot be definitively determined. Researchers should, therefore, design more rigorous studies in order to evaluate the effect of exercise on constipation.

Influence of longitudinal rise of coolant temperature on the thermal strain in a cylindrical laser rod.

The thermal strain in a laser rod with a longitudinal temperature increase is modeled and analytically derived through the method of thermoelastic displacement potential and the method of Love displacement function. The analytical results show that in the absence of external forces, the longitudinal rise of fluid temperature has an unnoticeable effect on the thermal stress profile in the laser rod. However, the thermal strain field caused by the temperature distribution under the traction free boundary condition has an evident variation in the longitudinal direction, which will considerably affect the laser transmission characteristics and the beam quality.

Analysis of thermal effects in an orthotropic laser medium.

The temperature, thermal stress, thermal strain, and optical path difference (OPD) in an orthotropic laser medium under Gaussian, top-hat, and uniform pumping schemes are solved both analytically and numerically. The results indicate that, provided the same total heat loading, the thermal effects under the top-hat pumping scheme are lower than under the Gaussian pumping scheme, whereas the thermal effects under uniform pumping are the least significant of all; in the absence of external forces, the orthotropic thermal properties have more significant effects on the thermal strain than on the thermal stress. The theoretical OPD agrees well with published experimental data and shows evident orthotropy.

Chlorido{2-[1-(2-pyridylmethyl-imino)eth-yl]pyrrolato-κN,N',N''}copper(II).

The potential tridentate Schiff base ligand 2-[1-(2-pyridyl-methyl-imino)eth-yl]pyrrole (HL) was synthesized from the condensation of 2-acetyl-pyrrole with 2-amino-methyl-pyridine. The title compound, [Cu(C(12)H(12)N(3))Cl], was synthesized from HL and copper(II) chloride using triethyl-amine as a base to deprotonate the pyrrole NH group. The title compound is a monomer and the central copper(II) ion is bound to three N atoms of the deprotonated tridentate ligand and to one chloride ion in a square-planar N(3)Cl coordination.