Discovery of a Series of 4-Amide-thiophene-2-carboxyl Derivatives as Highly Potent P2Y Receptor Antagonists for Inflammatory Bowel Disease Treatment.

The P2Y receptor has been proven to be a potential target for IBD. Herein, we designed and synthesized a series of 4-amide-thiophene-2-carboxyl derivatives as novel potent P2Y receptor antagonists based on the scaffold hopping strategy. The optimized compound (5-((5-fluoropyridin-2-yl)oxy)-4-(4-methylbenzamido)thiophene-2-carboxylic acid) exhibited subnanomolar antagonistic activity (IC: 0.

Rationally designed nanotrap structures for efficient separation of rare earth elements over a single step.

Extracting rare earth elements (REEs) from wastewater is essential for the growth and an eco-friendly sustainable economy. However, it is a daunting challenge to separate individual rare earth elements by their subtle differences. To overcome this difficulty, we report a unique REE nanotrap that features dense uncoordinated carboxyl groups and triazole N atoms in a two-fold interpenetrated metal-organic framework (named NCU-1).

Identification of potential pathogenic targets and survival strategies of through population genomics.

, a foodborne pathogen, has a high mortality rate. Despite its relevance to public health, the identification of virulence genes associated with the pathogenicity of currently known clinical isolates of is incomplete and its synergistic pathogenesis remains unclear. Here, we integrate whole genome sequencing (WGS), genome-wide association studies (GWAS), and genome-wide epistasis studies (GWES), along with phenotype characterization to investigate the pathogenesis and survival strategies of .

Retrospective on global pulmonary hypertension clinical trials: 1999-2021.

Background: Data are quite sparse on the comprehensive analyses of pulmonary hypertension (PH) clinical trials worldwide.

Methods: Information including participating countries (developed or developing), intervention type, trial size, PH categories, sponsorship, study phase, design strategies, and participants' demographic characteristics was extracted from PH trials registered on ClinicalTrials.gov from 1999 to 2021.

Relationship between ambulatory arterial stiffness index and the severity of angiographic atherosclerosis in patients with H-type hypertension and coronary artery disease.

Objective: To investigate coronary artery disease (CAD) and its correlation with the ambulatory arterial stiffness index (AASI) in patients with H-type hypertension (essential hypertension combined with hyper-homocysteinemia) and coronary heart disease (CHD).

Methods: Patients with essential hypertension and CHD who were undergoing coronary angiography were enrolled. The general clinical data, biochemical indicators, ambulatory blood pressure monitoring results and coronary angiography results of the selected patients were collected, and the AASI and Gensini scores were calculated.

Mitochondrial stress induces hepatic stellate cell activation in response to the ATF4/TRIB3 pathway stimulation.

Background: The activation of hepatic stellate cells (HSCs) is the key step in the pathogenesis of liver fibrosis, which directly leads to fibrotic pathological changes in the hepatic tissue. Mitochondrial stress exacerbates inflammatory diseases by inducing pathogenic shifts in normal cells. However, the role of mitochondrial stress in HSC activation remains to be elucidated.

Halogen microregulation in metal-organic frameworks for enhanced adsorption performance of ReO/TcO.

Effective and selective removal of TcO, one of the most nuisance radionuclides in nuclear waste, is highly desirable but remains a significant challenge. Herein, two isostructural MOFs, NCU-3-X (X = Cl, Br) were constructed by ZnX coordinated to nitrogen-containing neutral ligand tri(4-(1H-imidazole-1-l) phenyl) amine for efficient adsorption ReO/TcO. Owning to the twofold interpenetrating structure, both of them exhibit strong alkaline resistance.

CaM/CaMKII mediates activation and proliferation of hepatic stellate cells regulated by ASIC1a.

The activation of hepatic stellate cells (HSCs) is closely related to hepatic fibrosis and plays a key role in its occurrence and development. In the damaged liver, inhibition of the activation, proliferation, and clearance of HSCs is an important therapeutic strategy. However, the mechanism underlying the activation of HSCs is not completely clear.

