Interaction Pathways Research Articles

Ultrafast four-wave-mixing spectroscopy with two vacuum fields and coincidence-double-heterodyne detection

In classical macroscopic ultrafast optical four-wave mixing signals, phase matching selects three classes of light–matter interaction pathways: double quantum coherence; non-rephasing; and photon-echo. Multiple pathways contribute to each of these signals. We show that a coincidence-double-heterodyne detection scheme that employs two classical and two vacuum fields can isolate a single pathway contribution to each of these signals. We further demonstrate the advantage of the proposed technique by comparing it with the classical photon-echo signal for a model Frenkel-exciton dimer.

Female-specific mechanisms of meiotic initiation and progression in mammalian oocyte development.

Meiosis is regulated in sexually dimorphic manners in mammals. In females, the commitment to and entry into meiosis are coordinated with the developmental program of oocytes. Female germ cells initiate meiosis within a short time window during the fetal period and then undergo meiotic arrest until puberty. However, the genetic mechanisms underlying the orchestration of oocyte development and meiosis to maximize the reproductive lifespan of mammalian females remain largely elusive. While meiotic initiation is regulated by a sexually common mechanism, where meiosis initiator and Stimulated by Retinoic Acid Gene 8 (STRA8) activate the meiotic genes, the female-specific mode of meiotic initiation is mediated by the interaction between retinoblastoma (RB) and STRA8. This review highlights the female-specific mechanisms of meiotic initiation and meiotic prophase progression in the context of oocyte development. Furthermore, the downstream pathway of the RB-STRA8 interaction that may regulate meiotic arrest will be discussed in the context of oocyte development, highlighting a potential genetic link between the female-specific mode of meiotic entry and meiotic arrest.

A multifunctional self-reinforced injectable hydrogel for enhancing repair of infected bone defects by simultaneously targeting macrophages, bacteria, and bone marrow stromal cells

Injectable hydrogels (IHs) have demonstrated huge potential in promoting repair of infected bone defects (IBDs), but how to endow them with desired anti-bacterial, immunoregulatory, and osteo-inductive properties as well as avoid mechanical failure during their manipulation are challenging. In this regard, we developed a multifunctional AOHA-RA/Lap nanocomposite IH for IBDs repair, which was constructed mainly through two kinds of reversible cross-links: (i) the laponite (Lap) crystals mediated electrostatic interactions; (ii) the phenylboronic acid easter bonds between the 4-aminobenzeneboronic acid grafted oxidized hyaluronic acid (AOHA) and rosmarinic acid (RA). Due to the specific structural composition, the AOHA-RA/Lap IH demonstrated superior injectability, self-recoverability, spatial adaptation, and self-reinforced mechanical properties after being injected to the bone defect site. In addition, the RA molecules could be locally released from the hydrogel following a Weibull model for over 10 days. Systematic in vitro/vivo assays proved the strong anti-bacterial activity of the hydrogel against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Moreover, its capability of inducing M2 polarization of macrophages (Mφ) and osteogenic differentiation of bone marrow stromal cells (BMSCs) was verified either, and the mechanism of the former was identified to be related to the JAK1-STAT1 and PI3K-AKT signaling pathways and that of the latter was identified to be related to the calcium signaling pathway, extracellular matrix (ECM) receptor interaction and TGF-β signaling pathway. After being implanted to a S. aureus infected rat skull defect model, the AOHA-RA/Lap IH significantly accelerated repair of IBDs without causing significant systemic toxicity. Statement of significanceRosmarinic acid and laponite were utilized to develop an injectable hydrogel, promising for accelerating repair of infected bone defects in clinic. The gelation of the hydrogel was completely driven by two kinds of reversible cross-links, which endow the hydrogel superior spatial adaption, self-recoverability, and structural stability. The as-prepared hydrogel demonstrated superior anti-bacterial/anti-biofilm activity and could induce M2 polarization of macrophages and osteogenic differentiation of BMSCs. The mechanism behind macrophages polarization was identified to be related to the JAK1-STAT1 and PI3K-AKT signaling pathways. The mechanism behind osteogenic differentiation of BMSCs was identified to be related to the ECM receptor interaction and calcium signaling/TGF-β signaling pathways.

Transcriptome Responses in Medicago sativa (Alfalfa) Associated with Regrowth Process in Different Grazing Intensities.

