Drug repurposing of pyrazolotriazine derivatives as potential anti-SARS-CoV-2 agents: in vitro and in silico studies.

The search for new molecules targeting SARS-CoV-2 has been a priority since 2020. The continuous evolution of new mutants increases the need for more research in the area. One way to find new leads is to repurpose existing drugs and molecules against the required target. Here, we present the in vitro and in silico screening of ten previously synthesized and reported compounds as anti-COVID 19 agents. The compounds were screened in vitro against VERO-E6 cells to find their Cytotoxic Concentration (CC50) and their Inhibitory Concentration (IC50). Compounds 1, 2, and 5 revealed a promising anti-SARS-CoV-2 of (IC50 = 2.4, 11.2 and 2.8 µM), respectively while compounds 3 and 7 showed moderate activity of (IC50 = 17.8 and 26.1 µM) compared to Chloroquine which showed an IC50 of 24.9 µM. Among tested compounds, 1 showed the highest selectivity (CC50/IC50) of 192.8. Docking, molecular dynamics and ADME studies were done to investigate potential interactions between compounds and SARS-CoV-2 targets as well as to study the possibility of using them as lead compounds.

Comprehensive risk assessment of Pakistan railway network: A semi-quantitative risk matrix approach.

Pakistan Railway (PR) is vital to the country's transportation infrastructure, facilitating passenger and freight transportation. However, the growing number of accidents associated with PR has raised concerns about its overall safety. In addition, there have been limited research efforts to investigate PR accidents and their underlying causes The present study conducts a comprehensive risk assessment and safety management of PR using a semi-quantitative risk matrix approach. The study combines historical accident data and expert evaluations to assess the likelihood and consequences of different railway accident types and potential contributing factors. The descriptive statistics analysis has revealed varying degrees of severity for different types of railway accidents in Pakistan. For instance, accidents like passenger and goods train derailments and collisions at unmanned level crossings were identified as extreme and intolerable, whereas train fire accidents were categorized as high and undesirable. Moreover, accidents attributed to human error are classified as extreme and intolerable, while those caused by negligence of road users and track defects are classified as high and undesirable. The study utilized the risk matrix approach and identified critical risk areas that can help the decision-makers prioritize effective risk mitigation strategies. In light of the present study's findings, policy implications, such as investment in infrastructure to mitigate risks associated with aging or deteriorating tracks, bridges, and tunnels, and human resource development for railway personnel to improve their skills, decision-making abilities, and awareness of safety protocols, are recommended.

[Nutritional status and nutritional support of patients with chronic disorders of consciousness at the stage of medical rehabilitation].

Chronic disturbances of consciousness (CDC) are a consequence of severe brain damage and are conditions that arise after emerging from a coma with the preservation of the sleep-wake cycle in the absence of signs of conscious behavior. When conducting inpatient medical rehabilitation of this group of patients, the state of nutritional status is not always taken into account and, as a rule, there is no nutritional support with an assessment of metabolic needs, including the introduction of various modes of physical activity during physical therapy and an increase in physical load on the patient's body. The purpose of the study was to assess the nutritional status and optimize the nutritional support system in patients with CDC at the inpatient stage of medical rehabilitation (MR). Material and methods. The study analyzed the results of examination and treatment of 152 patients with CDC of traumatic origin who received medical rehabilitation from 2016 to 2022 in the Department of Physical and Rehabilitation Medicine of the Nikiforov Russian Center of Emergency and Radiation Medicine, Ministry of Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters. Results. In patients with CDC of traumatic genesis, signs of malnutrition (objective, anthropometric, laboratory) were diagnosed at the inpatient stage of MR, and there were also risks of malnutrition progression with the introduction of additional physical activity. Conclusion. To create an effective and adequate nutritional support system during inpatient MR, metabolic monitoring (indirect calorimetry) is of fundamental importance, taking into account the influence of additional physical activity. The use of a calculation method for estimating energy requirements can lead to hyperalimentation.

Anti-tumor withanolides as signal transducers and activators of transcription 3 (STAT3)-inhibition from Withania obtusifolia.

The Solanaceae family and the Withania genus specifically are rich sources of medicinal plants. Liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS/MS) revealed a predominance of withanolides from an organic extract of Withania obtusifolia. A constructed molecular network uncovered the presence of potentially novel withanolides. A series of withanolides were then isolated and structurally characterized from the extract including two new withanolides (withafolia A and withafolia B) and seven previously reported metabolites. Of the isolated compounds, cytotoxicity of withanolide J, physaperuvin G, and a commercial STAT3 inhibitor (S3I-201) were assessed against a human leukemia HL-60 cell line resulting in IC50 values of 26, 29, and 120 µM, respectively. In silico molecular docking simulations indicate that withanolide J and physaperuvin G can bind as an inhibitor in the active site of STAT3 with docking scores comparable to the selective STAT3 inhibitor, S3I-201.

