Fanlian Huazhuo Formula alleviates high-fat diet-induced non-alcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway.

BACKGROUND: Fanlian Huazhuo Formula (FLHZF) has the functions of invigorating spleen and resolving phlegm, clearing heat and purging turbidity. It has been identified to have therapeutic effects on type 2 diabetes mellitus (T2DM) in clinical application. Non-alcoholic fatty liver disease (NAFLD) is frequently diagnosed in patients with T2DM. However, the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation. AIM: To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro. METHODS: HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model. Subsequently, experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours. C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD, and then treated with the different concentrations of FLHZF for 10 weeks. RESULTS: FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro. Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress, regulating the AMPKα/SREBP-1C signaling pathway, activating autophagy, and inhibiting hepatocyte apoptosis. CONCLUSION: FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species, autophagy, apoptosis, and lipid synthesis signaling pathways, indicating its potential for clinical application in NAFLD.

The correlation between anti-phospholipase A2 receptor antibodies and hypercoagulability in patients with idiopathic membranous nephropathy.

BACKGROUND: Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN. METHODS: A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed. RESULTS: Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value. CONCLUSION: Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.

Idebenone Antagonizes P53-Mediated Neuronal Oxidative Stress Injury by Regulating CD38-SIRT3 Protein Level.

Idebenone, an antioxidant used in treating oxidative damage-related diseases, has unclear neuroprotective mechanisms. Oxidative stress affects cell and mitochondrial membranes, altering Adp-ribosyl cyclase (CD38) and Silent message regulator 3 (SIRT3) protein expression and possibly impacting SIRT3's ability to deacetylate Tumor protein p53 (P53). This study explores the relationship between CD38, SIRT3, and P53 in H2O2-injured HT22 cells treated with Idebenone. Apoptosis was detected using flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining after determining appropriate H2O2 and Idebenone concentrations.In this study, Idebenone was found to reduce apoptosis and decrease P53 and Caspase3 expression in H2O2-injured HT22 cells by detecting apoptosis-related protein expression. Through bioinformatics methods, CD38 was identified as the target of Idebenone, and it further demonstrated that Idebenone decreased the expression of CD38 and increased the level of SIRT3. An increased NAD+/NADH ratio was detected, suggesting Idebenone induces SIRT3 expression and protects HT22 cells by decreasing apoptosis-related proteins. Knocking down SIRT3 downregulated acetylated P53 (P53Ac), indicating SIRT3's importance in P53 deacetylation.These results supported that CD38 was used as a target of Idebenone to up-regulate SIRT3 to deacetylate activated P53, thereby protecting HT22 cells from oxidative stress injury. Thus, Idebenone is a drug that may show great potential in protecting against reactive oxygen species (ROS) induced diseases such as Parkinson's disease, and Alzheimer's disease. And it might be able to compensate for some of the defects associated with CD38-related diseases.

Fractal analysis of left ventricular trabeculae in heart failure with preserved ejection fraction patients with multivessel coronary artery disease.

OBJECTIVES: Endocardial trabeculae undergo varicose changes and hyperplasia in response to hemodynamic influences and are a variable phenotype reflecting changes in disease. Fractal analysis has been used to analyze the complexity of endocardial trabeculae in a variety of cardiomyopathies. The aim of this paper was to quantify the myocardial trabecular complexity through fractal analysis and to investigate its predictive value for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with multivessel coronary artery disease (CAD). METHODS: The retrospective study population consisted of 97 patients with multivessel CAD, 39 of them were diagnosed with HFpEF, while 46 healthy volunteers were recruited as controls. Fractal dimension (FD) was obtained through fractal analysis of endocardial trabeculae on LV short-axis cine images. Logistic regression analyses were used to confirm the predictors and compare different prediction models. RESULTS: Mean basal FD was significantly higher in patients with HFpEF than in patients without HFpEF or in the healthy group (median: 1.289; IQR: 0.078; p < 0.05). Mean basal FD was also a significant independent predictor in univariate and multivariate logistic regression (OR: 1.107 and 1.043, p < 0.05). Furthermore, adding FD to the prediction model improved the calibration and accuracy of the model (c-index: 0.806). CONCLUSION: The left ventricular FD obtained with fractal analysis can reflect the complexity of myocardial trabeculae and has an independent predictive value for the diagnosis of HFpEF in patients with multivessel CAD. Including FD into the diagnostic model can help improve the diagnosis. CRITICAL RELEVANCE STATEMENT: Differences show in the complexity of endocardial trabeculae in multivessel coronary artery disease patients, and obtaining fractal dimensions (FD) by fractal analysis can help identify heart failure with preserved ejection fraction (HFpEF) patients. KEY POINTS: The complexity of myocardial trabeculae differs among patients with multivessel coronary artery disease. Left ventricular fractal dimensions can reflect the complexity of the myocardial trabecular. Fractal dimensions have predictive value for the diagnosis of heart failure with preserved ejection fraction.

