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Abstract There is a large body of evidence that cellular metabolism governs inflammation, and that inflammation contributes to the progression of atherosclerosis. However, whether mitochondrial DNA synthesis affects macrophage function and atherosclerosis pathology is not fully understood. Here we show, by transcriptomic analyzes of plaque macrophages, spatial single cell transcriptomics of atherosclerotic plaques, and functional experiments, that mitochondrial DNA (mtDNA) synthesis in atherosclerotic plaque macrophages are triggered by vascular cell adhesion molecule 1 (VCAM-1) under inflammatory conditions in both humans and mice. Mechanistically, VCAM-1 activates C/EBPα, which binds to the promoters of key mitochondrial biogenesis genes - Cmpk2 and Pgc1a. Increased CMPK2 and PGC-1α expression triggers mtDNA synthesis, which activates STING-mediated inflammation. Consistently, atherosclerosis and inflammation are less severe in Apoe −/− mice lacking Vcam1 in macrophages. Downregulation of macrophage-specific VCAM-1 in vivo leads to decreased expression of LYZ1 and FCOR, involved in STING signalling. Finally, VCAM-1 expression in human carotid plaque macrophages correlates with necrotic core area, mitochondrial volume, and oxidative damage to DNA. Collectively, our study highlights the importance of macrophage VCAM-1 in inflammation and atherogenesis pathology and proposes a self-acerbating pathway involving increased mtDNA synthesis.

Abstract Regioselective distal C−H functionalization of nitroarenes by overriding proximal C−H activation has remained an unsolved challenge. Herein, we present a palladium-catalyzed meta-C−H alkenylation of nitroarene substrate, achieved through leveraging the non-covalent hydrogen bonding interactions. Urea-based templates comprising an elongated biphenyl linker designed in such a way that it interacts with nitro group via strong hydrogen bonding interaction, while a cyano based directing group is attached along the template to coordinate with the palladium center, thereby facilitating the activation of the remote meta-C−H bond of nitrobenzene. Computational mechanistic investigation and the analysis of non-covalent interaction deciphers the crucial role of H-bonding in regulating the regioselectivity.

Abstract Genome-wide association studies (GWAS) have found widespread evidence of pleiotropy, but characterization of global patterns of pleiotropy remain highly incomplete due to insufficient power of current approaches. We develop fastASSET, a method that allows efficient detection of variant-level pleiotropic association across many traits. We analyze GWAS summary statistics of 116 complex traits of diverse types collected from the GRASP repository and large GWAS Consortia. We identify 2293 independent loci and find that the lead variants in nearly all these loci (~99%) to be associated with $$\ge 2$$ ≥ 2 traits (median = 6). We observe that degree of pleiotropy estimated from our study predicts that observed in the UK Biobank for a much larger number of traits (K = 4114) (correlation = 0.43, p-value $$ < 2.2\times {10}^{-16}$$ < 2.2 × 10 − 16 ). Follow-up analyzes of 21 trait-specific variants indicate their link to the expression in trait-related tissues for a small number of genes involved in relevant biological processes. Our findings provide deeper insight into the nature of pleiotropy and leads to identification of highly trait-specific susceptibility variants.

Abstract Strong coupling between molecules and confined light modes of optical cavities to form polaritons can alter photochemistry, but the origin of this effect remains largely unknown. While theoretical models suggest a suppression of photochemistry due to the formation of new polaritonic potential energy surfaces, many of these models do not account for the energetic disorder among the molecules, which is unavoidable at ambient conditions. Here, we combine simulations and experiments to show that for an ultra-fast photochemical reaction such thermal disorder prevents the modification of the potential energy surface and that suppression is due to radiative decay of the lossy cavity modes. We also show that the excitation spectrum under strong coupling is a product of the excitation spectrum of the bare molecules and the absorption spectrum of the molecule-cavity system, suggesting that polaritons can act as gateways for channeling an excitation into a molecule, which then reacts normally. Our results therefore imply that strong coupling provides a means to tune the action spectrum of a molecule, rather than to change the reaction.

Abstract Skin cancer is a lethal disease, and its early detection plays a pivotal role in preventing its spread to other body organs and tissues. Artificial Intelligence (AI)-based automated methods can play a significant role in its early detection. This study presents an AI-based novel approach, termed 'DualAutoELM' for the effective identification of various types of skin cancers. The proposed method leverages a network of autoencoders, comprising two distinct autoencoders: the spatial autoencoder and the FFT (Fast Fourier Transform)-autoencoder. The spatial-autoencoder specializes in learning spatial features within input lesion images whereas the FFT-autoencoder learns to capture textural and distinguishing frequency patterns within transformed input skin lesion images through the reconstruction process. The use of attention modules at various levels within the encoder part of these autoencoders significantly improves their discriminative feature learning capabilities. An Extreme Learning Machine (ELM) with a single layer of feedforward is trained to classify skin malignancies using the characteristics that were recovered from the bottleneck layers of these autoencoders. The 'HAM10000' and 'ISIC-2017' are two publicly available datasets used to thoroughly assess the suggested approach. The experimental findings demonstrate the accuracy and robustness of the proposed technique, with AUC, precision, and accuracy values for the 'HAM10000' dataset being 0.98, 97.68% and 97.66%, and for the 'ISIC-2017' dataset being 0.95, 86.75% and 86.68%, respectively. This study highlights the possibility of the suggested approach for accurate detection of skin cancer.

Summary: Streptococcus pneumoniae is a global priority respiratory pathogen that kills over a million people annually. The pore-forming cytotoxin, pneumolysin (PLY) is a major virulence factor. Here, we found that recombinant PLY as well as wild-type pneumococcal strains, but not the isogenic PLY mutant, upregulated the shedding of extracellular vesicles (EVs) harboring membrane-bound toxin from human THP-1 monocytes. PLY-EVs induced cytotoxicity and hemolysis dose-dependently upon internalization by recipient monocyte-derived dendritic cells. Proteomics analysis revealed that PLY-EVs are selectively enriched in key inflammatory host proteins such as IFI16, NLRC4, PTX3, and MMP9. EVs shed from PLY-challenged or infected cells induced dendritic cell maturation and primed them to infection. In vivo, zebrafish administered with PLY-EVs showed pericardial edema and mortality. Adoptive transfer of bronchoalveolar-lavage-derived EVs from infected mice to healthy recipients induced lung damage and inflammation in a PLY-dependent manner. Our findings identify that host EVs released during infection mediate pneumococcal pathogenesis.

Abstract The constantly changing nature of cyber threats presents unprecedented difficulties for people, institutions, and governments across the globe. Cyber threats are a major concern in today’s digital world like hacking, phishing, malware, and data breaches. These can compromise anyone’s personal information and harm the organizations. An intrusion detection system plays a vital responsibility to identifying abnormal network traffic and alerts the system in real time if any malicious activity is detected. In our present research work Artificial Neural Networks (ANN) layers are optimized with the execution of Spider Monkey Optimization (SMO) to detect attacks or intrusions in the system. The developed model SMO-ANN is examined using publicly available dataset Luflow, CIC-IDS 2017, UNR-IDD and NSL -KDD to classify the network traffic as benign or attack type. In the binary Luflow dataset and the multiclass NSL-KDD dataset, the proposed model SMO-ANN has the maximum accuracy, at 100% and 99%, respectively.

