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An enhanced DC–DC converter is proposed in this paper, based on the combination of the Cuk converter and single-ended primary-inductor converter (SEPIC). This converter uses a single switching node which is common to both Cuk and SEPIC energy transfer stages. The converter uses only one switch, yet provides dual outputs in the form of a bipolar DC bus with a common ground. Since the switch is grounded, a simple, non-isolated gate driver may be used. The proposed converter uses integrated magnetic cores to couple the input and output inductors, which significantly reduces the input current ripple. The new converter is referred to as the Coupled-Inductors Combined Cuk-SEPIC (CI-CCS) converter.

Soft magnetic composites (SMCs) based magnetic cores are attractive in high-frequency inductor design. The desired overall core permeability of SMC core can be achieved by adjusting the powder size, addition of insulation material and phosphoric acid, and pressure during the preparation process to reduce the air gap loss and ease the inductor design. The nanocrystalline alloy (Fe-Cu–Nb–Si–B) is an emerging SMC with high saturation flux density and low hysteresis loss, showing potential suitability for SMC-based magnetic cores. To date, nanocrystalline alloys are mostly used in form of laminated ribbon for magnetic cores, and nanocrystalline powder SMCs have been seldom used in practice. Also, neither experimental validation nor comparison with other commercialized and commonly used SMC cores has been reported. In this article, the structure and manufacturing process of nanocrystalline powder cores are introduced. The calculation of core loss is defined for the nanocrystalline powder core. The characteristics and performance of the nanocrystalline powder toroidal core are compared with those of existing commercial SMC cores, such as Fe–Si powder (X flux), Fe–Ni powder (High flux), Fe–Si–Al powder (Kool Mμ), and Fe-Ni–Mo powder (MPP). Experimental results are conducted at frequencies from 100 to 600 kHz to verify the loss calculation and feasibility of this new nanocrystalline powder core. [ABSTRACT FROM AUTHOR]

An enhanced DC–DC converter is proposed in this paper, based on the combination of the Cuk converter and single-ended primary-inductor converter (SEPIC). This converter uses a single switching node which is common to both Cuk and SEPIC energy transfer stages. The converter uses only one switch, yet provides dual outputs in the form of a bipolar DC bus with a common ground. Since the switch is grounded, a simple, non-isolated gate driver may be used. The proposed converter uses integrated magnetic cores to couple the input and output inductors, which significantly reduces the input current ripple. The new converter is referred to as the Coupled-Inductors Combined Cuk-SEPIC (CI-CCS) converter. [ABSTRACT FROM AUTHOR]

Sediment samples from the Karnaphuli river estuary, nearshore, and off-shore regions off the coast of Chittagong in the Bay of Bengal were analyzed for the natural radioactivity contents of 232Th, 238U and 40K and anthropogenic radioactivity contents of 137Cs and 134Cs using HPGe gamma spectrometry, together with the measurement of sediment pH and grain size analyses of the collected samples. The activity of 232Th found in sediment ranged from 10.44 q 2.31 to 64.02 q 8.13 Bq kg-1,238U activity ranged from 5.87 q 1.21 to 27.85 q 1.71 Bq kg-1, 40K activity from 118.28 q 19.70 to 608.21 q 75.70 Bq kg-1, and the activity 137Cs ranged from 0.09 q 0.06 to 4.64 q 0.19 Bq kg-1, no 134Cs radioactivity was detected at any of the sampling stations. [ABSTRACT FROM AUTHOR]

Toxic metal(loid)s, e.g., mercury, arsenic, lead, and cadmium are known for several environmental disturbances creating toxicity to humans if accumulated in high quantities. Although not discussed critically, the organo-forms of these inorganic metal(loid)s are considered a greater risk to humans than their elemental forms possibly due to physico-chemical modulation triggering redox alterations or by the involvement of biological metabolism. This extensive review describes the chemical and physical causes of organometals and organometal(loid)s distribution in the environment with ecotoxicity assessment and potential remediation strategies. Organo forms of various metal(loid)s, such as mercury (Hg), arsenic (As), lead (Pb), tin (Sn), antimony (Sb), selenium (Se), and cadmium (Cd) have been discussed in the context of their ecotoxicity. In addition, we elaborated on the transformation, speciation and transformation pathways of these toxic metal(loid)s in soil-water-plant-microbial systems. The present review has pointed out the status of toxic organometal(loid)s, which is required to make the scientific community aware of this pressing condition of organometal(loid)s distribution in the environment. The gradual disposal and piling of organometal(loid)s in the environment demand a thorough revision of the past-present status with possible remediation strategies prescribed as reflected in this review., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Static field (B 0 ) inhomogeneities present a major challenge in high-field MRI. Multicoil shimming using independent, local, direct-current (DC) shim coils has emerged as a powerful and flexible technique to address this issue. However, many-turn DC coils can lead to significant mutual coupling with radiofrequency (RF) coils, causing transmit field (B 1 + ) distortions and signal-to-noise ratio degradation., Methods: We introduce an innovative RF-transparent DC coil that performs B 0 shimming while minimizing RF performance impact. The design incorporates float traps to maintain high RF impedance, allowing flexible placement relative to the RF coil without compromising signal-to-noise ratio or affecting B 1 + . We fabricated square-shaped DC coils with float traps for 3T MRI and compared them with conventional DC coils. To demonstrate high ΔB 0 /Amp efficiency, we conducted a B 0 shimming experiment around a metal hip implant., Results: Bench tests and MRI experimental results demonstrated that the RF-transparent DC coil effectively minimized RF interference, preserved signal-to-noise ratio, and maintained B 1 + , even when placed near the RF receive coil. Additionally, the DC coil significantly improved B 0 homogeneity near metal implants and substantially reduced image distortion., Conclusion: The RF-transparent DC coil offers a flexible, effective solution for managing B 0 inhomogeneities, paving the way for integrating multiturn DC coils in clinical MRI settings without extensive hardware modifications., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: We developed a whole transcriptome sequencing (WTS)-based Consensus Molecular Subtypes (CMS) classifier using FFPE tissue and investigated its prognostic and predictive utility in a large clinico-genomic database of CRC patients (n = 24,939)., Methods: The classifier was trained against the original CMS datasets using an SVM model and validated in an independent blinded TCGA dataset (88.0% accuracy). Kaplan-Meier estimates of overall survival (OS) and time-on-treatment (TOT) were calculated for each CMS (p < 0.05 considered significant)., Results: CMS2 tumors were enriched on left-side of colon and conferred the longest median OS. In RAS-wildtype mCRC, left-sided tumors and CMS2 classification were associated with longer TOT with anti-EGFR antibodies (cetuximab and panitumumab). When restricting to only CMS2, there was no significant difference in TOT between right- versus left-sided tumors. CMS1 tumors were associated with a longer median TOT with pembrolizumab relative to other CMS groups, even when analyzing only microsatellite stable (MSS) tumors., Discussion: A WTS-based CMS classifier allowed investigation of a large multi-institutional clinico-genomic mCRC cohort, suggesting anti-EGFR therapy benefit for right-sided RAS-WT CMS2 tumors and immune checkpoint inhibitor benefit for MSS CMS1. Routine CMS classification of CRC provides important treatment associations that should be further investigated., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Liver transplantation (LT) normalizes fasting tolerance in glycogen storage disease type (GSD) 1b. However, reported outcomes post-LT with respect to correction of neutropenia, infection risk and growth are varied. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been recently shown to improve neutropenia in GSD1b patients., Methods: In this single-center retrospective study, we reviewed all children who underwent LT for GSD1b. Neutropenia, dose of granulocyte colony-stimulating factor (G-CSF), unplanned hospital attendance, anthropometrics, graft rejection, survival, and the effects of dapagliflozin were analyzed. Data from protocol biopsies obtained at 1, 5, and 10 years post-LT and immunosuppression levels were collected., Results: Eight children (6 female), all on G-CSF pre-transplant, underwent cadaveric LT for GSD1b at median age 3.6 years (IQR 3.3-5.1) with mean follow-up time of 10.3 years (95% CI 7.5-13.1). Neutrophil count and G-CSF requirement did not improve post-LT. Although a reduction in unplanned hospital attendance due to infection (0.98 [95% CI 0.76-1.26] vs. 0.49 [95% CI 0.41 to 0.57] per person-year, p < 0.01) was observed, gastrointestinal complaints and graft dysfunction accounted for a similar hospitalization burden pre- versus post-LT. Body mass index (BMI) reduced post-LT (Z-score 1.47 [95%CI 0.39-2.23] vs. 0.56 [95% CI -0.74 to 1.45], p = 0.02), with no significant change in height. Although all children and grafts have survived, 75% of recipients developed rejection, despite adequate immunosuppression levels, with two children having been found to have developed significant fibrosis on their 5-year protocol biopsy. Although dapagliflozin allowed cessation of G-CSF, no improvement in neutrophil count was observed. Despite this, a reduction in gastrointestinal and infection-related morbidity was noted following dapagliflozin., Conclusion: Although LT normalizes fasting tolerance in GSD1b and reduces hospital attendance due to infection, morbidity from infection and gastrointestinal manifestations persist. Children in our cohort experienced high rates of rejection necessitating titration of immunosuppression to balance risk of infection against organ rejection. Future studies should investigate whether early introduction of SGLT2 inhibitors post-LT impact morbidity in this group., (© 2024 Wiley Periodicals LLC.)

