Synthesis, Structural Modification, and Antismall Cell Lung Cancer Activity of 3-Arylisoquinolines with Dual Inhibitory Activity on Topoisomerase I and II.

To overcome the compensatory effect between Topo I and II, one of the reasons accounting for the resistance of SCLC patients, we are pioneering the use of 3-arylisoquinolines to develop dual inhibitors of Topo I/II for the management of SCLC. A total of 46 new compounds were synthesized. Compounds (IC = 1.

Prevalence of drug resistance mutations in low-level viremia patients under antiretroviral therapy in Southwestern China: a cross-sectional study.

Objectives: This study aimed to evaluate the prevalence and characteristics of drug resistance mutations (DRMs) in patients with low-level viremia (LLV) in Southwestern China, as it has become a growing challenge in AIDS clinical practice.

Methods: This cross-sectional study was performed in Yunnan Province, Southwestern China. LLV was defined as 50-999 copies/mL of plasma viral load with antiretroviral therapy (ART) for at least 6 months.

Rolling-Translated circRUNX2.2 Promotes Lymphoma Cell Proliferation and Cycle Transition in Marek's Disease Model.

Marek's disease (MD), an immunosuppressive disease induced by the Marek's disease virus (MDV), is regarded as an ideal model for lymphoma research to elucidate oncogenic and anti-oncogene genes. Using this model, we found that circRUNX2.2, derived from exon 6 of RUNX2, was significantly upregulated in MDV-infected tumorous spleens.

Trajectories of CD4 T-cell count, CD8 T-cell count, and CD4/CD8 ratio in patients with HIV and long-term virological suppression based on Yunnan HIV cohort.

Objective: Our objective was to evaluate the trajectory of immunology in patients with HIV with different baseline CD4 T-cell count strata after antiretroviral therapy (ART) under long-term viral suppression.

Methods: This was a sub-analysis focused on patients with virological suppression for at least 5 years after ART. Data were obtained from the Yunnan HIV cohort in China.

Endothelin-3 Suppresses Luteinizing Hormone Receptor Expression by Regulating the cAMP-PKA Pathway in Hen Granulosa Cells.

Previous research identified the expression of in granulosa cells of preovulatory follicles in chickens. Notably, the expression level of in Silky Fowl with low egg-laying performance was significantly higher than that in high-yield laying breed White Leghorn. Given the crucial role of granulosa cells in follicular development and maturation, it is very important to study the effect of on the biological function of granular cells.

Combined transcriptome and metabolome analysis reveals breed-specific regulatory mechanisms in Dorper and Tan sheep.

Background: Dorper and Tan sheep are renowned for their rapid growth and exceptional meat quality, respectively. Previous research has provided evidence of the impact of gut microbiota on breed characteristics. The precise correlation between the gastrointestinal tract and peripheral organs in each breed is still unclear.

Non‑synchronous bilateral metastatic ovarian cancer originating from small bowel adenocarcinoma with multidisciplinary treatment: A case report.

Primary small bowel adenocarcinoma (SBA) is a rare gastrointestinal cancer with a low incidence of ovarian metastasis. Differential diagnosis of metastatic and primary ovarian cancer is often challenging. The present study reported the case of a 45-year-old woman with jejunal adenocarcinoma who presented with right ovarian, left ovarian, abdominopelvic implant and local recurrent bowel wall metastases successively after primary tumor resection.

Regulates the PTPRF/β-Catenin Axis in Hair Follicle Development: Insights into the Pathogenic Mechanism of Alopecia Areata.

Alopecia areata is an autoimmune disease characterized by the immune system attacking self hair follicles, mainly in the scalp. There is no complete cure, and the pathogenesis is still not fully understood. Here, sequencing of skin tissues collected from 1-month-old coarse- and fine-wool lambs identified as the only small RNA significantly overexpressed in the fine-wool group, suggesting a role in hair follicle development.

Techno-economic analysis of municipal solid waste treatment for poly-generation system.

Municipal solid waste (MSW) is characterized by complex composition, low calorific value and high moisture content. Using a single treatment technology is costly and difficult to achieve optimal results. A poly-generation system that integrates classified waste pyrolysis and incineration is proposed, producing fuel, electricity, and steam.

Effect of melatonin on cryopreservation of Beijing you chicken (gallus gallus) spermatozoa.

Beijing You Chicken, a valuable local chicken breed from Beijing, China, was once listed as an endangered breed. From the point of view of conservation, the preservation of this breed is an important task for the local researchers. Semen cryopreservation is a popular method to maintain valuable species.

Imprinted Dlk1-Gtl2 cluster miRNAs are potential epigenetic regulators of lamb fur quality.

Background: Tan and Hu sheep are well-known local breeds in China, producing lamb fur with unique ornamental and practical values highly appreciated by consumers worldwide. Fur quality is optimal at one month of age and gradually declines with time. Despite active research on its genetic mechanism using transcriptomic and whole genome bisulfite sequencing analysis, the main effective gene locus has not been found, and its regulatory mechanism is still unclear, which limits the breeding and improvement of fur traits.

