Countering Zoonotic Diseases: Current Scenario and Advances in Diagnostics, Monitoring, Prophylaxis and Therapeutic Strategies.

Human life and health have interacted reciprocally with the surrounding environment and animal fauna for ages. This relationship is evident in developing nations, where human life depends more on the animal population for food, transportation, clothing, draft power, and fuel sources, among others. This inseparable link is a potent source of public health issues, especially in outbreaks of zoonotic diseases transmitted from animals to humans. Zoonotic diseases are referred to as diseases that are naturally transmitted between vertebrate animals and humans. Among the globally emerging diseases in the last decade, 75% are of animal origin, most of which are life-threatening. Since most of them are caused by potent new pathogens capable of long-distance transmission, the impact is widespread and has serious public health and economic consequences. Various other factors also contribute to the transmission, spread, and outbreak of zoonotic diseases, among which industrialization-led globalization followed by ecological disruption and climate change play a critical role. In this regard, all the possible strategies, including advances in rapid and confirmatory disease diagnosis and surveillance/monitoring, immunization/vaccination, therapeutic approaches, appropriate prevention and control measures to be adapted, and awareness programs, need to be adopted collaboratively among different health sectors in medical, veterinary, and concerned departments to implement the necessary interventions for the effective restriction, minimization, and timely control of zoonotic threats. The present review focuses on the current scenario of zoonotic diseases and their counteracting approaches to safeguard their health impact on humans.

MediatorWeb: a protein-protein interaction network database for the RNA polymerase II Mediator complex.

The protein-protein interaction (PPI) network of the Mediator complex is very tightly regulated and depends on different developmental and environmental cues. Here, we present an interactive platform for comparative analysis of the Mediator subunits from humans, baker's yeast Saccharomyces cerevisiae, and model plant Arabidopsis thaliana in a user-friendly web-interface database called MediatorWeb. MediatorWeb provides an interface to visualize and analyze the PPI network of Mediator subunits. The database facilitates downloading the untargeted and unweighted network of Mediator complex, its submodules, and individual Mediator subunits to better visualize the importance of individual Mediator subunits or their submodules. Further, MediatorWeb offers network visualization of the Mediator complex and interacting proteins that are functionally annotated. This feature provides clues to understand functions of Mediator subunits in different processes. In an additional tab, MediatorWeb provides quick access to secondary and tertiary structures, as well as residue-level contact information for Mediator subunits in each of the three model organisms. Another useful feature of MediatorWeb is detection of interologs based on orthologous analyses, which can provide clues to understand the functions of Mediator complex in less explored kingdoms. Thus, MediatorWeb and its features can help the user to understand the role of Mediator complex and its subunits in the transcription regulation of gene expression.

A review on strategies for crop improvement against drought stress through molecular insights.

The demand for food goods is rising along with the world population growth, which is directly related to the yield of agricultural crops around the world. However, a number of environmental factors, including floods, salinity, moisture, and drought, have a detrimental effect on agricultural production around the world. Among all of these stresses, drought stress (DS) poses a constant threat to agricultural crops and is a significant impediment to global agricultural productivity. Its potency and severity are expected to increase in the future years. A variety of techniques have been used to generate drought-resistant plants in order to get around this restriction. Different crop plants exhibit specific traits that contribute to drought resistance (DR), such as early flowering, drought escape (DE), and leaf traits. We are highlighting numerous methods that can be used to overcome the effects of DS in this review. Agronomic methods, transgenic methods, the use of sufficient fertilizers, and molecular methods such as clustered regularly interspaced short palindromic repeats (CRISPRs)-associated nuclease 9 (Cas9), virus-induced gene silencing (VIGS), quantitative trait loci (QTL) mapping, microRNA (miRNA) technology, and OMICS-based approaches make up the majority of these techniques. CRISPR technology has rapidly become an increasingly popular choice among researchers exploring natural tolerance to abiotic stresses although, only a few plants have been produced so far using this technique. In order to address the difficulties imposed by DS, new plants utilizing the CRISPR technology must be developed.

