Synthesis and biological evaluation of novel withangulatin A derivatives as potential anticancer agents.

Novel withangulatin A (WA) derivatives were synthesized and evaluated for antiproliferative activity against four human cancer cell lines (U2OS, MDA-MB-231, HepG2, and A549). Among these derivatives, 10 exhibited the most potent antiproliferative activity, with an IC value of 74.0 nM against the human breast cancer cell line MDA-MB-231 and potency that was 70-fold that of WA (IC = 5.

Comprehensive landscape of epigenetic-dysregulated lncRNAs reveals a profound role of enhancers in carcinogenesis in BC subtypes.

Aberrant expression of long non-coding RNAs (lncRNA) is associated with altered DNA methylation and histone modifications during carcinogenesis. However, identifying epigenetically dysregulated lncRNAs and characterizing their functional mechanisms in different cancer subtypes are still major challenges for cancer studies. In this study, we systematically analyzed the epigenetic alterations of lncRNAs at important regulatory elements in three breast cancer subtypes.

Albumin-to-alkaline phosphatase ratio: A novel prognostic index for patients with driver mutation-negative advanced non-small cell lung cancer.

Introduction: Albumin-to-Alkaline Phosphatase Ratio (AAPR), a novel developed prognostic index for cancers. Chemotherapy was the only method for driver mutation-negative advanced non-small cell lung cancer (DANSCLC).

Objectives: To evaluate the clinical significance of AAPR in these patients.

Target separation and antitumor metastasis activity of sesquiterpene-based lysine-specific demethylase 1 inhibitors from zedoary turmeric oil.

Lysine-specific histone demethylase 1 (LSD1) was the first histone demethylase identified in epigenetics and has recently emerged as an attractive therapeutic target for treating tumors. To date, almost all reported LSD1 inhibitors have been chemosynthesized; however, natural products possess pharmacological and biological activity and can be sources for drug development. Here, we established a target separation countercurrent chromatography technique to isolate LSD1 inhibitors from zedoary turmeric oil.

New dimeric phthalides from the rhizomes of Ligusticum sinense Oliv.

Two new phthalide dimers (1 and 2) were obtained from the rhizomes of Ligusticum sinense Oliv., along with three known dimeric phthalides (3-5). Their structures were determined with the aid of the spectroscopic data, and their absolute configurations were elucidated based on the comparison of calculated and experimental electronic circular dichroism (ECD) spectra.

[A Case Report of Primary Pulmonary NUT Carcinoma and Literature Review].

NUT carcinoma is a rare, high lethal cancer which feature as the rearrangement of the nuclear protein in testis (NUT) gene on chromosome 15q14, and its pathogenesis and treatment is not yet clear, the prognosis is poor. Due to NUT carcinoma often occurred on the middle position of the body, such as eyes, nose and palate, mediastinum, so it is also called NUT midline carcinoma (NMC). In this case, we report a 70 years old man who was diagnosed as primary pulmonary NUT carcinoma in the Department of Thoracic Oncology, West China Hospital of Sichuan University.

Silver-Catalyzed Radical Cascade Sulfonation/Cycloaddition for the Construction of Multifunctional Succimides Containing Separable /-Isomers.

A silver-catalyzed cascade cycloaddition of -1,6-enynes, affording multifunctional succimide frameworks initiated by the arylsulfonyl radical addition, has been developed. This process shows mild reaction conditions, excellent structural selectivity, and broad functional group tolerance. In addition, the /-isomers can be easily separated, which provides an efficient method for obtaining pure /-configuration products.

Semaphorin 4A restricts tumor progression by inhibiting angiogenesis of oral squamous cell carcinoma cells.

Objective: To investigate the effects of Semaphorin 4A (Sema4A) on the angiogenesis, migration and invasion of oral squamous cell carcinoma (OSCC) cells.

Methods: Sema4A expression in OSCC patients was detected by Immunohistochemistry, and its relationship with clinicopathological features and prognosis of patients was analyzed. The mRNA and protein expression of Sema4A in primary human oral keratinocytes (HOKs) and OSCC cells (SCC-25, HSC-3, CAL-27) were determined by Western blotting and qRT-PCR.

