Direct C-H Alkylation of Benzothiadiazoles via Organic Photoredox Catalysis.

2,1,3-Benzothiadiazole is widely used as a privileged scaffold in pharmaceuticals and organic functional materials. Nonetheless, many current methods for the functionalization of 2,1,3-benzothiadiazole rely on preactivation, transition metal catalysts/promoters, or an elevated reaction temperature. Herein we disclose a transition-metal-free visible-light-induced photocatalytic method for the direct C-H alkylation of 2,1,3-benzothiadiazole using readily accessible carboxylic acid derivatives, i.e., N-hydroxyphthalimide esters (NHPEs), as alkylating reagents under room temperature. This mild and scalable method is highlighted by the late-stage installation of the benzothiadiazole scaffold in drugs and natural products.

Relationship between caffeine intake and thyroid function: results from NHANES 2007-2012.

BACKGROUND: Moderate caffeine intake decreases the risk of metabolic disorders and all-cause mortality, and the mechanism may be related to its ergogenic actions. Thyroid hormones are vital in metabolic homeostasis; however, their association with caffeine intake has rarely been explored. OBJECTIVE: To investigate the association between caffeine intake and thyroid function. METHODS: We collected data on demographic background, medical conditions, dietary intake, and thyroid function from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Subgroups were classified using two-step cluster analysis, with sex, age, body mass index (BMI), hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD) being used for clustering. Restrictive cubic spline analysis was employed to investigate potential nonlinear correlations, and multivariable linear regression was used to evaluate the association between caffeine consumption and thyroid function. RESULTS: A total of 2,582 participants were included, and three subgroups with different metabolic features were clustered. In the most metabolically unhealthy group, with the oldest age, highest BMI, and more cases of hypertension, hyperglycemia, and CVD, there was a nonlinear relationship between caffeine intake and serum thyroid stimulating hormone (TSH) level. After adjusting for age, sex, race, drinking, smoking, medical conditions, and micronutrient and macronutrient intake, caffeine intake of less than 9.97 mg/d was positively associated with serum TSH (p = 0.035, standardized ß = 0.155); however, moderate caffeine consumption (9.97-264.97 mg/d) indicated a negative association (p = 0.001, standardized ß = - 0.152). CONCLUSIONS: Caffeine consumption had a nonlinear relationship with serum TSH in people with metabolic disorders, and moderate caffeine intake (9.97 ~ 264.97 mg/d) was positively associated with serum TSH.

Electrochemical Detection of ompA Gene of C. sakazakii Based on Glucose-Oxidase-Mimicking Nanotags of Gold-Nanoparticles-Doped Copper Metal-organic Frameworks.

The present work developed an electrochemical genosensor for the detection of virulence outer membrane protein A (ompA, tDNA) gene of Cronobacter sakazakii (C. sakazakii) by exploiting the excellent glucose-oxidase-mimicking activity of copper Metal-organic frameworks (Cu-MOF) doped with gold nanoparticle (AuNPs). The signal nanotags of signal probes (sDNA) that biofunctionalized AuNPs@Cu-MOF (sDNA-AuNPs@Cu-MOF) were designed using an Au-S bond. The biosensor was prepared by immobilization capture probes (cDNA) onto an electrodeposited AuNPs-modified glassy carbon electrode (GCE). AuNPs@Cu-MOF was introduced onto the surface of the GCE via a hybridization reaction between cDNA and tDNA, as well as tDNA and sDNA. Due to the enhanced oxidase-mimicking activity of AuNPs@Cu-MOF to glucose, the biosensor gave a linear range of 1.0 × 10-15 to 1.0 × 10-9 mol L-1 to tDNA with a detection limit (LOD) of 0.42 fmol L-1 under optimized conditions using differential pulse voltammetry measurement (DPV). It can be applied in the direct detection of ompA gene segments in total DNA extracts from C. sakazakii with a broad linear range of 5.4-5.4 × 105 CFU mL-1 and a LOD of 0.35 CFU mL-1. The biosensor showed good selectivity, fabricating reproducibility and storage stability, and can be used for the detection of ompA gene segments in real samples with recovery between 87.5% and 107.3%.