Medicago sativa L. (alfalfa), a perennial legume, is generally regarded as a valuable source of protein for livestock and is subjected to long and repeated grazing in natural pastures. Studying the molecular response mechanism of alfalfa under different grazing treatments is crucial for understanding its adaptive traits and is of great significance for cultivating grazing-tolerant grass. Here, we performed a transcriptomic analysis to investigate changes in the gene expression of M. sativa under three grazing intensities. In total, 4184 differentially expressed genes (DEGs) were identified among the tested grazing intensities. The analysis of gene ontology (GO) revealed that genes were primarily enriched in cells, cellular processes, metabolic processes, and binding. In addition, two pathways, the plant-pathogen interaction pathway and the plant hormone signal pathway, showed significant enrichment in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Protein kinases and transcription factors associated with hormones and plant immunity were identified. The plant immunity-related genes were more activated under high grazing treatment, while more genes related to regeneration were expressed under light grazing treatment. These results suggest that M. sativa exhibits different strategies to increase resilience and stress resistance under various grazing intensities. Our findings provide important clues and further research directions for understanding the molecular mechanisms of plant responses to grazing.

Phytol exerts sedative-like effects and modulates the diazepam and flumazenil’s action, possibly through the GABAA receptor interaction pathway

This study aimed at the evaluation of the sedative effect of phytol (PHY) with possible molecular mechanisms through in vivo and in silico studies. For this, adult male mice were randomly divided into six individual groups, namely control (vehicle), two standards (DZP: diazepam at 2 m/kg, FLU: flumazenil at 0.1 mg/kg), three test groups (PHY at 25, 50, and 75 mg/kg), and three combined groups with the DZP-2 and/or FLU-0.1 with PHY-75 mg/kg. After thirty minutes, each animal was treated with thiopental sodium (TS) at 40 mg/kg to produce sedation and observed for latency and duration of sleep up to 4 h. In silico studies were performed with the 6X3X protein of the GABAA receptor α1 and β2 subunits. The results demonstrate that PHY dose-dependently enhanced sleep duration in animals. However, it produced an insignificant sleep duration compared to the control and standard groups. It also significantly (p < 0.05) decreased the latency and increased the duration of sleep with DZP-2, while reducing these parameters with FLU-0.1. In in silico studies, DZP and FLU exhibited binding affinities with 6X3X by −6.8 and −6.9 kcal/mol, respectively, while PHY exhibited −6.9 kcal/mol. Taken together, PHY may exert a sedative-like effect in TS-induced sleeping mice and modulate the effects of DZP and FLU, possibly through interacting with the 6X3X protein of the GABAA receptor. PHY may be one of the good candidates for the management of sleep disturbances, such as insomnia.

A FRAMEWORK TO CONNECT VIRAL QUASISPECIES, MICROBIOME, AND HOST

COVID-19 is a pandemic that was detected in Wuhan, China, in 2019 and spread all around the world. COVID-19 is caused by SARS-CoV-2, which spreads through close contact. Many studies have been conducted on the transmission, virulence, and immune response of SARS-CoV-2. The intracellular mechanism of action of the virus and various host interaction pathways are also known, and there are many studies on the mutant types of the virus. Spike protein, which is one of the most important structural proteins of the virus, allows the virus to enter the cell. In this study, it has been investigated whether such an interaction occurs between Spike protein variants and host microbiota. For this purpose, the association of Sars-CoV-2 variants with different host factors that belong to the urban ecosystems has been analyzed statistically and host factors associated with different microbiota compositions were analyzed via a Bayesian Network. As a result, it is suggested that different variants of Spike protein may exist in the hosts that have dissimilar microbial compositions, and the microbiota may be a carrier that allows external factors -such as environment and human organisation- acting on hosts in the population to influence the selection of viral mutants

Transcriptome Profiling Revealed ABA Signaling Pathway-Related Genes and Major Transcription Factors Involved in the Response to Water Shock and Rehydration in Ginkgo biloba