Cardiovascular diseases pose a major threat to both life expectancy and quality of life worldwide, and a concerning level of disease burden has been attained, particularly in middle- and low-income nations. Several drugs presently in use lead to multiple adverse events. Thus, it is urgently needed to develop safe, affordable, and effective management of cardiovascular diseases. Emerging evidence reveals a positive association between polyphenol consumption and cardioprotection. Whole wheat grain and allied products are good sources of polyphenolic compounds bearing enormous cardioprotective potential. Polyphenolic extract of the entire wheat grain contains different phenolic compounds viz. ferulic acid, caffeic acid, chlorogenic acid, p-coumaric acid, sinapic acid, syringic acid, vanillic acid, apigenin, quercetin, luteolin, etc. which exert cardioprotection by reducing oxidative stress and interfering with different toxicological processes. The antioxidant capacity has been thought to exert the cardioprotective mechanism of wheat grain polyphenolics, which predominantly suppresses oxidative stress, inflammation and fibrosis by downregulating several pathogenic signaling events. However, the combined effect of polyphenolics appears to be more prominent than that of a single molecule, which might be attained due to the synergy resulting in multimodal cardioprotective benefits from multiple phenolics. The current article covers the bioaccessibility and possible effects of wheat-derived polyphenolics in protecting against several cardiovascular disorders. This review discusses the mechanistic pharmacology of individual wheat polyphenols on the cardiovascular system. It also highlights the comparative superiority of polyphenolic extracts over a single phenolic., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Monitoring the genetic diversity and emerging mutations in SARS-CoV-2 remains crucial for understanding its evolution, given the virus's persistence in India. This study analyzes lineage dynamics, mutation screening, structural analysis, and phylodynamics of SARS-CoV-2 variants of concern (VOC) in India from October 2020 to September 2023. The predominant variants identified were alpha, beta, delta, and omicron, with delta and omicron making up 76.05 % of sequenced genomes. The B.1.617.2 lineage of the delta variant was the major contributor to COVID-19 cases before the rise of omicron. Mutation screening of non-structural proteins (NSPs) and spike proteins revealed distinct profiles for each VOC. Co-mutation patterns were analyzed, showing structural and energetic alterations. Phylogenetic analysis indicated that nsp1, nsp3, nsp4, nsp13, and nsp14 were strongly associated with increased mutation load. The study also highlighted that nsp14 and spike have similar mutability patterns, underscoring nsp14's critical role in SARS-CoV-2 infectivity and persistence. This research provides a comprehensive view of SARS-CoV-2's evolution and persistence in India., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ankur Chaudhuri reports financial support was provided by ICMR for postdoctoral Research fellowship. Subhrangshu Das reports financial support was provided by India Ministry of Science & Technology Department of Biotechnology., (Copyright © 2024. Published by Elsevier B.V.)

Brittle fracturing of materials is common in natural and industrial processes over a variety of length scales. Knowledge of individual particle dynamics is vital to obtain deeper insight into the atomistic processes governing crack propagation in such materials, yet it is challenging to obtain these details in experiments. We propose an experimental approach where isotropic dilational strain is applied to a densely packed monolayer of attractive colloidal microspheres, resulting in fracture. Using brightfield microscopy and particle tracking, we examine the microstructural evolution of the monolayer during fracturing. Furthermore, we propose and test a parameter termed Weakness that estimates the likelihood for particles to be on a crack line, based on a quantified representation of the microstructure in combination with a machine learning algorithm. Regions that are more prone to fracture exhibit an increased Weakness value, however the exact location of a crack depends on the nucleation site, which cannot be predicted a priori . An analysis of the microstructural features that most contribute to increased Weakness values suggests that local density is more important than orientational order. Our methodology and results provide a basis for further research on microscopic processes during the fracturing process.

