Self-assembly of Antisense DNA-Camptothecin Amphiphile into Glutathione-Responsive Nanoparticles for Combination Cancer Therapy.

Recent years have witnessed the rapid growth of combination therapy for the treatment of cancer. Chemo and antisense DNA therapies are two clinically proven and efficient treatment modalities for cancer. However, direct delivery of both chemo and antisense oligonucleotides into the cancerous cells is challenging and hence there is a high demand for the development of new strategies that permit the direct delivery of chemo and antisense therapeutic agents in a targeted fashion.

Molecular dynamics simulations of functionalized hBN nanopores in water: Ab initio force field and implications for water desalination.

Heteropolar two-dimensional materials, including hexagonal boron nitride (hBN), are promising candidates for seawater desalination and osmotic power harvesting, but previous simulation studies have considered bare, unterminated nanopores in molecular dynamics (MD) simulations. There is presently a lack of force fields to describe functionalized nanoporous hBN in aqueous media. To address this gap, we conduct density functional theory (DFT)-based ab initio MD simulations of hBN nanopores surrounded by water molecules.

Fluoropolymer-Single Crystal Nanocomposite Based Transducer Fabrication for Bio-Imaging.

Fluoropolymer alone, as an alternative to lead-based piezoelectric materials, has shown multiple challenges to develop useful sensors for solving real-world problems such as photoacoustic, ultrasound pulse echo, and other non-destructive testing. This work demonstrates the fabrication of high frequency and wide bandwidth transducers with fluoropolymer and highly polarizing cubic single crystal Barium titanate (BaTiO) ceramic composite for high resolution in-vivo photo-acoustic and ultrasound imaging. For transducer fabrication, a customized bio-compatible nanocomposite sensor film of PVDF-TrFE (Polyvinylidene fluoride trifluoroethylene)/BaTiO (BTO) is synthesized by drop and dry in heating-cum-electro-poling system for advancing polarization, crystallinity, and higher charge generation.

Measurement of multidifferential cross sections for dijet production in proton-proton collisions at .

A measurement of the dijet production cross section is reported based on proton-proton collision data collected in 2016 at by the CMS experiment at the CERN LHC, corresponding to an integrated luminosity of up to 36.3 . Jets are reconstructed with the anti- algorithm for distance parameters of and 0.

Total Synthesis of (+)-7,7'-Bistaxodione via Late-Stage Electrochemical Dimerization.

The first asymmetric total synthesis of the tetraterpenoid (+)-7,7'-bistaxodione () via a unique late-stage electrochemical oxidative dimerization of a diterpenoid quinone methide tumor Inhibitor (+)-taxodione () has been described. The naturally occurring monomer was synthesized from aromatic abietane diterpenoid, ferruginol (1e) . Further, an efficient convergent synthetic route toward the naturally occurring aromatic abietane terpenoids has been shown via a Lewis acid-mediated diastereoselective cationic epoxy-ene cyclization.

Ribose Sugar Alters Conformational Sampling of G•T Mismatched Duplex DNA.

Polymerases erroneously incorporate Guanine-Thymine (dG•dT) mismatches in genomic DNA that further evades repair by transient sampling of tautomeric/ionic states compromising fidelity of repairing dG•dT mismatches. In conjunction, significant frequency of ribose (mis)incorporation in duplex DNA permits for misincorporated-mismatch in the genome. Ribose incorporated G(rG) mismatched with T(rG•dT) is the most stable across all misincorporated-mismatch calling into question the conformational consequences of the ribose sugar in addition to the mismatch.

Single-Crystal-to-Single-Crystal Synthesis of a Polymer in Two Distinct Topologies.

A squaramide-based monomer, designed for topochemical azide-alkyne cycloaddition (TAAC) polymerization, crystallizes as two polymorphs, M1 and M2, both having crystal packing suitable for topochemical polymerization. The hydrogen-bonding between squaramide units  bias the molecular organization in both the polymorphs. 3D packing of H-bonded stacks of monomer lead to juxtaposition of  azide and alkyne units of adjacent molecules in a transition-state-like arrangement for their regiospecific cycloaddition reaction.

Global transcriptome profiling of ST09 treated breast cancer cells identifies miR-197-5p/GPX3 antioxidant axis as a regulator of tumorigenesis.

ROS (Reactive Oxygen Species) has a dual role in tumorigenesis. Some cancers have high ROS conditions, and others have low ROS. TNBC thrives on high ROS compared to other Breast Cancer subtypes.

Mechanistic Cooperation of the Two Pore-Forming Transmembrane Motifs Regulates the β-Barrel Pore Formation by Listeriolysin O.

