Biological Processes Research Articles

CYRI controls epidermal wound closure and cohesion of invasive border cell cluster in Drosophila.

Cell motility is crucial for many biological processes including morphogenesis, wound healing, and cancer invasion. The WAVE regulatory complex (WRC) is a central Arp2/3 regulator driving cell motility downstream of activation by Rac GTPase. CYFIP-related Rac1 interactor (CYRI) proteins are thought to compete with WRC for interaction with Rac1 in a feedback loop regulating lamellipodia dynamics. However, the physiological role of CYRI proteins in vivo in healthy tissues is unclear. Here, we used Drosophila as a model system to study CYRI function at the cellular and organismal levels. We found that CYRI is not only a potent WRC regulator in single macrophages that controls lamellipodial spreading but also identified CYRI as a molecular brake on the Rac-WRC-Arp2/3 pathway to slow down epidermal wound healing. In addition, we found that CYRI limits invasive border cell migration by controlling cluster cohesion and migration. Thus, our data highlight CYRI as an important regulator of cellular and epithelial tissue dynamics conserved across species.

Bioinformatic Analysis of Neuropeptide Related Genes in Patients Diagnosed with Invasive Breast Carcinoma

PurposeNeuropeptide receptors are expressed in many malignancies. Effectors involved in the action mechanisms of HCRTR1, HCRTR2, NPY4R (PPYR1) may be related to breast cancer (BC). Genes encoding these receptors and PPY and PTPN11 genes were aimed to examine via bioinformatics tools in the BRCA cohort. To our knowledge, this is the first study in which these receptor genes and PP, which have not found much research in BC, are examined together with PTPN11 and analyzed comprehensively in large patient cohorts from public databases. MethodscBioPortal was used for gene alteration analyses, GeneMania for association analyses with other genes, Kaplan-Meier Plotter for Overall Survival (OS) and Relapse Free Survival (RFS) analyses, UALCAN for methylation analyses, TIMER2.0 for expression analyses, The Human Protein Atlas database for expression validations, TIMER for immune infiltration analyses, WEKA 3.8.6 for diagnostic classification performances of the genes based on Random Forest Classifier and Enrichr-KG for Gene Ontology (GO) Biological Process (BP) and KEGG analysis. Results19 (1.9%) nucleotide changes were found in 996 cases. Missense mutation is most common. Decreased expression levels of the HCRTR1 gene were associated with shorter OS and RFS, but decreased expression levels of the PTPN11 gene were associated with longer OS and RFS. Decreased expression levels NPY4R (PPYR1) gene were associated with shorter RFS. Increased expression levels of HCRTR2 and PPY genes were associated with longer RFS. HCRTR1 and NPY4R (PPYR1) genes were statistically hypermethylated; conversely HCRTR2 and PPY genes were hypomethylated. There was no significant change in PTPN11 gene promoter methylation level. HCRTR1, NPY4R (PPYR1) and PTPN11 gene expressions were downregulated; conversely, HCRTR2 and PPY gene expressions upregulated. Weak correlations were observed between NPY4R (PPYR1) gene expression and CD4+ T Cell, Neutrophil, Dendritic Cell and between PTPN11 gene expression and CD8+ T Cell, Macrophage, Neutrophil, Dendritic Cell infiltrations. Area under the receiver operating characteristics curve values of the 10-fold cross-validation and by splitting the dataset in a ratio of 80:20 models were 0.930 and 0.963 respectively. HCRTR2 and HCRTR1 belong to regulation of cytosolic calcium ion concentration, cellular calcium ion homeostasis GO BPs. ConclusionIn BC patients, increases in HCRTR2 and PPY gene expressions could be considered as positive prognostic factors. Decreases in HCRTR1 and NPY4R (PPYR1) gene expressions could be considered as negative prognostic factors. Decreased expression of PTPN11 gene may have a positive prognostic factor. Changes in existing genes are likely to be both a biomarker and therapeutic target for BC. However, experimental and clinical studies are needed to elucidate the mechanisms underlying these neuropeptide receptors in terms of breast carcinogenesis.

