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Background:: Tissue clearing enables deep imaging in various tissues by increasing the transparency of tissues, but there were limitations of immunostaining of the large-volume tissues such as the whole brain. Methods:: Here, we cleared and immune-stained whole mouse brain tissues using a novel clearing technique termed high-speed clearing and high-resolution staining (HCHS). We observed neural structures within the cleared brains using both a confocal microscope and a light-sheet fluorescence microscope (LSFM). The reconstructed 3D images were analyzed using a computational reconstruction algorithm. Results:: Various neural structures were well observed in three-dimensional (3D) images of the cleared brains from Gad-green fluorescent protein (GFP) mice and Thy 1-yellow fluorescent protein (YFP) mice. The intrinsic fluorescence signals of both transgenic mice were preserved after HCHS. In addition, large-scale 3D imaging of brains, immune-stained by the HCHS method using a mild detergent-based solution, allowed for the global topological analysis of several neuronal markers such as c-Fos, neuronal nuclear protein (NeuN), Microtubule-associated protein 2 (Map2), Tuj1, glial fibrillary acidic protein (GFAP), and tyrosine hydroxylase (TH) in various anatomical regions in the whole mouse brain tissues. Finally, through comparisons with various existing tissue clearing methodologies such as CUBIC, Visikol, and 3DISCO, it was confirmed that the HCHS methodology results in relatively less tissue deformation and higher fluorescence retention. Conclusion:: In conclusion, the development of 3D imaging based on novel tissue-clearing techniques (HCHS) will enable detailed spatial analysis of neural and vascular networks present within the brain.

K-means algorithm is one of the well-known unsupervised machine learning algorithms. The algorithm typically finds out distinct non-overlapping clusters in which each point is assigned to a group. The minimum squared distance technique distributes each point to the nearest clusters or subgroups. One of the K-means algorithm’s main concerns is to find out the initial optimal centroidsof clusters. It is the most challenging taskto determine the optimum position of the initial clusters’ centroids at the very first iteration. This paper proposes an approach to find the optimal initial centroids efficiently to reduce the number of iterations and execution time. To analyze the effectiveness of our proposed method, we have utilized different real-world datasets to conduct experiments. We have first analyzed COVID-19 and patient datasets to show our proposed method’s efficiency. A synthetic dataset of 10M instances with 8 dimensions is also used to estimate the performance of the proposed algorithm. Experimental results show that our proposed method outperforms traditional kmeans++ and random centroids initialization methods regarding the computation time and the number of iterations.

The current review of tea and its parts is focused on the antibacterial properties, considering the possible applications and modes of action against bacterial illnesses. It shows the backdrop of antibiotic resistance and the huge demand for antibacterial treatments out there. From the interactions with bacterial components, the theory presented that tea polyphenols are antibacterial and therefore would be a substitute or supplementary therapy to the usual antibiotics. The study highlighted the role of tea polyphenols as potential antibacterial compounds that may interact with various bacterial components and different polyphenolic compounds occurring in tea. Future research directions may be directed toward testing more plant-based sources for antibacterial properties, in vivovalidation of the studies, and possible synergistic effects with classical antibiotics. By addressing the controversies and disagreements involved, the present understanding of the topic of tea’s antibacterial properties and enable the entry of new ways for fighting microorganisms resistant to antibiotics. In conclusion, this review adds to the growing body of evidence regarding the antimicrobial properties of tea and emphasizes the need for further studies that will allow the full exploitation of its therapeutic potential for countering the rising problem of antibiotic resistance in healthcare.