To assess the regulatory mechanisms involved in the transcriptomic response of Ginkgo biloba to water shock and rehydration, ginkgo seedlings were subjected to dehydration for 0, 3, 6, 12, and 24 h, followed by rehydration for 12 h (Re12 h). A total of 1388, 1802, 2267, 2667, and 3352 genes were upregulated, whereas 1604, 1839, 1934, 2435, and 3035 genes were downregulated, at 3, 6, 12, 24, and Re12 h, respectively, compared to 0 h. Two KEGG pathways—the plant pathogen interaction pathway and mitogen-activated protein kinase (MAPK) signaling pathway—were enriched under water shock but not under rehydration. Moreover, plant hormone signal transduction was enriched under both water shock and rehydration. Differentially expressed genes (DEGs) involved in the ABA signaling pathway (PYR/PYLs, PP2Cs, and SnRK2s) and major differentially expressed transcription factors (MYB, bHLH, AP2/ERF, NAC, WRKY, and bZIP TFs) were identified. qRT-PCR analysis further revealed GbWRKY3 as a negative regulator of the water shock response in G. biloba. The subcellular localization results revealed GbWRKY3 as a nuclear protein. These phenotype-related DEGs, pathways, and TFs provide valuable insight into the water shock and rehydration response in G. biloba.

Molecular evolution of intestinal-type early gastric cancer according to Correa cascade.

Early screening is crucial for the prevention of intestinal-type gastric cancer. The objective of the current study was to ascertain molecular evolution of intestinal-type gastric cancer according to the Correa cascade for the precise gastric cancer screening. We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection-resected specimens from 14 Chinese patients by microdissection, and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using the whole exome sequencing, identifying multiple variants at different Correa stages. The results showed that TP53, PCLO, and PRKDC were the most frequently mutated genes in the early gastric cancer (EGC). A high frequency of TP53 alterations was found in low-grade intraepithelial neoplasia (LGIN), which further increased in high-grade intraepithelial neoplasia (HGIN) and EGC. Intestinal metaplasia (IM) had no significant correlation with EGC in terms of mutational spectra, whereas both LGIN and HGIN showed higher genomic similarities to EGC, compared with IM. Based on Jaccard similarity coefficients, three evolutionary models were further constructed, and most patients showed linear progression from LGIN to HGIN, ultimately resulting in EGC. The ECM-receptor interaction pathway was revealed to be involved in the linear evolution. Additionally, the retrospective validation study of 39 patients diagnosed with LGIN indicated that PRKDC mutations, in addition to TP53 mutations, may drive LGIN progression to HGIN or EGC. In conclusion, the current study unveils the genomic evolution across the Correa cascade of intestinal-type gastric cancer, elucidates the underlying molecular mechanisms of gastric carcinogenesis, and provides some evidence for potential personalized gastric cancer surveillance.

Theoretical investigation of potential energetic material CL-20/TNBP co-crystal explosive based on molecular dynamics method.

The exploration of CL-20 eutectic has been a subject of fervent interest within the realm of high-energy material modification. Through the utilization of density functional and molecular dynamics methods, an investigation into the characteristics of hexanitrohexaazaisowurtzitane (CL-20)/4,4',5,5'-tetranitro-2H,2'H-3,3'-bipyrazole (TNBP)within the molar ratio range of 4:1-1:4 was conducted. This inquiry encompassed the scrutiny of molecular interaction pathways, attachment force, initiating molecular distance, unified energy concentration, and physical characteristics. Furthermore, the EXPLO-5 was harnessed to prognosticate the explosion features and byproducts of unadulterated CL-20, TNBP, and CL-20/TNBP frameworks. The findings delineate a substantial differentiation in the electrostatic charge distribution on the surface between CL-20 and TNBP particles, signifying the preeminence of intermolecular interactions between disparate entities over those within similar entities, thus intimating the plausibility of the eutectic constitution. Remarkably, the identification of maximal attachment force at a molar ratio of 1:1 suggests the heightened likelihood of eutectic formation, propelled primarily by electrostatic and van der Waals forces. The resultant eutectic explosive evinces intermediate reactivity and exemplary mechanical attributes. Moreover, the detonation achievement of the eutectic with a molar proportion of 1:1 straddles that of CL-20 and TNBP, representing a new type of insensitive high-energy material. The testing method employs the Materials Studio software and utilizes the molecular dynamics (MD) method to predict the properties of CL-20/TNBP cocrystals with different ratios and crystal faces. The MD simulation time step is set to 1fs, and the total MD simulation time is 2ns. An isothermal-isobaric (NPT) ensemble is used for the 2ns MD simulation. The COMPASS force field is employed, with the temperature set to 295K. The prediction of detonation characteristics and products is conducted using the EXPLO-5 software.

