Integrated bioinformatics and multiomics reveal Liupao tea extract alleviating NAFLD via regulating hepatic lipid metabolism and gut microbiota.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) poses a significant global public health concern. Liupao tea (LPT) is a Chinese national geographical indication product renowned for its lipid-lowering properties. However, the precise mechanisms and active constituents contributing to the efficacy of LPT against NAFLD remain unclear. PURPOSE: This study aims to comprehensively explore the therapeutic potential of Liupao tea extract (LPTE) in alleviating NAFLD through an integrated strategy. METHODS: Initially, network pharmacology analysis was conducted based on LPTE chemical ingredient analysis, identifying core targets and key components. Potential active ingredients were validated through chemical standards based on LC-MS/MS. To confirm the pharmacological efficacy of LPTE in NAFLD, NAFLD mice models were employed. Alterations in hepatic lipid metabolism were comprehensively elucidated through integration of metabolomics, lipidomics, network pharmacology analysis, and real-time PCR analysis. To further explore the binding interactions between key components and core targets, molecular docking and microscale thermophoresis (MST) analysis were employed. Furthermore, to investigate LPTE administration effectiveness on gut microbiota in NAFLD mice, a comprehensive approach was employed. This included Metorigin analysis, 16S rRNA sequencing, molecular docking, and fecal microbiome transplantation (FMT). RESULTS: Study identified naringenin, quercetin, luteolin, and kaempferol as the potential active ingredients of LPTE. These compounds exhibited therapeutic potential for NAFLD by targeting key proteins such as PTGS2, CYP3A4, and ACHE, which are involved in the metabolic pathways of hepatic linoleic acid (LA) and glycerophospholipid (GP) metabolism. The therapeutic effectiveness of LPTE was observed to be comparable to that of simvastatin. Furthermore, LPTE exhibited notable efficacy in alleviating NAFLD by influencing alterations in gut microbiota composition (Proteobacteria phylum, Lactobacillus and Dubosiella genus) that perhaps impact LA and GP metabolic pathways. CONCLUSION: LPTE could be effective in preventing high-fat diet (HFD)-induced NAFLD by modulating hepatic lipid metabolism and gut microbiota. This study firstly integrated bioinformatics and multi-omics technologies to identify the potential active components and key microbiota associated with LPTE's effects, while also primally elucidating the action mechanisms of LPTE in alleviating NAFLD. The findings offer a conceptual basis for LPTE's potential transformation into an innovative pharmaceutical agent for NAFLD prevention.

Delivery of dental pulp stem cells by an injectable ROS-responsive hydrogel promotes temporomandibular joint cartilage repair via enhancing anti-apoptosis and regulating microenvironment.

Temporomandibular joint (TMJ) cartilage repair poses a considerable clinical challenge, and tissue engineering has emerged as a promising solution. In this study, we developed an injectable reactive oxygen species (ROS)-responsive multifunctional hydrogel (RDGel) to encapsulate dental pulp stem cells (DPSCs/RDGel in short) for the targeted repair of condylar cartilage defect. The DPSCs/RDGel composite exhibited a synergistic effect in the elimination of TMJ OA (osteoarthritis) inflammation via the interaction between the hydrogel component and the DPSCs. We first demonstrated the applicability and biocompatibility of RDGel. RDGel encapsulation could enhance the anti-apoptotic ability of DPSCs by inhibiting P38/P53 mitochondrial apoptotic signal in vitro. We also proved that the utilization of DPSCs/RDGel composite effectively enhanced the expression of TMJOA cartilage matrix and promoted subchondral bone structure in vivo. Subsequently, we observed the synergistic improvement of DPSCs/RDGel composite on the oxidative stress microenvironment of TMJOA and its regulation and promotion of M2 polarization, thereby confirmed that M2 macrophages further promoted the condylar cartilage repair of DPSCs. This is the first time application of DPSCs/RDGel composite for the targeted repair of TMJOA condylar cartilage defects, presenting a novel and promising avenue for cell-based therapy.

Case report: Report of a rare encounter: metastasis of renal cell carcinoma to the thyroid.