Circ-XPO1 upregulates XPO1 expression by sponging multiple miRNAs to facilitate osteosarcoma cell progression.

Circular RNAs (circRNAs) act as a key role in mediating carcinogenesis. Nevertheless, the functions and mechanisms of circRNAs in osteosarcoma (OS) are still not fully understood. In the present study, we aim to investigate the functions of circ-XPO1 in OS and its potential mechanism underlying OS progression. CircRNA microarray indicated elevation of circ-XPO1 in OS specimens relative to normal samples. Elevation of circ-XPO1 and XPO1 mRNA was identified in OS tissue specimens and cells by qRT-PCR. In addition, enhanced expression of circ-XPO1 and XPO1 mRNA both correlated with poor prognosis for the patients with OS, as estimated by Kaplan-Meier analysis. Functionally, circ-XPO1 and XPO1 both facilitated the growth and invasion and decreased the apoptosis of OS cells. Moreover, we constructed the circ-XPO1-miRNAs-XPO1 3'-UTR interaction network and verified that circ-XPO1 could sponge miR-23a-3p, miR-23b-3p, miR-23c, and miR-130a-5p to regulate XPO1 expression. Furthermore, rescue assay indicated that the effect of circ-XPO1 on cell progression was partly relying on these miRNAs. Taken together, we found that circ-XPO1 regulated the expression of XPO1 through sponging miRNAs as a competing endogenous (ceRNA), providing the possibility that circ-XPO1 might play as a new therapeutic target for OS.

Design, synthesis and antitumor activity of icotinib derivatives.

EGFR-TK pathway is of high importance for the treatment of non-small-cell lung cancers (NSCLC), and it will be challenging to develop anti-tumor drugs that could inhibit both EGFR wild-type and mutant tumor cells. Here, a series of icotinib derivatives containing 1,2,3-triazole moiety were designed and synthesized through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Preliminary CCK-8 assay showed that the prepared icotinib-1,2,3-triazole compounds such as a7 or a12 demonstrated potent in vitro antitumor activity against the NSCLC cells expressing both wild type EGFR and mutational EGFR. Further, the mechanism of action for compounds a7 and a12 induced NSCLC cells death was also detailed, and the results suggested a possible induced NSCLC cells death via inducing mitochondrial apoptosis and arresting cell cycle. Remarkably, the inhibition of EGFR by these icotinib derivatives was also studied. The results showed that compound a12 was a potent inhibitor for EGFR with IC50 value of 1.49 µM. Combining these results, an EGFR inhibitor a12 represents a promising new anti-NSCLC candidate that could induce apoptosis and arrest cell cycle.

Targeting POH1 inhibits prostate cancer cell growth and enhances the suppressive efficacy of androgen deprivation and docetaxel.

BACKGROUND: POH1, a member of the JAMM domain containing deubiquitinases, functions in malignant progression of certain types of cancer. However, the role of POH1 in prostate cancer (PCa) remains unclear. METHODS: We performed RNA interference against the JAMM members in PC3 cells and analyzed cell proliferation. POH1 knockdown was established to evaluate the effects of POH1 on cell growth in vitro and in vivo. RNA-sequencing was utilized to explore the molecular details underlying the biological function of POH1 in PCa. The expression of POH1 in PCa tissues was detected by immunohistochemistry. The POH1 inhibitor capzimin was evaluated to explore whether pharmacologically inhibiting POH1 significantly affected PCa cell proliferation alone or enhanced the inhibitory efficacy of docetaxel and androgen deprivation. RESULTS: Functional analyses identified POH1 as a JAMM deubiquitinase that is required for PCa proliferation. Importantly, expression of POH1 was higher in human PCa tissues (PCas) than that in normal prostate tissues, and a positive correlation was detected between elevated POH1 expression and higher pathological grades in PCas. In vivo experiments further demonstrated that depleting POH1 significantly suppressed the growth of PCa cell xenografts. POH1 deficiency profoundly inhibited the expression of a set of genes involving the cell cycle and caused G0/G1 phase arrest. Furthermore, the POH1 inhibitor capzimin phenotypically recapitulated the effects of POH1 knockdown and improved the efficacy of docetaxel and androgen deprivation in PCa cells. CONCLUSIONS: POH1 was overexpressed in PCas and was correlated with pathological grades in human PCas. Inhibiting POH1 by gene silencing or pharmacological inhibition with capzimin suppressed PCa cell growth. Exploring the inhibition of POH1 in combination with other drugs may provide a strategy to benefit patients with PCa.

Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation.

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L-1 (NCI-H1299), 3.16 ± 0.11 µmol L-1 (A549), and 1.83 ± 0.13 µmol L-1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L-1 (NCI-H1299), 3.86 ± 0.38 µmol L-1 (A549), and 1.69 ± 0.25 µmol L-1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.

Soil microbial community shifts explain habitat heterogeneity in two Haloxylon species from a nutrient perspective.

Haloxylon ammodendron and Haloxylon persicum (as sister taxa) are dominant shrubs in the Gurbantunggut Desert. The former grows in inter-dune lowlands while the latter in sand dunes. However, little information is available regarding the possible role of soil microorganisms in the habitat heterogeneity in the two Haloxylon species from a nutrient perspective. Rhizosphere is the interface of plant-microbe-soil interactions and fertile islands usually occur around the roots of desert shrubs. Given this, we applied quantitative real-time PCR combined with MiSeq amplicon sequencing to compare their rhizosphere effects on microbial abundance and community structures at three soil depths (0-20, 20-40, and 40-60 cm). The rhizosphere effects on microbial activity (respiration) and soil properties had also been estimated. The rhizospheres of both shrubs exerted significant positive effects on microbial activity and abundance (e.g., eukarya, bacteria, and nitrogen-fixing microbes). The rhizosphere effect of H. ammodendron on microbial activity and abundance of bacteria and nitrogen-fixing microbes was greater than that of H. persicum. However, the fertile island effect of H. ammodendron was weaker than that of H. persicum. Moreover, there existed distinct differences in microbial community structure between the two rhizosphere soils. Soil available nitrogen, especially nitrate nitrogen, was shown to be a driver of microbial community differentiation among rhizosphere and non-rhizosphere soils in the desert. In general, the rhizosphere of H. ammodendron recruited more copiotrophs (e.g., Firmicutes, Bacteroidetes, and Proteobacteria), nitrogen-fixing microbes and ammonia-oxidizing bacteria, and with stronger microbial activities. This helps it maintain a competitive advantage in relatively nutrient-rich lowlands. Haloxylon persicum relied more on fungi, actinomycetes, archaea (including ammonia-oxidizing archaea), and eukarya, with higher nutrient use efficiency, which help it adapt to the harsher dune crests. This study provides insights into the microbial mechanisms of habitat heterogeneity in two Haloxylon species in the poor desert soil.

Quantifying the effects of precipitation exclusion and groundwater drawdown on functional traits of Haloxylon ammodendron - How does this xeric shrub survive the drought?

The increasing frequency of drought and decline in groundwater levels are causing ecophysiological changes in woody plants, particularly in desert ecosystems in arid regions. However, the combined effects of meteorological and hydrological droughts on perennial desert plants, especially phreatophytes, remain poorly understood. To address this knowledge gap, we conducted a 5-year precipitation exclusion experiment at two sites with contrasting groundwater depths in the Gurbantunggut Desert located in northwest China. Our study aimed to investigate the impacts of precipitation exclusion and groundwater depth decline on multiple traits of H. ammodendron. We found that long-term precipitation exclusion enhanced midday leaf water potential, stomatal conductance, chlorophyll content, root nonstructural carbohydrates concentration, leaf starch concentration, but decreased water use efficiency. Groundwater drawdown decreased predawn and midday leaf water potentials, maximum net photosynthetic rate, stomatal conductance, Huber value, stem water δ18O, but enhanced water use efficiency and branch nonstructural carbohydrates concentration. A combination of precipitation exclusion and groundwater depth decline reduced Huber value, but did not show exacerbated effects. The findings demonstrate that hydrological drought induced by groundwater depth decline poses a greater threat to the survival of H. ammodendron than future changes in precipitation.

