Discovering New Metallo-Deubiquitinase CSN5 Inhibitors by a Non-Catalytic Activity Assay Platform.

COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, , that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5.

[Medicinal plant biodiversity in Jilin province based on big data of the fourth national survey of traditional Chinese medicine resources].

Using Origin2022Pro, PAST4.09, GraphPad, and ArcGIS, this study analyzed the big data of the fourth national survey of traditional Chinese medicine resources in Jilin province from five dimensions: differences in resource quantity, taxonomic group, family, and genus, regional distribution, and spatiotemporal distribution, aiming to fully elucidate the biodiversity of medicinal plants in Jilin province. The results indicated that 2 241 species of medicinal plants existed in Jilin province, belonging to 881 genera of 243 families, with 20 dominant families and 3 dominant genera.

Mindset profiles of secondary school students: Associations with academic achievement, motivation and school burnout symptoms.

Background: According to Dweck's mindset theory, implicit beliefs (a.k.a.

Structure-Based Design of the Indole-Substituted Triazolopyrimidines as New EED-H3K27me3 Inhibitors for the Treatment of Lymphoma.

Interrupting the embryonic ectoderm development (EED)-H3K27me3 interaction represents a promising strategy to allosterically inhibit polycomb repressive complex 2 (PRC2) for cancer therapy. In this work, we report the structure-based design of new triazolopyrimidine-based EED inhibitors, which structurally feature the electron-rich indole ring at the C8 position. Particularly, ZJH-16 directly binds to EED (HTRF IC = 2.

MeDBA: the Metalloenzyme Data Bank and Analysis platform.

Metalloenzymes are attractive research targets in fields of chemistry, biology, and medicine. Given that metalloenzymes can manifest conservation of metal-coordination and ligand binding modes, the excavation and expansion of metalloenzyme-specific knowledge is of interest in bridging metalloenzyme-related fields. Building on our previous metalloenzyme-ligand association database, MeLAD, we have expanded the scope of metalloenzyme-specific knowledge and services, by forming a versatile platform, termed the Metalloenzyme Data Bank and Analysis (MeDBA).

Does Digital Inclusive Finance Mitigate the Negative Effect of Climate Variation on Rural Residents' Income Growth in China?

Global anthropogenic greenhouse gas emissions have exacerbated climate variation. Climate variation impacts the agricultural production and rural residents' income negatively, further widening the urban-rural income gap and harming the co-benefits. Narrowing the income gap has always been a global concern and an important part of China's rural revitalization strategy.

[Responses of soil moisture at different slope positions to rainfall in dry-hot valley].

The study of short-term dynamics of soil moisture in the dry-hot valley area during rainfall process will help identify soil hydrological function. In this study, we analyzed the short-term responses of soil moisture to rainfall in Huajiang dry-hot valley of Guizhou, using monitoring method to yield high-frequency soil moisture monitoring data of different slope positions. The results showed that, during the whole monitoring period, soil moisture at each layer was at a moderate variation level (15.

Targeting Metalloenzymes by Boron-Containing Metal-Binding Pharmacophores.

Metalloenzymes have critical roles in a wide range of biological processes and are directly involved in many human diseases; hence, they are considered as important targets for therapeutic intervention. The specific characteristics of metal ion(s)-containing active sites make exploitation of metal-binding pharmacophores (MBPs) critical to inhibitor development targeting metalloenzymes. This Perspective focuses on boron-containing MBPs, which display unique binding modes with metalloenzyme active sites, particularly via mimicking native substrates or tetrahedral transition states.

Deep learning in target prediction and drug repositioning: Recent advances and challenges.

Drug repositioning is an attractive strategy for discovering new therapeutic uses for approved or investigational drugs, with potentially shorter development timelines and lower development costs. Various computational methods have been used in drug repositioning, promoting the efficiency and success rates of this approach. Recently, deep learning (DL) has attracted wide attention for its potential in target prediction and drug repositioning.

AncPhore: A versatile tool for anchor pharmacophore steered drug discovery with applications in discovery of new inhibitors targeting metallo--lactamases and indoleamine/tryptophan 2,3-dioxygenases.

We herein describe AncPhore, a versatile tool for drug discovery, which is characterized by pharmacophore feature analysis and anchor pharmacophore (, most important pharmacophore features) steered molecular fitting and virtual screening. Comparative analyses of numerous protein-ligand complexes using AncPhore revealed that anchor pharmacophore features are biologically important, commonly associated with protein conservative characteristics, and have significant contributions to the binding affinity. Performance evaluation of AncPhore showed that it had substantially improved prediction ability on different types of target proteins including metalloenzymes by considering the specific contributions and diversity of anchor pharmacophore features.

Design and enantioselective synthesis of 3-(α-acrylic acid) benzoxaboroles to combat carbapenemase resistance.

Chiral 3-substituted benzoxaboroles were designed as carbapenemase inhibitors and efficiently synthesised via asymmetric Morita-Baylis-Hillman reaction. Some of the benzoxaboroles were potent inhibitors of clinically relevant carbapenemases and restored the activity of meropenem in bacteria harbouring these enzymes. Crystallographic analyses validate the proposed mechanism of binding to carbapenemases, i.

X-ray Structure-Guided Discovery of a Potent, Orally Bioavailable, Dual Human Indoleamine/Tryptophan 2,3-Dioxygenase (hIDO/hTDO) Inhibitor That Shows Activity in a Mouse Model of Parkinson's Disease.