Seasonal nitrogen sources and its transformation processes revealed by dual-nitrate isotopes in Xiamen Bay, China

The eutrophication load in coastal waters is gradually increasing due to excessive nitrate (NO3−) input caused by intense human activities. The tracing of NO3− sources as well as their biogeochemistry is crucial for the development of effective measures to alleviate the eutrophication load. In this study, seasonal seawater samples from Xiamen Bay were investigated to explore the sources and fates of NO3− using dual nitrate isotopes. The results indicated that the NO3− is less affected by biological processes and mainly influenced by the terrestrial sewage discharges (48%) during rainy seasons. Contrarily, as runoff input decreases and external seawater intrusion increases, the assimilation of phytoplankton dominates the process of nitrate removal during dry seasons. This study suggests that the increase in the input of terrestrial sewage nutrients is responsible for the increase in eutrophication in Xiamen Bay, providing a basis for controlling water eutrophication and regional environmental governance.

Proteomic study of cerebrospinal fluid in adult tethered cord syndrome: Chemical structure and function of apolipoprotein B.

Adult tethered cord syndrome (ATCS) has a hidden onset and delayed clinical symptoms. The purpose of this study is to identify hub proteins in the cerebrospinal fluid of ATCS patients through bioinformatics analysis, and to find significant heterogeneity in these proteins between ATCS patients and non ATCS patients (control group). Firstly, differential genes were screened based on proteomic results. Compared with the control group, 18 differentially expressed proteins were upregulated and 18 differentially expressed proteins were downregulated in the cerebrospinal fluid of ATCS patients. Then, GO, KEGG, and GESA functional enrichment analysis showed that ATCS patients were active in biological processes such as coagulation, inflammatory response, and regulation of humoral immune response, suggesting the possibility of spinal cord injury. In addition, protein network interaction analysis indicates that APOB, APOC3, FGA, and FGG are defined as hub proteins. The correlation between ATCS patients and immune characteristics was analyzed using the CIBERSORT algorithm, which may have generated a unique immune microenvironment. Finally, Western blotting was used to experimentally validate APOB, APOC3, FGA, and FGG. The results showed that APOB, APOC3, FGA, and FGG were upregulated in the cerebrospinal fluid of ATCS patients and had an important impact on the repair and functional maintenance of spinal cord injury. They can be used as key proteins for early and accurate diagnosis and treatment of spinal cord thrombosis syndrome, and suggest that the spinal cord of ATCS patients may be damaged, which can serve as potential therapeutic targets.

Recent Advancements in Bioelectronic Medicine: A Review.

Bioelectronic medicine is a multidisciplinary field that combines molecular medicine, neurology, engineering, and computer science to design devices for diagnosing and treating diseases. The advancements in bioelectronic medicine can improve the precision and personalization of illness treatment. Bioelectronic medicine can produce, suppress, and measure electrical activity in excitable tissue. Bioelectronic devices modify specific neural circuits using electrons rather than pharmaceuticals and uses of bioelectronic processes to regulate the biological processes underlining various diseases. This promotes the potential to address the underlying causes of illnesses, reduce adverse effects, and lower costs compared to conventional medication. The current review presents different important aspects of bioelectronic medicines with recent advancements. The area of bioelectronic medicine has a lot of potential for treating diseases, enabling non-invasive therapeutic intervention by regulating brain impulses. Bioelectronic medicine uses electricity to control biological processes, treat illnesses, or regain lost capability. These new classes of medicines are designed by the technological developments in the detection and regulation of electrical signaling methods in the nervous system. Peripheral nervous system regulates a wide range of processes in chronic diseases; it involves implanting small devices onto specific peripheral nerves, which read and regulate the brain signaling patterns to achieve therapeutic effects specific to the signal capacity of a particular organ. The potential for bioelectronic medicine field is vast, as it investigates for treatment of various diseases, including rheumatoid arthritis, diabetes, hypertension, paralysis, chronic illnesses, blindness, etc.