A step‐by‐step progressive strategy exploring whole metabolic profiles in vivo for Polygalae Radix with/without licorice

AbstractIntroductionPolygalae Radix (PR) is known to relieve toxicity and increase efficiency in various diseases after processing. However, there were few studies for aromatic carboxylic acids (ACAs) due to the limited detection, especially for the metabolites within m/z 100–2000.ObjectivesThis study aims to elucidate the whole metabolism of PR with/without licorice (LP), focusing on metabolites within m/z 100–2000 and pharmacodynamics in vivo.Material and methodsThis study was established by the combination of multidimensional ultra‐high performance liquid chromatography coupled with a mass spectrometer (UPLC–MS) technology with protein sedimentation method to analyze metabolites in plasma, brain, colon, and stomach contents. Quantitative monitoring ACAs was enhanced with our novel stable isotope derivatization (SILD) technique. And then the pharmacokinetics (PK) study of relatively large metabolites was carried out. A targeted network pharmacology approach was established to avoid false positive results, mapping interactions relevant to Alzheimer's disease (AD), and other conditions.ResultsThe 85 polygala metabolites were qualitatively analyzed in plasma, brain, colon, and stomach contents. The 11 types of relatively large metabolites and 8 types of ACAs were quantitatively monitored. Among them, nine types of relatively large metabolites were assessed through PK studies. In targeted network pharmacology, it highlighted the significance of small molecular metabolites, including ACAs et al, which were frequently overlooked. LP may play a more key role mainly through neural active ligand‐receptor interaction, AD, and pertussis pathways. These findings have outlined a step‐by‐step strategy for in‐depth research in vivo, laying a foundation for further verification of biological function.

Abstract C081: Exploring signaling pathways of tumor-nerve interactions in breast cancer

Abstract C081: Exploring signaling pathways of tumor-nerve interactions in breast cancer

Mast cells as indicators of foreign particle biocompatibility

The key problem of introducing nanoparticles into clinical practice for diagnostic and therapeutic purposes is their safety. Connective tissue, an important component of which are mast cells, reacts actively in response to foreign particles. The reaction of mast cells can be an indicator of the biocompatibility of foreign particles. The study was conducted on male Wistar rats. Iron-carbon nanoparticles in the FeC modification stabilized in an aqueous medium using an auxiliary substance were used. Tissue examination (liver, lungs, heart, thymus, kidneys) was performed 1, 7 and 30 days after injection. After the injection of nanoparticles, the largest quantity of them is found in the liver and lungs, a smaller quantity is found in the heart, kidneys and thymus. The liver and lungs are the main organs of excretion of nanoparticles due to phagocytes. The accumulation of nanoparticles in the liver leads to the development of destructive processes and to the activation of compensatory and adaptive mechanisms in the form of cellular and intracellular regeneration of hepatocytes. In organs with a low content of nanoparticles, structural changes are poorly expressed. The mast cells of the studied organs react differently to the introduction of nanoparticles. The first to react are the mast cells of the liver by reducing the quantity and increasing degranulation. The population of lung mast cells reacts unidirectionally by sharply activating degranulation without changing the amount. An increase in the secretory activity of mast cells in the lungs and liver indicates the participation of mast cells in the regulation of particle elimination through intercellular signaling pathways of interaction with the system of phagocytic mononuclear cells. Heart mast cells are involved in maintaining the inflammatory process in the early period of the experiment, contribute to the return of myocardial parameters to homeostatic norm in the late period of the experiment. Mast cells can be considered as indicators of biocompatibility nanoparticles. The absence of an inflammatory process and the preservation of the structural and functional characteristics of the tissues where nanoparticles accumulate, as well as the reaction of mast cells in them, indicate the relative safety of the particles under study.

The prognostic value of bioinformatics analysis of ECM receptor signaling pathways and LAMB1 identification as a promising prognostic biomarker of lung adenocarcinoma.