Background: The response of superheated emulsion detector with different halocarbons as active liquid to poly-energetic and mono-energetic neutrons has been carried out by different workers. The C2H2F4detectors have not been explored much. This liquid has shown the potentiality of sensitivity to low-mass dark matter. The previous calibration of this liquid was carried out with the poly-energetic neutrons. Purpose: In the present work, to better characterize the detector with neutrons, it is irradiated with quasi-mono-energetic neutrons and the results are compared with neutrons from 241Am-Be. To run the detector for the dark matter search, it is required to calibrate it with neutrons, preferably with mono-energetic neutrons. But mono-energetic neutron is not available at all establishments; hence, it was calibrated with quasi-mono-energetic neutrons. Method: The response of superheated emulsion consisting of the droplets of C2H2F4has been studied using the quasi-mono-energetic neutrons. The superheated droplets have been fabricated in a visco-elastic gel matrix. The shock waves generated by the passage of the energetic particles are detected by the acoustic sensors coupled to the emulsion. The measurement has also been carried out for the blank target and beam-off conditions. Results and conclusion: It is observed that the (Pvar) response of the emulsion in the low-frequency range is sharper for the quasi-mono-energetic neutrons from 7Li (p, n) reaction and wider for the poly-energetic neutrons from 241Am-Be. The fundamental frequency associated with bubble nucleation (FF values) is similar for the neutrons from 7Li-target and 241Am-Be source. The precise characterization of such detector is required for the application in neutron measurement as well as for the dark matter search experiment apart from the basic understanding of the radiation-induced bubble nucleation.

In this study, we investigate a set of organic diradical structures in which two oxo-verdazyl radicals are selected as radical spin centers that are connected (coupled) via six coupler molecules (CM), resulting in various magnetic (ferromagnetic (FM) or antiferromagnetic (AFM)) characteristics, as reflected by their exchange coupling constants (J). We have designed 12 diradicals with 6-antiaromatic couplers coupled with bis-oxo-verdazyl diradicals with meta–meta (m–m) and para–meta (p–m) positional connectivities. The nature of the magnetic coupling (ferromagnetic, nonmagnetic, or antiferromagnetic) and the magnitude of the exchange constant Jdepend on the type of coupler, the connecting point between each radical center and CM, the degree of aromaticity of the coupler, and the length of the through-bond distance between radical centers. The computed magnetic exchange coupling constants Jfor these diradicals at the B3LYP/6-311++G(d,p) and MN12SX/6-311++G(d,p) levels of theory are large for many of these structures, indicating strong ferromagnetic coupling (with positive Jvalues). In some cases, magnetic couplings are observed with J> 1000 cm–1(B3LYP/6-311++G(d,p)) and strong antiferromagnetic coupling (with negative Jvalues) with J< −1000 cm–1(B3LYP/6-311++G(d,p)). Similarly, in some cases, magnetic couplings are observed with J> 289 cm–1(MN12SX/6-311++G(d,p)) and strong antiferromagnetic coupling (with negative Jvalues) with J< −568 cm–1(MN12SX/6-311++G(d,p)). Furthermore, while numerous studies have reported that the degree of aromaticity of molecular couplers often favors strong ferromagnetic coupling, displaying the high-spin character of diradicals in their ground states, the couplers chosen in this study are characterized as antiaromatic or nonaromatic. The current investigation provides evidence that, remarkably, antiaromatic couplers are able to enhance stability by favoring electronic diradical structures with very strong ferromagnetic coupling when the length of the through-bond distance and connectivity pattern between radical centers are selected in such a way that the FM coupling is optimized. The findings in this study offer new strategies in the design of novel organic materials with interesting magnetic properties for practical applications.

Melatonin (MT), discovered as N‑acetyl-5-methoxytryptamine in 1958, exhibits significant potential as a regulator of plant growth, development and responses to environmental stressors. Its diverse levels across organs and species make it an intriguing subject for functional studies. This review explores the potential of MT, whether administered endogenously or exogenously, in mitigating various environmental stressors such as cold, metal toxicity, drought, salinity, chilling injuries, temperature fluctuations etc. A pivotal aspect of MT action involves its direct inhibition of reactive oxygen species (ROS) and reactive nitrogen species (RNS), pivotal players in oxidative stress. Mechanisms like enhanced antioxidant enzyme activity, bolstered non-enzymatic antioxidant systems, and activation of enzymes repairing oxidized proteins contribute to MT’s ability to confer resistance against abiotic stresses. Furthermore, by inducing the expression of genes related to antioxidant enzymes during stress, MT acts as a key regulator in orchestrating plant defense responses against environmental challenges. These collective actions underscore the role of MT in enhancing plant resilience to such challenges. The interaction of MT with various phytohormones in drought stress regulation prompts exploration of similar mechanisms to address diverse stressors in horticultural crops. MT’s collaborative synergy with fungicides presents a promising strategy for reducing reliance on harmful chemicals in fruit crop cultivation, thereby minimizing the environmental impact and enhancing crop management practices. However, this review also underscores the need for further research to explore how MT protects fruit crops from environmental challenges, potentially leading to environmentally friendly agricultural practices and safer food production.

