Biological Molecular Mechanisms Research Articles

Brassica rapa L. (Tibetan Turnip) polysaccharide improves the immune function and regulates intestinal microbiota in immunosuppressive mice.

In this paper, active polysaccharides were extracted from Brassica rapa L. polysaccharide (BRP), and structural characterization was preliminarily investigated. Its immunomodulatory activity and molecular biological mechanisms in cyclophosphamide-induced immunosuppressed mice were also explored, as well as its effects on intestinal microbiota. Results indicate that BRP is an acidic heteropolysaccharide with the main components of Ara, GalA, and GlcA and has α- and β-glycosidic linkages with pyranose bonds. The results of the study showed that BRP could effectively improve the thymus and spleen indices and repair Cy-induced immune tissue damage in immunosuppressed mice. Meanwhile, BRP increased the immune cell activity and antioxidant levels in mice. In addition, BRP increased the secretion of cytokines (IL-1β, IL-6, IL-10, and TNF-α) and immunoglobulins (IgA, IgG) in mouse serum. It also regulates the relative expression of genes related to the TLR4/NF-κB signaling pathways as well as regulates the diversity and composition of mouse intestinal microbiota. In conclusion, BRP was able to regulated the immune function in immunosuppressed mice, providing a theoretical basis for the development of immunomodulators.

Physiological and Transcriptomic Analyses Reveal the Role of the Antioxidant System and Jasmonic Acid (JA) Signal Transduction in Mulberry (Morus alba L.) Response to Flooding Stress

In recent decades, the frequency of flooding has increased as a result of global climate change. Flooding has become one of the major abiotic stresses that seriously affect the growth and development of plants. Mulberry (Morus alba L.) is an important economic tree in China. Flooding stress is among the most severe abiotic stresses that affect the production of mulberry. However, the physiological and molecular biological mechanisms of mulberry responses to flooding stress are still unclear. In the present study, reactive oxygen species (ROS) metabolism, antioxidant mechanism, and plant hormones in mulberry associated with the response to flooding stress were investigated using physiological and transcriptomic analysis methods. The results showed significant increases in the production rate of superoxide anion (O2•−) and the content of hydrogen peroxide (H2O2) in leaves on the 5th day of flooding stress. This led to membrane lipid peroxidation and elevated malondialdehyde (MDA) levels. Antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) exhibited enhanced activities initially, followed by fluctuations. The ascorbic acid–glutathione (AsA-GSH) cycle played a crucial role in scavenging ROS, promoting the reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH). Transcriptomic analysis revealed the up-regulation of the gene-encoding antioxidant enzymes (APX, MDHAR, GPX, GR, GST) involved in ROS scavenging and stress tolerance mechanisms. Jasmonic acid (JA) levels and the expression of JA synthesis-related genes increased significantly in mulberry leaves under flooding stress. This activation of the JA signaling pathway contributed to the plant’s adaptability to flooding conditions. Proline (Pro) and soluble sugar (SS) contents increased notably in response to flooding stress. Proline helped maintain cell turgor and protected enzymes and membranes from damage, while soluble sugars supported anaerobic respiration and energy supply. However, soluble protein (SP) content decreased, suggesting inhibition of protein synthesis. The study provides insights into mulberry’s flooding tolerance mechanisms, guiding future molecular breeding efforts. This summary captures the key findings and implications of the study on mulberry’s response to flooding stress, focusing on physiological and molecular mechanisms identified in the research.

Hydrogen-Rich Water to Enhance Exercise Performance: A Review of Effects and Mechanisms.

