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Recent emergence of cephalosporin-resistant <i>Salmonella</i> Typhi in India due to the endemic clone acquiring IncFIB(K) plasmid encoding <i>bla</i> <sub>CTX-M-15</sub> gene
No full textThe emergence and spread of Salmonella Typhi (S. Typhi) resistant to third-generation cephalosporins is a serious global health concern. In this study, we genomically characterized 142 cephalosporin-resistant S. Typhi strains isolated from India. Comparative genome analysis revealed the emergence of a new clone of ceftriaxone-resistant S. Typhi harboring three plasmids of the incompatibility groups IncFIB(K), IncX1, and IncFIB(pHCM2). Among these, the IncFIB(K) plasmid confers resistance to third-generation cephalosporins through the blaCTX-M-15 gene, along with other resistance determinants such as aph(3"), aph(6'), sul2, dfrA14, qnrS, and tet(A). Phylogenetic analysis showed that the isolates from Gujarat (n = 140/142) belong to a distinct subclade (genotype 4.3.1.2.2) within genotype 4.3.1.2 (H58 lineage II). Single nucleotide polymorphism-based phylogenetic analysis of the core genes in IncFIB(K) suggested a close relatedness of the plasmid backbone to that of IncFIB(K) from other Enterobacteriales, indicating that H58 lineage II possesses the capability to acquire MDR plasmids from these organisms. This could indicate the potential onset of a new wave of ceftriaxone-resistant S. Typhi in India. The implementation of control measures—such as vaccination and improved water, sanitation, and hygiene systems—is crucial in areas where MDR or extensively drug-resistant S. Typhi strains are prevalent to curb the spread and impact of these resistant strains
Nonlinear Optical Properties of 0D Chiral Hybrid Bismuth Iodides
No full textChiral hybrid metal halides show great promise for nonlinear optical (NLO) applications like circularly polarized second harmonic generation (SHG). The inherent toxicity of lead is a concern for the widespread adoption of frequently explored lead-based chiral hybrid halides. Here, we report the second and third-order NLO properties of lead-free 0D chiral compounds, (R-/S-MBA)4Bi2I10, and their achiral counterpart, (Rac-MBA)4Bi2I10 (MBA: methylbenzylammonium) under excitation wavelength ranging 1360–1590 nm. Chiral (R-/S-MBA)4Bi2I10 exhibits strong SHG along with stronger third harmonic generation (THG). The chiral crystals showed high sensitivity to the handedness of circularly polarized pump light (gSHG - CD ≈ 9% at 1510 nm). The THG response shows resonance enhancement matching the excitonic absorption. Achiral (Rac-MBA)4Bi2I10 exhibits the maximum THG response (χ(3) = 1.05 × 10-18 m2 V-2). Z-scan measurements with non-resonant femtosecond pulse excitation at 800 nm yield high nonlinear absorption coefficients (β) and nonlinear refractive index (n2) for all three samples, with (Rac-MBA)4Bi2I10 exhibiting the highest values. These hybrid chiral metal halides, with efficient second and third-order nonlinearity, and high optical stability, are potential candidates for NLO applications such as Kerr-based optical switching, circularly polarized up-conversion, and communication
Nonlinear Optical Properties of 0D Chiral Hybrid Bismuth Iodides
No full textChiral hybrid metal halides show great promise for nonlinear optical (NLO) applications like circularly polarized second harmonic generation (SHG). The inherent toxicity of lead is a concern for the widespread adoption of frequently explored lead-based chiral hybrid halides. Here, we report the second and third-order NLO properties of lead-free 0D chiral compounds, (R-/S-MBA) 4Bi2I10, and their achiral counterpart, (Rac-MBA)4Bi2I10 (MBA: methylbenzylammonium) under excitation wavelength ranging 1360–1590 nm. Chiral (R-/S-MBA)4Bi2I10 exhibits strong SHG along with stronger third harmonic generation (THG). The chiral crystals showed high sensitivity to the handedness of circularly polarized pump light (qSHG - CD ≈ 9% at 1510 nm). The THG response shows resonance enhancement matching the excitonic absorption. Achiral (Rac-MBA)4Bi2I10 exhibits the maximum THG response (χ(3) = 1.05 × 10-18 m2 V-2). Z-scan measurements with non-resonant femtosecond pulse excitation at 800 nm yield high nonlinear absorption coefficients (β) and nonlinear refractive index (n2) for all three samples, with (Rac-MBA)4Bi2I10 exhibiting the highest values. These hybrid chiral metal halides, with efficient second and third-order nonlinearity, and high optical stability, are potential candidates for NLO applications such as Kerr-based optical switching, circularly polarized up-conversion, and communication
Defect-Mediated Exciton Storage in Ag–In–Ga–S Nanocrystals