Listeriolysin O (LLO) is a potent membrane-damaging pore-forming toxin (PFT) secreted by the bacterial pathogen . LLO belongs to the family of cholesterol-dependent cytolysins (CDCs), which specifically target cholesterol-containing cell membranes to form oligomeric pores and induce membrane damage. CDCs, including LLO, harbor designated pore-forming motifs.

Intramolecular Redox-driven Synthesis of Mono- and Diradical Iridium(III) Complexes: Insights into Molecular and Electronic Structure, Electrochemistry, and Spin-Communication.

Two π-radical complexes containing bisazo-aromatic-centered radical anion (1•-) were synthesized through in-situ electron transfer from metal-to-ligand using [IrI] and 2-(2-Pyridylazo)azobenzene (1) in inert hydrocarbon solvent. These are characterized as diradical [IrIII(1•-)2]+[2]+ and monoradical [IrIII(1•-)Cl2(PPh3)] 3. In contrast, a rare metal-mediated hydrolytic cleavage of the C(sp2)-N bond occurred in protic solvent resulting in quaternary radical complex [IrIII(1•-)(1')(PPh3)]+(4)+.

An Open-Label Phase II Trial of Pembrolizumab, an Immune Checkpoint Inhibitor Alone or in Combination With Oral Azacitidine as Second-Line Therapy for Advanced Head and Neck Squamous Cell Cancers.

Background And Aims: Sensitivity to immune checkpoint inhibitor (ICI) therapy depends in part on the genetic and epigenetic makeup of cancer cells, and CD8 T-lymphocytes that mediate immune responses. Epigenetics are heritable reversible changes in gene expression that occur without any changes in the nuclear DNA sequence or DNA copy number.

Primary Objective: i.

Primordial black holes and their gravitational-wave signatures.

In the recent years, primordial black holes (PBHs) have emerged as one of the most interesting and hotly debated topics in cosmology. Among other possibilities, PBHs could explain both some of the signals from binary black hole mergers observed in gravitational-wave detectors and an important component of the dark matter in the Universe. Significant progress has been achieved both on the theory side and from the point of view of observations, including new models and more accurate calculations of PBH formation, evolution, clustering, merger rates, as well as new astrophysical and cosmological probes.

Biomimic models for glycemic index: Scope of sensor integration and artificial intelligence.

The accurate quantification of glycemic index (GI) remains crucial for diabetes management, yet current methodologies are constrained by resource intensiveness and methodological limitations. digestion models face challenges in replicating the dynamic conditions of the human gastrointestinal tract, such as enzyme variability and multi-time point analysis, leading to suboptimal predictive accuracy. This review proposes an integrated technological framework combining non-enzymatic electrochemical sensing with artificial intelligence to revolutionize GI assessment.

Experimental adaptation to singular pathogen challenge reduces susceptibility to novel pathogens in .

Hosts often encounter and must respond to novel pathogens in the wild, that is pathogens that they have not encountered in recent evolutionary history, and therefore are not adapted to. How hosts respond to these novel pathogens and the outcome of such infections can be shaped by the host's evolutionary history, especially by how well adapted the host is to its native pathogens, that is pathogens they have evolved with. Host adaptation to one pathogen can either increase its susceptibility to a novel pathogen, due to specialization of immune defenses and trade-offs between different arms of the immune system, or can decrease susceptibility to novel pathogens by virtue of cross-resistance.

CoS/CoTe n-n Type Heterojunction: A Heterogenic Interfacial Integration of CoS and CoTe Phases for Energy-Efficient Hydrazine Oxidation Assisted Hydrogen Production.

Controlled and optimized heterogenic interfacial coupling is the key to enhance the electrochemical performance. Herein, for the first time, telluride-based CoS/CoTe heterostructure is reported as a bifunctional catalyst for energy-efficient H generation. Detailed investigations suggest that the heterogenic interfacial coupling leads to superior bifunctional electrochemical performance of the CoS/CoTe heterostructure.

Drug-assisted White Light Generation via Self-assembly.

White-light generation using small organic molecules has gained significant attention from researchers working on the interface of supramolecular chemistry and organic materials. Self-assembled multi-chromophoric materials utilizing a drug molecule and microenvironment-sensitive intramolecular charge transfer dye as an emitter offer the possibility of tunable emission. In this investigation, we focused on white light generation via the combination of a polarity-sensitive red-emitting styryl chromone (SC) and a blue-emitting anticancer and psychotherapeutic drug Norharmane (NHM) in a self-assembled micellar system.

