Visible Light-Induced Regioselective to Isomerization of Polarized 1,3-Dienes: Experimental and Theoretical Insights.

The stereocontrol of → isomerization on a (1,3)-diene, instead of a simple alkene, can be more challenging due to the increased number of isomerization possibilities. Herein, we report visible light-mediated regioselective (1,3 → 1,3) isomerization of (1,3)-diene. The reaction conditions are mild and easy to apply and can be applied to a wide range of substances, with an excellent yield and selectivity (90:10).

Measuring Piezo1 and Actin Polarity in Chemokine-Stimulated Jurkat Cells During Live-Cell Imaging.

The process of T-lymphocyte migration involves a complex interplay of chemical and mechanical signals. Mechanotransduction mechanisms in T lymphocytes enable them to efficiently navigate through diverse architectural and topographical features of the dynamic tissue macro- and micro-niches encountered during immune responses. Piezo1 mechanosensors are crucial for driving optimal T-cell migration by driving actin-cytoskeletal remodeling.

Copper(II)-Mediated Dual Reactivity of 2-(5-Phenylisoxazol-3-yl)aniline: Directed Amination and Oxidative C(═O)─C Cleavage of Amides Enabling Direct Access to Urea Derivatives.

The dual reactivity of amides fused to 2-(5-phenylisoxazol-3-yl)aniline as a directing group for the formation of urea derivatives via chemospecific cleavage of the C(═O)─C bond and C(sp)-H amination is reported here. Employing inexpensive copper as the catalyst and O in air as the oxidant, this protocol exhibited broad functional group tolerance for both the transformations. Detailed mechanistic studies and DFT calculations were performed to gain insights into a plausible mechanism for the formation of urea derivatives.

External photocatalyst-free photocycloaddition between triplet vinylnitrenes with 1,3-biradical character and activated olefins under 420 nm LEDs.

Herein, we report that triplet vinylnitrenes with 1,3-biradical character can directly participate in photocycloaddition reactions with olefins to produce single diastereomers of the corresponding 1-pyrrolines under 420 nm LEDs in acetonitrile solvent. Moreover, a one-pot method has been developed to produce pyrroles directly through photocycloaddition and oxidation sequences. The excited state of the substrate olefin can sensitize vinyl azide energy transfer, eliminating the need for an external photocatalyst or sensitizer.

Transition-metal-free iterative two-fold reductive coupling and 1,3-borotropic shift to form 1,4-skipped dienes.

We report herein a transition-metal-free two-fold reductive coupling between prenal (allyl) tosylhydrazone and boronic acids/1,3-borotropic shift cascade to furnish 1,4-skipped dienes. In this work, a single batch operation produces (,)-1,4-skipped dienes by undergoing a second reductive coupling of the transient boronic acid, which developed following the first reductive allylation and a cascade 1,3-boron migration. Remarkably, the protocol is compatible with various aryl- and alkyl-substituted boronic acids, is scalable and has demonstrated on 61 substrates with yields up to 98%.

The EXO1/Polη/Polι axis as a promising target for miR-3163-mediated attenuation of cancer stem-like cells in non-small cell lung carcinoma.

Background: Cancer stem-like cells (CSLCs) drive tumour progression and chemoresistance. The concerted efforts of EXO1 and TLS polymerases safeguard DNA integrity against chemotherapeutic drugs. In absence of potential drug targets, non-small cell lung carcinoma (NSCLC) patients have few therapeutic options.

Transcriptional upregulation of MMP-9 gene under hyperglycemic conditions in AGS cells: Role of AP-1 transcription factor.

Gastric cancer and diabetes are two complex and interrelated diseases having significant impact on global health. Hyperglycemic condition notably exacerbates cancer by promoting inflammation, angiogenesis, and metastasis. Elevated glucose levels can also upregulate the expression of specific matrix metalloproteinases (MMPs), especially MMP-9, which is associated with cancer cell migration and invasion.

Cdc25A phosphatase is activated and mediates neuronal cell death by PUMA via pRb/E2F1 pathway in a model of Parkinson's disease.

Parkinson's disease (PD) is a predominant movement disorder caused mainly due to selective loss of the dopaminergic neurons in the substantia nigra pars compacta of the mid brain. There is currently no cure for PD barring treatments to manage symptoms. The reasons might be due to lack of precise understanding of molecular mechanisms leading to neurodegeneration.