Renal cell carcinoma (RCC) is the most common renal tumor, with lung, bone, and liver being the primary sites of metastasis. Thyroid metastasis, on the other hand, is relatively uncommon. Metastatic tumors in the thyroid gland typically manifest as multiple or isolated nodules, which can be easily overlooked due to the lack of specific clinical and imaging features. However, the identification of thyroid metastasis suggests the presence of systemic metastasis and is indicative of a poor prognosis for patients. In this paper, we present two cases of thyroid metastasis following nephrectomy, with the objective of enhancing understanding among medical community regarding the diagnosis and treatment of thyroid metastasis originating from renal cell carcinoma. By raising awareness about this phenomenon, we emphasize the importance of early detection and diagnosis to improve patient prognoses. The implementation of standardized treatment protocols at the earliest possible stage is also emphasized. Through this research, we aim to contribute to the early identification and management of thyroid metastasis in patients with renal cell carcinoma, ultimately leading to improved outcomes.

Analysis of changes and correlation in condyle-fossa relationship after maxillary skeletal expansion.

OBJECTIVE: To investigate the changes in condyle-glenoid fossa relationship after maxillary skeletal expansion (MSE) and to verify the correlation between the condyle positional changes and expansion effect. METHODS: In this study, 20 patients (mean age 21.1 ± 5.7 years, 8 male, 12 female) with maxillary transverse deficiency (MTD) were treated with the MSE appliance, which contained molar bands and a expander with four micro-implants. The CBCT images were taken before expansion (T0), after expansion (T1) and after 6 months of maintenance (T2). The posterior TMJ space (PS), superior TMJ space (SS), anterior TMJ space, coronal lateral TMJ space (CLS), coronal medial TMJ space (CMS), condyle axis angle, maxillary basal bone width (BWM), inter-molars width, nasal bone width, molar inclination and molar palatal cusp height (U6H) were measured using Dolphin Imaging. RESULTS: At T1, compared with T0, the PS and SS significantly increased by 0.41 mm (P = .008) and 0.3 mm (P = .007). But only the SS significantly increased by 0.21 mm (P = .025) at T2. There was a significant difference of 0.37 mm (left-right, P = .014) between the left and right SS at T0, but no significant difference at T1 and T2. The increased BMW showed weak positive correlations with the change of PS (P = .015) and CMS (P = .031), and the decreased U6H showed weak negative correlations with the change of PS (P = .015) and CLS (P = .031) at T1. CONCLUSIONS: The use of MSE led to an increase in the SS and PS, which were weakly correlated with BWM and U6H. But this effect in the TMJ space gradually diminished after 6 months of maintenance, and the symmetry of the condyle-fossa relationship was preserved.

Radiation polymerization for the preparation of universal coatings: remarkable anti-fogging and frost-resisting performance.

Hydrophilic anti-fogging coatings have attracted considerable attention due to their ease of preparation and excellent fog resistance. In this study, a hydrophilic anti-fogging coating based on the random copolymer p(AA-co-SAS) was prepared using acrylic acid (AA) and sodium allylsulfonate (SAS) as monomers through radiation polymerization. The introduction of SAS successfully transformed the random copolymer from a gel state into a film-forming polymer solution. The presence of AA structural units in p(AA-co-SAS) improved the film-forming properties of the polymer solution. Additionally, there was a positive correlation between the proportion of SAS structural units in the random copolymer and the scratch hardness and wetting properties of the coating. After coating polycarbonate (PC) sheets, the surface hydrophilicity was significantly enhanced, with the contact angle of PC-AA10/SAS5 decreasing from 100.1° to 18.8° within 50 seconds. The outstanding wetting properties endowed the coating with exceptional anti-fogging and frost-resisting performance. It exhibited optimal transparency under both testing conditions and demonstrated good stability during cyclic testing. Tape adhesion tests indicated that the adhesion between the coating and PC reached a 5B level. When AA10/SAS5 was applied to PET film, glass, and PMMA goggles, all samples showed excellent anti-fog performance. Even after being naturally placed for one year under ambient conditions, the PMMA goggles still maintained good performance in the anti-fog and frost resistance tests. The remarkable comprehensive properties of the polymer coating based on p(AA-co-SAS) suggest enormous potential applications in industries such as packaging, healthcare, and optical equipment.

