Multifunctional biocatalyst for conjugate reduction and reductive amination.

Chiral amine diastereomers are ubiquitous in pharmaceuticals and agrochemicals1, yet their preparation often relies on low-efficiency multi-step synthesis2. These valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of the molecule. Herein we characterize a multifunctional biocatalyst for amine synthesis, which operates using a mechanism that is, to our knowledge, previously unreported. This enzyme (EneIRED), identified within a metagenomic imine reductase (IRED) collection3 and originating from an unclassified Pseudomonas species, possesses an unusual active site architecture that facilitates amine-activated conjugate alkene reduction followed by reductive amination. This enzyme can couple a broad selection of α,ß-unsaturated carbonyls with amines for the efficient preparation of chiral amine diastereomers bearing up to three stereocentres. Mechanistic and structural studies have been carried out to delineate the order of individual steps catalysed by EneIRED, which have led to a proposal for the overall catalytic cycle. This work shows that the IRED family can serve as a platform for facilitating the discovery of further enzymatic activities for application in synthetic biology and organic synthesis.

Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program.

While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived polygenic transcriptome risk score (PTRS) to improve cross-ethnic portability of risk prediction. We constructed the PTRS using summary statistics from application of PrediXcan on large-scale GWASs of lung function (forced expiratory volume in 1 s [FEV1] and its ratio to forced vital capacity [FEV1/FVC]) in the UK Biobank. We examined prediction performance and cross-ethnic portability of PTRS through smoking-stratified analyses both on 29,381 multi-ethnic participants from TOPMed population/family-based cohorts and on 11,771 multi-ethnic participants from TOPMed COPD-enriched studies. Analyses were carried out for two dichotomous COPD traits (moderate-to-severe and severe COPD) and two quantitative lung function traits (FEV1 and FEV1/FVC). While the proposed PTRS showed weaker associations with disease than PRS for European ancestry, the PTRS showed stronger association with COPD than PRS for African Americans (e.g., odds ratio [OR] = 1.24 [95% confidence interval [CI]: 1.08-1.43] for PTRS versus 1.10 [0.96-1.26] for PRS among heavy smokers with ≥ 40 pack-years of smoking) for moderate-to-severe COPD. Cross-ethnic portability of the PTRS was significantly higher than the PRS (paired t test p < 2.2 × 10-16 with portability gains ranging from 5% to 28%) for both dichotomous COPD traits and across all smoking strata. Our study demonstrates the value of PTRS for improved cross-ethnic portability compared to PRS in predicting COPD risk.

SARS-CoV-2 infection induces thymic atrophy mediated by IFN-γ in hACE2 transgenic mice.

Pathogenic infections cause thymic atrophy, perturb thymic T-cell development, and alter immunological response. Previous studies reported dysregulated T-cell function and lymphopenia in coronavirus disease-19 (COVID-19). However, immunopathological changes in the thymus associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have not been elucidated. Here, we report that SARS-CoV-2 infects thymocytes, and induces CD4+CD8+ (double positive; DP) T-cell apoptosis leading to thymic atrophy and loss of peripheral TCR repertoire in K18-hACE2 transgenic mice. Infected thymus led to increased CD44+CD25- T-cells, indicating an early arrest in the T-cell maturation pathway. Thymic atrophy was notably higher in male hACE2-Tg mice than in females and involved an upregulated de-novo synthesis pathway of thymic glucocorticoid. Further, IFN-γ was crucial for thymic atrophy, as anti-IFN-γ -antibody neutralization blunted thymic involution. Therapeutic use of Remdesivir also rescued thymic atrophy. While the Omicron variant and its sub-lineage BA.5 variant caused marginal thymic atrophy, the delta variant of SARS-CoV-2 exhibited severe thymic atrophy characterized by severely depleted DP T-cells. Recently characterized broadly SARS-CoV-2 neutralizing monoclonal antibody P4A2 was able to rescue thymic atrophy and restore the thymic maturation pathway of T-cells. Together, we report SARS-CoV-2-associated thymic atrophy resulting from impaired T-cell maturation pathway which may contribute to dyregulated T cell response during COVID-19.