The extracellular matrix (ECM) is a complex and dynamic network of cross-linked proteins and a fundamental building block in multicellular organisms. Our study investigates the impact of genes related to the ECM receptor interaction pathway on immune-targeted therapy and lung adenocarcinoma (LUAD) prognosis. This study obtained LUAD chip data (GSE68465, GSE31210, and GSE116959) from NCBI GEO. Moreover, the gene data associated with the ECM receptor interaction pathway was downloaded from the Molecular Signature Database. Differentially expressed genes were identified using GEO2R, followed by analyzing their correlation with immune cell infiltration. Univariate Cox regression analysis screened out ECM-related genes significantly related to the survival prognosis of LUAD patients. Additionally, Lasso regression and multivariate Cox regression analysis helped construct a prognostic model. Patients were stratified by risk score and survival analyses. The prognostic models were evaluated using receiver operating characteristic curves, and risk scores and prognosis associations were analyzed using univariate and multivariate Cox regression analyses. A core gene was selected for gene set enrichment analysis and CIBERSORT analysis to determine its function and tumor-infiltrating immune cell proportion, respectively. The results revealed that the most abundant pathways among differentially expressed genes in LUAD primarily involved the cell cycle, ECM receptor interaction, protein digestion and absorption, p53 signaling pathway, complement and coagulation cascade, and tyrosine metabolism. Two ECM-associated subtypes were identified by consensus clustering. Besides, an ECM-related prognostic model was validated to predict LUAD survival, and it was associated with the tumor immune microenvironment. Additional cross-analysis screened laminin subunit beta 1 (LAMB1) for further research. The survival time of LUAD patients with elevated LAMB1 expression was longer than those with low LAMB1 expression. Gene set enrichment analysis and CIBERSORT analyses revealed that LAMB1 expression correlated with tumor immune microenvironment. In conclusion, a prognostic model of LUAD patients depending on the ECM receptor interaction pathway was constructed. Screening out LAMB1 can become a prognostic risk factor for LUAD patients or a potential target during LUAD treatment.

Anxiolytic-like effect of daidzin possibly through GABAA receptor α2 and α3 subunits interaction pathway: In vivo and in silico studies

The soy plant-derived isoflavone daidzin (DZN) has diverse biological activities, including neuroprotective (e.g., memory-enhancing and antiepileptic) effects. This study emphasizes evaluating the anxiolytic effect of DZN on mice. Additionally, in silico investigations were also carried out to check the potential molecular mechanisms for the anxiolytic effect of DZN. For this, adult male Swiss albino mice were intraperitoneally (i.p.) treated with DZN (5, 10, and 20 mg/kg) with or without the standard GABAergic agonist drug diazepam (DZP: 2 mg/kg) and/or antagonist drug flumazenil (FLU: 0.1 mg/kg) and checked for different locomotor behaviors using various mouse models. The molecular docking study of DZN was conducted against GABAA receptor subunits. Findings suggest that DZN dose-dependently and significantly (p <0.05) increased locomotor activities such as the number of field crosses, hole crosses, swings, grooming, and light residence time while decreasing the rearing of the animals. With DZP, it significantly (p <0.05) reduced the test parameters, while altering these parameters with FLU. Our molecular docking studies demonstrate that DZN has a strong binding affinity of −7.4 and −6.9 kcal/mol for α2 and α3 subunits of the GABAA receptor, respectively, whereas the standard drugs DZP and FLU showed binding affinities between −6.0 and −6.7 kcal/mol for these subunits. Taken together, DZN augmented the anxiolytic effect of DZP while reducing the effect of FLU in mice. We suppose that DZN may show anxiolytic-like effects on Swiss mice, possibly through α2 and α3 subunits of the GABAA receptor interaction pathway.

Investigating immune dysregulation and hub genes in septic cardiomyopathy development

Septic cardiomyopathy is a life-threatening heart dysfunction caused by severe infection. Considering the complexity of pathogenesis and high mortality, the identification of efficient biomarkers are needed to guide clinical practice. Based on multimicroarray analysis, this study aimed to explore the pathogenesis of septic cardiomyopathy and the related immune landscape. The results showed that septic cardiomyopathy resulted in organ dysfunction due to extreme pro- and anti-inflammatory effects. In this process, KLRG1, PRF1, BCL6, GAB2, MMP9, IL1R1, JAK3, IL6ST, and SERPINE1 were identified as the hub genes regulating the immune landscape of septic cardiomyopathy. Nine transcription factors regulated the expression of these genes: SRF, STAT1, SP1, RELA, PPARG, NFKB1, PPARA, SMAD3, and STAT3. The hub genes activated the Th17 cell differentiation pathway, JAK-STAT signaling pathway, and cytokine‒cytokine receptor interaction pathway. These pathways were mainly involved in regulating the inflammatory response, adaptive immune response, leukocyte-mediated immunity, cytokine-mediated immunity, immune effector processes, myeloid cell differentiation, and T-helper cell differentiation. These nine hub genes could be considered biomarkers for the early prediction of septic cardiomyopathy.

