Chlorambucil-conjugated platinum(IV) prodrugs to treat triple-negative breast cancer in vitro and in vivo.

Modification of platinum (II) into lipophilic platinum (IV) compounds by introducing biologically active molecules were widely employed to develop new platinum-based prodrugs in the past decade. In this paper, two chlorambucil platinum (IV) complexes, CLB-Pt and CLB-Pt-CLB, were synthesized and displayed very potent antiproliferative activity against all the tested cancer cell lines, such as A549, HeLa and MCF-7, especially to treat the well-known refractory triple-negative breast cancer. CLB-Pt-CLB significantly improved cell-killing effect in triple-negative subtype MDA-MB-231 cells, and showed much stronger cytotoxicity than either monotherapy or combination of cisplatin and chlorambucil.

Basonuclin 1 deficiency is a cause of primary ovarian insufficiency.

Primary ovarian insufficiency (POI) leads to infertility and premature menopause in young women. The genetic etiology of this disorder remains unknown in most patients. Using whole exome sequencing of a large Chinese POI pedigree, we identified a heterozygous 5 bp deletion inducing a frameshift in BNC1, which is predicted to result in a non-sense-mediated decay or a truncated BNC1 protein.

CRISPR/Cas9-mediated gene knockout reveals a guardian role of NF-κB/RelA in maintaining the homeostasis of human vascular cells.

Vascular cell functionality is critical to blood vessel homeostasis. Constitutive NF-κB activation in vascular cells results in chronic vascular inflammation, leading to various cardiovascular diseases. However, how NF-κB regulates human blood vessel homeostasis remains largely elusive.

Spontaneous separation of on-surface synthesized tris-helicenes into two-dimensional homochiral domains.

The on-surface Ullmann coupling of 2,3-dibromo[4]helicene molecules is studied on Au(111) and Cu(111) surfaces. Bis-helicene and tris-helicene are identified with scanning tunnelling microscopy and X-ray photoelectron spectroscopy as reaction products. The produced star-shaped tris-helicenes self-assemble on Au(111) spontaneously into large homochiral domains.

TLR4CXCR4 plasma cells drive nephritis development in systemic lupus erythematosus.

Objectives: In patients with systemic lupus erythematosus (SLE), immune tolerance breakdown leads to autoantibody production and immune-complex glomerulonephritis. This study aimed to identify pathogenic plasma cells (PC) in the development of lupus nephritis.

Methods: PC subsets in peripheral blood and renal tissue of patients with SLE and lupus mice were examined by flow cytometry and confocal microscopy, respectively.

Exenatide ameliorates hepatic steatosis and attenuates fat mass and FTO gene expression through PI3K signaling pathway in nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with metabolic syndrome and can lead to life-threatening complications like hepatic carcinoma and cirrhosis. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist antidiabetic drug, has the capacity to overcome insulin resistance and attenuate hepatic steatosis but the specific underlying mechanism is unclear. This study was designed to investigate the underlying molecular mechanisms of exenatide therapy on NAFLD.

Fibrinogen Concentrate in Cardiovascular Surgery: A Meta-analysis of Randomized Controlled Trials.

Background: Postoperative bleeding remains a frequent complication after cardiovascular surgery and may contribute to serious morbidity and mortality. Observational studies have suggested a relationship between low endogenous plasma fibrinogen concentration and increased risk of postoperative blood loss in cardiac surgery. Although the transfusion of fibrinogen concentrate has been increasing, potential benefits and risks associated with perioperative fibrinogen supplementation in cardiovascular surgery are not fully understood.

Selective CO Production by Photoelectrochemical Methane Oxidation on TiO.

The inertness of the C-H bond in CH poses significant challenges to selective CH oxidation, which often proceeds all the way to CO once activated. Selective oxidation of CH to high-value industrial chemicals such as CO or CHOH remains a challenge. Presently, the main methods to activate CH oxidation include thermochemical, electrochemical, and photocatalytic reactions.