Background: Hydrogen-rich water (HRW) has garnered significant interest within the sports and exercise science community due to its selective antioxidant properties. Despite its potential benefits, comprehensive reviews specifically addressing its effects on athletic performance are limited. This review aims to assess the impact of HRW on sports performance and explore the underlying molecular biological mechanisms, with the goal of elucidating how HRW might enhance athletic performance. Methods: This review synthesizes research on HRW by examining articles published between 1980 and April 2024 in databases such as PubMed, the Cochrane Library, Embase, Scopus, and Web of Science. Results: It highlights HRW's effects on various aspects of athletic performance, including endurance, strength, sprint times, lunge movements, countermovement jump height, and time to exhaustion. While the precise mechanisms by which HRW affects athletic performance remain unclear, this review investigates its general molecular biological mechanisms beyond the specific context of sports. This provides a theoretical foundation for future research aimed at understanding how HRW can enhance athletic performance. HRW targets the harmful reactive oxygen and nitrogen species produced during intense exercise, thereby reducing oxidative stress-a critical factor in muscle fatigue, inflammation, and diminished athletic performance. HRW helps to scavenge hydroxyl radicals and peroxynitrite, regulate antioxidant enzymes, mitigate lipid peroxidation, reduce inflammation, protect against mitochondrial dysfunction, and modulate cellular signaling pathways. Conclusions: In summary, while a few studies have indicated that HRW may not produce significant beneficial effects, the majority of research supports the conclusion that HRW may enhance athletic performance across various sports. The potential mechanisms underlying these benefits are thought to involve HRW's role as a selective antioxidant, its impact on oxidative stress, and its regulation of redox homeostasis. However, the specific molecular biological mechanisms through which HRW improves athletic performance remain to be fully elucidated.

Explore the mechanism of yishenjiangya formula in the treatment of senile hypertension based on multi-omics technology

Ethnopharmacological relevanceThe Yishenjiangya formula (YSJ) is a traditional Chinese medicine (TCM) primarily composed of qi-tonifying components. This classic formula is commonly utilized to treat kidney qi deficiency in elderly patients with hypertension. According to TCM, maintaining a balance between qi and blood is crucial for stable blood pressure. Kidney qi deficiency can disrupt this balance, altering fluid shear force and, ultimately, leading to hypertension, particularly in elderly populations. Despite YSJ's efficacy in treating hypertension, its specific anti-hypertensive mechanisms remain unclear. Aim of the studyYSJ is commonly prescribed for elderly patients with hypertension. Earlier metabolomics studies demonstrated that YSJ exerts antihypertensive effects by influencing four key pathways: linoleic acid metabolism, glycerol phospholipid metabolism, arginine and proline metabolism, and steroid hormone biosynthesis. This study aims to combine metabolomic and proteomic analyses to thoroughly understand the molecular biological mechanisms responsible for YSJ's anti-hypertensive properties. MethodsUltra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) metabolomics, combined with Label-Free Quantitation (LFQ) proteomics, was employed to analyze serum samples from elderly individuals with and without hypertension pre- and post-YSJ intervention. Serum levels of candidate proteins were assessed using enzyme-linked immunosorbent assay, and receiver operating characteristic curves were used to evaluate the diagnostic performance of the target proteins. ResultsEight differentially expressed metabolites and three differentially expressed proteins were identified as potential therapeutic targets of YSJ. These substances are primarily involved in unsaturated fatty acid metabolism, fluid shear stress and atherosclerosis pathway, primary bile acid biosynthesis, proline metabolism, apoptosis, and endoplasmic reticulum stress. YSJ exerts its therapeutic effects on hypertension in the elderly by modulating these pathways. ConclusionsYSJ effectively treats senile hypertension. By analyzing the correlation between therapeutic targets and pathways, YSJ's anti-hypertensive effect was achieved by inhibiting lipid peroxidation and matrix degeneration. Combining metabolomics and proteomics provides an effective method for uncovering YSJ's anti-hypertensive mechanisms.

Functional role of lncRNA MEG3 on pyroptosis through interacting with EZH2 and YTHDC1 in postoperative cognitive dysfunction

BackgroundThe molecular biology mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear, resulting in a lack of specific therapeutic targets and limited clinical treatment options. The NLRP3 pyroptotic pathway, induced by neuroinflammation, is known to promote the development of POCD. Research has shown that lncRNA MEG3 exacerbates cell pyroptosis in various neurological injuries, though the precise mechanism remains to be investigated. MethodsIn vitro and in vivo models of POCD were established through treatment with sevoflurane. Gene and protein expression were investigated using qRT-PCR, Western blot analysis, ELISA, and histological staining. Additionally, cell viability and injury were assessed through CCK-8 and LDH assays. Hippocampal-dependent memory and cognitive abilities were evaluated using the Morris Water Maze (MWM) test. Furthermore, the interactions between MEG3 and EZH2/YTHDC1 were validated through RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP). ResultsOur findings reveal that sevoflurane significantly reduced MEG3 and pyroptosis-related proteins in mice. The overexpression of MEG3 protected mice against sevoflurane-induced cognitive dysfunction and reversed sevoflurane-induced pyroptosis in hippocampal neurons. MEG3 induced the downregulation of NLRP3 expression and reduced mRNA stability through its interaction with EZH2/YTHDC1. ConclusionIn conclusion, our study elucidates that MEG3 inhibits the NLRP3 inflammasome and hippocampal neuron pyroptosis through the recruitment of EZH2/YTHDC1. These findings shed light on the underlying mechanism of MEG3 in the regulation of POCD and suggest that MEG3 could serve as a potential therapeutic target for the treatment of POCD.

