Hhatl ameliorates endoplasmic reticulum stress through autophagy by associating with LC3.

Endoplasmic reticulum (ER) stress, a common cellular stress response induced by various factors that interfere with cellular homeostasis, may trigger cell apoptosis. Autophagy is an important and conserved mechanism for eliminating aggregated proteins and maintaining protein stability of cells, which is closely associated with ER stress and ER stress-induced apoptosis. In this paper, we report for the first time that Hhatl, an ER-resident protein, is downregulated in response to ER stress. Hhatl overexpression alleviated ER stress and ER stress induced apoptosis in cells treated with tunicamycin or thapsigargin, whereas Hhatl knockdown exacerbated ER stress and apoptosis. Further study showed that Hhatl attenuates ER stress by promoting autophagic flux. Mechanistically, we found that Hhatl promotes autophagy by associating with autophagic protein LC3 (microtubule-associated protein 1A/1B-light chain 3) via the conserved LC3-interacting region motif. Noticeably, the LC3-interacting region motif was essential for Hhatl-regulated promotion of autophagy and reduction of ER stress. These findings demonstrate that Hhatl ameliorates ER stress via autophagy activation by interacting with LC3, thereby alleviating cellular pressure. The study indicates that pharmacological or genetic regulation of Hhatl-autophagy signaling might be potential for mediating ER stress and related diseases.

Joint association of physical activity and diet quality with dyslipidemia: a cross-sectional study in Western China.

OBJECTIVE: This study aims to investigate the prevalence of dyslipidemia and assess the joint association of physical activity (PA) and diet quality on dyslipidemia risk in urban areas of Xinjiang. METHODS: Conducted from July 2019 to September 2021 in Xinjiang, China, this cross-sectional study involved 11,855 participants (mean age 47.1 ± 9.4 years, 53.1% male). Standard methods were used to measure plasma cholesterol levels, and validated questionnaires were employed to evaluate dietary habits and PA. The definition of dyslipidemia is based on 2023 Chinese guidelines for lipid management. PA was divided into guideline-recommended moderate-to-vigorous physical activity (MVPA) and non-MVPA, following World Health Organization guidelines. The Food Frequency Questionnaire was used to obtain the intake frequency of each dietary term. Each item was scored based on consumption frequency and divided into three groups (good, intermediate, and poor) based on total dietary score. Multivariate logistic regression analysis was performed to identify dyslipidemia risk factors, as well as the joint association of PA and diet quality. RESULTS: Dyslipidemia prevalence among urban adults in Xinjiang was 39.3%, with notable sex disparities (52.6% in males vs. 24.3% in females, P < 0.001). Among participants with dyslipidemia, the awareness, treatment and control rates were 6.9%, 3.1%, and 1.9%, respectively. A significant multiplicative interaction between PA and diet quality is associated with dyslipidemia (P for interaction < 0.05). Less PA and poor diet quality were associated with an increased odds of dyslipidemia. Even individuals with poor (OR = 1.464, 95% CI: 1.106-1.939) or intermediate (OR = 1.229, 95% CI: 1.003-1.505) diet quality but adhering to recommended MVPA had lower odds of dyslipidemia compared to those with good diet quality but inadequate MVPA (OR = 1.510, 95% CI: 1.252-1.821). CONCLUSIONS: Dyslipidemia prevalence was 39.3% in urban adults in Xinjiang, with limited awareness, treatment, and control. Following guideline-recommended MVPA and maintaining good diet quality were protective against dyslipidemia. Low levels of PA associated with a higher prevalence of dyslipidemia, even in individuals with good diet quality.

Severer air pollution, poorer cognitive function: Findings from 176,345 elders in Northwestern China.