A microfluidic device for real-time on-demand intravenous oxygen delivery.

SignificanceThe treatment of hypoxemia that is refractory to the current standard of care is time-sensitive and requires skilled caregivers and use of specialized equipment (e.g., extracorporeal membrane oxygenation). Most patients experiencing refractory hypoxemia will suffer organ dysfunction, and death is common in this cohort. Here, we describe a new strategy to stabilize and support patients using a microfluidic device that administers oxygen gas directly to the bloodstream in real time and on demand using a process that we call sequential shear-induced bubble breakup. If successful, the described technology may help to avoid or decrease the incidence of ventilator-related lung injury from refractory hypoxemia.

Structure-guided mutations in CDRs for enhancing the affinity of neutralizing SARS-CoV-2 nanobody.

The optimization of antibodies to attain the desired levels of affinity and specificity holds great promise for the development of next generation therapeutics. This study delves into the refinement and engineering of complementarity-determining regions (CDRs) through in silico affinity maturation followed by binding validation using isothermal titration calorimetry (ITC) and pseudovirus-based neutralization assays. Specifically, it focuses on engineering CDRs targeting the epitopes of receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. A structure-guided virtual library of 112 single mutations in CDRs was generated and screened against RBD to select the potential affinity-enhancing mutations. Protein-protein docking analysis identified 32 single mutants of which nine mutants were selected for molecular dynamics (MD) simulations. Subsequently, biophysical ITC studies provided insights into binding affinity, and consistent with in silico findings, six mutations that demonstrated better binding affinity than native nanobody were further tested in vitro for neutralization activity against SARS-CoV-2 pseudovirus. Leu106Thr mutant was found to be most effective in virus-neutralization with IC50 values of ∼0.03 µM, as compared to the native nanobody (IC50 ∼0.77 µM). Thus, in this study, the developed computational pipeline guided by structure-aided interface profiles and thermodynamic analysis holds promise for the streamlined development of antibody-based therapeutic interventions against emerging variants of SARS-CoV-2 and other infectious pathogens.

Stoichiometrically Optimized Electrochromic Complex [V2O2+ξ(OH)3-ξ] Based Electrode: Prototype Supercapacitor with Multicolor Indicator.

The systematic structure modification of metal oxides is becoming more attractive, and effective strategies for structural tunning are highly desirable for improving their practical color-modulating energy storage performances. Here, the ability of a stoichiometrically tuned oxide-hydroxide complex of porous vanadium oxide, namely [V2O2+ξ(OH)3-ξ]ξ = 0:3 for multifunctional electrochromic supercapacitor application is demonstrated. Theoretically, the pre-optimized oxide complex is synthesized using a simple wet chemical etching technique in its optimized stoichiometry [V2O2+ξ(OH)3-ξ] with ξ = 0, providing more electroactive surface sites. The multifunctional electrode shows a high charge storage property of 610 Fg-1 at 1A g-1, as well as good electrochromic properties with high color contrast of 70% and 50% at 428 and 640 nm wavelengths, faster switching, and high coloration efficiency. When assembled in a solid-state symmetric electrochromic supercapacitor device, it exhibits an ultrahigh power density of 1066 mWcm-2, high energy density of 246 mWhcm-2, and high specific capacitance of 290 mFcm-2 at 0.2 mAcm-2. A prepared prototype device displays red when fully charged, green when half charged, and blue when fully discharged. A clear evidence of optimizing the multifunctional performance of electrochromic supercapacitor by stoichiometrical tuning is presented along with demonstrating a device prototype of a 25 cm2 large device for real-life applications.

A broadly neutralizing monoclonal antibody overcomes the mutational landscape of emerging SARS-CoV-2 variants of concern.