CNN-HT: A Two-Stage Algorithm Selection Framework.

The No Free Lunch Theorem tells us that no algorithm can beat other algorithms on all types of problems. The algorithm selection structure is proposed to select the most suitable algorithm from a set of algorithms for an unknown optimization problem. This paper introduces an innovative algorithm selection approach called the CNN-HT, which is a two-stage algorithm selection framework. In the first stage, a Convolutional Neural Network (CNN) is employed to classify problems. In the second stage, the Hypothesis Testing (HT) technique is used to suggest the best-performing algorithm based on the statistical analysis of the performance metric of algorithms that address various problem categories. The two-stage approach can adapt to different algorithm combinations without the need to retrain the entire model, and modifications can be made in the second stage only, which is an improvement of one-stage approaches. To provide a more general structure for the classification model, we adopt Exploratory Landscape Analysis (ELA) features of the problem as input and utilize feature selection techniques to reduce the redundant ones. In problem classification, the average accuracy of classifying problems using CNN is 96%, which demonstrates the advantages of CNN compared to Random Forest and Support Vector Machines. After feature selection, the accuracy increases to 98.8%, further improving the classification performance while reducing the computational cost. This demonstrates the effectiveness of the first stage of the CNN-HT method, which provides a basis for algorithm selection. In the experiments, CNN-HT shows the advantages of the second stage algorithm as well as good performance with better average rankings in different algorithm combinations compared to the individual algorithms and another algorithm combination approach.

Multi-omics Combined with Machine Learning Facilitating the Diagnosis of Gastric Cancer.

Gastric cancer (GC) is a highly intricate gastrointestinal malignancy. Early detection of gastric cancer forms the cornerstone of precision medicine. Several studies have been conducted to investigate early biomarkers of gastric cancer using genomics, transcriptomics, proteomics, and metabolomics, respectively. However, endogenous substances associated with various omics are concurrently altered during gastric cancer development. Furthermore, environmental exposures and family history can also induce modifications in endogenous substances. Therefore, in this study, we primarily investigated alterations in DNA mutation, DNA methylation, mRNA, lncRNA, miRNA, circRNA, and protein, as well as glucose, amino acid, nucleotide, and lipid metabolism levels in the context of GC development, employing genomics, transcriptomics, proteomics, and metabolomics. Additionally, we elucidate the impact of exposure factors, including HP, EBV, nitrosamines, smoking, alcohol consumption, and family history, on diagnostic biomarkers of gastric cancer. Lastly, we provide a summary of the application of machine learning in integrating multi-omics data. Thus, this review aims to elucidate: i) the biomarkers of gastric cancer related to genomics, transcriptomics, proteomics, and metabolomics; ii) the influence of environmental exposure and family history on multi- -omics data; iii) the integrated analysis of multi-omics data using machine learning techniques.

Exploring genetic associations of Crohn's disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations.

Background: Previous studies have reported associations of Crohn's disease (CD) and ulcerative colitis (UC) with the risks of extraintestinal cancers, but the causality remains unclear. Methods: Using genetic variations robustly associated with CD and UC extracted from genome-wide association studies (GWAS) as instrumental variables. Nine types of extraintestinal cancers of European and Asian populations were selected as outcomes. We used the inverse variance weighted method as the primary approach for two-sample Mendelian randomization analysis. Sensitivity analyses were carried out to evaluate the reliability of our findings. Results: In the European population, we found that CD showed a potential causal relationship with pancreatic cancer (OR: 1.1042; 95% CI: 1.0087-1.2088; P=0.0318). Meanwhile, both CD (outliers excluded: OR: 1.0208; 95% CI: 1.0079-1.0339; P=0.0015) and UC (outliers excluded: OR: 1.0220; 95% CI: 1.0051-1.0393; P=0.0108) were associated with a slight increase in breast cancer risk. Additionally, UC exhibited a potential causal effect on cervical cancer (outliers excluded: OR: 1.1091; 95% CI: 1.0286-1.1960; P=0.0071). In the East Asian population, CD had significant causal effects on pancreatic cancer (OR: 1.1876; 95% CI: 1.0741-1.3132; P=0.0008) and breast cancer (outliers excluded: OR: 0.9452; 95% CI: 0.9096-0.9822; P=0.0040). For UC, it exhibited significant causal associations with gastric cancer (OR: 1.1240; 95% CI: 1.0624-1.1891; P=4.7359×10-5), bile duct cancer (OR: 1.3107; 95% CI: 1.0983-1.5641; P=0.0027), hepatocellular carcinoma (OR: 1.2365; 95% CI: 1.1235-1.3608; P=1.4007×10-5) and cervical cancer (OR: 1.3941; 95% CI: 1.1708-1.6599; P=0.0002), as well as a potential causal effect on lung cancer (outliers excluded: OR: 1.1313; 95% CI: 1.0280-1.2449; P=0.0116). Conclusions: Our study provided evidence that genetically predicted CD may be a risk factor for pancreatic and breast cancers in the European population, and for pancreatic cancer in the East Asian population. Regarding UC, it may be a risk factor for cervical and breast cancers in Europeans, and for gastric, bile duct, hepatocellular, lung, and cervical cancers in East Asians. Therefore, patients with CD and UC need to emphasize screening and prevention of site-specific extraintestinal cancers.