Recently, buffer molecules have been known to affect intermolecular protein-protein interactions at physiological pH. However, the roles of buffer molecules and different monolayer protein concentrations remain elusive in controlling the interaction of gold nanoparticles (Au NPs) with protein molecules. Herein, for the first time taking phenylalanine functionalized gold nanoparticles (Au-Phe NPs) and lysozyme (Lyz) protein as model systems, we report that buffer molecules of different charges (at a particular pH) play diverse roles in protein-Au NPs interaction, particularly in protein induced Au NPs aggregation. Among different buffers, negatively charged buffer (citrate and phosphate) induces aggregation of both Au-Phe NPs and Lyz protein, whereas zwitterionic and positive buffer (HEPES, MOPS, and Tris) only cause the Au NPs aggregation. Taking the diverse role of buffer into account, we propose multimodal models for stability and protein induced aggregation mechanism of NPs at different monolayer (sub-, near-, and excess) concentrations of Lyz in different medium.

Extending upper echelon theory perspective, the paper extends the past research literatures on the effects of CEO characteristics in determining strategic choices of firms, and examines the effects of CEO's temporal orientation on entrepreneurial orientation of firms. Moreover, examining the contingent effects of environmental munificence, complexity, and dynamism in the U-shaped relationship between CEO's temporal orientation and entrepreneurial orientation of firm contributes to the understanding of the boundary conditions and determines the strength of the relationship between CEO's temporal orientation and EO of firm. We test our hypotheses using panel data analysis of Indian firms during 2007-2016., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: From 2020, with advent of COVID-19 pandemic, Tripura has experienced SARS-CoV-2 viral evolution in accordance with other parts of India. Since January 2022, the Omicron variant of SARS-CoV-2 virus became the predominant lineage circulating in India and neighboring countries. This study characterizes the viral genome of the omicron variant circulating in the state since its inception to June, 2023., Methods and Results: The current study was performed on nasopharyngeal and oropharyngeal samples received from the various departments of AGMC, as well as eight district hospitals from Tripura. The positive samples with a cycle threshold value of 25 or less for the E and/or N gene were considered for whole genome sequencing using Illumina Miseq NGS platform. Majority of the sequences belonged to Clade 21 L, with BA.5.2 being the major sub variant detected during the study period. Majority of the mutations were detected in the Spike protein region, including L24-, P25-, P26-, V213G, G339D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, S477N, T478K, Q498R, Y505H, Q954H and N969K. All the sequences uniquely showed the mutations A27S and G142D in N terminal domain in Spike protein, not being reported from other Indian sequences like BA.5 variants. T9I, A63T and P13L were major substitutions in E, M and N protein regions respectively. Escape of mutants from vaccine induced immunity was mostly observed in BA.2 sub variants, majority endowed with the triplet mutation of K417N + E484K + N501Y., Conclusion: The current study indicates that Omicron variants circulating in the state of Tripura is comparable to other regions of India and the neighbouring country of Bangladesh. Genetic mutations increasing viral transmissibility have been identified in the circulating viral genomes., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Cilia are specialized structures found on a variety of mammalian cells, with variable roles in the transduction of mechanical and biological signals (by primary cilia, PC), as well as the generation of fluid flow (by motile cilia). Their critical role in the establishment of a left-right axis in early development is well described, as is the innate immune function of multiciliated upper airway epithelium. By contrast, the dynamics of ciliary status during organogenesis and postnatal development is largely unknown. In this study, we define the progression of ciliary status within the endothelium, epithelium, and mesenchyme of the lung. Remarkably, we find that endothelial cells (ECs) lack PC at all stages of development, except in low numbers in the most proximal portions of the pulmonary arteries. In the lung epithelium, a proximodistal ciliary gradient is established over time, as the uniformly mono-ciliated epithelium transitions into proximal, multiciliated cells, and the distal alveolar epithelium loses its cilia. Mesenchymal cells, interestingly, are uniformly ciliated in early development, but with restriction to PDGFRα+ fibroblasts in the adult alveoli. This dynamic process in multiple cellular populations both challenges prior assertions that PC are found on all cells, and highlights a need to understand their spatiotemporal functions., Highlights: Primary cilia are found broadly throughout early embryonic tissues.Primary cilia are observed in both epithelial and mesenchymal cells in the early lung.Pulmonary endothelial cells largely do not possess primary cilia during embryonic development.Differential multiciliation and loss of epithelial cilia in a proximal-distal axis.Maintenance of cilia in adult pulmonary PDGFRα+ fibroblasts.

The endothelium forms a monolayer, which functions to ensure tissue homeostasis. Barrier hyperpermeability has been associated with lung, brain and eye disease. An emerging body of evidence reports the involvement of Never-in-Mitosis A - Related Kinases in vascular responses, suggesting their potential value as potential therapeutic targets in endothelial-dependent disorders., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hydrogels are indispensable for a variety of applications. Conventional biomaterial-based hydrogels, typically made from proteins or polysaccharides, often suffer from high costs, poor mechanical properties, and limited chemical functionality for modification. In this work, we present a novel hydrogel developed from modified castor oil, which is a renewable and cost-effective resource. Castor oil-based oligomer (CG) was synthesized using glycidyl methacrylate and triethylamine via ring-opening polymerization. The oligomer formed a gel only with Cu 2+ ions among the various systematically studied metal ions. Comprehensive density functional theory calculations, atoms in molecules analysis, and steady and dynamic shear rheology were conducted to investigate the metal-binding sites and metal-oligomer interactions as well as the self-healing and viscoelastic properties of the oil-based hydrogels. The hydrogel exhibited 94% self-healing efficiency and performed as a recyclable rhodamine B dye adsorbent (73-90%). This innovative approach offers a novel, cost-effective, and sustainable alternative to traditional hydrogels, paving the way for advanced applications.

India is dealing with both nutritional and agricultural issues. The maximum area of agricultural land with irrigation capabilities has been largely utilized, while the amount of dry land is expanding. The influence is distinct on farmer's livelihoods and earnings, which ultimately affects nutritional security. In order to attain nutritional security and the goal of SDG (Sustainable Development Goals), millets are sustainable solutions, with respect to high nutritional content, bioactive and medicinal properties, and climate resilience. The nutrient profile of millet includes 60%-70% carbohydrate content, 3.5%-5.2% fat, and 7.52%-12.1% protein sources. A wide spectrum of amino acids, including cysteine, isoleucine, arginine, leucine, tryptophan, lysine, histidine, methionine, tyrosine, phenylalanine, threonine, and valine are generally present in millets. Mineral content in millets includes calcium, phosphorus, potassium, sodium, and magnesium. Additionally, millets are an excellent source of bioactive molecules such as polyphenol, phenolic acid, flavonoids, active peptides, and soluble fiber, which have a wide range of therapeutic applications, including the prevention of free radical damage, diabetes, anti-microbial, anti- biofilm, and anti-cancer effects. This review will focus on the nutritional profile and health benefits of millet considering the present-day food security problems.

