Cryo-EM Structure and Biochemical Analysis of the Human Chemokine Receptor CCR8.

The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein-coupled receptor that has emerged as a promising therapeutic target in cancer and autoimmune diseases. In the present study, we solved the cryo-electron microscopy (cryo-EM) structure of the human CCR8-G complex in the absence of a ligand at 2.58 Å.

Chiral phosphoric acid-catalyzed asymmetric epoxidation of alkenyl aza-heteroarenes using hydrogen peroxide.

The synthesis of chiral α-azaheteroaryl oxiranes via enantioselective catalysis is a formidable challenge due to the required complex stereoselectivity and diverse N-heterocyclic structures. These compounds play a crucial role in developing bioactive molecules, where precise chirality significantly influences biological activity. Here we show that using chiral phosphoric acid as a catalyst, our method efficiently addresses these challenges.

Discovery of a First-in-Class GPR183 Antagonist for the Potential Treatment of Rheumatoid Arthritis.

GPR183 is required for humoral immune responses, and its polymorphisms have been associated with inflammatory autoimmune diseases. Despite increasing attention to GPR183 as a potential therapeutic target for autoimmune diseases, relatively few antagonists have been reported, and none of them have progressed to the clinical stage. In this study, we discovered a highly potent GPR183 antagonist, compound , with good aqueous solubility, excellent selectivity, and pharmacokinetic properties.

The Tautomerase Activity of Tumor Exosomal MIF Promotes Pancreatic Cancer Progression by Modulating MDSC Differentiation.

Pancreatic cancer is a deadly disease that is largely resistant to immunotherapy, in part because of the accumulation of immunosuppressive cells in the tumor microenvironment (TME). Much evidence suggests that tumor-derived exosomes (TDE) contribute to the immunosuppressive activity mediated by myeloid-derived suppressor cells (MDSC) within the pancreatic cancer TME. However, the underlying mechanisms remain elusive.

Discovery of a First-in-Class CD38 Inhibitor for the Treatment of Mitochondrial Myopathy.

CD38 is a crucial NADase in mammalian tissues that degrades NAD and thus regulates cellular NAD levels. Abnormal CD38 expression is linked to mitochondrial dysfunction under several pathological conditions. We present a novel CD38 inhibitor, compound , with high potency for CD38 (IC of 11 nM) and minimal activity against other targets.

Discovery of a Potent and Selective CCR8 Small Molecular Antagonist IPG7236 for the Treatment of Cancer.

Recently, there has been increasing evidence indicating that the CC chemokine receptor 8 (CCR8) plays an important role in mediating the recruitment and immunosuppressive function of regulatory T (T) cells in the tumor microenvironment. Therefore, the development of a specific CCR8 antagonist presents a potential therapeutic strategy against cancer. Despite a few small molecules having been reported as CCR8 antagonists, none has progressed to the clinical stage.

Autoimmunity associates with severity of illness in elderly patients with drug-induced liver injury.

Drug-induced liver injury (DILI) is a potentially serious adverse drug reaction. Due to the lack of definite etiology, specific clinical manifestations, and diagnostic methods, its prediction and diagnosis are challenging. Elderly individuals are deemed to be at high risk for DILI due to abnormal pharmacokinetics, aging tissue repair function, comorbidities, and taking multiple drugs.

Enantioselective Conjugate Addition of Alkenyl Trifluoroborates to Alkenyl-Substituted Benzimidazoles Catalyzed by Chiral Binaphthols.

The enantioselective organocatalytic conjugate alkenylation of β-substituted alkenyl benzimidazoles afforded β-stereogenic 2-alkyl benzimidazole derivatives in excellent enantioselectivities. Chiral binaphthols were effective catalysts for promoting the nucleophilic addition of bench-stable alkenyl trifluoroborate salts under mild conditions, expanding their applications by utilizing C=N-containing azaarenes as activating groups. The synthetic utility of this strategy is demonstrated by conversions into several useful enantiomerically enriched benzimidazole building blocks.

Microencapsulation of blueberry anthocyanins by spray drying with soy protein isolates/high methyl pectin combination: Physicochemical properties, release behavior in vitro and storage stability.