Effect of amisulpride on the expression of serotonin receptors, neurotrophic factor BDNF and its receptors in mice with overexpression of the aggregation-prone [R406W] mutant tau protein.

Serotonin 5-HT7 receptors (5-HT7R) are attracting increasing attention as important participants in the mechanisms of Alzheimer's disease and as a possible target for the treatment of various tau pathologies. In this study, we investigated the effects of amisulpride (5-HT7R inverse agonist) in C57BL/6J mice with experimentally induced expression of the gene encoding the aggregation-prone human Tau[R406W] protein in the prefrontal cortex. In these animals we examined short-term memory and the expression of genes involved in the development of tauopathy (Htr7 and Cdk5), as well as biomarkers of neurodegenerative processes - the Bdnf gene and its receptors TrkB (the Ntrk2 gene) and p75NTR (the Ngfr gene). In a short-term memory test, there was no difference in the discrimination index between mice treated with AAV-Tau[R406W] and mice treated with AAV-EGFP. Amisulpride did not affect this parameter. Administration of AAV-Tau[R406W] resulted in increased expression of the Htr7, Htr1a, and Cdk5 genes in the prefrontal cortex compared to AAV-EGFP animals. At the same time, amisulpride at the dose of 10 mg/kg in animals from the AAV-Tau[R406W] group caused a decrease in the Htr7, Htr1a genes mRNA levels compared to animals from the AAV-Tau[R406W] group treated with saline. A decrease in the expression of the Bdnf and Ntrk2 genes in the prefrontal cortex was revealed after administration of AAV-Tau[R406W]. Moreover, amisulpride at various doses (3 and 10 mg/kg) caused the same decrease in the transcription of these genes in mice without tauopathy. It is also interesting that in mice of the AAV-EGFP group, administration of amisulpride at the dose of 10 mg/kg increased the Ngfr gene mRNA level. The data obtained allow us to propose the use of amisulpride in restoring normal tau protein function. However, it should be noted that prolonged administration may result in adverse effects such as an increase in Ngfr expression and a decrease in Bdnf and Ntrk2 expression, which is probably indicative of an increase in neurodegenerative processes.

History, status and genetic characteristics of native cattle breeds from the Republic of Kazakhstan.

This work provides a comprehensive review of the history, status, and genetic characteristics of cattle breeds in Kazakhstan. The current breeding status is analysed, including information on popular breeds such as Kazakh white-headed, Auliekol, Alatau, Aulieata, and Kalmyk, their production and economic significance. An overview of genetic studies using DNA fingerprinting, microsatellites, and SNPs aimed at identifying unique characteristics, genetic diversity, and genes under selection, as well as markers of economically important and productive traits of Kazakh cattle breeds, is also provided. The study examined the genetic structure of the Kazakh white-headed and Alatau breeds based on whole-genome SNP genotyping. Unique genetic components characterizing Kazakhstan cattle breeds were described, and comparisons were made with genetic data from other breeds. Structural analysis showed that the Kazakh white-headed breed contains genetic components of the Hereford, Kalmyk, and Altai cattle. The Alatau breed has a composite structure, containing components of the Brown Swiss, Braunvieh, Kalmyk, and Holstein breeds. The results not only reveal the genetic diversity and characteristics of cattle breeds in Kazakhstan and the historical development and current state of animal husbandry in the country, but also emphasize the importance of further research to identify adaptive and unique genetic markers affecting economically important traits of local breeds.

Natural products and long noncoding RNA signatures in gallbladder cancer: a review focuses on pathogenesis, diagnosis, and drug resistance.