Abstract Dehydrogenation chemistry has long been established as a fundamental aspect of organic synthesis, commonly encountered in carbonyl compounds. Transition metal catalysis revolutionized it, with strategies like transfer-dehydrogenation, single electron transfer and C–H activation. These approaches, extended to multiple dehydrogenations, can lead to aromatization. Dehydrogenative transformations of aliphatic carboxylic acids pose challenges, yet engineered ligands and metal catalysis can initiate dehydrogenation via C–H activation, though outcomes vary based on substrate structures. Herein, we have developed a catalytic system enabling cyclohexane carboxylic acids to undergo multifold C–H activation to furnish olefinated arenes, bypassing lactone formation. This showcases unique reactivity in aliphatic carboxylic acids, involving tandem dehydrogenation-olefination-decarboxylation-aromatization sequences, validated by control experiments and key intermediate isolation. For cyclopentane carboxylic acids, reluctant to aromatization, the catalytic system facilitates controlled dehydrogenation, providing difunctionalized cyclopentenes through tandem dehydrogenation-olefination-decarboxylation-allylic acyloxylation sequences. This transformation expands carboxylic acids into diverse molecular entities with wide applications, underscoring its importance.

Abstract DNA binding transcription factors possess the ability to interact with lipid membranes to construct ion-permeable pathways. Herein, we present a thiazole-based DNA binding peptide mimic TBP2, which forms transmembrane ion channels, impacting cellular ion concentration and consequently stabilizing G-quadruplex DNA structures. TBP2 self-assembles into nanostructures, e.g., vesicles and nanofibers and facilitates the transportation of Na+ and K+ across lipid membranes with high conductance (~0.6 nS). Moreover, TBP2 exhibits increased fluorescence when incorporated into the membrane or in cellular nuclei. Monomeric TBP2 can enter the lipid membrane and localize to the nuclei of cancer cells. The coordinated process of time-dependent membrane or nuclear localization of TBP2, combined with elevated intracellular cation levels and direct G-quadruplex (G4) interaction, synergistically promotes formation and stability of G4 structures, triggering cancer cell death. This study introduces a platform to mimic and control intricate biological functions, leading to the discovery of innovative therapeutic approaches.

Abstract While better management of loco-regional prostate cancer (PC) has greatly improved survival, advanced PC remains a major cause of cancer deaths. Identification of novel targetable pathways that contribute to tumor progression in PC could open new therapeutic options. The di-ganglioside GD2 is a target of FDA-approved antibody therapies in neuroblastoma, but the role of GD2 in PC is unexplored. Here, we show that GD2 is expressed in a small subpopulation of PC cells in a subset of patients and a higher proportion of metastatic tumors. Variable levels of cell surface GD2 expression were seen on many PC cell lines, and the expression was highly upregulated by experimental induction of lineage progression or enzalutamide resistance in CRPC cell models. GD2high cell fraction was enriched upon growth of PC cells as tumorspheres and GD2high fraction was enriched in tumorsphere-forming ability. CRISPR-Cas9 knockout (KO) of the rate-limiting GD2 biosynthetic enzyme GD3 Synthase (GD3S) in GD2high CRPC cell models markedly impaired the in vitro oncogenic traits and growth as bone-implanted xenograft tumors and reduced the cancer stem cell and epithelial-mesenchymal transition marker expression. Our results support the potential role of GD3S and its product GD2 in promoting PC tumorigenesis by maintaining cancer stem cells and suggest the potential for GD2 targeting in advanced PC.

Abstract Coconut (Cocos nucifera) leaves, an unutilized resource, enriched with valuable bioactive compounds. Spectral analysis of purified pentane fraction of coconut leaves revealed the presence of a squalene analog named 4,4′-diapophytofluene or in short 4,4′-DPE (C30H46). Pure squalene standard (PSQ) showed cytotoxicity after 8 µg/ml concentration whereas 4,4′-DPE exhibited no cytotoxic effects up to 16 µg/ml concentration. On senescence-induced WI38 cells, 4,4′-DPE displayed better percentage of cell viability (164.5% at 24 h, 159.4% at 48 h and 148% at 72 h) compared to PSQ and BSQ (bio-source squalene) with same time duration. Similar trend of result was found in HaCaT cells. SA-β-gal assay showed that number of β-galactosidase positive cells were significantly decreased in senescent cells (WI38 and HaCaT) after treated with 4,4′-DPE than PSQ, BSQ. Percentage of ROS was increased to 60% in WI38 cells after olaparib treatment. When PSQ, BSQ and 4,4′-DPE were applied separately on these oxidative-stress-induced cells for 48 h, the overall percentage of ROS was decreased to 39.3%, 45.6% and 19.3% respectively. This 4,4′-DPE was found to be more effective in inhibiting senescence by removing ROS as compared to squalene. Therefore, this 4,4′-DPE would be new potent senotherapeutic agent for pharmaceuticals and dermatological products.

Abstract This study proposes an integrated approach of assessing CO2 storage potential and geothermal energy prospect based on the data of seventeen depleted wells of Upper Assam Basin which could assist the global objective of net zero transition. The petrophysical properties of Tipam, Barail and Lakadong + Therria Formations from the seventeen wells have been utilised to perform the Monte Carlo simulation for probabilistic estimation of the CO2 storage in the Upper Assam Basin. This preliminary work showed that the mean storage capacity of 18.8 ± 0.7 MT, 19.8 ± 0.9 MT and 4.5 ± 0.8 MT could potentially be stored in the three geological formations of the basin. The corrected bottom hole temperature values for the studied seventeen wells were determined using the well log data and Waples and Harrison method; these values provided a static geothermal gradient for each well, which varies widely from 0.017 to 0.033 °C/m. In order to enable geothermal prospectivity, static formation temperature maps have been generated for the studied wells. The probabilistic assessment of stored heat-in-place and formation temperature maps delimited five prospective sites for the extraction of geothermal energy in the basin. The study also presented a risk assessment for CO2 storage development in the basin. Further, the study illustrated an economic analysis of the implementation of a CO2 storage project and geothermal operations in the basin.

Abstract Hypomyelinating leukodystrophy (HLD) is an autosomal recessive disorder characterized by defective central nervous system myelination. Exome sequencing of two siblings with severe cognitive and motor impairment and progressive hypomyelination characteristic of HLD revealed homozygosity for a missense single-nucleotide variant (SNV) in EPRS1 (c.4444 C > A; p.Pro1482Thr), encoding glutamyl-prolyl-tRNA synthetase, consistent with HLD15. Patient lymphoblastoid cell lines express markedly reduced EPRS1 protein due to dual defects in nuclear export and cytoplasmic translation of variant EPRS1 mRNA. Variant mRNA exhibits reduced METTL3 methyltransferase-mediated writing of N 6-methyladenosine (m6A) and reduced reading by YTHDC1 and YTHDF1/3 required for efficient mRNA nuclear export and translation, respectively. In contrast to current models, the variant does not alter the sequence of m6A target sites, but instead reduces their accessibility for modification. The defect was rescued by antisense morpholinos predicted to expose m6A sites on target EPRS1 mRNA, or by m6A modification of the mRNA by METTL3-dCas13b, a targeted RNA methylation editor. Our bioinformatic analysis predicts widespread occurrence of SNVs associated with human health and disease that similarly alter accessibility of distal mRNA m6A sites. These results reveal a new RNA-dependent etiologic mechanism by which SNVs can influence gene expression and disease, consequently generating opportunities for personalized, RNA-based therapeutics targeting these disorders.