The prognostic significance of preoperative neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma receiving hepatectomy: A systematic review and meta-analysis.

Background And Aims: Numerous reports have indicated that preoperative Neutrophil-Lymphocyte ratio (NLR) was correlated with the prognosis of hepatocellular carcinoma who underwent hepatectomy. However, the results still remained controversial. Therefore, the present meta-analysis of 17 studies was performed to evaluate the prognostic value of preoperative NLR in HCC patients.

Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate.

Obesity is characterized by excessive fatty acid conversion to triacylglycerols (TAGs) in adipose tissues. However, how signaling networks sense fatty acids and connect to the stimulation of lipid synthesis remains elusive. Here, we show that homozygous knock-in mice carrying a point mutation at the Ser phosphorylation site of acetyltransferase Tip60 (Tip60 ) display remarkably reduced body fat mass, and Tip60 females fail to nurture pups to adulthood due to severely reduced milk TAGs.

Preoperative screening for illicit drug use in patients undergoing emergency surgery: A prospective observational study.

Knowledge of illicit drug users (IDUs) is important because of the comorbidity related to drug use. In this prospective, observational study, we screened 1007 patients undergoing emergency surgery and found that 75 of them (7.5%) were IDUs The results of preoperative screening showed that the rates of HIV and syphilis infection were significantly higher in IDUs (HIV (+) 2.

MSIQ: JOINT MODELING OF MULTIPLE RNA-SEQ SAMPLES FOR ACCURATE ISOFORM QUANTIFICATION.

Next-generation RNA sequencing (RNA-seq) technology has been widely used to assess full-length RNA isoform abundance in a high-throughput manner. RNA-seq data offer insight into gene expression levels and transcriptome structures, enabling us to better understand the regulation of gene expression and fundamental biological processes. Accurate isoform quantification from RNA-seq data is challenging due to the information loss in sequencing experiments.

Spliceosome Profiling Visualizes Operations of a Dynamic RNP at Nucleotide Resolution.

Tools to understand how the spliceosome functions in vivo have lagged behind advances in the structural biology of the spliceosome. Here, methods are described to globally profile spliceosome-bound pre-mRNA, intermediates, and spliced mRNA at nucleotide resolution. These tools are applied to three yeast species that span 600 million years of evolution.

Full-Length Transcriptome Sequencing and Modular Organization Analysis of the Naringin/Neoeriocitrin-Related Gene Expression Pattern in Drynaria roosii.

Drynaria roosii (Nakaike) is a traditional Chinese medicinal fern, known as 'GuSuiBu'. The effective components, naringin and neoeriocitrin, share a highly similar chemical structure and medicinal function. Our HPLC-tandem mass spectrometry (MS/MS) results showed that the accumulation of naringin/neoeriocitrin depended on specific tissues or ages.

Sources of particulate matter in China: Insights from source apportionment studies published in 1987-2017.

Particulate matter (PM) in the atmosphere has adverse effects on human health, ecosystems, and visibility. It also plays an important role in meteorology and climate change. A good understanding of its sources is essential for effective emission controls to reduce PM and to protect public health.

Hydroa vacciniforme-like cutaneous T-cell lymphoma in a child: A case report.

Rationale: Hydroa vacciniforme (HV)-like T-cell lymphoma is a rare malignancy in childhood associated with Epstein-Barr virus infection.

Patient Concerns: A 6-year old girl presented with complaint of 3-year history of recurrent skin lesions, 3 months of fever accompanied by cough for 8 days.

Diagnoses: Skin biopsy revealed a HV-like lymphoma presentation and positive signals of EBER were detected by in situ hybridization.

Mechanisms in hypertension and target organ damage: Is the role of the thymus key? (Review).

A variety of cells and cytokines have been shown to be involved in the whole process of hypertension. Data from experimental and clinical studies on hypertension have confirmed the key roles of immune cells and inflammation in the process. Dysfunction of the thymus, which modulates the development and maturation of lymphocytes, has been shown to be associated with the severity of hypertension.

