Patterns Of Regulation Research Articles

Rational design and characterization of enhanced alcohol-inducible synthetic promoters in Pichia pastoris.

The C1 and C2 alcohols hold great promise as substrates for biomanufacturing due to their low cost and rich resources. Pichia pastoris is considered a preferred host for methanol and ethanol bioconversion due to its natural utilization of methanol and ethanol. However, the scarcity of strong and tightly regulated alcohol-inducible promoters limits its extended use. This study aimed to develop enhanced methanol- and ethanol-inducible promoters capable of improving gene expression in P. pastoris. Rational design strategies were employed to rewire the upstream regulatory sequence of the methanol-inducible PAOX1, generating several high-strength methanol-inducible promoters with a stringent regulatory pattern. Eleven strong promoters were identified from 36 endogenous ethanol-inducible candidates recognized from transcriptome analysis. Core promoter regions, the crucial element influencing transcriptional strength, were also characterized. Five high-activity core promoters were then combined with four upstream regulatory sequences of high-strength promoters, resulting in four groups of synthetic promoters. Ultimately, the highly active methanol-inducible PA13 and ethanol-inducible P0688 and PsynIV-5 were selected for the expression of an α-amylase and yielded enzyme activity 1.6, 2.6, and 4.5 times higher as compared to that of PAOX1. This work expands the genetic toolkit available for P. pastoris, providing more precise and efficient options for regulating gene expression. It benefits the use of P. pastoris as an efficient platform for the C1 and C2 alcohol-based biotransformation in industrial biotechnology.IMPORTANCEP. pastoris represents a preferred microbial host for the bio-utilization of C1 and C2 alcohols that are regarded as renewable carbon sources based on clean energy. However, lack of efficient and regulated expression tools highly limits the C1 and C2 alcohols based bioproduction. By exploring high-strength and strictly regulated alcohol-inducible promoters, this study expands the expression toolkit for P. pastoris on C1 and C2 alcohols. The newly developed methanol-inducible PA13 and ethanol-inducible PsynIV-5 demonstrate significantly higher expression levels than the commercial PAOX1 system. The endogenous and synthetic promoter series established in this study provides new construction references and alternative tools for expression control in P. pastoris for C1 and C2 alcohols based biomanufacturing.

Multiple mechanisms of allosteric regulation of the luteninizing hormone receptor

The regulatory effects of luteinizing hormone (LH) and chorionic gonadotropin (CG) are realized through the activation of the G-protein coupled LH/CG receptor (LH/CG-R). The result of this is the activation of various types of G proteins, which leads to stimulation (Gs) or inhibition (Gi) of the cAMP-dependent pathway and stimulation of calcium signaling (Gq/11, Gi), and the recruitment of β-arrestins, which prevent G protein signaling through receptor internalization and downregulation, but can also activate the mitogen-activated protein kinase cascade. Despite a certain similarity in the effects of LH and CG, there are differences between them both in efficiency and in the pattern of regulation of LH/CG-R. This is a consequence of differences in the affinity of LH and CG to the orthosteric site of the receptor, as well as differences at the level of allosteric regulation of the receptor, which is due to the presence of a C-terminal extension in the β-subunit of CG, including sites for O-glycosylation, and the variability of N-glycosylation of α- and β-subunits of gonadotropins. Moreover, the number of N-glycans, the degree of their branching and charge differ, which leads to different efficiency of activation of intracellular cascades, affecting the physiological response of the reproductive system to gonadotropins. Of great importance is the formation of homodi(oligo)meric complexes of LH/CG-R and its heterocomplexes with the follicle-stimulating hormone receptor, where protomers allosterically influence the efficiency of LH/CG-R activation and the bias of signal transduction. Taking into account the large number of allosteric sites in LH/CG-R, the development of low-molecular allosteric regulators is underway, including agonists based on thieno[2,3-d]-pyrimidine and peptides derived from the cytoplasmic loops of LH/CG-R. These regulators can become prototypes of drugs for correcting the functions of the reproductive system. This review is devoted to the analysis of data on the similarities and differences in the signaling and physiological effects of gonadotropins with LH activity, the role of allosteric mechanisms in this, and the prospects for creating allosteric regulators of LH/CG-R.

