What Triggers the Dynamic Self-Assembly of Molecules and Materials?

Dynamic self-assembly has emerged as one of the reliable approaches to create complex materials with more life-like functions. In a typical dynamic self-assembly process, the external triggers activate the building blocks to initiate the assembly step to form transiently stable higher-order structures. These external triggers provide a constant supply of energy to maintain the transiently stable self-assembled states.

Electrostatically driven unidirectional molecular flux for high performance alkaline flow batteries.

To mitigate the mismatch between energy availability and energy demand due to day/night shifts and seasonal variations, intensive efforts have been dedicated to storing renewable energy in various energy storage modules. Redox flow batteries have an upper hand over conventional batteries as energy storage modules due to their capability of decoupling energy and power. However, interfacial events, such as mass transport and electron transfer, play pivotal roles in flow batteries' energy storage and conversion mechanisms.

Exploring the human microbiome - A step forward for precision medicine in breast cancer.

Background: The second most frequent cancer in the world and the most common malignancy in women is breast cancer. Breast cancer is a significant health concern in India with a high mortality-to-incidence ratio and presentation at a younger age.

Recent Findings: Recent studies have identified gut microbiota as a significant factor that can have an influence on the development, treatment, and prognosis of breast cancer.

NAD(P)H:Quinone Acceptor Oxidoreductase 1 (NQO1) Activatable Salicylamide H /Cl Transporters.

NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a detoxifying enzyme overexpressed in tumors, plays a key role in protecting cancer cells against oxidative stress and thus has been considered an attractive candidate for activating prodrug(s). Herein, we report the first use of NQO1 for the selective activation of 'protransporter' systems in cancer cells leading to the induction of apoptosis. Salicylamides, easily synthesizable small molecules, have been effectively used for efficient H /Cl symport across lipid membranes.

Unprecedented energy storage in metal-organic complexes constitutional isomerism.

The essence of any electrochemical system is engraved in its electrical double layer (EDL), and we report its unprecedented reorganization by the structural isomerism of molecules, with a direct consequence on their energy storage capability. Electrochemical and spectroscopic analyses in combination with computational and modelling studies demonstrate that an attractive field-effect due to the molecule's structural-isomerism, in contrast to a repulsive field-effect, spatially screens the ion-ion coulombic repulsions in the EDL and reconfigures the local density of anions. In a laboratory-level prototype supercapacitor, those with β-structural isomerism exhibit nearly 6-times elevated energy storage compared to the state-of-the-art electrodes, by delivering ∼535 F g at 1 A g while maintaining high performance metrics even at a rate as high as 50 A g.

Bacteria evolve macroscopic multicellularity by the genetic assimilation of phenotypically plastic cell clustering.

The evolutionary transition from unicellularity to multicellularity was a key innovation in the history of life. Experimental evolution is an important tool to study the formation of undifferentiated cellular clusters, the likely first step of this transition. Although multicellularity first evolved in bacteria, previous experimental evolution research has primarily used eukaryotes.

Dissecting the contributions of membrane affinity and bivalency of the spider venom protein DkTx to its sustained mode of TRPV1 activation.

The spider venom protein, double-knot toxin (DkTx), partitions into the cellular membrane and binds bivalently to the pain-sensing ion channel, TRPV1, triggering long-lasting channel activation. In contrast, its monovalent single knots membrane partition poorly and invoke rapidly reversible TRPV1 activation. To discern the contributions of the bivalency and membrane affinity of DkTx to its sustained mode of action, here, we developed diverse toxin variants including those containing truncated linkers between individual knots, precluding bivalent binding.

Probing juxtaposed G-quadruplex and hairpin motifs using a responsive nucleoside probe: a unique scaffold for chemotherapy.

Paucity of efficient probes and small molecule ligands that can distinguish different G-quadruplex (GQ) topologies poses challenges not only in understanding their basic structure but also in targeting an individual GQ form from others. Alternatively, G-rich sequences that harbour unique chimeric structural motifs (, GQ-duplex or GQ-hairpin junctions) are perceived as new therapeutic hotspots. In this context, the epidermal growth factor receptor (EGFR) gene, implicated in many cancers, contains a 30 nucleotide G-rich segment in the promoter region, which adopts two unique architectures each composed of a GQ topology (parallel and hybrid-type) juxtaposed with a hairpin domain.

Direct Access to Strained Fused Dihalo-Aziridino Quinoxalinones via C3-Alkylation Followed by Tandem Cyclization.

Quinoxalinones are a privileged class of compounds, and their structural framework is found in many bioactive compounds, natural compounds, and pharmaceuticals. Quinoxalinone is a promising scaffold for different types of functionalization, and the slight modification of the quinoxalinone skeleton is known to offer a wide range of compounds for drug discovery. Owing to the importance of the quinoxalinone scaffold, we have developed a base-mediated protocol for the C3-alkylation of quinoxalinone followed by tandem cyclization to access novel types of strenuous and fused dihalo-aziridino-quinoxalinone heterocycles via the construction of C-C and C-N bonds.