A CRISPR/Cas9-Mediated, Homology-Independent Tool Developed for Targeted Genome Integration in Yarrowia lipolytica.

has been extensively used to produce essential chemicals and enzymes. As in most other eukaryotes, nonhomologous end joining (NHEJ) is the major repair pathway for DNA double-strand breaks in Although numerous studies have attempted to achieve targeted genome integration through homologous recombination (HR), this process requires the construction of homologous arms, which is time-consuming. This study aimed to develop a homology-independent and CRISPR/Cas9-mediated targeted genome integration tool in Through optimization of the cleavage efficiency of Cas9, targeted integration of a fragment was achieved with 12.

Maternal antibiotic use during pregnancy and asthma in children: population-based cohort study and sibling design.

Antibiotic use during pregnancy may affect asthma risk in offspring. However, epidemiological studies yielded conflicting findings, with an observed association possibly confounded by shared familial factors. We sought to assess the association between maternal antibiotic use during pregnancy and childhood asthma in the offspring, by accounting for time-stable familial factors.

Hybridization with TiCT MXene: An Effective Approach to Boost the Hydrothermal Stability and Catalytic Performance of Metal-Organic Frameworks.

Metal-organic frameworks (MOFs) have attracted increasing research enthusiasm owing to their tunable functionality, diverse structure characteristics, and large surface area. However, poor hydrothermal stability restricts the utilization of some MOFs in practical applications. Our work aims at improving the hydrothermal stability of a representative MOF, namely, HKUST-1, by incorporating a two-dimensional material TiCT MXene for the first time.

Separation of the Sound Power Spectrum of Multiple Sources by Three-Dimensional Sound Intensity Decomposition.

The identification and separation of sources are the prerequisite of industrial noise control. Industrial machinery usually contains multiple noise sources sharing same-frequency components. There are usually multiple noise sources in mechanical equipment, and there are few effective methods available to separate the spectrum intensity of each sound source.

Rapid Increase in the IS-Mediated Gene in Isolates with IncP and IncX4 Plasmids and Co-Existing and Genes in a Swine Farm.

This paper aimed to investigate the molecular epidemiological features of the gene in isolates in a typical swine farm during 2014-2017. A total of 617 isolates were screened for the gene using PCR amplification. A susceptibility test, pulsed-field gel electrophoresis (PFGE), S1-PFGE, southern blotting hybridization, and the genetic context of the gene were all used for analyzing all -positive isolates.

Fasudil reduces β-amyloid levels and neuronal apoptosis in APP/PS1 transgenic mice via inhibition of the Nogo-A/NgR/RhoA signaling axis.

Recent studies have shown that Nogo-A and the Nogo-A receptor affect β-amyloid metabolism and the downstream Rho GTP enzyme signaling pathway, which may affect the levels of β-amyloid and tau. Nogo-A may play a key role in the pathogenesis of Alzheimer's disease. However, the underlying molecular mechanisms of Fasudil treatment in Alzheimer's disease are not yet clear.

A risk score based on pediatric sequential organ failure assessment predicts 90-day mortality in children with Klebsiella pneumoniae bloodstream infection.

Background: Klebsiella pneumoniae bloodstream infection (Kp-BSI) is a serious threat to pediatric patients. The objective of this study was to explore the risk factors, validate the prediction efficiency of pediatric Sequential Organ Failure Assessment (SOFA) and establish better early predictors of mortality in pediatric patients with Kp-BSI.

Methods: All children diagnosed with Kp-BSI were included in this retrospective cohort study from January 2009 to June 2019.

MicroRNA as an early diagnostic biomarker for contrast-induced acute kidney injury.

Contrast-induced acute kidney injury (CI-AKI) is a common clinical complication and an important cause of increased mortality, prolonged hospitalization, and increased medical costs. For taking effective interventions in CI-AKI, early diagnosis and active prevention are of key importance. Currently, early CI-AKI detection depends on serum creatinine (Scr) levels, which lags behind the actual time of renal injury and seriously affects early diagnosis and interventions.