Roles and regulatory patterns of protein isoforms in plant adaptation and development.

Protein isoforms (PIs) play pivotal roles in regulating plant growth and development that confer adaptability to diverse environmental conditions. PIs are widely present in plants and generated through alternative splicing (AS), alternative polyadenylation (APA), alternative initiation (AI), and ribosomal frameshifting (RF) events. The widespread presence of PIs not only significantly increases the complexity of genomic information but also greatly enriches regulatory networks and enhances their flexibility. PIs may also play important roles in phenotypic diversity, ecological niche differentiation, and speciation, thereby increasing the dimensions of research in molecular ecology. However, PIs pose new challenges for the quantitative analysis, annotation, and identification of genetic regulatory mechanisms. Thus, focus on PIs make genomic and epigenomic studies both more powerful and more challenging. This review summarizes the origins, functions, regulatory patterns of isoforms, and the challenges they present for future research in molecular ecology and molecular biology.

Impact of Exercise on Vitals in Racing Horses

Background: This article delves into a comprehensive analysis of a dataset that sheds light on the intricate relationship between exercise and equine physiology. By examining temperature, pulse rate and respiratory rate, we uncover how exercise type, duration and ground surface significantly influence the well-being of horses during physical activities. Methods: The choice of exercise type, whether it’s show jumping, free ride, or lunge, has a profound impact on the horses’ physiological responses. Each activity elicits distinct patterns of temperature regulation, cardiovascular demand (pulse rate) and respiratory effort. The animal material of the study consisted of 20 different horses (10 Thoroughbred, 2 Arabian, 8 Belgian) which were housed in Adana and Mersin provinces. Horses were housed in similar conditions of care and they were healthy. The study encompassed the measurement and recording of key parameters, including pulse rate (heart rate), respiration rate (breathing rate) and body temperature, at various critical time points: before the commencement of exercise, immediately post-exercise, 30 min after exercise and 1 hour after exercise. Exercise duration varied between 15 to 40 min, with each session commencing with a standardized warm-up period of approximately 5 min, including a rider on the horse. The horses were observed at four specific time points. Result: This analysis underscores the need for a nuanced approach to equine training, considering the specific exercise type, duration and ground surface. Horse owners, trainers and veterinarians can use these insights to optimize exercise programs, ensuring the health and performance of their equine companions. Ultimately, this understanding of equine physiology paves the way for responsible and effective equine training practices.

Multi-omics analysis reveals genetic architecture and local adaptation of coumarins metabolites in Populus

BackgroundAccumulation of coumarins plays key roles in response to immune and abiotic stress in plants, but the genetic adaptation basis of controlling coumarins in perennial woody plants remain unclear.ResultsWe detected 792 SNPs within 334 genes that were significantly associated with the phenotypic variations of 15 single-metabolic traits and multiple comprehensive index, such as principal components (PCs) of coumarins metabolites. Expression quantitative trait locus mapping uncovered that 337 eQTLs associated with the expression levels of 132 associated genes. Selective sweep revealed 55 candidate genes have potential selective signature among three geographical populations, highlighting that the coumarins biosynthesis have been encountered forceful local adaptation. Furthermore, we constructed a genetic network of seven candidate genes that coordinately regulate coumarins biosynthesis, revealing the multiple regulatory patterns affecting coumarins accumulation in Populus tomentosa. Validation of candidate gene variations in a drought-tolerated population and DUF538 heterologous transformation experiments verified the function of candidate genes and their roles in adapting to the different geographical conditions in poplar.ConclusionsOur study uncovered the genetic regulation of the coumarins metabolic biosynthesis of Populus, and offered potential clues for drought-tolerance evaluation and regional improvement in woody plants.