Novel Therapeutic Mechanisms and Strategies for Intracerebral Hemorrhage: Focusing on Exosomes.

Intracerebral hemorrhage (ICH) is a primary, non-traumatic cerebral event associated with substantial mortality and disability. Despite advancements in understanding its etiology and refining diagnostic techniques, a validated treatment to significantly improve ICH prognosis remains elusive. Exosomes, a subtype of extracellular vesicles, encapsulate bioactive components, predominantly microRNAs (miRNAs), facilitating and regulating intercellular communication. Currently, exosomes have garnered considerable interests in clinical transformation for their nanostructure, minimal immunogenicity, low toxicity, inherent stability, and the ability to traverse the blood-brain barrier. A wealth of studies has demonstrated that exosomes can improve the prognosis of ICH through anti-apoptosis, neurogenesis, angiogenesis, anti-inflammation, immunomodulation, and autophagy, primarily via the transportation or overexpression of selected miRNAs. More importantly, exosomes can be easily customized with specific miRNAs or bioactive compounds to establish delivery systems, broadening their potential applications. This review focuses on the therapeutic potential of exosomes in ICH, reviewing the mechanisms of molecular biology mediated by certain miRNAs, discussing the benefits, challenges, and future prospects in ICH treatment. We hope comprehensive understanding of exosomes based on miRNAs will provide new insights into the treatment of ICH and guide the translation of exosome's research from laboratory to clinical practice.

Jianpi Huayu Prescription Prevents Atherosclerosis by Improving Inflammation and Reshaping the Intestinal Microbiota in ApoE−/− Mice

This study established an LPS-induced RAW264.7 macrophage inflammatory injury model and an AS mouse vulnerable plaque model to observe the effect of JPHYP on macrophage inflammation, plaque formation, blood lipids, inflammation levels, intestinal flora and the influence of TLR4/MyD88/MAPK pathway, and explore the anti-AS effect and molecular mechanism of JPHYP, and detected 16S rRNA of mice intestinal microbes. The difference of intestinal flora in different groups of mice was compared to further explore the intervention effect of JPHYP and clarify the molecular biological mechanism of JPHYP in preventing and treating AS by regulating TLR4/MyD88/MAPK inflammatory signaling pathway and improving intestinal flora.

ERT-GFAN: A multimodal drug–target interaction prediction model based on molecular biology and knowledge-enhanced attention mechanism

In drug discovery, precisely identifying drug–target interactions is crucial for finding new drugs and understanding drug mechanisms. Evolving drug/target heterogeneous data presents challenges in obtaining multimodal representation in drug–target prediction(DTI). To deal with this, we propose ‘ERT-GFAN’, a multimodal drug–target interaction prediction model inspired by molecular biology. Firstly, it integrates bio-inspired principles to obtain structure feature of drugs and targets using Extended Connectivity Fingerprints(ECFP). Simultaneously, the knowledge graph embedding model RotatE is employed to discover the interaction feature of drug–target pairs. Subsequently, Transformer is utilized to refine the contextual neighborhood features from the obtained structure feature and interaction features, and multi-modal high-dimensional fusion features of the three-modal information constructed. Finally, the final DTI prediction results are outputted by integrating the multimodal fusion features into a graphical high-dimensional fusion feature attention network (GFAN) using our innovative multimodal high-dimensional fusion feature attention. This multimodal approach offers a comprehensive understanding of drug–target interactions, addressing challenges in complex knowledge graphs. By combining structure feature, interaction feature, and contextual neighborhood features, ‘ERT-GFAN’ excels in predicting DTI. Empirical evaluations on three datasets demonstrate our method’s superior performance, with AUC of 0.9739, 0.9862, and 0.9667, AUPR of 0.9598, 0.9789, and 0.9750, and Mean Reciprocal Rank(MRR) of 0.7386, 0.7035, and 0.7133. Ablation studies show over a 5% improvement in predictive performance compared to baseline unimodal and bimodal models. These results, along with detailed case studies, highlight the efficacy and robustness of our approach.