Impairments of GABAergic transmission in hippocampus mediate increased susceptibility of epilepsy in the early stage of Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease (AD) are often co-morbid with unprovoked seizures, making clinical diagnosis and management difficult. Although it has an important role in both AD and epilepsy, abnormal γ-aminobutyric acid (GABA)ergic transmission is recognized only as a compensative change for glutamatergic damage. Neuregulin 1 (NRG1)-ErbB4 signaling can promote GABA release and suppress epileptogenesis, but its effects on cognition in AD are still controversial. METHODS: Four-month-old APPswe/PS1dE9 mice (APP mice) were used as animal models in the early stage of AD in this study. Acute/chronic chemical-kindling epilepsy models were established with pentylenetetrazol. Electroencephalogram and Racine scores were performed to assess seizures. Behavioral tests were used to assess cognition and emotion. Electrophysiology, western blot and immunofluorescence were performed to detect the alterations in synapses, GABAergic system components and NRG1-ErbB4 signaling. Furthermore, NRG1 was administrated intracerebroventricularly into APP mice and then its antiepileptic and cognitive effects were evaluated. RESULTS: APP mice had increased susceptibility to epilepsy and resulting hippocampal synaptic damage and cognitive impairment. Electrophysiological analysis revealed decreased GABAergic transmission in the hippocampus. This abnormal GABAergic transmission involved a reduction in the number of parvalbumin interneurons (PV+ Ins) and decreased levels of GABA synthesis and transport. We also found impaired NRG1-ErbB4 signaling which mediated by PV+ Ins loss. And NRG1 administration could effectively reduce seizures and improve cognition in four-month-old APP mice. CONCLUSION: Our results indicated that abnormal GABAergic transmission mediated hippocampal hyperexcitability, further excitation/inhibition imbalance, and promoted epileptogenesis in the early stage of AD. Appropriate NRG1 administration could down-regulate seizure susceptibility and rescue cognitive function. Our study provided a potential direction for intervening in the co-morbidity of AD and epilepsy.

Growth arrest specific protein 6 alleviated white matter injury after experimental ischemic stroke.

Ischemic white matter injury leads to long-term neurological deficits and lacks effective medication. Growth arrest specific protein 6 (Gas6) clears myelin debris, which is hypothesized to promote white matter integrity in experimental stroke models. By the middle cerebral artery occlusion (MCAO) stroke model, we observed that Gas6 reduced infarcted volume and behavior deficits 4 weeks after MCAO. Compared with control mice, Gas6-treatment mice represented higher FA values in the ipsilateral external capsules by MRI DTI scan. The SMI32/MBP ratio of the ipsilateral cortex and striatum was profoundly alleviated by Gas6 administration. Gas6-treatment group manifested thicker myelin sheaths than the control group by electron microscopy. We observed that Gas6 mainly promoted OPC maturation, which was closely related to microglia. Mechanically, Gas6 accelerated microglia-mediated myelin debris clearance and cholesterol transport protein expression (abca1, abcg1, apoc1, apoe) in vivo and in vitro, accordingly less myelin debris and lipid deposited in Gas6 treated stroke mice. HX531 (RXR inhibitor) administration mitigated the functions of Gas6 in speeding up debris clearance and cholesterol transport protein expression. Generally, we concluded that Gas6 cleared myelin debris and promoted cholesterol transportation protein expression through activating RXR, which could be one critical mechanism contributing to white matter repair after stroke.

