Ag(I)-Catalyzed Oxidative Cyclization of 1,4-Diynamide-3-ols with N-Oxide for Divergent Synthesis of 2-Substituted Furan-4-carboxamide Derivatives.

This work reports Ag(I)-catalyzed oxidative cyclizations of 1,4-diynamide-3-ols with 8-methylquinoline oxide to form 2-substituted furan-4-carboxamides. The reaction chemoselectivity is distinct from that reported in previous work by Hashmi. We performed density functional theory calculations to elucidate our proposed mechanism after evaluation of the energy profiles of two possible pathways.

Solid-State Fluorescent Organic Polymers for Visual Detection and Elimination of Heavy Metals in Water.

Selective sensing and removal of toxic heavy metals from water are highly essential since their presence poses significant health and environmental hazards. Herein, we designed and synthesized a novel fluorescent nonconjugated organic polymer by strategically incorporating two key functional groups, namely, a dansyl fluorophore and dithiocarbamate (DTC). Different characterization techniques, including H nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive X-ray analysis (EDAX), Fourier transform infrared (FTIR), and fluorescence spectroscopy, were performed to understand its structure and material properties.

Dansyl-tagged xanthate ester as a capping agent to synthesize fluorescent silver nanoparticles with binding affinity toward serum albumin.

Developing multifunctional nanomaterials with distinct photochemical properties, such as high quantum yield, improved photostability, and good biocompatibility is critical for a wide range of biomedical applications. Motivated by this, we designed and synthesized a dansyl-tagged xanthate-based capping agent (DX) for the synthesis of fluorescent silver nanoparticles (AgNPs). The capping agent DX was characterized by H and C-NMR, LC-MS, and FT-IR.

Association of Interleukin 23 Receptor Polymorphisms with Predisposition to Rheumatoid Arthritis: An Updated Meta and Trial Sequential Analysis.

The etiology of Rheumatoid Arthritis (RA) development remained unclear, and several factors, such as environmental, genetic, and immune system dysfunction, have been attributed to the susceptibility. Interleukin 23 (IL23) induces expansion of the Th17 cells through the IL-23 receptor (IL-23R) and believes in playing a major role in RA pathogenesis. Various genetic mutants in the IL23R gene (rs10489629, rs1343151, rs2201841, rs7517847, rs1004819, rs10889677, rs11209026, rs7530511) have been associated with the susceptibility RA, but results are contradictories.

Sequence-Defined Tertiary Amine-Based Oligomer Employing a Scalable, Support-Free, and Protection/Deprotection-Free Iterative Strategy.

Sequence-defined oligomers (SDOs) with their unique monomeric sequence and customizable nature are attracting the attention of researchers globally. The structural and functional diversity attainable in SDOs makes this platform promising, albeit with challenges in the synthesis. Herein, we report the design and synthesis of a novel class of SDO by incorporating tertiary amines into the backbone from commercially available inexpensive materials.

Investigating Lycotoxin-An1a (An1a), a defense antiviral peptide from Alopecosa nagpag venom as prospective anti-dengue agent against DENV-2 NS2B-NS3 protease.

Dengue fever is a global health concern with no effective therapy. Screening synthetic chemicals, animal-originated compounds, and phytocompounds against Dengue virus (DENV) targets has failed to find dengue antivirals. The current study examines animal drugs as antagonists against NS2B-NS3, one of DENV's most promising therapeutic targets for dengue fever.

Small Molecule Targeting Immune Cells: A Novel Approach for Cancer Treatment.

Conventional and cancer immunotherapies encompass diverse strategies to address various cancer types and stages. However, combining these approaches often encounters limitations such as non-specific targeting, resistance development, and high toxicity, leading to suboptimal outcomes in many cancers. The tumor microenvironment (TME) is orchestrated by intricate interactions between immune and non-immune cells dictating tumor progression.