Identification of critical amino acids in the DNA binding domain of LuxO: Lessons from a constitutive active LuxO.

Quorum sensing plays a vital role in the environmental and host life cycles of Vibrio cholerae. The quorum-sensing circuit involves the consorted action of autoinducers, small RNAs, and regulatory proteins to control a plethora of physiological events in this bacterium. Among the regulatory proteins, LuxO is considered a low-cell-density master regulator.

Computational investigation of novel synthetic analogs of C-1'β substituted remdesivir against RNA-dependent RNA-polymerase of SARS-CoV-2.

Remdesivir, a C-nucleotide prodrug binds to the viral RNA-dependent-RNA polymerase () and inhibits the viral replication by terminating RNA transcription prematurely. It is reported in literature that interaction between the C-1'β-CN moiety of Remdesivir () and the Ser861 residue in enzyme, causes a delayed chain termination during the RNA replication process and is one of the important aspect of its mechanism of action. In the pursuance of increasing the biological activity of and enhancing the SAR studies, against RNA viruses, we have designed its fourteen C1'β substituted analogs, - bearing 4/5-membered heterocyclic rings.

Deubiquitinase JOSD1 tempers hepatic proteotoxicity.

Derangements in protein homeostasis and associated proteotoxicity mark acute, chronic, and drug-induced hepatocellular injury. Metabolic dysfunction-associated proteasomal inhibition and the use of proteasome inhibitors often underlie such pathological hepatic proteotoxicity. In this study, we sought to identify a candidate deubiquitinating enzyme (DUB) responsible for reversing the proteotoxic damage.

Exploring the uncharted seas: Metabolite profiling unleashes the anticancer properties of .

Marine cyanobacteria offer a rich source of varied natural products with both chemical and biological diversity. () is a filamentous non-heterocystous marine cyanobacterium from Oscillatoriaceae family. In this investigation, we have unveiled bioactive extracts from using two distinct solvent systems, revealing significant anticancer properties.

Adipose tissue-derived adipsin marks human aging in non-type 2 diabetes population.

Introduction: Adipsin or complement factor D is an adipokine that augments insulin secretion, is altered in various degrees of obesity, and is involved in alternative complement pathway. However, whether adipsin has any independent association with risk factors and biomarkers in patients with type 2 diabetes (T2D) remains elusive.

Research Design And Methods: We performed an oral glucose tolerance test on a subset of 43 patients with T2D from the community health cohort to access the role of adipsin in insulin secretion.

A SARS-CoV-2 peptide antigen purified from bacteria and displayed in a high-density repetitive manner on a virus-like particle could generate anti-SARS-CoV-2 neutralizing antibodies unlike free peptide.

SARS-CoV-2 is an enveloped virus. Proteins of the lipid based envelope are not rigidly arranged as compared to non-enveloped viruses lacking lipid based outer layer. Rigidly arranged multivalent display has been reported to be important for potent immune stimulation.

EpCAM-targeted betulinic acid analogue nanotherapy improves therapeutic efficacy and induces anti-tumorigenic immune response in colorectal cancer tumor microenvironment.

Background: Betulinic acid (BA) has been well investigated for its antiproliferative and mitochondrial pathway-mediated apoptosis-inducing effects on various cancers. However, its poor solubility and off-target activity have limited its utility in clinical trials. Additionally, the immune modulatory role of betulinic acid analogue in the tumor microenvironment (TME) is largely unknown.

ETS1 drives EGF-induced glycolytic shift and metastasis of epithelial ovarian cancer cells.

Epithelial ovarian cancer (EOC), a leading cause of gynecological cancer-related morbidity and mortality and the most common type of ovarian cancer (OC), is widely characterized by alterations in the Epidermal Growth Factor (EGF) signaling pathways. The phenomenon of metastasis is largely held accountable for the majority of EOC-associated deaths. Existing literature reports substantiate evidence on the indispensable role of metabolic reprogramming, particularly the phenomenon of the 'Warburg effect' or aerobic glycolysis in priming the cancer cells towards Epithelial to Mesenchymal transition (EMT), subsequently facilitating EMT.

Metal-free internal nucleophile-triggered domino route for synthesis of fused quinoxaline [1,4]-diazepine hybrids and the evaluation of their DNA binding properties.