Melt Polycondensation Strategy for Amide-Functionalized l-Aspartic Acid Amphiphilic Polyester Nano-assemblies and Enzyme-Responsive Drug Delivery in Cancer Cells.

Aliphatic polyesters are intrinsically enzymatic-biodegradable, and there is ever-increasing demand for safe and smart next-generation biomaterials including drug delivery nano-vectors in cancer research. Using bioresource-based biodegradable polyesters is one of the elegant strategies to meet this requirement; here, we report an l-amino acid-based amide-functionalized polyester platform and explore their lysosomal enzymatic biodegradation aspects to administrate anticancer drugs in cancer cells. l-Aspartic acid was chosen and different amide-side chain-functionalized di-ester monomers were tailor-made having aromatic, aliphatic, and bio-source pendant units.

Efficient Chemical and Enzymatic Syntheses of FAD Nucleobase Analogues and Their Analysis as Enzyme Cofactors.

Flavin adenine dinucleotide (FAD) is an essential redox cofactor in cellular metabolism. The organic synthesis of FAD typically involves coupling flavin mononucleotide (FMN) with adenosine monophosphate, however, existing synthesis routes present limitations such as multiple steps, low yields, and/or difficult-to-obtain starting materials. In this study, we report the synthesis of FAD nucleobase analogues with guanine/cytosine/uracil in place of adenine and deoxyadenosine in place of adenosine using chemical and enzymatic approaches with readily available starting materials, achieved in 1-3 steps with moderate yields (10-57 %).

Protein-Metabolite Interactions: Discovery and Significance.

Metabolites orchestrate cellular processes as either substrates, co-enzymes, inhibitors, or activators of cellular proteins such as enzymes and receptors. Although traditional biochemical and structural biology-based approaches have been successfully employed for the discovery of protein-metabolite interactions, they often fail to detect transient and low-affinity biomolecular relationships. Another limitation of these approaches is that they are performed under in vitro conditions lacking the physiological context.

Bill shape imposes biomechanical tradeoffs in cavity-excavating birds.

Organisms are subject to physical forces that influence morphological evolution. Birds use their bills as implements to perform various functions, each exerting unique physical demands. When excavating cavities, bird bills must resist a range of mechanical stresses to prevent fracture.

Kinetics of Arf1 inactivation regulates Golgi organisation and function in non-adherent fibroblasts.

Arf1 belongs to the Arf family of small GTPases that localise at the Golgi and plasma membrane. Active Arf1 plays a crucial role in regulating Golgi organisation and function. In mouse fibroblasts, loss of adhesion triggers a consistent drop (∼50%) in Arf1 activation that causes the Golgi to disorganise but not fragment.

Redox Assisted Reversible Aromaticity Transition Between 30π Hückel and 28π Möbius Dication of a Core-Modified Isophlorinoid.

The electronic properties of a hexaphyrin was fine-tuned via core-modification leading to the formation of a Hückel aromatic 30π hexaphyrin which incorporates two pyrrole and four furan rings in the π-conjugated pathway. This Hückel aromatic hexaphyrin modified its conformation upon two-electron ring oxidation either with triflic acid or Meerwein salt [Et O] [SbCl ] to yield 28π Möbius aromatic dication species. Reversible aromatic transition was established by spectroscopic techniques and further supported by quantum chemical calculations.

Increasing species richness along elevational gradients is associated with niche packing in bat assemblages.

The change in species richness along elevational gradients is a well-known pattern in nature. Niche theory predicts that increasing species richness in assemblages can either lead to denser packing of niche space ('niche packing') or an expansion into its novel regions ('niche expansion'). Traditionally, these scenarios have been studied using functional traits but stable isotopes provide advantages such as identifying the degree of resource specialisation, or niche partitioning among functionally similar species.

Proceedings of the 3rd Indian Cancer Genome Atlas Conference 2022: Biobanking to Omics: Collecting the Global Experience.

On January 13th and 14th 2022, the Center for Translational Cancer Research organized the virtual third Indian Cancer Genome Atlas (ICGA) Conference 2022 "Biobanking to Omics - Collecting the Global Experience." This conference was planned as the steppingstone to help ICGA understand the road ahead and the probable roadblocks in its preparatory phase as ICGA begins to streamline the tumor tissue biobanking and multi-omics efforts in the Indian subcontinent. The first day of the conference was dedicated to updates on the current status of ICGA, the future prospect, and the global understanding of multi-omics efforts.

Base Dependent Rearrangement of Dithiane and Dithiolane under Visible-light Photoredox catalysis.

