Efficient removal of Chromium(VI) from wastewater based on magnetic multiwalled carbon nanotubes coupled with deep eutectic solvents.

Industrial wastewater containing heavy metal Cr(VI) seriously affects the health of organisms and may even lead to cancer. Developing efficient adsorbents that can quickly separate heavy metals is crucial for treating wastewater. In this study, magnetic multiwalled carbon nanotubes (MMWCNTs) with moderate particle size and abundant surface active sites were prepared by coating multiwalled carbon nanotubes with magnetic nanoparticles. The results of FTIR, XRD, TG, VSM, BET, and EDS showed MWCNTs completely encapsulated on the surface of the magnetic nanoparticles, with a particle size of approximately 30 nm. Oxygenated groups provided abundant surface active sites and formed numerous mesopores. The response surface methodology was used to optimize the adsorbent dose, adsorption contact time and adsorption temperature, and the removal rate of Cr(VI) was more than 95%. The quasi-second order kinetics and Freundlich adsorption isotherm model explained the adsorption process to Cr(VI). MMWCNTs interacted with Cr(VI) through electrostatic attraction, reduction reactions, complexation, and other means. The extensive hydrogen bonding of the green solvent deep eutectic solvent (DES) was employed to desorb the MMWCNTs and desorption rate exceed 90%. Even after five adsorption-regeneration cycles, the adsorbent maintained a high capacity. In conclusion, these novel MMWCNTs, as efficient adsorbents paired with DES desorption, hold broad potential for application in the treatment of Cr(VI)-contaminated wastewater.

Enhancing the high-temperature energy storage properties of PEI dielectrics by constructing trap-rich covalently cross-linked networks via POSS-functionalized BNNS.

Polymer films are ideal dielectric materials for energy storage capacitors due to their light weight and flexibility, but lower energy density and poor heat resistance greatly limit their application in high-temperature energy storage. Unlike the traditional method of solely adding wide-bandgap inorganic fillers to enhance energy density, in this study we constructed trap-rich hybrid covalently cross-linked networks in polyetherimide (PEI) via reactive polyhedral oligomeric silsesquioxane (POSS)-functionalized boron nitride nanosheets (BNNS@POSS), which not only serve as interfacial layers for dielectric transitions and insulating barriers but also create deeper traps and higher energy barriers in the region of cross-linked chains. This strategy based on the co-modulation of interfaces and traps achieved the compatibility of high polarization and high breakdown strength and improved energy storage performance. Therefore, the composite film BNNS@POSS/PEI with the addition of 5 wt% BNNS@POSS achieved a maximum discharge energy density and charge-discharge efficiency at 150 °C of 6.16 J cm-3 and 89.92%, and maintained high values at 200 °C of 4.12 J cm-3 and 88.38%, respectively. Moreover, the glass transition temperature (Tg) of the composite dielectrics increased by 20.2 °C. This work provides a promising candidate material and development directions for research in the field of high-temperature energy storage capacitors.

Sideroflexin-1 promotes progression and sensitivity to lapatinib in triple-negative breast cancer by inhibiting TOLLIP-mediated autophagic degradation of CIP2A.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and it lacks specific therapeutic targets and effective treatment protocols. By analyzing a proteomic TNBC dataset, we found significant upregulation of sideroflexin 1 (SFXN1) in tumor tissues. However, the precise function of SFXN1 in TNBC remains unclear. Immunoblotting was performed to determine SFXN1 expression levels. Label-free quantitative proteomics and liquid chromatography-tandem mass spectrometry were used to identify the downstream targets of SFXN1. Mechanistic studies of SFXN1 and cellular inhibitor of PP2A (CIP2A) were performed using immunoblotting, immunofluorescence staining, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Functional experiments were used to investigate the role of SFXN1 in TNBC cells. SFXN1 was significantly overexpressed in TNBC tumor tissues and was associated with unfavorable outcomes in patients with TNBC. Functional experiments demonstrated that SFXN1 promoted TNBC growth and metastasis in vitro and in vivo. Mechanistic studies revealed that SFXN1 promoted TNBC progression by inhibiting the autophagy receptor TOLLIP (toll interacting protein)-mediated autophagic degradation of CIP2A. The pro-tumorigenic effect of SFXN1 overexpression was partially prevented by lapatinib-mediated inhibition of the CIP2A/PP2A/p-AKT pathway. These findings may provide a new targeted therapy for patients with TNBC.

