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Kinetics of pIgR and IgM immune responses in snakehead (Channa argus) to inactivated Aeromonas hydrophila via immersion and intraperitoneal injection
Realization of a three-dimensional photonic higher-order topological insulator
Correction: Depression in the COVID-19 endemic era: Analysis of online self-disclosures by young South Koreans
Kinetic and isotherm studies of cr (VI) adsorption from aqueous media by using a synthetic chitosan-allophane nanocomposite
Mechanistic insights into dengue virus inhibition by a clinical trial compound NITD-688
Dengue, caused by the dengue virus (DENV), presents a significant public health challenge with limited effective treatments. NITD-688 is a potent panserotype DENV inhibitor currently in Phase II clinical trials. However, its mechanism of action is not fully understood. Here, we present the molecular details of how NITD-688 inhibits DENV. NITD-688 binds directly to the nonstructural protein 4B (NS4B) with nanomolar affinities across all four DENV serotypes and specifically disrupts the interaction between NS4B and nonstructural protein 3 (NS3) without significantly changing the interactions between NS4B and other viral or host proteins. NS4B mutations that confer resistance to NITD-688 reduce both NITD-688 binding to NS4B and disruption of the NS4B/NS3 interaction. Specifically, NITD-688 blocks the interaction of NS3 with a cytosolic loop within NS4B. This inhibits the formation of new NS4B/NS3 complexes and disrupts preexisting complexes in vitro and DENV-infected cells, ultimately inhibiting viral replication. Consistent with this mechanism, NITD-688 retains greater potency in cellular assays with delayed treatment compared to JNJ-1802, another NS4B inhibitor that has been studied in Phase II clinical trials. Together, these findings provide critical insights into the mechanism of action of NITD-688, facilitating the development of novel flavivirus NS4B inhibitors and informing future clinical interventions against DENV.
Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus
Extraction of total flavonoids from Chaenomeles speciosa (Sweet) Nakai and its antioxidant and lipoxygenase inhibition effects
Ultrasound-assisted extraction technology was utilized to extract total flavonoids from Chaenomeles speciosa (Sweet) Nakai, and response surface methodology was employed to optimize the extraction process. The anti-oxidant and lipoxygenase inhibitory activities were evaluated, along with an analysis of the type of inhibition. The results revealed that the optimal extraction conditions for total flavonoids from Chaenomeles speciosa (Sweet) Nakai were as follows: an ethanol concentration of 62%, a liquid-to-solid ratio of 15:1 mL/g, an ultrasonic temperature of 68°C, and an ultrasonic time of 40 min, resulting in a total flavonoid extraction rate of 10.18%. Antioxidant assays demonstrated that the Chaenomeles speciosa (Sweet) Nakai extract exhibited significant radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl radicals, 2,2’-azinobis (3-ethylbenzothiazoline-6-sulfonic acid ammonium salt) radicals, and hydroxyl radicals, with IC50 values of 582 µg/mL, 538 µg/mL, and 1709 µg/mL, respectively. Furthermore, enzyme inhibition assays indicated that the Chaenomeles speciosa (Sweet) Nakai extract possesses notable inhibitory activity against lipoxygenase, with an IC50 value of 2658 µg/mL. This inhibition is mediated through a mixed reversible inhibition mechanism.
USP4 promotes proliferation and metastasis in human lung adenocarcinoma
Discovery and functional characterization of a bombesin-type neuropeptide signaling system in an invertebrate
Neuropeptide signaling systems are key regulators of physiological and behavioral processes in animals. However, the evolutionary history of some neuropeptides originally discovered in vertebrates is unknown. The peptide bombesin (BN) was first isolated from the skin of the toad Bombina bombina and subsequently BN-related neuropeptides have been identified in other chordates, including gastrin-releasing peptide (GRP) and neuromedin B (NMB) in mammals, and a GRP-like peptide in the cephalochordate Branchiostoma japonicum . However, BN-type neuropeptides have hitherto not been identified in any nonchordate animals. Here, we report the discovery and functional characterization of a BN-type neuropeptide signaling system in an echinoderm—the starfish Asterias rubens . BN-type precursor proteins were identified in several echinoderm species based on their amino acid sequences and gene structures, and the mature structure of the A. rubens BN-type neuropeptide ArBN was determined using mass spectrometry. A protein related to vertebrate GRP/NMB-type G protein–coupled receptors was identified experimentally as the receptor for ArBN in A. rubens . Analysis of the distribution of the ArBN precursor in A. rubens using mRNA in situ hybridization and immunohistochemistry revealed a widespread pattern of expression in the central nervous system, digestive system, and locomotory organs. Moreover, effects of ArBN in A. rubens included contraction and retraction of the evertible stomach and inhibition of feeding behavior. Our findings show that the evolutionary history of BN-type neuropeptide signaling can be traced back to the deuterostome common ancestor of echinoderms and chordates. Furthermore, an ancient role of BN-type neuropeptides as regulators of feeding behavior has been revealed.
A toxin-antitoxin system provides phage defense via DNA damage and repair
Explainable classification of goat vocalizations using convolutional neural networks
Efficient precision livestock farming relies on having timely access to data and information that accurately describes both the animals and their surrounding environment. This paper advances classification of goat vocalizations leveraging a publicly available dataset recorded at diverse farms breeding different species. We developed a Convolutional Neural Network (CNN) architecture tailored for classifying goat vocalizations, yielding an average classification rate of 95.8% in discriminating various goat emotional states. To this end, we suitably augmented the existing dataset using pitch shifting and time stretching techniques boosting the robustness of the trained model. After thoroughly demonstrating the superiority of the designed architecture over the contrasting approaches, we provide insights into the underlying mechanisms governing the proposed CNN by carrying out an extensive interpretation study. More specifically, we conducted an explainability analysis to identify the time-frequency content within goat vocalisations that significantly impacts the classification process. Such an XAI-driven validation not only provides transparency in the decision-making process of the CNN model but also sheds light on the acoustic features crucial for distinguishing the considered classes. Last but not least, the proposed solution encompasses an interactive scheme able to provide valuable information to animal scientists regarding the analysis performed by the model highlighting the distinctive components of the considered goat vocalizations. Our findings underline the effectiveness of data augmentation techniques in bolstering classification accuracy and highlight the significance of leveraging XAI methodologies for validating and interpreting complex machine learning models applied to animal vocalizations.
