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The thermo-solvent-tolerant lipase-producing actinomycete, Streptomyces sp. A3301, was utilized as a biocatalyst for poly (lactic acid) or PLA polymerization. The study aimed to optimize lipase immobilization conditions, characterize the immobilized lipase and apply it for PLA polymerization. The results showed using a sponge as the immobilizing matrix was the most effective method, achieving a maximum activity of 277 U/g of sponge. The optimal sponge size was determined to be 0.125 cm³ and pre-soaking the sponge in 0.1 M phosphate buffer at pH 7.0 for 24 h before use proved advantageous. Immobilization significantly enhanced the thermo-stability of the enzyme, with a relative activity ranging from 140 to 190% within the temperature range of 30 to 60 °C. In contrast, the crude lipase exhibited thermo-stability only within the 30 - 50 °C range. The immobilized lipase demonstrated stability under PLA polymerization conditions, which involved a reaction mixture containing toluene and lactic acid and performed at 60 °C for 8 h. The immobilized lipase maintained its activity under this condition for 5 h, retaining a relative activity of 230%, which was 1.2 times higher than the activity of the crude lipase. When the immobilized lipase was used in PLA polymerization, the resulting PLA product exhibited a molecular weight of 5,333 ± 0.02 Da, and the degree of polymerization was approximately 72. These findings underscore the potential of the immobilization technique to enhance lipase activity for PLA polymerization. [ABSTRACT FROM AUTHOR]

Introduction: Early-onset Alzheimer's disease (EOAD) is sporadic, highly heterogeneous, and its underlying pathogenic mechanisms remain largely elusive. Proteomics research aims to uncover the biological processes and key proteins involved in disease progression. However, no proteomic studies to date have specifically focused on EOAD brain tissue. Method: We integrated proteomic data from brain tissues of two Alzheimer's disease (AD) cohorts and constructed a protein co-expression network using weighted gene co-expression network analysis (WGCNA). We identified modules associated with EOAD, conducted functional enrichment analysis to understand the biological processes involved in EOAD, and pinpointed potential key proteins within the core modules most closely linked to AD pathology. Results: In this study, we identified a total of 2,749 proteins associated with EOAD. Through protein co-expression network analysis, we discovered 41 distinct co-expression modules. Notably, the proteins within the core module most closely linked to AD pathology were significantly enriched in neutrophil degranulation. Additionally, we identified two potential key proteins within this core module that have not been previously reported in AD and validated their expression levels in 5xFAD mice. Conclusion: In summary, through a protein co-expression network analysis, we identified EOAD-related biological processes and molecular pathways, and screened and validated two key proteins, ERBB2IP and LSP1. These proteins may play an important role in the progression of EOAD, suggesting they could serve as potential therapeutic targets for the disease. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease, mainly characterized by perifibrocartilage osteitis of the sacroiliac joints and spinal enthesitis. To date, the exact pathogenesis of AS remains elusive. It is generally believed that AS is a multifactorial disease involving genetics, infection, environment, and immunity. Among them, genetic factors are the primary determinants of disease risk and severity. In recent years, epigenetic mechanisms such as DNA methylation have been extensively surveyed with respect to the pathogenesis of AS. This review summarizes the latest research progress of methylation in AS, from whole-genome sequencing to individual differentially methylated gene. And finally, the role of methylase in AS inflammation, autophagy, and osteogenic differentiation was explored. In summary, the results of this review attempt to explain the role of methylation in the occurrence and development of AS and point out the shortcomings of current methylation research, providing directions for subsequent methylation research in AS. [ABSTRACT FROM AUTHOR]

Background Although numerous neuroimaging studies have depicted neural alterations in individuals with obsessive–compulsive disorder (OCD), a psychiatric disorder characterized by intrusive cognitions and repetitive behaviors, the molecular mechanisms connecting brain structural changes and gene expression remain poorly understood. Methods This study combined the Allen Human Brain Atlas dataset with neuroimaging data from the Meta-Analysis (ENIGMA) consortium and independent cohorts. Later, partial least squares regression and enrichment analysis were performed to probe the correlation between transcription and cortical thickness variation among adults with OCD. Results The cortical map of case-control differences in cortical thickness was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms preferentially expressed across different cell types and cortical layers. These genes were specifically expressed in brain tissue, spanning all cortical developmental stages. Protein–protein interaction analysis revealed that these genes coded a network of proteins encompassing various highly interactive hubs. Conclusions The study findings bridge the gap between neural structure and transcriptome data in OCD, fostering an integrative understanding of the potential biological mechanisms. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are typically small, endogenous, non-coding RNAs molecules that regulate gene expression at post-transcriptional level by mRNA degradation or translational repression. They are composed of 18-26 nucleotides and are conserved during evolution for the development of new miRNAs in a variety of plants. Sugarcane (Saccharum officinarum) is generally a valuable food and forage crop grown all over the world. Until now, different sugarcane miRNAs have been characterized for plant development and stress responses. In this research, 50 unique conserved sugarcane miRNAs from 44 different miRNA families have been predicted using a variety of genomics-based tools. The predicted sugarcane miRNAs were validated using a set of 15 randomly chosen primers and RT-PCR. Stem loop secondary structures are created using MFOLD tool. The psRNA-Target algorithm identified 7,976 various protein targets of sof-miRNAs including 55 specific GO terms. They have significant targets in biological, cellular, and molecular functions. Moreover, the sof-miR5205a regulates sulfur compound biosynthetic process and 9653a directs ubiquitin-dependent protein catabolic process. Consequently, the RNA binding and thylakoid membrane are controlled by sof-miR9657b and 2091, respectively. As a result, the outcomes of the novel sugarcane miRNAs target a variety of substantial genes that aid in controlling the environment for sugarcane to produce a higher quality crop. [ABSTRACT FROM AUTHOR]

Drought poses a significant threat to global food security, particularly impacting crops like oil palm. Selecting genes for genome editing to enhance drought tolerance presents formidable challenges. To ensure that the target gene is chosen correctly and results in the desired character, a pilot study is necessary to determine the target gene for knockout. Two genes drought-related, AtBRL3 and AtOST2, were scrutinized in this context. Aligned with the Elaeis guineensis genome, their neighbouring proteins and gene ontology were analysed to identify potential targets for genome editing. AtBRL3, identified as BRL1 (XP_010913986.1) in E. guineensis, exhibited 58.48% identity and 100% coverage. It interacts with 12 nodes, including BIR1, BRI1, and AT2G20050, crucial for signalling pathways and cellular responses. Molecular function analysis revealed kinase activity. AtOST2 showed high similarity to plasma membrane ATPase/HA1 (XP_010913679.1) in E. guineensis, with 87.46% identity and 100% query cover. It correlated with 14 genes associated with ABA stimulus, stomatal movement, and hormone response. EgBRL1 and EgHA1, resembling AtBRL3 and AtOST2, respectively, emerge as promising targets for developing drought-tolerant oil palm cultivars through gene editing. Nonetheless, further validation through in vitro gRNA target selection and in vivo conversion of OST2/BRL3-containing plasmids in oil palm calluses is indispensable to demonstrate their efficacy in conferring novel drought resistance traits. [ABSTRACT FROM AUTHOR]