Microplastics in freshwater systems: A review on occurrence, environmental effects, and methods for microplastics detection.

The continuous increase in synthetic plastic production and poor management in plastic waste have led to a tremendous increase in the dumping into our aqueous environment. Consequently, microplastics commonly defined as sizes less than 5 mm are produced and stay in both seawater and freshwater environment. The presence of microplastics as a new type of emerging contaminant has become a great issue of concerns from public and government authorities.

CD10-positive mantle cell lymphoma: clinicopathologic and prognostic study of 30 cases.

Mantle cell lymphoma is usually negative for CD10 which is useful in distinguishing MCL from other CD10 + B cell lymphomas. Here we assessed the clinicopathologic features of 30 cases of CD10+ MCL, the largest series to date in the English literature, and compared them with a group of 212 typical MCL cases (CD5+, CD10-negative, CD23-negative, cyclin D1+). The 30 patients with CD10+ MCL included 17 men and 13 women with a median age of 68 years.

Acute myeloid leukemia with t(4;12)(q12;p13): an aggressive disease with frequent involvement of and .

We describe the clinical, morphologic, immunophenotypic and molecular genetic features of 15 cases of acute myeloid leukemia (AML) with t(4;12)(q12;p13). There were 9 men and 6 women, with a median age of 50 years (range, 17-76). Most patients had hypercellular bone marrow with a median blast count of 58% and multilineage dysplasia.

An accurate and robust imputation method scImpute for single-cell RNA-seq data.

The emerging single-cell RNA sequencing (scRNA-seq) technologies enable the investigation of transcriptomic landscapes at the single-cell resolution. ScRNA-seq data analysis is complicated by excess zero counts, the so-called dropouts due to low amounts of mRNA sequenced within individual cells. We introduce scImpute, a statistical method to accurately and robustly impute the dropouts in scRNA-seq data.

Neyman-Pearson classification algorithms and NP receiver operating characteristics.

In many binary classification applications, such as disease diagnosis and spam detection, practitioners commonly face the need to limit type I error (that is, the conditional probability of misclassifying a class 0 observation as class 1) so that it remains below a desired threshold. To address this need, the Neyman-Pearson (NP) classification paradigm is a natural choice; it minimizes type II error (that is, the conditional probability of misclassifying a class 1 observation as class 0) while enforcing an upper bound, α, on the type I error. Despite its century-long history in hypothesis testing, the NP paradigm has not been well recognized and implemented in classification schemes.

Large-scale comparative epigenomics reveals hierarchical regulation of non-CG methylation in .

Genome-wide characterization by next-generation sequencing has greatly improved our understanding of the landscape of epigenetic modifications. Since 2008, whole-genome bisulfite sequencing (WGBS) has become the gold standard for DNA methylation analysis, and a tremendous amount of WGBS data has been generated by the research community. However, the systematic comparison of DNA methylation profiles to identify regulatory mechanisms has yet to be fully explored.

Protein Expression Landscape of Mouse Embryos during Pre-implantation Development.

Pre-implantation embryo development is an intricate and precisely regulated process orchestrated by maternally inherited proteins and newly synthesized proteins following zygotic genome activation. Although genomic and transcriptomic studies have enriched our understanding of the genetic programs underlying this process, the protein expression landscape remains unexplored. Using quantitative mass spectrometry, we identified nearly 5,000 proteins from 8,000 mouse embryos of each stage (zygote, 2-cell, 4-cell, 8-cell, morula, and blastocyst).

Liver-specific deficiency of unc-51 like kinase 1 and 2 protects mice from acetaminophen-induced liver injury.

Unlabelled: unc-51-like autophagy activating kinase 1 and 2 (Ulk1/2) regulate autophagy initiation under various stress conditions. However, the physiological functions of these Ser/Thr kinases are not well characterized. Here, we show that mice with liver-specific double knockout (LDKO) of Ulk1 and Ulk2 (Ulk1/2 LDKO) are viable, but exhibit overt hepatomegaly phenotype.