Protocol for potential energy-based bifurcation analysis, parameter searching, and phase diagram analysis of noncanonical bistable switches.

We have explored the design principles of noncanonical bistable switches using high-throughput bifurcation analysis of positive feedback loops under dual signaling. Here, we present a protocol to carry out bifurcation analysis using pseudo-potential energy of the dynamical system. We also describe steps to perform automated parameter searching for canonical and noncanonical switches and multi-parameter phase diagram analysis of these switches.

Unveiling Novel Avenues in mTOR-Targeted Therapeutics: Advancements in Glioblastoma Treatment.

The mTOR signaling pathway plays a pivotal and intricate role in the pathogenesis of glioblastoma, driving tumorigenesis and proliferation. Mutations or deletions in the PTEN gene constitutively activate the mTOR pathway by expressing growth factors EGF and PDGF, which activate their respective receptor pathways (e.g.

Investigation of airborne spread of COVID-19 using a hybrid agent-based model: a case study of the UK.

Agent-based models have been proven to be quite useful in understanding and predicting the SARS-CoV-2 virus-originated COVID-19 infection. Person-to-person contact was considered as the main mechanism of viral transmission in these models. However, recent understanding has confirmed that airborne transmission is the main route to infection spread of COVID-19.

Evaluation of the inhibitory potency of anti-dengue phytocompounds against DENV-2 NS2B-NS3 protease: virtual screening, ADMET profiling and molecular dynamics simulation investigations.

Dengue fever has been a worldwide concern, with 50-100 million new infections each year mainly due to five different serotypes of the Dengue virus (DENV). Designing a perfect anti-dengue agent that can inhibit all the serotypes by distinguishing antigenic differences is quite difficult. Previous anti-dengue researches have included chemical compounds screening against DENV enzymes.

Origin, heterogeneity, and interconversion of noncanonical bistable switches from the positive feedback loops under dual signaling.

Designing new functional motifs with unique properties is an important objective in the realm of synthetic biology. We uncover emergent properties of positive feedback loops (PFLs) under dual input signaling using pseudo potential energy-based high-throughput bifurcation analysis. We show that under dual signaling a single PFL generates a variety of noncanonical bistable switches, with one or more bistable regions, due to fusion of multiple canonical bistable switches.

Nitrosoarenes Implement Cascade Cyclization of 1-Allenyl-2-alkynylbenzenes through Diradical Mechanism.

This work reports cascade cyclization between 1-allenyl-2-alkynylbenzenes and nitrosoarenes. When these two components reacted alone under N, N,O-functionalized indane-fused isoxazolidines were obtained selectively. DFT calculations verify that this reaction sequence involves unprecedented nitrone/alkyne cycloadditions, followed by diradical rearrangement.

Roughness in the periodic potential induces absolute negative mobility in a driven Brownian ratchet.

Absolute negative mobility, where particles move opposite to the direction as governed by the external load, is an anomalous transport property of a Brownian ratchet and has technological implications in mass separation and bioanalytical applications. We numerically investigated here the effect of roughness in symmetric periodic potential on the negative mobility of a driven inertial Brownian ratchet in the presence of an external load. We show that the microscopic spatial heterogeneity of the potential can generate negative mobility which would not otherwise be possible under smooth potential in the concerned parameter space.

Aza-Oxa-Triazole Based Macrocycles with Tunable Properties: Design, Synthesis, and Bioactivity.

A modular platform for the synthesis of tunable aza-oxa-based macrocycles was established. Modulations in the backbone and the side-chain functional groups have been rendered to achieve the tunable property. These aza-oxa-based macrocycles can also differ in the number of heteroatoms in the backbone and the ring size of the macrocycles.

Gold(I)-Catalyzed [4 + 2] Annulation between Arylynes and C,N-Diaryl Nitrones for Chemoselective Synthesis of Quinoline Scaffolds via Gold Acetylide Intermediates.