Histone methylation can affect chromosome structure and binding to other proteins, depending on the type of amino acid being modified and the number of methyl groups added, this modification may promote transcription of genes (H3K4me2, H3K4me3, and H3K79me3) or reduce transcription of genes (H3K9me2, H3K9me3, H3K27me2, H3K27me3, and H4K20me3). In addition, advances in tumor immunotherapy have shown that histone methylation as a type of protein post-translational modification is also involved in the proliferation, activation and metabolic reprogramming of immune cells in the tumor microenvironment. These post-translational modifications of proteins play a crucial role in regulating immune escape from tumors and immunotherapy. Lysine methyltransferases are important components of the post-translational histone methylation modification pathway. Lysine methyltransferase 2C (KMT2C), also known as MLL3, is a member of the lysine methyltransferase family, which mediates the methylation modification of histone 3 lysine 4 (H3K4), participates in the methylation of many histone proteins, and regulates a number of signaling pathways such as EMT, p53, Myc, DNA damage repair and other pathways. Studies of KMT2C have found that it is aberrantly expressed in many diseases, mainly tumors and hematological disorders. It can also inhibit the onset and progression of these diseases. Therefore, KMT2C may serve as a promising target for tumor immunotherapy for certain diseases. Here, we provide an overview of the structure of KMT2C, disease mechanisms, and diseases associated with KMT2C, and discuss related challenges. [ABSTRACT FROM AUTHOR]

The nutritional composition of honey is determined by environmental conditions, and botanical and geographical origin. In addition to carbohydrates, honey also contain pollen grains, proteins, free amino acids, and minerals. Although the content of proteins in honey is low, they are an important component that confirms the authenticity and quality of honey; therefore, they became a popular study object. The aim of the study was to evaluate protein content and composition of monofloral red clover and rapeseed honey collected from five different districts of Lithuania. Forty-eight proteins were identified in five different origin honey samples by liquid chromatography. The number of red clover proteins identified in individual honey samples in monofloral red clover honey C3 was 39 in polyfloral honey S22–36, while in monofloral rapeseed honey S5, S15, and S23 there was 33, 32, and 40 respectively. Aphids' proteins and lactic acid bacteria were identified in all honey samples tested. The linear relationship and the strongest correlation coefficient (r = 0.97) were determined between the content of Apilactobacillus kunkeei and Apilactobacillus apinorum, as well as between the number of faba bean (Vicia faba) pollen and lactic acid bacteria (r = 0.943). The data show a strong correlation coefficient between the amount of lactic acid and aphid protein number (r = 0.693). More studies are needed to evaluate the relationship between the pollination efficiency of red clover by bees and the multiplicity of red clover proteins in honey protein, as well as microbiota diversity and the influence of nature or plant diversity on the occurrence of microbiota in honey. [ABSTRACT FROM AUTHOR]

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Chloro-haloacetonitrile (Cl-HAN), belongs to a group of nitrogenous disinfection by-products (N-DBPs) found in surface water, and are known to pose a major risk to the safety of human drinking water. However, the exact biological toxicity mechanism and the extent of the stress response caused by Cl-HAN remain unclear, resulting in a lack of effective measures to control its presence. Thus, the quantitative toxicological genomics and bioinformatics methods were applied to explore the effects of three chloro-haloacetonitriles (Cl-HANs) on the transcription of fusion genes under varying concentrations of stress in E. coli over 2-hour period. The initial stress response and their toxic mechanism were analyzed. The study also identified the molecular toxicity endpoint, and the core genes that are responsible for the specific toxicity of different Cl-HANs. Cl-HANs exhibited concentration-dependent characteristics of toxic effects, and caused changes in gene expression related oxidative and membrane stress. The stress response results showed that dichloroacetonitrile (dCAN) still caused significant DNA damage under the lowest concentration stress. Chloroacetonitrile (CAN) and trichloroacetonitrile (tCAN) exhibited lower genetic toxicity levels at 513 μg/L and 10.7 μg/L, respectively. The toxic effects of tCAN were widespread. And there was a good correlation between the molecular endpoint (EC-TELI1.5) and the phenotypic endpoint (LD50) with rp=-0.8634 (P=0.0593). In all concentrations of stress in CAN, dCAN, and tCAN, the number of overexpressed genes shared was 15, 2, and 14, respectively. Furthermore, bioinformatics analysis demonstrated that Cl-HANs affected genes associated with general stress pathways, such as cell biochemistry and physical homeostasis, resulting in changes in biological processes. And for CAN-induced DNA damage, polA played a dominant role, while katG, oxyR, and ahpC were the core genes involved in oxidative stress induced by dCAN and tCAN, respectively. These findings provide valuable data for the toxic effect of Cl-HANs.

The advent of FLASH radiotherapy (FLASH-RT) has brought forth a paradigm shift in cancer treatment, showcasing remarkable normal cell sparing effects with ultra-high dose rates (>40 Gy/s). This review delves into the multifaceted mechanisms underpinning the efficacy of FLASH effect, examining both physicochemical and biological hypotheses in cell biophysics. The physicochemical process encompasses oxygen depletion, reactive oxygen species, and free radical recombination. In parallel, the biological process explores the FLASH effect on the immune system and on blood vessels in treatment sites such as the brain, lung, gastrointestinal tract, skin, and subcutaneous tissue. This review investigated the selective targeting of cancer cells and the modulation of the tumor microenvironment through FLASH-RT. Examining these mechanisms, we explore the implications and challenges of integrating FLASH-RT into cancer treatment. The potential to spare normal cells, boost the immune response, and modify the tumor vasculature offers new therapeutic strategies. Despite progress in understanding FLASH-RT, this review highlights knowledge gaps, emphasizing the need for further research to optimize its clinical applications. The synthesis of physicochemical and biological insights serves as a comprehensive resource for cell biology, molecular biology, and biophysics researchers and clinicians navigating the evolution of FLASH-RT in cancer therapy. [ABSTRACT FROM AUTHOR]