BACKGROUND: Limited evidence exists regarding the link between air pollution exposure and cognitive function in developing countries, particularly in areas with abundant natural sources of particulate matter. OBJECTIVES: To investigate this association in a large representative sample of the elderly in northwestern China. METHODS: We performed a cross-sectional study among 176,345 participants aged 60-100 years in northwestern China in 2020. A satellite-based spatiotemporal model was applied to assess three-year annual averages of particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5), ≤ 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) at residential address. Poor cognitive function was assessed using the Mini-Mental State Examination (MMSE). Generalized linear mixed models were used to assess associations. RESULTS: Compared with participants with the lowest quartiles of PM2.5, PM10, and O3 levels, those with the second, third, and highest quartiles of air pollutants consistently showed increased odds of poor cognitive function and decreased MMSE scores. The odds ratios of poor cognitive function associated with a 10 µg/m3 increment in PM2.5, PM10, and O3 were 1.26 (95 % confidence interval [CI]: 1.17, 1.36), 1.06 (95 %CI: 1.04, 1.08), and 2.76 (95 %CI: 2.11, 3.62), respectively. Subgroup analyses suggested stronger associations between air pollution exposures and poor cognitive function among participants who were younger, were non-Uyghur and were physically active. CONCLUSION: Long-term exposures to PM2.5, PM10 and O3 were associated with poor cognitive function in elders. Our results suggest that reducing air pollution may alleviate the burden of poor cognitive function in the elderly.

Exposure to ambient air pollution and metabolic dysfunction-associated fatty liver disease: Findings from over 2.7 million adults in Northwestern China.

Ambient air pollutants exposures may lead to aggravated Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD). However, there is still a scarcity of empirical studies that have rigorously estimated this association, especially in regions where air pollution is severe. To fill in the literature gap, we conducted a cross-sectional study involving 2711,207 adults living in five regions of southern Xinjiang Uyghur Autonomous Region in 2021. Using a Space-Time Extra-Trees model, we assessed the four-year (2017-2020) average concentrations of particulate matter with aerodynamic diameter ≤1 µm (PM1), particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), particulate matter with aerodynamic diameter ≤10 µm (PM10), ozone (O3), sulfur dioxide (SO2), and carbon monoxide (CO), and then assigned these values to the participants. Generalized linear mixed models were employed to examine the relationships between air pollutants and the prevalence of MAFLD, with adjustment for multiple confounding factors. The odds ratios and 95% confidence intervals of MAFLD were 2.002 (1.826-2.195), 1.133 (1.108-1.157), 1.034 (1.027-1.040), 1.077 (1.023-1.134), 2.703 (2.322-3.146) and 1.033 (1.029-1.036) per 10 µg/m3 increase in the 4-year average PM1, PM2.5, PM10, O3, SO2 and CO exposures, respectively. The robustness of the findings was confirmed by a series of sensitivities. In summary, long-term exposure to ambient air pollutants was associated with increased odds of MAFLD, particularly in males and individuals with unhealthy lifestyles.

Canine diffuse large b-cell lymphoma downregulates the activity of CD8 + T-cells through tumor-derived extracellular vesicles.

BACKGROUND: Tumor-derived extracellular vesicles (EVs) have been proposed as the essential mediator between host immunity and cancer development. These EVs conduct cellular communication to facilitate tumor growth, enable invasion and metastasis, and shape the favorable tumor microenvironment. Lymphoma is one of the most common hematological malignancies in humans and dogs. Effective T-cell responses are required for the control of these malignancies. However, the immune crosstalk between CD8 + T-cells, which dominates anti-tumor responses, and canine lymphoma has rarely been described. METHODS: This study investigates the immune manipulating effects of EVs, produced from the clinical cases and cell line of canine B cell lymphoma, on CD8 + T-cells isolated from canine donors. RESULTS: Lymphoma-derived EVs lead to the apoptosis of CD8 + T-cells. Furthermore, EVs trigger the overexpression of CTLA-4 on CD8 + T-cells, which indicates that EV blockade could serve as a potential therapeutic strategy for lymphoma patients. Notably, EVs transform the CD8 + T-cells into regulatory phenotypes by upregulating their PD-1, PD-L1, and FoxP3 mRNA expression. The regulatory CD8 + T-cells secret the panel of inhibitory cytokines and angiogenic factors and thus create a pro-tumorigenic microenvironment. CONCLUSION: In summary, the current study demonstrated that the EVs derived from canine B cell lymphoma impaired the anti-tumor activity of CD8 + T-cells and manipulated the possible induction of regulatory CD8 + T-cells to fail the activation of host cellular immunity.

Identification of pivotal genes with prognostic evaluation value in lung adenocarcinoma by bioinformatics analysis.