Meta-analysis of effectiveness and safety of proteasome inhibitor-dependent maintenance treatment for multiple myeloma a systematic review

BackgroundEven with significant advancements, treating multiple myeloma (MM) remains difficult. At present, the main treatment methods include combined treatment of stem cell transplantation, drug treatment, etc. With the clarification of the molecular biological mechanism of MM, as well as the in-depth study of the internal signal of myeloma cells and the microenvironment of MM patients, more and more new drugs targeting myeloma and microenvironment are gradually used in clinical maintenance treatment, such as inhibit the proteosome: ixazomib, bortezomib and carfilzomib, immune - modulators: thalidomide and lenalidomide, monoclonal antibodies, etc. have made great progress in MM maintenance treatment. With the continuous development of proteasome inhibitor maintenance treatment in MM, the prognosis of the disease has been significantly improved. Our aim is to evaluate the effectiveness and adverse reactions of proteasome inhibitors in maintenance therapy for multiple myeloma, providing new ideas for clinical medication. MethodsFour databases containing randomized controlled studies on the effectiveness and safety of proteasome inhibitors in the maintenance therapy of multiple myeloma are retrieved by the computer. Once the quality of the literature has been thoroughly evaluated, run the data via the RevMan 5.3 software. ResultsEventually 8 studies were added in this systematic review. Compared with the placebo group, proteasome inhibitor in maintenance treatment of multiple myeloma patients with prolonged the survival without progression and overall existence. 5 studies reported the peripheral neuropathy of multiple myeloma in the treatment group compared to placebo group, which was remarkably greater (OR: 1.98; 95 % Cl: 1.35, 2.92; P < 0.001) compared to placebo group, Serious adverse events (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01), Rash (OR: 2.23; 95 % Cl: 1.62, 3.05; P < 0.001) and Vomiting (OR: 5.12; 95 % Cl: 3.36, 7.80; P < 0.001). The Serious adverse events of the treatment group were remarkably greater compared with the untreated group (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01). ConclusionThe study results proposed that proteasome inhibitors are effective in the multiple myeloma maintenance treatment compared with the placebo group. Bortezomib has certain advantages in prolonging PFS, followed by ixazomib and carfilzomib in terms of efficacy. Bortezombib may be superior to carfilzombib in extending OS. However, the adverse reactions caused by proteasome inhibitors, such as Peripheral neuropathy, Serious adverse events, Rash, Vomiting, etc., should be paid enough attention.

Comparison among different preclinical models derived from the same patient with a non-functional pancreatic neuroendocrine tumor.

Pancreatic neuroendocrine tumors are the second most common tumors of the pancreas, and approximately half of patients are diagnosed with liver metastases. Currently, the improvement in the efficacy of relevant treatment methods is still limited. Therefore, there is an urgent need for in-depth research on the molecular biological mechanism of pancreatic neuroendocrine tumors. However, due to their relatively inert biology, preclinical models are extremely scarce. Here, the patient-derived organoid, and patient-derived xenograft were successfully constructed. These two models and the previously constructed cell line named SPNE1 all derived from the same patient with a grade 3 non-functional pancreatic neuroendocrine tumor, providing new tumor modeling platforms, and characterized using immunohistochemistry, whole-exome sequencing, and single-cell transcriptome sequencing. Combined with a tumor formation experiment in immunodeficient mice, we selected the model that most closely recapitulated the parental tumor. Overall, the patient-derived xenograft model most closely resembled human tumor tissue.

Exosome-mediated Repair of Intervertebral Disc Degeneration: The Potential Role of miRNAs.