Gallbladder cancer (GBC) is an aggressive and lethal malignancy with a poor prognosis. Long noncoding RNAs (lncRNAs) and natural products have emerged as key orchestrators of cancer pathogenesis through widespread dysregulation across GBC transcriptomes. Functional studies have revealed that lncRNAs interact with oncoproteins and tumor suppressors to control proliferation, invasion, metastasis, angiogenesis, stemness, and drug resistance. Curcumin, baicalein, oleanolic acid, shikonin, oxymatrine, arctigenin, liensinine, fangchinoline, and dioscin are a few examples of natural compounds that have demonstrated promising anticancer activities against GBC through the regulation of important signaling pathways. The lncRNAs, i.e., SNHG6, Linc00261, GALM, OIP5-AS1, FOXD2-AS1, MINCR, DGCR5, MEG3, GATA6-AS, TUG1, and DILC, are key players in regulating the aforementioned processes. For example, the lncRNAs FOXD2-AS1, DILC, and HOTAIR activate oncogenes such as DNMT1, Wnt/ß-catenin, BMI1, and c-Myc, whereas MEG3 and GATA6-AS suppress the tumor proteins NF-κB, EZH2, and miR-421. Clinically, specific lncRNAs can serve as diagnostic or prognostic biomarkers based on overexpression correlating with advanced TNM stage, metastasis, chemoresistance, and poor survival. Therapeutically, targeting aberrant lncRNAs with siRNA or antisense oligos disrupts their oncogenic signaling and inhibits GBC progression. Overall, dysfunctional lncRNA regulatory circuits offer multiple avenues for precision medicine approaches to improve early GBC detection and overcome this deadly cancer. They have the potential to serve as novel biomarkers as they are detectable in bodily fluids and tissues. These findings enhance gallbladder treatments, mitigating resistance to chemo- and radiotherapy.

Disentangling the veil line for Brazilian biodiversity: An overview from two long-term research programs reveals huge gaps in ecological data reporting.

The lack of synthesized information regarding biodiversity is a major problem among researchers, leading to a pervasive cycle where ecologists make field campaigns to collect information that already exists and yet has not been made available for a broader audience. This problem leads to long-lasting effects in public policies such as spending money multiple times to conduct similar studies in the same area. We aim to identify this knowledge gap by synthesizing information available regarding two Brazilian long-term biodiversity programs and the metadata generated by them. Using a unique dataset containing 1904 metadata, we identified patterns of metadata distribution and intensity of research conducted in Brazil, as well as where we should concentrate research efforts in the next decades. We found that the majority of metadata were about vertebrates, followed by plants, invertebrates, and fungi. Caating was the biome with least metadata, and that there's still a lack of information regarding all biomes in Brazil, with none of them being sufficiently sampled. We hope that these results will have implications for broader conservation and management guiding, as well as to funding allocation programs.

Nightside clouds and disequilibrium chemistry on the hot Jupiter WASP-43b.

Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5 µm to 12 µm with the JWST's Mid-Infrared Instrument. The spectra reveal a large day-night temperature contrast (with average brightness temperatures of 1,524 ± 35 K and 863 ± 23 K, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase-curve shape and emission spectra strongly suggest the presence of nightside clouds that become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2σ upper limit of 1-6 ppm, depending on model assumptions). Our results provide strong evidence that the atmosphere of WASP-43b is shaped by disequilibrium processes and provide new insights into the properties of the planet's nightside clouds. However, the remaining discrepancies between our observations and our predictive atmospheric models emphasize the importance of further exploring the effects of clouds and disequilibrium chemistry in numerical models.

Spherically symmetric teleparallel geometries.

We are interested in the development of spherically symmetric geometries in F(T) teleparallel gravity which are of physical importance. We first express the general forms for the spherically symmetric frame and the zero curvature, metric compatible, spin connection. We then analyse the antisymmetric field equations (the solutions of which split into two cases, which we subsequently consider separately), and derive and analyse the resulting symmetric field equations. In order to further study the applications of spherically symmetric teleparallel models, we study 3 subcases in which there is an additional affine symmetry so that the resulting field equations reduce to a system of ordinary differential equations. First, we study static spherical symmetric geometries and solve the antisymmetric field equations and subsequently derive the full set of symmetric field equations. In particular, we investigate vacuum spacetimes and obtain a number of new solutions. Second, we consider an additional affine frame symmetry in order to expand the affine frame symmetry group to that of a spatially homogeneous Kantowski-Sachs geometry. Third, we study the special case of spherical symmetry with an additional fourth similarity affine vector.

Biomimetic Antifungal Materials: Countering the Challenge of Multidrug-Resistant Fungi.