Human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) have been closely linked to the pathogenesis of Parkinson's disease (PD); nevertheless, development of dual hIDO1 and hTDO inhibitors to evaluate their potential efficacy against PD is still lacking. Here, we report biochemical, biophysical, and computational analyses revealing that 1-indazole-4-amines inhibit both hIDO1 and hTDO by a mechanism involving direct coordination with the heme ferrous and ferric states. Crystal structure-guided optimization led to , which manifested IC values of 0.

Discovery of 3-aryl substituted benzoxaboroles as broad-spectrum inhibitors of serine- and metallo-β-lactamases.

The production of β-lactamases represents the main cause of resistance to clinically important β-lactam antibiotics. Boron containing compounds have been demonstrated as promising broad-spectrum β-lactamase inhibitors to combat β-lactam resistance. Here we report a series of 3-aryl substituted benzoxaborole derivatives, which manifested broad-spectrum inhibition to representative serine-β-lactamases (SBLs) and metallo-β-lactamases (MBLs).

Complete chloroplast genome of (ranunculaceae), an important cardiac folk medicinal plant in east asia.

Regel et Radde is an important cardiac folk medicinal plant which endemic to Northeast Asia. We determined the first complete chloroplast genome of using genome skimming approach. The cp genome was 157,032 bp long, with a large single-copy region (LSC) of 86,218 bp and a small single-copy region (SSC) of 18,212 bp separated by a pair of inverted repeats (IRs) of 26,301 bp.

The complete chloroplast genome of a medicinal plant, Medik. (Malvaceae).

Medik. is an annual weed, widely distributed in Asia and Europe. The complete chloroplast genome reported here is 160,446 bp in length, including two inverted repeats (IRs) of 25,064 bp, which are separated by a large single-copy (LSC) and a small single-copy (SSC) of 89,089 and 21,229 bp, respectively.

Bilirubin Can Be Used as a Prognostic Factor for Lung Adenocarcinoma Patients with EGFR Mutations.

Background And Objectives: Non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor () mutation demonstrate only a median progression-free survival (PFS) of 8 to 10 months and undergo EGFR tyrosine kinase inhibitors (EGFR-TKIs) therapy. For decades, bilirubin has been reported to be associated with the onset and prognosis of lung cancer as a prooxidant. This study aimed to investigate the prediction of pretreatment circulating bilirubin for PFS in lung adenocarcinoma (LAC) patients who underwent EGFR-TKIs targeted therapy.

Which Boys and Which Girls Are Falling Behind? Linking Adolescents' Gender Role Profiles to Motivation, Engagement, and Achievement.

Research on gender gaps in school tends to focus on average gender differences in academic outcomes, such as motivation, engagement, and achievement. The current study moved beyond a binary perspective to unpack the variations within gender. It identified distinct groups of adolescents based on their patterns of conformity to different gender norms and compared group differences in motivation, engagement, and achievement.

Evaluation of total phenolic, flavonoid, carbohydrate contents and antioxidant activities of various solvent extracts from root.

We investigated the antioxidant activities of different solvent extracts of root (AAR). The yield of aqueous extract was the highest. The methanol extract had the highest total phenolic content and total flavonoid content.

Complete chloroplast genome of and its implications for the phylogenetic position within (Rosaceae).

is one of the two native cherry species of North America. We determined the first complete chloroplast genome of using genome-skimming approach. The cp genome was 157,953 bp long, with a large single-copy region (LSC) of 86,030 bp and a small single-copy region (SSC) of 19,135 bp separated by a pair of inverted repeats (IRs) of 26,394 bp.

Long noncoding RNA DIO3OS interacts with miR-122 to promote proliferation and invasion of pancreatic cancer cells through upregulating ALDOA.

Background: Long noncoding RNA (lncRNA) has been implicated in numerous tumors, including pancreatic cancer (PC). However, the precise cellular roles and molecular mechanisms of lncRNA DIO3OS on PC development remains to be fully clarified.

Methods: We performed the meta-analysis on PC samples and non-tumor samples retrieved from the TCGA database, and measured the levels of DIO3OS in PC cell lines and a normal pancreatic duct epithelial cell line HPDE6-C7.

Recent progress in nanomaterials for nucleic acid delivery in cancer immunotherapy.

The combination of gene therapy and immunotherapy has the potential to systemically promote anti-tumor effects while reducing adverse reactions. Small interfering RNA (siRNA) has generated great interest in biology, engineering and medicine, especially for cancer treatment due to its ability to knock down genes of interest. Nanomaterials play significant roles in the design of delivery systems of siRNA, and nanomaterial-mediated siRNA delivery in cancer immunotherapy is one of the most important directions for future clinical cancer treatment.

Draft Genome Sequence of Bifidobacterium longum BB-79, a Strain That Produces Acid Exopolysaccharide.

The surface exopolysaccharide of Bifidobacterium spp. was found to be involved in many processes, including bacterial colonization and host immune modulation. Here, we report the draft genome sequence of an exopolysaccharide-producing strain of Bifidobacterium longum, BB-79.

[Study on the live state of Pieris rapaes using near infrared hypserspectral imaging technology].

Near-infrared hypserspectral imaging technology was applied for the discrimination of a variety of life states, the judgment of being alive or death. Discrimination models were built based on spectral data of Pieris rapaes acquired during different life states. The wavelengths from 951.