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Research indicates that around 1% of the global population experiences epileptic seizures, described as an undue neuronal discharge in the brain, which can significantly impact the quality of life for those affected. Children who experience frequent or prolonged seizures may experience lasting cognitive damage and psychological difficulties, and sudden seizures can pose a serious risk of injury or even death. Therefore, developing an accurate machine learning model to predict seizures is crucial. This study introduces an Event-based Stacked Convolutional Restricted Boltzmann Machine architecture that can detect ictal periods in EEG signals. The model was trained and evaluated on a publicly available dataset of EEG recordings from 24 pediatric patients, achieving a high prediction accuracy of 94.2%, with a mean prediction time of 19.62 min. The model's mean sensitivity and specificity rates were also comparable to those of state-of-the-art predictive models on the CHB-MIT dataset. [ABSTRACT FROM AUTHOR]

The Neutrosophic Bonferroni operator is a novel operator that we provide in this paper. Then the arithmetic operations for Neutrosophic Bonferroni operator is developed which tells the existence of Neutrosophic Bonferroni operator. Then its properties were discussed with special cases. To group decision-making issues with several attributes, arithmetic ranking operations and the Neutrosophic approach are used. The result is compared with the existing methodology. The suggested approach will more accurately give the decision maker the ideal attribute than the existing system does. Neutrophic multicriteria is a method of decision-making that makes use of ambiguity to integrate various criteria or factors--often with imprecise or ambiguous data--to reach a result. The neutrosophic multicriteria analysis enables the assessment of subjective and qualitative factors, which can assist in resolving conflicting goals and preferences. In Neutrosophic Multi-Attribute Group Decision Making (NMAGDM) problems, all the data supplied by the decision makers (DMs) is expressed in single-value Neutrosophic triangular and trapezoidal numbers, which are studied in this work and can improve the flexibility and precision of capturing uncertainty and aggregating preferences. Studying this operator is crucial because it can be utilised to resolve multi-attribute. [ABSTRACT FROM AUTHOR]

The aquaculture industry is under the framework of the food-water-energy nexus due to the extensive use of water and energy. Sustainable practices are required to support the tremendous growth of this sector. Currently, the aquaculture industry is challenged by its reliance on capture fisheries for feed, increased use of pharmaceuticals, infectious outbreaks, and solid/liquid waste management. This review posits microalgal technology as a comprehensive solution for the current predicaments in aquaculture in a sustainable way. Microalgae are microscopic, freshwater and marine photosynthetic organisms, capable of carbon mitigation and bioremediation. They are indispensable in aquaculture due to their key role in marine productivity and their position in the marine food chain. Microalgae are nutritious and are currently used as feed in specific sectors of aquaculture. Due to their bioremediation potential, direct application of microalgae in shellfish ponds and in recirculating systems have been adopted to improve water quality and aquatic animal health. The potential of microalgae for integration into various aspects of aquaculture processes, namely hatcheries, feed, and waste management has been critically analyzed. Seamless integration of microalgal technology in aquaculture is feasible, and this review will provide new insights into using microalgal technology for sustainable aquaculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Childhood neuroblastoma with MYCN-amplification is classified as high-risk and often relapses after intensive treatments. Immune checkpoint blockade therapy against the PD-1/L1 axis shows limited efficacy in neuroblastoma patients and the cancer intrinsic immune regulatory network is poorly understood. Here, we leverage genome-wide CRISPR/Cas9 screens and identify H2AFY as a resistance gene to the clinically approved PD-1 blocking antibody, nivolumab. Analysis of single-cell RNA sequencing datasets reveals that H2AFY mRNA is enriched in adrenergic cancer cells and is associated with worse patient survival. Genetic deletion of H2afy in MYCN-driven neuroblastoma cells reverts in vivo resistance to PD-1 blockade by eliciting activation of the adaptive and innate immunity. Mapping of the epigenetic and translational landscape demonstrates that H2afy deletion promotes cell transition to a mesenchymal-like state. With a multi-omics approach, we uncover H2AFY-associated genes that are functionally relevant and prognostic in patients. Altogether, our study elucidates the role of H2AFY as an epigenetic gatekeeper for cell states and immunogenicity in high-risk neuroblastoma.