Despite the efficacy of antiretroviral therapy (ART) in reducing the global incidence of vertical HIV transmissions, more than 120,000 children are still infected with the virus each year. Since ART cannot clear the HIV reservoir that is established soon after infection, children living with HIV (CLWH) are forced to rely on therapy for their lives and suffer from long-term drug-related complications. Pediatric HIV infection, like adult infection, is associated with gut microbial dysbiosis, loss of gut epithelial integrity, bacterial translocation, CD4 + T cell depletion, systemic immune activation, and viral reservoir establishment. However, unlike in adults, HIV that is vertically acquired by infants interacts with a gut microbiome that is continuously evolving while concomitantly shaping the infant's immune ontogeny. Therefore, to determine whether there may be interventions that target the HIV reservoir through microbiome-directed approaches, understanding the complex tripartite interactions between the transmitted HIV, the maturing gut microbiome, and the developing immune system during early life is crucial. Importantly, early life is the time when the gut microbiome of an individual is highly dynamic, and this temporal development of the gut microbiome plays a crucial role in educating the maturing immune system of a child. Therefore, manipulation of the gut microbiome of CLWH to a phenotype that can reduce HIV persistence by fostering an antiviral immune system might be an opportune strategy to achieve ART-free viral suppression in CLWH. This review summarizes the current state of knowledge on the vertical transmission of HIV, the developing gut microbiome of CLWH, and the immune landscape of pediatric elite controllers, and explores the prospect of employing microbial modulation as a potential therapeutic approach to achieve ART-free viral suppression in the pediatric population., (© 2024. The Author(s).)

The interaction of N -alkoxy-1 H -indole-1-carboxamides with transition metals leads to indole-fused heterocyclic scaffolds through directing group leaving/migration, [3 + 2], N-C2 [4 + 1], and [4 + 2] annulations. However, the corresponding O-C2 [4 + 2] annulation reactions have never been reported. Herein, we report the chemoselective annulation of N -alkoxy-1 H -indole-1-carboxamides catalyzed by Rh(III), affording [1,3]oxazinoindolones through a hitherto unknown reaction pathway. This unprecedented C2 oxygen cyclization, rather than the known C2 nitrogen cyclization to form oxazinoindolones via five key steps, has been explained using density functional theory.

S2P intramembrane metalloproteases regulate diverse signaling pathways across all three domains of life. However, the mechanism by which S2P metalloproteases engage substrates and catalyze peptide hydrolysis within lipid membranes has remained elusive. Here we determine the cryo-EM structure of the S2P family intramembrane metalloprotease SpoIVFB from Bacillus subtilis bound to its native substrate Pro-σ K . The structure and accompanying biochemical data demonstrate that SpoIVFB positions Pro-σ K at the enzyme active site through a β-sheet augmentation mechanism, and reveal key interactions between Pro-σ K and the interdomain linker connecting SpoIVFB transmembrane and CBS domains. The cryo-EM structure and molecular dynamics simulation reveal a plausible path for water to access the membrane-buried active site of SpoIVFB, and suggest a possible role of membrane lipids in facilitating substrate capture. These results provide key insight into how S2P intramembrane metalloproteases capture and position substrates for hydrolytic proteolysis within the hydrophobic interior of a lipid membrane., (© 2024. The Author(s).)

The collision-induced rate coefficients of ortho-para conversion for the H + + H 2 reaction provide accurate information to probe the lifetime of cold environments in interstellar media. Rotationally resolved reaction probabilities are calculated at the low collision energy regime (0 < E col ≤ 0.3 eV) by employing the coupled three-dimensional (3D) time-dependent wave packet (TDWP) formalism in hyperspherical coordinates on a recently constructed ab initio ground adiabatic potential energy surface of H 3 + [ J. Chem. Phys. 2014 , 141 , 204306] for the process H + + H 2 ( v = 0, j = 0-5) → H + + H 2 ( v ' = 0, j '). Cross-sections are then computed from the converged reaction probabilities as a function of total angular momentum ( J ) over the same energy regime and subsequently employed to obtain the rate constants for the ortho-to-para (O-P) and para-to-ortho (P-O) conversions and their ratio. The ratio of ortho-para conversion shows (a) appropriate convergence with the inclusion of a higher number of initial rotational states as well as a reasonable agreement with the results from a quantum statistical method and (b) a peak at lower temperature that could be due to the available collision energy for transitions involving lower rotational states ( j = 0 → j ' = 1).

Brain cancer is regarded as one of the most life-threatening forms of cancer worldwide. Oxidative stress acts to derange normal brain homeostasis, thus is involved in carcinogenesis in brain. The Nrf2/Keap1/ARE pathway is an important signaling cascade responsible for the maintenance of redox homeostasis, and regulation of anti-inflammatory and anticancer activities by multiple downstream pathways. Interestingly, Nrf2 plays a somewhat, contradictory role in cancers, including brain cancer. Nrf2 has traditionally been regarded as a tumor suppressor since its cytoprotective functions are considered to be the principle cellular defense mechanism against exogenous and endogenous insults, such as xenobiotics and oxidative stress. However, hyperactivation of the Nrf2 pathway supports the survival of normal as well as malignant cells, protecting them against oxidative stress, and therapeutic agents. Plants possess a pool of secondary metabolites with potential chemotherapeutic/chemopreventive actions. Modulation of Nrf2/ARE and downstream activities in a Keap1-dependant manner, with the aid of plant-derived secondary metabolites exhibits promise in the management of brain tumors. Current article highlights the effects of Nrf2/Keap1/ARE cascade on brain tumors, and the potential role of secondary metabolites regarding the management of the same., (© 2024. The Author(s).)