Virgin coconut oil (VCO) is renowned for its numerous health benefits and widespread culinary applications. Fermentation is one of the simplest cold press methods used for the production of VCO. However, the longer fermentation time affects the scale ability and VCO quality. To enhance its production process and improve overall product quality, this study investigates the impact of using aerobic fermented skimmed coconut milk starter (SCMS) at different concentrations of the culture (5–15%) to maximize the yield and quality and minimize the cost, time, and energy during the production of virgin coconut oil (VCO) in fermentation process. It was observed that 24-h-old SCMS at 10% concentration recorded a maximum yield (19.2%) in the 19-h fermentation process. Individual and interactive effects of culture type (24-h and 48-h fermented SCMS) and its concentration significantly affect yield; however, its effects on physical (moisture content, viscosity, specific gravity, and refractive index) and chemical profile (free fatty acid, peroxide value, acid value, saponification value, iodine value, and total phenolic content) of the resultant VCO remain insignificant. The physicochemical properties of VCO prepared to utilize the SCMS-induced fermentation method confirmed the standards stipulated by the Food Safety and Standards Authority of India (FSSAI) and Asian and Pacific Coconut Community (APCC). SCMS is the cheapest alternative that could be exploited to enhance the fermentation rate during the production of VCO.

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The understanding of interactions between organic chromophores and biocompatible luminescent noble metal nanoclusters (NCs) leading to an energy transfer process that has applications in light-harvesting materials is still in its nascent stage. This work describes a photoluminescent supramolecular assembly, made in two stages, employing an energy transfer process between silver (Ag) NCs as the donor and a host–guest system as the acceptor that can find potential applications in diverse fields. Initially, we explored the host–guest chemistry between a cationic guest ethidium bromide and cucurbit[8]uril host to modulate the fluorescence property of the acceptor. The host–guest interactions were characterized by using UV–vis absorption, steady-state and time-resolved spectroscopy, molecular docking, proton 1H nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and isothermal calorimetry studies. Next, we prepared a series of blue-emitting AgNCs using different templates such as proteins and peptides. We have found that these AgNCs can be employed as a donor in the energy transfer process upon mixing with the above acceptor for emission color tuning. Our in-depth studies also revealed that surface ligands could play a key role in modulating the energy transfer efficiency. Overall, by employing a noncovalent strategy, we have tried to develop Förster resonance energy transfer (FRET) pairs using blue-emitting NCs and a host–guest complex that could find potential applications in constructing advanced sustainable light-harvesting, white light-emitting, and anti-counterfeiting materials.

Organic cocrystals based on H-bonding as well as π-stacking interactions between 4,4′-bipyridine–pyromellitic acid (1) and 4,4′-bipyridine–phthalic acid (2) are reported. Cocrystals 1and 2were fully characterized by single-crystal X-ray diffraction and NMR and IR spectroscopy. The single-crystal X-ray diffraction shows the H stacking pattern of the adjacent 4,4′-bipyridine molecules in the construction of a 3D chain structure for cocrystal 1. Cocrystal 2, however, formed a zigzag 3D chain where the adjacent 4,4′-bipyridyl molecules are involved in a J-stacking mode. Experimental conductivity measurements of the cocrystals 1and 2with a Keithley 4200 SCS parameter analyzer showed the temperature-dependent semiconducting behavior in the case of cocrystal 1, whereas cocrystal 2remained as an insulator. The favorable H-stacking interaction of 4,4′-bipyridine molecules which is the prime origin of semiconductivity in cocrystal 1may become out of phase due to the free rotation along the C–C bond of 4,4′-bipyridine with an increase in temperature. Although the semiconducting behavior of a material increases with increasing temperature and decreases in resistivity, in the case of cocrystal 1due to the probable phase transition of the 4,4′-bipyridyl molecules the material became an insulator with an increase in temperature from 20 °C to higher temperature, whereas the semiconducting behavior was restored after cooling the crystals to 20 °C again. The theoretical study conducted with the optimized structures of 1and 2showed the higher electron hopping rate in the case of cocrystal 1as compared to 2which can account for the charge conduction in the case of 1.