The remediation of copper and nickel-afflicted sites is challenged by the different physiological effects imposed by each metal on a given plant system. Pinus banksiana is resilient against copper and nickel, providing an opportunity to build a valuable resource to investigate the responding gene expression toward each metal. The objectives of this study were to (1) extend the analysis of the Pinus banksiana transcriptome exposed to nickel and copper, (2) assess the differential gene expression in nickel-resistant compared to copper-resistant genotypes, and (3) identify mechanisms specific to each metal. The Illumina platform was used to sequence RNA that was extracted from seedlings treated with each of the metals. There were 449 differentially expressed genes (DEGs) between copper-resistant genotypes (RGs) and nickel-resistant genotypes (RGs) at a high stringency cut-off, indicating a distinct pattern of gene expression toward each metal. For biological processes, 19.8% of DEGs were associated with the DNA metabolic process, followed by the response to stress (13.15%) and the response to chemicals (8.59%). For metabolic function, 27.9% of DEGs were associated with nuclease activity, followed by nucleotide binding (27.64%) and kinase activity (10.16%). Overall, 21.49% of DEGs were localized to the plasma membrane, followed by the cytosol (16.26%) and chloroplast (12.43%). Annotation of the top upregulated genes in copper RG compared to nickel RG identified genes and mechanisms that were specific to copper and not to nickel. NtPDR, AtHIPP10, and YSL1 were identified as genes associated with copper resistance. Various genes related to cell wall metabolism were identified, and they included genes encoding for HCT, CslE6, MPG, and polygalacturonase. Annotation of the top downregulated genes in copper RG compared to nickel RG revealed genes and mechanisms that were specific to nickel and not copper. Various regulatory and signaling-related genes associated with the stress response were identified. They included UGT, TIFY, ACC, dirigent protein, peroxidase, and glyoxyalase I. Additional research is needed to determine the specific functions of signaling and stress response mechanisms in nickel-resistant plants. [ABSTRACT FROM AUTHOR]

Drought poses a significant threat to global food security, particularly impacting crops like oil palm. Selecting genes for genome editing to enhance drought tolerance presents formidable challenges. To ensure that the target gene is chosen correctly and results in the desired character, a pilot study is necessary to determine the target gene for knockout. Two genes drought-related, AtBRL3 and AtOST2, were scrutinized in this context. Aligned with the Elaeis guineensis genome, their neighbouring proteins and gene ontology were analysed to identify potential targets for genome editing. AtBRL3, identified as BRL1 (XP_010913986.1) in E. guineensis, exhibited 58.48% identity and 100% coverage. It interacts with 12 nodes, including BIR1, BRI1, and AT2G20050, crucial for signalling pathways and cellular responses. Molecular function analysis revealed kinase activity. AtOST2 showed high similarity to plasma membrane ATPase/HA1 (XP_010913679.1) in E. guineensis, with 87.46% identity and 100% query cover. It correlated with 14 genes associated with ABA stimulus, stomatal movement, and hormone response. EgBRL1 and EgHA1, resembling AtBRL3 and AtOST2, respectively, emerge as promising targets for developing drought-tolerant oil palm cultivars through gene editing. Nonetheless, further validation through in vitro gRNA target selection and in vivo conversion of OST2/BRL3-containing plasmids in oil palm calluses is indispensable to demonstrate their efficacy in conferring novel drought resistance traits.

Background: Myocardial infarction (MI) is the common manifestation of coronary heart disease that develops from occlusion of coronary arteries. Several risk factors of MI were identified, but data pertaining to genetics and molecular mechanisms involved in the development of MI is limited. Therefore, the present study attempts to analyze the peripheral blood transcriptome information of MI patients and unveil the key genes involved in the pathogenesis of MI. Methods: Total RNA was extracted from the blood sample for illumine sequencing, and raw data obtained were subjected to quality control (QC) using the FastQC tool, followed by trimming of raw data by the fastp tool. Further processed high-quality data were aligned onto the human reference genome using HISAT2 aligner. Gene quantification was done using the feature Counts plugin in the subread package. The raw read counts were given as input to the differential expression analysis (DESeq2) R package for the computation of differentially expressed genes. Gene set enrichment analysis for gene ontology was done using the clusterProfiler R package. Results: A total of 609 genes were significantly expressed in the present study, of which 561 genes were upregulated and 48 genes were downregulated. This study presents overall changes in genes involved in different categories such as biological processes, molecular functions, and cellular components in responses to MI. Conclusions: The significantly deregulated genes identified in the present study not only indicate the molecular and cellular changes but also suggest the scope for the detection of specific gene markers for MI.

Introduction: Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance. Methods: Pre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using clinical benefit and overall survival as endpoints. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes. Results: The levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status, and, in the ICI monotherapy dataset, an association with improved overall survival. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network, including CD8A connected to ten other proteins, suggestive of T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage. Conclusions: Our study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and biomarkers for outcome. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are generated in a cell endogenously which have a nucleotide length of 18 to 26 and are also known as short non-protein coding RNAs. The majority of them are evolutionarily conserved in nature, suggesting a logical foundation for the anticipation of new miRNAs in association with their clusters in numerous plants. Considering this study, physical, bioinformatics and efficient methods are integrated to predict the fresh miRNA clusters along with their targets in sugar cane. In sugar cane, there were a total of 21 new miRNA clusters identified, which were linked to 15 miRNA families. These families are as 165a, 166b, 528a, 827, 2118, 2120b, 5168, 5564c, 5565g, 5568c, 6220, 6225, 6226, 6232a and 7540a. Multiple characteristics of such miRNA clusters, including web logo, phylogenetic tree and secondary structures have been developed. The minimal free energy (MFE) of the secondary structures has been attained and reported as well. In addition, mature miRNAs have been sought in stem section of the structure. Consequently, 115 miRNA targets were also found. These targets include substantial GO term which have important targets in the reproduction, DNA packaging, multicellular organismal process, gene expression, translation, transcription factors, protein binding, transporter activity, secretion, cell division, binding, growth & development and aging. Hence, the achieved results of novel sugar cane miRNA clusters target several types of significant genes which help in managing the environment for sugar cane for better crop production. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the production of H 2 by dark fermentation of brewer's spent grain (BSG) hydrolysate. The process was evaluated under different conditions of temperature, initial pH, and inoculum ratio. The maximum cumulative H 2 production (P H2), H 2 production rate (R H2), and H 2 yield (Y H2) was 4160 mL/L of working volume, 760 mL/L.h, and 5154.26 mL/g glucose cons , respectively. The assay with initial pH 7.5, inoculum 30%, and 35 °C, resulted in the highest P H2 , and assay with initial pH 7.5, inoculum 30%, and 45 °C resulted in the highest R H2 and Y H2. It is observed that P H2 and R H2 were statistically influenced by the initial pH, showing the negative effect of low pH. The initial concentration of furfural (<0.0047 g/L) and 5-(hydroxymethyl)furfural (<0.0220 g/L) were low. Therefore, BSG hydrolysate would be a suitable substrate for dark fermentative H 2 production. [Display omitted] • The highest H 2 production obtained from the BSG hydrolysate was 4160 mL H2 /L. • The H 2 production was better than other studies found in the literature using BSG. • The initial pH was the variable with the greatest statistical influence. • Furfural and 5-HMF concentrations in BSG hydrolysate did not inhibit H 2 production. [ABSTRACT FROM AUTHOR]