No full textColloidal Ag–In–Ga–S nanocrystals (NCs) represent a promising class of RoHS-compliant light emitters exhibiting narrow excitonic photoluminescence (PL). Here, we unveil a unique exciton storage mechanism in Ag–In–Ga–S NCs. Temperature-dependent PL and ultrafast transient absorption spectroscopy show that thermally activated back transfer from long-lived (∼1.8 μs) shallow defects repopulates the excitons, increasing both exciton lifetime and PL intensity. The thermally activated back transfer increases the excitonic PL lifetime systematically from a few nanoseconds at 6.5 K to about 100 ns at 300 K, a reverse trend compared to typical semiconductor NCs like CdSe. This reverse trend of Ag–In–Ga–S NCs mirrors dopant-mediated exciton dynamics in Mn-doped CdSe NCs but arises here from intrinsic defects of the undoped NCs. Our results establish a generalizable pathway for prolonging excitonic lifetime (exciton storage) with high PL intensity in semiconductor NCs (quantum dots), enabling potential applications in photocatalysis, photonic memory, and optoelectronic devices
PPARγ mediated enhanced lipid biogenesis fuels Mycobacterium tuberculosis growth in a drug-tolerant hepatocyte environment
No full textMycobacterium tuberculosis (Mtb) infection of the lungs, besides producing prolonged cough with mucus, also causes progressive fatigue and cachexia with debilitating loss of muscle mass. While anti-tuberculosis (TB) drug therapy is directed toward eliminating bacilli, the treatment regimen ignores the systemic pathogenic derailments that probably dictate TB-associated mortality and morbidity. Presently, it is not understood whether Mtb spreads to metabolic organs and brings about these impairments. Here we show that Mtb creates a replication-conducive milieu of lipid droplets in hepatocytes by upregulating transcription factor PPARγ and scavenging lipids from the host cells. In hepatocytes, Mtb shields itself against the common anti-TB drugs by inducing drug-metabolizing enzymes. Infection of the hepatocytes in the in vivo aerosol mice model can be consistently observed post-week 4 along with enhanced expression of PPARγ and drug-metabolizing enzymes. Moreover, histopathological analysis indeed shows the presence of Mtb in hepatocytes along with granuloma-like structures in human biopsied liver sections. Hepatotropism of Mtb during the chronic infectious cycle results in immuno-metabolic dysregulation that could magnify local and systemic pathogenicity, altering clinical presentations
A combination of systemic mannitol and mannitol modified polyester nanoparticles for caveolae-mediated gene delivery to the brain
No full textOvercoming the blood-brain barrier (BBB) remains a significant challenge for nucleic acid delivery to the brain. We have explored a combination of mannitol-modified poly (β-amino ester) (PBAE) nanoparticles and systemic mannitol injection for crossing the BBB. We incorporated mannitol in the PBAE polymer for caveolae targeting and selected monomers that may help avoid delivery to the liver. We also induced caveolae at the BBB through systemic mannitol injection in order to create an opportunity for the caveolae-targeting nanoparticles (M30 D90) containing plasmid DNA to cross the BBB. When a clinically relevant dose was administered intravenously in this caveolae induction model, M30 D90 demonstrated significant transgene expression of a reporter plasmid in the brain, with selective uptake by neuronal cells and minimal liver accumulation. We demonstrate that caveolae modulation using systemic mannitol administration and caveolae targeting using designed nanoparticles are necessary for efficient delivery to the brain. This delivery platform offers a simple, scalable, and controlled delivery solution and holds promise for treating brain diseases with functional targets
Weighted Deformable Network for Efficient Segmentation of Lung Tumors in CT
No full textThe computerized delineation and prognosis of lung cancer is typically based on Computed Tomography (CT) image analysis, whereby the region of interest (ROI) is accurately demarcated and classified. Deep learning in computer vision provides a different perspective to image segmentation. Due to the increasing number of cases of lung cancer and the availability of large volumes of CT scans every day, the need for automated handling becomes imperative. This requires efficient delineation and diagnosis through the design of new techniques for improved accuracy. In this article, we introduce the novel Weighted Deformable U-Net (WDU-Net) for efficient delineation of the tumor region. It incorporates the Deformable Convolution (DC) that can model arbitrary geometric shapes of region of interests. This is enhanced by the Weight Generation (WG) module to suppress unimportant features while highlighting relevant ones. A new Focal Asymmetric Similarity (FAS) loss function helps handle class imbalance. Ablation studies and comparison with state-of-the-art models help establish the effectiveness of WDU-Net with ensemble learning, tested on five publicly available lung cancer datasets. Best results were obtained on the LIDC-IDRI lung tumor test dataset, with an average Dice score of 0.9137, the Hausdorff Distance 95% (HD95) of 5.3852, and Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.9449
Mitochondrial Sorting and Assembly Machinery: Chaperoning a Moonlighting Role?