Abstract Assembling atomic layers of van der Waals materials (vdW) combines the physics of two materials, offering opportunities for novel functional devices. Realization of this has been possible because of advancements in nanofabrication processes which often involve chemical processing of the materials under study; this can be detrimental to device performance. To address this issue, we have developed a modified micro-manipulator setup for cryogenic exfoliation, pick up, and transfer of vdW materials to assemble heterostructures. We use the glass transition of a polymer PDMS to cleave a flake into two, followed by its pick-up and drop to form pristine twisted junctions. To demonstrate the potential of the technique, we fabricated twisted heterostructure of Bi2Sr2CaCu2O8+x (BSCCO), a van der Waals high-temperature cuprate superconductor. We also employed this method to re-exfoliate NbSe2 and make twisted heterostructure. Transport measurements of the fabricated devices indicate the high quality of the artificial twisted interface. In addition, we extend this cryogenic exfoliation method for other vdW materials, offering an effective way of assembling heterostructures and twisted junctions with pristine interfaces.

Abstract Antimicrobial resistance in fungal pathogens (both human and plant) is increasing alarmingly, leading to massive economic crises. The existing anti-fungal agents are becoming ineffective, and the situation worsens on a logarithmic scale. Novel antifungals from unique natural sources are highly sought to cope sustainably with the situation. Metabolites from endophytic microbes are the best-fitted alternatives in this case. Endophytes are the untapped sources of ‘plants’ internal microbial population’ and are promising sources of effective bio-therapeutic agents. Fungal endophytes were isolated from Tropaeolum majus and checked for antifungal activity against selected plant and human pathogens. Bioactive metabolites were identified through chromatographic techniques. The mode of action of those metabolites was evaluated through various spectroscopic techniques. The production of antifungal metabolite was optimized also. In particular VOCs (volatile organic compounds) of TML9 were tested in vitro for their anti-phytopathogenic activity. Ethyl acetate (EA) extract of cell-free culture components of Colletotrichum aenigma TML3 exhibited broad-spectrum antifungal activity against four species of Candida and the major constituents reported were 6-pentyl-2H-pyran-2-one, 2-Nonanone, 1 propanol 2-amino. The volatile metabolites, trans-ocimene, geraniol, and 4-terpinyl acetate, produced from Curvularia lunata TML9, inhibited the growth of some selected phyto pathogens. EA extract hampered the biofilm formation, minimised the haemolytic effect, and blocked the transformation of Candida albicans (MTCC 4748) from yeast to hyphal form with a Minimum Fungicidal Concentration (MFC) of 200–600 µg mL−1. Central carbohydrate metabolism, ergosterol synthesis, and membrane permeability were adversely affected and caused the lethal leakage of necessary macromolecules of C. albicans. Volatile metabolites inhibited the growth of phytopathogens i.e., Rhizoctonia solani, Alternaria alternata, Botrytis cinerea, Cercospora beticola, Penicillium digitatum, Aspergillus fumigatus, Ceratocystis ulmi, Pythium ultimum up to 89% with an IC50 value of 21.3–69.6 µL 50 mL−1 and caused leakage of soluble proteins and other intracellular molecules. Citrusy sweet odor volatiles of TML9 cultured in wheat-husk minimised the infections of Penicillium digitatum (green mold), in VOC-exposed sweet oranges (Citrus sinensis). Volatile and non-volatile antifungal metabolites of these two T. majus endophytes hold agricultural and pharmaceutical interests. Metabolites of TML3 have strong anti-Candida activity and require further assessment for therapeutic applications. Also, volatile metabolites of TML9 can be further studied as a source of antifungals. The present investigational outcomes bio-prospects the efficacy of fungal endophytes of Garden Nasturtium.

Abstract Extracting information-bearing signal from a noisy environment has been a practical challenge in both classical and quantum computing formalism, especially in critical signal processing applications. To filter out the effect of noise, we propose a quantum smoothing filter built upon quantum formalism-based circuits applied for electrocardiogram signal denoising. The proposed quantum filter is a conceptually novel framework with an advantage in computational complexity as compared to the existing classical filters, such as discrete wavelet transform and empirical mode decomposition, whereas it achieves similar performance metrics for the accuracy of the filter. Further, we exploit the penta-diagonal Toeplitz structure of the smoothing filter, which gives approximately $$48\%$$ 48 % gate cost reduction for 10 qubit circuit compared to the standard Hamiltonian simulation without structure. The run-time complexity using the quantum matrix inversion technique for the structured matrix is given by $$\tilde{{\mathscr {O}}}\left( \frac{\kappa ^2 \text {poly}(\log {N})}{\varepsilon _P}\right)$$ O ~ κ 2 poly ( log N ) ε P for condition number $$\kappa$$ κ of the $$N\times N$$ N × N filter matrix within precision $$\varepsilon _P$$ ε P . Embedding fixed sparsity of the banded matrix, the quantum filter shows potentially better run-time complexity than classical filtering techniques. For the quantifiable research results of our work, we have shown several performance metrics, such as mean-square error and peak signal-to-noise ratio analysis, with a bound of error due to observation noise, simulation error and quantum measurement uncertainty.

Abstract Epilepsy is a chronic neurological disease, characterized by spontaneous, unprovoked, recurrent seizures that may lead to long-term disability and premature death. Despite significant efforts made to improve epilepsy detection clinically and pre-clinically, the pervasive presence of noise in EEG signals continues to pose substantial challenges to their effective application. In addition, discriminant features for epilepsy detection have not been investigated yet. The objective of this study is to develop a hybrid model for epilepsy detection from noisy and fragmented EEG signals. We hypothesized that a hybrid model could surpass existing single models in epilepsy detection. Our approach involves manual noise rejection and a novel statistical channel selection technique to detect epilepsy even from noisy EEG signals. Our proposed Base-2-Meta stacking classifier achieved notable accuracy (0.98 ± 0.05), precision (0.98 ± 0.07), recall (0.98 ± 0.05), and F1 score (0.98 ± 0.04) even with noisy 5-s segmented EEG signals. Application of our approach to the specific problem like detection of epilepsy from noisy and fragmented EEG data reveals a performance that is not only superior to others, but also is translationally relevant, highlighting its potential application in a clinic setting, where EEG signals are often noisy or scanty. Our proposed metric DF-A (Discriminant feature-accuracy), for the first time, identified the most discriminant feature with models that give A accuracy or above (A = 95 used in this study). This groundbreaking approach allows for detecting discriminant features and can be used as potential electrographic biomarkers in epilepsy detection research. Moreover, our study introduces innovative insights into the understanding of these features, epilepsy detection, and cross-validation, markedly improving epilepsy detection in ways previously unavailable.