Impact of Social Media and Anxiety among College Students

This study aims explore the relationship between social media use and Generalized Anxiety Disorder (GAD) among students. A sample of 76 participants aged 18 to 25 was assessed using two standardized tools: the Hamilton Anxiety Scale, which measures the severity of anxiety, and the Social Media Addiction Scale (SMAS), designed to quantify the extent of social media dependency. Data analysis revealed a Pearson correlation coefficient of 0.330, with a p-value of 0.004, indicating a moderate positive correlation between social media addiction and anxiety. These findings suggest that higher levels of social media addiction are significantly associated with increased anxiety symptoms. The results imply that students who exhibit addictive behaviours related to social media are more likely to experience anxiety, potentially due to factors such as constant connectivity, social comparison, and fear of missing out (FOMO). Given the moderate correlation, this study underscores the importance of addressing excessive social media use as a factor in mental health interventions. The findings call for the development of strategies that can help students manage their social media habits and reduce the psychological distress associated with its overuse. Future research could further investigate the causality of this relationship and examine additional variables, such as self-esteem, emotional regulation, or sleep patterns, that may mediate the link between social media addiction and anxiety. Keywords: Social Media Use, Generalized Anxiety Disorder

Sex-Specific Differences in Lipid Metabolism in Obesity: Implications for Cardiometabolic Risk

Sex-specific differences in lipid metabolism play a critical role in the pathophysiology of obesity and its related cardiometabolic risks. Men and women exhibit distinct patterns of fat distribution, lipid handling, and hormonal regulation, contributing to varying susceptibilities to conditions like dyslipidemia, insulin resistance, cardiovascular diseases (CVD), and metabolic syndrome. In women, subcutaneous fat deposition is more prominent, whereas men tend to accumulate visceral fat, which is associated with greater cardiometabolic risk. These differences are influenced by sex hormones, particularly estrogen, which has protective effects on lipid profiles in premenopausal women, but diminishes post-menopause, increasing CVD risk. Furthermore, genetic, epigenetic, and lifestyle factors modulate these sex-specific lipid metabolic processes. Understanding these differences is crucial for developing targeted therapeutic strategies aimed at reducing the burden of obesity-associated cardiometabolic disorders. This review explores the mechanisms underlying sex differences in lipid metabolism, their implications for cardiometabolic risk, and potential interventions to address sex-specific metabolic dysfunction in obesity. Keywords: Sex differences, lipid metabolism, obesity, cardiometabolic risk, estrogen, visceral fat, metabolic syndrome

Human-specific epigenomic states in spermatogenesis

Infertility is becoming increasingly common, affecting one in six people globally. Half of these cases can be attributed to male factors, many driven by abnormalities in the process of sperm development. Emerging evidence from genome-wide association studies, genetic screening of patient cohorts, and animal models highlights an important genetic contribution to spermatogenic defects, but comprehensive identification and characterization of the genes critical for male fertility remain lacking. High divergence of gene regulation in spermatogenic cells across species poses challenges for delineating the genetic pathways required for human spermatogenesis using common model organisms. In this study, we leveraged post-translational histone modification and gene transcription data for 15,491 genes in four mammalian species (human, rhesus macaque, mouse, and opossum), to identify human-specific patterns of gene regulation during spermatogenesis. We combined H3K27me3 ChIP-seq, H3K4me3 ChIP-seq, and RNA-seq data to define epigenetic states for each gene at two stages of spermatogenesis, pachytene spermatocytes and round spermatids, in each species. We identified 239 genes that are uniquely active, poised, or dynamically regulated in human spermatogenic cells distinct from the other three species. While some of these genes have been implicated in reproductive functions, many more have not yet been associated with human infertility and may be candidates for further molecular and epidemiologic studies. Our analysis offers an example of the opportunities provided by evolutionary and epigenomic data for broadly screening candidate genes implicated in reproduction, which might lead to discoveries of novel genetic targets for diagnosis and management of male infertility and male contraception.