Lung cancer remains the leading cause of cancer morbidity and mortality worldwide, and over-diagnosis causes various unnecessary losses in patients' lives and health. How to more effectively screen lung cancer patients and their potential prognostic risk become the focus of our current study. By analyzing the LUAD expression profile in The Cancer Genome Atlas (TCGA), we constructed a weighted gene co-expression network using differentially expressed genes (DEGs) to find the key modules and pivotal genes. A COX proportional risk regression model based on the least absolute shrinkage and selection operator (LASSO) was used to assess the predictive value of the model for the prognosis of LUAD patients. A total of 4107 up-regulated DEGs and 2022 down-regulated DEGs were identified in this study, and enrichment analysis showed that these analyzes were associated with the extracellular matrix of cells and adhesion. Ten gene markers consisting of LDHA, TOP2A, UBE2C, TYMS, TRIP13, EXO1, TTK, TPX2, ZWINT, and UHRF1 were established by extracting the central genes in the key modules, and the upregulation of these genes was accompanied by an increased prognostic risk of patients. Among them, high expression of LDHA, TRIP13, and TTK in LUAD was associated with shorter overall survival and could be used as independent prognostic factors to participate in metabolic processes such as tumor NAD. The present study provides a powerful molecular target for the study of LUAD prognosis and provides a theoretical basis for the diagnosis and treatment of LUAD and the development of targeted inhibitors.

'Triple clear': a systematic and comprehensive surgical process for Campanacci grades II and III giant cell tumors of the bone, with or without pathological fracture and slight joint invasion.

BACKGROUND: In recent years, researchers have proposed a number of adjuvant methods for extended curettage of giant cell tumors of the bone. However, various schemes have significant differences in efficacy and safety. Therefore, this article will describe an empirical expanded curettage protocol, 'triple clear', in detail to show the effect of the efficient surgical protocol. METHOD: Patients with Campanacci grades II and III primary GCTB who were treated with either SR (n = 39) or TC (n = 41) were included. Various perioperative clinical indicators, including the therapy modality, operation time, Campanacci grade, and filling material were recorded and compared. The pain level was determined by the visual analog scale. Limb function was determined by the Musculoskeletal Tumour Society (MSTS) score. Follow-up time, recurrence rates, reoperation rates, and complication rates were also recorded and compared. RESULT: The operation time was 135.7 ± 38.4 min in the TC group and 174.2 ± 43.0 min in the SR group (P < 0.05). The recurrence rates were 7.3% in the TC group and 8.3% in the SR group (P = 0.37). The MSTS scores at three months after surgery were 19.8 ± 1.5 in the TC group and 18.8 ± 1.3 in the SR group. The MSTS scores at two years were 26.2 ± 1.2 in the TC group and 24.3 ± 1.4 in the SR group (P < 0.05). CONCLUSION: TC is recommended for patients with Campanacci grade II-III GCTB and for those with a pathological fracture or slight joint invasion. Bone grafts may be more suitable than bone cement in the long term.

The new clinical classification of metastatic spinal malignancies serves as a vital reference for surgical management: a retrospective case-control study.

BACKGROUND: It is commonly accepted that surgical treatment is an essential component of the comprehensive management of metastatic spinal malignancies. However, up until now, the clinical classification of metastatic spinal malignancies has not been well-structured. METHODS: After IRB approval, 86 patients with metastatic spinal malignancies were adopted. According to the vascular distribution, stability of vertebrae, and degree of nerve compression, metastatic spinal malignancies can be classified into five types. Tumors classified as type I typically appear in the vertebral body. Type II tumors are those that develop in the transverse processes, superior and inferior articular processes, and spinal pedicles. Type III denotes malignancies that are present in the spinous process and vertebral plate. Types IVa and IVb are included in type IV. Type IVa combines type I and type II, whereas type IVb combines type II and type III. Type V tumors are those of types I, II, and III that co-occur and spread in different directions into the spinal canal. 20 of included 86 patients who did not receive segmental arterial embolization were set as the non-embolization group. The embolization group included 24 patients who received segmental arterial embolization on both sides of the diseased vertebrae. 42 patients were included in the offending embolization group after receiving responsible arterial embolization. A surgical intervention was performed within 24 h following an embolization. Surgical intervention with the purpose of removing as much of the tumor as possible and providing an effective reconstruction of the spinal column. RESULTS: In comparison with the non-embolization group and embolization group, the offending embolization group presented unique advantages in terms of bleeding volume (p<0.001), operation time (p<0.001), and local recurrence rate within 12 months (p=0.006). CONCLUSION: By significantly reducing surgical trauma and local recurrence rate (12 months), responsible arterial vascular embolization procedures together with associated surgical protocols developed on the basis of the clinical classification of metastatic spinal malignancies, are worthy of clinical dissemination.

