Discovery of novel dihydropyrrolidone-thiadiazole compound crosstalk between the YycG/F two-component regulatory pathway and cell membrane homeostasis to combat methicillin-resistant Staphylococcus aureus.

The rapid emergence and spread of multidrug-resistant (MDR) Gram-positive pathogens present a significant challenge to global healthcare. Methicillin-resistant Staphylococcus aureus (MRSA) is a particular concern because of its high resistance to most antibiotics. Based on our previously reported chemical structure of compound 62, a series of novel derivatives were synthesized and evaluated for their antibacterial activities.

Effect of the p-Estrogen Receptor at Serine on Its Function and Breast Growth.

Background: Estrogen receptor (ER) signaling plays an important role in the development and functional differentiation of the breast and participates in the process of breast cancer. Activated ER can affect various aspects of the cell's behavior, including proliferation, via modulating the expression of many downstream target genes. Phosphorylation is one of the activation pathways of ER.

Effect of Heat Treatment Parameters on the Modification of Nano Residual Austenite of Low-Carbon Medium-Chromium Steel.

The ball milling lining board operates in a harsh environment, and the current materials fail to meet the requirements for large-sized boards due to the lack of synergistic properties between impact toughness and wear resistance. To address this issue, a low-carbon medium-chromium steel with martensite and nano residual austenite phases have been designed for future use. However, the residual austenite network could decrease the properties.

Electrochemical bromocyclization enables 3,5-diversification of heterocyclic indolines.

Electrophilic bromocyclization reactions are widely used as key steps in the synthesis of diverse functionalized tetrahydrofuroindolines and hexahydropyrroloindolines. However, the direct dibromination variants of these reactions for the synthesis of 3,5-dibromoindolines remain undeveloped. Here, we report a protonic-acid-promoted electrooxidative protocol for the dearomative C3,C5-dibromocyclizations of tryptophol and tryptamine derivatives.

Rare ectopic thyroid tissue as multiple bilateral pulmonary nodules: a case report and literature review.

Background: The prevalence of ectopic thyroid tissue is 1 in every 100,000 to 300,000 persons in the general population, and ectopic thyroid tissue in the bilateral lung lobes is even rarer. Due to its rarity, there is no definitive or standard guidance on the diagnosis and treatment of ectopic thyroid tissue presenting as multiple bilateral pulmonary nodules.

Case Presentation: A 56-year-old woman presented with multiple bilateral pulmonary nodules, and the patient had a history of hyperthyroidism but had no symptoms of ectopic thyroid tissue.

Copper-Catalyzed Aerobic Selective Oxidation of Tetrahydrocarbolines.

We report a safe and convenient open-flask copper-catalyzed selective oxidation/functionalization methodology for tetrahydrocarbolines and tetrahydro-β-carbolines that employs atmospheric O as the terminal oxidant. The system is applicable to oxidative rearrangement of tetrahydro-β-carbolines, tetrahydrocarboline oxidation to α-alkoxy carbazoles and spirooxindoles, and Witkop oxidation. Mechanistic experiments indicated that a single-electron oxidation process is responsible for the tunable selectivity control.

Copper-Catalyzed Cyclization/Dimerization of Tryptamines with O/Air as the Sole Oxidant: Direct Access to Complex Bispyrrolidino[2,3-]indoline.

The first transition metal catalytic one-step synthesis of the 3a, 3a'-bispyrrolidino [2,3-] indoline scaffold via tandem cyclization/dimerization of tryptamines has been realized with the environmentally friendly O/air as the sole oxidant. Different from the traditional direct oxidation of indole "N-H" group by excess amount of metal salts, a copper-catalyzed oxidative cyclization reaction is developed for the formation of the radical pyrrolidinoindoline intermediate in the current strategy. The robustness and practicality of this methodology is demonstrated by the step-economic, divergent total synthesis of natural products (±)-folicanthine and -folicanthine.

Life history tradeoffs in humans: increased life expectancy with sperm count reduction.

Although not without controversy, as a general trend, the human sperm count is declining world-wide. One major reason for such a decline is an increase in the human life-span.  According to the life history tradeoff theory, fecundity is inversely related to the lifespan; the longer the lifespan, the lower the fecundity.

Combined use of alcohol in conventional chemical-induced mouse liver cancer model improves the simulation of clinical characteristics of human hepatocellular carcinoma.

Liver cancer is the one of most common types of cancer and the 2nd cause of cancer-associated mortalities worldwide. Establishing appropriate animal models of liver cancer is essential for basic and translational studies. The present study evaluated the effects of the combined use of alcohol with a conventional chemical-induced mouse liver cancer model.

Metastasis-Associated Protein 1 Deficiency Results in Compromised Pulmonary Alveolar Capillary Angiogenesis in Mice.

BACKGROUND The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved. MATERIAL AND METHODS The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry.

Life history tradeoffs of pathogens and the treatment principle of antibiogenesis.

There are no eternal individual lives so life continues by relaying with reproduction. Consequently, lifespan and fecundity are two essential genetic traits of life. The life history tradeoffs theory holds that there is an inverse relationship between lifespan and fecundity.

Differential distribution of immune cells in breast invasive carcinoma vs. breast carcinoma and its significance in interpretation of immune surveillance.

Immune surveillance is a highly controversial subject in both the field of immunology and cancer biology. On one hand, in spite of extensive studies, there is no cancer specific antigens identified. Yet, the organisms do exert immune response to tumors.

