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NOD1 and NOD2, founding members of the NOD-like receptor (NLR) family, play a crucial role in host defense against bacterial infections. Recognition of peptidoglycan-derived ligands triggers ATP-dependent oligomerization of the NACHT domain, exposing the CARD domains that recruit the adaptor protein RIP2 via CARD-CARD interactions to activate the NF-κB signaling cascade. Although NOD1/2-RIP2 interactions and RIP2CARD filament assembly are established, the precise interfaces that stabilize hetero-CARD filaments remain poorly defined. Here, we integrate in silico structural modeling with molecular dynamics (MD) simulations to elucidate structurally compatible arrangements of NOD1-RIP2 and NOD2-RIP2 hetero-CARD filaments. Our results reveal that NOD1CARD subunits form a structurally compatible homomeric scaffold via canonical (type-I-III) interfaces, accommodating multiple tiers of RIP2CARD rings at both filament termini. Meanwhile, the NOD2 tandem CARDs adopt multiple discrete conformations, reflecting a more intricate structural mechanism. In stable filament conformations, tandem CARDs converge at the type-II interface, with RIP2CARD rings stacking onto CARDa (top-down) and CARDb (bottom-up) interfaces, highlighting the structural role of NOD2CARDb in RIP2-mediated CARD-CARD interaction. In silico mutagenesis, involving charge-reversal and alanine scanning of key interfacial residues, disrupts NOD1-RIP2 and NOD2-RIP2 interactions at both top-down and bottom-up interfaces, leading to rapid interface destabilization within 0.1-0.4 μs of simulation. Together, these results reveal conserved and receptor-specific mechanisms governing NOD1/2-RIP2 CARD-CARD interactions and provide deeper structural and dynamic insights into the complex structural mechanisms for NLR-mediated inflammatory signaling.

A 24-year-old man with a kidney transplant presented with a 3-day history of diarrhea. An examination of a saline wet mount of a stool sample showed an organism moving in a “falling leaf” pattern (shown in a video).

Extensively drug-resistant (XDR) gram-negative pathogens represent a critical therapeutic challenge in intensive care units, with mortality rates exceeding 50 %. The synergistic combination of ceftazidime-avibactam with aztreonam offers a novel therapeutic approach, particularly in carbapenemase-producing Enterobacterales. This prospective observational study analysed 24 critically ill adult ICU patients with confirmed XDR gram-negative infections from October 2024 to April 2025. Comprehensive antimicrobial susceptibility testing, carbapenemase detection, and E- strip based synergy testing of ceftazidime-avibactam (CZA) with aztreonam (ATM), cefepime-enmetazobactam (FEP-ENM) testing were performed. Primary outcomes included clinical response, microbiological clearance, and 30-day mortality. Statistical analysis included descriptive statistics, Fisher's exact test, Mann-Whitney U test, logistic regression analysis and Kaplan-Meier survival analysis. Twenty-four XDR isolates were analysed: Klebsiella pneumoniae (n = 18, 75 %) and Escherichia coli (n = 6, 25 %). All demonstrated resistance to individual agents (CZA; MIC >16 μg/ml), (ATM; MIC >256 μg/mL) and FEP-ENM (zone size <6 mm). Carbapenemase detection revealed NDM in 91.7 % (22/24), with NDM + OXA-48 co- production in 66.7 % (16/24). Synergy was demonstrated in 62.5 % (15/24) cases with significant MIC reduction (median 0.5 μg/mL, IQR 0.25–1.0). Clinical improvement occurred in 31.3 % (5/16) of synergy-positive versus 12.5 % (1/8) of synergy-negative cases (p = 0.631). Microbiological clearance was achieved exclusively in synergy- positive cases (18.8 % vs 0 %, p = 0.534). Independent predictors of mortality included septic shock presentation (OR 3.5, 95 % CI 0.7–17.8, p = 0.134). Ceftazidime-avibactam plus aztreonam combination demonstrated significant in vitro synergy against XDR pathogens with promising trends toward improved clinical outcomes in critically ill patients, representing a crucial salvage therapy option warranting larger randomized controlled trials.

Composites derived from polyvinylidene fluoride (PVDF) play an important role in advanced dielectric energy storage due to their outstanding characteristics, including remarkable flexibility, low density, high dielectric permittivity, and superior dielectric breakdown strength. The strategically designed composition significantly enhances the energy storage performance, such as discharge energy density (Ue) and charge–discharge energy efficiency (η). Consequently, we employed the solution cast method to create flexible composite films, combining PVDF polymer with strontium tungstate (SrWO4) ceramic. X-ray diffraction analysis revealed the coexistence of α and electroactive β phases in PVDF. These phases have a substantial effect on the dielectric characteristics and energy storage density of composites. Flexible nanocomposites of PVDF and SrWO4 exhibit high dielectric constant and low tangent loss. Micrographs obtained using scanning electron microscopy (SEM) showed that the morphology of the composite varies according to the amount of filler present in the matrix. The impedance spectroscopy method yielded intriguing findings regarding the roles of both grain and grain boundaries in the overall resistance characteristics of the composites. The frequency-dependent behavior of alternating conductivity follows Jonscher’s power law. The hysteresis loops indicate that the nanocomposite film maintains favorable ferroelectric properties. The present study suggests some promising applications for advanced dielectric capacitors and energy storage devices.