Correction of multi-scale sunglint reflections from the water surface in airborne high-spatial resolution optical images.

Airborne optical images (AOI) are often with complex sunglint reflections, which brings a certain influence to watercolor retrieval. This includes the sunglint reflection with water surface statistical distribution characteristics caused by imaging viewing angles differences, with high spatial resolution surface discrete characteristics sharing similar viewing angles, and the surface Fresnel reflection sunglint differences caused by the skylight difference during the flight of unmanned aerial vehicles. Aiming at the multiscale optical characteristics of sunglint reflection in high spatial resolution AOI, based on multi-path optical radiation transmission, the sunglint reflection interference from three different imaging processes is clarified.

Discovery of a Series of 5-Amide-1-pyrazole-3-carboxyl Derivatives as Potent P2YR Antagonists with Anti-Inflammatory Characters.

UDPG/P2YR signaling pathway has been considered as a potential therapeutic target for innate immune system diseases. Based on the scaffold hopping strategy, a series of pyrazole analogues were designed and synthesized as novel P2YR antagonists with improved physicochemical properties, together with potential anti-inflammatory activities. Additionally, we designed and synthesized a fluorescent probe based on highly selective and potent PPTN to study the affinity of synthesized compounds.

Tailor-Made Multiple Interpenetrated Metal-Organic Framework for Selective Detection and Adsorption of ReO.

Rationally designed new materials for the selective detection and adsorption of Tc, a problematic element in nuclear waste, are important and challenging in environmental monitoring. Here, we utilize an interpenetration approach to develop a cationic fluorescent metal-organic framework (NCU-2), which was constructed by a flexible tridentate nitrogen-containing ligand and Ag metal ions. The NCU-2 is a scarce case of 14-fold interpenetrated with excellent chemical stability even under 0.

Synthesis of cationic polymer decorated with halogen for highly efficient trapping TcO/ReO.

The elimination of anion is of great importance from radioactive nuclear waste containing TcO by rationally designing anion-scavenging materials with high density of charge and more accessible adsorption sites. Herein, a tailor-made cationic organic polymer with donor-acceptor (D-A) structure, namely TrDCPN, was successfully synthesized by rationally modifying the benzimidazole unit for efficient trapping the perrhenate (ReO) as a Tc surrogate. Systematic control of the skeleton affect enables the material to integrate a variety of features, surmounting the long-term challenge of TcO/ReO remediation under extreme conditions of high acid/base and high ionic strength.

An alkali-resistant metal-organic framework as halogen bond donor for efficient and selective removing of ReO/TcO.

Tc is one of the most problematic nuclear fuel products due to its long half-life and high environmental mobility. Direct removal of TcO from the highly alkaline solution of nuclear fuel is a serious and challenging environmental issue. In this work, the first efficient synthetic approach introducing halogens into a two-dimensional metal-organic framework, named Mn-MOF, is established using MnCl·4HO coordinating with neutral nitrogen-donor ligand, showing ultrahigh stability in alkaline aqueous even under 1 M NaOH.

[Effects of 12-week Tai Chi exercise on the microvascular reactivity of the middle-aged and elderly patients with mild hypertension and its mechanism].

To study the effects of 12-week Taijiquan exercise on the microvascular reactivity of middle-aged and elderly patients with mild hypertension and to explore the mechanisms of microvascular reactivity. Thirty patients with mild hypertension were divided into exercise group (53.8±6.

[Comparison of clinical efficacy of femoral calcar prosthesis replacement and intramedullary nail in the treatment of elderly patients with intertrochanteric fracture].

Objective: To analyze the clinical efficacy of hip arthroplasty with femoral calcar prosthesis and proximal femoral nail fixation(PFNA) in the treatment of elderly patients(≥80 years old) with unstable intertrochanteric fractures(Evans Ⅲ, Ⅳ).