Visualizing and measuring molecular-scale interactions in living cells represents a major challenge, but recent advances in single-molecule super-resolution microscopy are bringing us closer to achieving this goal. Single-molecule super-resolution microscopy enables high-resolution and sensitive imaging of the positions and movement of molecules in living cells. HP1 proteins are important regulators of gene expression because they selectively bind and recognize H3K9 methylated (H3K9me) histones to form heterochromatin-associated protein complexes that silence gene expression, but several important mechanistic details of this process remain unexplored. Here, we extended live-cell single-molecule tracking studies in fission yeast to determine how HP1 proteins interact with their binding partners in the nucleus. We measured how genetic perturbations that affect H3K9me alter the diffusive properties of HP1 proteins and their binding partners, and we inferred their most likely interaction sites. Our results demonstrate that H3K9 methylation spatially restricts HP1 proteins and their interactors, thereby promoting ternary complex formation on chromatin while simultaneously suppressing off-chromatin binding. As opposed to being an inert platform to direct HP1 binding, our studies propose a novel function for H3K9me in promoting ternary complex formation by enhancing the specificity and stimulating the assembly of HP1-protein complexes in living cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Organic compounds bearing one or more carbocycles in their molecular structure have a discernible presence in all major classes of organic products of industrial significance. However, sourcing carbocyclic compounds from exhaustible, anthropogenic carbon (e.g., petroleum) raises serious concerns about sustainability in the chemical industries. This review discusses recent advances in the renewable synthesis of carbocyclic compounds from biomass components following catalytic pathways. The mechanistic insights, process optimizations, green metrics, and alternative synthetic strategies of carbocyclic compounds have been detailed. Moreover, the renewable syntheses of carbocycles have been assessed against their existing synthetic routes from petroleum for better perspectives on their sustainability and technological preparedness. This work will assist the researchers in acquiring updated information on the sustainable synthesis of carbocyclic compounds from various biomass components, comprehending the research gaps, and developing superior synthetic processes for their commercial production., (© 2024 Wiley‐VCH GmbH.)

Nuisance imposed by biotic and abiotic stressors on diverse agroecosystems remains an area of focus for the scientific fraternity. However, emerging contaminants such as microplastics (MP) have imposed additional dimension (alone or in combinations with other stressors) in agroecosystems and keep escalating the challenges to achieve sustainability. MP are recognized as persistent anthropogenic contaminants, fetch global attention due to their unique chemical features that keeps themselves unresponsive to the decaying process. This review has been theorized to assess the current research trends (along with possible gap areas), widespread use of MP, enhancement of the harshness of heavy metals (HMs), complex interactions with physico-chemical constituents of arable soil, accumulation in the edible parts of field crops, dairy products, and other sources to penetrate the food web. So far, the available review articles are oriented to a certain aspect of MP and lack a totality when considered from in soil-water-food perspective. In short, a comprehensive perspective of the adverse effects of MP on human health has been assessed. Moreover, an agro-techno-socio-health prospective-oriented critical assessment of policies and remedial measures linked with MP has provided an extra edge over other similar articles in influential future courses of research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The onset of malaria causes the induction of various inflammatory markers in the host's body, which in turn affect the body's homeostasis and create several cerebral complications. Polarization of myeloid-derived suppressor cells (MDSCs) from the classically activated M1 to alternatively activated M2 phenotype increases the secretion of pro-inflammatory molecules. Treatment with recombinant IL-33 (rIL-33) not only alters this MDSC's polarization but also targets the glycolysis pathway of the metabolism in MDSCs, rendering them less immunosuppressive. Along with that, the Helper T-cells subset 17 (Th17)/T regulatory cells (Tregs) ratio is skewed towards Th17, which increases inflammation by producing more IL-17. However, treating with rIL-33 also helps to restore this ratio, which brings back homeostasis. During malaria infection, there is an upregulation of IL-12 production from dendritic cells along with a distorted myeloid dendritic cells (mDC)/plasmacytoid dendritic cells (pDC) ratio towards mDCs promoting inflammation. Administering rIL-33 will also subvert this IL-12 production and increase the population of pDC in the host's immune system during malaria infection, thus restoring mDC/pDC to homeostasis. Therefore, treatment with rIL-33 to reduce the pro-inflammatory signatures and maintenance of immune homeostasis along with the increase in survivability could be a potential therapeutic approach for cerebral malaria.

GHRH is a neuropeptide associated with a diverse variety of activities in human physiology and immune responses. The present study reviews the latest information on the involvement of GHRH in the immune system and inflammation, suggesting that GHRH antagonists may deliver a new therapeutic possibility in disorders related to immune system dysfunction and inflammation., (© 2024. The Author(s).)

Primary cilia on granule cell neuron progenitors in the developing cerebellum detect sonic hedgehog to facilitate proliferation. Following differentiation, cerebellar granule cells become the most abundant neuronal cell type in the brain. While granule cell cilia are essential during early developmental stages, they become infrequent upon maturation. Here, we provide nanoscopic resolution of cilia in situ using large-scale electron microscopy volumes and immunostaining of mouse cerebella. In many granule cells, we found intracellular cilia, concealed from the external environment. Cilia were disassembled in differentiating granule cell neurons-in a process we call cilia deconstruction-distinct from premitotic cilia resorption in proliferating progenitors. In differentiating granule cells, cilia deconstruction involved unique disassembly intermediates, and, as maturation progressed, mother centriolar docking at the plasma membrane. Unlike ciliated neurons in other brain regions, our results show the deconstruction of concealed cilia in differentiating granule cells, which might prevent mitogenic hedgehog responsiveness. Ciliary deconstruction could be paradigmatic of cilia removal during differentiation in other tissues., (© 2024 Ott et al.)

Site-selective C-H bond functionalization of arenes at the para position remains extremely challenging primarily due to its relative inaccessibility from the catalytic site. As a consequence, it is significantly restricted to limited molecular scaffolds. Herein, we report a method for the para-C-H borylation of aromatic aldimines and benzylamines using commercially available ligands under iridium catalysis. The established method displays excellent para selectivity for variously substituted aromatic aldimines, benzylamines and bioactive molecules. Based on several control experiments, it is proposed that a Lewis acid-base interaction between the nitrogen and boron functionality guides the para selectivity via a steric shield for the aromatic aldimines, where Bpin acts as a transient directing group. However, the steric shield of the in situ generated N-Bpin moiety controlled the overall selectivity for the para borylation of benzylamines., (© 2024 Wiley-VCH GmbH.)