The report in the article has emphasised the characterisation (structural analysis, sample microstructure, dielectric, impedance, and modulus) of a layered perovskite ceramic oxide LiNdSnO 4 (LNSO) prepared by solid-state reaction method. The compound formation and phase identification with multiphase are confirmed using X-ray diffraction (XRD). This XRD shows that the material contains LNSO as the predominant and minor impurity phases. The crystallite size and strain are calculated to be 106 nm and 0.001, respectively. SEM study shows that the grains formed in the sample are a combination of the big (~ 2.23 μm) and small grains (~ 0.95 μm). The ac conductivity follows the Jonscher’s power law. The non-Debye type of relaxation mechanism and the hopping mechanism are shown by the shifting of the curve in the high-frequency zone in modulus spectra. The FT/IR study demonstrates the presence of a vibrational band in each element of the sample. The dielectric constant and loss increased sharply at 300 °C. The maximum activation energy (0.5598 eV) was found at a lower frequency. Nyquist spectrum indicates the presence of grain and grain boundary properties of the material. The semicircular behaviour of impedance spectra demonstrated that the material might be semiconducting. This study concluded that the compound is useful for NTCR thermistor devices.

This article thoroughly investigates the structural and electrical properties of a layered perovskite structure, KSmSnO 4 (KSSO), which was synthesized using the solid-state method at high temperatures. The compound has a cubic crystal structure (a = b = c = 10.535 Å). The surface morphology is done by scanning electron microscope (SEM), which shows the homogenous distribution of grains. The compositional analysis was carried out by EDX. The study of conductivity, modulus, dielectric constant, dielectric loss and impedance analysis was done. The electrical analysis of the compound has been done which describes the change of dielectric constant and dielectric loss concerning temperature and frequency. The complex impedance spectroscopy (CIS) is done for the frequency (100 Hz to 1 MHz) and for the temperature (25–500 °C). The calculated data and fitted data matches well in the nyquist plot. The variation of imaginary part of the modulus with frequency was fitted using KWW function. The variation of the ac conductivity of the material under alternating current varies according to Jonscher's universal power law. The activation energy was calculated for the frequency 100 Hz to 1 MHz.This article concludes by discussing future possibilities and scientific challenges in NTCR thermistor using KSSO.

Abstract New Delhi Metallo beta-lactamase (NDM) is of significant public health concern due to its enormous potential to hydrolyse all major beta-lactams including carbapenems. Amino acid substitutions outside the active site reportedly affect NDM beta-lactamase activities. Here, the effect of amino acid substitutions in the possible omega-like loop region of NDM-5 has been elucidated. Overall, three substitution mutations near active site of NDM-5 were done, namely, E152A, S191A and D223A and subsequently, the change in antimicrobial resistance was monitored upon expressing each mutant in a suitable host. Among the three mutants, E152A substitution on a loop near the active site resulted in significant reduction in beta-lactam antibiotic resistance as compared to NDM-5 that compelled us to conduct further studies on the E152A-substituted NDM-5. The purified NDM-5 was able to hydrolyse all the beta-lactams tested whereas the E152A mutation suppressed its activities. NDM-5 showed maximum kcat/Km ratio against penicillins and carbapenems and had lower Km as compared to NDM-5_E152A. Though, the amino acid substitution did not affect the overall folding pattern of NDM-5, significant differences in thermal stability between the wild-type and mutated protein were observed. Therefore, we infer that the E152 residue is important in regulating the beta-lactam hydrolysing properties of NDM-5. Glutamic acid at 152nd position is important for NDM-5 activity.

Dopa-responsive dystonia (DRD) encompasses a group of clinically and genetically heterogeneous disorders that typically manifest as limb-onset, diurnally fluctuating dystonia presenting in early life and exhibits a robust and sustained response to levodopa treatment. DRD is one of the treatable dystonia syndromes of childhood. It starts with the involvement of lower limb and associated with characteristic diurnal variation. Many times it is misdiagnosed as cerebral palsy due to selective lower limb preference. We report a series of three cases of DRD which were previously misdiagnosed. The first case presented as myelopathy and other two were diagnosed as cerebral palsy. It is a treatable condition with very good response to drugs. Early diagnosis and adequate therapy can prevent from catastrophic complications.

Dystroglycanopathy is a type of congenital muscular dystrophy caused by mutations causing defective glycosylation of a dystrophin-associated glycoprotein, dystroglycan and as such is a very rare disease entity. We are reporting a 1-year-old girl child with dystroglycanopathy who presented with motor predominant developmental delay. She had motor development quotient of 52, mental development quotient of 75, facial dysmorphism, mixed hypotonia with a global decrease in muscle power, and areflexia. Serum CPK level was elevated; magnetic resonance imaging brain revealed multiple intraparenchymal cysts in the cerebellum with disorganized folia. Next-generation sequencing revealed a homozygous missense mutation in exon 3 of the ISPD gene (p.Gln215His; ENST00000407010) consistent with the diagnosis of dystroglycanopathy muscle-eye-brain disease. Genetic counseling and prenatal diagnosis for subsequent pregnancies were advised for the family, apart from appropriate rehabilitation for the child.