The rearrangement of dithiolanes and dithianes to access disulfide-linked-dithioesters under visible-light photoredox catalysis via controlled C-S bond cleavage has been disclosed. Unlike, the usual deprotection of dithioacetals to corresponding aldehydes under the oxidative conditions, we observed unique regioselective oxidative reactivity of five and six membered cyclic dithioacetals to form disulfide-linked-dithioesters by exchanging DMAP and imidazole bases. The generality of the protocol has been demonstrated by exploring a wide range of substrates.

Theranostic FRET Gate to Visualize and Quantify Bacterial Membrane Breaching.

Designing new antimicrobial-cum-probes to study real-time bacterial membrane breaching and concurrently developing inquisitorial image-based analytical tools is essential for the treatment of infectious diseases. An array of aggregation-induced emission (AIE) polymers (donor) consisting of neutral, anionic, and cationic charges were designed and employed as antimicrobial theranostic gatekeepers for the permeabilization of the peptidoglycan layer-adherable crystal violet (CV, acceptor). An AIE-active tetraphenylethylene (TPE)-tagged polycaprolactone biodegradable platform was chosen, and their self-assembled tiny amphiphilic nanoparticles were employed as a gatekeeper in the construction of bacterial membrane-reinforced fluorescent resonance energy transfer (FRET) probes.

Structural Engineering of Star Block Biodegradable Polymer Unimolecular Micelles for Drug Delivery in Cancer Cells.

The present investigation reports the structural engineering of biodegradable star block polycaprolactone (PCL) to tailor-make aggregated micelles and unimolecular micelles to study their effect on drug delivery aspects in cancer cell lines. Fully PCL-based star block copolymers were designed by varying the arm numbers from two to eight while keeping the arm length constant throughout. Multifunctional initiators were exploited for stepwise solvent-free melt ring-opening polymerization of ε-caprolactone and γ-substituted caprolactone to construct star block copolymers having a PCL hydrophobic core and a carboxylic PCL hydrophilic shell, respectively.

Antagonistic Activities of Fmn2 and ADF Regulate Axonal F-Actin Patch Dynamics and the Initiation of Collateral Branching.

Interstitial collateral branching of axons is a critical component in the development of functional neural circuits. Axon collateral branches are established through a series of cellular processes initiated by the development of a specialized, focal F-actin network in axons. The formation, maintenance and remodeling of this F-actin patch is critical for the initiation of axonal protrusions that are subsequently consolidated to form a collateral branch.

Evaluation of tumor-infiltrating lymphocytes (TILs) in molecular subtypes of an Indian cohort of breast cancer patients.

Objectives: Evaluation of tumor-infiltrating lymphocytes (TILs) distribution in an Indian cohort of breast cancer patients for its prognostic significance.

Methods: A retrospective cohort of breast cancer patients from a single onco-surgeon's breast cancer clinic with a uniform treatment strategy was evaluated for TILs. Tumor sections were H&E stained and scored for the spatial distribution and percent stromal TILs infiltration by a certified pathologist.

Gemdimethyl Peptide Nucleic Acids (α/β/γ-PNA): E/Z-Rotamers Influence the Selectivity in the Formation of Parallel/Antiparallel -PNA:DNA/RNA Duplexes.

Peptide nucleic acids (PNAs) consist of an aminoethylglycine () backbone to which the nucleobases are linked through a tertiary amide group and bind to complementary DNA/RNA in a sequence-specific manner. The flexible backbone has been the target for several chemical modifications of the PNA to improve its properties such as specificity, solubility, etc. PNA monomers exhibit a mixture of two rotamers (Z/E) arising from the restricted rotation around the tertiary amide N-CO bond.

l-Amino Acid Based Phenol- and Catechol-Functionalized Poly(ester-urethane)s for Aromatic π-Interaction Driven Drug Stabilization and Their Enzyme-Responsive Delivery in Cancer Cells.

Exploiting aromatic π-interaction for the stabilization of polyaromatic anticancer drugs at the core of the polymer nanoassemblies is an elegant approach for drug delivery in cancer research. To demonstrate this concept, here we report one of the first attempts on enzyme-responsive polymers from aryl-unit containing amino acid bioresources such as l-tyrosine and 3,4-dihydroxy-l-phenylalanine (l-DOPA). A silyl ether protection strategy was adopted to make melt polymerizable monomers, which were subjected to solvent free melt polycondensation to produce silyl-protected poly(ester-urethane)s.

A pan-cancer analysis of matrisome proteins reveals CTHRC1 and a related network as major ECM regulators across cancers.

The extracellular matrix in the tumour microenvironment can regulate cancer cell growth and progression. A pan-cancer analysis of TCGA data from 30 cancer types, identified the top 5% of matrisome genes with amplifications or deletions in their copy number, that affect their expression and cancer survival. A similar analysis of matrisome genes in individual cancers identified CTHRC1 to be significantly altered.