Intervertebral disc degeneration (IVDD) is a serious condition that manifests as low back pain, intervertebral disc protrusion, and spinal canal stenosis. At present, the main treatment methods for IVDD are surgical interventions such as discectomy, total disc replacement, and spinal fusion. However, these interventions have shown limitations, such as recurrent lumbar disc herniation after discectomy, lesions in adjacent segments, and failure of fixation. To overcome these shortcomings, researchers have been exploring stem cell transplantation therapy, such as mesenchymal stem cell (MSC) transplantation, but the treatment results are still controversial. Therefore, researchers are in search of new methods that are more efficient and have better outcomes. The exosomes from stem cells contain a variety of bioactive molecules that mediate cell interactions, and these components have been investigated for their potential therapeutic role in the repair of various tissue injuries. Recent studies have shown that MSC-derived miRNAs in exosomes and vesicles have therapeutic effects on nucleus pulposus cells, annulus fibrosus, and cartilage endplate. miRNAs play a role in many cell activities, such as cell proliferation, apoptosis, and cytokine release, by acting on mRNA translation, and they may have immense therapeutic potential, especially when combined with stem cell therapy. This article reviews the current status of research on intervertebral disc repair, especially with regard to the latest research findings on the molecular biological mechanisms of miRNAs in MSC-derived exosomes in intervertebral disc repair.

A Number of the N-terminal RASSF Family: RASSF7.

The Ras association domain family 7 (RASSF7, also named HRC1), a potential tumor-related gene, located on human chromosome 11p15, has been identified as an important member of the N-terminal RASSF family. Whereas, the molecular biological mechanisms of RASSF7 in tumorigenesis remain to be further established. We perform a systematic review of the literature and assessment from PUBMED and MEDLINE databases in this article. RASSF7 plays a significant role in mitosis, microtubule growth, apoptosis, proliferation and differentiation. Many research literature shows that the RASSF7 could promote the occurrence and advance of human tumors by regulating Aurora B, MKK4, MKK7, JNK, YAP, MEK, and ERK, whereas, it might inhibit c-Myc and thus lead to the suppression of tumorigenesis. The pregulation of RASSF7 often occurs in various malignancies such as lung cancer, neuroblastoma, thyroid neoplasm, hepatocellular cancer, breast cancer and gastric cancer. The expression stage of RASSF7 is positively correlated with the tumor TNM stage. In this review, we primarily elaborate on the acknowledged structure and progress in the various biomechanisms and research advances of RASSF7, especially the potential relevant signaling pathways. We hope that RASSF7 , a prospective therapeutic target for human malignancies, could play an available role in future anti-cancer treatment.

The mechanism of Taohong Siwu decoction in treating chemotherapy-induced peripheral neuropathy: a network pharmacology and molecular docking study.

Taohong Siwu decoction (THSWD) is a classic traditional Chinese medicine (TCM) formula known for its effects in promoting blood circulation, removing blood stasis, and rejuvenating energy. There have been clinical reports of THSWD treating chemotherapy-induced peripheral neuropathy (CIPN) caused by paclitaxel. We conducted a network pharmacology and molecular docking analysis to further clarify the molecular mechanisms by which THSWD exerts its protective effects against CIPN. Chemical components of THSWD and their corresponding targets were obtained through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and related targets of CIPN were searched in disease databases including Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), GeneCards, and DrugBank. Common targets between THSWD and CIPN were identified using Venn diagrams. A protein-protein interaction (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), which was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. AutoDock and PyMOL were used for the molecular docking validation of the key components of THSWD with core targets. At total of 69 chemical components of THSWD were identified, corresponding to 856 targets; 2,297 targets were associated with CIPN, with an intersection of 105 common targets. PPI analysis identified eight core targets: MYC, TNF, MAPK14, AKT1, ESR1, RELA, TP53, and HSP90AA1; KEGG enrichment analysis implicated signaling pathways such as PI3K-Akt, NF-κB, and HIF-1, etc. Molecular docking results indicated that the selected active components and their corresponding target proteins have good binding activity. Through network pharmacology, this study found that THSWD has significant advantages in treating CIPN. By analyzing potential core targets, biological functions, and involved signaling pathways, we clarified the potential molecular biological mechanisms involved in THSWD's treatment effect. This study provides a theoretical basis for the clinical application of THSWD in treating CIPN.