Natural astaxanthin is synthesized by diverse organisms including: bacteria, fungi, microalgae, and plants involving complex cellular processes, which depend on numerous interrelated parameters. Nonetheless, existing knowledge regarding astaxanthin biosynthesis and the conditions influencing astaxanthin accumulation is fairly limited. Thus, manipulation of the growth conditions to achieve desired biomass and astaxanthin yields can be a complicated process requiring cost-intensive and time-consuming experiment-based research. As a potential solution, modeling and simulation of biological systems have recently emerged, allowing researchers to predict/estimate astaxanthin production dynamics in selected organisms. Moreover, mathematical modeling techniques would enable further optimization of astaxanthin synthesis in a shorter period of time, ultimately contributing to a notable reduction in production costs. Thus, the present review comprehensively discusses existing mathematical modeling techniques which simulate the bioaccumulation of astaxanthin in diverse organisms. Associated challenges, solutions, and future perspectives are critically analyzed and presented.

While many computational methods accurately predict destabilizing mutations, identifying stabilizing mutations has remained a challenge, because of their relative rarity. We tested ΔΔG 0 predictions from computational predictors such as Rosetta, ThermoMPNN, RaSP, and DeepDDG, using 82 mutants of the bacterial toxin CcdB as a test case. On this dataset, the best computational predictor is ThermoMPNN, which identifies stabilizing mutations with a precision of 68%. However, the average increase in T m for these predicted mutations was only 1°C for CcdB, and predictions were poorer for a more challenging target, influenza neuraminidase. Using data from multiple previously described yeast surface display libraries and in vitro thermal stability measurements, we trained logistic regression models to identify stabilizing mutations with a precision of 90% and an average increase in T m of 3°C for CcdB. When such libraries contain a population of mutants with significantly enhanced binding relative to the corresponding wild type, there is no benefit in using computational predictors. It is then possible to predict stabilizing mutations without any training, simply by examining the distribution of mutational binding scores. This avoids laborious steps of in vitro expression, purification, and stability characterization. When this is not the case, combining data from computational predictors with high-throughput experimental binding data enhances the prediction of stabilizing mutations. However, this requires training on stability data measured in vitro with known stabilized mutants. It is thus feasible to predict stabilizing mutations rapidly and accurately for any system of interest that can be subjected to a binding selection or screen., (© 2024 Wiley Periodicals LLC.)

Melanin is an amorphous, highly heterogeneous polymer found across all kingdoms of life. Although the properties of melanin can greatly vary, most forms are insoluble and strongly absorb light, appearing dark brown to black. Here, we describe a water-soluble form of melanin (peptidomelanin) secreted by the spores of Aspergillus niger (strain: melanoliber) during germination. Peptidomelanin is composed of an insoluble L-DOPA core polymer that is solubilized via short, copolymerized heterogeneous peptide chains forming a "corona" with a mean amino acid length of 2.6 ± 2.3. Based on in vitro experiments, we propose a biochemical copolymerization mechanism involving the hydroxylation of tyrosynylated peptides. Peptidomelanin is capable of chelating heavy metals such as lead, mercury, and uranium (as uranyl) in large quantities. Preliminary data indicates that peptidomelanin may have applications for the remediation of heavy metals in situ , including in agricultural settings., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Autism spectrum disorder (ASD) presents with diverse cognitive and behavioral abnormalities beginning during early development. Although the neural circuit mechanisms remain unclear, recent work suggests pathology in cortical inhibitory interneurons (INs) plays a crucial role. However, we lack fundamental information regarding changes in the physiology of synapses to and from INs in ASD. Here, we used transgenic mice to conditionally knockout one copy of the high confidence ASD risk gene Arid1b from the progenitors of parvalbumin-expressing fast-spiking (PV-FS) INs and somatostatin-expressing non-fast-spiking (SST-NFS) INs. In brain slices, we performed paired whole-cell recordings between INs and excitatory projection neurons (PNs) to investigate changes in synaptic physiology. In neonates, we found reduced synaptic input to INs but not PNs, with a concomitant reduction in the frequency of spontaneous network events, which are driven by INs in immature circuits. In mature mice, we found a reduction in the number of PV-FS INs in cortical layers 2/3 and 5. However, changes in PV-FS IN synaptic physiology were cortical layer and PN cell-type dependent. In layer 5, synapses from PV-FS INs to subcortical-projecting PNs were weakened. In contrast, in layer 2/3, synapses to and from PV-FS INs and corticocortical-projecting PNs were strengthened, leading to enhanced feedforward inhibition of input from layer 4. Finally, we found a novel synaptic deficit among SST-NFS INs, in which excitatory synapses from layer 2/3 PNs failed to facilitate. Our data highlight that changes in unitary synaptic dynamics among INs in ASD depend on neuronal cell-type.