The emergence of new variants of SARS-CoV-2 necessitates unremitting efforts to discover novel therapeutic monoclonal antibodies (mAbs). Here, we report an extremely potent mAb named P4A2 that can neutralize all the circulating variants of concern (VOCs) with high efficiency, including the highly transmissible Omicron. The crystal structure of the P4A2 Fab:RBD complex revealed that the residues of the RBD that interact with P4A2 are a part of the ACE2-receptor-binding motif and are not mutated in any of the VOCs. The pan coronavirus pseudotyped neutralization assay confirmed that the P4A2 mAb is specific for SARS-CoV-2 and its VOCs. Passive administration of P4A2 to K18-hACE2 transgenic mice conferred protection, both prophylactically and therapeutically, against challenge with VOCs. Overall, our data shows that, the P4A2 mAb has immense therapeutic potential to neutralize the current circulating VOCs. Due to the overlap between the P4A2 epitope and ACE2 binding site on spike-RBD, P4A2 may also be highly effective against a number of future variants.

HIV cure: Are we going to make history?

BACKGROUND: At present, combination antiretroviral therapy (cART) is the mainstay for the treatment of people living with HIV/AIDS. cART can suppress the viral load to a minimal level; however, the possibility of the emergence of full-blown AIDS is always there. In the latter part of the first decade of the 21st century, an HIV-positive person received stem cell transplantation (SCT) for treatment of his haematological malignancy. The patient was able to achieve remission of the haematological condition as well as of HIV following SCT. Thorough investigations of various samples including blood and biopsy could not detect the virus in the person's body. The person was declared to be the first cured case of HIV. LITERATURE SEARCH: Over the next decade, a few more similar cases were observed and have recently been declared cured of the infection. A comprehensive search was performed in PubMed, Cochrane library and Google Scholar. Four such additional cases were found in literature. DESCRIPTION & DISCUSSION: These cases all share a common proposed mechanism for the HIV cure, that is, transplantation of stem cells from donors carrying a homozygous mutation in a gene encoding for CCR5 (receptor utilized by HIV for entry into the host cell), denoted as CCR5△32. This mutation makes the host immune cells devoid of CCR5, causing the host to acquire resistance against HIV. To the best of our knowledge, this is the first review to look at relevant and updated information of all cured cases of HIV as well as the related landmarks in history and discusses the underlying mechanism(s).

Brain gray matter changes in children at risk for sudden unexpected death in epilepsy.

BACKGROUND: Potential failing adult brain sites, stratified by risk, mediating Sudden Unexpected Death in Epilepsy (SUDEP) have been described, but are unknown in children. METHODS: We examined regional brain volumes using T1-weighted MRI images in 21 children with epilepsy at high SUDEP risk and 62 healthy children, together with SUDEP risk scores, calculated from focal seizure frequency. Gray matter tissue type was partitioned, maps normalized, smoothed, and compared between groups (SPM12; ANCOVA; covariates, age, sex, and BMI). Partial correlations between regional volumes and seizure frequency were examined (SPM12, covariates, age, sex, and BMI); 67% were at high risk for SUDEP. RESULTS: The cerebellar cortex, hippocampus, amygdala, putamen, cingulate, thalamus, and para-hippocampal gyrus showed increased gray matter volumes in epilepsy, and decreased volumes in the posterior thalamus, lingual gyrus, and temporal cortices. The cingulate, insula, and putamen showed significant positive relationships with focal seizure frequency indices using whole-brain voxel-by-voxel partial correlations. Tissue volume changes in selected sites differed in direction from adults; particularly, cerebellar sites, key for hypotensive recovery, increased rather than adult declines. CONCLUSION: The volume increases may represent expansion by inflammatory or other processes that, with sustained repetitive seizure discharge, lead to tissue volume declines described earlier in adults. IMPACT: Children with epilepsy, who are at risk for Sudden Unexplained Death, show changes in brain volume that often differ in direction of change from adults at risk for SUDEP. Sites of volume change play significant roles in mediating breathing and blood pressure, and include areas that serve recovery from prolonged apnea and marked loss of blood pressure. The extent of volume changes correlated with focal seizure frequency. Although the underlying processes contributing to regional volume changes remain speculative, regions of tissue swelling in pediatric brain areas may represent transitory conditions that later lead to tissue loss in the adult condition.