1α,25-hydroxyvitamin D3 alleviated rotavirus infection induced ferroptosis in IPEC-J2 cells by regulating the ATF3-SLC7A11-GPX4 axis

Rotavirus (RV) mainly infects mature intestinal epithelial cells and impairs intestinal absorption function, which leads to the death of infected cells and eventually fatal diarrhea. Ferroptosis is a novel regulatory cell death pattern, which can be caused by virus infection. 1α,25-hydroxyvitamin D3 (1,25D3) has an anti-RV infection effect and can regulate ferroptosis. However, whether RV infection can induce ferroptosis, and whether 1,25D3 can inhibit RV infection by regulating ferroptosis has not yet been studied. Present study shows that RV infection or erastin treatment induces IPEC-J2 cell death, which results in mitochondrial shrinkage, decreased mitochondrial membrane potential (MMP) and glutathione (GSH) content, increased MMP, intracellular Fe2+, reactive oxygen species (ROS), and malondialdehyde (MDA) contents. Meanwhile, ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1), and deferoxamine (DFO) treatment can effectively reverse the increase of intracellular Fe2+, ROS and MDA levels induced by RV infection. Moreover, RV infection increases activating transcription factor 3 (ATF3) mRNA and protein expressions, and inhibited SLC7A11 and glutathione peroxidase 4 (GPX4) expressions, which was partially alleviated by siATF3. 1,25D3 treatment significantly eliminates RV induced ferroptosis via ATF3-SLC7A11-GPX4 axis. Therefore, our results reveals that RV infection induces ferroptosis in IPEC-J2 cell and 1,25D3 alleviates RV induced ferroptosis by regulating the ATF3-SLC7A11-GPX4 axis.

Tissue-specific, temporal, and core gene-dependent expression patterns of Hsp70s reveal functional allocation in Chlamys farreri under heat stress

Heat shock proteins 70 KDa (Hsp70s) engage in a broad spectrum of cellular functions in response to various stressors. Marine bivalves face substantial threats from the rising seawater temperature attributed to global warming. In the present study, expression patterns of Hsp70s in Zhikong scallop Chlamys farreri (CfHsp70s) were determined in embryos and larvae at all developmental stages, in healthy adult tissues, and across four various tissues exposed to high temperature for acute and chronic periods through in silico analysis. Spatiotemporal expressions suggested CfHsp70s performed specific functional differentiations in scallop's development and growth. Regulatory expression patterns of CfHsp70s, characterized by predominant down-regulation in the mantle, gill and hemocytes, as well as contrasting up-regulation in the heart, suggest differential functional allocation of CfHsp70s among tissues in response to heat stress. Particularly, a core set of 14 CfHsp70s, especially the nine members of the Hsp70B2s, characterized by gene expansion, intron-less structure, shorter gene length, preference for hydrophilic amino acids, and coordinated expression profiles, was predominantly responsible for the inducible up-regulations observed across all four tissue types. Collectively, the tissue-specific, temporal and core gene-dependent expression patterns of CfHsp70s illustrate the functional allocation and molecular evolution of Hsp70 family members in Zhikong scallops.

A self-consistent design method of the autothermal dual circulating fluidized bed reactor for in-situ gasification chemical looping combustion of coal