8-port MIMO antenna at 27 GHz for n261 band and exploring for body centric communication.

This paper presents a compact 5G wideband antenna designed for body-centric networks (BCN. The single element antenna design includes a simple T-shaped radiator patch with ring shaped ground plane and transformer impedance feedline. First, the antenna was simulated in free-space, and its resonant frequency is found to be 27 GHz, falling within 5G's n261 band. The proposed single radiator antenna has a size of 23.375 mm3, and it offers a wide impedance bandwidth of 2.0 GHz (26-28 GHz). Parametric studies demonstrated that by increasing the length of slots in patch, the antenna frequency can be reduced further. Single radiator antenna is used as 8-element MIMO structure. Parallel adjacent antenna in X-direction has minimal coupling effect, whereas antenna placed in Y-direction has high coupling effect. Thus, coupling is reduced by etching a wall of slots in ground plane. It alters the surface current interference in Y-direction and limits the coupling effect. The antenna is investigated to use in body area network applications. To evaluate its on-body performance, an equivalent body model is virtually developed. The on-body performance is assessed by placing the antenna in close proximity to body model. Stable and robust performance is achieved for the on-body operation. At the resonant point, the antenna exhibits a reflection coefficient of -30 dB (free space) and -40 dB (on-body), high isolation of above 20 dB between adjacent radiators and above 30 dB for other radiators. Antenna has stable performance for different body tissues and on the non-planar structures. Bidirectional radiation pattern with gain of 2.53 dB and broadside type orientations with gain of 4.64 dB are achieved for free space and on body operations respectively. low specific absorption rate makes antenna safe for health care devices. Further, diversity performance is measured in terms of envelope correlation coefficient (ECC), and diversity gain (DG). Maximum Value of ECC is 0.005 and minimum value DG is 9.97 at 27 GHz which confirms the excellence of antenna for MIMO applications.

Temporal dynamics of urban air pollutants and their correlation with associated meteorological parameters: an investigation in northern Indian cities.

This study delves into the intricate dynamics of air pollution in the rapidly expanding northern regions of India, examining the intertwined influences of agricultural burning, industrialization, and meteorological conditions. Through comprehensive analysis of key pollutants (PM2.5, PM10, NO2, SO2, CO, O3) across ten monitoring stations in Uttar Pradesh, Haryana, Delhi, and Punjab, a consistent pattern of high pollution levels emerges, particularly notable in Delhi. Varanasi leads in SO2 and O3 concentrations, while Moradabad stands out for CO levels, and Jalandhar for SO2 concentrations. The study further elucidates the regional distribution of pollutants, with Punjab receiving significant contributions from SW, SE, and NE directions, while Haryana and Delhi predominantly face air masses from SE and NE directions. Uttar Pradesh's pollution sources are primarily local, with additional inputs from various directions. Moreover, significant negative correlations (p < 0.05) between PM10, NO2, SO2, O3, and relative humidity (RH) underscore the pivotal role of meteorological factors in shaping pollutant levels. Strong positive correlations between PM2.5 and NO2 (0.71 to 0.93) suggest shared emission sources or similar atmospheric conditions in several cities. This comprehensive understanding highlights the urgent need for targeted mitigation strategies to address the multifaceted drivers of air pollution, ensuring the protection of public health and environmental sustainability across the region.

Hypoxia related genes modulate in similar fashion in skin fibroblast cells of yak (Bos grunniens) adapted to high altitude and native cows (Bos indicus) adapted to tropical climate during hypoxia stress.