Growth hormone (GH) is a crucial regulator of growth, cell reproduction, and regeneration; and it is controlled by growth hormone-releasing hormone (GHRH) and somatostatin. Lipopolysaccharides (LPS) can compromise endothelial function, leading to increased inflammation and vascular leak. Octreotide (OCT) is an FDA-approved synthetic somatostatin analog (SSA) used to treat acromegaly and neuroendocrine tumors. The present study investigates the effects of OCT on LPS-induced injury in bovine and human lung endothelial cells, as well as in mouse lungs. Our in vitro observations suggest that OCT effectively counteracts LPS-induced endothelial leak, inflammation, and reactive oxygen species (ROS) generation. Furthermore, OCT reduces bronchoalveolar lavage fluid (BALF) protein concentration in an experimental model of Acute Lung Injury (ALI). Our study suggests that OCT mitigates LPS-induced endothelial cell and lung injury, suggesting that it may represent an exciting therapeutic possibility in diseases related to barrier dysfunction., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In cultured cells, herpes simplex virus (HSV) infectivity is successfully inhibited by sulfated polysaccharides. Herein, we utilized an amalgamated extraction-sulfation procedure to produce two xylogalactofucan sulfates (S203 and S204) from Spatoglossum asperum using ClSO 3 H.Pyr/DMF and SO 3 .Pyr/DMF reagents, respectively. Among these xylogalactofucans, the 17 ± 12 kDa polymer (S203) with 14 % sulfate exhibited activity on several HSV variants, including an acyclovir-resistant HSV-1 strain. This is the first report of the anti-HSV activity of a sulfated xylogalactofucan of S. asperum. The effective concentration 50 % (EC 50 ) value of S203 against HSV-1 strain F was 0.6 μg/mL with a selectivity index of 833. The backbone of this polymer (S203) is made up mostly of (1 → 4)-linked-α-l-Fucp units having sulfate groups typically at O-3 and sometimes at O-2 positions. Oligosaccharides containing Xyl, Gal and Fuc units confirms that they are an integral part of a single polymer, another novelty of this study. The EC 50 values of the native xylogalactofucan (S202) and the SO 3 .Pyr/DMF modified polymer (S204), containing 2 % and 6 % sulfates, were >100 and 3.3 μg/mL, respectively. Introduction of sulfate groups enhanced their capability to inhibit the infection of cells by HSV-1. These findings suggest feasibility of inhibiting HSV attachment to cells by blocking viral entry with polysaccharide having specific structure., Competing Interests: Declaration of competing interest I have nothing to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We present an elegant and efficient method for Ru(II)-catalyzed C-H activation, followed by a diverse range of intermolecular cross-dehydrogenative coupling reactions. This process is facilitated by an intrinsic directing group (DG) and includes the in situ transformation of the DG into common and useful functional groups. Notably, this method avoids the installation and deinstallation of the directing group. Our approach enables the selective functionalization of benzimidate, coupled with the cyclization of o -alkynyl-aniline, resulting in the high-yield synthesis of diverse compounds such as indoles, and indenones. The sequential formation of C-N, C-C, and C-O bonds, followed by hydrolysis, underscores the versatile in situ transformation of the directing group. This work not only broadens the synthetic toolbox for constructing complex heterocyclic structures but also highlights the potential for sustainable and selective synthesis of valuable compounds.

Installing coordinately unsaturated Fe-N-C structural units on polymer-composite-derived N-doped carbon offers highly active Fe-N x sites for the electrochemical oxygen evolution reaction (OER) and reactive oxygen species (ROS) generation in tumor cells. An NH 4 Cl-driven high-temperature etching method was employed for the formation of FeSA950NC with coordinately unsaturated single Fe-atoms in an Fe-N(sp 2 )-C structural unit together with N vacancies ( V N ) and sp 3 defects. The carbonization of Fe-phen@ZIF-8 at 800 °C for 30 min under argon, followed by grinding Fe-ZIF-8@RF-urea with NH 4 Cl at 950 °C for 2 hours, resulted in sp 3 carbon defects and V N sites with coordination unsaturation in Fe-N x due to NH 4 Cl decomposition to NH 3 and HCl, which produced substantial internal stress for etching the carbon matrix. FeSA950NC was used to treat both A549 lung cancer cells and NIH3T3 mouse fibroblast cells to determine its potential as an efficient tumor therapeutic strategy using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and ROS assays. Additionally, FeSA950NC provided high stability and excellent OER activity through the Fe-N(sp 2 )-C structural unit on pyridinic nitrogen by delivering at a minimum overpotential of 300 mV, which is much lower than that of structurally similar Fe-atom sites. The significantly stronger ROS and OER activities of FeSA950NC suggested the role of V N and sp 3 -carbon defects with coordinately unsaturated Fe-N 2 sites in improving its catalytic performance.

This report demonstrates a unique route for translating a non-responsive fluorophore into a responsive one to optically recognize uric acid (UA) in physiological-mimicking conditions. The explicit 'turn ON-turn OFF' fluorescence switching upon sequential disaggregation-reaggregation of the self-aggregated 3,3'-bisindolyl(phenyl)methane molecules materializes a straightforward, trouble-free supramolecular UA sensing platform.

Evapotranspiration is one of the crucial elements in water balance equations and plays a pivotal role in the water and energy cycle of an area. An accurate and precise estimation and prediction of reference evapotranspiration (ETo) is necessary for regional management of water resources and irrigation scheduling. The challenge of predicting daily evapotranspiration with limited meteorological data in Bangladesh. This study aims to predict daily evapotranspiration using limited meteorological data of Bangladesh by three deep learning (CNN, GRU, LSTM) and one hybrid (CNN-GRU) model. The novel method of hybrid CNN-GRU models, which have not been commonly used for this purpose. The performance of models was evaluated by five accuracy matrices R 2 , RMSE, MAE, MAPE, and CE and comparison is visualized by radar graphs. The study's novelty lies in the use of hybrid CNN-GRU models to estimate reference evapotranspiration, as this algorithm has not been commonly used for this purpose. In the case of the Rangpur station, the hybrid CNN-GRU algorithm outperformed other models, achieving the best values across various statistical metrics during both the training and testing phases. The highest correlation coefficient values of approximately 0.994 and 0.995. Moreover, during training and testing stages, the hybrid model had the lowest MAE (0.076, 0.068) and RMSE (0.138, 0.106) at the Rangpur station. Additionally, in the Sreemangal station, it can be notable that the statistical parameter RSME found superior results in the hybrid model around 0.225 and 0.174, respectively. In addition, the highest R 2 and CE values were noted as 0.986, 0.987 and 0.985, 0.986 during the training and testing phases, respectively. The comparison suggests that the hybrid model will be best suited for prediction with the limited meteorological data. The outcome of the present research signifies the ability of deep learning methods in the prediction of evapotranspiration and the dominant variables affecting the changes the in context of Bangladesh., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Efficient and sustainable seawater electrolysis is still limited due to the interference of chloride corrosion at the anode. The designing of suitable electrocatalysts is one of the crucial ways to boost electrocatalytic activity. However, the approach may fall short as achieving high current density often occurs in chlorine evolution reaction (CER)-dominating potential regions. Thereby, apart from developing an OER-active high-entropy alloy-based electrocatalyst, the present study also offers a unique way to protect anode surface under high current density or potential by using MoO 4 2- as an effective inhibitor during seawater oxidation. The wide variation of d-band center of high-entropy alloy-based electrocatalyst allows great oxygen evolution reaction (OER) proficiency exhibiting an overpotential of 230 mV at current density of 20 mA cm -2 . Besides, the electrocatalyst demonstrates impressive stability over 500 h at high current density of 1 A cm -2 or at a high oxidation potential of 2.0 V versus RHE in the presence of a molybdate inhibitor. Theoretical and experimental studies reveal MoO 4 2- electrostatically accumulated at anode surface due to higher adsorption ability, thereby creating a protective layer against chlorides without affecting OER., (© 2024 Wiley‐VCH GmbH.)

