Discovery of N-Benzylpiperidinol derivatives as USP7 inhibitors against Hematology.

USP7 has been recognized as a potential target for the treatment of hematologic malignancies by stabilizing multiple cancer-relevant proteins. Nevertheless, drug-like USP7 inhibitors are still lacking. Herein, compound J21 (USP7 IC: 41.

Isolation of the Initial Bovine Alphaherpesvirus 1 Isolate from Yanbian, China.

Bovine infectious rhinotracheitis (IBR), caused by bovine alphaherpesvirus 1 (BoAHV1), poses significant challenges to the global cattle industry due to its high contagiousness and economic impact. In our study, we successfully isolated a BoAHV1 strain from suspected infected bovine nasal mucus samples in Yanji city, revealing genetic similarities with strains from Sichuan, Egypt, and the USA, while strains from Xinjiang, Beijing, Hebei, and Inner Mongolia showed more distant associations, indicating potential cross-border transmission. Additionally, our investigation of BoAHV1 infection dynamics within host cells revealed early upregulation of , which is critical for sustained infection, while the expression of and showed variations compared to previous studies.

Discovery of a Highly Potent, Selective and Efficacious USP7 Degrader for the Treatment of Acute Lymphoblastic Leukemia.

USP7 is an attractive therapeutic target for cancers, especially for acute lymphoblastic leukemia (ALL) with wild-type p53. Herein, we report the discovery of as a highly potent, selective and efficacious USP7 proteolysis-targeting chimera degrader. achieves DC values of 0.

Chloroquine enhances the efficacy of chemotherapy drugs against acute myeloid leukemia by inactivating the autophagy pathway.

Current therapy for acute myeloid leukemia (AML) is largely hindered by the development of drug resistance of commonly used chemotherapy drugs, including cytarabine, daunorubicin, and idarubicin. In this study, we investigated the molecular mechanisms underlying the chemotherapy drug resistance and potential strategy to improve the efficacy of these drugs against AML. By analyzing data from ex vivo drug-response and multi-omics profiling public data for AML, we identified autophagy activation as a potential target in chemotherapy-resistant patients.

Targeting C/EBPα overcomes primary resistance and improves the efficacy of FLT3 inhibitors in acute myeloid leukaemia.

The outcomes of FLT3-ITD acute myeloid leukaemia (AML) have been improved since the approval of FLT3 inhibitors (FLT3i). However, approximately 30-50% of patients exhibit primary resistance (PR) to FLT3i with poorly defined mechanisms, posing a pressing clinical unmet need. Here, we identify C/EBPα activation as a top PR feature by analyzing data from primary AML patient samples in Vizome.

Isolation of feline panleukopenia virus from Yanji of China and molecular epidemiology from 2021 to 2022.

Background: Feline panleukopenia virus (FPV) is a widespread and highly infectious pathogen in cats with a high mortality rate. Although Yanji has a developed cat breeding industry, the variation of FPV locally is still unclear.

Objectives: This study aimed to isolate and investigate the epidemiology of FPV in Yanji between 2021 and 2022.

Design, synthesis, and biological evaluation of Wee1 kinase degraders.

Proteolysis targeting chimera (PROTAC) technology has received widespread attention in recent years as a promising strategy for drug development. Herein, we report a series of novel Wee1 degraders, which were designed and synthesized based on PROTAC technology by linking AZD1775 with CRBN ligands through linkers of different lengths and types. All degraders could effectively and completely degrade cellular Wee1 protein in MV-4-11 cell line at IC concentrations.

Development and Evaluation of NanoPCR for the Detection of Goose Parvovirus.

Gosling plague (GP) is an acute and hemorrhagic infectious disease caused by goose parvovirus (GPV). The goose industry suffers significant economic losses as a result of GP, which is found to be widespread worldwide, with high rates of morbidity and mortality. Our group developed a novel technique for detecting GPV nanoparticle-assisted polymerase chain reaction (nanoPCR) and the characterization of its specificity and sensitivity.

Molecular epidemiology of canine parvovirus 2 from 2014, 2019, and 2021 shows CPV2 circulating and CPV2c increasing in Yanbian, China.

Canine parvovirus 2 (CPV2) causes one of the most serious canine viral infections, with high mortality in young dogs. In 2014, 2019, and 2021, we determined genetic sequences of CPV2 strains obtained from 39 fecal samples collected from the Yanbian Korean Autonomous Prefecture in the Jilin Province of China. Sequence alignments were performed using the major capsid protein () gene; protein sequences of these samples had high nucleotide (>97.

Discovery of a Potent and Selective Degrader for USP7.

The tumor suppressor p53 is the most frequently mutated gene in human cancer and more than half of cancers contain p53 mutations. The development of novel and effective therapeutic strategies for p53 mutant cancer therapy is a big challenge and highly desirable. Ubiquitin-specific protease 7 (USP7), also known as HAUSP, is a deubiquitinating enzyme and proposed to stabilize the oncogenic E3 ubiquitin ligase MDM2 that promotes the proteosomal degradation of p53.

Comparative studies of senescence-related enzymes in the cotyledon of chlorophyll b-deficient mutant and its wild type oilseed rape during senescence.

The change patterns of senescence-related enzymes during cotyledon senescence were studied in a chlorophyll (Chl) b-deficient mutant type (MT, Cr3529) and its wild type (WT) of Brassica napus L. seedlings. The fresh weight on the basis of cotyledon number initially increased till 20 days after planting (DAP) and then kept relative constant.