Abstract Myocarditis is considered a fatal form of foot-and-mouth disease (FMD) in suckling calves. In the present study, a total of 17 calves under 4 months of age and suspected clinically for FMD were examined for clinical lesions, respiratory rate, heart rate, and heart rhythm. Lesion samples, saliva, nasal swabs, and whole blood were collected from suspected calves and subjected to Sandwich ELISA and reverse transcription multiplex polymerase chain reaction (RT-mPCR) for detection and serotyping of FMD virus (FMDV). The samples were found to be positive for FMDV serotype “O”. Myocarditis was suspected in 6 calves based on tachypnoea, tachycardia, and gallop rhythm. Serum aspartate aminotransferase (AST), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH), and cardiac troponins (cTnI) were measured. Mean serum AST, cTn-I and LDH were significantly higher (P 2 months 2 months

Abstract The realization of lithium‐metal (Li) batteries faces challenges due to dendritic Li deposition causing internal short‐circuit and low Coulombic efficiency. In this regard, the Li‐deposition stability largely depends on the electrolyte, which reacts with Li to form a solid electrolyte interphase (SEI) with diverse physico‐chemical properties, and dictates the interphasial kinetics. Therefore, optimizing the electrolyte for stability and performance remains pivotal. Hereof, glyme ethers are an emerging class of electrolytes, showing improved compatibility with metallic Li and enhanced stability in Li─Air and Li─Sulfur batteries. Yet, the criteria for selecting glyme solvents, particularly concerning Li deposition and dissolution processes, remain unclear. The SEI characteristics and Li deposition/dissolution processes are investigated in glyme‐ether‐based electrolytes with varying chain lengths, using lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) and lithium nitrate (LiNO₃) salts under high capacity and limited electrolyte conditions. Longer glymes led to more homogeneous SEI, particularly pronounced with LiNO₃, minimizing surface roughness during stripping, and promoting compact Li deposits. Higher reductive stability, resulting in homogeneous interphasial properties, and slower kinetics due to high desolvation barrier and viscosity, underline stable Li growth in longer glymes. This study clarifies factors guiding the selection of glyme ether‐based electrolytes in Li metal batteries, offering insights for next‐generation energy storage systems.

In this work, various physicochemical properties are investigated in nanostructured WOx thin films prepared by radio-frequency magnetron sputtering for optoelectronic applications. A glancing angle of 87° is employed to grow films of different thicknesses, which are then exposed to post-growth annealing. Detailed local probe analyses in terms of morphology and work function of WOx films are carried out to investigate thickness-dependent property modulations of the as-deposited and annealed films. The analyses show a reasonably good correlation with photoelectron spectroscopic measurements on the films and the bulk I–V characteristics acquired on a series of WOx/p-Si heterojunction diodes. The presence of a critical WOx thickness is identified to regulate the rectification ratio values at the WOx/p-Si heterostructures and increase in series resistance within the bulk of the films. The present study provides valuable insights to correlate optical, electrical, and structural properties of WOx thin films, which will be beneficial for fabricating WOx-based optoelectronic devices, including photovoltaic cells.

Abstract Colletotrichum is an important plant pathogenic fungi that causes anthracnose/-twister disease in onion. This disease was prevalent in the monsoon season from August to November months and the symptoms were observed in most of the fields. This study aimed to investigate the pathogenicity and cumulative effect, if any of Colletotrichum gloeosporioides and Fusarium acutatum. The pot experiment was laid out to identify the cause responsible for inciting anthracnose-twister disease, whether the Colletotrichum or Fusarium or both, or the interaction of pathogens and GA3. The results of the pathogenicity test confirmed that C. gloeosporioides and F. acutatum are both pathogenic. C. gloeosporioides caused twisting symptoms independently, while F.acutatum independently caused only neck elongation. The independent application of GA3 did not produce any symptoms, however, increased the plant height. The combined treatment of C. gloeosporioides and F. acutatum caused twisting, which enhanced upon interaction with GA3 application giving synergistic effect. The acervuli were found in lesions infected with C. gloeosporioides after 8 days of inoculation on the neck and leaf blades. Symptoms were not observed in untreated control plants. Koch's postulates were confirmed by reisolating the same pathogens from the infected plants.

Abstract The diagnostic assays currently used to detect Shigella spp. (Shigella) and enterotoxigenic Escherichia coli (ETEC) are complex or elaborate which make them difficult to apply in resource poor settings where these diseases are endemic. The simple and rapid nucleic acid amplification-based assay "Rapid LAMP-based Diagnostic Test (RLDT)" was evaluated to detect Shigella spp (Shigella) and enterotoxigenic Escherichia coli (ETEC) and determine the epidemiology of these pathogens in Kolkata, India. Stool samples (n = 405) from children under five years old with diarrhea seeking care at the hospitals were tested, and 85(21%) and 68(17%) by RLDT, 91(23%) and 58(14%) by quantitative PCR (qPCR) and 35(9%) and 15(4%) by culture, were positive for Shigella and ETEC, respectively. The RLDT showed almost perfect agreement with qPCR, Kappa 0.96 and 0.89; sensitivity 93% and 98%; specificity 100% and 97% for Shigella and ETEC, respectively. While RLDT detected additional 12% Shigella and 13% ETEC than culture, all culture positives for Shigella and ETEC except one each were also positive by the RLDT, sensitivity 97% and 93% respectively. RLDT is a simple, sensitive, and rapid assay that could be implemented with minimum training in the endemic regions to strengthen the disease surveillance system and rapid outbreak detection.

Abstract Cdk8 in Drosophila is the orthologue of vertebrate CDK8 and CDK19. These proteins have been shown to modulate transcriptional control by RNA polymerase II. We found that neuronal loss of Cdk8 severely reduces fly lifespan and causes bang sensitivity. Remarkably, these defects can be rescued by expression of human CDK19, found in the cytoplasm of neurons, suggesting a non-nuclear function of CDK19/Cdk8. Here we show that Cdk8 plays a critical role in the cytoplasm, with its loss causing elongated mitochondria in both muscles and neurons. We find that endogenous GFP-tagged Cdk8 can be found in both the cytoplasm and nucleus. We show that Cdk8 promotes the phosphorylation of Drp1 at S616, a protein required for mitochondrial fission. Interestingly, Pink1, a mitochondrial kinase implicated in Parkinson’s disease, also phosphorylates Drp1 at the same residue. Indeed, overexpression of Cdk8 significantly suppresses the phenotypes observed in flies with low levels of Pink1, including elevated levels of ROS, mitochondrial dysmorphology, and behavioral defects. In summary, we propose that Pink1 and Cdk8 perform similar functions to promote Drp1-mediated fission.

Abstract Glutamate (Glu) is important for memory and learning. Hence, Glu imbalance is speculated to affect autism spectrum disorder (ASD) pathophysiology. The action of Glu is mediated through receptors and we analyzed four metabotropic Glu receptors (mGluR/GRM) in Indo-Caucasoid families with ASD probands and controls. The trait scores of the ASD probands were assessed using the Childhood Autism Rating Scale2-ST. Peripheral blood was collected, genomic DNA isolated, and GRM5 rs905646, GRM6 rs762724 & rs2067011, and GRM7 rs3792452 were analyzed by PCR/RFLP or Taqman assay. Expression of mGluRs was measured in the peripheral blood by qPCR. Significantly higher frequencies of rs2067011 ‘A’ allele/ AA’ genotype were detected in the probands. rs905646 ‘A ‘exhibited significantly higher parental transmission. Genetic variants showed independent as well as interactive effects in the probands. Receptor expression was down-regulated in the probands, especially in the presence of rs905646 ‘AA’, rs762724 ‘TT’, rs2067011 ‘GG’, and rs3792452 ‘CC’. Trait scores were higher in the presence of rs762724 ‘T’ and rs2067011 ‘G’. Therefore, in the presence of risk genetic variants, down-regulated mGluR expression may increase autistic trait scores. Since our investigation was confined to the peripheral system, in-depth exploration involving peripheral as well as central nervous systems may validate our observation.

