Collective total synthesis of chartreusin derivatives and bioactivity investigations.

Capitalizing on Hauser annulation and Yu glycosylation, the chemical synthesis of chartreusin-type aromatic polycyclic polyketide glycosides has been investigated, culminating in the successful establishment of chemical approaches toward chartreusin derivatives with intricate chemical structures but promising bioactivities. Based on the chemical synthesis strategy, the first and collective chemical syntheses of chartreusin, D329C, and elsamicins A and B have been accomplished. The chemical strategy was featured by two complementary routes to secure chartarin 10--monosaccharide glycosides, the key intermediates in chartreusin derivative synthesis, as well as the highly stereoselective construction of the difficult glycosidic linkages.

Artificial cavernosa-like tissue based on multibubble Matrigel and a human corpus cavernous fibroblast scaffold.

Ex vivo tissue culture of the human corpus cavernosum (CC) can be used to explore the tissue structural changes and complex signaling networks. At present, artificial CC-like tissues based on acellular or three-dimensional (3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples. However, inconvenience and high costs limit the wide application of such methods.

Clinical features and microsurgical reconstruction of congenital unilateral absence of the vas deferens with obstructive azoospermia: a tertiary care center experience.

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA.

Effectiveness of adjunctive corticosteroid therapy in patients with severe COVID-19: A retrospective cohort study.

Background: The effectiveness of adjunctive corticosteroid use in patients with coronavirus disease 2019 (COVID-19) remains inconclusive.

Aim: To investigate the effectiveness of adjunctive corticosteroid therapy in patients with severe COVID-19.

Methods: We conducted a retrospective analysis of the difference in several outcomes between patients with severe COVID-19 who received corticosteroid therapy (the corticosteroid group) and patients with severe COVID-19 who did not receive corticosteroid therapy (the non-corticosteroid group).

Predictive factors of progression to severe COVID-19.

Aim: Early diagnosis and treatment are crucial for the survival of severe Coronavirus Disease 2019 (COVID-19) patients, but data with regard to risk factors for disease progression from milder COVID-19 to severe COVID-19 remain scarce.

Methods: We conducted a retrospective analysis on 116 patients.

Results: Three factors were observed to be independently associated with progression to severe COVID-19 during 14 days after admission: (a) age 65 years or older (hazard ratio [HR] = 8.

Enhanced carbon dioxide conversion at ambient conditions via a pore enrichment effect.

Chemical fixation of carbon dioxide (CO) may be a pathway to retard the current trend of rapid global warming. However, the current economic cost of chemical fixation remains high because the chemical fixation of CO usually requires high temperature or high pressure. The rational design of an efficient catalyst that works at ambient conditions might substantially reduce the economic cost of fixation.

Exploiting Cancer's Tactics to Make Cancer a Manageable Chronic Disease.

The history of modern oncology started around eighty years ago with the introduction of cytotoxic agents such as nitrogen mustard into the clinic, followed by multi-agent chemotherapy protocols. Early success in radiation therapy in Hodgkin lymphoma gave birth to the introduction of radiation therapy into different cancer treatment protocols. Along with better understanding of cancer biology, we developed drugs targeting cancer-related cellular and genetic aberrancies.

Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial.

Background: At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.

Methods: The present study will be conducted as an open-labeled, randomized, controlled trial.

Dual antivascular function of human fibulin-3 variant, a potential new drug discovery strategy for glioblastoma.

The ECM protein EFEMP1 (fibulin-3) is associated with all types of solid tumor through its cell context-dependent dual function. A variant of fibulin-3 was engineered by truncation and mutation to alleviate its oncogenic function, specifically the proinvasive role in glioblastoma multiforme (GBM) cells at stem-like state. ZR30 is an in vitro synthesized 39-kDa protein of human fibulin-3 variant.

Color-induced changes in oxygen consumption and swimming performance of juvenile bighead carp (Aristichthys nobilis).

Fish physiology and behavior are affected by exposure to light of varying colors, but little is known about the effects on swimming performance and metabolism. The purpose of this study was to measure the effects of light color on the swimming performance of bighead carp (Aristichthys nobilis), a planktivorous fish species widely used in aquaculture. Stepped velocity testing was conducted in a modified Brett-type swim tunnel respirometer to determine critical swimming speed (U), oxygen consumption (MO), and excess post-exercise oxygen consumption (EPOC) for juvenile bighead carp under red, yellow, blue, and green lights at 25 °C.

Human fibulin-3 protein variant expresses anti-cancer effects in the malignant glioma extracellular compartment in intracranial xenograft models.

Background: Decades of cytotoxic and more recently immunotherapy treatments for malignant glioma have had limited success due to dynamic intra-tumoral heterogeneity. The dynamic interplay of cancer cell subpopulations has been found to be under the control of proteins in the cancer microenvironment. EGF-containing fibulin-like extracellular matrix protein (EFEMP1) (also fibulin-3) has the multiple functions of suppressing cancer growth and angiogenesis, while promoting cancer cell invasion.

Tracking Functional Tumor Cell Subpopulations of Malignant Glioma by Phasor Fluorescence Lifetime Imaging Microscopy of NADH.

Intra-tumoral heterogeneity is associated with therapeutic resistance of cancer and there exists a need to non-invasively identify functional tumor subpopulations responsible for tumor recurrence. Reduced nicotinamide adenine dinucleotide (NADH) is a metabolic coenzyme essential in cellular respiration. Fluorescence lifetime imaging microscopy (FLIM) of NADH has been demonstrated to be a powerful label-free indicator for inferring metabolic states of living cells.