Within-crown plasticity of hydraulic properties influence branch dieback patterns of two woody plants under experimental drought conditions.

In recent year, widespread declines of Populus bolleana Lauche trees (P. bolleana, which dieback from the top down) and Haloxylon ammodendron shrubs (H. ammodendron, which dieback starting from their outer canopy) have occurred. To investigate how both intra-canopy hydraulic changes and plasticity in hydraulic properties create differences in vulnerability between these two species, we conducted a drought simulation field experiment. We analyzed branch hydraulic vulnerability, leaf water potential (Ψ), photosynthesis (A), stomatal conductance (gs), non-structural carbohydrate (NSCs) contents and morphological traits of the plants as the plants underwent a partial canopy dieback. Our results showed that: (1) the hydraulic architecture was very different between the two life forms; (2) H. ammodendron exhibited a drought tolerance response with weak stomatal control, and thus a sharp decline in Ψ while P. bolleana showed a drought avoidance response with tighter stomatal control that maintained a relatively stable Ψ; (3) the Ψ of H. ammodendron showed relative consistent symptoms of drought stress with increasing plant stature, but the Ψ of P. bolleana showed greater drought stress in higher portions of the crown; (4) prolonged drought caused P. bolleana to consume and H. ammodendron to accumulate NSCs in the branches of their upper canopy. Thus, the prolonged drought caused the shoots of the upper canopy of P. bolleana to experience greater vulnerability leading to dieback of the upper branches first, while all the twigs of the outer canopy of H. ammodendron experienced nearly identical degrees of vulnerability, and thus dieback occurred uniformly. Our results indicate that intra-canopy hydraulic change and their plasticity under drought was the main cause of the observed canopy dieback patterns in both species. However, more work is needed to further establish that hydraulic limitation as a function of plant stature was the sole mechanism for causing the divergent canopy dieback patterns.

Calf thymus DNA binding studies of the new neodymium-naproxen complex.

Fluorescence spectroscopy in combination with UV absorption spectroscopy was carried out to investigate the interaction between the neodymium-naproxen complex (Nd-NAP) and calf thymus DNA (ctDNA). The experimental results showed that Nd-NAP intercalated with the ctDNA base pairs. Analysis of fluorescence quenching data of Nd-NAP by ctDNA at different temperatures using a Stern-Volmer equation revealed that dynamic and static quenching occurred simultaneously. The binding constants and the number of binding sites at 293 and 310 K were obtained as 2.904 × 10(4) L mol(-1), 1.172 and 2.432 × 10(4) L mol(-1), 1.143, respectively. The thermodynamic parameters ΔG, ΔH, and ΔS calculated at different temperatures indicated that hydrogen bonding and van der Waals force were the main binding forces.

Overcoming O-H Insertion to Para-Selective C-H Functionalization of Free Phenols: Rh(II)/Xantphos Catalyzed Geminal Difunctionalization of Diazo Compounds.

Para-selective C-H functionalization of free phenols by metal carbenoids is rather challenging due to the generally more favorable competing O-H insertion. Herein, with the use of the combination of Rh(II) and a Xantphos ligand as the catalyst, a novel multicomponent reaction of free phenols, diazoesters, and allylic carbonates was successfully developed, affording a wide variety of phenol derivatives, bearing an all-carbon quaternary center and a synthetically useful allylic unit. This reaction is likely to occur through a tandem process of carbene-induced para-selective C-H functionalization, followed by Rh(II)/Xantphos-catalyzed allylation. The distinctive reactivity of para-selective C-H rather than O-H insertion for the carbenoid intermediate, combined with features of excellent functional group compatibility, high atom and step economy, and ease in further diversification of the products, might render this protocol highly attractive in facile functionalization of unprotected phenols.