Abstract One of the frontier research areas in the field of gas sensing is high-performance room temperature-based novel sensing materials, and new family of low-cost and eco-friendly carbon nanomaterials with a unique structure has attracted significant attention. In this work, we propose a novel low-cost flexible room temperature ammonia gas sensor based on nitrogen-doped carbon nano-onions/polypyrrole (NCNO-PPy) composite material mounted low-cost membrane substrate was synthesized by combining hydrothermal and in-situ chemical polymerization methods. The proposed flexible sensor revealed high sensing performance when employed as the sensing material for ammonia detection at room temperature. The NCNO-PPy ammonia sensor exhibited 17.32% response for 100 ppm ammonia concentration with a low response time of 26 s. The NCNO-PPy based flexible sensor displays high selectivity, good repeatability, and long-term durability with 1 ppm as the lower detection limit. The proposed flexible sensor also demonstrated remarkable mechanical robustness under extreme bending conditions, i.e., up to 90° bending angle and 500 bending cycles. This enhanced sensing performance can be related to the potential bonding and synergistic interaction between nitrogen-doped CNOs and PPy, the formation of defects from nitrogen doping, and the presence of high reactive sites on the surface of NCNO-PPy composites. Additionally, the computational study was performed on optimized NCNO-PPy nanocomposite for both with and without NH3 interaction. A deeper understanding of the sensing phenomena was proposed by the computation of several electronic characteristics, such as band gap, electron affinity, and ionization potential, for the optimized composite.

Abstract Essential oil from Thymus vulgaris L. has valuable therapeutic potential that is highly desired in pharmaceutical, food, and cosmetic industries. Considering these advantages and the rising market demand, induced polyploids were obtained using oryzalin to enhance essential oil yield. However, their therapeutic values were unexplored. So, this study aims to assess the phytochemical content, and antimicrobial, antioxidant, and anti-inflammatory activities of tetraploid and diploid thyme essential oils. Induced tetraploids had 41.11% higher essential oil yield with enhanced thymol and γ-terpinene content than diploid. Tetraploids exhibited higher antibacterial activity against all tested microorganisms. Similarly, in DPPH radical scavenging assay tetraploid essential oil was more potent with half-maximal inhibitory doses (IC50) of 180.03 µg/mL (40.05 µg TE/mg) than diploid with IC50 > 512 µg/mL (12.68 µg TE/mg). Tetraploids exhibited more effective inhibition of in vitro catalytic activity of pro-inflammatory enzyme cyclooxygenase-2 (COX-2) than diploids at 50 µg/mL concentration. Furthermore, molecular docking revealed higher binding affinity of thymol and γ-terpinene towards tested protein receptors, which explained enhanced bioactivity of tetraploid essential oil. In conclusion, these results suggest that synthetic polyploidization using oryzalin could effectively enhance the quality and quantity of secondary metabolites and can develop more efficient essential oil-based commercial products using this induced genotype.

Abstract Physician marriage is a valuable indicator of how vocational factors (e.g. work hours, stressors) impact satisfaction in relationships and physician wellness overall. Previous studies suggest that gender and specialty influence marriage satisfaction for physicians, though these often come from limited, local, cohorts. A cross-sectional survey was designed and distributed to publicly available email addresses representing academic and private practice physician organizations across the United States, receiving 321 responses (253 complete). Responses included data on demographics, medical specialty, age at marriage, stage of training at marriage, number of children, and factors leading to marital satisfaction/distress. A multivariable ordinal logistic regression was conducted to find associations between survey variables and marriage satisfaction. Survey results indicated that 86.5% of physicians have been married (average age at first marriage was 27.8 years old), and the rate of first marriages ending is at least 14.7%. Men had significantly more children than women. Physicians married at least once averaged 1.98 children. “Other” specialty physicians had significantly more children on average than psychiatrists. Marrying before medical school predicted practicing in private practice settings. Job stress, work hours, children, and sex were most frequently sources of marital distress, while strong communication, finances, and children were most frequently sources of marital stability. Sex differences were also found in distressing and stabilizing marital factors: Female physicians were more likely to cite their spouse’s work hours and job stress as sources of marital distress. Finally, surgery specialty and Judaism were associated with higher marriage satisfaction, whereas possession of an M.D. degree was associated with lower marriage satisfaction. This study elucidated new perspectives on physician marriage and families based on specialty, practice setting, and stage of training at marriage. Future studies may focus on factors mediating specialty and sex’s impact on having children and marriage satisfaction. To our knowledge, this study is the first physician marriage survey which integrates multiple factors in the analysis of physician marriages.

Abstract The traditional rice genotypes of Assam are considered to have biological value due to the presence of several bioactive compounds like flavonoids, polyphenols, and anthocyanins, which have antioxidant, anti-cancer, anti-diabetic, and anti-aging properties. The pigmented genotypes are considered to have high iron (Fe) content. However, the effect of Fe and Zinc (Zn) accumulation on anthocyanin content is yet to be studied in pigmented rice of Assam. We studied the Fe, Zn, and anthocyanin content in grains of 204 traditional rice of Assam, which are traditionally preferred for their nutraceutical properties. We performed phenotypic and biochemical compositional analyses of 204 genotypes to identify those having high Fe, Zn, and anthocyanin. We also carried out the differential expression of a few selected Fe and Zn transporter genes along with the expression of anthocyanin biosynthesis genes. Interestingly, all pigmented rice genotypes contained a higher amount of phenolic compound than the non-pigmented form of rice. We found the highest (32.73 g) seed yield per plant for genotype Jengoni followed by Kajoli chokuwa and Khau Pakhi 1. We also listed 30 genotypes having high levels of Fe and Zn content. The genotype Jengoni accumulated the highest (186.9 μg g−1) Fe, while the highest Zn (119.9 μg g−1) content was measured in genotype Bora (Nagaon), The levels of Ferritin 2 gene expression were found to be significantly higher in Bora (Nagaon) (> 2-fold). For Zn accumulation, the genotype DRR Dhan-45, which was released as a high Zn content variety, showed significant up-regulation of the ZIP4 gene at booting (> 7-fold), post-anthesis (7.8-fold) and grain filling (> 5-fold) stages followed by Bora (Nagaon) (> 3-fold) at post-anthesis. Anthocyanidin synthase gene, Flavanone 3-dioxygenase 1-like (FDO1), and Chalcone-flavanone isomerase-like genes were up-regulated in highly pigmented genotype Bora (Nagaon) followed by Jengoni. Based on our data there was no significant correlation between iron and zinc content on the accumulation of anthocyanin. This challenges the present perception of the higher nutritive value in terms of the micronutrient content of the colored rice of Assam. This is the first report on the detailed characterization of traditional rice genotypes inclusive of phenotypic, biochemical, nutritional, and molecular attributes, which would be useful for designing the breeding program to improve Fe, Zn, or anthocyanin content in rice.

Complex spatio-temporal systems like lakes, forests and climate systems exhibit alternative stable states. In such systems, as the threshold value of the driver is crossed, the system may experience a sudden (discontinuous) transition or smooth (continuous) transition to an undesired steady state. Theories predict that changes in the structure of the underlying spatial patterns precede such transitions. While there has been a large body of research on identifying early warning signals of critical transitions, the problem of forecasting the type of transitions (sudden versus smooth) remains an open challenge. We address this gap by developing an advanced machine learning (ML) toolkit that serves as an early warning indicator of spatio-temporal critical transitions, Spatial Early Warning Signal Network (S-EWSNet). ML models typically resemble a black box and do not allow envisioning what the model learns in discerning the labels. Here, instead of naively relying upon the deep learning model, we let the deep neural network learn the latent features characteristic of transitions via an optimal sampling strategy (OSS) of spatial patterns. The S-EWSNet is trained on data from a stochastic cellular automata model deploying the OSS, providing an early warning indicator of transitions while detecting its type in simulated and empirical samples.