An unprecedented metal-free synthesis of fused quinoxaline 1,5-disubstituted-[1,4]-diazepine hybrids have been reported under mild conditions through a domino intermolecular SAr followed by an internal nucleophile-triggered intramolecular SAr pathway. Our strategy offers the flexibility for the introduction of a broad variety of functionalities at the N-1 position of fused diazepine moiety by using suitable diamine tails to design structurally diverse scaffolds. The DNA binding properties of representative quinoxaline diazepine hybrids were studied using UV-vis absorbance and EtBr displacement assay and were found to be governed by the functionalities at the N-1 position.

Requirement of a Wnt5A-microbiota axis in the maintenance of gut B-cell repertoire and protection from infection.

We investigated the influence of a Wnt5A-gut microbiota axis on gut B-cell repertoire and protection from infection, having previously demonstrated that Wnt5A in association with gut commensals helps shape gut T-cell repertoire. Accordingly, Wnt5A heterozygous mice, which express less than wild-type level of Wnt5A, and their isolated Peyer's patches (PPs) were studied in comparison with the wild-type counterparts. The percentages of IgM- and IgA-expressing B cells were quite similar in the PP of both sets of mice.

Organophotoredox-Catalyzed Synthesis of Unnatural α/β Amino Acids and Peptides via Deaminative Three-Component Coupling.

Herein, we disclose an expedient visible-light-mediated, organophotoredox-catalyzed multicomponent synthesis of unnatural amino acids using a Katritzky salt, glyoxal derivatives, and substituted anilines. Mechanistically, an alkyl radical is generated from the Katritzky salt via a deaminative process that undergoes addition to the -generated imine to furnish α-amino acids in a moderate diastereoisomeric ratio. For the first time, we have demonstrated this deaminative protocol to access substituted β-amino acids from α-amino acid-derived Katritzky salts.

Differential Proteomic Profiling at Different Phases of Dengue Infection: An Intricate Insight from Proteins to Pathogenesis.

Dengue fever is a rapidly emerging tropical disease and an important cause of morbidity in its severe form worldwide. A wide spectrum of the pathophysiology is associated with the transition of dengue fever to severe dengue, which is driven by the host immune response and might reflect in patients' proteome profile. This study aims to analyze the plasma from different phases of dengue-infected patients at two time points.

Monoamine oxidase and neurodegeneration: Mechanisms, inhibitors and natural compounds for therapeutic intervention.

Mammalian flavoenzyme Monoamine oxidase (MAO) resides on the outer mitochondrial membrane (OMM) and it is involved in the metabolism of different monoamine neurotransmitters in brain. During MAO mediated oxidative deamination of relevant substrates, HO is released as a catalytic by-product, thus serving as a major source of reactive oxygen species (ROS). Under normal conditions, MAO mediated ROS is reported to propel the functioning of mitochondrial electron transport chain and phasic dopamine release.

Shatavarin-IV, a steroidal saponin from Asparagus racemosus, inhibits cell cycle progression and epithelial-to-mesenchymal transition in AGS cells under hyperglycemic conditions.

Gastric cancer (GC)-diabetes co-morbidity is nowadays growing into a rising concern. However, no separate treatment procedures have been outlined for such patients. Phytochemicals and their derivatives can therefore be used as therapeutics as they have greater effectiveness, reduced toxicity, and a reduced likelihood of developing multi-drug resistance in cancer treatments.

The molecular prognostic score, a classifier for risk stratification of high-grade serous ovarian cancer.

Background: The clinicopathological parameters such as residual tumor, grade, the International Federation of Gynecology and Obstetrics (FIGO) score are often used to predict the survival of ovarian cancer patients, but the 5-year survival of high grade serous ovarian cancer (HGSOC) still remains around 30%. Hence, the relentless pursuit of enhanced prognostic tools for HGSOC, this study introduces an unprecedented gene expression-based molecular prognostic score (mPS). Derived from a novel 20-gene signature through Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression, the mPS stands out for its predictive prowess.

Evaluation of lamin A/C mechanotransduction under different surface topography in LMNA related muscular dystrophy.

Most of the single point mutations of the LMNA gene are associated with distinct muscular dystrophies, marked by heterogenous phenotypes but primarily the loss and symmetric weakness of skeletal muscle tissue. The molecular mechanism and phenotype-genotype relationships in these muscular dystrophies are poorly understood. An effort has been here to delineating the adaptation of mechanical inputs into biological response by mutant cells of lamin A associated muscular dystrophy.