Evolutionary lability underlies drought adaptation of Australian shrubs along aridity gradients.

Leaf drought tolerance traits influence plant survival in water deficit conditions, and these traits are influenced by both the plant's evolutionary history and the environment in which the plant is currently growing. However, due to the substantial phenotypic plasticity in leaf traits, we still do not know to what degree variation in leaf traits is governed by species' phylogenetic history or by their environment. To explore this question, we re-examined a drought tolerance dataset from 37 native Australian shrub species with varying climate origins growing in a common garden located in Melbourne, Australia. We previously measured seven leaf morphophysiological traits, and here, we estimated how phylogenetically conserved these traits are. We quantified phylogeny and the strength of correlation between the morphological traits and physiological traits before and after accounting for shared phylogenetic history. We also evaluated the relationship between species' leaf traits and the climate of their native ranges. We present three main findings: (a) most leaf drought tolerance traits had weak phylogenetic signals, which is consistent with the convergent evolution of these traits. (b) There is weak but consistent coordination between distinct leaf drought tolerance traits, which can be masked due to species' phylogenetic histories. (c) Leaf drought tolerance traits show strong correlations with the climate of species' origins, and this relationship is only weakly impacted by phylogenetic signals. Therefore, the role of phylogeny on the coordination among leaf functional traits and their links to climate were limited. A better understanding of trait-environment relationships might be more pivotal than understanding the evolution of these traits for improving the predictions of species' response to climate change-type drought, especially for shrub species that span substantial aridity gradients.

Climate of origin has no influence on drought adaptive traits and the drought responses of a widely distributed polymorphic shrub.

Climate has a significant influence on species distribution and the expression of functional traits in different plant species. However, it is unknown if subspecies with different climate envelopes also show differences in their expression of plant functional traits or if they respond differently to drought stress. We measured functional traits and drought responses of five subspecies of a widely distributed, cosmopolitan polymorphic shrub, Dodonaea viscosa (L.) Jacq., in an experiment with 1-year-old plants. Functional traits, such as leaf size, specific leaf area, turgor loss point (ΨTLP), maximum stomatal conductance and maximum plant hydraulic conductance, differed among the five subspecies. However, while the were some differences among traits, these were not related to their climate of origin, as measured by mean annual temperature, mean annual precipitation and mean annual aridity index. Drought response was also not related to climate of origin, and all subspecies showed a combination of drought avoiding and drought tolerance responses. All subspecies closed their stomata at very high water potentials (between -1.0 and -1.3 MPa) and had large hydraulic safety margins (drought avoidance). All subspecies adjusted their ΨTLP via osmotic adjustment, and subspecies with inherently lower ΨTLP showed greater osmotic adjustment (drought tolerance). All subspecies adjusted their midday water potentials in response to drought but subspecies from more arid environments did not show greater adjustments. The results indicated that climate niche was not related to plant trait expression or response to drought. The combination of drought avoidance and drought tolerance behavior seems to be a successful strategy for this widely distributed species that occupies many different climate zones and ecosystems. Hence, the wide distribution of D. viscosa seems to be related to plasticity of trait expression and drought response rather than long-term genetic adaptations to different environmental conditions.

Synthesis and Anti-Tumor Effects of Novel Pomalidomide Derivatives Containing Urea Moieties.