The present study was conducted to understand transcriptional response of skin fibroblast of yak (Bos grunniens) and cows of Bos indicus origin to hypoxia stress. Six primary fibroblast cell lines derived from three individuals each of Ladakhi yak (Bos grunniens) and Sahiwal cows (Bos indicus) were exposed to low oxygen concentration for a period of 24 h, 48 h and 72 h. The expression of 10 important genes known to regulate hypoxia response such as HIF1A, VEGFA, EPAS1, ATP1A1, GLUT1, HMOX1, ECE1, TNF-A, GPx and SOD were evaluated in fibroblast cells of Ladakhi yak (LAY-Fb) and Sahiwal cows (SAC-Fb) during pre- and post-hypoxia stress. A panel of 10 reference genes (GAPDH, RPL4, EEF1A1, RPS9, HPRT1, UXT, RPS23, B2M, RPS15, ACTB) were also evaluated for their expression stability to perform accurate normalization. The expression of HIF1A was significantly (p < 0.05) induced in both LAY-Fb (2.29-fold) and SAC-Fb (2.07-fold) after 24 h of hypoxia stress. The angiogenic (VEGFA), metabolic (GLUT1) and antioxidant genes (SOD and GPx) were also induced after 24 h of hypoxia stress. However, EPAS1 and ATP1A1 induced significantly (p < 0.05) after 48 h whereas, ECE1 expression induced significantly (p < 0.05) at 72 h after exposure to hypoxia. The TNF-alpha which is a pro-inflammatory gene induced significantly (p < 0.05) at 24 h in SAC-Fb and at 72 h in LAY-Fb. The induction of hypoxia associated genes indicated the utility of skin derived fibroblast as cellular model to evaluate transcriptome signatures post hypoxia stress in populations adapted to diverse altitudes.

Outcome Study of Mandibular Fractures Treated by Surgical Stabilization With Plates and Screws.

This study aims to assess the outcomes of mandibular fractures treated through surgical stabilization using plates and screws, focusing on factors such as postoperative complications, patient satisfaction, and functional recovery. A total of 42 patients were included in the study. Surgical interventions involved the application of plates and screws at the fracture sites. Postoperative complications, including infection, hardware failure, and malocclusion, were recorded. Surgical stabilization of mandibular fractures using plates and screws demonstrates favorable outcomes in terms of stability, occlusal alignment, and patient satisfaction. The findings of this study contribute valuable insights into the efficacy of this surgical approach, highlighting its role in achieving successful outcomes for mandibular fracture management. Further prospective studies and randomized controlled trials are recommended to strengthen the evidence base and refine treatment protocols.

Rhes, a striatal enriched protein, regulates post-translational small-ubiquitin-like-modifier (SUMO) modification of nuclear proteins and alters gene expression.

Rhes (Ras homolog enriched in the striatum), a multifunctional protein that regulates striatal functions associated with motor behaviors and neurological diseases, can shuttle from cell to cell via the formation of tunneling-like nanotubes (TNTs). However, the mechanisms by which Rhes mediates diverse functions remain unclear. Rhes is a small GTPase family member which contains a unique C-terminal Small Ubiquitin-like Modifier (SUMO) E3-like domain that promotes SUMO post-translational modification of proteins (SUMOylation) by promoting "cross-SUMOylation" of the SUMO enzyme SUMO E1 (Aos1/Uba2) and SUMO E2 ligase (Ubc-9). Nevertheless, the identity of the SUMO substrates of Rhes remains largely unknown. Here, by combining high throughput interactome and SUMO proteomics, we report that Rhes regulates the SUMOylation of nuclear proteins that are involved in the regulation of gene expression. Rhes increased the SUMOylation of histone deacetylase 1 (HDAC1) and histone 2B, while decreasing SUMOylation of heterogeneous nuclear ribonucleoprotein M (HNRNPM), protein polybromo-1 (PBRM1) and E3 SUMO-protein ligase (PIASy). We also found that Rhes itself is SUMOylated at 6 different lysine residues (K32, K110, K114, K120, K124, and K245). Furthermore, Rhes regulated the expression of genes involved in cellular morphogenesis and differentiation in the striatum, in a SUMO-dependent manner. Our findings thus provide evidence for a previously undescribed role for Rhes in regulating the SUMOylation of nuclear targets and in orchestrating striatal gene expression via SUMOylation.