Unlocking the Microbial Potential of Intercalated Calcium-aluminum Layered Double Hydroxide-palmitic Acid

Introduction: An efficient and coherent drug delivery system is imperative in detouring a repetitive administration of high doses of the drug to achieve an effective therapeutic effect. This study, therefore, aims to synthesize the nanocomposite (CAPA) utilizing the layered double hydroxide as a drug carrier that can safeguard the medicine and improve its bioavailability while minimizing the adverse impact on the biological process. Method: The Calcium-aluminum Layered Double Hydroxide (CAL) was synthesized via the coprecipitation method followed by integrating palmitic acid (PA) drug into that host employing a similar approach. The successful intercalation was assessed utilizing X-ray diffraction (PXRD) analysis and Fourier transform infrared spectroscopy (FTIR). The characterization of the material was evaluated by using a thermogravimetric-derivative thermogravimetric analysis (TGA-DTG) and accelerated surface area and porosity (ASAP) analyzer. Result: The increment of basal spacing of CAPA (15.21Å) synthesized in this study implies the retainment of PA in the interlayer space of CAL. The FTIR spectra of CAPA, with the elimination of the nitrate ion peak at 1359.87 cm-1 and the appearance of carboxylate ion at 1643.17 cm-1, hint at the existence of PA in the host layer. The surface area of CAPA exhibited a value of 19.8 m2g-1, bigger than that of hosts, while its pore size is within the micropores range. Conclusion: The TGA analysis revealed that the thermal stability of PA was improved following the intercalation process due to the decomposition of the PA core that occurs at 260°C. The antimicrobial activity proposes that the synthesized CAPA can retain the drug's activity against S. aureus, emphasizing the ability of CAL as a potential drug delivery vehicle for PA.

The role of microRNAs regulation of endoplasmic reticulum stress in ischemia-reperfusion injury: A review.

The endoplasmic reticulum (ER) is an important organelle in eukaryotic cells, responsible for a range of biological functions such as the secretion, modification and folding of proteins, maintaining Ca2+ homeostasis and the synthesis of steroids/lipids, secreted proteins and membrane proteins. When cells are affected by internal or external factors, including abnormal energy metabolism, disrupted Ca2+ balance, altered glycosylation, drug toxicity, and so on, the unfolded or misfolded proteins accumulate in the ER, leading to the unfolded protein response (UPR) and ER stress. The abnormal ER stress has been reported to be involved in various pathological processes. MicroRNAs (miRNAs) are non-coding RNAs with the length of approximately 19-25 nucleotides. They control the expression of multiple genes through posttranscriptional gene silencing in eukaryotes or some viruses. Increasing evidence indicates that miRNAs are involved in various cellular functions and biological processes, such as cell proliferation and differentiation, growth and development, and metabolic homeostasis. Hence, miRNAs participate in multiple pathological processes. Recently, many studies have shown that miRNAs play an important role by regulating ER stress in ischemia-reperfusion (I/R) injury, but the relevant mechanisms are not fully understood. In this review, we reviewed the current understanding of ER stress, as well as the biogenesis and function of miRNAs, and focused on the role of miRNAs regulation of ER stress in I/R injury, with the aim of providing new targets for the treatment of I/R injury.

TAT-PPA1 protects against oxidative stress-induced loss of dopaminergic neurons.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) of the midbrain, resulting in severe motor impairments. Inorganic pyrophosphatase 1 (PPA1) plays a key role in various biological processes, and this study introduces a cell-penetrating PPA1 fusion protein (TAT-PPA1) to explore its transduction into cells and brain tissues. TAT-PPA1 effectively penetrates SH-SY5Y cells and the SN region of PD animal models without toxicity, exhibiting protective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-)-induced cell death. TAT-PPA1 revealed an inhibitory influence on the MAPK signaling pathway and MPTP-induced reactive oxygen species (ROS) production. TAT-PPA1 suppresses JNK, AKT, p53, ERK, and p38 phosphorylation, showcasing its multifaceted role in cell survival pathways. In the MPTP-induced PD animal model, TAT-PPA1 prevents dopaminergic cell death and enhances motor function. This study shows that TAT-PPA1 protects against oxidative stress and cell death in neurodegenerative diseases, suggesting potential as a PD treatment.