This paper establishes a design method for the autothermal dual circulating fluidized bed reactor (DCFBR) of the coal-fueled in-situ gasification chemical looping combustion (iG-CLC) process. This method, grounded in a self-consistent phenomenological model, comprehensively elucidates the factors of mass and energy conservation, fuel and oxygen carrier (OC) reaction processes, and fluidization characteristics within the reactor. It is particularly suitable for the rapid screening of numerous potential designs, obtaining detailed design parameters, and studying their interrelationships. Utilizing this method, the regulation patterns of dual-bed interactive transport-reaction phenomena within a 5 MWthiG-CLC DCFBR are studied. Firstly, the effects of key design parameters on the OC circulation rate and bed inventory are analyzed. Following this, the impacts of circulation rate on the interactive heat and mass transfer between two beds are examined, delineating a reasonable range for the control of autothermal CLC process (circulation rate of 50–90 kg/m2s, temperature difference of 30–90 °C, OC conversion of 0.2–0.35, and oxygen-fuel ratio of 3–6). Subsequently, this paper investigates the influences of main design parameters on the performance metrics, such as gas/solid fuel conversion, operational costs, and operational benefits. It is found that the carbon stripper significantly enhances the carbon capture efficiency of the device, provided that its separation efficiency is maintained above 70–95 %. Sensitivity analysis is employed to study the response patterns of performance metrics to changes in input parameters. Ultimately, based on these analyses, a design scheme for the 5 MWth reactor is determined, with a detailed examination of the pressure balance state of the reactor under the design conditions, and the balanced material and energy flows at the reactor inlets and outlets.

Full-length transcriptome reveals alternative splicing regulation pattern of skin color variant in red tilapia (Oreochromis spp.)

The hybrid species red tilapia (Oreochromis spp.) is favored in aquaculture for its bright color, rapid growth, and high market value. However, color variation hinders market development, which is influenced by both genetic and environmental factors. We aim to identify candidate genes and pathways related to pigmentation, uncovering the molecular basis of these color variations in red tilapia by employing third-generation full-length transcriptome sequencing combined with second-generation transcriptome analysis. Our analysis focused on three distinct phenotypic classes: whole pink, pink with black blotch, and whole black. Pigment cell and pigment composition analysis highlighted that the pigment pattern in red tilapia is primarily determined by the distribution and interaction of various pigment cells, including melanophores, xanthophores, erythrophores, and iridophores. The whole pink individuals were characterized by an absence of melanophores and a high concentration of carotenoids, while the whole black individuals exhibited active melanogenesis. Transcriptomic data indicated that genes associated with melanin synthesis (wnt, fzd7, lef, tcf7, tyrp1, oca2, pmel, bmp2, cbs) were up-regulated in whole black individuals, while genes related to carotenoid uptake and deposition (scarb1, ldlr, ttc39b, stard5, stard10, plin2, fitm2, bscl2), as well as pteridine synthesis (gch1, ptps), were more actively expressed in whole pink individuals. Retinol metabolism was identified as a mediator of the interaction between melanin synthesis and carotenoid deposition. Further, alternative splicing (AS) act as a crucial post-transcriptional mechanism regulating body coloration, beyond transcriptional differences. Analysis of AS events identifies multiple splice variants of pigment-related genes (scarb1, pax7, ctnnb1, rxrb, bscl2, gjb10, bmp4, frzb) that exhibit differential expression and splicing patterns across different color phenotypes. Notably, AS events of the scarb1 gene, related to carotenoid deposition, and the polr2d gene, associated with the transcription machinery, may significantly influence pigment deposition patterns in red tilapia. Our work not only deepens the genetic understanding of pigmentation in red tilapia but also establishes a solid foundation for improving color stability through selective breeding and genetic improvement programs across various hybrid species in aquaculture, which is crucial for marketability and consumer attraction.

Leaf carbohydrate metabolic enzyme activities are associated with salt tolerance and yield stability in the climate-resilient crop Camelina sativa

Soil salinity is an increasingly severe problem affecting plant growth and development thus posing a threat to agricultural production worldwide. Many crops currently grown are susceptible to even moderate salt stress, and crop diversification is sought to cope with increasingly challenging environmental conditions. Camelina sativa is a versatile, underutilized, low-input Brassicaceae oilseed crop valued for its high-quality seeds and its resilience to a wide range of climate conditions. In this study, the effects of salt stress on the growth and productivity of two camelina cultivars and six landraces from different geographic regions were examined. The performance of these lines was related to adjustments in their carbohydrate metabolic enzyme activity profiles in leaves as a central physiological hub. Profiling enzyme activities and their regulation in response to salt stress revealed significant genotype × treatment (G × T) interactions and allowed the identification of specific activity signatures associated with differences in yield stability in the tested lines. Yield-stable landraces showed distinct regulation patterns contrasting those of less yield-stable lines. In particular, upregulation of specific enzyme activities was associated with yield stability under salt stress. Camelina landraces may be promising resources to improve tolerance to salinity, with plasticity in carbohydrate metabolism as a contributing mechanism. Overall, these results provide a valuable basis for enzyme activity signatures as new physiological markers for supporting breeding programmes.