Amomum dealbatum Roxb. parts have been traditionally used as remedies for joint pain, diabetes, muscular rheumatism, antiseptic, and abscesses in Arunachal Pradesh, Assam, and Tripura. Ethyl acetate sub-fraction E3 had significantly inhibited the α-glucosidase (IC 50 5.385 μg/mL). The molecular docking revealed quercetin-3-O-galactoside to be the most potent α-glucosidase inhibitor (binding energy -43.214 kcal/mol). Using the QSAR model, the pIC 50 values of myricetin, gallic acid, quercetin-3-O-galactoside, and acarbose were predicted to be 5.65235, 4.39858, 5.65235, and 6.03058, respectively. For the first time, quercetin-3-O-galactoside, myricetin, and gallic acid have been isolated from the flowers of A. dealbatum (ADF). E3 decreased blood glucose level to a near-normal concentration (100.60 ± 2.94 mg/dL) in comparison to diabetic control rats (575.20 ± 24.80 mg/dL). The results have strongly suggested the potential of ADF in treating diabetes. This lesser-known plant has the potential to uncover its full medicinal properties through further in-depth research.

Non-canonical nucleotides, generated as oxidative metabolic by-products, significantly threaten the genome integrity of Plasmodium falciparum and thereby, their survival, owing to their mutagenic effects. PfHAM1, an evolutionarily conserved inosine/xanthosine triphosphate pyrophosphohydrolase, maintains nucleotide homeostasis in the malaria parasite by removing non-canonical nucleotides, although structure-function intricacies are hitherto poorly reported. Here, we report the X-ray crystal structure of PfHAM1, which revealed a homodimeric structure, additionally validated by size-exclusion chromatography-multi-angle light scattering analysis. The two monomeric units in the dimer were aligned in a parallel fashion, and critical residues associated with substrate and metal binding were identified, wherein a notable structural difference was observed in the β-sheet main frame compared to human inosine triphosphate pyrophosphatase. PfHAM1 exhibited Mg ++ -dependent pyrophosphohydrolase activity and the highest binding affinity to dITP compared to other non-canonical nucleotides as measured by isothermal titration calorimetry. Modifying the pfham1 genomic locus followed by live-cell imaging of expressed mNeonGreen-tagged PfHAM1 demonstrated its ubiquitous presence in the cytoplasm across erythrocytic stages with greater expression in trophozoites and schizonts. Interestingly, CRISPR-Cas9/DiCre recombinase-guided pfham1-null P. falciparum survived in culture under standard growth conditions, indicating its assistive role in non-canonical nucleotide clearance during intra-erythrocytic stages. This is the first comprehensive structural and functional report of PfHAM1, an atypical nucleotide-cleansing enzyme in P. falciparum., (© 2024 Federation of European Biochemical Societies.)

The present study tends to evaluate the possible potential of bio-active Morroniside (MOR), against alloxan (ALX)-induced genotoxicity and hyperglycaemia. In silico prediction revealed the interaction of MOR with Poly (ADP-ribose) polymerase (PARP) protein which corroborated well with experimental in vitro L6 cell line and in vivo mice models. Data revealed the efficacy of MOR in the selective activation of PARP protein and modulating other stress proteins NF-κB, and TNF-α to initiate protective potential against ALX-induced genotoxicity and hyperglycaemia. Further, the strong interaction of MOR with CT-DNA (calf thymus DNA) analyzed through CD spectroscopy, UV-Vis study and ITC data revealed the concerted action of bio-factors involved in inhibiting chromosomal aberration and micronucleus formation associated with DNA damage. Finally, MOR does not play any role in microbial growth inhibition which often occurs due to hyperglycemic dysbiosis. Thus, from the overall findings, we may conclude that MOR could be a potential drug candidate for the therapeutic management of induced-hyperglycaemia and genotoxicity.Communicated by Ramaswamy H. Sarma.

The present treatment for Alzheimer's disease (AD) involves well known synthetic acetylcholine esterase (AChE) inhibitor drugs which besides having short duration of action also have deleterious impact on human health. Therefore, there is a need for natural plant-based biomolecule(s) with potential AChE inhibition activity (ies). The aim of the work is to design a spice-based nano-vehicle as a novel green alternative of synthetic AD drugs by nanoencapsulating a solvent-less supercritical CO 2 extract of small cardamom seeds (SC E ) having a synergistic consortium of five antioxidant molecules, using polyethylene glycol and emulsifiers, selected based on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analyses. Ellman's assay and enzyme inhibition kinetics of the antioxidant molecules as well as the extract and its nanoliposomal formulation (SC E -NL) were performed, followed by rigorous molecular docking and dynamics studies using MM-PBSA and umbrella sampling. The antioxidants exhibited significant AChE inhibition in vitro , individually with 1, 8-cineole having the least IC 50 value of 65.53 ± 0.05 µg/mL. . Although SC E -NL had higher IC 50 value (575.67 ± 0.5 µg/mL) vis-à-vis that of rivastigmine (67.52 ± 0.02 µg/mL), it is safer for usage being 'green'.The Lineweaver-Burk plots (V max ∼1.04 mM/min) revealed competitive mode(s) of inhibition of AChE with each of these antioxidants. Binding energy analyses suggested very good binding free energies and stable docking/binding complexes (between the antioxidants and AChE). This study has delivered a nanoliposomal vehicle of food antioxidants as a putative 'green' alternative of synthetic AChE inhibitor drugs.Communicated by Ramaswamy H. Sarma.