In light of rising public health threats like antifungal and antimicrobial resistance, alongside the slowdown in new antimicrobial development, biomimetics have shown promise as therapeutic agents. Multidrug-resistant fungi pose significant challenges as they quickly develop resistance, making traditional antifungals less effective. Developing new antifungals is also complicated by the need to target eukaryotic cells without harming the host. This review examines biomimetic antifungal materials that mimic natural biological mechanisms for targeted and efficient action. It covers a range of agents, including antifungal peptides, alginate-based antifungals, chitosan derivatives, nanoparticles, plant-derived polyphenols, and probiotic bacteria. These agents work through mechanisms such as disrupting cell membranes, generating reactive oxygen species, and inhibiting essential fungal processes. Despite their potential, challenges remain in terms of ensuring biocompatibility, optimizing delivery, and overcoming potential resistance. Production scalability and economic viability are also concerns. Future research should enhance the stability and efficacy of these materials, integrate multifunctional approaches, and develop sophisticated delivery systems. Interdisciplinary efforts are needed to understand interactions between these materials, fungal cells, and the host environment. Long-term health and environmental impacts, fungal resistance mechanisms, and standardized testing protocols require further study. In conclusion, while biomimetic antifungal materials represent a revolutionary approach to combating multidrug-resistant fungi, extensive research and development are needed to fully realize their potential.

Do Phagostimulants, Alone or Combined with Ammonium Acetate, Di-Ammonium Phosphate, and Acetic Acid, Effectively Attract Both Sexes of Peach Fruit Flies, Bactrocera zonata (Diptera: Tephritidae)?: Insights from Laboratory and Field Bioassays.

Laboratory and field assays of three sets of experiments were conducted to evaluate the impact of different phagostimulants alone and in combination with other phagostimulant lure sources, such as ammonium acetate, DAP, and acetic acid, on the attractancy of both sexes of B. zonata. In the first experiment, the laboratory olfactometer study revealed that out of eleven phagostimulants, banana, mulberry, mango, guava, molasses, and protein hydrolysate exhibited moderate attractancy (15.2-60.2%) to B. zonata. Unexpectedly, banana and protein hydrolysate were demonstrated to be highly attractive phagostimulants for starved female B. zonata (53.6% and 60.2%, respectively). In the field study, none of the tested phagostimulants exhibited high attractancy; however, banana, mulberry, protein hydrolysate, guava, mango, and molasses demonstrated moderate attractancy (5.6-35.6%) to B. zonata. In the second experiment, out of five phagostimulant-mixtures, phagostimulant-mixture-4 proved highly attractive (40.5-68.6% and 45.5-51.2%), followed by phagostimulant-mixture-3, which proved to be moderately attractive (17.0-22.5% and 28.4-36.1%) to B. zonata in olfactometer and field studies, respectively. In the third experiment, out of five phagostimulant-AdMixtures, phagostimulant-AdMixture-4 demonstrated strong attractiveness in the olfactometer (41.6-68.7%) and field studies (52.7-58.7%) for B. zonata, while the rest of the AdMixtures demonstrated moderate to no attractiveness for B. zonata. So, phagostimulant-AdMixture-4 with GF-120 could be used in the development of a phagostimulant bait station which attracts the maximum B. zonata population and ultimately provides pest-free fruits to the farmers.

Reconstruction of Z-pinch emission spectra in the wavelength range of less than 10 Å using a crystal X-ray spectrograph.

This work is devoted to the reconstruction of Z-pinch plasma emission spectra in the wavelength range of less than 10 Å recorded by using a crystal x-ray spectrograph at the Angara 5-1 mega-ampere facility. The spectrograph JA-1 used in experiments has a cylindrical mica crystal with dimensions of 50 × 40 mm2 and radius of curvature of 100 mm. Registration of spectra is performed on the photographic film UF-4 with dimensions of 30 × 10 mm2. To reconstruct the spectra, the previously developed method based on iterative approximation of a true spectrum shape while minimizing a residual between experimental and calculated spectrograms is used. The calculated spectrogram was obtained taking into account the instrumental function of the spectrograph. To define the instrumental function a virtual Monte-Carlo model in the Geant4 toolkit has been developed. This model takes into account the interaction of radiation with the mica crystal using dynamical theory of diffraction. A true spectrum of Z-pinch plasma radiation is reconstructed for a 16 mm high load made of two nested cylindrical wire liners. External liner with a diameter of 12 mm has 40 Al wires with a diameter of 18 µm. The internal liner with a diameter of 5 mm has 4 W wires with a diameter of 6 µm. The W wires have a sputtered layer of Re that is 0.5 µm thick.

SARS-CoV-2 clearance in term of Cycle Threshold (Ct) during first two waves of COVID-19 in Pakistan: a phenomenon of delayed viral clearance post-corticosteroid treatment.