CzcR-dependent reduction of catalase gene expression and induction of catalase activity in Pseudomonas aeruginosa during zinc excess

BackgroundPseudomonas aeruginosa is able to survive, grow, and cause severe infections at different sites throughout the human body owing to its ability to sense diverse signals and precisely modulate target gene expression using its abundant signaling systems. Release of zinc (Zn) and hydrogen peroxide (H2O2) within the phagocyte are two major host strategies to defend against bacterial infections. It was previously shown that the response regulator CzcR controls global gene expression including catalase genes during Zn excess, but regulatory mechanisms of catalase gene expression and the role of CzcR in H2O2 tolerance remain unclear.ResultsIn the study, comparative transcriptome analysis comprehensively described the CzcR-dependent and -independent gene regulatory pattern in P. aeruginosa during Zn excess, which revealed the counteractive co-regulation of two key H2O2-detoxifying catalase genes katA and katB through CzcR-dependent and -independent pathways in response to Zn excess. Protein-DNA interaction assay demonstrated that CzcR negatively regulates the expression of catalase genes katA and katB by directly binding to their promoters. While interestingly, we further showed that CzcR positively regulates H2O2 tolerance by inducing the catalase activity during Zn excess.ConclusionThis study reported the opposite functions of CzcR in negatively regulating the expression of catalase genes katA and katB but in positively regulating the activity of catalase and H2O2 tolerance during Zn excess in P. aeruginosa.

Blood-based microRNAs as the potential biomarkers for Alzheimer's disease: evidence from a systematic review.

Alzheimer's disease (AD) is a neurodegenerative disorder that progresses over time and is identified by the development of neurofibrillary tangles and amyloid deposits in the brain. Mounting evidence has revealed that microRNAs (miRNAs) are significantly involved in AD progression, and may be used as promising biomarkers for diagnosis and prognosis. Nevertheless, the existing body of data regarding dysregulated circulating miRNAs in AD and their therapeutic applications are characterized by a lack of consistency. A comprehensive search was performed across various databases (PubMed, EMBASE, Web of Science, Scopus, Google Scholar, Cochrane, and ProQuest), starting from its inception and ending in January 2023. The criteria for inclusion consisted of original research studies written in English, which utilized Real-Time PCR to analyze miRNA expression in the blood, serum, or plasma of AD patients and healthy controls. The extracted data included the miRNA(s) investigated, dysregulation status, study type, human sample(s), and major findings. The search produced 608 records, which after careful examination, resulted in 48 suitable articles for data extraction. The research revealed a wide range of sample types used, with whole blood (39.59%) and serum (27.09%, including serum-exosome at 4.17%) emerging as the most prominent. The compiled dataset featured 4001 AD patients and 3886 healthy controls, revealing intricate regulatory patterns among 83 up-regulated (35.78%), 66 down-regulated (28.44%), and 83 not significantly altered (35.78%) miRNAs. Our results demonstrated that specific circulating miRNAs are consistently dysregulated in AD and could serve as non-intrusive biomarkers for the identification, prognosis, and prediction of cognitive decline. Further large-scale prospective studies are required to validate their clinical applications.