Density Functional Theory Study of CO2 Hydrogenation on Transition-Metal-Doped Cu(211) Surfaces.

The massive emission of CO2 has caused a series of environmental problems, including global warming, which exacerbates natural disasters and human health. Cu-based catalysts have shown great activity in the reduction of CO2, but the mechanism of CO2 activation remains ambiguous. In this work, we performed density functional theory (DFT) calculations to investigate the hydrogenation of CO2 on Cu(211)-Rh, Cu(211)-Ni, Cu(211)-Co, and Cu(211)-Ru surfaces. The doping of Rh, Ni, Co, and Ru was found to enhance CO2 hydrogenation to produce COOH. For CO2 hydrogenation to produce HCOO, Ru plays a positive role in promoting CO dissociation, while Rh, Ni, and Co increase the barriers. These results indicate that Ru is the most effective additive for CO2 reduction in Cu-based catalysts. In addition, the doping of Rh, Ni, Co, and Ru alters the electronic properties of Cu, and the activity of Cu-based catalysts was subsequently affected according to differential charge analysis. The analysis of Bader charge shows good predictions for CO2 reduction over Cu-based catalysts. This study provides some fundamental aids for the rational design of efficient and stable CO2-reducing agents to mitigate CO2 emission.

Automated three-dimensional echocardiographic quantification for left ventricular volume and function in patients with hypertrophic cardiomyopathy.

BACKGROUND: Accurate, reproducible, noninvasive determination of left ventricular (LV) volumes and ejection fraction (EF) is important for clinical assessment, selection of therapy, and serial monitoring of patients with hypertrophic cardiomyopathy (HCM). Current clinical Two-dimensional echocardiography (2DE) may cause inaccurate measurements in patients with HCM because of their asymmetric ventricles and limitations of 2DE technology. Three-dimensional echocardiography (3DE) have demonstrated significantly greater accuracy. However, the time-consuming workflow limits the clinical utility of 3DE. AIM: We aim to compare the performance of a novel automated 3DE system (HeartModel, Philips Healthcare) with 2DE in a group of patients with HCM. Cardiac magnetic resonance (CMR) was reference standard. METHODS: Fifty-three patients with HCM were examined by automated 3DE (3DEA), two-dimensional biplane Simpson's method (2DBP), manual 3DE method, and CMR, respectively. For patients with poor automated quantification, manual correction was performed. The Pearson correlation coefficient and Bland-Altman analysis and paired Student t tests were used to assess inter-technique agreement. RESULTS: 3DEA measurements with contour editing correlate well with CMR and manual 2DE and 3DE measurements (r = .80-.96). The analysis time of 3DEA was shorter than that of 2DBP (3DEA, 141 ± 15s; 2DBP, 174 ± 17 s). Inter-observer variability was reduced significantly with use of 3DEA. CONCLUSION: Compared with current clinical 2DBP method, the analysis time of automated 3DE was much shorter with the added benefit of enhanced accuracy and reproducibility. Patients with asymmetric chamber may rely more on the timesaving automated 3DE quantification in the future.

27-Hydroxycholesterol-Induced Dysregulation of Cholesterol Metabolism Impairs Learning and Memory Ability in ApoE ε4 Transgenic Mice.