Identification of functional sgRNA mutants lacking canonical secondary structure using high-throughput FACS screening.

Coexpressing multiple identical single guide RNAs (sgRNAs) in CRISPR-dependent engineering triggers genetic instability and phenotype loss. To provide sgRNA derivatives for efficient DNA digestion, we design a high-throughput digestion-activity-dependent positive screening strategy and astonishingly obtain functional nonrepetitive sgRNA mutants with up to 48 out of the 61 nucleotides mutated, and these nonrepetitive mutants completely lose canonical secondary sgRNA structure in simulation. Cas9-sgRNA complexes containing these noncanonical sgRNAs maintain wild-type level of digestion activities in vivo, indicating that the Cas9 protein is compatible with or is able to adjust the secondary structure of sgRNAs. Using these noncanonical sgRNAs, we achieve multiplex genetic engineering for gene knockout and base editing in microbial cell factories. Libraries of strains with rewired metabolism are constructed, and overproducers of isobutanol or 1,3-propanediol are identified by biosensor-based fluorescence-activated cell sorting (FACS). This work sheds light on the remarkable flexibility of the secondary structure of functional sgRNA.

Impact of high fat and low lean mass phenotype on bone mineral content: A cross-sectional study of Chinese adolescent population.

BACKGROUND AND OBJECTIVE: Research on body composition phenotypes and bone health in adolescents is limited. Hence, this study aimed to analyze the relationship between different body composition phenotypes, bone mineral content, and bone metabolism markers in Chinese adolescents. METHODS: In this cross-sectional study, 1852 adolescents aged 12 to 18 years were selected from six schools in Yinchuan City between 2017 and 2020 using stratified cluster random sampling. The participant's body composition and bone mineral content (BMC) were measured using bioelectrical impedance analysis (BIA). Serum bone metabolic markers (OC, CTX, and Ca) were measured. Based on their FMI and LMI, individuals were categorized into four body composition phenotypes: low fat mass-low lean mass (LFMI-LLMI), low fat mass-high lean mass (LFMI-HLMI), high fat mass-high lean mass (HFMI-HLMI), high fat mass-low lean mass (HFMI-LLMI). RESULTS: There was a statistically significant difference between the four different body composition phenotypes with BMC, CTX and Ca in boys (all P < 0.05), similar conclusions were found in girls, except the OC and CTX. After adjusting for age, gender, smoking, drinking, and others, compared with the LFMI-HLMI reference group, the two high FMI groups (HFMI-LLMI and HFMI-HLMI) had a greater negative correlation with BMC, while the low BMC risk of the HFMI-LLMI group was the highest (OR = 33.28; 95%CI: 11.12-99.63; P < 0.001). The correlation between BMC of different body composition phenotypes in boys was greater than that in girls. HFMI-HLMI is a risk phenotype negatively associated with Ca content (ß = -0.12; 95%CI: -0.19 to -0.04; P < 0.05). Regardless of body composition level, BMC was always negatively correlated with fat mass (LLMI: ß = -0.27; 95%CI: -0.32-0.21; HLMI: ß = -0.52, 95%CI: -0.65-0.40) and positively correlated with lean mass (LFMI: ß =0.24; 95%CI: 0.20-0.28; HFMI: ß =0.23, 95%CI:0.13-0.33) (all P < 0.001). The fat mass showed different correlations with OC and CTX in girls and boys based on LLMI or HLMI (all P < 0.05). CONCLUSION: HFMI-LLMI is a risk phenotype of low BMC in Chinese adolescents, and the relationship between fat mass and bone metabolism markers is affected by lean body mass and gender.

Recent advances in germinated cereal and pseudo-cereal starch: Properties and challenges in its modulation on quality of starchy foods.