Introduction: Increasing global warming has made heat stress a serious threat to crop productivity and global food security in recent years. One of the most promising solutions to address this issue is developing heat-stress-tolerant plants. Hence, a thorough understanding of heat stress response mechanisms, particularly molecular ones, is crucial. Methods: Although numerous studies have used microarray expression profiling technology to explore this area, these experiments often face limitations, leading to inconsistent results. To overcome these limitations, a random effects meta-analysis was employed using advanced statisticalmethods. Ameta-analysis of 16 microarray datasets related to heat stress response in Arabidopsis thaliana was conducted. Results: The analysis revealed 1,972 significant differentially expressed genes between control and heat-stressed plants (826 over-expressed and 1,146 downexpressed), including 128 differentially expressed transcription factors from different families. The most significantly enriched biological processes, molecular functions, and KEGG pathways for over-expressed genes included heat response, mRNA splicing via spliceosome pathways, unfolded protein binding, and heat shock protein binding. Conversely, for down-expressed genes, the most significantly enriched categories included cell wall organization or biogenesis, protein phosphorylation, transmembrane transporter activity, ion transmembrane transporter, biosynthesis of secondary metabolites, and metabolic pathways. Discussion: Through our comprehensive meta-analysis of heat stress transcriptomics, we have identified pivotal genes integral to the heat stress response, offering profound insights into the molecular mechanisms by which plants counteract such stressors. Our findings elucidate that heat stress influences gene expression both at the transcriptional phase and posttranscriptionally, thereby substantially augmenting our comprehension of plant adaptive strategies to heat stress. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) is the common manifestation of coronary heart disease that develops from occlusion of coronary arteries. Several risk factors of MI were identified, but data pertaining to genetics and molecular mechanisms involved in the development of MI is limited. Therefore, the present study attempts to analyze the peripheral blood transcriptome information of MI patients and unveil the key genes involved in the pathogenesis of MI. Methods: Total RNA was extracted from the blood sample for illumine sequencing, and raw data obtained were subjected to quality control (QC) using the FastQC tool, followed by trimming of raw data by the fastp tool. Further processed high-quality data were aligned onto the human reference genome using HISAT2 aligner. Gene quantification was done using the feature Counts plugin in the subread package. The raw read counts were given as input to the differential expression analysis (DESeq2) R package for the computation of differentially expressed genes. Gene set enrichment analysis for gene ontology was done using the clusterProfiler R package. Results: A total of 609 genes were significantly expressed in the present study, of which 561 genes were upregulated and 48 genes were downregulated. This study presents overall changes in genes involved in different categories such as biological processes, molecular functions, and cellular components in responses to MI. Conclusions: The significantly deregulated genes identified in the present study not only indicate the molecular and cellular changes but also suggest the scope for the detection of specific gene markers for MI. [ABSTRACT FROM AUTHOR]

Traditional clinical methodologies often fall short of revealing the complex interplay of multiple components and targets within the human body. This study was designed to explore the complex and synergistic effects of phytochemicals in a plant-based multivitamin/mineral supplement (PBS) on oxidative stress and inflammation in healthy individuals. Utilizing a systems biology framework, we integrated clinical with multi-omics analyses, including UPLC-Q-TOF-MS for 33 phytochemicals, qPCR for 42 differential transcripts, and GC-TOF-MS for 17 differential metabolites. A Gene Ontology analysis facilitated the identification of 367 biological processes linked to oxidative stress and inflammation. As a result, a comprehensive network was constructed consisting of 255 nodes and 1579 edges, featuring 10 phytochemicals, 26 targets, and 218 biological processes. Quercetin was identified as having the broadest target spectrum, succeeded by ellagic acid, hesperidin, chlorogenic acid, and quercitrin. Moreover, several phytochemicals were associated with key genes such as HMOX1, TNF, NFE2L2, CXCL8, and IL6, which play roles in the Toll-like receptor, NF-kappa B, adipocytokine, and C-type lectin receptor signaling pathways. This clinical data-driven network system approach has significantly advanced our comprehension of a PBS's effects by pinpointing pivotal phytochemicals and delineating their synergistic actions, thus illuminating potential molecular mechanisms. [ABSTRACT FROM AUTHOR]

Summary: As the global aging population rises, finding effective interventions to improve aging health is crucial. Drug repurposing, utilizing existing drugs for new purposes, presents a promising strategy for rapid implementation. We explored naltrexone from the Library of Integrated Network-based Cellular Signatures (LINCS) based on several selection criteria. Low-dose naltrexone (LDN) has gained attention for treating various diseases, yet its impact on longevity remains underexplored. Our study on C. elegans demonstrated that a low dose, but not high dose, of naltrexone extended the healthspan and lifespan. This effect was mediated through SKN-1 (NRF2 in mammals) signaling, influencing innate immune gene expression and upregulating oxidative stress responses. With LDN’s low side effects profile, our findings underscore its potential as a geroprotector, suggesting further exploration for promoting healthy aging in humans is warranted.

The nutritional composition of honey is determined by environmental conditions, and botanical and geographical origin. In addition to carbohydrates, honey also contain pollen grains, proteins, free amino acids, and minerals. Although the content of proteins in honey is low, they are an important component that confirms the authenticity and quality of honey; therefore, they became a popular study object. The aim of the study was to evaluate protein content and composition of monofloral red clover and rapeseed honey collected from five different districts of Lithuania. Forty-eight proteins were identified in five different origin honey samples by liquid chromatography. The number of red clover proteins identified in individual honey samples in monofloral red clover honey C3 was 39 in polyfloral honey S22–36, while in monofloral rapeseed honey S5, S15, and S23 there was 33, 32, and 40 respectively. Aphids’ proteins and lactic acid bacteria were identified in all honey samples tested. The linear relationship and the strongest correlation coefficient (r = 0.97) were determined between the content of Apilactobacillus kunkeei and Apilactobacillus apinorum, as well as between the number of faba bean (Vicia faba) pollen and lactic acid bacteria (r = 0.943). The data show a strong correlation coefficient between the amount of lactic acid and aphid protein number (r = 0.693). More studies are needed to evaluate the relationship between the pollination efficiency of red clover by bees and the multiplicity of red clover proteins in honey protein, as well as microbiota diversity and the influence of nature or plant diversity on the occurrence of microbiota in honey.

IntroductionImmune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.MethodsPre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using clinical benefit and overall survival as endpoints. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes.ResultsThe levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status, and, in the ICI monotherapy dataset, an association with improved overall survival. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network, including CD8A connected to ten other proteins, suggestive of T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage.ConclusionsOur study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and biomarkers for outcome.

Summary: Although the Visual Word Form Area (VWFA) in left temporal cortex is considered the pre-eminent region in visual word processing, other regions are also implicated. We examined the entire text-selective circuit, using functional MRI. Ten regions of interest (ROIs) per hemisphere were defined, which, based on clustering, grouped into early vision, high-level vision, and language clusters. We analyzed the responses of the ROIs and clusters to words, inverted words, and consonant strings using univariate, multivariate, and functional connectivity measures. Bilateral modulation by stimulus condition was evident, with a stronger effect in left hemisphere regions. Last, using graph theory, we observed that the VWFA was equivalently connected with early visual and language clusters in both hemispheres, reflecting its role as a mediator in the circuit. Although the individual ROIs and clusters bilaterally were flexibly altered by the nature of the input, stability held at the level of global circuit connectivity, reflecting the complex hierarchical distributed system serving visual text perception.