Silver cluster-assembled materials (SCAMs) epitomize well-defined extended crystalline frameworks that combine the ingenious designability at the atomic/molecular level and high structural robustness. They have captivated the interest of the scientific fraternity because of their modular construction which enables to systematically tailor their functions, and their capacity to not only inherit the characteristics of component building units but also introduce their uniqueness in endowing the final material with extraordinary properties. Herein, we demonstrate the synthesis of a novel (3,6)-connected two-dimensional (2D) SCAM [Ag 12 (S t Bu) 6 (CF 3 COO) 6 (THIT) 6 ] n (described as TUS 5, THIT = 2,4,6-tri(1 H -imidazol-1-yl)-1,3,5-triazine) composed of Ag 12 cluster nodes and tritopic imidazolyl linkers. We have leveraged, for the first time, this precisely architected extended SCAM structure as a support matrix for enzyme immobilization. The electrostatic attraction between the negatively charged amano lipase PS and positively charged TUS 5 as well as the surface hydrophobicity of TUS 5 catered to great binding of lipase onto the TUS 5 matrix, in addition to boosting the activity of lipase via interfacial activation. Capitalizing on the cooperative benefits of organic and inorganic support matrices wherein organic supports impart with cost-efficiency, biocompatibility, and improved enzyme stability and reusability and inorganic supports confer high thermal, mechanical and microbial resistance, we have utilized the immobilized lipase on TUS 5 SCAM (lipase@TUS 5) for the kinetic resolution of ( R , S )-1-phenylethanol by transesterification reaction. Importantly, lipase@TUS 5 could attain appreciably higher conversion into ( R )-1-phenylethyl acetate, besides featuring superior thermal stability, solvent tolerance and recyclability, over the native lipase.

Background: While serum Krebs von den Lungen-6 (KL-6) has been found to be a helpful    biomarker in interstitial lung diseases for evaluating disease severity and progression, especially in connective tissue disease-associated interstitial lung disease (CTD ILD) and idiopathic non-specific interstitial pneumonia (NSIP), data on correlation of serum KL-6 levels with radiological fibrosis and pulmonary function parameters is lacking in treatment naïve Idiopathic Pulmonary Fibrosis (IPF) patients., Methods: Serum KL-6 levels were measured in thirty-nine treatment naïve newly detected IPF patients using automated immunofluorescence enzyme assay (AIA) by Tosoh Corporation, bioscience division, Tokyo, Japan. Fibrosis score was calculated by independent visual assessment of the pattern and severity of abnormalities on high resolution computed tomography (HRCT) thorax. HRCT fibrosis scores were correlated with serum KL-6 levels and pulmonary function parameters like forced vital capacity (FVC), diffusion capacity of lung for carbon monoxide (DLco)., Results: Median value of serum KL-6 levels was 1519 U/ml (range 199.41-6055 U/ml). There was positive correlation of serum KL-6 with HRCT fibrosis score (r=0.692, p<0.001) and negative correlation with FVC (r=-0.511, p=0.001) and DLco (r=-0.354, p=0.043). In the HRCT fibrosis score pattern subset analysis, the presence of reticulation revealed weak negative and statistically insignificant correlation (r=-0.116, p=0.481) while traction bronchiectasis and honeycombing exhibited statistically significant positive correlation (r=0.425, p=0.007; r=0.584, p<0.001 respectively) with serum KL-6 levels., Conclusion: Serum KL-6 levels showed a positive correlation with the degree of fibrotic abnormalities on HRCT thorax and pulmonary function parameters, indicating a potential use of serum KL-6 in monitoring of parenchymal fibrosis in Idiopathic Pulmonary fibrosis.

The syntheses of novel spirobenzazepinoindole derivatives has been achieved through a highly efficient and synthetic route. The approach involves a two-step reaction, utilizing indole derivatives, 2-amino benzyl alcohol, and ninhydrin as key starting materials under mild reaction conditions. The reaction proceeds via a sequential cascade process involving cyclization, condensation and spiro-annulation, leading to the formation of the spirobenzazepinoindole core structure in good to excellent yields. The method offers broad substrate scope, high atom economy, and operational simplicity. The synthesized spirobenzazepinoindoles were fully characterized by spectroscopic techniques, including NMR ( 1 H & 13 C), IR and mass spectrometry. The methodology provides a valuable tool for the rapid generation of structurally complex spirobenzazepinoindoles, which could serve as scaffolds for the development of new therapeutic agents., (© 2024 Wiley-VCH GmbH.)

Azomethine ylides are generated using either organocatalysts or metal catalysts via a ballet of decarboxylative C-N coupling choreographed by prolines. These strategies enable diastereoselective [3 + 2] cycloaddition, C-C coupling, and ring annulation, providing sustainable routes. The synthesized pyrrolizines and other heterocycles have potential applications in the development of crucial biomolecules and pharmaceuticals. The endoselectivity of the azomethine ylide is realized and supported through DFT calculations.

Introduction: Persons with non-ambulatory spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have marked loss of bone mineral density below the level of lesion that is directly associated with increased risk of long-bone fractures. There is a paucity of research that has successfully implemented rehabilitation and/or exercise training interventions to mitigate bone loss after acute SCI or reverse bone loss that has already occurred in chronic SCI. This paper describes a research protocol to compare the effect of exoskeletal-assisted walking (EAW) alone versus EAW plus transcutaneous spinal cord stimulation (EAW+tSCS) on bone density, geometry and strength in a cohort of chronic SCI participants., Methods and Analysis: After meeting eligibility criteria and completing baseline testing, sixteen participants will be block randomised into the EAW alone group or the EAW+tSCS combined group (n=8 each group). Each group will receive a total of 108 overground training sessions (60 min sessions, 3 times a week, for 36 weeks) for the 9-month training period. Imaging for bone density and geometry by dual-energy X-ray absorptiometry and peripheral quantitative CT will be performed prior to starting the intervention (baseline), after 72 training sessions, and again after 108 sessions in each of the intervention arms. CT imaging of both lower extremities will be performed at baseline and at the 9-month time point in each of the intervention arms. Finite element models of bone loading will be generated based on three-dimensional (3D) reconstruction of bone architecture from CT imaging prior to and 9 months after the intervention., Ethics and Dissemination: This study is currently approved by the Kessler Foundation and James J. Peters VA Medical Center Institutional Review Board. A member of the research team will review and explain the study consent form and will have all eligible participants sign prior to participation in the study. Results from this study will be disseminated to clinicians and researchers in the SCI community at national and international conferences., Trial Registration Number: NCT03096197., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)