Immunohistochemical expression of perforin in adult systemic lupus erythematosus associated macrophage activation syndrome: Clinicohematological correlation and literature review.

OBJECTIVE: To study the bone marrow (BM) immunohistomorphological characteristics in adult systemic lupus erythematosus (SLE) associated macrophage activation syndrome (SLE-MAS). MATERIALS AND METHODS: Immunohistochemical (IHC) expression of CD3, CD8, perforin (PFN), and CD163 was studied on BM trephine biopsies from 30 cytopenic adult SLE cases (male: female = 1:5, age; 24 years, range; 19-32) and compared them with ten age matched controls. Clinicopathological parameters were compared among the cases likely (L) or unlikely (U) to have MAS using probability scoring criteria. The best cut off laboratory parameters to discriminate between the two were obtained through receiver operator curve (ROC) analysis. RESULTS: MAS occurred in 12/30 (40%) cases and was more commonly associated with prior immunosuppressive therapy (p = .07), ≥ 3 system involvement (p = .09), lower fibrinogen (p < .01), increased triglyceride (p = .002), increased BM hemophagocytosis (p = .002), and higher MAS score [185 (176-203) vs. 105 (77-119), p < .01] than MAS-U subgroup. Although PFN+CD8+ T lymphocytes significantly decreased among cases than controls (p < .05), it was comparable between MAS-L and MAS-U subgroups. Fibrinogen (< 2.4 g/L, AUC; 0.93, p < .01), hemophagocytosis score (> 1.5, AUC; 0.71, p = .03), and an MAS probability score of ≥ 164 (AUC; 1, p < .01) discriminated MAS from those without MAS. CONCLUSION: We noted a decrease in perforin mediated CD8 + T cell cytotoxicity in SLE. Immunohistochemical demonstration of the same along with histiocytic hemophagocytosis on BM biopsy may be useful adjunct in early diagnosis and management of MAS in SLE.

Regio- and Stereoselective Intermolecular 1,2-Difunctionalization of Terminal Alkynes: An Approach to Access (Z)-ß-Amidovinylsulfones.

We have developed the first I2/base-catalyzed regio- and stereoselective intermolecular ß-amidosulfonylation of terminal alkynes using sodium sulfinates and quinoxalinone derivatives. The present methodology is compatible with a broad spectrum of various heterocyclic amides, terminal alkynes, and sodium sulfinates. It provides rapid access to valuable (Z)-ß-amidovinyl sulfones at mild conditions. Moreover, the synthetic application of this methodology was demonstrated by the late-stage functionalization of numerous bioactive molecules.

Europium-based ß-hydroxyketone complexes: synthesis, optoelectronic, thermal and computational analyses.

Six red-light-emitting Eu(III) complexes having a ß-hydroxyketone as ligand and heterocyclic ring containing compounds as ancillary ligands were synthesized to explore their use in displays and optoelectronics. The coordinating behavior of complexes was determined by various techniques such as FTIR (Fourier transform infrared), 1H-NMR (Nuclear magnetic resonance), and 13C-NMR that establishes a bonding of ligand and ancillary ligand with the Eu(III) ion. Morphology and purity were investigated through XRD (X-ray diffraction), SEM (scanning electron microscopy) and EDS (energy-dispersive X-ray spectroscopy) analyses that suggest semicrystalline and pure complex formation. Thermal analysis of complexes by TGA/DTG (thermogravimetric/derivative thermogravimetric) indicates that complexes are stable upto 200 ºC temperature making them suitable for use in display devices. Analysis of the photophysical properties was carried out in both solid and solution states using PL (photoluminescence) studies, color parameters, J-O (Judd-Ofelt) analysis and bandgap. Most emissive transition (5D0 → 7F2) is responsible for the red emission in the complexes. The CIE (Commission International de I'Eclairage) coordinates of complexes also indicate the red emission on UV excitation. The bandgap which was obtained in the range of 2.54-3.02 eV reveals the semiconducting behavior of complexes. Values of J-O parameters and Ω2 in the complexes reflect asymmetric chemical environment around Eu (III) and less covalence and the Ω4 indicates that complexes are less rigid. Bandgap calculated through DFT (density function theory) for complexes is in range of 2.37-2.77 eV, and intensity parameters (J-O), energy transfer rates, and spherical coordinates were determined by LUMPAC software. The computational data are in good harmony with the experimental data. Further biological aspects of complexes were studied using antioxidant and antimicrobial studies.