Eleven anthocyanins in the blueberry anthocyanins powders (BAP) were identified and quantified by HPLC-DAD-ESI-MS. BAP microcapsules (MBAP) were produced by spray drying using high methyl pectin (HMP) combined with whey protein isolates (WPI) or soy protein isolates (SPI) in different proportions as wall materials. Generally, SPI/HMP combination was more efficient in increasing the encapsulation efficiency and T, and in decreasing the particle size and hygroscopicity of the microcapsules than WPI or HMP or WPI/HMP combination.

Behavioral analyses in mouse models of autism spectrum disorders.

Autism spectrum disorder is a group of genetically-related developmental disorders of the nervous system. Patients mainly present with core symptoms such as social behavior defects, repetitive stereotyped behaviors, and learning and memory disorders. The mouse models are critical for the studies of the pathogenic mechanisms and potential therapeutic strategies of autism spectrum disorder.

Kinetic Resolution of Tertiary Allylic Alcohols: Highly Enantioselective Access to Cyclic Ethers Bearing an α-Tetrasubstituted Stereocenter.

A chiral phosphoric acid-catalyzed kinetic resolution of tertiary allylic alcohols was developed to provide structurally valuable enantioenriched 2,2-disubstituted tetrahydrofurans, tetrahydropyrans, and oxepane. A variety of tertiary allylic alcohols were resolved with selectivity factors of ≤120. A tertiary allylic carbocationic intermediate mediates the enantioselective intramolecular substitution to achieve high regio- and enantioselectivity.

Organocatalytic Enantioselective Conjugate Alkynylation of β-Aminoenones: Access to Chiral β-Alkynyl-β-Amino Carbonyl Derivatives.

Readily available potassium alkynyltrifluoroborates were used for organocatalytic asymmetric conjugate alkynylation of β-enaminones. The interception of a modified binaphthol catalyst and in situ generated organodifluoroboranes proved important to access functionalized β-alkynyl-β-amino carbonyls and derivatives with improved chemo-reactivity and enantio-induction. Mechanistic studies revealed the impact of molecular sieves on efficiency and stereocontrol.

Effect of microwave radiation on antioxidant capacities of Tartary buckwheat sprouts.

This study aimed to investigate the effects of different microwave radiation power and treatment time on the antioxidant enzyme activities and radical scavenging potency in Tartary buckwheat sprouts. The results indicated that the optimal microwave irradiation conditions for superoxide dismutase, catalase, peroxidise and ascorbate peroxidise antioxidant enzymes was the power 300 W for 75 s, and their activities were all higher than those of the control and the ungerminated seeds. In addition, under the above microwave conditions, the total reducing power and the ability to scavenge DPPH, ABTS, O- and •OH were also optimal.

Comparative study of gene expression profiles rooted in acute myocardial infarction and ischemic/reperfusion rat models.

Mining data in depth of genome-wide sequencing data generated from pathological target tissues under disease conditions is necessary for seeking novel functional genes, and developing more biological study directions for the field. Based on our previous published RNA-seq data generated from acute myocardial ischemia and ischemia-reperfusion in rat heart, we re-analysed these two data sets using bioinformatics tools. All these raw fastq files were extracted from Illumina BCL using the Illumina CASAVA program.

[Selenium Uptake Characteristics of Reclaimed Soil-Crop from Mining Wasteland and Its Antagonistic Effects on Heavy Metals].

To fully exploit selenium-rich land resources and ensure crop safety, the phenomenon of "double high" of Se and heavy metals in reclaimed soil of mining wasteland was studied. Soil and maize samples collected from "point-to-point" were weighted by the inverse distance weighted (IDW) method; multiple linear regression (MLR), partial least squares regression (PLSR), random forest regression (RFR), and other methods were used to predict selenium uptake by maize in a sulfur mine reclamation area in southwest China. Meanwhile, the antagonistic effects of selenium (Se) on heavy metals (Hg, As, Cd, and Cr) were analyzed.

Delirium after primary percutaneous coronary intervention in aged individuals with acute ST-segment elevation myocardial infarction: A retrospective study.