Germination is an environmentally friendly process with no use of additives, during which only water spraying is done to activate endogenous enzymes for modification. Furthermore, it could induce bioactive phenolics accumulation. Controlling endogenous enzymes' activity is essential to alleviate granular disruption, crystallinity loss, double helices' dissociation, and molecular degradation of cereal and pseudo-cereal starch. Post-treatments (e.g. thermal and high-pressure technology) make it possible for damaged starch to reassemble towards well-packed structure. These contribute to alleviated loss of solubility and pasting viscosity, improved swelling power, or enhanced resistant starch formation. Cereal or pseudo-cereal flour (except that with robust structure) modified by early germination is more applicable to produce products with desirable texture and taste. Besides shortening duration, germination under abiotic stress is promising to mitigate starch damage for better utilization in staple foods.

The mechanism of polyphyllin in the treatment of gastric cancer was verified based on network pharmacology and experimental validation.

Background: Polyphyllin is a class of saponins extracted from Paris polyphylla rhizomes and has been used in clinical application in China for more than 2000 years. However, the mechanism for treating gastric cancer (GC) is still unclear. This study was designed to predict the targets and mechanisms of total Polyphyllin from Paris polyphylla rhizomes for the treatment of GC. Method: Firstly, PubChem and Swiss Target Prediction databases were utilized to collect the 12 ingredients of total Polyphyllin from Paris polyphylla rhizomes and their targets. GC-related genes were obtained from the GEO database. Then the intersecting targets to all these molecules that identified using Venny. Secondly, the intersecting targets were imported into STRING platform for protein-protein interaction (PPI) network. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted in DAVID website. In addition, the GEPIA was applied to perform the expression levels, transcript levels, staging, and overall survival of hub genes. In addition, we used AutoDock Vina to evaluate binding affinity of molecular docking between key ingredients and anti-GC targets. In vitro cell experiments, we detected the cell viability of gastric cancer cells at 24, 36, and 48 h using CCK-8 assay. The G0/G1 of cell cycle and apoptosis were detected by flow cytometry. Finally, quantitative real time polymerase chain reaction (qRT-PCR) was used to detect the level of hub genes, and Western blot was used to detect the changes of PI3K/Akt signal pathway. Results: Firstly, we identified 12 ingredients and 286 targets of total Polyphyllin. A total of 2653 GC-related differentially expressed genes (DEGs) were collected, including 1366 up-regulated genes and 1287 down-regulated genes. Moreover, 45 targets were obtained after intersection. Secondly, results of the GO enrichment suggested that these genes were closely related to cell proliferation, migration and aging. KEGG analysis suggested that Polyphyllin in GC therapy were mostly regulated by multiple pathways, including the pathways in cancer, calcium signaling pathway, Rap1 signaling pathway, phospholipase D signaling pathway, etc. In addition, GEPIA results exhibited that PDGFRB, KIT, FGF1, GLI1, F2R, and HIF1A were associated with GC progression, stage, and survival. Besides, the molecular docking results further confirmed that the binding energy of Polyphyllin Ⅲ with HIF1A was minimal. In vitro cell experiments, Polyphyllin Ⅲ inhibited the cell viability of gastric cancer cells, blocked the cell cycle G0/G1 phase, and induced cell apoptosis. In addition, Polyphyllin Ⅲ down-regulated the mRNA levels of PDGFRB, KIT, FGF1, GLI1, F2R, and HIF1A, and regulated the PI3K/Akt signal pathway. Conclusions: The results revealed that total Polyphyllin treated GC through multiple targets, multiple channels, and multiple pathways. In addition, Polyphyllin Ⅲ played an anti-gastric cancer role by inhibiting the proliferation of gastric cancer.

