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ISG15 plays a crucial role in the innate immune response and has been well-studied due to its antiviral activity and regulation of signal transduction, apoptosis, and autophagy. ISG15 is a ubiquitin-like protein that is activated by an E1 enzyme (Uba7) and transferred to a cognate E2 enzyme (UBE2L6) to form a UBE2L6-ISG15 intermediate that functions with E3 ligases that catalyze conjugation of ISG15 to target proteins. Despite its biological importance, the molecular basis by which Uba7 catalyzes ISG15 activation and transfer to UBE2L6 is unknown as there is no available structure of Uba7. Here, we present cryo-EM structures of human Uba7 in complex with UBE2L6, ISG15 adenylate, and ISG15 thioester intermediate that are poised for catalysis of Uba7-UBE2L6-ISG15 thioester transfer. Our structures reveal a unique overall architecture of the complex compared to structures from the ubiquitin conjugation pathway, particularly with respect to the location of ISG15 thioester intermediate. Our structures also illuminate the molecular basis for Uba7 activities and for its exquisite specificity for ISG15 and UBE2L6. Altogether, our structural, biochemical, and human cell-based data provide significant insights into the functions of Uba7, UBE2L6, and ISG15 in cells. ISGylation plays a crucial role in the innate immune response and requires sequential activity of E1, E2, and E3 enzymes. Here, the authors present cyro-EM structures that reveal the molecular mechanisms underlying ISG15 activation by the E1 enzyme Uba7 and transfer to its cognate E2 enzyme UBE2L6.

The SARS-CoV-2 non-structural protein 1 (Nsp1) contains an N-terminal domain and C-terminal helices connected by a short linker region. The C-terminal helices of Nsp1 (Nsp1-C-ter) from SARS-CoV-2 bind in the mRNA entry channel of the 40S ribosomal subunit and blocks mRNA entry, thereby shutting down host protein synthesis. Nsp1 suppresses host immune function and is vital for viral replication. Hence, Nsp1 appears to be an attractive target for therapeutics. In this study, we have in silico screened Food and Drug Administration (FDA)-approved drugs against Nsp1-C-ter. Among the top hits obtained, montelukast sodium hydrate binds to Nsp1 with a binding affinity (K D ) of 10.8 ± 0.2 µM in vitro. It forms a stable complex with Nsp1-C-ter in simulation runs with –95.8 ± 13.3 kJ/mol binding energy . Montelukast sodium hydrate also rescues the inhibitory effect of Nsp1 in host protein synthesis, as demonstrated by the expression of firefly luciferase reporter gene in cells. Importantly, it shows antiviral activity against SARS-CoV-2 with reduced viral replication in HEK cells expressing ACE2 and Vero-E6 cells. We, therefore, propose montelukast sodium hydrate can be used as a lead molecule to design potent inhibitors to help combat SARS-CoV-2 infection.

RAD51C is a tumor suppressor gene with over 285 variants of unknown significance (VUS) found in primary ovarian tumors. RAD51C is a paralog of the recombinase RAD51, and it forms complexes with other paralogs to regulate RAD51 activity. We screened 27 ovarian cancer-derived RAD51C VUS to identify those that affect the assembly of functional tetrameric RAD51B-C-D-XRCC2 (BCDX2) complex. With yeast 3-hybrid and biochemical analyses, we identify a mutation cluster of the RAD51C Walker B region affecting protein interactions with other RAD51 paralogs. By further analyzing these variants for homologous recombination (HR), replication fork regression, DNA binding and ATPase activity, and RAD51 filament formation, we identified separation-of-function alleles that uncouple RAD51C distinct enzymatic activities with HR and replication. Thus, our analysis of RAD51C identifies additional VUS with functional defects, which will aid in pathogenicity classification and inform future strategies to treat individuals harboring RAD51C loss-of-function alleles. The tumor suppressor RAD51C is mutated in ovarian cancers. Through variant analysis the authors identify a mutation cluster in the RAD51C Walker B region important for the repair of DNA double-strand breaks and replicative damage. By identifying Walker B separation-of-function alleles, they show that these activities can be uncoupled.