Characterization of natural compounds derived from diatom C. gracilis as potential therapeutic agents: An in-silico networking and docking study

Marine diatom Chaetoceros gracilis have been known as the key player regulating the nutritional content of aquaculture species. Being able to synthesize an array of high value bioactive compounds like amino acids, lipids, terpenoids and polysaccharides, it also serves as potential therapeutic and nutraceutical agent. This in silico-based study elucidates the interactive association of different compounds, proteins and pathways of the diatom C. gracilis through an integrated network pharmacology and molecular docking approach. According to the Network analysis of the 41 compounds detected, saturated hydrocarbons, diterpenoids and phenolic compounds scored the highest degree (score > 140). These compounds were further coded for approximately 349 protein targets and almost 490 different pathways. HSP90AA1, STAT3, HIF1A, MTOR, ESR1, PIK3CA, MAPK1 and PTGS2 secured highest degree of protein-protein interaction according to STRING database. The gene enrichment analysis further revealed that these proteins were closely associated with metabolic pathways like Pathways in cancer, neuroactive ligand-receptor interaction, calcium and cAMP signaling pathway, PI3K-Akt signaling pathway, Alzheimer's disease and pathways of neurodegeneration which played an instrumental role in the metabolism of diseases and disorders like cancers of breast, prostrate, and liver, schizophrenia and other mental and hypertensive disorders. Furthermore, the molecular docking and toxicity assessment of a few novel compounds was done with mTOR and HSP90AA1 which revealed promising and stable interactions. Thus, this study provides the first in silico insight outlining the anti-cancerous and neuroprotective potential of novel bioactive compounds derived from marine diatom C.gracilis.

Prefrontal cortex astrocytes in major depressive disorder: exploring pathogenic mechanisms and potential therapeutic targets.

Major depressive disorder (MDD) is a prevalent mental health condition characterized by persistent feelings of sadness and hopelessness, affecting millions globally. The precise molecular mechanisms underlying MDD remain elusive, necessitating comprehensive investigations. Our study integrates transcriptomic analysis, functional assays, and computational modeling to explore the molecular landscape of MDD, focusing on the DLPFC. We identify key genomic alterations and co-expression modules associated with MDD, highlighting potential therapeutic targets. Functional enrichment and protein-protein interaction analyses emphasize the role of astrocytes in MDD progression. Machine learning is employed to develop a predictive model for MDD risk assessment. Single-cell and spatial transcriptomic analyses provide insights into cell type-specific expression patterns, particularly regarding astrocytes. We have identified significant genomic alterations and co-expression modules associated with MDD in the DLPFC. Key genes involved in neuroactive ligand-receptor interaction pathways, notably in astrocytes, have been highlighted. Additionally, we developed a predictive model for MDD risk assessment based on selected key genes. Single-cell and spatial transcriptomic analyses underscored the role of astrocytes in MDD. Virtual screening of compounds targeting GPR37L1, KCNJ10, and PPP1R3C proteins has identified potential therapeutic candidates. In summary, our comprehensive approach enhances the understanding of MDD's molecular underpinnings and offers promising opportunities for advancing therapeutic interventions, ultimately aiming to alleviate the burden of this debilitating mental health condition. KEY MESSAGES: Our investigation furnishes insightful revelations concerning the dysregulation of astrocyte-associated processes in MDD. We have pinpointed specific genes, namely KCNJ10, PPP1R3C, and GPR37L1, as potential candidates warranting further exploration and therapeutic intervention. We incorporate a virtual screening of small molecule compounds targeting KCNJ10, PPP1R3C, and GPR37L1, presenting a promising trajectory for drug discovery in MDD.