SARS-CoV-2 is recently emerged virus, which caused millions of deaths, all over the world. To tackle COVID-19 pandemic, there is an utmost need for in-depth analysis of viral replication. We aimed to examine viral load in SARS-CoV-2 patients during first two waves of COVID-19 in Pakistan. 225,615 suspected subjects from 75 different regions of Pakistan were selected in the study. SARS-CoV-2 RNAs were detected via real time PCR. During first wave (period of June-July, 2020) of COVID-19 the prevalence of SARS-CoV-2 was 20.38%. However, during second wave (period of November-December, 2020) of COVID-19, the rate of prevalence was 9.41%. During first wave of COVID-19 96.31% of participants remained PCR positive for 14 to 21 days, 3.39% of subjects showed positive results for 22 to 35 days, while delayed Ct values were observed among 0.26% of participants for 36 to 49 days. However, during second wave of COVID-19 89.31% of the subjects exhibited symptoms and showed real-time PCR positive results for 14 to 21 days, 9.42% showed positive results for 22 to 35 days, while significantly delayed Ct value results were observed among 1.026% of participants for 36 to 63 days (3.95 times higher than first wave). In contrast to first wave of COVID-19, the factors that were different in second wave were neither viral (different strains) nor host (same population). But treatment factors changed significantly. As during second wave besides azithromycin, corticosteroid dexamethasone consumption was increased consequently causing delayed Ct value negativity. This suggests that corticosteroid treatment might be linked with delayed Ct value or viral clearance. This study is crucial for re-considering effective therapeutic options against COVID-19.

Reply to Bourgeois, P. Comment on "Devoogdt et al. The Effectiveness of Fluoroscopy-Guided Manual Lymph Drainage as Part of Decongestive Lymphatic Therapy on the Superficial Lymphatic Architecture in Patients with Breast Cancer-Related Lymphoedema: A Randomised Controlled Trial. Cancers 2023, 15, 1545".

We appreciate the commentary by Pierre Bourgeois [...].

Analysis of Methylome of Different Forms of Basal Cell Hyperplasia and Squamous Cell Metaplasia of Bronchial Epithelium.

Squamous cell lung cancer (SCLC) occurs as a result of dysregenerative changes in the bronchial epithelium: basal cell hyperplasia (BCH), squamous cell metaplasia (SM), and dysplasia. We previously suggested that combinations of precancerous changes detected in the small bronchi of patients with SCLC may reflect various "scenarios" of the precancerous process: isolated BCH→stopping at the stage of hyperplasia, BCH+SM→progression of hyperplasia into metaplasia, SM+dysplasia→progression of metaplasia into dysplasia. In this study, DNA methylome of various forms of precancerous changes in the bronchial epithelium of SCLC patients was analyzed using the genome-wide bisulfite sequencing. In BCH combined with SM, in contrast to isolated BCH, differentially methylated regions were identified in genes of the pathogenetically significant MET signaling pathway (RNMT, HPN). Differentially methylated regions affecting genes involved in inflammation regulation (IL-23, IL-23R, IL12B, IL12RB1, and FIS1) were detected in SM combined with dysplasia in comparison with SM combined with BCH. The revealed changes in DNA methylation may underlie various "scenarios" of the precancerous process in the bronchial epithelium.

Family conflict and less parental monitoring were associated with greater screen time in early adolescence.

AIM: The current study investigated the prospective relationships between parental monitoring, family conflict, and screen time across six screen time modalities in early adolescents in the USA. METHODS: We utilised prospective cohort data of children (ages 10-14 years) from the Adolescent Brain Cognitive Development (ABCD) Study (years baseline to Year 2 of follow-up; 2016-2020; N = 10 757). Adjusted coefficients (B) and 95% confidence intervals (CIs) were estimated using mixed-effect models with robust standard errors. RESULTS: A higher parental monitoring score was associated with less total screen time (B = -0.37, 95% CI -0.58, -0.16), with the strongest associations being with video games and YouTube videos. Conversely, a higher family conflict score was associated with more total screen time (B = 0.08, 95% CI 0.03, 0.12), with the strongest associations being with YouTube videos, video games, and watching television shows/movies in Years 1 and 2. CONCLUSION: The current study found that greater parental monitoring was associated with less screen time, while greater family conflict was linked to more screen time. These results may inform strategies to reduce screen time in adolescence, such as improving communication between parents and their children to strengthen family relationships.

The Japanese Esophageal Society classification for prediction of superficial esophageal squamous cell neoplasia invasion depth: Validation in a Western population.