No full textThe mitochondrial outer membrane (OMM) β-barrel proteins link the mitochondrion with the cytosol, endoplasmic reticulum, and other cellular membranes, establishing cellular homeostasis. Their active insertion and assembly in the outer mitochondrial membrane is achieved in an energy-independent yet highly effective manner by the Sorting and Assembly Machinery (SAM) of the OMM. The core SAM constituent is the 16-stranded transmembrane β-barrel Sam50. For over two decades, the primary role of Sam50 has been linked to its function as a chaperone in the OMM, wherein it assembles all β-barrels through a lateral gating and β-barrel switching mechanism. Interestingly, recent studies have demonstrated that despite its low copy number, Sam50 performs various diverse functions beyond assembling β-barrels. This includes maintaining cristae morphology, bidirectional lipid shuttling between the ER and mitochondrial inner membrane, import of select proteins, regulation of PINK1-Parkin function, and timed trigger of cell death. Given these multifaceted critical regulatory functions of SAM across all eukaryotes, we now reason that SAM merely moonlights as the hub for β-barrel biogenesis and has indeed evolved a diverse array of primary roles in maintaining mitochondrial function and cellular homeostasis
An investigation into substitution‐kinetics, biomolecular responses and multimodal anticancer potential of a dihalide pd(ii) complex
No full textThis study addresses a novel palladium dihalide complex, cis-[Pd(PCAH)Cl₂] (C1), as a promising anticancer agent. XRD analysis reveals a deformed square planar geometry stabilized by hydrogen bonds and π•••π interactions. The M−Cl bonds in C1 demonstrate susceptibility to nucleophilic substitution by 2,2′-bipyridine (Bpy), with kinetic parameters evaluated using spectrophotometry. Fluorometric and spectrophotometric investigations demonstrate that C1 binds to CT DNA and protein with an avidity of around 105 M−1. The interaction with DNA is multifaceted, employing covalent bonding and intercalation, as supported by viscosity measurements. Fluorescence lifetime experiments illustrate that C1 produces static dampening of BSA fluorescence, implying structural adjustments near the tryptophan residue, further corroborated by spectroscopic analyses. The pair's (BSA and C1) FRET distance has also been computed. In vitro cytotoxicity tests suggest that C1 selectively suppresses the growth of breast carcinoma, MDA-MB-231 with IC50=20±2.64 μM, while showing minimal effects on non-cancerous HEK-293 cells. The mechanism of action includes the creation of ROS, leading to mitochondrial apoptosis, as evidenced by various assays, including annexin-V-FITC/PI labeling. Overall, complex C1 exhibits encouraging promise as a selective anticancer drug with a ROS-triggered apoptotic mechanism, particularly effective against breast carcinoma MDA-MB-231 cells
Dynamic analysis of the effect of vertical clearance on an existing perpendicular crossing tunnel in soil.
No full textA 3D finite element modelling was carried out to analyse the dynamic response of two perpendicular crossing tunnels in sandy soil to understand the linings’ behaviour and surrounding soil. The parametric study included the analysis of three different amplitudes of harmonic sine waves across five cases of cross-tunnels. The results indicated that the most favourable case regarding surface settlement, maximum absolute dynamic bending moment, and horizontal convergence is when the second tunnel is located at a significant pillar depth below the first. The critical cases experience a settlement of 1.1% of the tunnel diameter, a dynamic bending moment of 13.7% lower than the single tunnel case and a dynamic horizontal convergence of 0.26%. Whilst considering dynamic earth pressure and axial thrust, the preferred location of the second tunnel can be below the first tunnel, irrespective of pillar depth. This investigation can provide a reference for designing and constructing cross-tunnels at different vertical spacing under dynamic loading conditions for dry sandy soil