Effect of electroacupuncture on expression of protein phosphorylation in hippocampus tissues of rats with chronic fatigue syndrome. / ç”µé’ˆå¹²é¢„å¯¹æ ¢æ€§ç–²åŠ³ç»¼åˆå¾å¤§é¼ æµ·é©¬ç»„ç»‡è›‹ç™½è´¨ç£·é ¸åŒ–è¡¨è¾¾çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on behavior and hippocampal protein phosphorylation in rats with chronic fatigue syndrome (CFS), so as to explore its mechanisms underlying improvement of CFS. METHODS: Male SD rats were randomly divided into control, model and EA groups (n=12 rats in each group). The CFS model was established by chronic multifactor combined with stress stimulation (treadmill training + restraint stress + sleep disturbance + crowded environment). For rats of the EA group, EA (1 mA, frequency of 10 Hz) was applied to "Shenting" (GV24) (with an acupuncture needle penetrated from GV24 to "Baihui" ï¼»GV20ï¼½) and "Dazhui" (GV14) for 15 min, once daily for 28 days. After treatment, the body weight, food intake and water intake of rats in each group were observed. The fatigue degree of rats was evaluated by Semi-quantitative score observation table of the general condition of experimental rats.The open field test (OFT) was used to assess the rats'anxiety severity by detecting the total number of grid-crossing and the times of the central area entered in 5 min, and Morris water maze test was employed to assess the rats' learning-memory ability by detecting the escape latency in 1 min, and the times of the original platform quadrant crossing in 1 min. The hippocampaus was taken for phosphorylated Label-free quantitative proteomics analysis by using Maxquant technology based on full scan mode to calculate the integral of each peptide signal of liquid chromatography-mass spectrometry(LC-MS). The differentially-expressed proteins (>1.5 folds for up-regulation or <0.67 folds for down-regulation) were evaluated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. RESULTS: Compared with the control group, the body weight, food intake, and the times of original-platform quadrant crossing of spatial exploring of Morris water maze test were significantly decreased (P<0.01, P<0.05) , and the score of general conditions, times of grid-crossing and center area-entering of OFT, and the escape latency of navigation task were apparently increased (P<0.01) in rats of the model group. After EA intervention, the decreased original-platform quadrant crossing, and the increased score of general conditions, times of grid-crossing and the escape latency of navigation task were all reversed (P<0.01, P<0.05). Outcomes of proteomics analysis indicated that compared with the model group, there were 297 differentially expressed peptide (48 up-regulated and 249 down-regulated) segments in the control group, and there were 245 differentially expressed peptide (185 up-regulated and 60 down-regulated) segments in the EA group, in which, 25 overlapping peptide segments were reversed after EA treatment, corresponding to 24 proteins, mainly involving cytoskeletal structure. GO function annotation analysis showed that the top three differentially expressed phosphorylated proteins involved in the effect of EA intervention were the actin filament polymerization, protein depolymerization and cytoskeletal tissue in the biological process, the actin binding, structural molecular activity and cytoskeletal protein binding in the molecular function, and the cytoskeleton, dendrites and dendritic trees in the cellular component, respectively. The KEGG pathway annotation analysis for differentially expressed phosphorylated proteins showed that theinsulin secretion, axon guidance, phosphatidylinositol signaling system and lysine biosynthesis, etc. were involved in the effect of EA intervention. CONCLUSIONS: EA of GV24-GV20 and GV14 can improve the general state, anxiety and learning-memory ability of CFS model rats, which may be related to its functions in regulating the hippocampal protein phosphorylation level, and repairing the structure and function of synapses in hippocampus.