Gold-catalyzed synthesis of quinoline derivatives via [4 + 2] annulation between terminal arylynes and nitrones is described. Our mechanistic analysis supports the participation of alkynylgold intermediates, instead of a typical gold-carbene species in recently reported gold catalysis. These nucleophilic alkynylgold species react with nitrones via Povarov-type reactions.

Interleukin 17A rs2275913 polymorphism is associated with susceptibility to systemic lupus erythematosus: A meta and trial sequential analysis.

Background: The role of cytokines in the development of systemic lupus erythematosus (SLE) has received much attention. Interleukin-17 A upregulates several inflammation-related genes and is thought to have a crucial role in SLE development. The susceptibility to SLE development has been linked to functional genetic variations of the gene; nevertheless, the findings have been conflicting.

Pulsatile signaling of bistable switches reveal the distinct nature of pulse processing by mutual activation and mutual inhibition loop.

Cells often encounter various external and internal signals in a non-sustained pulsatile manner with varying amplitude, duration and residual value. However, the effect of signal pulse on the regulatory networks is poorly understood. In order gain a quantitative understating of pulse processing by bistable switches, we investigated pulse induced population inversion kinetics in bistable switches generated either by mutual activation or by mutual inhibition motifs.

Emergent Bistable Switches from the Incoherent Feed-Forward Signaling of a Positive Feedback Loop.

Bistability is intrinsically connected to various decision making processes in living systems. The operating principles of a bistable switch, generated from a positive feedback loop, are well understood both in natural and synthetic settings. However, the fate of dynamic modularity of a positive feedback loop is unknown when it is connected to another dynamically modular signaling motif.

Roughness in the periodic potential enhances transport in a driven inertial ratchet.

We study the effects of roughness in the asymmetric periodic potential on the transport and diffusion of an inertial Brownian particle driven by a time-periodic force in a Gaussian environment. We find that moderate roughness leads to the loss of transient anomalous diffusion, and it helps to establish normal diffusion in the weak noise limit. We uncover a contrasting effect of roughness on the transport of particles in the weak and moderate to large noise limit.

Scaling of intrinsic noise in an autocratic reaction network.

Biochemical reactions in living cells often produce stochastic trajectories due to the fluctuations of the finite number of the macromolecular species present inside the cell. A significant number of computational and theoretical studies have previously investigated stochasticity in small regulatory networks to understand its origin and regulation. At the systems level regulatory networks have been determined to be hierarchical resembling social networks.

Potential Landscapes, Bifurcations, and Robustness of Tristable Networks.

Bistable switches that produce all-or-none responses have been found to regulate a number of natural cellular decision making processes, and subsequently synthetic switches were designed to exploit their potential. However, an increasing number of studies, particularly in the context of cellular differentiation, highlight the existence of a mixed state that can be explained by tristable switches. The criterion for designing robust tristable switches still remains to be understood from the perspective of network topology.

Qualitative and quantitative nature of mutual interactions dictate chemical noise in a democratic reaction network.

The functions of a living cell rely on a complex network of biochemical reactions that allow it to respond against various internal and external cues. The outcomes of these chemical reactions are often stochastic due to intrinsic and extrinsic noise leading to population heterogeneity. The majority of calculations of stochasticity in reaction networks have focused on small regulatory networks addressing the role of timescales, feedback regulations, and network topology in propagation of noise.

Investigation of chemical noise in multisite phosphorylation chain using linear noise approximation.

Quantitative and qualitative nature of chemical noise propagation in biochemical reaction networks depend crucially on the topology of the networks. Multisite reversible phosphorylation-dephosphorylation of target proteins is one such recurrently found topology that regulates host of key functions in living cells. Here we analytically calculated the stochasticity in multistep reversible chemical reactions by determining variance of phosphorylated species at the steady state using linear noise approximation to investigate the effect of mass action and Michaelis-Menten kinetics on the noise of phosphorylated species.