Dysregulated brain cholesterol metabolism is one of the characteristics of Alzheimer's disease (AD). 27-Hydroxycholesterol (27-OHC) is a cholesterol metabolite that plays an essential role in regulating cholesterol metabolism and it is suggested that it contributes to AD-related cognitive deficits. However, the link between 27-OHC and cholesterol homeostasis, and how this relationship relates to AD pathogenesis, remain elusive. Here, 12-month-old ApoE ε4 transgenic mice were injected with saline, 27-OHC, 27-OHC synthetase inhibitor (anastrozole, ANS), and 27-OHC+ANS for 21 consecutive days. C57BL/6J mice injected with saline were used as wild-type controls. The indicators of cholesterol metabolism, synaptic structure, amyloid ß 1-42 (Aß1-42), and learning and memory abilities were measured. Compared with the wild-type mice, ApoE ε4 mice had poor memory and dysregulated cholesterol metabolism. Additionally, damaged brain tissue and synaptic structure, cognitive decline, and higher Aß1-42 levels were observed in the 27-OHC group. Moreover, cholesterol transport proteins such as ATP-binding cassette transporter A1 (ABCA1), apolipoprotein E (ApoE), low-density lipoprotein receptor (LDLR), and low-density lipoprotein receptor-related protein1 (LRP1) were up-regulated in the cortex after the 27-OHC treatment. The levels of cholesterol metabolism-related indicators in the hippocampus were not consistent with those in the cortex. Additionally, higher serum apolipoprotein A1 (ApoA1) levels and lower serum ApoE levels were observed in the 27-OHC group. Notably, ANS partially reversed the effects of 27-OHC. In conclusion, the altered cholesterol metabolism induced by 27-OHC was involved in Aß1-42 deposition and abnormalities in both the brain tissue and synaptic structure, ultimately leading to memory loss in the ApoE ε4 transgenic mice.

Deep learning model for classifying endometrial lesions.

BACKGROUND: Hysteroscopy is a commonly used technique for diagnosing endometrial lesions. It is essential to develop an objective model to aid clinicians in lesion diagnosis, as each type of lesion has a distinct treatment, and judgments of hysteroscopists are relatively subjective. This study constructs a convolutional neural network model that can automatically classify endometrial lesions using hysteroscopic images as input. METHODS: All histopathologically confirmed endometrial lesion images were obtained from the Shengjing Hospital of China Medical University, including endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyps, and submucous myomas. The study included 1851 images from 454 patients. After the images were preprocessed (histogram equalization, addition of noise, rotations, and flips), a training set of 6478 images was input into a tuned VGGNet-16 model; 250 images were used as the test set to evaluate the model's performance. Thereafter, we compared the model's results with the diagnosis of gynecologists. RESULTS: The overall accuracy of the VGGNet-16 model in classifying endometrial lesions is 80.8%. Its sensitivity to endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyp, and submucous myoma is 84.0%, 68.0%, 78.0%, 94.0%, and 80.0%, respectively; for these diagnoses, the model's specificity is 92.5%, 95.5%, 96.5%, 95.0%, and 96.5%, respectively. When classifying lesions as benign or as premalignant/malignant, the VGGNet-16 model's accuracy, sensitivity, and specificity are 90.8%, 83.0%, and 96.0%, respectively. The diagnostic performance of the VGGNet-16 model is slightly better than that of the three gynecologists in both classification tasks. With the aid of the model, the overall accuracy of the diagnosis of endometrial lesions by gynecologists can be improved. CONCLUSIONS: The VGGNet-16 model performs well in classifying endometrial lesions from hysteroscopic images and can provide objective diagnostic evidence for hysteroscopists.

Optics metrology and at-wavelength wavefront characterization by a microfocus X-ray grating interferometer.

A microfocus X-ray grating interferometer (MFXGI) is proposed to measure the profile of the X-ray wavefront and slope error of X-ray optical elements. This device consists of a phase grating G1 to modulate the incoming wavefront and an absorption grating G2 as a transmission mask for the position-sensitive detector. The wavefront distortions caused by the deformable mirror were analyzed under operating conditions for in situ investigation of X-ray optical elements. The MFXGI can obtain direct and reflected beams in one recorded image at the same time through a microfocus X-ray source. The direct beam can be used to calculate the parameter errors and spherical shape for error compensation and retrieve the aspherical shape of the height profile. This instrument is expected to be a valuable tool for further technical progress in X-ray adaptive optics and X-ray mirror manufacturing and mounting.

Acute and chronic infection of H. pylori caused the difference in apoptosis of gastric epithelial cells.