The DRAP1/DR1 Repressor Complex Increases mTOR Activity to Promote Progression and Confer Everolimus Sensitivity in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Transcriptional dysregulation is a hallmark of cancer, and several transcriptional regulators have been demonstrated to contribute to cancer progression. Here, we identified upregulation of the transcriptional corepressor DRAP1 in TNBC, which was closely associated with poor recurrence-free survival in TNBC patients. DRAP1 promoted TNBC proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, the DR1/DRAP1 heterodimer complex inhibited expression of the arginine sensor CASTOR1 and thereby increased activation of mTOR, which sensitized TNBC to treatment with the mTOR inhibitor everolimus. DRAP1 and DR1 also formed a positive feedback loop. DRAP1 enhanced the stability of DR1, recruiting the deubiquitinase USP7 to inhibit its proteasomal degradation; in turn, DR1 directly promoted DRAP1 transcription. Collectively, this study uncovered a DRAP1-DR1 bidirectional regulatory pathway that promotes TNBC progression, suggesting that targeting the DRAP1/DR1 complex might be a potential therapeutic strategy to treat TNBC.

Current research insights into the role of CTLA-4 in hepatitis B virus (HBV) infection.

Chronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV-specific T cells, which is regulated by various co-suppressor molecules. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is among these co-suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV-specific T cells. CTLA-4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA-4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA-4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA-4 may contribute to HBV infection, as well as the development of HBV-induced cirrhosis and hepatocellular carcinoma.

Multifunctional Integrated Organic-Inorganic-Metal Hybrid Aerogel for Excellent Thermal Insulation and Electromagnetic Shielding Performance.

Vehicles operating in space need to withstand extreme thermal and electromagnetic environments in light of the burgeoning of space science and technology. It is imperatively desired to high insulation materials with lightweight and extensive mechanical properties. Herein, a boron-silica-tantalum ternary hybrid phenolic aerogel (BSiTa-PA) with exceptional thermal stability, extensive mechanical strength, low thermal conductivity (49.6 mW m-1 K-1), and heightened ablative resistance is prepared by an expeditious method. After extremely thermal erosion, the obtained carbon aerogel demonstrates noteworthy electromagnetic interference (EMI) shielding performance with an efficiency of 31.6 dB, accompanied by notable loading property with specific modulus of 272.8 kN·m kg-1. This novel design concept has laid the foundation for the development of insulation materials in more complex extreme environments.

Nurses' knowledge, attitudes and practices regarding the application of the injury severity score in emergency departments: A cross-sectional multicentre study.

AIMS AND OBJECTIVES: To investigate knowledge, attitudes, and practices regarding the application of the Injury Severity Score (ISS) among emergency department nurses in China and the factors influencing these variables. BACKGROUND: ISS is the first trauma scoring method to be developed and the most widely used in clinical practice. The correct application of the ISS by emergency department nurses plays an important role in assisting in the diagnosis and treatment of trauma patients, and it is crucial to understand nurses' knowledge, attitudes and practices. DESIGN: A cross-sectional multicentre study. METHODS: Nurses from the emergency departments of 25 grade II and grade III hospitals in Gansu Province, China participated in this study. Data was collected online using a self-administered questionnaire. Student's t-test or analysis of variance was performed to compare the differences between the groups. Multiple logistic regression analysis identified factors influencing nurses' knowledge, attitudes and practices regarding applying ISS. A STROBE checklist was used to report findings. RESULTS: Among 459 nurses, a good level of attitude and passing levels of knowledge and practice regarding applying the ISS were revealed. Nurses in higher hospital grades, who had been exposed to ISS and received training had higher levels of knowledge and practices. Previous exposure to the ISS and training related to it were factors that influenced nurses' attitudes. CONCLUSIONS: Chinese emergency department nurses' knowledge, attitudes and practices of applying the ISS still need to be improved. Hospitals and nursing managers should provide training opportunities for nurses about ISS knowledge and practices, while grade II hospitals should pay more attention to training and continuing education in this area. RELEVANCE TO CLINICAL PRACTICE: In hospitals, nursing managers may benefit from enhancing related education and training to promote the emergency department nurses' knowledge and practice of the ISS, by developing specific curricula and providing continuing education and training opportunities, while grade II hospitals should pay more attention to training and continuing education in this area. NO PATIENT OR PUBLIC CONTRIBUTIONS: This study focused on emergency department nurses' knowledge, attitudes, and practices regarding the application of the ISS. The research questions and design were derived from clinical nursing practice, literature review, and expert panel review, and patients or the public are temporarily not involved.