Genome-wide identification and expression analysis of genes encoding late embryogenesis proteins in Cicer arietinum

Late embryogenesis abundant (LEA) proteins play defensive roles during seed maturation and seed germination processes. However, there is no such investigation was carried out in chickpea. In present study, genome wide identification and characterization of LEA encoding genes has been investigated, and identified 65 and 74 LEA encoding genes in desi and kabuli cultivar of chickpea, respectively. All these genes have been classified into eight subfamilies on the bases of their phylogenetic analysis and conserved domain. Maximum members of LEA encoding genes were found to be a part of the LEA_2 gene family. The analysis of physicochemical properties of LEAs was also conducted. LEA encoding genes have been found to be located in all chromosomes (8 chr) of chickpea and identified as involved in response to stimulus, biological processes, molecular functions and cellular components based upon gene ontology analysis. Gene expression analysis of randomly selected 8 LEA encoding genes has been carried out during different seed developmental stages which revealed the higher expression of LEA encoding genes during later stage of seed development in chickpea and proved their potential role in desiccation process during seed maturation. During seed germination, expression analysis of LEA encoding genes was found to be higher during the initial stages of seed germination. In conclusion, this work highlights the genome wide identification and characterization of LEA encoding genes in chickpea and proposed potential roles during seed developmental processes. This information could also be useful as a reference investigation for molecular breeding of chickpea for recalcitrant behaviour of seed.

Comprehensive analysis of the oligopeptide transporter gene family in maize: Genome-wide identification, structural characterization, and stress-responsive expression

Oligopeptide transporter (OPT) proteins are integral proteins in cell membranes that perform a crucial role in cellular metal homeostasis, mineral uptake, transport of small peptides and abiotic stress tolerance. Hence, in-depth evolutionary, structural, molecular and expression analysis could guide in exploring the mechanism of how these transporters contribute to nutrient balance and abiotic stress tolerance in maize. Following a series of bioinformatic analyses, eight OPTs in maize were identified. These transporters showed significant variations in molecular weight, and have one to five introns, 11 to 15 motifs, 11 to 18 transmembrane domains, multiple beta-strands, multiple alpha and transmembrane helices. ZmOPT1, 5, and 6 are plasma membranes and the rest are endoplasmic reticulum localized. All ZmOPTs are distributed in six different chromosomes having significant phytohormone-responsive cis-elements might be due to their great roles in hormonal regulation in maize. The significant transport activity of these transporters plays a great role in biological processes, cellular components and molecular functions in maize during gene ontology analysis. Co-expression of five genes among eight OPTs with 56 genes might be due to their great role in regulating other genes in multiple signaling pathways or vice-versa. Significant tissue-specific and drought, salinity, nitrogen starvation, and heat stress induced in silico expression following real time PCR validation of ZmOPT1, 7, and 8 genes might guide to elucidate the potential roles of these transporters in specific tissues and abiotic stress tolerance. Hence, the findings of the research might guide plant biologists to develop new varieties of maize having higher efficiency of peptide and metal ion transport, balance, and abiotic stress tolerance. Findings of these structural and expression analyzes might guide the plant biologist for single transgenesis, or developing and transforming programming-based synthetic genetic circuits in maize for advancing research in peptide transport, metal hemostasis, and increasing abiotic stress tolerance in maize.

An overview of the relationship between inflammation and cognitive function in humans, molecular pathways and the impact of nutraceuticals

Inflammation has been associated with cognitive decline, whether in the peripheral or central nervous systems. The primary mechanism involves the response of microglia, an immune cell in the brain, which generates pro-inflammatory mediators such as cytokines, chemokines, and adhesion molecules. The excessive production of pro-inflammatory mediators may accelerate the damage to neurons, contributing to the development of neurodegenerative diseases such as Alzheimer’s disease, mild cognitive impairment, and vascular dementia, as well as a general decline in cognitive function. Various studies have supported the correlation between elevated pro-inflammatory mediators and a decline in cognitive function, particularly in aging and age-related neurodegenerative diseases. Moreover, this association has also been observed in other inflammatory-related conditions, including post-operative cognitive impairment, diabetes, stroke, obesity, and cancer. However, the interaction between inflammatory processes and cognitive function in humans remains unclear and varies according to different health conditions. Therefore, this review aims to consolidate and evaluate the available evidence from original studies as well as meta-analyses in order to provide a greater understanding of the inflammatory process in connection with cognitive function in humans. Furthermore, relevant biological cellular processes, putative inflammatory biomarkers, and the role of nutraceuticals on the interaction between cognitive performance and inflammatory status are outlined.