This paper aims to establish the notion of Hamming distance under the possible environment and propose a multi-attribute decision-making (MADM) strategy based on grey relational analysis (GRA) under the Possibility environment. This study identified the most critical parameter or factors affected by climate change, urbanization, and machine failures. Furthermore, we validate the proposed MADM strategy by solving a real-world numerical example, namely, “identification of the most important parameters affecting climate change and the impact of urbanization on hydropower plants.”

Mangrove forests are natural protectors of several tropical deltas but are severely degraded, and their restoration often fails due to the lack of a holistic approach. Here, we share lessons from the recent Indian Sundarban delta mangrove plantation program and discuss potential solutions to remove barriers for successful mangrove restoration.

Purpose: Hemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors. Methods: This study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared. Results: Each of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0–21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment. Conclusion: These first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

Background: To investigate the clinical treatment status, such as treatment regimen, bleeding events, and drug dose, in patients with hemophilia B in South Korea. Methods: In this retrospective chart review, data of patients with hemophilia B from eight university hospitals were collected. Demographic and clinical data, treatment data, such as regimen and number of injections, dose of factor IX concentrate, and bleeding data were reviewed. Descriptive analyses were performed with annual data for 2019, 2020, and 2021, as well as the three years consecutively. Results: The medical records of 150 patients with hemophilia B between January 1, 2019, and December 31, 2021, were collected. Among these, 72 (48.0%) were severe, 47 (31.3%) were moderate, and 28 (18.7%) were mild. The results showed approximately two times more patients receiving prophylaxis as those receiving on-demand therapy, with 66.1% of patients receiving prophylaxis in 2019, 64.9% in 2020, and 72.1% in 2021. Annualized bleeding rates were 2.2% (± 3.1) in 2019, 1.8% (± 3.0) in 2020, and 1.8% (± 2.9) in 2021 among patients receiving prophylaxis. For the doses of factor IX concentrate, patients receiving prophylaxis received an average of 41.6 (± 11.9) IU/Kg/Injection in 2019, 45.7 (± 12.9) IU/Kg/Injection in 2020, and 60.1 (± 24.0) IU/Kg/Injection in 2021. Conclusions: Clinically, prophylaxis is more prevalent than reported. Based on insights gained from current clinical evidence, it is expected that the unmet medical needs of patients can be identified, and physicians can evaluate the status of patients and actively manage hemophilia B using more effective treatment strategies.

The flavin adenine dinucleotide (FAD) is an indispensable coenzyme in live cells. It acts as a catalyst in many redox responsive metabolic reactions, including oxidative phosphorylation in mitochondria. The real-time monitoring of flavin is important to understand the disorder in the metabolic process, redox system, etc. Thus, we have developed a fluorescent probe CPy-1that noncovalently binds with flavin to exhibit the FRET process. 1H- NMR and docking study indicated that there is a strong hydrophobic interaction between flavins and CPy-1. Also, a π–π stacking between isoalloxazine ring in flavin and quinoline and coumarin moieties of CPy-1favors self-assembly. The nontoxic probe CPy-1could distinguish cancer cells from normal cells based on expressions of endogenous FAD.