ObjectiveNeurocognitive disabilities in Duchenne muscular dystrophy (DMD) children beginning in early childhood and distal DMD gene deletions involving disruption of Dp140 isoform are more likely to manifest significant neurocognitive impairments. MRI data analysis techniques like brain-network metrics can provide information on microstructural integrity and underlying pathophysiology.MethodsA prospective study on 95 participants [DMD = 57, and healthy controls (HC) = 38]. The muscular dystrophy functional rating scale (MDFRS) scores, neuropsychology batteries, and multiplex ligand-dependent probe amplification (MLPA) testing were used for clinical assessment, IQ estimation, and genotypic classification. Diffusion MRI and network-based statistics were used to analyze structural connectomes at various levels and correlate with clinical markers.ResultsMotor and executive sub-networks were extracted and analyzed. Out of 57 DMD children, 23 belong to Dp140 + and 34 to Dp140- subgroup. Motor disabilities are pronounced in Dp140- subgroup as reflected by lower MDFRS scores. IQ parameters are significantly low in all-DMD cases; however, the Dp140- has specifically lowest scores. Significant differences were observed in global efficiency, transitivity, and characteristic path length between HC and DMD. Subgroup analysis demonstrates that the significance is mainly driven by participants with Dp140- than Dp140 + isoform. Finally, a random forest classifier model illustrated an accuracy of 79% between HC and DMD and 90% between DMD- subgroups.ConclusionsCurrent findings demonstrate structural network-based characterization of abnormalities in DMD, especially prominent in Dp140-. Our observations suggest that participants with Dp140 + have relatively intact connectivity while Dp140- show widespread connectivity alterations at global, nodal, and edge levels. This study provides valuable insights supporting the genotype–phenotype correlation of brain-behavior involvement in DMD children.

The development of efficient and non-toxic fuels for direct liquid fuel cells has highlighted ascorbic acid (AA) as a sustainable energy source. This study presents a combined theoretical and experimental investigation of ascorbate oxidation on an Au-Pt electrode in alkaline medium. Density functional theory (DFT) calculations reveal that Au deposition on Pt creates a more homogeneous and active surface, significantly enhancing the adsorption energy of ascorbate (−7.54 eV vs. −5.80 eV on bare Pt). Electrochemically, this translates to a superior performance, where the Au-Pt electrode achieves a 38% reduction in charge-transfer resistance, a higher current density, and a lower Tafel slope of 77 mV dec−1, indicating accelerated kinetics. The electrode also retains its activity over 1000 cycles, confirming exceptional durability. This synergistic combination of theoretical and experimental results establishes Au-Pt as a premier catalyst for sustainable ascorbate-based energy conversion.

Two truxene‐based porous polymers incorporating dibenzothiophene dioxide units are synthesized via Cu(I)‐catalyzed azide–alkyne cycloaddition and evaluated as fluorescence sensors for nitroanilines in 1,3‐dioxolane and water. The polymers differ in alkyl chain length on the truxene methylene units (methyl vs hexyl), which strongly influences fluorescence behavior and porosity. Both exhibit similar absorption profiles, while TX(C6)DBTO shows a much larger BET surface area and retains fluorescence in the solid state and in water, unlike TX(Me)DBTO . This stability is attributed to steric hindrance from hexyl groups, which disrupt packing and suppress aggregation, as supported by single‐crystal data of its halogenated precursor. Both polymers display selective quenching toward 4‐nitroaniline (p‐NA) and 2,6‐dichloro‐4‐nitroaniline (DCN) in 1,3‐dioxolane, achieving micromolar detection limits. Time‐resolved fluorescence measurements confirm that quenching is not associated with energy transfer processes, but rather with the inner filter effect, consistent with the strong spectral overlap between analyte absorption and polymer excitation bands. TX(C6)DBTO preserves sensing performance in water, offering a robust, metal‐free platform for detecting nitroaniline‐based pollutants under environmentally relevant conditions.