Impact of ozonation on disinfection byproducts formation from phenylalanine during chlorination.

As a strong oxidizing agent, ozone is used in some water treatment facilities for disinfection, taste and odor control, and removal of organic micropollutants. Phenylalanine (Phe) was used as the target amino acid to comprehensively investigate variability of disinfection byproducts (DBPs) formation during chlorine disinfection and residual chlorine conditions subsequent to ozonation. The results showed that subsequent to ozonation, the typical regulated and unregulated DBPs formation potential (DBPsFP), including trichloromethane (TCM), dichloroacetonitrile (DCAN), chloral hydrate (CH), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), and trichloroacetamide (TCAcAm) increased substantially, by 2.4, 3.3, 5.6, 1.2, 2.5, and 6.0 times, respectively, compared with only chlorination. Ozonation also significantly increased the DBPs yield under a 2 day simulated residual chlorine condition that mimicked the water distribution system. DBPs formations followed pseudo first order kinetics. The formation rates of DBPs in the first 6 hr were higher for TCM (0.214 hr-1), DCAN (0.244 hr-1), CH (0.105 hr-1), TCAcAm (0.234 hr-1), DCAA (0.375 hr-1) and TCAA (0.190 hr-1) than thereafter. The peak DBPsFP of TCM, DCAN, CH, TCAcAm, DCAA, and TCAA were obtained when that ozonation time was set at 5-15 min. Ozonation times > 30 min increased the mineralization of Phe and decreased the formation of DBPs upon chlorination. Increasing bromine ion (Br-) concentration increased production of bromine- DBPs and decreased chlorine-DBPs formation by 59.3%-92.2% . Higher ozone dosages and slight alkaline favored to reduce DBP formation and cytotoxicity. The ozonation conditions should be optimized for all application purposes including DBPs reduction.

Experimental and theoretical studies on the compatibility of DNTF and typical hydrocarbon polymer binders.

3,4-bis(3-nitrofurazan-4-yl) furoxan (DNTF) is one of the third-generation energetic compounds with excellent comprehensive properties, which can be added to polymer bonded explosive (PBX) to improve energy levels and regulate sensitivity, so the compatibility of DNTF with other components in PBX, especially the binder, is the first question. Herein, two typical hydrocarbon polymers commonly used in PBX, which are hydroxyl-terminated polybutadiene (HTPB) and polyisobutylene (PIB), were selected as the binder, and the compatibility of HTPB and PIB with DNTF was investigated by differential scanning calorimetry (DSC), the vacuum stability test (VST), and in situ infrared spectroscopy (in situ IR). The results of compatibility experiments were verified by using the binding energy and solubility parameter criteria in molecular dynamics (MD). Experimental and MD simulation results showed that DNTF could be compatible with PIB but incompatible with HTPB. The frontier molecular orbital theory in quantum chemistry (QC) was adopted to explore the frontier orbital electron distribution and energy levels of DNTF/HTPB and DNTF/PIB composite systems to better understand the microscopic compatibility mechanism. The compatibility results of the two composite systems were explained from the perspective of electron transfer. All these can deduce that a hydrocarbon polymer binder with a saturated carbon-hydrogen bond at the end of the molecular chain has good compatibility with DNTF, compared with a hydroxyl group, which has bad compatibility with DNTF.

Elongin B promotes breast cancer progression by ubiquitinating tumor suppressor p14/ARF.