Phosphorylation of the Retinal Ribbon Synapse Specific t-SNARE Protein Syntaxin3B Is Regulated by Light via a Ca-Dependent Pathway.

Neurotransmitter release at retinal ribbon-style synapses utilizes a specialized t-SNARE protein called syntaxin3B (STX3B). In contrast to other syntaxins, STX3 proteins can be phosphorylated at T14 by Cacalmodulin-dependent protein kinase II (CaMKII). This modification has the potential to modulate SNARE complex formation required for neurotransmitter release in an activity-dependent manner.

Ring trial of 2nd generation RT-QuIC diagnostic tests for sporadic CJD.

Objective: Real-time quaking-induced conversion (RT-QuIC) assays detect prion-seeding activity in a variety of human biospecimens, including cerebrospinal fluid and olfactory mucosa swabs. The assay has shown high diagnostic accuracy in patients with prion disorders. Recently, advances in these tests have led to markedly improved diagnostic sensitivity and reduced assay times.

Discovery and optimization of withangulatin A derivatives as novel glutaminase 1 inhibitors for the treatment of triple-negative breast cancer.

To develop novel GLS1 inhibitors as effective therapeutic agents for triple-negative breast cancer (TNBC), 25 derivatives were synthesized from the natural inhibitor withangulatin A (IC = 18.2 μM). Bioassay optimization identified a novel and selective GLS1 inhibitor 7 (IC = 1.

Population pharmacokinetics of the anti-PD-1 antibody camrelizumab in patients with multiple tumor types and model-informed dosing strategy.

Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been approved for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma, nasopharyngeal cancer and non-small cell lung cancer. The aim of this study was to perform a population pharmacokinetic (PK) analysis of camrelizumab to quantify the impact of patient characteristics and to investigate the appropriateness of a flat dose in the dosing regimen. A total of 3092 camrelizumab concentrations from 133 patients in four clinical trials with advanced melanoma, relapsed or refractory classical Hodgkin lymphoma and other solid tumor types were analyzed using nonlinear mixed effects modeling.

Reconstruction of Periodic Band Limited Signals from Non-Uniform Samples with Sub-Nyquist Sampling Rate.

Important state parameters, such as torque and angle obtained from the servo control and drive system, can reflect the operating condition of the equipment. However, there are two problems with the information obtained through the network from the control and drive system: the low sampling rate, which does not meet the sampling theorem and the nonuniformity of the sampling points. By combing equivalent sampling and nonuniform signal reconstruction theory, this paper proposes a reconstruction method for signal obtained from servo system in periodic reciprocating motion.

A proteomic analysis of grain yield-related traits in wheat.

Grain yield, which is mainly contributed by tillering capacity as well as kernel number and weight, is the most important trait to plant breeders and agronomists. Label-free quantitative proteomics was used to analyse yield-contributing organs in wheat. These were leaf sample, tiller initiation, spike initiation, ovary and three successive kernel development stages at 5, 10 and 15 days after anthesis (DAA).

Psychometric properties of the Chinese version of the recovery locus of control (RLOC) Scale among patients with myocardial infarction.

Aim: To translate the RLOC Scale into Chinese and test its psychometric properties in the Chinese patients with myocardial infarction (MI).

Design: A cross-sectional design was used.

Methods: A convenience sample of 233 patients with MI who have undergone percutaneous coronary intervention and were ready for discharge were recruited in a level A tertiary hospital of Shandong Province from January 2019 to April 2019.

Cytotoxic Germacranolides from the Whole Plant of .

Eight new germacranolides, minusolides A-H (-), along with two known analogues, and , were isolated from the whole plant of . Their structures were elucidated by spectroscopic analysis. Compounds and , and and are two pairs of rare epimers with opposite configurations at C-2 of the 2-methylbutyryloxy group.

MiR-184 directly targets Wnt3 in cardiac mesoderm differentiation of embryonic stem cells.

Embryonic stem (ES) cells have the property of self-renewal and multi-directional differentiation, and provide an ideal model for studying early embryo development in vitro. Wnt3, as Wnt family member 3, plays a vital role during ES cell differentiation. However, the exact regulatory mechanism of Wnt3 remains to be elucidated.