Hydrogels are rapidly emerging as a versatile and promising platform for advancing energy storage and conversion technologies. Their intrinsic properties—such as high water content, excellent ionic conductivity, and inherent mechanical flexibility—position them as key materials for a wide range of applications, including supercapacitors, flexible membranes, and components in fuel cells and solar cells. Despite significant progress, challenges remain in enhancing their mechanical durability, developing scalable fabrication methods, and ensuring environmental sustainability. Recent breakthroughs in composite hydrogel systems, innovative manufacturing techniques such as 3D printing, and self-healing strategies are driving substantial improvements in device performance and operational lifespan. Emphasizing the importance of interdisciplinary approaches and innovative material design, this review highlights the transformative potential of hydrogel-based energy systems in shaping a sustainable and flexible energy future. The advancements discussed herein have promising implications for the development of high-performance, environmentally friendly, and adaptable energy devices capable of meeting the demands of next-generation applications.

Background: DM1 is a multisystem disorder caused by expansion of a CTG triplet repeat in the 3' non-coding region of DMPK. Neuropsychological consequences and sleep abnormalities are important associations in DM1. Objective: To describe the clinical phenotype, disease progression and characterize the sleep alterations and cognitive abnormalities in a sub-set of patients. Materials and Methods: A retrospective study on 120 genetically confirmed DM1 cases. Findings in neuropsychological assessment and multiple sleep questionnaires were compared with 14 age and sex matched healthy individuals. All 120 patients were contacted through letters/telephonic consultation/hospital visits to record their latest physical and functional disabilities. Results: The mean age at symptom onset was 23.1 ± 11.4 years, M: F = 3.8:1, mean duration of illness = 14.3 ± 9.5 years. Clinically 54.2% had adult onset form, juvenile = 27.5%, infantile = 10.8%, late adult onset = 7.5%. Paternal transmission occurred more frequently. The predominant initial symptoms were myotonia (37.5%), hand weakness (21.7%), lower limb weakness (23.3%) and bulbar (10%). Twenty patients completed sleep questionnaires (SQ). Abnormal scores were noted in Epworth sleepiness scale (55%); Pittsburgh sleep quality index (45%); Berlin SQ (30%); Rapid eye movement sleep Behaviour Disorder SQ (15%); Restless leg syndrome rating scale (10%). Neuropsychological assessment of 20 patients revealed frontal executive dysfunction, attention impairment and visuospatial dysfunction. Frontal lobe was most affected (72%) followed by parietal (16%) and temporal lobe (12%). Conclusions: The current study provides a comprehensive account of the clinical characteristics in Indian patients with DM1. Hypersomnolence was most commonly seen. Excessive daytime sleepiness and Sleep disordered breathing were the most common sleep related abnormality. Cognitive impairment comprised predominantly of frontal lobe dysfunction.

This book is about a popular manifestation of Islamic devotion that embraces a pluralist setting, keeping itself in a dynamic dialogue with non–Muslim practices. With evidence from various public devotional narratives and ritual practices, this book argues that even universal understanding of living Islam remains incomplete, if we do not consider this locally produced pluralized devotional setting that surrounds it. This book seeks to address various aspects of local and localized Islams through an examination of Gugudu’s local and popular transformation of normative Islam, giving particular focus to the various devotional rituals that blend Muslim and Hindu practices in the public event of Muharram.

Chemotherapy is one of the important treatment modules in early as well as advanced stages of cancer. However, the major limitation of chemotherapy is the development of chemoresistance in the transformed cells of cancer patients, which leads to cancer recurrence. Long non-coding RNAs (lncRNA) are the transcripts longer than 200 nucleotides in length, which are reported to associate with the initiation, progression, recurrence, and metastasis of different cancers. Several lncRNAs have been implicated in the prevalence of chemoresistant phenotypes and also in the restoration of drug sensitivity in chemoresistant cells. LncRNAs such as HOTAIR, H19, and a lot more are involved in the chemoresistance of cancer cells. Therefore, targeting the lncRNAs may serve as a novel strategy for treating chemoresistant cancer. This review throws light on the role of lncRNA in chemoresistance along with the perspective of the therapeutic targets for the treatment of multiple cancers.