Nitrate assimilation pathway is impacted in young tobacco plants overexpressing a constitutively active nitrate reductase or displaying a defective CLCNt2

BackgroundWe have previously shown that the expression of a constitutively active nitrate reductase variant and the suppression of CLCNt2 gene function (belonging to the chloride channel (CLC) gene family) in field-grown tobacco reduces tobacco-specific nitrosamines (TSNA) accumulation in cured leaves and cigarette smoke. In both cases, TSNA reductions resulted from a strong diminution of free nitrate in the leaf, as nitrate is a precursor of the TSNA-producing nitrosating agents formed during tobacco curing and smoking. These nitrosating agents modify tobacco alkaloids to produce TSNAs, the most problematic of which are NNN (N-nitrosonornicotine) and NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone). The expression of a deregulated nitrate reductase enzyme (DNR) that is no longer responsive to light regulation is believed to diminish free nitrate pools by immediately channeling incoming nitrate into the nitrate assimilation pathway. The reduction in nitrate observed when the two tobacco gene copies encoding the vacuolar nitrate transporter CLCNt2 were down-regulated by RNAi-mediated suppression or knocked out using the CRISPR-Cas technology was mechanistically distinct; likely attributable to the inability of the tobacco cell to efficiently sequester nitrate into the vacuole where this metabolite is protected from further assimilation. In this study, we used transcriptomic and metabolomic analyses to compare the nitrate assimilation response in tobacco plants either expressing DNR or lacking CLCNt2 function.ResultsWhen grown in a controlled environment, both DNR and CLCNt2-KO (CLCKO) plants exhibited (1) reduced nitrate content in the leaf; (2) increased N-assimilation into the amino acids Gln and Asn; and (3) a similar pattern of differential regulation of several genes controlling stress responses, including water stress, and cell wall metabolism in comparison to wild-type plants. Differences in gene regulation were also observed between DNR and CLCKO plants, including genes encoding nitrite reductase and asparagine synthetase.ConclusionsOur data suggest that even though both DNR and CLCKO plants display common characteristics with respect to nitrate assimilation, cellular responses, water stress, and cell wall remodeling, notable differences in gene regulatory patterns between the two low nitrate plants are also observed. These findings open new avenues in using plants fixing more nitrogen into amino acids for plant improvement or nutrition perspectives.

Biomechanics of Negative-Pressure-Assisted Liposuction and Their Influence on Fat Regeneration.

Autologous fat grafting has been widely adopted in cosmetic and reconstructive procedures recently. With the emerging of negative-pressure-assisted liposuction system, the harvesting process of fat grafting is more standardized, controllable, and efficient. Each component in the system could influence the biomechanical environment of lipoaspirate. Several reviews have studied the impact of negative pressure on fat regeneration. As the initial part of the harvesting system, cannulas possess their unique mechanical parameters and their influence on lipoaspirate biomechanical characters, biological behaviors, and regeneration patterns remains unclear. Basic invivo and in vitro studies have been performed to determine the possible mechanisms. Instant invivo studies focus on adipocytes, stromal vascular fraction cells, fat particles, and growth factors, while invivo grafting experiments analyze the graft retention rate and histology. Understanding the different regeneration patterns of lipoaspirate and the mechanisms behind may facilitate the choice of harvesting cannulas in clinical practice.

A multiomics investigation into the evolution and specialized metabolisms of three Toxicodendron cultivars.

Toxicodendron species are economically and medicinally important trees because of their rich sources of natural products. We present three chromosome-level genome assemblies of Toxicodendron vernicifluum 'Dali', Toxicodendron succedaneum 'Vietnam', and T. succedaneum 'Japan', which display diverse production capacities of specialized metabolites. Genome synteny and structural variation analyses revealed large genomic differences between the two species (T. vernicifluum and T. succedaneum) but fewer differences between the two cultivars within the species. Despite no occurrence of recent whole-genome duplications, Toxicodendron showed evidence of local duplications. The genomic modules with high expression of genes encoding metabolic flux regulators and chalcone synthase-like enzymes were identified via multiomics analyses, which may be responsible for the greater urushiol accumulation in T. vernicifluum 'Dali' than in other Toxicodendron species. In addition, our analyses revealed the regulatory patterns of lipid metabolism in T. succedaneum 'Japan', which differ from those of other Toxicodendron species and may contribute to its high lipid accumulation. Furthermore, we identified the key regulatory elements of lipid metabolism at each developmental stage, which could aid in molecular breeding to improve the production of urushiol and lipids in Toxicodendron species. In summary, this study provides new insights into the genomic underpinnings of the evolution and diversity of specialized metabolic pathways in three Toxicodendron cultivars through multiomics studies.