Associations and Mediating Pathways Between Childhood Adversity and Risk of Dementia: A Cohort Study in the UK Biobank.

BACKGROUND: While childhood adversity (CA) is known to be associated with multiple adverse outcomes, its link with dementia is an area with limited exploration and inconsistent agreement. The study aimed to examine the longitudinal associations of CA with incident all-cause dementia and to quantify the potential mediating pathways. METHODS: Data from the UK Biobank. CA, encompassing neglect and abuse, was evaluated retrospectively by an online mental health questionnaire. Physical performance, psychological factors, lifestyles, and biological indicators assessed at baseline were considered potential mediators. Incident all-cause dementia was defined by International Classification of Diseases, Tenth Revision codes obtained through self-reported medical conditions, primary care, hospital admission, and death registrations. Cox proportional hazard models were applied to estimate the longitudinal associations. Mediation analyses were conducted on potential mediators to examine their contribution. RESULTS: This cohort study comprised 150 152 nondemented individuals (mean [SD] age, 55.9 [7.7] years) at baseline (2006-2010). Compared to individuals who did not experience CA, those exposed to any CA exhibited a 30.0% higher risk of dementia (hazard ratio = 1.300, 95% confidence interval [CI]: 1.129-1.496). Each additional CA was associated with a 15.5% (95% CI: 8.8%-22.5%, pfor trend < .001) increased dementia risks. Depression, smoking, and low grip strength explained 8.7%, 2.4%, and 0.9% of the associations, respectively. Biomarkers involving inflammation, erythrocytes, liver, and kidney function mediated the associations by 0.6%-1.4%. CONCLUSIONS: The study revealed the detrimental effects of CA on dementia and identified some potential mediators, namely depression, smoking, low grip strength, and several targeted biomarkers. In addition to calling more attention to CA, the findings underscore the importance of interventions targeting modifiable mediators in preventing dementia.

The multifaceted role of RNA-based regulation in plant stress memory.

Plants have evolved interconnected regulatory pathways which enable them to respond and adapt to their environments. In plants, stress memory enhances stress tolerance through the molecular retention of prior stressful experiences, fostering rapid and robust responses to subsequent challenges. Mounting evidence suggests a close link between the formation of stress memories and effective future stress responses. However, the mechanism by which environmental stressors trigger stress memory formation is poorly understood. Here, we review the current state of knowledge regarding the RNA-based regulation on stress memory formation in plants and discuss research challenges and future directions. Specifically, we focus on the involvement of microRNAs (miRNAs), small interfering RNAs (siRNAs), long non-coding RNAs (lncRNAs), and alternative splicing (AS) in stress memory formation. miRNAs regulate target genes via post-transcriptional silencing, while siRNAs trigger stress memory formation through RNA-directed DNA methylation (RdDM). lncRNAs guide protein complexes for epigenetic regulation, and AS of pre-mRNAs is crucial to plant stress memory. Unraveling the mechanisms underpinning RNA-mediated stress memory formation not only advances our knowledge of plant biology but also aids in the development of improved stress tolerance in crops, enhancing crop performance and global food security.

Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

Regulation of TMEM100 expression by epigenetic modification, effects on proliferation and invasion of esophageal squamous carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

Non-centrosymmetric topological phase probed by non-linear Hall effect.

Non-centrosymmetric topological material has attracted intense attention due to its superior characteristics as compared with the centrosymmetric one, although probing the local quantum geometry in non-centrosymmetric topological material remains challenging. The non-linear Hall (NLH) effect provides an ideal tool to investigate the local quantum geometry. Here, we report a non-centrosymmetric topological phase in ZrTe5, probed by using the NLH effect. The angle-resolved and temperature-dependent NLH measurement reveals the inversion and ab-plane mirror symmetries breaking at <30 K, consistently with our theoretical calculation. Our findings identify a new non-centrosymmetric phase of ZrTe5 and provide a platform to probe and control local quantum geometry via crystal symmetries.

A long non-coding RNA functions as a competitive endogenous RNA to modulate TaNAC018 by acting as a decoy for tae-miR6206.