The present prospective study aimed to investigate the incidence and risk factors of delirium after primary percutaneous coronary intervention (PCI) in older adults with acute ST-segment elevation myocardial infarction (STEMI). A total of 111 patients (age, ≥65 years) with acute STEMI following primary PCI were included in the present study. Neurocognitive testing was performed using the Mini-mental State Examination on the first day of hospitalization.

OsSYP121 Accumulates at Fungal Penetration Sites and Mediates Host Resistance to Rice Blast.

is a fungal pathogen that causes rice () blast. SNAREs (soluble -ethylmaleimide-sensitive factor attachment protein receptors) are key components in vesicle trafficking in eukaryotic cells and are known to contribute to fungal pathogen resistance. Syntaxin of Plants121 (SYP121), a Qa-SNARE, has been reported to function in nonhost resistance in Arabidopsis ().

TLR3 contributes to persistent autophagy and heart failure in mice after myocardial infarction.

Toll-like receptors (TLRs) are essential immunoreceptors involved in host defence against invading microbes. Recent studies indicate that certain TLRs activate immunological autophagy to eliminate microbes. It remains unknown whether TLRs regulate autophagy to play a role in the heart.

Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism.

Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition.

[Effect of Water and Nitrogen Fertilizer Coupling on Water Use Efficiency of Chuzhou Chrysanthemum morifolium].

Objective: To discuss the suitable water and nitrogen management modes in cultivating Chuzhou Chrysanthemum morifolium.

Methods: According to two-factors quadratic regression rotation experimental designs, the effect of water and nitrogen fertilizer coupling on water consumption and water use efficiency( WUE) of Chuzhou Chrysanthemum morifolium were studied by pot experiment.

Results: The water consumption of Chuzhou Chrysanthemum morifolium in different growth stages had big variation, and the water consumption rate( WCR) of squaring stage was higher.

[Effect of Crop Rotation and Biological Manure on Quality and Yield of "Chuju" Chrysanthemum morifolium and Continuous Cropping Soil Enzyme Activities].

Objective: To investigate the effects of chrysanthemum-wheat rotation system and biological manure on continuous cropping soil enzyme activities and quality and yield of Chrysanthemum morifolium.

Methods: Field experiments were conducted at the research base of Anhui Jutai Chuju Chrysanthemum morifolium Herbal Technology Co. , Ltd.

[Effects of crop rotation and bio-organic manure on soil microbial characteristics of Chrysanthemum cropping system].

We conducted a field experiment to evaluate the effects of rotation system and bio-organic manure on soil microbial characteristics of Chrysanthemum cropping system. Taking Chrysanthemum morifolium Ramat and wheat as experimental plants, treatments under Chrysanthemum continuous cropping system (M1), conventional Chrysanthemum-wheat rotation system (M2), and Chrysanthemum-wheat rotation system receiving bio-organic manure application of 200 kg · 667 m(-2) (M3) were designed. Soil chemical properties, soil microbial biomass carbon (MBC) and nitrogen (MBN), and the amounts of different types of soil microorganisms were determined.

CXCL1 Triggers Caspase-3 Dependent Tau Cleavage in Long-Term Neuronal Cultures and in the Hippocampus of Aged Mice: Implications in Alzheimer's Disease.

Truncation of tau protein is considered an early event in Alzheimer's disease (AD) and is believed to play a major pathogenic role in sporadic AD. However, causative factors that trigger tau truncation in AD remain poorly understood. In the present study, we demonstrate that CXCL1 (C-X-C motif ligand 1), a specific ligand for the chemokine receptor CXCR2, induced cleavage of tau at ASP421 in a caspase-3-dependent manner in long-term but not short-term cultured neurons.

A protocol of histone modification-based mechanistic study of acupuncture in patients with stable angina pectoris.

Background: Angina pectoris (Angina) is a medical condition related to myocardial ischemia. Although acupuncture has been widely accepted as a clinical approach for angina, there is no sufficient evidence of its effectiveness against this syndrome, and its mechanisms have not yet been well elucidated. We develop this protocol to confirm the clinical efficacy of electro-acupuncture on stable angina pectoris by needling on acupoint Neiguan (PC6).