Methods: From June 2016 to March 2018, 60 elderly patients with unstable intertrochanteric fractures treated with prosthetic replacement and PFNA were retrospectively analyzed. According to the surgical methods, they were divided into PFNA group and prosthesis group.

Silencing of Gasdermin D by siRNA-Loaded PEI-Chol Lipopolymers Potently Relieves Acute Gouty Arthritis through Inhibiting Pyroptosis.

Gasdermin D (GSDMD) plays a causal role in NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis eruption, which has been regarded as a potential therapeutic target for pyroptosis-related diseases including acute gouty arthritis. In the present study, the synthesized PEI-Chol (cholesterol grafted polyethylenimine) was assembled with GSDMD small interfering RNA (siRNA) to form PEI-Chol/siGSDMD polyplexes, which provided high transfection efficiency for siRNA-mediated GSDMD knockdown. Then we evaluated the effect of GSDMD siRNA-loaded PEI-Chol on inflammatory cascades in bone-marrow-derived macrophages (BMDMs) and acute gouty arthritis animal models under MSU exposure.

ERα and/or ERβ activation ameliorates cognitive impairment, neurogenesis and apoptosis in type 2 diabetes mellitus mice.

Estrogen receptors (ERs) are thought to be associated with the onset and progression of neurodegenerative injuries and diseases, but the relationship and mechanisms underlying between ERs and cognition in type 2 diabetes remain elusive. In the current study, we investigated the effects of ERα and ERβ on the cognition, neurogenesis and apoptosis in high-fat diet and streptozocin-induced diabetic mice. We found that ERα and/or ERβ activation using their agonists (0.

Activation of ERα and/or ERβ ameliorates cognitive impairment and apoptosis in streptozotocin-induced diabetic mice.

Estrogen receptors (ERs) are thought to be associated with the onset and progression of neurodegenerative injuries and diseases, but the relationship and mechanisms underlying between ERs and cognition in type 1 diabetes remain elusive. In the current study, we investigated the effects of ERα and ERβ on the memory impairment and apoptosis in streptozotocin-induced diabetic mice. We found that ERα and/or ERβ activation using their agonists (0.

[Seasonal Variations in PM and Associated Chemical Species in Jiuxian Mountain in Fujian Province].

PM samples were collected at the top of Jiuxian Mountain in Fujian Province from March 2011 to January 2012 and were analyzed for inorganic water-soluble ions and dicarboxylic acids to investigate their seasonal variations and sources. The results showed that PM and its associated species exhibited much higher levels in the spring than those in other seasons but the total contribution of the nine species of dicarboxylic acids to PM (0.51%±0.

Impact of Pituitary-Gonadal Axis Hormones on Pulmonary Arterial Hypertension in Men.

The association of sex hormone (estradiol, testosterone, and progesterone) with cardiopulmonary disease has already attracted great attention, especially in pulmonary arterial hypertension (PAH). However, the impact of sex hormones and their pituitary stimulators (follicle-stimulating hormone and luteinizing hormone) on PAH in men remains unclear. We conducted a prospective cohort study recruiting 95 patients with idiopathic PAH from 2008 to 2014 and following up for a median of 65 months for death.

[Role of p38MAPK signaling pathway in autophagy of Henle-407 cells induced by spvB of Salmonella typhimurium].

Objective: To investigate the role of p38MAPK signaling pathway in autophagy of intestinal epithelial cells induced by spvB of S.typhimurium.

Methods: Henle-407 cells in exponential growth were infected with wild-type S.

[Mechanism of action of BET bromodomain inhibitor JQ1 in treating airway remodeling in asthmatic mice].

Objective: To investigate the molecular mechanism of action of BET bromodomain inhibitor JQ1 in treating airway remodeling in asthmatic mice.

Methods: A total of 24 mice were randomly divided into control group, ovalbumin (OVA)-induced asthma group (OVA group), and JQ1 intervention group (JQ1+OVA group), with 8 mice in each group. OVA sensitization/challenge was performed to establish a mouse model of asthma.