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.

The close association of micronutrients with COVID-19.

Objectives: The present study was conducted to explore the performance of micronutrients in the prediction and prevention of coronavirus disease 2019 (COVID-19). Methods: This is an observational case-control study. 149 normal controls (NCs) and 214 COVID-19 patients were included in this study. Fat-soluble and water-soluble vitamins were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and inorganic elements were detected by inductively coupled plasma-mass spectrometry (ICP-MS) analysis. A logistic regression model based on six micronutrients were constructed using DxAI platform. Results: Many micronutrients were dysregulated in COVID-19 compared to normal control (NC). 25-Hydroxyvitamin D3 [25(OH)D3], magnesium (Mg), copper (Cu), calcium (Ca) and vitamin B6 (pyridoxic acid, PA) were significantly independent risk factors for COVID-19. The logistic regression model consisted of 25(OH)D3, Mg, Cu, Ca, vitamin B5 (VB5) and PA was developed, and displayed a strong discriminative capability to differentiate COVID-19 patients from NC individuals [area under the receiver operating characteristic curve (AUROC) = 0.901]. In addition, the model had great predictive ability in discriminating mild/normal COVID-19 patients from NC individuals (AUROC = 0.883). Conclusions: Our study showed that micronutrients were associated with COVID-19, and our logistic regression model based on six micronutrients has potential in clinical management of COVID-19, and will be useful for prediction of COVID-19 and screening of high-risk population.

Explaining how childhood physical abuse and physical neglect influence adult depression: An analysis with multiple sequential mediators.

BACKGROUND: Substantial evidence indicates that experiencing physical abuse and neglect during childhood significantly elevates the likelihood of developing depression in adulthood. Nevertheless, there remains a dearth of understanding regarding the mechanisms underpinning this correlation. OBJECTIVE: In this study, we aimed to examine the associations of childhood physical abuse and physical neglect with depression using follow-up data from UK Biobank and quantified the contribution of smoking, insomnia, and BMI in these associations. PARTICIPANTS AND SETTINGS: This study included 144,704 participants (64,168 men and 80,536 women) from UK Biobank, most of whom were white (97 %). METHODS: Physical abuse and physical neglect were measured using two items of Childhood Trauma Screener (CTS). Data on the incidence of depression were obtained from primary care, hospital inpatient records, self-reported medical conditions, and death registries. We used a sequential mediation analysis based on the "g-formula" approach to explore the individual and joint effects of potential mediators. RESULTS: The depression incidence rate was 1.85 per 1000 person-years for men and 2.83 per 1000 person-years for women, respectively. Results of Cox proportional risk regression showed that physical abuse (HRs: 1.39-1.53, P < 0.001) and physical neglect (HRs: 1.43-1.60, P < 0.001) are associated with depression. Smoking, insomnia, and BMI together mediated 3 %-26 % of the associations. CONCLUSIONS: These findings contribute to our understanding of how physical abuse and physical neglect influence depression. Furthermore, a more effective reduction in the burden of depression can be achieved by managing modifiable mediators.