Benefits and Pitfalls of Re-Operation for Recurrent Meningioma

Malignant forms of meningioma, such as atypical and anaplastic meningiomas, commonly relapse. Recently, there have been many reports elucidating the molecular biological mechanisms underlying meningioma recurrence. Tumors with loss of CDKN(cyclin dependent kinase)2A and 2B or lack of the tri-methylation of lysine 27 on histone H3 protein have a particularly high recurrence rate. In general, primary treatment for recurrent meningiomas comprises stereotactic radiosurgery(SRS)or stereotactic radiotherapy(SRT). However, re-operation is recommended for SRS-, SRT-refractory tumors. One of the benefits of reoperation is that it allows tumor control while decompressing the normal tissue, and changing the tumor microenvironment. Another is that it facilitates the acquisition of pathological and molecular genetic information, which can enable clinicians to recommend precision medicine. However, during reoperation, it is often difficult to detach the tumor from the surrounding brain tissue and cranial nerves because of severe adhesion. In cases of malignant meningiomas with multiple relapses, it is important to share the purpose and goal of the surgery with the patients and their families. In other words, which is being prioritized more, a high resection rate or functional outcomes? Furthermore, salvage surgery should also be a consideration.

Screening of potential hub genes involved in Kidney Wilms tumor via bioinformatics analysis and experimental validation

BackgroundWilms tumor (WT) is the most common pediatric embryonal tumor. Improving patient outcomes requires advances in understanding and targeting the multiple genes and cellular control pathways, but its pathogenesis is currently not well-researched. We aimed to identify the potential molecular biological mechanism of WT and develop new prognostic markers and molecular targets by comparing gene expression profiles of Wilms tumors and fetal normal kidneys.MethodsDifferential gene expression analysis was performed on Wilms tumor transcriptomic data from the GEO and TARGET databases. For biological functional analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were utilized. Out of 24 hub genes identified, nine were found to be prognostic-related through univariate Cox regression analysis. These nine genes underwent LASSO regression analysis to enhance the predictive capability of the model. The key hub genes were validated in the GSE73209 datasets, and cell function experiments were conducted to identify the genes’ functions in WiT-49 cells.ResultsThe enrichment analysis revealed that DEGs were significantly involved in the regulation of angiogenesis and regulation of cell differentiation. 24 DEGs were identified through PPI networks and the MCODE algorithm, and 9 of 24 genes were related to WT patients’ prognosis. EMCN and CCNA1 were identified as key hub genes, and related to the progression of WT. Functionally, over-expression of EMCN and CCNA1 knockdown inhibited cell viability, proliferation, migration, and invasion of Wilms tumor cells.ConclusionsEMCN and CCNA1 were identified as key prognostic markers in Wilms tumor, suggesting their potential as therapeutic targets. Differential gene expression and enrichment analyses indicate significant roles in angiogenesis and cell differentiation.

Reveling the micromolecular biological mechanism of acetate, thiosulfate and Fe0 in ecological floating beds for treating low C/N wastewater: Insight into nitrogen removals and greenhouse gases reductions

Selecting an appropriate electron donor to enhance nitrogen removal for treating low C/N wastewater in ecological floating beds (EFBs) is controversy. In this study, a systematic and comprehensive evaluation of sodium acetate (EFB-C), sodium thiosulfate (EFB-S) and iron scraps (EFB-Fe) was performed in a 2-year experiment on long-term viability including nitrogen removal and greenhouse gas emissions associated with key molecular biological mechanisms. The results showed that EFB-C (43–85 %) and EFB-S (40–88 %) exhibited superior total nitrogen (TN) removal. Temperature and hydraulic retention time (HRT) have significant impacts on TN removal of EFB-Fe, however, it could reach 86 % under high temperature (30–35 °C) and a long HRT (3 days), and it has lowest N2O (0–6.2 mg m−2 d−1) and CH4 (0–5.3 mg m−2 d−1) fluxes. Microbial network analysis revealed that the microbes changed from competing to cooperating after adding electron donors. A higher abundance of anammox genera was enriched in EFB-Fe. The Mantel's test and structural equation model provided proof of the differences, which showed that acetate and thiosulfate were similar, whereas Fe0 was different in the nitrogen removal mechanism. Molecular biology analyses further verified that heterotrophic, autotrophic, and mixotrophic coupled with anammox were the main TN removal pathways for EFB-C, EFB-S, and EFB-Fe, respectively. These findings provide a better understanding of the biological mechanisms for selecting appropriate electron donors for treating low C/N wastewater.