Multi-omics analyses reveal the mechanisms underlying the responses of Casuarina equisetifolia ssp. incana to seawater atomization and encroachment stress

Casuarina equisetifolia trees are used as windbreaks in subtropical and tropical coastal zones, while C. equisetifolia windbreak forests can be degraded by seawater atomization (SA) and seawater encroachment (SE). To investigate the mechanisms underlying the response of C. equisetifolia to SA and SE stress, the transcriptome and metabolome of C. equisetifolia seedlings treated with control, SA, and SE treatments were analyzed. We identified 737, 3232, 3138, and 3899 differentially expressed genes (SA and SE for 2 and 24 h), and 46, 66, 62, and 65 differentially accumulated metabolites (SA and SE for 12 and 24 h). The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that SA and SE stress significantly altered the expression of genes related to plant hormone signal transduction, plant–pathogen interaction, and starch and sucrose metabolism pathways. The accumulation of metabolites associated with the biosynthetic pathways of phenylpropanoid and amino acids, as well as starch and sucrose metabolism, and glycolysis/gluconeogenesis were significantly altered in C. equisetifolia subjected to SA and SE stress. In conclusion, C. equisetifolia responds to SA and SE stress by regulating plant hormone signal transduction, plant–pathogen interaction, biosynthesis of phenylpropanoid and amino acids, starch and sucrose metabolism, and glycolysis/gluconeogenesis pathways. Compared with SA stress, C. equisetifolia had a stronger perception and response to SE stress, which required more genes and metabolites to be regulated. This study enhances our understandings of how C. equisetifolia responds to two types of seawater stresses at transcriptional and metabolic levels. It also offers a theoretical framework for effective coastal vegetation management in tropical and subtropical regions.

Biopsychosocial pathways model of early childhood appetite self-regulation: Temperament as a key to modulation of interactions among systems

The widespread discrimination against individuals with obesity often stems from a simplistic perception of obesity as a mere consequence of personal choices of overeating and insufficient physical activity. This reductionist perception fails to acknowledge the complexity of the epidemic of obesity, which extends beyond diet and exercise decisions. The concept of appetite self-regulation (ASR) has been explored as a crucial element in identifying obesogenic behavioral approaches to food. Although an extensive understanding of ASR in children is essential as an early precursor and modifiable factor influencing obesity, the prevailing view of self-regulation of eating solely as a matter of cognitive and behavioral processing tends to overlook interacting systems of influences. This narrow approach attributes obesity to the lack of voluntary self-control in food consumption while neglecting to account for the biological, psychological, and social influences implicated in the developmental processes of ASR, which may further contribute to the stigmatization of obesity. The current critical analysis provides a comprehensive developmental framework that could guide future studies with testable hypotheses, outlining pathways of interactions among biopsychosocial systems, all of which contribute to the development of ASR in early childhood. Adopting developmental perspectives allows a holistic approach to investigating ASR, which accounts for intricate interactions between biological (B), psychological (P), and social (S) factors influential in the early manifestation of ASR.

Molecular biomarkers involved in the progression of gallbladder inflammatory lesions to invasive cancer: A proteomic approach.

The progression of gallbladder inflammatory lesions to invasive cancer remains poorly understood, necessitating research on biomarkers involved in this transition. This study aims to identify and validate proteins associated with this progression, offering insights into potential diagnostic biomarkers for gallbladder cancer (GBC). Label-free liquid chromatography assisted tandem mass spectrometry (LC-MS/MS) proteomics was performed on samples from 10 cases each of GBC and inflammatory lesions, with technical duplicates.Validation was conducted through the enzyme-linked immunosorbent assay (ELISA) using 80 samples (40 GBC and 40 inflammatory lesions). Bioinformatics tools analyzed protein-protein interaction (PPI) networks and pathways. Statistical correlations with clinicopathological variables were assessed. Prognostic evaluation utilized Kaplan-Meier survival analysis and Cox regression analyses. mRNA expressions were studied using real time-polymerase chain reaction (RT-PCR). Out of 5,714 proteins analyzed, 621 were differentially expressed. Three upregulated (the S100 calcium-binding protein P [S100P], polymeric immunoglobulin receptor [PIGR], and complement C1q-binding protein [C1QBP]) and two downregulated (transgelin [TAGLN] and calponin 1 [CNN1]) proteins showed significant expression. Pathway analysis implicated involvement of proteoglycans in cancer and glycosaminoglycan metabolism. Significant correlations were observed between protein concentrations and clinicopathological variables.Prognostic factors such as tumor size, lymph node metastasis, and preoperative bilirubin levels were associated with overall survival. Protein-based assays demonstrated higher resolution compared to mRNA analysis, suggesting their utility in GBC risk stratification. S100P, PIGR, C1QBP, TAGLN, and CNN1 emerge as potential protein-based biomarkers involved in the progression from gallbladder inflammatory lesions to invasive cancer. These findings hold promise for improved diagnostic and prognostic strategies in GBC management.