Arid1b is a high confidence risk gene for autism spectrum disorder that encodes a subunit of a chromatin remodeling complex expressed in neuronal progenitors. Haploinsufficiency causes a broad range of social, behavioral, and intellectual disability phenotypes, including Coffin-Siris syndrome. Recent work using transgenic mouse models suggests pathology is due to deficits in proliferation, survival, and synaptic development of cortical neurons. However, there is conflicting evidence regarding the relative roles of excitatory projection neurons and inhibitory interneurons in generating abnormal cognitive and behavioral phenotypes. Here, we conditionally knocked out either one or both copies of Arid1b from excitatory projection neuron progenitors and systematically investigated the effects on intrinsic membrane properties, synaptic physiology, social behavior, and seizure susceptibility. We found that disrupting Arid1b expression in excitatory neurons alters their membrane properties, including hyperpolarizing action potential threshold; however, these changes depend on neuronal subtype. Using paired whole-cell recordings, we found increased synaptic connectivity rate between projection neurons. Furthermore, we found reduced strength of excitatory synapses to parvalbumin (PV)-expression inhibitory interneurons. These data suggest an increase in the ratio of excitation to inhibition. However, the strength of inhibitory synapses from PV interneurons to excitatory neurons was enhanced, which may rebalance this ratio. Indeed, Arid1b haploinsufficiency in projection neurons was insufficient to cause social deficits and seizure phenotypes observed in a preclinical germline haploinsufficient mouse model. Our data suggest that while excitatory projection neurons likely contribute to autistic phenotypes, pathology in these cells is not the primary cause.

In our previous studies, we showed that the generation of ovarian tumors in NSG mice (immune-compromised) resulted in the induction of muscle and cardiac cachexia, and treatment with withaferin A (WFA; a steroidal lactone) attenuated both muscle and cardiac cachexia. However, our studies could not address if these restorations by WFA were mediated by its anti-tumorigenic properties that might, in turn, reduce the tumor burden or WFA's direct, inherent anti-cachectic properties. To address this important issue, in our present study, we used a cachectic model induced by the continuous infusion of Ang II by implanting osmotic pumps in immunocompetent C57BL/6 mice. The continuous infusion of Ang II resulted in the loss of the normal functions of the left ventricle (LV) (both systolic and diastolic), including a significant reduction in fractional shortening, an increase in heart weight and LV wall thickness, and the development of cardiac hypertrophy. The infusion of Ang II also resulted in the development of cardiac fibrosis, and significant increases in the expression levels of genes (ANP, BNP, and MHCβ) associated with cardiac hypertrophy and the chemical staining of the collagen abundance as an indication of fibrosis. In addition, Ang II caused a significant increase in expression levels of inflammatory cytokines (IL-6, IL-17, MIP-2, and IFNγ), NLRP3 inflammasomes, AT1 receptor, and a decrease in AT2 receptor. Treatment with WFA rescued the LV functions and heart hypertrophy and fibrosis. Our results demonstrated, for the first time, that, while WFA has anti-tumorigenic properties, it also ameliorates the cardiac dysfunction induced by Ang II, suggesting that it could be an anticachectic agent that induces direct effects on cardiac muscles.