Synthesis of Vanadyl Complexes of N-Confused Porphyrins and Their Bromoperoxidase-like Catalytic Activity.

Two new vanadyl complexes of N-confused porphyrins (NCPs), [VONCTPP] (V-1) and [VONCP(OMe)8] (V-2), have been synthesized for the first time and investigated as a catalyst for the oxidative bromination reaction of phenol and its derivatives. This article further delineates crystal structures, photophysical, and redox properties of both the vanadyl complexes. Complexes V-1 and V-2 exhibited a significant red shift in their absorption spectra compared with their respective free bases. The single-crystal structure of V-1 revealed that the complex is in the 2H tautomeric form, while EPR studies revealed the +4 oxidation state of vanadium metal having an axial compression with dxy1 configuration. Catalytic potential for bromoperoxidases-like activity has been explored for both complexes V-1 and V-2 for the first time in NCP chemistry with excellent TOF values (4.7-6.3 s-1 for V-1 and 7.3-8.7 s-1 for V-2) using KBr as a source of bromine and H2O2 as a green oxidant in aqueous acidic medium at 298 K. Notably, both catalysts show excellent recyclability over five cycles. The vanadyl-metalated NCPs exhibit excellent stability in the air.

Phenyliodine bis(trifluoroacetate) as a sustainable reagent: exploring its significance in organic synthesis.

Iodine-containing molecules, especially hypervalent iodine compounds, have gained significant attention in organic synthesis. They are valuable and sustainable reagents, leading to a remarkable surge in their use for chemical transformations. One such hypervalent iodine compound, phenyliodine bis(trifluoroacetate)/bis(trifluoroacetoxy)iodobenzene, commonly referred to as PIFA, has emerged as a prominent candidate due to its attributes of facile manipulation, moderate reactivity, low toxicity, and ready availability. PIFA presents an auspicious prospect as a substitute for costly organometallic catalysts and environmentally hazardous oxidants containing heavy metals. PIFA exhibits remarkable catalytic activity, facilitating an array of consequential organic reactions, including sulfenylation, alkylarylation, oxidative coupling, cascade reactions, amination, amidation, ring-rearrangement, carboxylation, and numerous others. Over the past decade, the application of PIFA in synthetic chemistry has witnessed substantial growth, necessitating an updated exploration of this field. In this discourse, we present a concise overview of PIFA's applications as a 'green' reagent in the domain of synthetic organic chemistry. A primary objective of this article is to bring to the forefront the scientific community's awareness of the merits associated with adopting PIFA as an environmentally conscientious alternative to heavy metals.

Janus HfSSe monolayer: a promising candidate for SO2and COCl2gas sensing.

Janus monolayers based on transition metal dichalcogenides have garnered significant interest as potential materials for nano electronic device applications due to their exceptional physical and electronic properties. In this study, we investigate the stability of the Janus HfSSe monolayer usingab initiomolecular dynamics simulations and analyze the electronic properties in its pristine state. We then examine the impact of adsorbing toxic gas molecules (AsH3, COCl2, NH3, NO2, and SO2) on the monolayer's structure and electronic properties, testing their adsorption on different active sites on top of hafnium, selenium, and sulfur. The sensitivity of the gas molecules is quantified in terms of their adsorption energy, with the highest and lowest energies being observed for SO2(-0.278 eV) and NO2(-0.095 eV), respectively. Additionally, we calculate other properties such as recovery time, adsorption height, Bader charge, and charge difference density to determine the sensitivity and selectivity of the toxic gas molecules. Our findings suggest that the Janus HfSSe monolayer has the potential to function as SO2and COCl2gas sensor due to its high sensitivity for these two gases.

Study of Luminescence Phenomena of Tb (III) Containing Fluroquinoline for Application in Optoelectronic Devices.