INTRODUCTION: Cloud computing, a still emerging technology, allows customers to pay for services based on usage. It provides internet-based services, whilst virtualization optimizes a PC’s available resources. OBJECTIVES: The foundation of cloud computing is the data center, comprising networked computers, cables, electricity components, and various other elements that host and store corporate data. In cloud data centres, high performance has always been a critical concern, but this often comes at the cost of increased energy consumption. METHODS: The most problematic factor is reducing power consumption while maintaining service quality and performance to balance system efficiency and energy use. Our proposed approach requires a comprehensive understanding of energy usage patterns within the cloud environment. RESULTS: We examined power consumption trends to demonstrate that with the application of the right optimization principles based on energy consumption models, significant energy savings can be made in cloud data centers. During the prediction phase, tablet optimization, with its 97 % accuracy rate, enables more accurate future cost forecasts. CONCLUSION: Energy consumption is a major concern for cloud data centers. To handle incoming requests with the fewest resources possible, given the increasing demand and widespread adoption of cloud computing, it is essential to maintain effective and efficient data center strategies.

Despite current antifungal therapy, invasive candidiasis causes >40% mortality in immunocompromised individuals. Therefore, developing an antifungal vaccine is a priority. Here, we could for the first time successfully attenuate the virulence of Candida albicans by treating it with a fungistatic dosage of EDTA and demonstrate it to be a potential live whole cell vaccine by using murine models of systemic candidiasis. EDTA inhibited the growth and biofilm formation of C. albicans. RNA-seq analyses of EDTA-treated cells (CAET) revealed that genes mostly involved in metal homeostasis and ribosome biogenesis were up- and down-regulated, respectively. Consequently, a bulky cell wall with elevated levels of mannan and β-glucan, and reduced levels of total monosomes and polysomes were observed. CAET was eliminated faster than the untreated strain (Ca) as found by differential fungal burden in the vital organs of the mice. Higher monocytes, granulocytes, and platelet counts were detected in Ca- vs CAET-challenged mice. While hyper-inflammation and immunosuppression caused the killing of Ca-challenged mice, a critical balance of pro- and anti-inflammatory cytokines-mediated immune responses are the likely reasons for the protective immunity in CAET-infected mice.

Abstract The premise for effective prevention and treatment of obesity is the availability of accurate prevalence figures. However, the prevalence of pediatric obesity and overweight in South Asian countries has seldom been analyzed. This article provides a comprehensive review and meta-analysis of studies on overweight and obesity to provide a more precise prevalence estimate. The study protocol was registered on PROSPERO (CRD42022320625). PubMed and Embase databases were comprehensively searched from inception till September 2023. The random-effects model was utilized to derive the pooled prevalence of obesity and overweight. Subgroup meta-analysis was used to assess variations in prevalence estimates across subgroups. A meta-regression analysis was also performed to assess the trend of overweight and obesity over the years. 152 studies were included with 489,525 participants. The pooled prevalence was 12.4 (95% CI 11.1–13.6) for overweight, 6.6% (95% CI 5.6–7.8) for obesity, and 19.3% (95% CI 17.1–21.7) for obesity and overweight. In subgroup analysis, Bangladesh reported a higher prevalence for both obesity (8.9%; 95% CI 4.9–13.9) and overweight (13.6%; 95% CI 9.2–18.8). Meta-regression analysis found a significant association between obesity prevalence and the publication year (β = 0.004; p = 0.03; R2 = 2.74%). The results of this study indicate a relatively higher prevalence of childhood obesity in South Asia, emphasizing the necessity for large-scale awareness efforts and context-specific preventative methods.

Abstract An insight into the dynamics of soil phosphorus (P) pools with long-term cropping/management practices would help in designing efficient and sustainable management module(s). The study aimed to investigate the long-term impact of diversified rice-based rotations and variable nutrient management practices on the dynamic composition of P pools and their influence on systems’ base-crop productivity in an alkaline soil of Indo-Gangetic plain (Fluvisol). Treatments consisted of four rotations [rice–wheat (R–W), rice–wheat–mungbean (R–W–Mb), rice–wheat–rice–chickpea (R–W–R–C), rice–chickpea (R–C)] each with three nutrient treatments [control (CT), integrated nutrient management (INM), sole-chemical fertilizers (CF)]. Notably, R–C exhibited higher levels of bioavailable-P (soluble-P, Ca2-P, labile-Po), particularly in subsurface soil depth (0.2–0.4 m) compared to other rotations. Likewise, the inclusion of chickpea every alternate year (R–W–R–C) resulted in higher Ca2-P (40%), labile-Pi (15%), labile-Po (11%), and moderately labile Po (8%) compared to R–W rotation demonstrating an increased significance of chickpea in maintaining a favorable soil P regime in alkaline soil. Both R–C and R–W–R–C reduced the surface-to-subsurface depth ratio (SSBR) of soluble-P and Ca2-P while increasing the ratio for microbial biomass P. Even with a suboptimal fertilizer-P rate, INM significantly increased soluble-P (4–33%), labile-Po (13–17%), microbial biomass P (10–26%), moderately labile-Po (4–17%) compared to CF and exhibited higher SSBR values. Correlation analysis demonstrated the substantial influence of very-labile carbon, microbial and phosphatase activities on P availability. The treatment-induced changes in labile-P pools significantly influenced rice (base-crop) yields. In conclusion, chickpea-inclusive diversification and INM could be a sustainable approach to enhance P bioavailability and crop productivity in tropical rice soils.

Abstract Patients reporting to the outpatient departments of peripheral health care settings in India with symptoms of urinary tract infection (UTI) receive one or the other antibiotic before culture confirmation and out of the total culture confirmed UTI cases, in less than one third cases the prescribed antibiotics matches to the antibiotic sensitivity test result. Hence, in this study, an indigenous point-of-care (POCT) rapid diagnostic kit (Rapidogram) for UTI was validated against conventional urine culture and sensitivity to understand its possible applicability at peripheral health care settings. This cross-sectional study was conducted during November 2021 to June 2022 in OPDs of two peripheral hospitals. A sample size of 300 was calculated using prevalence of urinary tract infection (UTI) as 33% for sensitivity and specificity using Buderer’s formula. Urine specimens were collected following standard aseptic procedures from the recruited suspected UTI cases and transferred to laboratory maintaining the cold chain. The validation work up was done in two sections: lab validation and field validation. Out of 300 urine samples, 29 were found positive for the growth of UTI pathogen by both methods and 267 were found negative by both methods. Thus, the kit shows very high specificity (99.6%; 97.9–99.9%) and considerably high sensitivity (90.6%; 74.9–98.0%). We also observed higher PPV, NPV, test accuracy (> 96%). Diagnostic Odds Ratio and Youden index were respectively 2581 and 0.89. Clinical data showed that 44% of the suspected UTI cases were prescribed at least one antibiotic before urine test. Mostly they received Norfloxacin whereas the mostly identified organism E.coli was sensitive to Nitrofurantoin. In the context of absence of microbiology facility at peripheral setting and rampant empirical use of antibiotics in UTI, this highly specific and sensitive POCT for UTI may be used as it not only identifies the organism, also shows the antibiotic sensitivity pattern.