This study developed a food-grade fermentation process that efficiently isolated proteins and minerals from shrimp-processing waste (SPW). The in vitro antioxidant and enzyme inhibitory effects of SPW hydrolysates obtained from the fermentation process were investigated. SPW broths were prepared from the head (SPW-SH) and body carapace (SPW-SS) of Pacific white shrimp (Litopenaeus vannamei) and fermented using a 5-day successive co-culture fermentation approach with Bacillus amyloliquefaciens TISTR-1880 and Lactobacillus casei TBRC-388. This bacterial combination demonstrated optimal efficiency in extracting proteins (up to 93% deproteinization) and minerals (up to 83% demineralization) from SPW samples compared with other studied co-culture combinations. The resulting SPW-SH and SPW-SS hydrolysates were rich in proteins (∼70 and ∼59 g/100 g dry weight, respectively). They exhibited significantly enhanced antioxidant potential compared to their corresponding non-fermented controls at up to 2.3 and 3.7-fold higher, respectively as determined by the ORAC, FRAP, and DPPH radical scavenging assays. The two SPW hydrolysates also had significantly higher inhibitory activities against angiotensin-converting enzyme, α-amylase, and lipase than the controls, indicating their improved anti-hypertension, anti-diabetes, and anti-obesity properties, respectively; however, both SPW-SH and SPW-SS hydrolysates did not inhibit α-glucosidase at the tested concentrations. The SPW hydrolysates produced in this study showed high potential for use as functional ingredients in food and nutraceutical products. Knowledge gained from this study can promote the prospective valorization of industrial SPW as an inexpensive source of functional biomolecules for food-related applications using a fermentation approach. This will increase the commercial value of SPW and reduce the environmental impact.

The leather-making process necessitates large amounts of water and consequently generates tons of liquid waste as leather tannery wastewater (TWW) is disposed of directly in the open environment. Open disposal of untreated TWW into the natural environment causes an accumulation of various polluting compounds, including heavy metals, dyes, suspended solids inorganic matter, biocides, oils, tannins, and other toxic chemicals. It thus poses potential hazards to the environment and human health. This study primarily focuses on providing in-depth insight into the characteristics, treatment strategies, and regulatory frameworks for managing TWW in leather processing industries. Different technologies of conventional physico-chemical (equalization, coagulation, and adsorption), advanced approaches (Fenton oxidation, ozonation, cavitation), thermo-catalytic and biological treatments available to treat TWW, and their integrative approaches were also highlighted. This review also sheds light on the most frequently applied technologies to reduce contaminant load from TWW though there are several limitations associated with it such as being ineffective for large quantities of TWW, waste generation during treatment, and high operational and maintenance (O&M) costs. It is concluded that the sustainable alternatives applied in the current TWW technologies can minimize O&M costs and recirculate the treated water in the environment. The exhaustive observations and recommendations presented in this article are helpful in the industry to manage TWW and recirculate the water in a sustainable manner. [ABSTRACT FROM AUTHOR]

The potential of reactive oxygen species (ROS) cancer therapy in tumor treatment has been greatly enhanced by the introduction of catalytically superior polyoxometalate (POM)‐based nanoplatforms, mainly composed of atomic clusters consisting of pre‐transition metals and oxygen. These nanoplatforms have unique advantages, such as Fenton activity at neutral pH, induction of cellular ferroptosis instead of just apoptosis, and sensitivity to external field stimulation. However, there are also inevitable challenges such as neutralization of ROS by the antioxidant system of the tumor microenvironment (TME), hypoxia, and limited hydrogen peroxide concentrations. This review article aims to provide an overview of recent research advancements in POM‐based nanoplatforms for ROS therapy from the perspective of chemical reactions and biological processes, addressing endogenous and exogenous factors that affect the antitumor efficacy. Endogenous factors include the mechanism of ROS generation by POM, the impact of pH and antioxidant systems on POM, and the various manners of tumor cell death. Exogenous stimuli mainly include light, heat, X‐rays, and electricity. The article analyzes the specific mechanisms of action of each influencing factor in the first two sections, concluding with the limitations of the present study and some possible directions for future research. [ABSTRACT FROM AUTHOR]

The remediation of copper and nickel-afflicted sites is challenged by the different physiological effects imposed by each metal on a given plant system. Pinus banksiana is resilient against copper and nickel, providing an opportunity to build a valuable resource to investigate the responding gene expression toward each metal. The objectives of this study were to (1) extend the analysis of the Pinus banksiana transcriptome exposed to nickel and copper, (2) assess the differential gene expression in nickel-resistant compared to copper-resistant genotypes, and (3) identify mechanisms specific to each metal. The Illumina platform was used to sequence RNA that was extracted from seedlings treated with each of the metals. There were 449 differentially expressed genes (DEGs) between copper-resistant genotypes (RGs) and nickel-resistant genotypes (RGs) at a high stringency cut-off, indicating a distinct pattern of gene expression toward each metal. For biological processes, 19.8% of DEGs were associated with the DNA metabolic process, followed by the response to stress (13.15%) and the response to chemicals (8.59%). For metabolic function, 27.9% of DEGs were associated with nuclease activity, followed by nucleotide binding (27.64%) and kinase activity (10.16%). Overall, 21.49% of DEGs were localized to the plasma membrane, followed by the cytosol (16.26%) and chloroplast (12.43%). Annotation of the top upregulated genes in copper RG compared to nickel RG identified genes and mechanisms that were specific to copper and not to nickel. NtPDR, AtHIPP10, and YSL1 were identified as genes associated with copper resistance. Various genes related to cell wall metabolism were identified, and they included genes encoding for HCT, CslE6, MPG, and polygalacturonase. Annotation of the top downregulated genes in copper RG compared to nickel RG revealed genes and mechanisms that were specific to nickel and not copper. Various regulatory and signaling-related genes associated with the stress response were identified. They included UGT, TIFY, ACC, dirigent protein, peroxidase, and glyoxyalase I. Additional research is needed to determine the specific functions of signaling and stress response mechanisms in nickel-resistant plants.