Pd-catalyzed stereoselective synthesis of chromone C-glycosides.

Herein, we present an efficient Pd-catalysed method for stereoselective synthesis of chromone C-glycosides from various glycals. We successfully applied this method to various glycals with different protecting groups, yielding the corresponding glycosides in 41-78% yields. Additionally, we investigated the potential of this approach for the late-stage modification of natural products and pharmaceutical compounds linked to glycals, leading to the synthesis of their respective glycosides. Furthermore, we extended our research to gram-scale synthesis and demonstrated its applicability in producing various valuable products, including 2-deoxy-chromone C-glycosides. In summary, our work introduces a novel library of chromone glycosides, which holds promise for advancing drug discovery efforts.

A phase 1 trial of the MEK inhibitor selumetinib in combination with pembrolizumab for advanced or metastatic solid tumors.

MEK inhibitors have immunomodulatory activity and potential for synergistic activity when combined with PD-1 inhibitors. We evaluated selumetinib (inhibitor of MEK1/2) plus pembrolizumab (anti‒PD-1 antibody) in patients with advanced/metastatic solid tumors. In this phase 1b study, adults with previously treated advanced/metastatic solid tumors received pembrolizumab 200 mg intravenously every 3 weeks plus selumetinib on days 1‒14 per 3-week cycle (2 weeks on/1 week off); selumetinib dosing began at 50 mg orally twice daily with escalation in 25 mg increments for ≤ 35 cycles. Primary endpoints were dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. Thirty-two patients were enrolled. Dose escalation was completed up to selumetinib 125 mg twice daily. The target DLT rate of 30% was not reached at any dose level. In the selumetinib 100 mg group, 2/11 patients (18.2%) experienced DLTs (n = 1 grade 3 diarrhea, n = 1 grade 3 fatigue). In the selumetinib 125 mg group, 3/14 (21.4%) experienced DLTs (n = 1 grade 2 retinal detachment, n = 1 grade 3 retinopathy, n = 1 grade 3 stomatitis). Dose-related changes in pharmacokinetic exposures were observed for selumetinib and N-desmethyl selumetinib up to 100 mg (saturation at 125 mg). Two patients achieved partial responses (1 each with selumetinib 75 mg and 125 mg) for an objective response rate of 6%. The study was stopped early because of insufficient efficacy. Although the target DLT rate was not reached at any dose level and no new safety signals were identified, selumetinib plus pembrolizumab had limited antitumor activity in this population. Trial registration: ClinicalTrials.gov , NCT03833427.

Final results of urelumab, an anti-CD137 agonist monoclonal antibody, in combination with cetuximab or nivolumab in patients with advanced solid tumors.