Effect of electroacupuncture on behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome. / ç”µé’ˆå¯¹æ ¢æ€§ç–²åŠ³ç»¼åˆå¾å¤§é¼ è¡Œä¸ºå­¦åŠæµ·é©¬ç‚Žæ€§å› å­çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the changes of behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome (CFS), so as to explore its possible mechanisms in the treatment of CFS. METHODS: Twenty-seven SD rats were randomly divided into control, model and electroacupuncture (EA) groups (n=9 rats in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (10 Hz) at "Shenting" (GV24) penetrating "Baihui" (GV20), "Dazhui" (GV14) for 15 min, twice a day for 14 days. The general conditions, Morris water maze test, open field test, the exhausted running platform were conducted for determining the rats' locomotor and learning-memory activities. H.E. staining was used to observe the morphological structure of neurons in hippocampal CA1 region. The contents of interleukin (IL)-10, IL-17 and transforming growth factor (TGF) ß1 in hippocampus and serum of rats were detected by ELISA, and the positive expressions of IL-10, IL-17 and TGF-ß1 in hippocampal CA1 region were detected by immunofluorescence staining. RESULTS: Compared with the control group, the score of general condition was increased (P<0.05), the escape latency was prolonged (P<0.05), the number of crossing the original platform was decreased (P<0.05), the numbers of crossing the grid and entering the central area were increased (P<0.05), and the exhaustive treadmill time was shortened (P<0.05) in the model group. The contents of IL-10 in the hippocampus and serum were decreased (P<0.05), while IL-17 and TGF-ß1 contents were increased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was decreased (P<0.05), while the intensity of IL-17 and TGF-ß1 were increased (P<0.05). After treatment, compared with the model group, the score of general condition was decreased (P<0.05), the escape latency was shortened (P<0.05), the number of crossing the original platform was increased (P<0.05), the numbers of crossing the grid and entering the central area were decreased (P<0.05), and the exhaustive treadmill time was prolonged (P<0.05) in the EA group. The contents of IL-10 in the hippocampus and serum were increased (P<0.05), while IL-17 and TGF-ß1 levels were decreased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was increased (P<0.05), while the intensity of IL-17 and TGF-ß1 were decreased (P<0.05). H.E. staining showed that in the model group, the number of neurons in the hippocampus decreased, with disordered arrangement and loose structure, and a small numbers of neuronal nuclei were missing. The degree of tissue damage of the EA group was milder than that of the model group. CONCLUSIONS: EA can alleviate fatigue and spatial learning and memory impairment in CFS rats, which may be related to the regulation of peripheral and central inflammation.

A multifunctional biomimetic nanoplatform for image-guideded photothermal-ferroptotic synergistic osteosarcoma therapy.

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

Different Degrees of Sulfated Laminaria Polysaccharides Recovered Damaged HK-2 Cells and Inhibited Adhesion of Nano-COM and Nano-COD Crystals.

Purpose: The crystal adhesion caused by the damage of renal tubular epithelial cells (HK-2) is the key to the formation of kidney stones. However, no effective preventive drug has been found. This study aims to explore the recovery effects of four Laminaria polysaccharides (SLPs) with different sulfate (-OSO3-) contents on damaged HK-2 cells and the difference in the adhesion of damaged cells to nanometer calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) before and after recovery. Methods: Sodium oxalate (2.6 mmol/L) was used to damage HK-2 cells to establish a damaged model. SLPs (LP0, SLP1, SLP2, and SLP3) with -OSO3- contents of 0.73%, 15.1%, 22.8%, and 31.3%, respectively, were used to restore the damaged cells, and the effects of SLPs on the adhesion of COM and COD, with a size of about 100 nm before and after recovery, were measured. Results: The following results were observed after SLPs recovered the damaged HK-2 cells: increased cell viability, restored cell morphology, decreased reactive oxygen levels, increased mitochondrial membrane potential, decreased phosphatidylserine eversion ratio, increased cell migration ability, reduced expression of annexin A1, transmembrane protein, and heat shock protein 90 on the cell surface, and reduced adhesion amount of cells to COM and COD. Under the same conditions, the adhesion ability of cells to COD crystals was weaker than that to COM crystals. Conclusions: As the sulfate content in SLPs increases, the ability of SLPs to recover damaged HK-2 cells and inhibit crystal adhesion increases. SLP3 with high -OSO3- content may be a potential drug to prevent kidney stones.

Development and validation of a deep-learning model for the detection of non-displaced femoral neck fractures with anteroposterior and lateral hip radiographs.