Application of selected indicators to assess contamination of municipal landfill leachate and its impact on groundwater

Leachate formation is one of the most important factors taken into account during the operation and long-term management of municipal waste landfills. Systematic assessment of groundwater and leachate contamination may be useful in selecting the appropriate method of leachate management or treatment processes. The use of indicators to quantify the contamination potential of leachate and groundwater in the vicinity of MSW could help landfill managers assess their quality. Therefore, the aim of the study was to assess the representativeness of selected indicator methods for analyzing the temporal variability of leachate and groundwater properties in the vicinity of two municipal waste landfills in a Central European country (Poland). The leachate pollution index (LPI), sub-LPI and adjusted leachate pollution index (r-LPI) were used to assess the quality of leachate water, while the landfill water pollution index (LWPI) was used to assess the variability of groundwater quality. The results confirmed that LWPI is an effective method for assessing the quality of groundwater in the vicinity of municipal waste landfills. The obtained results confirm the negative impact of landfills, despite the insulation used. LWPI showed poor quality of groundwater and visible impact of the landfill (landfill W, average LWPI - 2.34) and moderately polluted waters and minor impact of the landfill (landfill S, average LWPI - 1.37). In most cases, it was observed that two parameters, EC and TOC, are the main factors contributing to the deterioration of groundwater quality. The sub-LPI analysis showed that leachates from both landfills have a very low content of heavy metals, so they should not have a negative impact on the biological treatment process. The obtained r-LPI values were in all cases higher than the calculated LPI values. For landfill S, the average r-LPI was 26.3 (Z-1) and 25.7 (Z-2). However, the average LPI was 13.5 (Z-1) and 13.2 (Z-2). For landfill W, the average r-LPI was 14.6 and the average LPI was 11.4. Analysis conducted on multi-year leachate and groundwater data using specific indicators can help managers better understand the impact of MSW on surrounding areas and help avoid potential operational problems in the future.

Icelandic glacial dissolved organic carbon fluxes, composition and variability - relevance for the global glacial carbon budget

Despite their relatively large size, organic carbon (OC) fluxes from Icelandic glaciers have not been explicitly considered in current global glacial OC flux calculations. Most global glacial OC estimates are based on limited individual flux estimates, which show considerable spatial differences, are often based on melt season fluxes, and rarely account for seasonal and diurnal variability of glacial dissolved organic matter (DOM). Using an annual dataset of 25 Icelandic glaciers (and their glacial streams) we investigate DOM concentration and composition, calculating an estimate for downstream OC fluxes from Icelandic glaciers, considering diurnal and seasonal variability. DOM source and composition distinctly changed from a terrestrial character toward a more proteinaceous character as melt increased, both on a seasonal and diurnal basis, likely reflecting the flow path of the meltwater. While DOC concentration did not change on a diurnal basis, DOM composition was more labile in the afternoons, possibly indicating photochemical or biological transformation processes. Overall, the glacial streams predominantly acted as CO2 sinks. However, higher DOC concentrations, along with contributions of more proteinaceous DOM in proglacial streams, led to a decrease in the uptake potential for CO2. Finally, we estimated an export flux of 0.0026 ± 0.0029 Gg C yr−1 km−2 of DOC, and 0.011 ± 0.007 Tg C yr−1 km−2 of POC, from Icelandic glaciers. We reveal larger than previously assumed DOC and POC fluxes from Icelandic glaciers, with higher-than-global-average areal fluxes (~3 % and 9 % of global glacial C flux respectively). Our findings underscore the importance of revising current global estimates to include the not-fully-accounted-for contribution of Icelandic, and other glaciers. This is particularly important considering ongoing climatic changes will likely affect glacial meltwater discharge and sources, leading to altered DOM composition and DOC concentration, having potentially considerable consequences for glacial OC export and CO2 uptake potentials of glacial streams.