This study presents a series of six vivid green Tb(III) complexes, denoted by the general formula [Tb(L)3.secondary sensitizers], where L represents 1-cyclopropyl-7-(4-ethylpiperazin-1-yl)-6-fluoro-4-oxoquinoline-3-carboxylic acid and secondary sensitizers consist of heterocyclic N-donor aromatic systems. The synthesis of these complexes were achieved through a solvent-assisted grinding method, and their characterization involved various techniques such as CHN analysis, FTIR, NMR, UV, XRD, and NIR spectroscopy. These analyses confirmed the successful synthesis of complexes with coordination between the quinoline moiety and the metal ion. Photoluminescence studies were conducted in solid and solution phases, revealing excellent luminescence properties. The bright green color emitted by the complexes upon exposure to UV rays was attributed to the hypersensitive 5D4 → 7F5 transition. J-O analysis indicated an asymmetrical coordination environment around in the complexes. Additionally, various radiative properties (Ared, Anred, η, ßexp, σs) and band gap values were determined, highlighting the potential applications of these complexes in diverse optoelectronic fields. Chromaticity evaluation demonstrated high color purity in both solid and solution phases. Furthermore, the CCT value identified the solid complexes as a cool light source. Overall, the analyses supported the exceptional luminosity of synthesized complexes, positioning them as promising luminescent materials for a wide range of devices.

Preparation and Judd-Ofelt Analysis of Warm Red Luminescent Eu3+ Complexes for Semiconductor Lasing Devices.

Six novel red photoluminescent Eu3+ complexes with 3-formyl chromone as the primary sensitizer (L) were synthesized using the solution precipitation method. These complexes are [Eu(L3).X] where X is 2H2O (C1), phen (C2), neo (C3), bipy (C4), dmph (C5), and biquno (C6). These complexes were characterized by elemental analysis, EDAX analysis, SEM, FT-IR, thermo-gravimetric analysis (TGA/DTA) and photoluminescence spectra. The transition rates, quantum efficiency, and J-O intensity parameters were calculated using emission data and luminescence decay time (τ). Complexes exhibit a strong emission peak (5D0 → 7F2) of the Eu3+ ion in their luminescence emission spectra in solid and solution states, making them an effective emitter of the red color in OLEDs. The branching ratio of these complexes ranges from 80.67-82.92 in solid and 50.53-62.65 in solution state; CIE color coordinate of complexes falls in the red region. The color purity ranges [CP(%)] values for solid 95.26-97.27% and for solution ranges 85.11-93.43%. Correlated color temperature (CCT) of the complexes (C1-C6) ranged from 2710 to 3049 K in the solid state and 1775 to 2450 K in the solution state. These complexes are promising red emitters in OLEDs, semiconductors, and leasing devices.

Influence of Ancillary Ligand on the Photosensitization and Photophysical Properties of Red Luminescent Tri-fluorinated Β-diketonate Eu(III) Complexes.

Highly emissive ternary Eu(III) complexes were synthesized with a tri-fluorinated ß-diketone as principal ligand and heterocyclic aromatic compounds as ancillary ligands to assess their utility as an illuminating material for display devices and other optoelectronics. The general characterizations, regarding the coordinating facets of complexes were accomplished via various spectroscopic techniques. Thermal stability was investigated via TGA/DTA. Photophysical analysis was accomplished by PL studies, Band gap value, color parameters and J-O analysis. DFT calculations were performed adopting geometrically optimized structure of complexes. Superb thermal stability has been achieved in complexes, which decides their concrete candidature for display devices. The bright red luminescence of complexes is ascribed to 5D0 → 7F2 transition of Eu(III) ion. Colorimetric parameters unlocked the applicability of complexes as warm light source and J-O parameters adequately summarized the coordinating surrounding around the metal ion. Various radiative properties were also evaluated which suggested the prospective use of complexes in lasers and other optoelectronic devices. The band gap and Urbach band tail, procured from absorption spectra, revealed the semiconducting behavior of synthesized complexes. DFT studies rendered the energies of FMO and various other molecular parameters. It can be summarized from the photophysical and optical analysis of synthesized complexes that these complexes are virtuous luminescent materials and possess potentiality to be used in diverse domain of display devices.