Conditional knockout of AIM2 in microglia ameliorates synaptic plasticity and spatial memory deficits in a mouse model of Alzheimer's disease.

AIMS: Synaptic dysfunction is a hallmark pathology of Alzheimer's disease (AD) and is strongly associated with cognitive impairment. Abnormal phagocytosis by the microglia is one of the main causes of synapse loss in AD. Previous studies have shown that the absence of melanoma 2 (AIM2) inflammasome activity is increased in the hippocampus of APP/PS1 mice, but the role of AIM2 in AD remains unclear. METHODS: Injection of Aß1-42 into the bilateral hippocampal CA1 was used to mimic an AD mouse model (AD mice). C57BL/6 mice injected with AIM2 overexpression lentivirus and conditional knockout of microglial AIM2 mice were used to confirm the function of AIM2 in AD. Cognitive functions were assessed with novel object recognition and Morris water maze tests. The protein and mRNA expression levels were evaluated by western blotting, immunofluorescence staining, and qRT-PCR. Synaptic structure and function were detected by Golgi staining and electrophysiology. RESULTS: The expression level of AIM2 was increased in AD mice, and overexpression of AIM2 induced synaptic and cognitive impairments in C57BL/6 mice, similar to AD mice. Elevated expression levels of AIM2 occurred in microglia in AD mice. Conditional knockout of microglial AIM2 rescued cognitive and synaptic dysfunction in AD mice. Excessive microglial phagocytosis activity of synapses was decreased after knockout of microglial AIM2, which was associated with inhibiting complement activation. CONCLUSION: Our results demonstrated that microglial AIM2 plays a critical role in regulating synaptic plasticity and memory deficits associated with AD, providing a new direction for developing novel preventative and therapeutic interventions for this disease.

A genetic variant in the CD40 gene is related to HBV infection in the Chinese Han population.

BACKGROUND: CD40 is an important immune costimulatory molecule that has recently been found to be associated with chronic hepatitis B. This study aims to explore the association between CD40 polymorphisms and HBV infection, as well as to investigate the impact of different rs1883832 genotypes on CD40 expression and its effect on the progression of chronic HBV infection. METHODS: We genotyped rs1883832 in 3433 individuals using MassARRAY, and quantified the CD40 expression, including CD40 mRNA, sCD40, and mCD40. The CD40 and HBV infection indicators were assessed to investigate the potential function of rs1883832 in suppressing HBV replication in HepG2.2.15 and HepAD38, CD40L in cytotoxic t lymphocytes (CTLs) and interferon-γ, TNF-α, granzyme B, and perforin were measured to elucidate the mechanism by which CD40 inhibits HBV replication. RESULTS: Our study revealed that the frequencies of CC genotype and C allele of rs1883832 were significantly higher in immune recovery compared to chronic hepatitis B. Individuals with CC genotype exhibited significantly elevated CD40 in serum and B cells compared to TT genotypes in chronic hepatitis B. Additionally, CD40 is capable of inhibiting HBV replication and transcription in hepatocytes by means of interaction with CD40L. A significant negative correlation was found between HBV DNA, HBeAg, and mCD40. Conversely, the expressions of ALT and mCD40 showed a positive correlation, which aligns with the trend of CD40L. CONCLUSIONS: rs1883832 C allele may have a protective role in HBV immune recovery. This protective effect could potentially be attributed to the regulation of CD40 expression. The activation of the anti-HBV immune response, which occurs through binding CD40L on CTL, can suppress HBV DNA replication and potentially facilitate immune recovery in HBV infection.

Measurement Properties and Optimal Cutoff Point of the WHO-5 Among Chinese Healthcare Students.