In order to explore novel immunomodulatory agents as anti-tumor drugs, we designed and synthesized a series of new pomalidomide derivatives containing urea moieties. Interestingly, in vitro biological experiments performed in several cancer cell lines showed that some of them displayed potent anti-tumor ability. These novel compounds 5a-5e and 6a-6e demonstrated the best cell growth inhibitive activity in human breast cancer cell lines MCF-7, but weaker inhibitive activity in human hepatocellular carcinoma cell lines Huh7. Moreover, compound 5d had the most powerful effects in this study, with an IC50 value of 20.2 µM in MCF-7. Further study indicated that compound 5d could inhibit cell growth and induce cell death in a concentration-dependent manner. Besides, compound 5d increased cellular ROS levels and induced DNA damage, thereby potentially leading to cell apoptosis. These observations suggest that the novel pomalidomide derivatives containing urea moieties may be worth further investigation to generate potential anti-tumor drugs.

ACE2 gene combined with exercise training attenuates central AngII/AT1 axis function and oxidative stress in a prehypertensive rat model.

Angiotensin-converting enzyme 2 (ACE2) or exercise training (ExT) is beneficial to hypertension, but their combined effects remain unknown. In this study, lentivirus containing enhanced green fluorescent protein (eGFP) and ACE2 were microinjected into the paraventricular nucleus (PVN) of young male spontaneous hypertensive rats (SHRs), and SHRs were assigned into five groups: sedentary (SHR), SHR-ExT, SHR-eGFP, ACE2 gene (SHR-ACE2), and ACE2 gene combined with ExT (SHR-ACE2-ExT). Wistar-Kyoto (WKY) rats were used as a control. ACE2 gene or ExT significantly delayed the elevation of blood pressure, and the combined effect prevented the development and progression of prehypertension. Either ACE2 overexpression or ExT improved arterial baroreflex sensitivity (BRS), whereas the combined effect normalized BRS in SHR. Compared with SHR, SHR-ACE2 and SHR-ExT displayed a significantly higher level of ACE2 protein but had lower plasma norepinephrine (NE) and angiotensin II (AngII) as well as angiotensin II type 1 receptor (AT1) protein expression in the PVN. SHR-ACE2-ExT showed the largest decrease in AngII and AT1 protein expression. Reactive oxygen species (ROS) level and NADPH oxidase (NOX2 and NOX4) protein expression in PVN were also decreased in SHR-ACE2-ExT group than in SHR-ACE2 and SHR-ExT groups. It was concluded that the combined effect has effectively prevented prehypertension progression and baroreflex dysfunction in SHR, which is associated with the reduction in AngII/AT1 axis function and oxidative stress in the PVN.NEW & NOTEWORTHY Angiotensin-converting enzyme 2 (ACE2) gene in combination with exercise training (ExT) delayed the progression of hypertension via normalizing the blunted baroreflex sensitivity (BRS) and inhibiting sympathetic nerve activity (SNA). Its underlying mechanism may be related to the inhibition of AngII/AT1 axis function and central oxidative stress in the paraventricular nucleus (PVN) of prehypertensive rats.

[Effects of groundwater depth on functional traits of young Haloxylon ammodendron.] / 地下水埋深对幼龄梭梭功能性状的影响.

Groundwater is an important water source for phreatophytic shrubs in arid desert areas. In order to understand the impacts of groundwater depth on functional traits of phreatophytic shrubs, two groups of groundwater levels (2 and 3.5 m) were set up using lysimeter with automatic water replenishing instrument. We measured hydraulic traits, gas exchange characteristics, and root morphological parameters of young Haloxylon ammodendron during the growing season. The results showed that predawn assimilating branch water potential, osmotic potential at full turgor, and root length ratio of young H. ammodendron in the groundwater depth of 3.5 m were lower by 48.2%, 41.5% and 56.7% than that under groundwater depth of 2 m, respectively, while maximum net photosynthetic rate of late growing season, root volume, specific root length and specific root area of fine root were 75.7%, 41.0%, 273.7% and 67.7% higher, respectively. Midday water potential and water content of assimilating branch tended to decrease first in the early growing season and then increase in the late growing season. Root distribution of young H. ammodendron along soil profile showed a significant positive correlation between the average root diameter and soil depth, while the proportion of fine root surface area showed a significant negative correlation with soil depth at both groundwater levels. There was synergy of aboveground assimilating branch hydraulic traits and photosynthetic capacity with belowground root morphological traits in young H. ammodendron. Under the condition of increasing groundwater depth, young H. ammodendron adopted the ecological strategies of reducing predawn assimilating branch water potential and osmotic potential at full turgor, and increasing root diameter and length to enhance water deficit tolerance and expanding the area of water uptake to sustain their survival.