Antibodies against H1N1 influenza virus cross-react with α-cells of pancreatic islets.

Epidemiological studies have documented that the incidence of human type 1 diabetes was significantly increased after H1N1 epidemic. However, a direct link between human type 1 diabetes and virus infection remains elusive. We generated 84 clones of murine monoclonal antibodies against the H1N1, and carried out immunohistochemistry in normal human tissue microarray.

Epithelial-mesenchymal transition as strategic microenvironment mimicry for cancer cell survival and immune escape?

Epithelial-mesenchymal transition (EMT) is the phenotypic transition of epithelial cells to mesenchymal cells characterized by loss of epithelial markers, loss of intercellular adherence and acquirement of mesenchymal cell markers and increased locomotive ability. EMT is widely considered to be a gene regulated process necessary for cancer metastasis. Yet it is a highly controversial issue.

Structure, expression and functions of MTA genes.

Metastatic associated proteins (MTA) are integrators of upstream regulatory signals with the ability to act as master coregulators for modifying gene transcriptional activity. The MTA family includes three genes and multiple alternatively spliced variants. The MTA proteins neither have their own enzymatic activity nor have been shown to directly interact with DNA.

Reasons for cancer metastasis: A holistic perspective.

Over several years, scientists investigating cancer have focused their efforts on elucidating the mechanisms underlying cancer metastasis, with the aim of finding a way to inhibit this process. These mechanisms, however, only explain the process of cancer metastasis, but do not explain why cancer would metastasize in the first place. Cancer metastasizes due to several factors, namely attack by the immune system, lack of oxygen and necessary nutrients, large amounts of lactic acid produced by glycolysis and increased cell death.

FoxO3α-mediated autophagy contributes to apoptosis in cardiac microvascular endothelial cells under hypoxia.

Hypoxic injury of cardiac microvascular endothelial cells (CMECs) is an important pathophysiological event in myocardial infarction, whereas, the underlying mechanism is still poorly understood. Autophagy, a highly conserved process of cellular degradation, is required for normal cardiac function and also has been implicated in various cardiovascular diseases. Here we investigated the potential role of autophagy in CMEC dysfunction under hypoxia.

MTA1--a stress response protein: a master regulator of gene expression and cancer cell behavior.

Gene mutation's role in initiating carcinogenesis has been controversial, but it is consensually accepted that both carcinogenesis and cancer metastasis are gene-regulated processes. MTA1, a metastasis-associated protein, has been extensively researched, especially regarding its role in cancer metastasis. In this review, I try to elucidate MTA1's role in both carcinogenesis and metastasis from a different angle.

EZH2 mutations in follicular lymphoma from different ethnic groups and associated gene expression alterations.

Purpose: Gain-of-function mutations of enhancer of Zeste homolog 2 (EZH2) occur frequently in diffuse large B-cell lymphomas and in follicular lymphomas. However, the frequency of EZH2 mutation in Chinese follicular lymphomas and the potential targets affected by this mutation are unknown.

Experimental Design: We determined EZH2 codon 641 mutations in Chinese follicular lymphomas (n = 124) and compared them with Western follicular lymphomas (n = 70) using a sensitive pyrosequencing assay.

Resistance to apoptosis should not be taken as a hallmark of cancer.

In the research community, resistance to apoptosis is often considered a hallmark of cancer. However, pathologists who diagnose cancer via microscope often see the opposite. Indeed, increased apoptosis and mitosis are usually observed simultaneously in cancerous lesions.

Central role of cellular senescence in TSLP-induced airway remodeling in asthma.

Background: Airway remodeling is a repair process that occurs after injury resulting in increased airway hyper-responsiveness in asthma. Thymic stromal lymphopoietin (TSLP), a vital cytokine, plays a critical role in orchestrating, perpetuating and amplifying the inflammatory response in asthma. TSLP is also a critical factor in airway remodeling in asthma.

Identification of a primary biliary cirrhosis associated protein as lysosome-associated membrane protein-2.

Unlabelled: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown etiology and abnormality of hepatobiliary transport might contribute to its pathogenesis. In this study, we aimed to isolate and identify new molecules associated with PBC. With hepatocyte canalicular membrane vesicles (CMVs) of PBC patients as immunogens, we screened the monoclonal antibody 1F9 (mAb1F9), whose antigen dominantly recognized the subapical domains in hepatocytes in normal livers.

c-Myc-mediated epigenetic silencing of MicroRNA-101 contributes to dysregulation of multiple pathways in hepatocellular carcinoma.

Unlabelled: The MYC oncogene is overexpressed in hepatocellular carcinoma (HCC) and has been associated with widespread microRNA (miRNA) repression; however, the underlying mechanisms are largely unknown. Here, we report that the c-Myc oncogenic transcription factor physically interacts with enhancer of zeste homolog 2 (EZH2), a core enzymatic unit of polycomb repressive complex 2 (PRC2). Furthermore, miR-101, an important tumor-suppressive miRNA in human hepatocarcinomas, is epigenetically repressed by PRC2 complex in a c-Myc-mediated manner.

Invasive cancers are not necessarily from preformed in situ tumours - an alternative way of carcinogenesis from misplaced stem cells.

Cancers are thought to be the result of accumulated gene mutations in cells. Carcinomas, which are cancers arising from epithelial tissues usually go through several stages of development: atypical hyperplasia, carcinoma in situ and then invasive carcinoma, which might further metastasize. However, we think that the present pathological data are enough to prove that there might be an alternative way of carcinogenesis.