BACKGROUND: Resistance to immune checkpoint inhibitors and targeted treatments for cancer is common; thus, novel immunotherapy agents are needed. Urelumab is a monoclonal antibody agonist that binds to CD137 receptors expressed on T cells. Here, we report two studies that evaluated urelumab in combination with cetuximab or nivolumab in patients with select, advanced solid tumors. METHODS: CA186-018: Patients with metastatic colorectal cancer or metastatic squamous cell carcinoma of the head and neck (SCCHN) were treated in a dose-evaluation phase with urelumab 0.1 mg/kg (urelumab-0.1) every 3 weeks (Q3W)+cetuximab 250 mg/m2 (cetuximab-250) weekly; and in a dose-expansion phase with urelumab 8 mg flat dose (urelumab-8) Q3W+cetuximab-250 weekly. CA186-107: The dose-escalation phase included patients with previously treated advanced solid tumors (or treated or treatment-naive melanoma); patients received urelumab 3 mg flat dose (urelumab-3) or urelumab-8 every 4 weeks+nivolumab 3 mg/kg (nivolumab-3) or 240 mg (nivolumab-240) every 2 weeks. In the expansion phase, patients with melanoma, non-small cell lung cancer, or SCCHN were treated with urelumab-8+nivolumab-240. Primary endpoints were safety and tolerability, and the secondary endpoint included efficacy assessments. RESULTS: CA186-018: 66 patients received study treatment. The most frequent treatment-related adverse events (TRAEs) were fatigue (75%; n=3) with urelumab-0.1+cetuximab-250 and dermatitis (45%; n=28) with urelumab-8+cetuximab-250. Three patients (5%) discontinued due to TRAE(s) (with urelumab-8+cetuximab-250). One patient with SCCHN had a partial response (objective response rate (ORR) 5%, with urelumab-8+cetuximab-250).CA186-107: 134 patients received study treatment. Fatigue was the most common TRAE (32%; n=2 with urelumab-3+nivolumab-3; n=1 with urelumab-8+nivolumab-3; n=40 with urelumab-8+nivolumab-240). Nine patients (7%) discontinued due to TRAE(s) (n=1 with urelumab-3+nivolumab-3; n=8 with urelumab-8+nivolumab-240). Patients with melanoma naive to anti-PD-1 therapy exhibited the highest ORR (49%; n=21 with urelumab-8+nivolumab-240). Intratumoral gene expression in immune-related pathways (CD3, CD8, CXCL9, GZMB) increased on treatment with urelumab+nivolumab. CONCLUSIONS: Although the addition of urelumab at these doses was tolerable, preliminary response rates did not indicate an evident additive benefit. Nevertheless, the positive pharmacodynamics effects observed with urelumab and the high response rate in treatment-naive patients with melanoma warrant further investigation of other anti-CD137 agonist agents for treatment of cancer. TRIAL REGISTRATION NUMBERS: NCT02110082; NCT02253992.

Ribosome Profiling and Mass Spectrometry Reveal Widespread Mitochondrial Translation Defects in a Striatal Cell Model of Huntington Disease.

Huntington disease (HD) is caused by an expanded polyglutamine mutation in huntingtin (mHTT) that promotes prominent atrophy in the striatum and subsequent psychiatric, cognitive deficits, and choreiform movements. Multiple lines of evidence point to an association between HD and aberrant striatal mitochondrial functions; however, the present knowledge about whether (or how) mitochondrial mRNA translation is differentially regulated in HD remains unclear. We found that protein synthesis is diminished in HD mitochondria compared to healthy control striatal cell models. We utilized ribosome profiling (Ribo-Seq) to analyze detailed snapshots of ribosome occupancy of the mitochondrial mRNA transcripts in control and HD striatal cell models. The Ribo-Seq data revealed almost unaltered ribosome occupancy on the nuclear-encoded mitochondrial transcripts involved in oxidative phosphorylation (SDHA, Ndufv1, Timm23, Tomm5, Mrps22) in HD cells. By contrast, ribosome occupancy was dramatically increased for mitochondrially encoded oxidative phosphorylation mRNAs (mt-Nd1, mt-Nd2, mt-Nd4, mt-Nd4l, mt-Nd5, mt-Nd6, mt-Co1, mt-Cytb, and mt-ATP8). We also applied tandem mass tag-based mass spectrometry identification of mitochondrial proteins to derive correlations between ribosome occupancy and actual mature mitochondrial protein products. We found many mitochondrial transcripts with comparable or higher ribosome occupancy, but diminished mitochondrial protein products, in HD. Thus, our study provides the first evidence of a widespread dichotomous effect on ribosome occupancy and protein abundance of mitochondria-related genes in HD.

Satellite or ground-based measurements for air pollutants (PM2.5, PM10, SO2, NO2, O3) data and their health hazards: which is most accurate and why?