Abstract Mesenchymal stem cells (MSCs) are known to facilitate angiogenesis and promote neo-vascularization via secretion of trophic factors. Here, we explored the molecular mechanism adopted by ADAMTS13 in modulating the expression of some key angiogenic markers in human umbilical cord-derived MSCs under serum-deprivation stress. Wharton’s jelly MSCs (WJ-MSCs) were isolated from the perivascular region of human umbilical cords by explant culture. ADAMTS13 was upregulated at both mRNA and protein levels in WJ-MSCs under serum-deprivation stress. Correspondingly, some key angiogenic markers were also seen to be upregulated. By screening signaling pathways, p38 and JNK pathways were identified as negative and positive regulators for expression of ADAMTS13, and the angiogenic markers, respectively. Our results also indicated the Notch pathway and p53 as other probable partners modulating the expression of ADAMTS13 and the angiogenic markers. Knockdown of ADAMTS13 using siRNA led to reversal in the expression of these angiogenic markers. Further, ADAMTS13 was shown to act via the EphrinB2/EphB4 axis followed by ERK signaling to control expression of the angiogenic markers. Interestingly, stronger expression levels were noted for ADAMTS13, VEGF and PDGF under a more stringent nutrient stress condition. Thus, we highlight a novel role of ADAMTS13 in WJ-MSCs under nutrient stress condition.

Abstract HfO2-based thin films hold huge promise for integrated devices as they show full compatibility with semiconductor technologies and robust ferroelectric properties at nanometer scale. While their polarization switching behavior has been widely investigated, their electromechanical response received much less attention so far. Here, we demonstrate that piezoelectricity in Hf0.5Zr0.5O2 ferroelectric capacitors is not an invariable property but, in fact, can be intrinsically changed by electrical field cycling. Hf0.5Zr0.5O2 capacitors subjected to ac cycling undergo a continuous transition from a positive effective piezoelectric coefficient d 33 in the pristine state to a fully inverted negative d 33 state, while, in parallel, the polarization monotonically increases. Not only can the sign of d 33 be uniformly inverted in the whole capacitor volume, but also, with proper ac training, the net effective piezoresponse can be nullified while the polarization is kept fully switchable. Moreover, the local piezoresponse force microscopy signal also gradually goes through the zero value upon ac cycling. Density functional theory calculations suggest that the observed behavior is a result of a structural transformation from a weakly-developed polar orthorhombic phase towards a well-developed polar orthorhombic phase. The calculations also suggest the possible occurrence of a non-piezoelectric ferroelectric Hf0.5Zr0.5O2. Our experimental findings create an unprecedented potential for tuning the electromechanical functionality of ferroelectric HfO2-based devices.

Abstract Research aimed at identifying indicators of persistent abrupt shifts in ecological communities, a.k.a regime shifts, has led to the development of a suite of early warning signals (EWSs). As these often perform inaccurately when applied to real-world observational data, it remains unclear whether critical transitions are the dominant mechanism of regime shifts and, if so, which EWS methods can predict them. Here, using multi-trophic planktonic data on multiple lakes from around the world, we classify both lake dynamics and the reliability of classic and second generation EWSs methods to predict whole-ecosystem change. We find few instances of critical transitions, with different trophic levels often expressing different forms of abrupt change. The ability to predict this change is highly processing dependant, with most indicators not performing better than chance, multivariate EWSs being weakly superior to univariate, and a recent machine learning model performing poorly. Our results suggest that predictive ecology should start to move away from the concept of critical transitions, developing methods suitable for predicting resilience loss not limited to the strict bounds of bifurcation theory.

Abstract In the modern world, wheat, a vital global cereal and the second most consumed, is vulnerable to climate change impacts. These include erratic rainfall and extreme temperatures, endangering global food security. Research on hydrogen-rich water (HRW) has gained momentum in plant and agricultural sciences due to its diverse functions. This study examined the effects of different HRW treatment durations on wheat, revealing that the 4-h treatment had the highest germination rate, enhancing potential, vigor, and germination indexes. This treatment also boosted relative water content, root and shoot weight, and average lengths. Moreover, the 4-h HRW treatment resulted in the highest chlorophyll and soluble protein concentrations in seeds while reducing cell death. The 4-h and 5-h HRW treatments significantly increased H2O2 levels, with the highest NO detected in both root and shoot after 4-h HRW exposure. Additionally, HRW-treated seeds exhibited increased Zn and Fe concentrations, along with antioxidant enzyme activities (CAT, SOD, APX) in roots and shoots. These findings suggest that HRW treatment could enhance wheat seed germination, growth, and nutrient absorption, thereby increasing agricultural productivity. Molecular analysis indicated significant upregulation of the Dreb1 gene with a 4-h HRW treatment. Thus, it shows promise in addressing climate change effects on wheat production. Therefore, HRW treatment could be a hopeful strategy for enhancing wheat plant drought tolerance, requiring further investigation (field experiments) to validate its impact on plant growth and drought stress mitigation.

Abstract Bladder cancer is a cancerous disease that mainly affects elder men and women. The immunotherapy that uses Bacillus of Calmette and Guerin (BCG) effectively treats bladder cancer by stimulating the immune response of patients. The therapeutic performance of BCG relies on drug dosing, and the design of an optimal BCG regimen is an open question. In this study, we propose the reparameterized multiobjective control (RMC) approach for seeking an optimal drug dosing regimen and apply it to the design of BCG treatment. This approach utilizes constrained optimization based on a nonlinear bladder cancer model with impulsive drug instillation. We compare the performance of RMC with Koopman model predictive control (MPC) and validate the efficacy of optimal BCG dosing regimens through numerical simulations, demonstrating the efficient elimination of cancerous cells. The proposed control framework holds the potential for generalization to other model-based treatment designs.

Abstract Attention deficit hyperactivity disorder (ADHD), a childhood-onset neurobehavioral disorder, often perturbs scholastic achievement and peer-relationship. The pivotal role of glutamate (Glu) in learning and memory indicated an influence of Glu in ADHD, leading to the exploration of Glu in different brain regions of ADHD subjects. We for the first time analyzed GluR genetic variations, Glu levels, as well as expression of Glu receptors (GluR) in the peripheral blood of eastern Indian ADHD probands to find out the relevance of Glu in ADHD prognosis. After obtaining informed written consent for participation, peripheral blood was collected for analyzing the genetic variants, Glu level, and expression of target genes. Since ADHD probands are often treated with methylphenidate or atomoxetine for providing symptomatic remediation, we have also tested post-therapeutic improvement in the ADHD trait scores in the presence of different GluR genotypes. Two variants, GRM7 rs3749380 “T” and GRIA1 rs2195450 “C”, exhibited associations with ADHD (P ≤ 0.05). A few GluR genetic variants showed significant association with higher trait severity, low IQ, lower plasma Glu level, down-regulated GluR mRNA expression, and poor response to medications. This indicates that down-regulated glutamatergic system may have an effect on ADHD etiology and treatment efficacy warranting further in-depth investigation.

Abstract Communication with hand gestures plays a significant role in human‐computer interaction by providing an intuitive and natural way for humans to communicate with machines. Ultrasound‐based devices have shown promising results in contactless hand gesture recognition without requiring physical contact. However, it is challenging to fabricate a densely packed wearable ultrasound array. Here, a stretchable ultrasound array is demonstrated with closely packed transducer elements fabricated using surface charge engineering between pre‐charged 1–3 Lead Zirconate Titanate (PZT) composite and thin polyimide film without using a microscope. The array exhibits excellent ultrasound properties with a wide bandwidth (≈57.1%) and high electromechanical coefficient (≈0.75). The ultrasound array can decipher gestures up to 10 cm in distance by using a contactless triboelectric module and identify materials from the time constant of the exponentially decaying impedance based on their triboelectric properties by utilizing the electrostatic induction phase. The newly proposed metric of the areal‐time constant is material‐specific and decreases monotonically from a highly positive human body (1.13 m2 s) to negatively charged polydimethylsiloxane (PDMS) (0.02 m2 s) in the triboelectric series. The capability of the closely packed ultrasound array to detect material along with hand gesture interpretation provides an additional dimension in the next‐generation human‐robot interaction.