The role of EGFR double minutes in modulating the response of malignant gliomas to radiotherapy.

amplification in cells having double minute chromosomes (DM) is commonly found in glioblastoma multiforme (GBM); however, how much it contributes to the current failure to treat GBM successfully is unknown. We studied two syngeneic primary cultures derived from a GBM with and without cells carrying DM, for their differential molecular and metabolic profiles, growth patterns, and responses to irradiation (IR). Each cell line has a distinct molecular profile consistent with an invasive "go" (with DM) or angiogenic "grow" phenotype (without DM) demonstrated and in intracranial xenograft models.

Effects of temperature and fatigue on the metabolism and swimming capacity of juvenile Chinese sturgeon (Acipenser sinensis).

Chinese sturgeon (Acipenser sinensis) is a critically endangered species. A flume-type respirometer, with video, was used to conduct two consecutive stepped velocity tests at 10, 15, 20, and 25 °C. Extent of recovery was measured after the 60-min recovery period between trials, and the recovery ratio for critical swimming speed (U ) averaged 91.

Weaponizing human EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) for 21 century cancer therapeutics.

De-regulated gene expression in solid tumors has been widely reported with conflicting roles. We dissected EFEMP1 to identify domains responsible for its cell context-dependent dual functions, with the goal being to construct an EFEMP1-derived tumor-suppressor protein (ETSP) that lacked tumor-promoting function. Exon/intron boundaries of were used as boundaries of functional modules in constructing EFEMP1 variants, with removal of various module(s), and/or mutating an amino acid residue to convert a weak integrin binding-site into a strong one.

Irradiation of primary human gliomas triggers dynamic and aggressive survival responses involving microvesicle signaling.

Malignant gliomas are heterogeneous populations of dynamically interacting cells. Genomic and transcriptional changes define this cellular hierarchy and allow certain tumor cells to co-opt metabolic machinery and adopt gene expression profiles that promote cellular reprogramming. Resultant expansion of privileged subpopulations can then rapidly adapt to microenvironmental stress that ultimately influence tumor response to therapeutic intervention.

Chronic inflammation: is it the driver or is it paving the road for malignant transformation?

Chronic inflammation in well-defined mouse models such as Giα2 knock out mouse has been shown to trigger formation and expansion of hypoxic niches and also leads to up regulation of NFĸB, offering cells which have adapted their genetic machinery to hypoxia a unique survival advantage. These adapted cells have been shown to acquire stem cell-like capabilities as shown by up regulation of stem cell markers. Such long lived cells become permanent residents in sub mucosa and acquire a malignant phenotype from long-term exposure to noxious environmental agents due to a barrier defect secondary to down regulation of barrier proteins such as Zo1 and Occludin.

Anti-EGFR function of EFEMP1 in glioma cells and patient prognosis.

EGFR is one of the key oncogenes subjected to targeted therapy for several cancers, as it is known to be amplified and/or mutated in up to 40% of malignant gliomas. EFEMP1, a fibulin-like extracellular protein, exerts both tumor suppressive and oncogenic effects in various cancers and glioma cell models. Although EFEMP1's anti-cancer activity has most commonly been attributed to its anti-angiogenic effects, we showed for gliomas that EFEMP1's binding to EGFR accounts for its suppression of the intracranial tumorigenicity of glioma cells expressing high levels of EGFR.

Linking differential radiation responses to glioma heterogeneity.

The phenotypic and genetic diversity that define tumor subpopulations within high-grade glioma can lead to therapeutic resistance and tumor recurrence. Given that cranial irradiation is a frontline treatment for malignant glioma, understanding how irradiation selectively effects different cellular subpopulations within these heterogeneous cancers should help identify interventions targeted to better combat this deadly disease. To analyze the radiation response of distinct glioma subpopulations, 2 glioma cells lines (U251, A172) were cultured under conditions that promoted either adherence or non-adherent spheroids.

Tumor-specific chromosome mis-segregation controls cancer plasticity by maintaining tumor heterogeneity.

Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7) copy number variation (CNV) in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas.

Differential glioma-associated tumor antigen expression profiles of human glioma cells grown in hypoxia.

Human U251 and D54 glioma cells were tested for expression of 25 glioma-associated tumor antigen precursor proteins (TAPP) under hypoxic (1% O(2)) or normoxic (21% O(2)) conditions. Hypoxic glioma cell lines increased their mRNA expression for nine TAPP (Aim2, Art-4, EphA2, EZH2, Fosl1, PTH-rP, Sox 11, Whsc2 and YKL-40), as assessed by quantitative reverse transcriptase real-time/polymerase chain reaction (qRT-PCR). Increased differences with three hypoxic-induced TAPP: EZH2, Whsc2 and YKL-40 were shown at the protein levels by fluorescent antibody staining and quantitative electrophoretic analysis.

Detection of 1p19q deletion by real-time comparative quantitative PCR.

1p/19q (1p and/or 19q) deletions are prognostic factors in oligodendroglial tumors (OT) and predict better survival after both chemotherapy and radiotherapy. While studying 1p/19q status as a potential variable within multivariate prognosis models for OT, we have frequently encountered unknown 1p/19q status within our glioma sample database due to lack of paired blood samples for loss of heterozygosity (LOH) assay and/or failure to perform fluorescence in situ hybridization (FISH). We realized that a 1p and 19q deletion assay that could be reliably performed solely on tumor DNA samples would allow us to fill in these molecular biology data "holes".

EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment.

Purpose: There are conflicting reports regarding the function of EFEMP1 in different cancer types. In this study, we sought to evaluate the role of EFEMP1 in malignant glioma biology.

Experimental Design: Real-time qRT-PCR was used to quantify EFEMP1 expression in 95 glioblastoma multiforme (GBM).