Network pharmacology mechanism exploration of forsythia in analgesic treatment of rheumatic arthritis

Objective: This paper aims to investigate the genetic intersections and molecular biological mechanisms among the principal components of rheumatic arthritis, pain, and Forsythia utilizing bioinformatics and network pharmacology. The study seeks to ascertain the potential utility of Forsythia in the analgesic treatment of rheumatic arthritis, offering valuable insights for future research endeavors. Methods: Initially, the primary components of Fructus Forsythia were identified in the TCMSP database, and the corresponding genes linked to these active constituents were determined. Subsequently, relevant genes associated with "rheumatic arthritis" and "pain" were extracted from the GeneCards database. The intersection genes between Forsythia and rheumatic arthritis/pain were identified through microarray analysis, visualized using a Venn diagram. Further analyses included Gene Ontology (GO) enrichment, KEGG pathway exploration, construction of protein-protein interaction (PPI) networks, and prediction of hub genes. The hub gene was validated using the GEO database to enhance data reliability and draw conclusive findings. Results: The study identified 108 active components, 1402 genes related to rheumatic arthritis, and 14183 pain-related targets. Through intersection analysis, 37 potential targets of Forsythia for rheumatic arthritis pain management were revealed. The PPI network highlighted Fos, HIF1A, RELA, EGFR, PRKCA, IKBKB, NFKBIA, MAPK8, and VEGFA as key therapeutic targets. Validation using the GEO database confirmed Fos, HIF1A, RELA, and EGFR as crucial targets for treatment. Conclusions: Based on an in-depth analysis of hub gene functionalities, it was observed that the active ingredient forsythin exhibited strong binding activity with the potential target Fos. Additionally, KEGG pathway analysis indicated the involvement of key pathways such as the cancer signaling pathway and tumor necrosis factor signaling pathway in the pathogenesis of rheumatic arthritis. Considering the experimental results and existing literature on the efficacy of Forsythia in rheumatic arthritis treatment, it is concluded that Forsythia shows promise for analgesic therapy in rheumatic arthritis.

Molecular biological mechanism of fillers with surface micro-electric field to enhance biodegradation of kitchen-oil wastewater

The kitchen-oil wastewater is characterized by a high concentration of organic matter, complex composition and refractory pollutants, which make wastewater treatment more difficult. Based on the study of using micro-electric field characteristic catalyst HCLL-S8-M to enhance the electron transfer between microorganisms in kitchen-oil wastewater which further improved the COD removal rate, we focus on the microbial community, intracellular metabolism and extracellular respiration, and make an in-depth analysis of the molecular biological mechanisms to microbial treatment in wastewater. It is found that electroactive microorganisms are enriched on the material surface, and the expression levels of cytochrome c and riboflavin genes related to electron transfer are up-regulated, confirming that the surface micro-electric field structure could enhance the electron transfer between microbial species and improve the efficiency of wastewater degradation. This study provides a new idea for the treatment of refractory organic wastewater.

Urine Proteomic Signatures of Mild Hypothermia Treatment in Cerebral Ischemia–Reperfusion Injury in Rats

Mild hypothermia (MH) is an effective measure to alleviate cerebral ischemia–reperfusion (I/R) injury. However, the underlying biological mechanisms remain unclear. This study set out to investigate dynamic changes in urinary proteome due to MH in rats with cerebral I/R injury and explore the neuroprotective mechanisms of MH. A Pulsinelli’s four-vessel occlusion (4-VO) rat model was used to mimic global cerebral I/R injury. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was employed to profile the urinary proteome of rats with/without MH (32 °C) treatment after I/R injury. Representative differentially expressed proteins (DEPs) associated with MH were validated by western blotting in hippocampus. A total of 597 urinary proteins were identified, among which 119 demonstrated significant changes associated with MH. Gene Ontology (GO) annotation of the DEPs revealed that MH significantly enriched in endopeptidase activity, inflammatory response, aging, response to oxidative stress and reactive oxygen species, blood coagulation, and cell adhesion. Notably, changes in 12 DEPs were significantly reversed by MH treatment. Among them, 8 differential urinary proteins were previously reported to be closely associated with brain disease, including NP, FZD1, B2M, EPCR, ATRN, MB, CA1and VPS4A. Two representative proteins (FZD1, B2M) were further validated by western blotting in the hippocampus and the results were shown to be consistent with urinary proteomic analysis. Overall, this study strengthens the idea that urinary proteome can sensitively reflect pathophysiological changes in the brain, and appears to be the first study to explore the neuroprotective effects of MH by urinary proteomic analysis. FZD1 and B2M may be involved in the most fundamental molecular biological mechanisms of MH neuroprotection.Graphical In a 4-VO rat model, 119 urinary proteins demonstrated significant changes associated with MH. MH is enriched in endopeptidase activity, inflammatory response, oxidative stress, etc, and significantly reversed changes in 12 DEPs. FZD1 and B2M are thought to be involved in the most fundamental molecular biological mechanisms of MH neuroprotection.