IntroductionIncreasing global warming has made heat stress a serious threat to crop productivity and global food security in recent years. One of the most promising solutions to address this issue is developing heat-stress-tolerant plants. Hence, a thorough understanding of heat stress response mechanisms, particularly molecular ones, is crucial.MethodsAlthough numerous studies have used microarray expression profiling technology to explore this area, these experiments often face limitations, leading to inconsistent results. To overcome these limitations, a random effects meta-analysis was employed using advanced statistical methods. A meta-analysis of 16 microarray datasets related to heat stress response in Arabidopsis thaliana was conducted.ResultsThe analysis revealed 1,972 significant differentially expressed genes between control and heat-stressed plants (826 over-expressed and 1,146 down-expressed), including 128 differentially expressed transcription factors from different families. The most significantly enriched biological processes, molecular functions, and KEGG pathways for over-expressed genes included heat response, mRNA splicing via spliceosome pathways, unfolded protein binding, and heat shock protein binding. Conversely, for down-expressed genes, the most significantly enriched categories included cell wall organization or biogenesis, protein phosphorylation, transmembrane transporter activity, ion transmembrane transporter, biosynthesis of secondary metabolites, and metabolic pathways.DiscussionThrough our comprehensive meta-analysis of heat stress transcriptomics, we have identified pivotal genes integral to the heat stress response, offering profound insights into the molecular mechanisms by which plants counteract such stressors. Our findings elucidate that heat stress influences gene expression both at the transcriptional phase and post-transcriptionally, thereby substantially augmenting our comprehension of plant adaptive strategies to heat stress.

A single-stage anaerobic fluidized membrane bioreactor (AnFMBR) was applied to investigate the effects of temperature changes on membrane fouling while treating real municipal wastewater. The AnFMBR was operated at four temperature phases: 25 °C for 42 days, 20 °C for 20 days, 15 °C for 15 days, and at 10 °C for 15 days. The systems achieved a total chemical oxygen demand (TCOD) removal efficiency of above 90% at all phases. As temperature decreased, accumulation of solids and possible incomplete hydrolysis led to an increase in TCOD and volatile fatty acids (VFAs) in the reactor. However, as temperature reduced to 10 °C, VFAs in the reactor reduced probably an indication of reactors adaptation. Total membrane filtration resistance gradually increased to 1.1 × 1011 m−1 from 2.1 × 1009 m−1 with a temperature decrease from 25 °C to 10 °C. This corresponded to a significant decrease in membrane permeability from 1.68 to 0.05 LMH/kpa. The protein fraction of the extracellular polymeric substances (EPS) was dominant in all phases, which was ascribed for significant membrane fouling causing permeability deterioration. Microbial richness and diversity analysis using next generation Ion torrent sequencing methods revealed that Proteobacteria phylum was most dominant at 25 °C, whereas Bacteroidetes, which are responsible for releasing proteinaceous EPS, were most dominant at low temperatures (15 °C and 10 °C), contributing to severe fouling. In conclusion, decrease in temperature did not affect the treatment efficiency but resulted in gradual increase in membrane fouling. [ABSTRACT FROM AUTHOR]

Cellular homeostasis of the micronutrient iron is highly regulated in plants and responsive to nutrition, stress, and developmental signals. Genes for iron management encode metal and other transporters, enzymes synthesizing chelators and reducing substances, transcription factors, and several types of regulators. In transcriptome or proteome datasets, such iron homeostasisrelated genes are frequently found to be differentially regulated. A common method to detect whether a specific cellular pathway is affected in the transcriptome data set is to perform Gene Ontology (GO) enrichment analysis. Hence, the GO database is a widely used resource for annotating genes and identifying enriched biological pathways in Arabidopsis thaliana. However, iron homeostasis-related GO terms do not consistently reflect gene associations and levels of evidence in iron homeostasis. Some genes in the existing iron homeostasis GO terms lack direct evidence of involvement in iron homeostasis. In other aspects, the existing GO terms for iron homeostasis are incomplete and do not reflect the known biological functions associated with iron homeostasis. This can lead to potential errors in the automatic annotation and interpretation of GO term enrichment analyses. We suggest that applicable evidence codes be used to add missing genes and their respective ortholog/ paralog groups to make the iron homeostasis-related GO terms more complete and reliable. There is a high likelihood of finding new iron homeostasis-relevant members in gene groups and families like the ZIP, ZIF, ZIFL, MTP, OPT, MATE, ABCG, PDR, HMA, and HMP. Hence, we compiled comprehensive lists of genes involved in iron homeostasis that can be used for custom enrichment analysis in transcriptomic or proteomic studies, including genes with direct experimental evidence, those regulated by central transcription factors, and missing members of small gene families or ortholog/paralog groups. As we provide gene annotation and literature alongside, the gene lists can serve multiple computational approaches. In summary, these gene lists provide a valuable resource for researchers studying iron homeostasis in A. thaliana, while they also emphasize the importance of improving the accuracy and comprehensiveness of the Gene Ontology. [ABSTRACT FROM AUTHOR]

Understanding the genetic response of plants to nickel stress is a necessary step to improving the utility of plants in environmental remediation and restoration. The main objective of this study was to generate whole genome expression profiles of P. banksiana exposed to nickel ion toxicity compared to reference genotypes. Pinus banksiana seedlings were screened in a growth chamber setting using a high concentration of 1600 mg of nickel per 1 kg of soil. RNA was extracted and sequenced using the Illumina platform, followed by de novo transcriptome assembly. Overall, 25,552 transcripts were assigned gene ontology. The biological processes in water-treated samples were analyzed, and 55% of transcripts were distributed among five categories: DNA metabolic process (19.3%), response to stress (13.3%), response to chemical stimuli (8.7%), signal transduction (7.7%) and response to biotic stimulus (6.0%). For molecular function, the highest percentages of genes were involved in nucleotide binding (27.6%), nuclease activity (27.3%) and kinase activity (10.3%). Sixty-two percent of genes were associated with cellular compartments. Of these genes, 21.7% were found in the plasma membrane, 16.1% in the cytosol, 12.4% with the chloroplast and 11.9% in the extracellular region. Nickel ions induced changes in gene expression, resulting in the emergence of differentially regulated categories. Overall, there were significant changes in gene expression with a total 4128 genes upregulated and 3754 downregulated genes detected in nickel-treated genotypes compared to water-treated control plants. For biological processes, the highest percentage of upregulated genes in plants exposed to nickel were associated with the response to stress (15%), the response to chemicals (11,1%), carbohydrate metabolic processes (7.4%) and catabolic processes (7.4%). The largest proportions of downregulated genes were associated with the biosynthetic process (21%), carbohydrate metabolic process (14.3%), response to biotic stimulus (10.7%) and response to stress (10.7%). For molecular function, genes encoding for enzyme regulatory and hydrolase activities represented the highest proportion (61%) of upregulated gene. The majority of downregulated genes were involved in the biosynthetic processes. Overall, 58% of upregulated genes were located in the extracellular region and the nucleus, while 42% of downregulated genes were localized to the plasma membrane and 33% to the extracellular region. This study represents the first report of a transcriptome from a conifer species treated with nickel. [ABSTRACT FROM AUTHOR]