Epigenetic mechanism of Gtl2-miRNAs causes the primitive sheep characteristics found in purebred Merino sheep.

Background: It is not uncommon for some individuals to retain certain primitive characteristics even after domestication or long-term intensive selection. Wild ancestors or original varieties of animals typically possess strong adaptability to environmental preservation, a trait that is often lacking in highly artificially selected populations. In the case of the Merino population, a world-renowned fine wool sheep breed, a phenotype with primitive coarse wool characteristic has re-emerged.

Cancer-Associated Fibroblast-Like Tumor Cells Remodel the Ewing Sarcoma Tumor Microenvironment.

Purpose: Despite limited genetic and histologic heterogeneity, Ewing sarcoma (EwS) tumor cells are transcriptionally heterogeneous and display varying degrees of mesenchymal lineage specification in vitro. In this study, we investigated if and how transcriptional heterogeneity of EwS cells contributes to heterogeneity of tumor phenotypes in vivo.

Experimental Design: Single-cell proteogenomic-sequencing of EwS cell lines was performed and integrated with patient tumor transcriptomic data.

Carcinoma-associated fibroblast-like tumor cells remodel the Ewing sarcoma tumor microenvironment.

Tumor heterogeneity is a major driver of cancer progression. In epithelial-derived malignancies, carcinoma-associated fibroblasts (CAFs) contribute to tumor heterogeneity by depositing extracellular matrix (ECM) proteins that dynamically remodel the tumor microenvironment (TME). Ewing sarcomas (EwS) are histologically monomorphous, mesenchyme-derived tumors that are devoid of CAFs.

Biogenesis aberration: One of the mechanisms of thrombocytopenia in COVID-19.

The pathogenesis of COVID-19, including thrombocytopenia, has not been fully clarified. The lungs are a major organ of platelet production and thrombocytopenia induced by severe COVID-19 was proposed. the change of platelet level was analysed with clinical parameters in 95 hospitalized COVID-19 patients in Wuhan Third Hospital.

Skin-specific transgenic overexpression of ovine β-catenin in mice.

β-catenin is a conserved molecule that plays an important role in hair follicle development. In this study, we generated skin-specific overexpression of ovine β-catenin in transgenic mice by pronuclear microinjection. Results of polymerase chain reaction (PCR) testing and Southern blot showed that the ovine β-catenin gene was successfully transferred into mice, and the exogenous β-catenin gene was passed down from the first to sixth generations.

Contribution of gut microbiomes and their metabolomes to the performance of Dorper and Tan sheep.

Background: Livestock is an excellent source of high nutritional value protein for humans; breeding livestock is focused on improving meat productivity and quality. Dorper sheep is a distinguished breed with an excellent growth performance, while Tan sheep is a Chinese local breed famous for its delicious meat. Several studies have demonstrated that the composition of gut microbiome and metabolome modulate host phenotype.

Near complete remission of a locally advanced giant melanoma of the vulva following hypo-fractionated radiotherapy and immune checkpoint inhibitors: A case report.

Melanoma is known to be insensitive to radiotherapy; however, the present study reports the case of a patient with vulvar malignant melanoma in which near complete remission of the target area was observed after implementing immune checkpoint inhibitors (ICIs) and hypo-fractionated radiotherapy (HFRT). The patient was treated with an intensity-modulated radiation therapy technique that delivered a hypo-fractionated dose of 3,000 cGy in six fractions. After 3 days, the patient underwent immunotherapy with two cycles of 240 mg triprizumab every 2 weeks.

m6A Methylation Analysis Reveals Networks and Key Genes Underlying the Coarse and Fine Wool Traits in a Full-sib Merino Family.

In our study, a set of lambs with coarse wool type all over their bodies were discovered within a full-sib family during an embryo transfer experiment of merino fine wool sheep. The difference between coarse and fine wool traits were studied from the perspective of RNA modification-N6-methyladenosine. A total of 31,153 peaks were collected, including 15,968 peaks in coarse skin samples and 15,185 peaks in fine skin samples.

Cecum microbiome and metabolism characteristics of Silky Fowl and White Leghorn chicken in late laying stages.

Cecal microflora plays a key role in the production performance and immune function of chickens. White Leghorn (WL) is a well-known commercial layer line chicken with high egg production rate. In contrast, Silky Fowl (SF), a Chinese native chicken variety, has a low egg production rate, but good immune performance.

C-H Alkenylation of Indoles through a Dual 1,3-Sulfur Migration Process.

Methods for the modification of indole derivatives are powerful techniques in organic, medicinal, and biomolecular chemistry. Here, we report a protocol for the C-H alkenylation of N-H indoles with β-chlorovinyl dithianes to furnish alkenyl indoles through dual 1,3-sulfur rearrangements. This alkenylation protocol could selectively prepare a variety of vinyl indoles in moderate to high yields with excellent functional group tolerance.