SARS-CoV-2 or COVID-19 was introduced into India by multiple sources generating local clusters and leading to the nationwide spread. A retrospective study has been conducted on the epidemiological features and spatial spread of COVID-19 in India during February 2020–March 2021. For each district, the cumulative number of confirmed COVID-19 cases were fitted to exponential growth model for the initial phase of the outbreak (the first 7–15 days). From the estimated growth rate, epidemiological parameters like the Basic reproduction number (R0) and epidemic doubling time (τ) were determined. Using Q-GIS software, we have generated the all India distribution maps for R0and τ. COVID-19 spread rapidly covering majority of the districts of India between March and June 2020. As on 1st March 2021, a total of 715 out of 717 districts have been affected. The R0range is at par with the global average. A few districts, where outbreaks were caused by migrant workers coming home, intense transmission was recorded R0> 7. We also found that the spread of COVID-19 was not uniform across the different districts of India. The methodology developed in the study can be used by researchers and public health professionals to analyze and study epidemics in future.

AbstractChandipura virus (CHPV) is an emerging pathogen responsible for acute encephalitic syndrome (AES) in pediatric population in India. Several outbreaks of CHPV have been reported from different states of India since the year 2003. At present there is no vaccine or therapeutic measures available to curtail the disease. In this study, we have identified both T-cell and B-cell epitopes of different antigenic proteins of CHPV like Nucleoprotein (N), Phosphoprotein (P) and Matrix protein (M) along with the immuno-dominant glycoprotein (G) and conducted in silicocharacterization for the same. The idea is to design a multi-epitope peptide construct using the epitopes, which were found to be non-toxic, non-allergenic and possessing high immunogenicity. The final multi-epitope construct named as: MEC-CHPV, comprised of β-defensin adjuvant at N-terminal for enhancement of immunogenicity followed by fourteen B-cell epitopes, four Helper T-cell epitopes and six Cytotoxic T-cell epitopes. The characterization of designed construct was carried out in terms of physicochemical parameters, antigenicity and allergenicity. The 3D structure prediction was performed. Molecular docking and molecular-dynamics simulation of MEC-CHPV with Toll like receptors (TLR-3 and TLR-8) showed stable interactions. In silicocloning of MEC-CHPV in pET30a(+) expression vector was also conducted using codon optimization. The in silicoimmune-simulation indicated a typical immune response against MEC-CHPV when used as a potential vaccine. This study provides a cost-effective and time-saving way to design a peptide vaccine candidate against CHPV using immuno-informatics approach. Development of the MEC-CHPV construct may pave the way for future laboratory experiments.Communicated by Ramaswamy H. Sarma

Elastase, a serine protease, plays important roles in our body in food digestion and defence against pathogens. Particularly, the elastase present in neutrophils is directly associated with inflammatory bowel disease (IBD). Through a rational approach, we have developed a fluorescent elastase probe that has multiple advantages for biological applications including two-photon ratiometric imaging capability. Using the probe, which is capable of detecting intracellular elastase activity associated with inflammation, we have investigated elastase level changes in various mouse organs under an IBD condition for the first time. The results reveal notably higher elastase levels in the liver and duodenum of the healthy mice than in the other investigated organs. Under the IBD condition, we observed significant elastase level changes in the liver, duodenum, colon, and lung. The downregulation of elastase in the liver under the IBD condition suggests migration of neutrophils into the upregulated organs. The notable upregulation of elastase in the duodenum is explained by self-production of elastase, in addition to the neutrophil migration from the liver. We have observed little elastase level changes in selected organs of immune-deficient mice raised under the normal and IBD conditions, which supports the neutrophil migration as the reason for perturbed elastase activity in the healthy mice. The results also suggest an important role of the liver in maintaining the immune response associated with the inflammation-induced elastase level changes. The probe offers an ideal tool for mapping neutrophil migration in body. Further understanding of the elastase-associated biology and diagnosis of IBD by monitoring affected organs are anticipated using the probe.

In this paper, we propose a Variable Neighborhood Search (VNS) algorithm based on Multi-AttributeDecision-Making (MADM) strategy under possibility environment. Further, we provide a numerical example to show the applicability and rationality of the proposed MADM strategy.