Elongin B (ELOB), a pivotal element in the ELOB/c-Cullin2/5-SOCS-box E3 ubiquitin-protein ligase complex, plays a significant role in catalyzing the ubiquitination and subsequent degradation of a broad spectrum of target proteins. Notably, it is documented to facilitate these processes. However, the regulatory role of ELOB in breast cancer remains ambiguous. In this study, through bio-informatic analysis of The Cancer Genome Atlas and Fudan University Shanghai Cancer Center database, we demonstrated that ELOB was over-expressed in breast cancer tissues and was related to unfavorable prognosis. Additionally, pathway enrichment analysis illustrated that high expression of ELOB was associated with multiple cancer promoting pathways, like cell cycle, DNA replication, proteasome and PI3K - Akt signaling pathway, indicating ELOB as a potential anticancer target. Then, we confirmed that both in vivo and in vitro, the proliferation of breast cancer cells could be significantly suppressed by the down-regulation of ELOB. Mechanically, immunoprecipitation and in vivo ubiquitination assays prompted that, as the core element of Cullin2-RBX1-ELOB E3 ligase (CRL2) complex, ELOB regulated the ubiquitination and the subsequent degradation of oncoprotein p14/ARF. Moreover, the anticancer efficacy of erasing ELOB could be rescued by simultaneous knockdown of p14/ARF. Finally, through analyzing breast cancer tissue microarrays and western blot of patient samples, we demonstrated that the expression of ELOB in tumor tissues was elevated in compared to adjacent normal tissues. In conclusion, ELOB is identified to be a promising innovative target for the drug development of breast cancer by promoting the ubiquitination and degradation of oncoprotein p14/ARF.

SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1.

Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer owing to the lack of effective therapeutic targets. Splicing factor 3a subunit 2 (SF3A2), a poorly defined splicing factor, was notably elevated in TNBC tissues and promoted TNBC progression, as confirmed by cell proliferation, colony formation, transwell migration, and invasion assays. Mechanistic investigations revealed that E3 ubiquitin-protein ligase UBR5 promoted the ubiquitination-dependent degradation of SF3A2, which in turn regulated UBR5, thus forming a feedback loop to balance these two oncoproteins. Moreover, SF3A2 accelerated TNBC progression by, at least in part, specifically regulating the alternative splicing of makorin ring finger protein 1 (MKRN1) and promoting the expression of the dominant and oncogenic isoform, MKRN1-T1. Furthermore, SF3A2 participated in the regulation of both extrinsic and intrinsic apoptosis, leading to cisplatin resistance in TNBC cells. Collectively, these findings reveal a previously unknown role of SF3A2 in TNBC progression and cisplatin resistance, highlighting SF3A2 as a potential therapeutic target for patients with TNBC.

Enhancer-promoter interactions are reconfigured through the formation of long-range multiway hubs as mouse ES cells exit pluripotency.

Enhancers bind transcription factors, chromatin regulators, and non-coding transcripts to modulate the expression of target genes. Here, we report 3D genome structures of single mouse ES cells as they are induced to exit pluripotency and transition through a formative stage prior to undergoing neuroectodermal differentiation. We find that there is a remarkable reorganization of 3D genome structure where inter-chromosomal intermingling increases dramatically in the formative state. This intermingling is associated with the formation of a large number of multiway hubs that bring together enhancers and promoters with similar chromatin states from typically 5-8 distant chromosomal sites that are often separated by many Mb from each other. In the formative state, genes important for pluripotency exit establish contacts with emerging enhancers within these multiway hubs, suggesting that the structural changes we have observed may play an important role in modulating transcription and establishing new cell identities.

Effects of Desmodium caudatum on Gastrointestinal Hormones and Intestinal Flora in Rats with Gastritis.

In order to preliminarily explore the effects of Desmodium caudatum on gastritis and intestinal flora in rats, a chronic gastritis rat model was established using the classic sodium salicylate method. Eighteen SPF rats were divided into three groups: the control group (Group C), the model group (Group M), and the treatment group (Group T). Pathological sections of the gastric wall were taken from rats in each group. Furthermore, the concentrations of gastrin and malondialdehyde in the serum of rats in each group were determined by ELISA. Additionally, the effects of D. caudatum on the intestinal flora of rats with gastritis were explored through a detailed comparison of gut bacterial communities in the three groups, employing Illumina-based 16S rRNA gene sequencing. The results indicated that D. caudatum decoction could reduce the malondialdehyde content and increase the gastrin content. Moreover, D. caudatum decoction was found to enhance the diversity and abundance of intestinal flora, exerting a positive impact on the treatment of gastritis by regulating and restoring the intestinal flora.