Skeletal muscle is the protein reservoir of our body and an important regulator of glucose and lipid homeostasis. The dystrophin gene is the largest gene and has a key role in skeletal muscle construction and function. Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophy in humans, mice, dogs, and cats. Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular condition causing progressive muscle weakness and premature death. β-hydroxy β-methylbutyrate (HMB) prevents deleterious muscle responses under pathological conditions, including tumor and chronic steroid therapy-related muscle losses. The use of HMB as a dietary supplement allows for increasing lean weight gain; has a positive immunostimulatory effect; is associated with decreased mortality; and attenuates sarcopenia in elderly animals and individuals. This study aimed to identify some genes, metabolic pathways, and biological processes which are common for DMD and HMB based on existing literature and then discuss the consequences of that interaction. [ABSTRACT FROM AUTHOR]

Currently, thermophilic membrane biological reactors (TMBRs) are used to treat industrial wastewaters and biological sewage sludge with the aim of nutrients recovery. The performance of the biological process is strongly influenced by rheological behaviour of the thermophilic biological sludge (TBS) inside the reactor. Considering the high concentration of heavy metals in matrices fed to the reactors, this work aims to evaluate the influence of heavy metal types and concentration on rheological properties of TBS. Sludge has been extracted from a full-scale TMBR and conditioned with Fe3+, Cu2+, and Al3+. Rheological measures have been conducted and constants k and n of Herschel–Bulkley model were used to define the rheological properties of TBS. Rheological properties of high consistency TBS (0.06 ≤ k0 < 0.2 and 0.6 ≤ n0 < 0.8) were not significantly affected by the conditioning with Fe3+, Cu2+, and Al3+. In case of TBS with initial low consistency (0.02 ≤ k0 < 0.06) and behaviour more similar to Newtonian fluids (0.8 ≤ n0 < 1), Fe3+ and Al3+ determined a significant increase in consistency. On the contrary, the addition of Cu2+ reduced k of conditioned TBS with a lower impact on the distance for Newtonian behaviour (n). This work demonstrates the strong influence of Fe3+, Cu2+, and Al3+ on the rheological properties of TBS depending on the initial consistency of the sludge, and the types and dosage of heavy metals. [ABSTRACT FROM AUTHOR]

Antibiotic-resistant bacteria (ARBs) can now be detected not only in clinical institutions but also in wastewater treatment plants (WWTPs), extending the range of emergence to residential areas. In this study, we investigated the change of antibiotic-resistant Escherichia coli (E. coli) and other coliforms in each treatment process at WWTPs. Throughout the treatment process, the numbers of E. coli and other coliforms were significantly reduced to less than 5.7 ± 0.5 CFU/100 ml and 2.4 ± 0.0×102 CFU/100 ml, respectively. However, ESBL-producing E. coli and other coliforms were detected in each treatment process (even after chlorination) at 5.6% and 4.8%, compared to the total E. coli and other coliforms counts. Then, ESBL-producing-related genes were identified via PCR analyses, and the most predominant gene was CTX-M-9 in both E. coli (47.2%) and other coliforms (47.3%). Although actual WWTPs greatly reduced the number of bacteria, the relative prevalence of ESBL-producing bacteria was increased, suggesting that ESBL-producing bacteria remain in the effluent at minimal concentrations and could be diffusing to water bodies. [ABSTRACT FROM AUTHOR]

One of the main issues addressed by phytology in recent years has been plant tolerance mechanisms for abiotic stress. No combined analysis has been made to identify the genes involved in drought stress tolerance. The meta-analysis of microarray data related to drought stress was analysed by the R software packages and showed 3 029 upregulated genes and 3 017 downregulated genes. The upregulated genes were mostly related to the drought tolerance protein, abiotic stress response, and the Cys2His2 Zinc Finger Transcription Factor (C2H2 zinc finger TF). The downregulated genes were mainly related to the late embryogenesis abundant protein, abiotic stress response, and the basic leucine zipper (bZIP) TF. The common gene ontology (GO) terms in the upregulated and downregulated genes were mainly related to the metabolic process, response to stimulus, cellular metabolic process, and photorespiration. The up and down meta-differential expressed genes (meta-DEGs) mainly belonged to the those following Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including: the biosynthesis of secondary metabolites, plant hormone signal transduction, mitogen-activated protein kinase (MAPK) signalling pathway, and RNA degradation. Moreover, in the upregulated and downregulated genes, the TFs with a high percentage mainly belonged to the Teosinte branched1/Cincinnata/proliferating cell factor (TCP), basic helix loop-helix (bHLH) and bZIP. Next, the hub upregulated genes were mainly related to the thiamine biosynthesis protein thiC, 4-hydroxyphenylpyruvate dioxygenase, ribose-5-phosphate isomerase precursor and heat shock protein. The hub downregulated genes were mainly associated with the elongation factor Ts, aldehyde dehydrogenase, and trigger factor. Finally, the data from the present meta-analysis were compared with previous studies on the qRT-PCR results and their up and down expressions were confirmed. Based on the findings of the current study, novel insights into the drought stress molecular response can be provided and various candidate genes can be introduced for barley drought stress tolerance breeding.

Background and objectives: Propolis is a natural product of honey bees that is characterized by therapeutic effects on diverse diseases. To elucidate the molecular mechanism of propolis effects on tumor, protein-protein interaction (PPI) network analysis of proteome data of Hep-2 cells treated with red propolis was conducted. Methods: Cytoscape V 3.9.1 and its plug-ins evaluated the differentially expressed proteins (DEPs) in terms of network construction and the corresponding topological features. Results: The results implied that six hub-bottlenecks including ACTB, GAPDH, HSP90AA1, HSPA8, HSP90AB1, and HSPA5 were present in the PPI network; however, only the last central protein was among DEPs. ClueGO+ CluePedia identified five related biological processes and three action types of their connections. Results refer to anticancer property of red propolis. Conclusion: The proposed crucial proteins and their linked biological processes may represent as key players in the anticancer underlying mechanism of red propolis.

Many tons of micro- and nano-sized plastic particles enter the aquatic environment every year, due to increasing plastic production, with the consequent risk of microplastics contaminating our environment. Addressing this multifaceted threat requires innovative technologies that can efficiently remove microplastics from the environment. Therefore, there is an urgent need to study the efficiency of the removal of microplastics by different water and wastewater treatment technologies. After short overviewed the source, occurrence, and potential adverse impacts of microplastics to human health, we then identified promising technologies for microplastics removal, including physical, chemical, and biological approaches. A detailed analysis of the advantages and limitations of different techniques was provided. According to literature data, the performance of microplastics removal is as follows: membrane bioreactor (>99%) > activated sludge process (~98%) > rapid sand filtration (~97.1%) > dissolved air floatation (~95%) > electrocoagulation (>90%) > constructed wetlands (88%). Chemical treatment methods such as coagulation, magnetic separation, Fenton, photo-Fenton and photocatalytic degradation also show moderate to high efficiency of microplastics removal. Hybrid treatment such as the MBR-UF/RO system, coagulation followed by ozonation, adsorption, dissolved air flotation, filtration, and constructed wetlands based hybrid technologies have shown very promising results in the effective removal of microplastics. Lastly, research gaps in this area are identified, and suggestions for future perspectives are provided. We concluded this review with the current challenges and future research priorities, which will guide us through the path addressing microplastics contamination.