Adhesion-driven vesicle translocation through membrane-covered pores.

Translocation across barriers and through constrictions is a mechanism that is often used in vivo for transporting material between compartments. A specific example is apicomplexan parasites invading host cells through the tight junction that acts as a pore, and a similar barrier crossing is involved in drug delivery using lipid vesicles penetrating intact skin. Here, we use triangulated membranes and energy minimization to study the translocation of vesicles through pores with fixed radii.

Exploring force-driven stochastic folding dynamics in mechano-responsive proteins and implications in phenotypic variation.

Single-point mutations are pivotal in molecular zoology, shaping functions and influencing genetic diversity and evolution. Here we study three such genetic variants of a mechano-responsive protein, cadherin-23, that uphold the structural integrity of the protein, but showcase distinct genotypes and phenotypes. The variants exhibit subtle differences in transient intra-domain interactions, which in turn affect the anti-correlated motions among the constituent β-strands.

Quantification of Through-Space Intervalence Charge Transfer in Cofacial Thiazolothiazole Metal-Organic Framework and Its Photochromic Behavior.

Electronic coupling between individual redox units in a molecular assembly dictates their charge transfer efficacy. Being a well-defined crystalline structure, the metal-organic framework (MOF) ensures proper positioning of redox-active moieties and provides a unique platform to unveil their charge transfer dynamics and quantification with structural relationships. Here, we demonstrate a novel redox-active MOF with near-infrared through-space intervalence charge transfer by introducing a mixed valence state inside redox-active thiazolothiazole-based ligands (DPTTZ) upon photo- or electrochemical reduction.

Synthetic transcription factors establish the function of nine amino acid transactivation domains of Komagataella phaffii Mxr1.

The zinc finger transcription factor Mxr1 (methanol expression regulator 1) of the methylotrophic yeast Komagataella phaffii (formerly Pichia pastoris) harbors a DNA-binding domain (DBD) consisting of two CH zinc fingers (Mxr1ZF) between amino acids 36-101 and a previously identified nine amino acid transactivation domain (9aaTAD) between residues 365-373 (TAD A, QELESSLNA). Beyond this, 21 putative 9aaTADs (designated TAD B-V) located between amino acids 401-1155 remain to be characterized. Here, we demonstrate that a compact synthetic transcription factor composed of Mxr1ZF and three tandem copies of TAD A can activate the transcription of Mxr1 target genes for ethanol and methanol metabolism with specificity and efficiency comparable to the full-length protein.

Host Manipulations Within Mutualisms: Role of Plant Hormones in Selective Resource Allocation.

In some mutualisms involving host plants, photoassimilates are provided as rewards to symbionts. Endophagous organisms often manipulate host plants to increase access to photoassimilates. Host manipulations by endophagous organisms that are also mutualists are poorly understood.

Unveiling Heavier Dihydropyridine Chalcogenol Esters in Metallaphotoredox Catalyst-Enabled Regioselective Hydrothio(seleno)carbonylation.

Herein, aromaticity-driven thio(seleno)ester group transfer from novel 1,4-dihydropyridine thio(seleno)esters to alkene feedstocks is disclosed by merging palladium and photoredox catalysis. In this process, photoactivation of dihydropyridine thio(seleno)esters is integrated with regioselective hydrometalation of alkenes, avoiding photoinduced Pd-C bond homolysis of organopalladium intermediates. Additionally, a regioselective hydroselenocarbonylation of an alkene is accomplished for the first time using a bench-stable selenoester reagent.

Mitochondria and its epigenetic dynamics: Insight into synaptic regulation and synaptopathies.

Mitochondria, the cellular powerhouses, are pivotal to neuronal function and health, particularly through their role in regulating synaptic structure and function. Spine reprogramming, which underlies synapse development, depends heavily on mitochondrial dynamics-such as biogenesis, fission, fusion, and mitophagy as well as functions including ATP production, calcium (Ca) regulation, and retrograde signaling. Mitochondria supply the energy necessary for assisting synapse development and plasticity, while also regulating intracellular Ca homeostasis to prevent excitotoxicity and support synaptic neurotransmission.

Amphoteric Cross-Linked Cellulose Nanoparticles as a Platform for Immobilization of Proteins and Cells, Enabling Bioanalyte Sensing.

Cellulosic nanomaterials have significantly promoted the development of sensing devices, drug delivery, and bioreactor processes. Their synthetic flexibility makes them a prominent choice for immobilizing biomolecules or cells. In this work, we developed a practical and user-friendly approach to accessing cellulose nanoparticles (CNPs).