Molecular mechanisms of quetiapine bidirectional regulation of bipolar depression and mania based on network pharmacology and molecular docking: Evidence from computational biology.

BACKGROUND: Quetiapine monotherapy is recommended as the first-line option for acute mania and acute bipolar depression. However, the mechanism of action of quetiapine is unclear. Network pharmacology and molecular docking were employed to determine the molecular mechanisms of quetiapine bidirectional regulation of bipolar depression and mania. METHODS: Putative target genes for quetiapine were collected from the GeneCard, SwissTargetPrediction, and DrugBank databases. Targets for bipolar depression and bipolar mania were identified from the DisGeNET and GeneCards databases. A protein-protein interaction (PPI) network was generated using the String database and imported into Cytoscape. DAVID and the Bioinformatics platform were employed to perform the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the top 15 core targets. The drug-pathway-target-disease network was constructed using Cytoscape. Finally, molecular docking was performed to evaluate the interactions between quetiapine and potential targets. RESULTS: Targets for quetiapine actions against bipolar depression (126 targets) and bipolar mania (81 targets) were identified. Based on PPI and KEGG pathway analyses, quetiapine may affect bipolar depression by targeting the MAPK and PI3K/AKT insulin signaling pathways via BDNF, INS, EGFR, IGF1, and NGF, and it may affect bipolar mania by targeting the neuroactive ligand-receptor interaction signaling pathway via HTR1A, HTR1B, HTR2A, DRD2, and GRIN2B. Molecular docking revealed good binding affinity between quetiapine and potential targets. LIMITATIONS: Pharmacological experiments should be conducted to verify and further explore these results. CONCLUSIONS: Our findings suggest that quetiapine affects bipolar depression and bipolar mania through distinct biological core targets, and thus through different mechanisms. Furthermore, our results provide a theoretical basis for the clinical use of quetiapine and possible directions for new drug development.

Efficacy of Core Muscle Exercise Combined with Interferential Therapy in Alleviating Chronic Low Back Pain in High-Performance Fighter Pilots: A Randomized Controlled Trial.

BACKGROUND: Chronic low back pain (LBP) related to flight is a prevalent health issue in military aviation, impacting pilots. The objective of this investigation was to ascertain if the application of core muscle training in conjunction with interferential current (IFC) therapy results in a reduction in pain severity and associated disability, consequently enhancing core muscle functionality in Chinese Air Force high-performance fighter pilots experiencing chronic LBP. METHODS: Fifty-three fighter pilots with chronic LBP were randomized into 3 groups: a core muscle exercise combined with IFC group (CG, n = 19), a core muscle exercise group (EG, n = 19), and an IFC group (IG, n = 15). The three groups underwent therapeutic intervention 5 times a week for 12 weeks. The primary outcomes were pain intensity, Oswestry Disability Index (ODI) score and SF-12 health-related quality of life (PCS and MCS) score. Secondary outcomes included evaluations of trunk muscle strength, endurance, and range of motion (ROM) during medial/lateral rotation to assess muscle functionality. Measurements were obtained both before and after the implementation of the intervention therapy. RESULTS: After 12 weeks of intervention therapy, all the health condition parameters significantly improved among the three groups. However, the CG had a significant improvement in pain intensity compared to the EG (MD = - 0.84 scores; 95% CI = - 1.54 to - 0.15; p = 0.013) and the IG (MD = - 1.22 scores; 95% CI = - 1.96 to - 0.48; p = 0.000). Additionally, the CG led to greater conservation of ODI and improved SF-12 PCS scores than did the IG (p < 0.05). Finally, compared with those at baseline, the core muscle function parameters in the CG and EG improved significantly at the end of the study, but no statistically significant differences were observed between the two groups (p > 0.05). CONCLUSION: Among participants with chronic LBP, three intervention therapies appear effective in reducing pain, diminishing disability, and enhancing quality of life. Also, combined therapy significantly improved pain and disability compared to the other two monotherapies; moreover, combined therapy and core muscle exercise provided similar benefits in terms of core muscle function after 12 weeks of intervention therapy.