Purpose: The World Health Organization-Five Well-Being Index (WHO-5) is widely used to assess subjective well-being. Nevertheless, measurement invariance and optimal cutoff point of the WHO-5 have not been examined in Chinese samples. We aimed to assess measurement properties of the Chinese version of the WHO-5 (WHO-5-C) among healthcare students. Patients and Methods: A two-wave longitudinal assessment was conducted among 343 Chinese healthcare students from September to November 2022. Measurement properties of the WHO-5-C were assessed through structural validity using confirmatory factor analysis (CFA), measurement invariance using multigroup CFA (MGCFA) and longitudinal CFA (LCFA), convergent validity using correlation analysis with the Self-Rated Health Questionnaire (SRHQ) and Patient Health Questionnaire-4 (PHQ-4), reliability using internal consistency and test-retest reliability, and optimal cutoff point using receiver operating characteristic (ROC) analysis. Results: The WHO-5-C demonstrated satisfactory structural validity with comparative fit index (CFI) of 0.968 at baseline and 0.980 at follow-up, and adequate measurement invariance in different sociodemographic variables at baseline (gender, age, major, home location, being only child, monthly household income, part-time job, physical exercise, hobby, frequency of visiting home, and stress coping strategy) (CFI changes [ΔCFI] = -0.009-0.003) and over a week (ΔCFI = -0.006-0.000). The WHO-5-C also had good internal consistency (Cronbach's α = 0.907-0.934; McDonald's ω = 0.908-0.935) and test-retest reliability (intraclass correlation coefficient [ICC] = 0.803). Convergent validity was supported by moderate correlations of the WHO-5-C with the SRHQ and PHQ-4. The optimal cutoff point of the WHO-5-C was found to be 50, with an area under the ROC curve of 0.882 at baseline data, with sensitivity of 0.803 and specificity of 0.762 at follow-up. Conclusion: The WHO-5-C demonstrated adequate measurement properties, especially concerning cross-sectional and longitudinal measurement invariance, with a recommended optimal cutoff point of ≥ 50 for assessing adequate level of psychological well-being in healthcare students.

Infiltrating myeloid cell-derived properdin markedly promotes microglia-mediated neuroinflammation after ischemic stroke.

BACKGROUND: Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear. METHODS: Global and conditional (myeloid-specific) properdin-knockout mice were subjected to transient middle cerebral artery occlusion (tMCAO). Histopathological and behavioral tests were performed to assess ischemic brain injury in mice. Single-cell RNA sequencing and immunofluorescence staining were applied to explore the source and the expression level of properdin. The transcriptomic profile of properdin-activated primary microglia was depicted by transcriptome sequencing. Lentivirus was used for macrophage-inducible C-type lectin (Mincle) silencing in microglia. Conditioned medium from primary microglia was administered to primary cortex neurons to determine the neurotoxicity of microglia. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, neuronal death, protein-protein interactions, and related signaling pathways, etc. RESULTS: The level of properdin was significantly increased, and brain-infiltrating neutrophils and macrophages were the main sources of properdin in the ischemic brain. Global and conditional myeloid knockout of properdin attenuated microglial overactivation and inflammatory responses at the acute stage of tMCAO in mice. Accordingly, treatment with recombinant properdin enhanced the production of proinflammatory cytokines and augmented microglia-potentiated neuronal death in primary culture. Mechanistically, recombinant properdin served as a novel ligand that activated Mincle receptors on microglia and downstream pathways to drive primary microglia-induced inflammatory responses. Intriguingly, properdin can directly bind to the microglial Mincle receptor to exert the above effects, while Mincle knockdown limits properdin-mediated microglial inflammation. CONCLUSION: Properdin is a new medium by which infiltrating peripheral myeloid cells communicate with microglia, further activate microglia, and exacerbate brain injury in the ischemic brain, suggesting that targeted disruption of the interaction between properdin and Mincle on microglia or inhibition of their downstream signaling may improve the prognosis of ischemic stroke.

Causal relationship between dietary factors and breast cancer risk: A Mendelian randomization study.