Source-specific fine particulates emission linked to prevalence of ophthalmic cases in India
Second coordination sphere regulates nanozyme inhibition to assist early drug discovery
Clinical breast cancer screening uptake and associated factors among reproductive age women in Kenya: further analysis of Kenyan Demographic and Health Survey 2022
Introduction Breast cancer is a global public health problem among reproductive-age women, with an estimated 670,000 deaths in 2022. It’s also a pressing health challenge in Sub-Saharan African countries, driven by late-stage diagnoses and limited healthcare access, underscoring the urgent need for early screening and treatment initiatives to combat this growing epidemic. In Kenya, the burden was also significant, and multilevel factors such as individual, household, and community level factors that influence screening uptake are undermined. Furthermore, there were no nationally representative studies. Therefore, this study aimed to assess clinical breast cancer screening uptake (CBCSU) and associated factors among reproductive-age women: further analysis of Kenyan demographic and health survey (KDHS) 2022. Methods This study used a weighted nationally representative sample of 16,649 women from the 2022 KDHS. A Multilevel mixed effects binary logistic regression analysis was performed and in the multivariable analysis, variables with a p-value less than 0.05 were considered statistically significant. The strength of the association was evaluated using Adjusted Odds Ratios (AOR) along with their corresponding 95% confidence intervals (CI). STATA version 17 software was to for data management and statistical analysis. Results The weighted prevalence of CBCSU in Kenya was 13.91% (95% CI: 13.33, 14.44). Besides, women aged 25 to 34 years (AOR = 1.86, 95% CI: 1.57, 2.21), and 35 to 49 years (AOR = 2.87, 95% CI: 2.40, 3.42) had higher odds of CBCSU. Women with primary education (AOR = 2.14, 95% CI: 1.56, 2.94) and those with secondary or higher education (AOR = 3.09, 95% CI: 2.23, 4.28) had higher odds of CBCSU. In addition, the odds of CBCSU were higher among women with a middle (AOR = 1.41, 95% CI: 1.19, 1.67) and a rich wealth index (AOR = 2.19, 95% CI: 1.84, 2.61). On the other hand, CBCSU was lower among non-contraceptive user women (AOR 0.78, 95% CI: 0.69, 0.87). Furthermore, women in communities with a high proportion of media exposure had higher CBCSU (AOR = 1.17, 95% CI: 1.04, 1.33). Conclusion In this study, the prevalence of CBCSU among reproductive-age women in Kenya was found to be low. Besides, factors such as age, educational status, wealth index, family planning utilization, and community media exposure were identified as significant contributors to screening uptake. Therefore, policymakers and stakeholders should design interventions that address factors contributing to low breast cancer screening uptake, particularly targeting women in areas with limited media exposure, to increase the uptake of clinical breast cancer screening.
Lipoic acid-plumbagin conjugate protects pancreatic beta cells against high glucose-induced toxicity
Structural basis for allosteric modulation of M. tuberculosis proteasome core particle
Abstract The Mycobacterium tuberculosis (Mtb) proteasome system selectively degrades damaged or misfolded proteins and is crucial for the pathogen’s survival within the host. Targeting the 20S core particle (CP) offers a viable strategy for developing tuberculosis treatments. The activity of Mtb 20S CP, like that of its eukaryotic counterpart, is allosterically regulated, yet the specific conformations involved have not been captured in high-resolution structures to date. Here, we use single-particle electron cryomicroscopy and H/D exchange mass spectrometry to determine the Mtb 20S CP structure in an auto-inhibited state that is distinguished from the canonical resting state by the conformation of switch helices at the α/β interface. The rearrangement of these helices collapses the S1 pocket, effectively inhibiting substrate binding. Biochemical experiments show that the Mtb 20S CP activity can be altered through allosteric sites far from the active site. Our findings underscore the potential of targeting allostery to develop antituberculosis therapeutics.
Retraction: Specific inhibition of tumor cells by oncogenic EGFR specific silencing by RNA interference
A population based study to analyse amyotrophic lateral sclerosis as a multi-step process
Dopaminergic neurons in the paraventricular hypothalamus extend the food consumption phase
Feeding behavior is controlled by various neural networks in the brain that are involved in different feeding phases: Food procurement, consumption, and termination. However, the specific neural circuits controlling the food consumption phase remain poorly understood. Here, we investigated the roles of dopaminergic neurons in the paraventricular nucleus of the hypothalamus (PVH) in the feeding behavior in mice. Our results indicated that the PVH dopaminergic neurons were critical for extending the food consumption phase and involved in the development of obesity through epigenetic mechanisms. These neurons synchronized with proopiomelanocortin neurons during consumption, were stimulated by proopiomelanocortin activation, and projected to the lateral habenula (LHb), where dopamine receptor D2 was involved in the increase in food consumption. In addition, upregulated tyrosine hydroxylase (TH) expression in PVH was associated with obesity and indispensable for obesity induction in mice lacking Dnmt3a . Taken together, our results highlight the roles of PVH dopaminergic neurons in promoting food consumption and obesity induction.