Background: Hip fractures, including femoral neck fractures, are a significant cause of morbidity and mortality in the elderly population and are typically diagnosed using plain radiography. However, diagnosing non-displaced femoral neck fractures can be challenging due to their subtle appearance on hip radiographs. Previous deep-learning models have shown low accuracy in identifying these fractures on anteroposterior (AP) radiographs; however, no studies have used lateral radiographs. This study aimed to evaluate the potential of using deep-learning with both AP and lateral hip radiographs to automatically identify non-displaced femoral neck fractures. Methods: We conducted a retrospective analysis of patients with femoral neck fractures at The First Affiliated Hospital of Xiamen University. All the hip radiographs were reviewed, and cases of non-displaced femoral neck fractures were included in the study. Additionally, 439 participants with normal hip radiographs were also included in the study. A vision transformer (Vit) model was developed using 1,536 AP and lateral hip radiograph. The model's performance was compared to the performance of two groups of human observers: an expert group comprising orthopedic surgeons and radiologists, and a non-expert group, including emergency physicians and general practice doctors. We also carried out the external validation using two additional data sets to assess the generalizability of the model. Results: The Vit model showed exceptional performance in detecting non-displaced femoral neck fractures on paired AP and lateral hip radiographs, achieving a binary accuracy of 95.8% [95% confidence interval (CI): 94.9%, 96.8%] and an area under the curve (AUC) of 0.988. Compared to the human observers, the model had a higher accuracy of 96.7% (95% CI: 93.9%, 99.5%) on the paired AP and lateral hip radiographs, while the accuracy of the expert group was 90.5% (95% CI: 85.7%, 95.2%). Further, the model maintained good performance during the external validation, with an AUC of 0.959 on the paired AP and lateral views. Conclusions: Our Vit model showed expert-level performance in identifying non-displaced femoral neck fractures on paired AP and lateral hip radiographs. This model has the potential to enhance diagnosis accuracy and improve patient outcomes by reducing the need for additional examinations and preoperative time.

Curcumin inhibits the invasion and migration of pancreatic cancer cells by upregulating TFPI-2 to regulate ERK- and JNK-mediated epithelial-mesenchymal transition.

PURPOSE: Pancreatic cancer (PC) is one of the most deadly human malignancies. Curcumin is a natural polyphenolic compound with wide-ranging pharmacological effects. Growing evidence suggests that curcumin has anticancer activity against PC, but the mechanism remains incompletely elucidated. This study aimed to investigate the effects and mechanisms of curcumin on the invasion and migration of PC cells. METHODS: Effect of curcumin on tissue factor pathway inhibitor (TFPI)-2 mRNA expression in PC cells was initially identified using qRT-PCR. Cytotoxicity of curcumin was assessed with MTT assays and IC50 was calculated. Involvement of ERK and JNK pathways, as well as protein expression of TFPI-2 and epithelial-mesenchymal transition (EMT)-related markers, were detected using immunoblotting. Invasion and migration of PC cells were examined using Transwell assays. TFPI-2 expression was manipulated by transfection with siRNA and shRNA. Rescue assays were used to validate the effect of curcumin on cell invasion and migration via TFPI-2. RESULTS: Curcumin increased the expression of TFPI-2 mRNA and protein in PC cells and attenuated cell invasion and migration. Curcumin also inhibited ERK and JNK pathways and EMT in PC cells. Knockdown of TFPI-2 partially reversed the inhibition of ERK and JNK pathways and EMT by curcumin. Mechanistically, curcumin upregulated TFPI-2, thereby inhibiting the ERK and JNK pathways, leading to the inhibition of EMT in PC cells. CONCLUSION: Collectively, curcumin inhibits ERK- and JNK-mediated EMT through upregulating TFPI-2, which in turn suppresses the migration and invasion of PC cells. These findings provide new insights into the antitumor mechanism of curcumin.

Pyroptosis: the dawn of a new era in endometrial cancer treatment.

Endometrial cancer (EC) is a malignancy of the inner epithelial lining of the uterus. While early-stage EC is often curable through surgery, the management of advanced, recurrent and metastatic EC poses significant challenges and is associated with a poor prognosis. Pyroptosis, an emerging form of programmed cell death, is characterized by the cleavage of gasdermin proteins, inducing the formation of extensive gasdermin pores in the cell membrane and the leakage of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), consequently causing cell swelling, lysis and death. It has been found to be implicated in the occurrence and progression of almost all tumors. Recent studies have demonstrated that regulating tumor cells pyroptosis can exploit synergies function with traditional tumor treatments. This paper provides an overview of the research progress made in molecular mechanisms of pyroptosis. It then discusses the role of pyroptosis and its components in initiation and progression of endometrial cancer, emphasizing recent insights into the underlying mechanisms and highlighting unresolved questions. Furthermore, it explores the potential value of pyroptosis in the treatment of endometrial cancer, considering its current application in tumor radiotherapy, chemotherapy, targeted therapy and immunotherapy.