Novel 1,2,3-Triazole Erlotinib Derivatives as Potent IDO1 Inhibitors: Design, Drug-Target Interactions Prediction, Synthesis, Biological Evaluation, Molecular Docking and ADME Properties Studies.

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a predominant role in cancer immunotherapy which catalyzes the initial and rate limiting steps of the kynurenine pathway as a key enzyme. To explore novel IDO1 inhibitors, five derivatives of erlotinib-linked 1,2,3-triazole compounds were designed by using a structure-based drug design strategy. Drug-target interactions (DTI) were predicted by DeePurpose, an easy-to-use deep learning library that contains more than 50 algorithms. The DTI prediction results suggested that the designed molecules have potential inhibitory activities for IDO1. Chemical syntheses and bioassays showed that the compounds exhibited remarkable inhibitory activities against IDO1, among them, compound e was the most potent with an IC50 value of 0.32 ± 0.07 µM in the Hela cell assay. The docking model and ADME analysis exhibited that the effective interactions of these compounds with heme iron and better drug-likeness ensured the IDO1 inhibitory activities. The studies suggested that compound e was a novel and interesting IDO1 inhibitor for further development.

Rh(III)-Catalyzed Chemodivergent Coupling of N-Phenoxyacetamides and Alkylidenecyclopropanes via C-H Activation.

Rh(III)-catalyzed C-H activation of N-phenoxyacetamides and chemodivergent coupling to alkylidenecyclopropanes (ACPs) have been accomplished. With the assistance of the ring strain of ACPs, the coupling can be transannulative or nonannulative, delivering 3-ethylidenedihydrobenzofurans or dienes, respectively, under different reaction conditions, and the selectivity is mainly solvent-controlled. All of the reactions proceeded under mild conditions with a good substrate scope and excellent chemo- and diastereoselectivity.

Effects of Kinesio Tape on Delayed Onset Muscle Soreness: A Systematic Review and Meta-analysis.

BACKGROUND: Kinesio tape (KT) may be useful for the treatment of delayed onset muscle soreness (DOMS), but there has been no systematic review assessing their efficacy. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate the efficacy of KT on DOMS. METHODS: We searched seven databases for randomized controlled trials (RCTs) and crossover randomized trials of KT in DOMS, from the earliest date available to December 31, 2019. The primary outcome was muscle soreness. The secondary outcome was muscle strength and serum creatine kinase (CK) level. The risk of bias was evaluated based on the Cochrane criteria. Data were analyzed using RevMan version 5.3.0 software. P values < 0.05 were considered statistically significant. Systematic review registration number is CRD42020157052. RESULTS: Eight trials (six RCTs and two crossover randomized trials) with 289 participants were included. KT use significantly reduced muscle soreness at 48 h (mean difference (MD): -0.67, 95% confidence interval (CI): -1.10 to 0.24, P = 0.002) and 72 h postexercise (MD: -0.81, 95% CI: -1.45 to -0.17, P = 0.01) but not at 24 h. KT use improved muscle strength at 72 h postexercise (standardized mean difference: 0.35, 95% CI: 0.02 to 0.69, P = 0.04) but not at 24 or 48 h. However, the serum CK level at 24, 48, and 72 h postexercise was not better in the KT group relative to the control group. CONCLUSIONS: Current evidence suggests that KT might help to alleviate DOMS after strenuous exercise to improve muscle strength. Thus, using KT on the skin for more than 48 hours postexercise, but not for 24 h, appears more effective at relieving pain and improving muscle strength.