Short-term continuous cropping leads to a decline in rhizosphere soil fertility by modulating the perilla root exudates

Continuous cropping obstacles are a prevalent issue in agricultural production worldwide. However, the key factors leading to these obstacles differ among various crops. This study utilized high-throughput sequencing and metabolomics to assess the community structure of microbes and the types and abundance of metabolites in rhizosphere soil after different continuous cropping years of Perilla frutescens L. Britt. (perilla). The results indicate that differential metabolites in soils of varying continuous cropping years are primarily associated with pathways for cellular lipid formation, oxidative stress responses, and energy metabolism. These findings suggest that the changes in soil composition over time are linked to specific biological processes related to lipid formation, oxidative stress, and energy metabolism. The relative abundance of beneficial bacteria in the soil, such as Sphingomonas, Gemmatimonas, and Blastococcus, decreased significantly (p < 0.05), while harmful fungi, such as Neocosmospora and Didymella, increased in response to the increase in continuous cropping years (p < 0.05). The symbiotic network between bacteria and fungi has become less dense and stable after continuous cropping. Enzymatic activities in rhizosphere soil decreased significantly (p < 0.05). Soil organic matter, total nitrogen, total phosphorus, total potassium, available phosphorus, and available potassium declined significantly (p < 0.05). Pearson correlation analysis identified 10 differential secondary metabolites that were closely related to the relative abundance of key microorganisms. Among them, cinnamic acid and flavonoid compounds are key factors leading to changes in microbial diversity, and they can regulate the microorganisms-soil- plants interactions. In summary, this study provides a novel scientific explanation for how continuous cropping can reduce soil fertility and a theoretical basis for subsequent cultivation strategies of perilla.

Siling Decoction Ameliorates Adenine-Induced Renal Fibrosis in Rats by the AKT/IKKβ/NFκB Signaling Pathway

ObjectiveInvestigating how Siling decoction (SLD) mitigates fibrosis in rats with chronic kidney disease CKD (chronic kidney disease) through network pharmacology analysis and experimental verification. MethodsInitially, the primary active components and their target actions of SLD (Fuling, Zhuling, Zexie, and Baizhu) were identified by the TCMSP database and liquid chromatography mass spectrometry (LC-MS). Treatment targets for renal fibrosis were screened through databases such as GeneCard, OMIM, PharmGkb, and GEO. Subsequently, a drug-disease-target network was constructed and subjected to PPI analysis. Intersecting targets underwent GO and KEGG pathway enrichment analyses. Renal fibrosis model was induced by adenine gavage, then treat with SLD. Masson, Sirius red, immunohistochemistry, and Western blot were used to detect renal function and fibrosis-related indicators. The mechanism was further validated in vitro experiments. ResultsNetwork pharmacology analysis identified 100 common targets associated with the active components of SLD, including core genes such as AKT1 and CCND1. GO enrichment analysis revealed that the top three biological processes impacted include response to xenobiotic stimulus, response to nutrient levels and response to oxidative stress. These processes involved cellular components such as membrane raft, membrane microdomain and synaptic membrane, with molecular functions predominantly associated with ubiquitin-like protein ligase binding, ubiquitin protein ligase binding, DNA-binding transcription factor binding, and RNA polymerase II-specific DNA binding transcription factor binding. KEGG pathway enrichment analysis indicated potential involvement of pathways like Lipid and atherosclerosis, PI3K-AKT signaling pathway, and prostate cancer are likely involved in the anti-fibrotic effect of SLD. Notably, the highlighted was the AKT/IKKβ/NFκB signaling pathway as a key mechanism. These findings were further confirmed in vivo and in vitro. ConclusionThe SLD effectively ameliorates adenine-induced chronic kidney disease fibrosis in rats, potentially by inhibiting the AKT/IKKβ/NFκB signaling pathway.