Background: Previous studies have discovered an association between dietary factors and breast cancer. However, few studies have used Mendelian randomization (MR) to assess the potential causal relationship between dietary factors and breast cancer. Methods: The exposure datasets for fresh fruit intake, dried fruit intake, salad/raw vegetable intake, cooked vegetable intake, oily fish intake, non-oily fish intake, cheese intake, and bread intake were obtained from the UK Biobank. The outcome dataset was extracted from the Breast Cancer Association Consortium (BCAC). We used the inverse variance weighted (IVW) method as the primary approach for the two-sample MR analysis. To ensure the accuracy of the results, we conducted heterogeneity and horizontal pleiotropy analyses. Additionally, multivariable MR analysis was conducted to ensure the stability of the results. Results: Dried fruit intake was found to be a protective factor for overall breast cancer (outliers excluded: OR: 0.549; 95 % CI: 0.429-0.702; p = 1.75 × 10-6). Subtype analyses showed that dried fruit intake was inversely associated with both estrogen receptor-positive (ER+) breast cancer (outliers excluded: OR: 0.669; 95 % CI: 0.512-0.875; p = 0.003) and ER-negative (ER-) breast cancer (OR: 0.559; 95 % CI: 0.379-0.827; p = 0.004), while fresh fruit intake was inversely associated with ER- breast cancer (excluded outliers: OR: 0.510; 95 % CI: 0.308-0.846; p = 0.009). No significant causal relationship was found between other dietary intakes and breast cancer. After adjusting for the effects of possible confounders, the causal relationships found by the two-sample MR analysis remained. Conclusion: Our study provides evidence that dried fruit intake may reduce the risk of both ER+ and ER- breast cancer, and fresh fruit intake may reduce the risk of ER- breast cancer. Other factors included in this study were not linked to breast cancer.

Visualization of breast cancer-related protein synthesis from the perspective of bibliometric analysis.

Breast cancer, as a daunting global health threat, has driven an exponential growth in related research activity in recent decades. An area of research of paramount importance is protein synthesis, and the analysis of specific proteins inextricably linked to breast cancer. In this article, we undertake a bibliometric analysis of the literature on breast cancer and protein synthesis, aiming to provide crucial insights into this esoteric realm of investigation. Our approach was to scour the Web of Science database, between 2003 and 2022, for articles containing the keywords "breast cancer" and "protein synthesis" in their title, abstract, or keywords. We deployed bibliometric analysis software, exploring a range of measures such as publication output, citation counts, co-citation analysis, and keyword analysis. Our search yielded 2998 articles that met our inclusion criteria. The number of publications in this area has steadily increased, with a significant rise observed after 2003. Most of the articles were published in oncology or biology-related journals, with the most publications in Journal of Biological Chemistry, Cancer Research, Proceedings of the National Academy of Sciences of the United States of America, and Oncogene. Keyword analysis revealed that "breast cancer," "expression," "cancer," "protein," and "translation" were the most commonly researched topics. In conclusion, our bibliometric analysis of breast cancer and related protein synthesis literature underscores the burgeoning interest in this research. The focus of the research is primarily on the relationship between protein expression in breast cancer and the development and treatment of tumors. These studies have been instrumental in the diagnosis and treatment of breast cancer. Sustained research in this area will yield essential insights into the biology of breast cancer and the genesis of cutting-edge therapies.

The association between socioeconomic status and health-related quality of life among young and middle-aged maintenance hemodialysis patients: multiple mediation modeling.

Objective: To explore the relationship between socioeconomic status (SES), illness perception, social functioning, and health-related quality of life (HRQoL) of young and middle-aged maintenance hemodialysis (MHD) patients and the internal mechanism of action. Design: A multicenter cross-sectional study. Methods: An aggregate of 332 young and middle-aged MHD patients were enrolled from hemodialysis centers in four general hospitals in Guangzhou, Guangdong, China, from June to December 2022. The questionnaires used included one for general demographic data, the Brief Illness Perception Questionnaire (BIPQ), Social Dysfunction Screening Scale (SDSS), and the 12-item Short Form Health Survey (SF-12). Results: Both SES and HRQoL were negatively correlated with illness perception and social functioning, respectively. SES was positively correlated with HRQoL. Illness perception was positively correlated with social functioning. The indirect effects of illness perception and social functioning on the relationship between SES and HRQoL were 0.33 and 0.31, making up 41.06% and 38.91% of the sum. The chain indirect effect of illness perception and social functioning was 0.10, making up 12.59% of the total effect, while gender did not play a moderating role. Conclusion: Illness perception and social functioning may independently and accumulatively mediate the association between SES and HRQoL. Nurses should consider developing individual intervention program for young and middle-aged MHD patients with low SES, focusing on establishing targeted counseling and health education strategies corresponding to illness perception and social functioning to help patients improve their HRQoL.

m6A modification and its role in neural development and neurological diseases.