The microalgal-based production of fucoxanthin has emerged as an imperative research endeavor due to its antioxidant, and anticancer properties. In this study, three brown marine microalgae, namely Skeletonema costatum, Chaetoceros gracilis, and Pavlova sp., were screened for fucoxanthin production. All strains displayed promising results, with Pavlova sp. exhibiting the highest fucoxanthin content (27.91 mg/g) and productivity (1.16 mg/L·day). Moreover, the influence of various cultivation parameters, such as culture media, salinity, sodium nitrate concentration, inoculum size, light intensity, and iron concentration, were investigated and optimized, resulting in a maximum fucoxanthin productivity of 7.89 mg/L·day. The investigation was further expanded to large-scale outdoor cultivation using 50 L tubular photobioreactors, illustrating the potential of Pavlova sp. and the cultivation process for future commercialization. The biomass and fucoxanthin productivity for the large-scale cultivation were 70.7 mg/L·day and 4.78 mg/L·day, respectively. Overall, the findings demonstrated considerable opportunities for fucoxanthin synthesis via microalgae cultivation and processing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Immune checkpoint blockade therapy aims to activate the immune system to eliminate cancer cells. However, clinical benefits are only recorded in a subset of patients. Here, we leverage genome-wide CRISPR/Cas9 screens in a Tumor-Immune co-Culture System focusing on triple-negative breast cancer (TNBC). We reveal that NEDD8 loss in cancer cells causes a vulnerability to nivolumab (anti-PD-1). Genetic deletion of NEDD8 only delays cell division initially but cell proliferation is unaffected after recovery. Since the NEDD8 gene is commonly essential, we validate this observation with additional CRISPR screens and uncover enhanced immunogenicity in NEDD8 deficient cells using proteomics. In female immunocompetent mice, PD-1 blockade lacks efficacy against established EO771 breast cancer tumors. In contrast, we observe tumor regression mediated by CD8+ T cells against Nedd8 deficient EO771 tumors after PD-1 blockade. In essence, we provide evidence that NEDD8 is conditionally essential in TNBC and presents as a synergistic drug target for PD-1/L1 blockade therapy., (© 2024. The Author(s).)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies, in comparison, has been much more complex, largely owing to the irregular shapes of protein structures 1 . Here we describe extendable linear, curved and angled protein building blocks, as well as inter-block interactions, that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight 'train track' assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence-structure relationships, it has not previously been possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank three-dimensional canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to 'back of an envelope' architectural blueprints., (© 2024. The Author(s).)

Salt stress is a recognized annihilating abiotic stress that has a significant impact on agricultural and horticulture crop productivity. Plant development faces three distinct dangers as a result of salt stress: oxidative stress, osmotic stress, and ionic toxicity. It has been shown that plants can forecast diurnal patterns using the circadian clock; moreover, they can manage their defensive mechanism for the detoxification of reactive oxygen species (ROS). Circadian rhythmicity in gene expression assembles transcription and translation feedback networks to govern plant shape, physiology, cellular and molecular activities. Both external and internal variables influence the systemic rhythm via input routes. The Malav Jyoti (MJ) and Delhi Green (DG) genotypes of spinach (Spinacia oleracea) were grown in the plant growth chamber. The chamber had an optimized temperature of 25 °C and humidity of 65% containing light emitting diode (LED) having Red: Blue: white (one side) and White fluorescent (other side) under salinity stress. The samples were collected on the basis of 4 h intervals of circadian hours (0 h, 4 h, 8 h and 12 h) during Day-10 and Day-20 of salt treatments. Under salt stress, the circadian and light-emitting diode-based strategy had a substantial influence on spinach's anti-oxidative responses, stomatal movement, CO 2 assimilation, PS-I and II efficiency, phytochrome pigment efficiency, and photosynthesis. Based on the findings of the free radical scavenging enzyme tests, the photoperiodic hours for the proteome analysis were set to 11 am and 3 pm on Day-20. When compared to white fluorescent, this study found that LED has the capacity to influence the entrainment cues of the circadian clock in the cultivation of salt-sensitive spinach genotypes. According to our findings, changing the cellular scavenging mechanism and chloroplast proteome has increased the survival rate of spinach genotypes under LED when compared to white fluorescent., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)