Helicobacter pylori (H. pylori) is one of the most important pathogenic bacteria associated with various gastrointestinal diseases. At present, its apoptotic or antiapoptotic mechanism on gastric epithelial cells remains unknown and needs further illustrated. In this study, acute infection model (H. pylori and GES-1 cells were co-cultured for 24 h at a multiplicity of infection MOI of 100:1) and chronic infection model (GES-1 cells were infected repeatedly every 24 h at a multiplicity of infection MOI of 100:1 for approximately 8 weeks) were established, respectively. the chronic H. pylori infected GES-1 cells underwent a typically morphological change and Western Blot results showed that there was slight decrease in expression of E-cadherin, and obvious increase in expression of Vimentin. Apoptosis of these two models were analyzed by flow cytometry compared with the control cells, meanwhile, apoptosis associated markers (Bcl-xL, Bcl-2, Bax, etc) were detected by Western blot, additional in clinical H. pylori-positive gastric cancer tissues. Results showed that compared with the control cells, acute infection of H. pylori significantly accelerated the apoptosis of GES-1, increased the expression of Bax and Cleaved caspase-3, down-regulated expression of Bcl-xL and Bcl-2. Moreover, an opposite result was found in chronic infection of model and clinical gastric cancer tissues, and enhanced expression of NF-κB p65. Taken together, these findings suggest that H. pylori infection plays differential effects on apoptosis of gastric epithelial cells.

Vitamin D Deficiency Is Associated with Disrupted Cholesterol Homeostasis in Patients with Mild Cognitive Impairment.

BACKGROUND: Several studies have reported that dietary and serum concentrations of vitamin D and cholesterol are correlated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, little is known about whether 25 hydroxyvitamin D [25(OH)D], lipids, and oxysterols are related to cognitive function. OBJECTIVE: This study sought to explore the relations between 25(OH)D, lipids, oxysterols, and cognitive function. METHODS: In this study, about 209 MCI patients and 209 age- and gender-matched healthy controls were recruited from the Shanxi province of China (49.5% male; median [IQR] age: 63 [59-66] y). Serum concentrations of 25(OH)D, lipids, and oxysterols were measured using ultra-performance LC-MS. Cognitive performance was determined via comprehensive mental, verbal, and auditory cognitive tests. Dietary information was collected using a semiquantitative FFQ and 3 consecutive days of 24-h dietary recalls. Logistic regression analyses, Spearman's correlation, and partial correlation analyses were used to explore correlation between the variables. RESULTS: Participants with vitamin D deficiency [serum 25(OH)D <20.0 ng/mL] were 3 times more likely to develop MCI compared to those with adequate vitamin D (≥30 ng/mL) concentrations. The AUC of 25(OH)D was 0.72 and the cut-off was 16.5 ng/mL (sensitivity:  50.3%,  specificity: 84.4%). Serum 25(OH)D concentrations were negatively correlated with total cholesterol (TC) (r = -0.19, P = 0.02), LDL-cholesterol (r = -0.17, P = 0.04), and 24S,25-epoxycholesterol (24S,25-epoxy-CHO) (r = -0.21, P = 0.01). Conversely, the Montreal Cognitive Assessment (MoCA) (r = 0.185, P < 0.001) and symbol digit modalities test (SDMT) (r = 0.11, P = 0.03) scores were positively correlated with serum 25(OH)D concentrations. CONCLUSION: The study identified significant differences in serum 25(OH)D concentrations between MCI patients and cognitive healthy controls, and there was a correlation between serum concentrations of 25(OH)D, lipids, and oxysterols and cognitive impairment among people. This study was registered at the Chinese Clinical Trial Registry as ChiCTR1900025452.

Can Kinesio taping improve discomfort after mandibular third molar surgery? A systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to evaluate whether Kinesio taping (KT) can improve patient discomfort after mandibular third molar surgery. MATERIALS AND METHODS: This systematic review and meta-analysis was conducted according to the PICO strategy. We searched 4 databases for related articles. All controlled trials or randomized controlled trials that evaluated the application of KT after mandibular third molar surgery were included. Screening and article selection were carried out by two independent reviewers. The main evaluation indicators were facial swelling, pain, and trismus. All statistical analyses were conducted using Review Manager 5.3 software. RESULT: This analysis included 8 articles. The combined results showed that compared with the control group, the postoperative application of KT significantly reduced pain in the early (early stage mean difference (MD), - 2.00; 95% confidence interval (CI), - 2.40 to - 1.60; P < 0.00001) and late (late stage MD, - 1.18; 95% CI, - 2.26 to - 0.11; P = 0.03) postoperative periods and, thus, reduced the intake of painkillers. KT also reduced facial swelling in the early and late postoperative periods (early stage standardized mean difference (SMD), - 1.34; 95% CI, - 1.99 to - 0.68; P < 0.0001; late stage SMD, - 0.31; 95% CI, - 0.51 to - 0.11; P = 0.002). In addition, the postoperative application of KT improved restricted mouth opening in the early and late postoperative periods (early stage MD, - 5.03 mm; 95% CI, - 6.32 to - 3.74 mm; P < 0.00001; late stage MD, - 3.42 mm; 95% CI, - 5.31 to - 1.52 mm; P = 0.0004). CONCLUSION: KT can significantly reduce postoperative pain, swelling, and trismus after impacted mandibular tooth extraction. Additional high-quality and rigorously designed randomized controlled trials should be conducted to verify these conclusions. CLINICAL RELEVANCE: KT is a low-cost, simple, effective nondrug therapy for the postoperative management of mandibular third molar extraction and has broad prospects for clinical application.