Brassica Microgreens as Novel Sources of Cardiovascular bio-compounds: insights into hypertension management via metabolomics

Hypertension remains a prevalent global health issue, with numerous strategies aimed at mitigating its widespread impact. Recently, there has been growing interest in developing nutraceuticals derived from natural bioactive compounds with cardio-protective properties. Brassica microgreens—young, edible seedlings—are rich sources of phytochemicals, such as glucosinolates, which modulate the biological processes influencing CVDs. However, the underlying pathogenesis pathways are not yet fully understood. This study aims to investigate the effects of phytochemicals from brassica microgreens (MG) on both hypertension modulation and metabolic pathways. To achieve this, a dietary intervention using brassica microgreens was conducted on spontaneously hypertensive rats (SHR) and normotensive ones (WKY). The treatment involved a diet with 5% w/w of lyophilized brassica MG incorporated into the standard food (ad-libitum) of the animals, for either 24 h (acute treatment) or 4 weeks (chronic treatment). Systolic blood pressure and different oxidative/inflammatory markers were evaluated at the beginning and end of the treatment. Urine and plasma samples were collected post-treatment and analyzed using untargeted metabolomic approaches based on UPLC-ESI-QTOF-MS to identify the metabolic pathways alterations induced by MG intake. Chronic treatment positively influenced hemodynamic parameters, which correlated with improvements in oxidative-inflammatory marker values. Metabolomics analysis provided a robust molecular characterization of normotensive, hypertensive, treated, and untreated groups with MG. Potential metabolites associated with brassica consumption, particularly cauliflower, were identified, such as sinigrin-derived and indolic metabolites, which may be linked to hypertension modulation. This study also highlighted the impact of lipid metabolism on the hypertensive phenotype, offering new insights into the physio-pathological metabolic pathways. From this, metabolomics shows potential to emerge as a novel tool for theragnosis in arterial hypertension. Moreover, the consumption of brassica microgreens may be a valuable addition to a healthy lifestyle, potentially offering a dietary strategy for cardiovascular risk prevention and management.

Prognostic Value and Therapeutic Significance of CCL Chemokines in Gastric Cancer.

Gastric cancer is one of the most common malignant tumours of the gastrointestinal tract, which has a significant negative impact on human health. CCL chemokines play important roles in a variety of tumor microenvironments; nevertheless, gastric cancer has surprisingly limited associations with CCL chemokines. In our study, we comprehensively utilized bioinformatics analysis tools and databases such as cBioPortal, UALCAN, GEPIA, GeneMANIA, STRING, and TRRUST to clarify the clinical significance and biology function of CCL chemokines in gastric cancer. The mRNA expression levels of CCL1/3/4/5/7/8/14/15/18/20/21/22/26 were up-regulated, while the mRNA expression levels of CCL2/11/13/16/17/19/23/24/25/28 were down-regulated. The chemokine significantly associated with the pathological stage of gastric cancer is CCL2/11/19/21. In gastric cancer, the expression level of CCL chemokines was not associated with disease-free survival, but low expression of CCL14 was significantly associated with longer overall survival. Therein, associated with the regulation of CCL chemokines are only 10 transcription factors (RELA, NFKB1, STAT6, IRF3, REL, SPI1, STAT1, STAT3, JUN and SP1). The major biological process and functional enrichment of CCL chemokines are to induce cell-directed migration. These results may indicate that CCL chemokines may be immunotherapeutic targets and promising prognostic biomarkers for gastric cancer.