Air pollution is growing at alarming rates on regional and global levels, with significant consequences for human health, ecosystems, and change in climatic conditions. The present 12 weeks (4 October 2021, to 26 December 2021) study revealed the different ambient air quality parameters, i.e., PM2.5, PM10, SO2, NO2, and O3 over four different sampling stations of Delhi-NCR region (Dwarka, Knowledge park III, Sector 125, and Vivek Vihar), India, by using satellite remote sensing data (MERRA-2, OMI, and Aura Satellite) and different ground-based instruments. The ground-based observation revealed the mean concentration of PM2.5 in Dwarka, Knowledge park III, Sector 125, and Vivek Vihar as 279 µg m-3, 274 µg m-3, 294 µg m-3, and 365 µg m-3, respectively. The ground-based instrumental concentration of PM2.5 was greater than that of satellite observations, while as for SO2 and NO2, the mean concentration of satellite-based monitoring was higher as compared to other contaminants. Negative and positive correlations were observed among particulate matter, trace gases, and various meteorological parameters. The wind direction proved to be one of the prominent parameter to alter the variation of these pollutants. The current study provides a perception into an observable behavior of particulate matter, trace gases, their variation with meteorological parameters, their health hazards, and the gap between the measurements of satellite remote sensing and ground-based measurements.

Salp-J Colony Optimization-based advanced hybrid ensemble deep predictor with LSTM for protein structure prediction.

Protein structure prediction (PSP) is a key concern in computational biology, which is considered a challenging task that is vital to determine the structure and the protein function since each protein possesses a definite shape, whereas the protein secondary structure prediction (PSSP) is the foundation for three-dimensional PSP. An Advanced hybrid ensemble deep predictor is utilized for predicting the structure of a protein using Long-Short Term Memory (LSTM), in which the performance of the predictor is improved for obtaining the features through the Salp-J Colony Optimization, which is developed by integrating the features of three optimizations the exploration behavior of Ulmaris, the immune system of virus colony and the teamwork of salp for solution update that helps to predict the accurate protein structure. The proposed method achieved the value of 99.1% accuracy, 99.5% sensitivity, 98.85% specificity, and 0.9% error at the 80% of training percentage 90 using CullPDB. Similarly, in Protein Net, the attained value of accuracy is 97.27%, sensitivity is 98.13%, specificity is 97%, and error is 2.7% concerning training percentage 90%.Communicated by Ramaswamy H. Sarma.

Experimental and computational studies on the corrosion inhibition potential of a novel synthesized thiophene and pyridine-based 1,3,4-oxadiazole hybrid against mild steel corrosion in 1 N HCl.

A convenient synthesis of a novel 1,3,4-oxadiazole derivative, specifically known as, 2-(5-methylthiophen-2-yl)-5-(pyridin-3-yl)-1,3,4-oxadiazole (MTPO), is reported along with a comprehensive evaluation of its ability to inhibit the corrosion of mild steel (MS) in a 1 N HCl environment using weight loss, EIS, PDP, SEM, EDX, and UV-Vis spectroscopy. The investigated inhibitor expressed excellent inhibition efficiency (99.05% at 500 ppm, 298 K) with a mixed-type inhibitory mechanism as demonstrated by the PDP technique. Furthermore, MTPO followed Langmuir adsorption isotherm, which provides insights into the adsorption phenomena, demonstrating that it exhibits superior adsorption behavior on the MS surface compared. In silico investigations, using DFT computation and MD simulation complements the experimental outcomes revealing strong adsorbing attributes of the MTPO hybrid with the ω - and ω + values of 8.8882 eV and 4.4787 eV, respectively. In addition, the radial distribution function also addressed the chemisorption behavior of MTPO. This article also takes into consideration the various ways in which the inhibitor interacts with the mild steel, offering potential insights for developing strategies to mitigate metal dissolution in acidic environments.

A Relative Bioavailability, Bioequivalence, and Food Effect Study of Niraparib Tablets in Patients with Advanced Solid Tumors.