The Role of Interferon-Induced Proteins with Tetratricopeptide Repeats 1 and 2 in Sepsis-Induced Acute Liver Injury.

Sepsis refers to a life-threatening organ dysfunction which can be resulted from the infection-induced dysregulated host response. A large number of inflammatory cytokines are released to act on the liver, making the liver one of the common target organs for the development of multiple organ dysfunction syndrome (MODS) in patients with sepsis. Sepsis-induced acute liver injury (SALI) can aggravate systemic disease. As a result, it is of great clinical significance to comprehend the molecular biological mechanism of SALI and to identify the markers for evaluating SALI. Interferon-induced proteins with tetratricopeptide repeats 1 and 2 (IFIT1, IFIT2) have been recognized as the anti-inflammatory factors that are widely expressed in various organs. The present study was aimed at clarifying the roles of IFIT1 and IFIT2 in the development of SALI. A two-sample Mendelian randomization (MR) analysis was employed. Summary statistics datas were obtained from GWAS for inflammatory factors [tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], IFIT2, and sepsis as well as liver injury. Independent SNPs were selected as instrumental variables (IVs). Inverse variance weighted (IVW) in the MR analysis was adopted as the primary method for estimating the causal associations of inflammatory factors and IFIT2 with two diseases, and the associations of inflammatory factors with IFIT2. Additionally, weighted median method, MR-Egger and sensitivity analyses were applied in assessing the robustness of the results and ensure the result reliability. Subsequently, 119 healthy volunteers, 116 patients with sepsis and 116 SALI patients were recruited. The ELISA method was employed to quantify the expression levels of TNF-α, IL-1β, and IL-6. Additionally, qRT-PCR was conducted to measure the expression of IFIT1 and IFIT2. Furthermore, the correlations of IFIT1 and IFIT2 with inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were explored. As shown by the MR analysis, the genetically predisposed sepsis was significantly associated with the risk of IL-1β, with an odds ratio (OR) of 1.069 (95% confidence interval (CI), 1.015-1.127, p = 0.0119), and negatively associated with the risk of IL-6, with an OR of 0.880 (95% CI: 0.792-0.979, p= 0.0184). Meanwhile, there were positive causal effects of IL-6 (OR = 1.269, 95% CI: 1.032-1.561, p= 0.0238), IL-1β (OR = 1.106, 95% CI: 1.010-1.211, p = 0.0299) and IFIT2 (OR = 1.191, 95% CI: 1.045-1.359, p = 0.0090) on liver injury. Additionally, there was a positive causal effect of IFIT2 (OR = 1.164, 95% CI: 1.035-1.309, p= 0.0110) on IL-1β. Upon sensitivity analyses, there was weak evidence of such effects, indicating that the findings of this study were robust and reliable. Our results revealed the elevated levels of TNF-α, IL-1β, and IL-6 in the blood samples of sepsis and SALI patients (p < 0.0001). Conversely, IFIT1 and IFIT2 demonstrated the significantly decreased levels in peripheral blood mononuclear cells (PBMCs) of SALI patients (p < 0.0001). Furthermore, the expression levels of IFIT1 and IFIT2 were both negatively correlated with ALT activity (r = -0.3426, p = 0.0002; r = -0.3069, p = 0.0008) and AST activity (r = -0.2483, p = 0.0072; r = -0.3261, p = 0.0004), respectively. Moreover, the expression of IFIT1 and IFIT2 was both negatively related to the levels of TNF-α (r = -0.5027, p < 0.0001; r = -0.4218, p < 0.0001), IL-1β (r = -0.3349, p = 0.0002; r = -0.4070, p < 0.0001) and IL-6 (r = -0.2734, p = 0.0030; r = -0.3536, p < 0.0001), respectively. IFIT1 and IFIT2 can serve as the diagnostic markers for sepsis-related liver injury, and IFIT1 and IFIT2 may participate in the pathological process of sepsis-related liver injury by regulating inflammation and liver function.