GATv2EPI: Predicting Enhancer–Promoter Interactions with a Dynamic Graph Attention Network

Background: The enhancer–promoter interaction (EPI) is a critical component of gene regulatory networks, playing a significant role in understanding the complexity of gene expression. Traditional EPI prediction methods focus on one-to-one interactions, neglecting more complex one-to-many and many-to-many patterns. To address this gap, we utilize graph neural networks to comprehensively explore all interaction patterns between enhancers and promoters, capturing complex regulatory relationships for more accurate predictions. Methods: In this study, we introduce a novel EPI prediction framework, GATv2EPI, based on dynamic graph attention neural networks. GATv2EPI leverages epigenetic information from enhancers, promoters, and their surrounding regions and organizes interactions into a network to comprehensively explore complex EPI regulatory patterns, including one-to-one, one-to-many, and many-to-many relationships. To avoid overfitting and ensure diverse data representation, we implemented a connectivity-based sampling method for dataset partitioning, which constructs graphs for each chromosome and assigns entire connected subgraphs to training or test sets, thereby preventing information leakage and ensuring comprehensive chromosomal representation. Results: In experiments conducted on four cell lines—NHEK, IMR90, HMEC, and K562—GATv2EPI demonstrated superior EPI recognition accuracy compared to existing similar methods, with a training time improvement of 95.29% over TransEPI. Conclusions: GATv2EPI enhances EPI prediction accuracy by capturing complex topological structure information from gene regulatory networks through graph neural networks. Additionally, our results emphasize the importance of epigenetic features surrounding enhancers and promoters in EPI prediction.

Enhanced HSP70 binding to m6A-methylated RNAs facilitates cold stress adaptation in mango seedlings

BackgroundCold stress poses a serious challenge to tropical fruit production, particularly in mango. N6-methyladenosine (m6A) modifications are key regulators of gene expression, enabling plants to respond to stress responses, enhance adaptation and improve resilience to environmental challenges.ResultsIn our study, transcriptome-wide m6A methylation profiling under cold stress identified 6,499 differentially methylated m6A peaks and 2,164 differentially expressed genes (DEGs) in mango seedlings. Among these genes, six exhibited both significant increases in m6A modification levels and gene expression, 21 showed a significant increase in m6A levels but a concurrent downregulation of gene expression, and 26 showed reduced m6A levels but exhibited increased gene expression, highlighting distinct regulatory patterns in m6A-mediated gene expression control. Gene Ontology (GO) enrichment analysis revealed significant involvement in pathways such as potassium ion import, nitrate response, and transcription regulation. Notably, HSP70 was one of the upregulated genes in response to cold stress. RNA immunoprecipitation (RNA-IP) assays confirmed the association of HSP70 with m6A-modified RNAs in vivo, supporting its role in regulating stress-responsive transcripts. Additionally, immunofluorescence analysis demonstrated the formation of HSP70 condensates in plant cells under cold stress, indicating a potential mechanism for localized RNA stabilization. Fluorescence polarization assays demonstrated that HSP70 binds preferentially to m6A-modified RNAs, suggesting its role in forming protective condensates under cold conditions. This interaction between m6A modification and HSP70 points to a potential mechanism that helps stabilize stress-responsive transcripts, contributing to the plant’s enhanced cold tolerance.Conclusionsm6A modifications play a vital role in regulating gene expression under cold stress, offering new insights into mango’s stress responses and potential breeding strategies for cold tolerance.