PURPOSE: The poly (ADP-ribose) polymerase inhibitor niraparib is indicated as maintenance treatment in patients with certain subtypes of advanced ovarian cancer, and is being investigated in patients with other solid tumors. Niraparib is available in 100-mg capsules with a starting dosage of 200 or 300 mg/d. This study assessed the relative bioavailability (BA) and bioequivalence (BE) between a 1 × 300-mg tablet relative to 3 × 100-mg niraparib capsules. In addition, the food effect (FE) of a high-fat meal on the pharmacokinetic (PK) properties of tablet-formulated niraparib was investigated. METHODS: This was a US-based, 3-stage, open-label, multicenter, single-crossover, randomized-sequence study. Enrolled patients were 18 years and older, with histologically or cytologically confirmed advanced solid tumors (metastatic or local) and disease progression despite standard therapy. Patients were randomly assigned 1:1 to receive niraparib 1 × 300-mg tablet or 3 × 100-mg capsules in the BA and BE stages or 1 × 300-mg tablet in a fasted or fed (high-fat meal) state in the FE stage. Across all study stages, PK parameters were assessed for 7 days after each dose (tablet or capsule) or prandial state (fasted or fed). In the BA stage, patients crossed over to the other treatment after a 7-day washout period, which was extended to 14 days in the BE and FE stages. Tolerability was assessed for patients who received any amount of niraparib. FINDINGS: The BA-, BE-, and FE-evaluable populations comprised 23, 108, and 19 patients, respectively, who completed both treatment periods in each study stage, had sufficient concentration data to accurately estimate PK parameters without niraparib carryover, and did not experience disqualifying events. PK parameters were similar after dosing with tablet or capsule formulations; the 90% CIs of the geometric least square means for Cmax, AUC0-t, and AUC0-∞ were within the 0.80 to 1.25 BE limits. In the FE stage, Cmax, AUC0-t, and AUC0-∞ were 11%, 32%, and 28% higher, respectively, in the fed versus fasted state. The safety population included 29, 168, and 28 patients in the BA, BE, and FE stages, respectively, who received niraparib. No new safety signals were identified. IMPLICATIONS: Niraparib tablets were found to be bioequivalent to capsules. A modest (≤32%) FE was observed with a high-fat meal, but was not considered to be clinically meaningful, given niraparib's PK variability. CLINICALTRIALS: gov identifier: NCT03329001. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.

Diversity in morpho-pomological attributes and biochemical profiling of bael (Aegle marmelos (L.) Correa) genotypes of North-Western India.

Bael is a medicinal cum fruit tree with multipurpose utility and propagated mostly through seeds. The present study aimed to assess and analyse the morpho-pomological and biochemical traits of eighty seedlings grown bael genotypes comparison with two commercial cultivars (NB-5 and NB-9) of bael. The significant differences were detected among the genotypes based on the measured morpho-pomological and biochemical traits. The morpho-pomological and biochemical traits of bael exhibited variation ranging from 6.17% to 133.65%. Trunk girth ranged from 29.50 to 63.40 cm and tree spread (N-S) varied 1.00-6.30 m. Fruit length ranged from 4.60 to 12.05 cm and fruit width ranged from 4.64 to 11.72 cm. Moreover, fruit weight ranged from 56.33 to 917.65 g and pulp percentage varied from 58.64 to 81.38%. Soluble Solid Content ranged from 25.90 to 36.77 0brix and ascorbic acid varied from 14.38 to 25.45 mg/100 g. Fruit length was positively correlated with fruit width, fruit weight, pulp percentage, seed length, seed diameter and number of seeds per fruit, while it was negatively correlated with fruit surface and total number of fruit per plant. Principal component analysis showed that 76.66% of the variability observed was explained by the 13 components. Ward cluster analysis using Euclidean distance classified the genotypes into two main clusters. These findings contribute to a better understanding of the diversity and relationships among the studied genotypes, aiding future breeding and selection programs for improved bael cultivation.

Design and performance analysis of an L-shaped radiator and defected ground antenna for enhancing wireless connectivity in brain implants.