Exploring transcriptomic mechanisms underlying pulmonary adaptation to diverse environments in Indian rams.

BACKGROUND: The Changthangi sheep thrive at high altitudes in the cold desert regions of Ladakh, India while Muzaffarnagri sheep are well-suited to the low altitude plains of northern India. This study investigates the molecular mechanisms of pulmonary adaptation to diverse environments by analyzing gene expression profiles of lung tissues through RNA sequencing. METHODS AND RESULTS: Four biological replicates of lung tissue from each breed were utilized to generate the transcriptomic data. Differences in gene expression analysis revealed discrete expression profiles in lungs of each breed. In Changthangi sheep, genes related to immune responses, particularly cytokine signaling, were significantly enriched. Pathway analysis highlighted the activation of NF-kB signaling, a key mediator of inflammation and immune response. Additionally, the gene network analysis indicated a strong association between cytokine signaling, hypoxia-inducible factor (HIF) and NF-kB activation, suggesting a coordinated response to hypoxic stress in lungs of Changthangi sheep. In Muzaffarnagri sheep, the gene expression profiles were enriched for pathways related to energy metabolism, homeostasis and lung physiology. Key pathways identified include collagen formation and carbohydrate metabolism, both of which are crucial for maintaining lung function and structural integrity. Gene network analysis further reinforced this by revealing a strong connection between genes associated with lung structure and function. CONCLUSIONS: Our findings shed light on the valuable insights into gene expression mechanisms that enable these sheep breeds to adapt to their respective environments and contribute to a better understanding of high altitude adaptation in livestock.

Photo/electro catalytic green hydrogen production promoted by Ga modified Co0.6Cu0.4Fe2O4 nano catalysts.

The current work concentrates on the fabrication of Ga doped Co0.6Cu0.4Fe2O4 nanocatalysts via sol-gel auto-combustion (SGA) for the production of green and sustainable source of energy i.e., hydrogen through photocatalytic and electrocatalytic routes. Single-phased cubic crystal structure with Fd3m geometry was observed through XRD patterns. FESEM images show the aggregated and spherical shaped grains with distinct grain boundaries and average grain size of 1.04 and 1.39 µm for the Co0.6Cu0.4Fe2O4, and Co0.6Cu0.4Ga0.02Fe1.98O4 nanomaterials. Soft magnetic behaviour with a coercivity (Hc) and saturation magnetization (Ms) of 235.32-357.26 Oe and 54.65-61.11 emu/g was obtained for the produced nanomaterials. The estimation of photocatalytic nature for generating H2 was conducted using the sacrificial agents i.e., 0.128 M Na2S and 0.079 M Na2SO3. The analysis focused on measuring the maximum H2 generation was achieved by photocatalysts throughout three consecutive 4-h cycles. Out of all compositions, Co0.6Cu0.4Ga0.02Fe1.98O4 nanomaterial have the highest photocatalytic activity of 16.71 mmol gcat-1. However, the electrocatalytic behaviour of prepared Co0.6Cu0.4GaxFe2-xO4 (x = 0.00-0.03) electrocatalysts were determined for HER (Hydrogen evolution reaction) reaction. The overpotential values of Co0.6Cu0.4Fe2O4, Co0.6Cu0.4Ga0.01Fe1.99O4, Co0.6Cu0.4Ga0.02Fe1.98O4, and Co0.6Cu0.4Ga0.03Fe1.97O4 catalysts at 10 mA cm-2 were -0.81, -0.85, -1.03, and 1.21 V, correspondingly. Thus, at cathode current density of 10 mA/cm-2, an elevation in overpotential was noted, which indicates that the undoped Co0.6Cu0.4Fe2O4 (x = 0.00) electrocatalyst have remarkable electrocatalytic HER activity. Consequently, owing to photo/electro catalytic water splitting traits, the prepared catalysts are highly efficient for the green hydrogen generation.