BACKGROUND: The Japan Esophageal Society proposed the JES microvessel classification to assess eligibility of early esophageal squamous cell neoplasia (ESCN) for endoscopic resection based on intrapapillary capillary loop assessment. We aimed to assess its diagnostic reproducibility and accuracy in Western ESCN patients. METHODS: Intrapapillary capillary loops on endoscopic images of Western ESCN lesions (n = 113) collected between 2010 and 2022 were assessed by nine endoscopists, including three Japanese expert endoscopists, three Western expert endoscopists, and three residents-in-training, and graded according to the JES microvessel classification where microvessel type A corresponds with normality or low-grade intraepithelial neoplasia, and microvessel types B1, B2, and B3 correspond with high-grade intraepithelial neoplasia or invasion into the lamina propria, muscularis mucosae or superficial submucosa, and deep submucosa, respectively. Outcomes included overall accuracy in predicting ESCN invasion depth and interobserver agreement. RESULTS: Good interobserver agreement was observed among expert endoscopists (Krippendorf's alpha 0.64, 95% CI 0.57-0.70), while agreement was moderate among residents-in-training (Krippendorf's alpha 0.58, 95% CI 0.52-0.72). Overall accuracy of the JES microvessel classification was 53% (95% CI 42-63), 52% (95% CI 41-62), and 44% (95% CI 34-55) for Japanese endoscopists, Western endoscopists, and residents-in-training, respectively. Sensitivity and specificity for vessel type A, B1, B2, and B3 across assessors were 0%-50% and 89%-100%, 55%-64% and 66%-77%, 42%-71% and 60%-76%, and 10%-24% and 92%-97%, respectively. Negative predictive value ranged between 80% and 85% for B3 vessels. CONCLUSION: Overall accuracy of the JES microvessel classification in Western ESCN patients is low, though absence of B3 vessels as assessed by experienced endoscopists may predict superficial ESCN amenable to endoscopic resection. TRIAL REGISTRY: www.trialregister.nl; NL8897 (6-9-2020).

Non-competitive NMDA antagonist MK-801 prevents memory reconsolidation impairment caused by protein synthesis inhibitors in young chicks.

Introduction: Reactivation of already consolidated memory can initiate its destabilization, making the memory trace labile. Normally, this destabilization is followed by reconsolidation of the memory trace, enriched by newly acquired experience. Disrupting the reconsolidation process, for example, by inhibiting protein synthesis, impairs subsequent memory retrieval, leading to reminder-related amnesia. Previous studies in various species have shown that this impairment can be prevented by using NMDA receptor antagonists, which interfere with memory destabilization. Methods: In the present study we examined this phenomenon using a one-trial passive avoidance learning model in newborn chicks, the hypothesis being that inactivation of the NMDA-mediated transmission during memory reactivation would inhibit the memory trace labilization and thus prevent the reminder-related amnesia. Results: We found that reminder-associated administration of the NMDA receptor antagonist MK-801 or one of the protein synthesis inhibitors (anisomycin, cycloheximide, 2-deoxygalactose) each alone produced amnesia. However, when combined, injection of MK-801 before the reminder prevented amnesia induced by protein synthesis inhibitors. Discussion: We suggest that the observed paradoxical effect implicates the involvement of NMDA receptors in both protein synthesis-independent engram destabilization upon its retrieval and protein synthesismediated engram stabilization after its updating. This puzzling dual role of NMDA receptors in memory destabilization/restabilization requires further investigation.

A spatially resolved multiomic single-cell atlas of soybean development.

Cis-regulatory elements (CREs) precisely control spatiotemporal gene expression in cells. Using a spatially resolved single-cell atlas of gene expression with chromatin accessibility across ten soybean tissues, we identified 103 distinct cell types and 303,199 accessible chromatin regions (ACRs). Nearly 40% of the ACRs showed cell-type-specific patterns and were enriched for transcription factor (TF) motifs defining diverse cell identities. We identified de novo enriched TF motifs and explored conservation of gene regulatory networks underpinning legume symbiotic nitrogen fixation. With comprehensive developmental trajectories for endosperm and embryo, we uncovered the functional transition of the three sub-cell types of endosperm, identified 13 sucrose transporters sharing the DOF11 motif that were co-up-regulated in late peripheral endosperm and identified key embryo cell-type specification regulators during embryogenesis, including a homeobox TF that promotes cotyledon parenchyma identity. This resource provides a valuable foundation for analyzing gene regulatory programs in soybean cell types across tissues and life stages.