N6-methyladenosine (m6A) methylation, the most prevalent post-transcriptional modification in eukaryotes, represents a highly dynamic and reversible process that is regulated by m6A methyltransferases, m6A demethylases and RNA-binding proteins during RNA metabolism, which affects RNA function. Notably, m6A modification is significantly enriched in the brain and exerts regulatory roles in neurogenesis and neurodevelopment through various mechanisms, further influencing the occurrence and progression of neurological disorders. This study systematically summarizes and discusses the latest findings on common m6A regulators, examining their expression, function and mechanisms in neurodevelopment and neurological diseases. Additionally, we explore the potential of m6A modification in diagnosing and treating neurological disorders, aiming to provide new insights into the molecular mechanisms and potential therapeutic strategies for neurological disorders.

A comprehensive quality evaluation strategy of Mailuoning oral liquid based on fingerprint, qualitative and quantitative analyses.

In order to obtain comprehensive quality evaluation of one traditional Chinese patent medicine of Mailuoning oral liquid (MLN), one smart strategy combined by fingerprint, qualitative and quantitative analyses were carried out in this study. Firstly, the fingerprints of MLN were established by HPLC-UV and HPLC-ELSD, and explained the similarity of twenty-seven batches of MLN by similarity analysis (SA). Secondly, qualitative analysis was performed by high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (HPLC-QTOF-MS/MS). A total of 60 compounds were identified or tentatively identified based on chemical standards and fragmentation information. Finally, the quantitative method based on UPLC combined with triple quadrupole mass spectrometry (UPLC-QqQ-MS/MS) was developed for the simultaneous determination of 40 target compounds. The results showed that MLN samples of different productive year were clearly discriminated and eight compounds (5-hydroxymethyl-2-furaldehyde, neochlorogenic acid, loganic acid, chlorogenic acid, cryptochlorogenic acid, caffeic acid, isoacteoside, angoroside C) were selected as differential markers for MLN. In a word, this strategy including fingerprint, identification of chemical composition and multiple-component quantification could be well applied to modern quality evaluation of MLN, which could be valuable for the further quality control of more other traditional Chinese patent medicines.

HDAC inhibitor attenuates rat traumatic brain injury induced neurological impairments.

Oxidative stress plays an important role in the secondary neuronal damage after traumatic brain injury (TBI). Inhibition of histone deacetylases (HDACs) has been shown to reduce reactive oxygen species (ROS) production and NADPH oxidases (Nox) transcription. Vorinostat is an HDAC inhibitor. This study investigated the influence of vorinostat on neurological impairments in a rat model of TBI induced by lateral fluid percussion injury (LFPI). Different concentrations of vorinostat (5, 25, and 50 mg/kg) were administered via intraperitoneal injection. Neurological deficits were evaluated by modified neurological severity scoring (mNSS). Evans blue extravasation was performed to assess blood-brain barrier (BBB) permeability. Morris water maze assay was performed to evaluate cognitive impairments. Protein levels were evaluated through ELISA and Western blot. Vorinostat was found to attenuate TBI induced brain edema and BBB permeability in rats. Vorinostat also alleviated TBI-induced neurological impairments and anxiety-like behavior in rats. Vorinostat attenuated TBI induced apoptosis and oxidative stresses in ipsilateral injury cortical tissue. Vorinostat inhibited HDAC1, HDAC3, and Nox4 while activated AMPK signaling in ipsilateral injury cortical tissue. In conclusion, administration of vorinostat alleviates the secondary damage of TBI in rat model. The oxidative stress in the ipsilateral injury cortical tissues is decreased by the inhibition of Nox4 expression and the activation of AMPK.