Advanced growing-season precipitation peak promotes soil nitrogen mineralization in a semi-arid grassland

Soil nitrogen (N) mineralization is a key process of global N cycling and profoundly regulates plant productivity and soil nutrient pools in the terrestrial biosphere. However, its response to seasonal precipitation redistribution remains largely unexplored. As part of a nine-year (2013–2021) field experiment that simulated advanced and/or delayed growing-season precipitation peaks in a semi-arid grassland on the Mongolian Plateau, this study was conducted for two years (2020–2021) in situ to examine the effects of changing precipitation distributions in the growing seasons on soil mineralization processes. The results showed that advanced precipitation peak (AP) increased soil ammonification (Ramm), nitrification (Rnit), and net mineralization rates (Rmin) by 45.8 %, 26.0 %, and 84.4 %, respectively (all p < 0.001), whereas delayed precipitation peak (DP) enhanced Ramm by 55.7 % (p < 0.001) only, but did not change Rnit or Rmin. The elevated soil N mineralization under the AP treatment could be primarily attributed to the increased soil water availability and microbial biomass N in the early growing season, both of which play essential roles in meditating biological processes in the soil. In addition, the large consumption of soil inorganic N in the early and middle growing seasons may lead to an enhancement of ammonification in September. These observations suggest that advanced rather than delayed growing-season precipitation peak has a stronger influence on soil N dynamics in the growing seasons. Moreover, our findings highlight the positive contributions of altered N transformations to soil respiration and net ecosystem productivity under the AP treatment and imply the crucial roles of intra-annual redistribution of precipitation in regulating ecosystem nutrient and carbon cycling in semi-arid regions.

Deciphering the Molecular Landscape of Dengue Infection: Insights from gene expression profiling and Protein Interactions

Dengue fever (DF) is a viral infection recognized as one of the most rapidly spreading vector-borne diseases among humans. However, the molecular mechanisms underlying disease aetiology and potential therapeutic targets remain unclear. This study presents a thorough examination of differentially expressed genes (DEGs) throughout the spectrum of Dengue infection stages, offering insights into disease mechanisms and therapeutic targets. Through meticulous analysis of DEGs within each infection stage, key genes pertinent to disease progression are identified, highlighting their roles in host-virus interactions. Noteworthy discoveries include the upregulation of IFI27 and USP18 in mild infection, suggesting involvement in viral replication inhibition and host defence, alongside the downregulation of CMTM2, indicating alterations in immune-related functions. Similarly, in severe infection, upregulated genes like IGHV1-69 are linked to illness severity, while downregulated IL-13RA1 signifies disruptions in cytokine signaling. Overlapping DEGs between infection groups unveil shared biological processes, further elucidated through functional enrichment analysis, showcasing coordinated regulation of cellular processes and pathways. Integration of Dengue virus and human interaction network analysis reveals crucial insights into the mechanisms by which the virus mediates the disease progression and offers potential therapeutic opportunities for disease management.

The sensor protein AaSho1 regulates infection structures differentiation, osmotic stress tolerance and virulence via MAPK module AaSte11-AaPbs2-AaHog1 in Alternaria alternata

The high-osmolarity-sensitive protein Sho1 functions as a key membrane receptor in phytopathogenic fungi, which can sense and respond to external stimuli or stresses, and synergistically regulate diverse fungal biological processes through cellular signaling pathways. In this study, we investigated the biological functions of AaSho1 in Alternaria alternata, the causal agent of pear black spot. Targeted gene deletion revealed that AaSho1 is essential for infection structure differentiation, response to external stresses and synthesis of secondary metabolites. Compared to the wild-type (WT), the ∆AaSho1 mutant strain showed no significant difference in colony growth, morphology, conidial production and biomass accumulation. However, the mutant strain exhibited significantly reduced levels of melanin production, cellulase (CL) and ploygalacturonase (PG) activities, virulence, resistance to various exogenous stresses. Moreover, the appressorium and infection hyphae formation rates of the ∆AaSho1 mutant strain were significantly inhibited. RNA-Seq results showed that there were four branches including pheromone, cell wall stress, high osmolarity and starvation in the Mitogen-activated Protein Kinase (MAPK) cascade pathway. Furthermore, yeast two-hybrid experiments showed that AaSho1 activates the MAPK pathway via AaSte11-AaPbs2-AaHog1. These results suggest that AaSho1 of A. alternata is essential for fungal development, pathogenesis and osmotic stress response by activating the MAPK cascade pathway via Sho1-Ste11-Pbs2-Hog1.