Brain implantable wireless microsystems has potential to treat neurological diseases and maintain the quality of life. Highly efficient miniaturized antenna is the fundamental part of BID (brain implantable device) for reliable signaling of data through dissipative intracranial material. In this paper, a patch antenna with L-shaped defected ground is demonstrated. L-shaped radiator contributed to achieve the resonance at 2.45 GHz industrial scientific and medical (ISM) band. Antenna size is reduced to 10 × 10 × 0.25 mm3. The proposed L-shaped ground plane geometry is contributing in improving the radiation performance. |S11| value shifts from 15 dB to 30 dB after modifying the ground plane. Proposed structure attained the gain of -14 dBi when located between the Dura and CSF layers at the depth of 12 mm in human brain model. Full wave simulated antenna prototype is fabricated and measured for performance verification. Impedance bandwidth of 270 MHz and broadside radiation pattern (for transferring maximum electromagnetic energy away from tissue) are maintained by the proposed antenna. Brain tissue safety is ensured by specific absorption rate which is 0.709 W/kg and in compliance with the safety limits of 1.6 W/kg for 1-g averaged tissue. Proposed antenna structure is the promising candidate for medical implant technology.

SUMO modifies GßL and mediates mTOR signaling.

The mechanistic target of rapamycin (mTOR) signaling is influenced by multiple regulatory proteins and post-translational modifications; however, underlying mechanisms remain unclear. Here, we report a novel role of small ubiquitin-like modifier (SUMO) in mTOR complex assembly and activity. By investigating the SUMOylation status of core mTOR components, we observed that the regulatory subunit, GßL (G protein ß-subunit-like protein, also known as mLST8), is modified by SUMO1, 2, and 3 isoforms. Using mutagenesis and mass spectrometry, we identified that GßL is SUMOylated at lysine sites K86, K215, K245, K261, and K305. We found that SUMO depletion reduces mTOR-Raptor (regulatory protein associated with mTOR) and mTOR-Rictor (rapamycin-insensitive companion of mTOR) complex formation and diminishes nutrient-induced mTOR signaling. Reconstitution with WT GßL but not SUMOylation-defective KR mutant GßL promotes mTOR signaling in GßL-depleted cells. Taken together, we report for the very first time that SUMO modifies GßL, influences the assembly of mTOR protein complexes, and regulates mTOR activity.

Automated detection of depression using wavelet scattering networks.

Today, depression is a common problem that affects many people all over the world. It can impact a person's mood and quality of life unless identified and treated immediately. Due to the hectic and stressful modern life seems to be, depression has become a leading cause of mental health illnesses. Signals from electroencephalograms (EEG) are frequently used to detect depression. It is difficult, time-consuming, and highly skilled to manually detect depression using EEG data analysis. Hence, in the proposed study, an automated depression detection system using EEG signals is proposed. The proposed study uses a clinically available dataset and dataset provided by the Department of Psychiatry at the Government Medical College (GMC) in Kozhikode, Kerala, India which consisted of 15 depressed patients and 15 healthy subjects and a publically available Multi-modal Open Dataset (MODMA) for Mental-disorder Analysis available at UK Data service reshare that consisted of 24 depressed patients and 29 healthy subjects. In this study, we have developed a novel Deep Wavelet Scattering Network (DWSN) for the automated detection of depression EEG signals. The best-performing classifier is then chosen by feeding the features into several machine-learning algorithms. For the clinically available GMC dataset, Medium Neural Network (MNN) achieved the highest accuracy of 99.95% with a Kappa value of 0.999. Using the suggested methods, the precision, recall, and F1-score are all 1. For the MODMA dataset, Wide Neural Network (WNN) achieved the highest accuracy of 99.3% with a Kappa value of 0.987. Using the suggested methods, the precision, recall, and F1-score are all 0.99. In comparison to all current methodologies, the performance of the suggested research is superior. The proposed method can be used to automatically diagnose depression both at home and in clinical settings.