Based on experimentally determined average inter-origin distances of ~100 kb, DNA replication initiates from ~50,000 origins on human chromosomes in each cell cycle. The origins are believed to be specified by binding of factors like the origin recognition complex (ORC) or CTCF or other features like G-quadruplexes. We have performed an integrative analysis of 113 genome-wide human origin profiles (from five different techniques) and five ORC-binding profiles to critically evaluate whether the most reproducible origins are specified by these features. Out of ~7.5 million union origins identified by all datasets, only 0.27% (20,250 shared origins) were reproducibly obtained in at least 20 independent SNS-seq datasets and contained in initiation zones identified by each of three other techniques, suggesting extensive variability in origin usage and identification. Also, 21% of the shared origins overlap with transcriptional promoters, posing a conundrum. Although the shared origins overlap more than union origins with constitutive CTCF-binding sites, G-quadruplex sites, and activating histone marks, these overlaps are comparable or less than that of known transcription start sites, so that these features could be enriched in origins because of the overlap of origins with epigenetically open, promoter-like sequences. Only 6.4% of the 20,250 shared origins were within 1 kb from any of the ~13,000 reproducible ORC-binding sites in human cancer cells, and only 4.5% were within 1 kb of the ~11,000 union MCM2-7-binding sites in contrast to the nearly 100% overlap in the two comparisons in the yeast, Saccharomyces cerevisiae. Thus, in human cancer cell lines, replication origins appear to be specified by highly variable stochastic events dependent on the high epigenetic accessibility around promoters, without extensive overlap between the most reproducible origins and currently known ORC- or MCM-binding sites.

The kidneys are crucial for maintaining Mg2+ homeostasis. Along the proximal tubule and thick ascending limb, Mg2+ is reabsorbed paracellularly, while along the distal convoluted tubule (DCT), Mg2+ is reabsorbed transcellularly via transient receptor potential melastatin 6 (TRPM6). TRPM6 and other renal transporter expressions are regulated by sex hormones. To investigate renal Mg2 handling, we have developed sex-specific computational models of electrolyte transport along rat superficial nephron. Model simulations indicated that along the proximal tubule and thick ascending limb, Mg2+ and Na+ transport occur parallelly, but they are dissociated along the DCT. In addition, our models predicted higher paracellular Mg2+ permeability in females to attain similar cortical thick ascending limb fractional Mg2+ reabsorption in both sexes. Furthermore, DCT fractional Mg2+ reabsorption is higher in females than in males, allowing females to better fine-tune Mg2+ excretion. We validated our models by simulating the administration of three classes of diuretics. The model predicted significantly increased, marginally increased and significantly decreased Mg2+ excretions for loop, thiazide and K-sparing diuretics, respectively, aligning with experimental findings. The models can be used to conduct in silico studies on kidney adaptations to Mg2+ homeostasis alterations during conditions such as pregnancy, diabetes and chronic kidney disease.

Summary: microRNAs (miRNAs) are small regulatory RNAs that repress target mRNA transcripts through base pairing. Although the mechanisms of miRNA production and function are clearly established, new insights into miRNA regulation or miRNA-mediated gene silencing are still emerging. In order to facilitate the discovery of miRNA regulators or effectors, we have developed sRNA-Effector, a machine learning algorithm trained on enhanced crosslinking and immunoprecipitation sequencing and RNA sequencing data following knockdown of specific genes. sRNA-Effector can accurately identify known miRNA biogenesis and effector proteins and identifies 9 putative regulators of miRNA function, including serine/threonine kinase STK33, splicing factor SFPQ, and proto-oncogene BMI1. We validated the role of STK33, SFPQ, and BMI1 in miRNA regulation, showing that sRNA-Effector is useful for identifying new players in small RNA biology. sRNA-Effector will be a web tool available for all researchers to identify potential miRNA regulators in any cell line of interest.

Abstract Facile conversion of CO2 to commercially viable carbon feedstocks offer a unique way to adopt a net-zero carbon scenario. Synthetic CO2-reducing catalysts have rarely exhibited energy-efficient and selective CO2 conversion. Here, the carbon monoxide dehydrogenase (CODH) enzyme blueprint is imitated by a molecular copper complex coordinated by redox-active ligands. This strategy has unveiled one of the rarest examples of synthetic molecular complex-driven reversible CO 2 reduction/CO oxidation catalysis under regulated conditions, a hallmark of natural enzymes. The inclusion of a proton-exchanging amine groups in the periphery of the copper complex provides the leeway to modulate the biases of catalysts toward CO2 reduction and CO oxidation in organic and aqueous media. The detailed spectroelectrochemical analysis confirms the synchronous participation of copper and redox-active ligands along with the peripheral amines during this energy-efficient CO 2 reduction/CO oxidation. This finding can be vital in abating the carbon footprint-free in multiple industrial processes.

The academic and industrial communities have proposed two-dimensional (2D) transition metal dichalcogenide (TMD) semiconductors as a future option to supplant silicon transistors at sub-10nm physical gate lengths. In this Comment, we share the recent progress in the fabrication of complementary metal-oxide-semiconductor (CMOS) devices based on stacked 2D TMD nanoribbons and specifically highlight issues that still need to be resolved by the 2D community in five crucial research areas: contacts, channel growth, gate oxide, variability, and doping. While 2D TMD transistors have great potential, more research is needed to understand the physical interactions of 2D materials at the atomic scale.

Abstract The implication of inflammation in the pathophysiology of several types of cancers has been under intense investigation. Conjugated fatty acids can modulate inflammation and present anticancer effects, promoting cancer cell death. In this paper, we evaluated the efficacy of new conjugated fatty acids isolated from marine Opisthopterus tardoore (Tapra fish) in human breast cancer cell lines MCF-7. Linoelaidic acid, a marine fish (O. tardoore) derived unsaturated fatty acids, showed effective anticancer activity against MCF-7. Cell viability (MTT) assay revealed a dose-dependent decline in cancer cell viability. It was noteworthy that 5 µM linoelaidic acid decreased the MCF-7 cell viability by 81.82%. Besides that, linoelaidic acid significantly (P

Abstract Gene therapy via retroviral vectors holds great promise for treating a variety of serious diseases. It requires the use of additives to boost infectivity. Amyloid-like peptide nanofibers (PNFs) were shown to efficiently enhance retroviral gene transfer. However, the underlying mode of action of these peptides remains largely unknown. Data-mining is an efficient method to systematically study structure–function relationship and unveil patterns in a database. This data-mining study elucidates the multi-scale structure–property–activity relationship of transduction enhancing peptides for retroviral gene transfer. In contrast to previous reports, we find that not the amyloid fibrils themselves, but rather µm-sized β-sheet rich aggregates enhance infectivity. Specifically, microscopic aggregation of β-sheet rich amyloid structures with a hydrophobic surface pattern and positive surface charge are identified as key material properties. We validate the reliability of the amphiphilic sequence pattern and the general applicability of the key properties by rationally creating new active sequences and identifying short amyloidal peptides from various pathogenic and functional origin. Data-mining—even for small datasets—enables the development of new efficient retroviral transduction enhancers and provides important insights into the diverse bioactivity of the functional material class of amyloids.