One of the main issues addressed by phytology in recent years has been plant tolerance mechanisms for abiotic stress. No combined analysis has been made to identify the genes involved in drought stress tolerance. The meta-analysis of microarray data related to drought stress was analysed by the R software packages and showed 3 029 upregulated genes and 3 017 downregulated genes. The upregulated genes were mostly related to the drought tolerance protein, abiotic stress response, and the Cys2His2 Zinc Finger Transcription Factor (C2H2 zinc finger TF). The downregulated genes were mainly related to the late embryogenesis abundant protein, abiotic stress response, and the basic leucine zipper (bZIP) TF. The common gene ontology (GO) terms in the upregulated and downregulated genes were mainly related to the metabolic process, response to stimulus, cellular metabolic process, and photorespiration. The up and down meta-differential expressed genes (meta-DEGs) mainly belonged to the those following Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including: the biosynthesis of secondary metabolites, plant hormone signal transduction, mitogen-activated protein kinase (MAPK) signalling pathway, and RNA degradation. Moreover, in the upregulated and downregulated genes, the TFs with a high percentage mainly belonged to the Teosinte branched1/Cincinnata/proliferating cell factor (TCP), basic helix loop--helix (bHLH) and bZIP. Next, the hub upregulated genes were mainly related to the thiamine biosynthesis protein thiC, 4-hydroxyphenylpyruvate dioxygenase, ribose-5-phosphate isomerase precursor and heat shock protein. The hub downregulated genes were mainly associated with the elongation factor Ts, aldehyde dehydrogenase, and trigger factor. Finally, the data from the present meta-analysis were compared with previous studies on the qRT-PCR results and their up and down expressions were confirmed. Based on the findings of the current study, novel insights into the drought stress molecular response can be provided and various candidate genes can be introduced for barley drought stress tolerance breeding. [ABSTRACT FROM AUTHOR]

Summary: Patients with the sleep disorder narcolepsy suffer from excessive daytime sleepiness, disrupted nighttime sleep, and cataplexy—the abrupt loss of postural muscle tone during wakefulness, often triggered by strong emotion. The dopamine (DA) system is implicated in both sleep-wake states and cataplexy, but little is known about the function of DA release in the striatum and sleep disorders. Recording DA release in the ventral striatum revealed orexin-independent changes across sleep-wake states as well as striking increases in DA release in the ventral, but not dorsal, striatum prior to cataplexy onset. Tonic low-frequency stimulation of ventral tegmental efferents in the ventral striatum suppressed both cataplexy and rapid eye movement (REM) sleep, while phasic high-frequency stimulation increased cataplexy propensity and decreased the latency to REM sleep. Together, our findings demonstrate a functional role of DA release in the striatum in regulating cataplexy and REM sleep.

Summary: The current TNM staging system for pancreatic ductal adenocarcinoma (PDAC) has revised the definitions of T and N categories as well as stage groups. However, studies validating these modifications have yielded inconsistent results. The existing TNM staging system in prognostic prediction remains unsatisfactory. The prognosis of PDAC is closely associated with pathological and biological factors. Herein, we propose a new staging system incorporating distant metastasis, postoperative serum levels of CA19-9 and CEA, tumor size, lymph node metastasis, lymphovascular involvement, and perineural invasion to enhance the accuracy of prognosis assessment. The proposed staging system exhibited a strong correlation with both overall survival and recurrence-free survival, effectively stratifying survival into five distinct tiers. Additionally, it had favorable discrimination and calibration. Thus, the proposed staging system demonstrates superior prognostic performance compared to the TNM staging system, and can serve as a valuable complementary tool to address the limitations of TNM staging in prognostication.

Cellular homeostasis of the micronutrient iron is highly regulated in plants and responsive to nutrition, stress, and developmental signals. Genes for iron management encode metal and other transporters, enzymes synthesizing chelators and reducing substances, transcription factors, and several types of regulators. In transcriptome or proteome datasets, such iron homeostasis-related genes are frequently found to be differentially regulated. A common method to detect whether a specific cellular pathway is affected in the transcriptome data set is to perform Gene Ontology (GO) enrichment analysis. Hence, the GO database is a widely used resource for annotating genes and identifying enriched biological pathways in Arabidopsis thaliana. However, iron homeostasis-related GO terms do not consistently reflect gene associations and levels of evidence in iron homeostasis. Some genes in the existing iron homeostasis GO terms lack direct evidence of involvement in iron homeostasis. In other aspects, the existing GO terms for iron homeostasis are incomplete and do not reflect the known biological functions associated with iron homeostasis. This can lead to potential errors in the automatic annotation and interpretation of GO term enrichment analyses. We suggest that applicable evidence codes be used to add missing genes and their respective ortholog/paralog groups to make the iron homeostasis-related GO terms more complete and reliable. There is a high likelihood of finding new iron homeostasis-relevant members in gene groups and families like the ZIP, ZIF, ZIFL, MTP, OPT, MATE, ABCG, PDR, HMA, and HMP. Hence, we compiled comprehensive lists of genes involved in iron homeostasis that can be used for custom enrichment analysis in transcriptomic or proteomic studies, including genes with direct experimental evidence, those regulated by central transcription factors, and missing members of small gene families or ortholog/paralog groups. As we provide gene annotation and literature alongside, the gene lists can serve multiple computational approaches. In summary, these gene lists provide a valuable resource for researchers studying iron homeostasis in A. thaliana, while they also emphasize the importance of improving the accuracy and comprehensiveness of the Gene Ontology.

Background: Despite the significant survival benefits of anti-PD-1/PDL1 immunotherapy, non-small cell lung cancer (NSCLC) remains one of the most common tumors and major causes of cancer-related deaths worldwide. Thus, there is an urgent need to identify new therapeutic targets for this refractory disease. Methods: In this study, microarray datasets GSE27262, GSE75037, GSE102287, and GSE21933 were integrated by Venn diagram. We performed functional clustering and pathway enrichment analyses using R. Through the STRING database and Cytoscape, we conducted protein-protein interaction (PPI) network analysis and identified the key genes, which were verified by the GEPIA2 and UALCAN portal. Validation of actin-binding protein anillin (ANLN) was performed by quantitative real-time polymerase chain reaction and Western blotting. Additionally, Kaplan-Meier methods were used to compute the survival analyses. Results: In total, 126 differentially expressed genes were identified, which were enriched in mitotic nuclear division, mitotic cell cycle G2/M transition, vasculogenesis, spindle, and peroxisome proliferator-activated receptor signaling pathway. 12 central node genes were identified in the PPI network complex. The survival analysis revealed that high transcriptional levels were associated with inferior survival in NSCLC patients. The clinical implication of ANLN was further explored; its protein expression showed a gradually increasing trend from grade I to III. Conclusion: These Key genes may be involved in the carcinogenesis and progression of NSCLC, which may serve as useful targets for NSCLC diagnosis and treatment. [ABSTRACT FROM AUTHOR]