27-Hydroxycholesterol contributes to cognitive deficits in APP/PS1 transgenic mice through microbiota dysbiosis and intestinal barrier dysfunction.

BACKGROUND: Research on the brain-gut-microbiota axis has led to accumulating interest in gut microbiota dysbiosis and intestinal barrier dysfunction in Alzheimer's disease (AD). Our previous studies have demonstrated neurotoxic effects of 27-hydroxycholesterol (27-OHC) in in vitro and in vivo models. Here, alterations in the gut microbiota and intestinal barrier functions were investigated as the possible causes of cognitive deficits induced by 27-OHC treatment. METHODS: Male APP/PS1 transgenic and C57BL/6J mice were treated for 3 weeks with 27-OHC (5.5 mg/kg/day, subcutaneous injection) and either a 27-OHC synthetase inhibitor (anastrozole, ANS) or saline. The Morris water maze and passive avoidance test were used to assess cognitive impairment. Injuries of the intestine were evaluated by histopathological examination. Intestinal barrier function was assessed by plasma diamine oxidase (DAO) activity and D-lactate. Systemic and intestinal inflammation were evaluated by IL-1ß, TNF-α, IL-10, and IL-17 concentrations as determined by ELISA. The fecal microbiome and short-chain fatty acids (SCFAs) were analyzed using 16S rDNA sequencing and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Tight junction proteins were evaluated in the ileum and colon by qRT-PCR and Western blots. Tight junction ultrastructure was examined by transmission electron microscopy. RESULTS: Treatment with 27-OHC resulted in severe pathologies in the ileum and colon. There was impaired intestinal barrier integrity as indicated by dilated tight junctions and downregulation of tight junction proteins, including occludin, claudin 1, claudin 5, and ZO-1, and signs of inflammation (increased IL-1ß, TNF-α, and IL-17). Fecal 16S rDNA sequencing and taxonomic analysis further revealed a decreased abundance of Roseburia and reduced fecal levels of several SCFAs in 27-OHC-treated mice. Meanwhile, co-treatment with ANS reduced intestinal inflammation and partially preserved intestinal barrier integrity in the presence of 27-OHC. CONCLUSIONS: The current study demonstrates for the first time that 27-OHC treatment aggravates AD-associated pathophysiological alterations, specifically gut microbiota dysbiosis and intestinal barrier dysfunction, which suggests that the gut microbiome and intestinal barrier function warrant further investigation as potential targets to mitigate the neurotoxic impact of 27-OHC on cognitive function and the development of AD.

Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia.

BACKGROUND: Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment. METHODS: This purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment. RESULTS: The results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages. CONCLUSIONS: The results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.

Identification of novel cell glycolysis related gene signature predicting survival in patients with endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is one of the three major gynecological malignancies. Numerous biomarkers that may be associated with survival and prognosis have been identified through database mining in previous studies. However, the predictive ability of single-gene biomarkers is not sufficiently specific. Genetic signatures may be an improved option for prediction. This study aimed to explore data from The Cancer Genome Atlas (TCGA) to identify a new genetic signature for predicting the prognosis of EC. METHODS: mRNA expression profiling was performed in a group of patients with EC (n = 548) from TCGA. Gene set enrichment analysis was performed to identify gene sets that were significantly different between EC tissues and normal tissues. Cox proportional hazards regression models were used to identify genes significantly associated with overall survival. Quantitative real-time-PCR was used to verify the reliability of the expression of selected mRNAs. Subsequent multivariate Cox regression analysis was used to establish a prognostic risk parameter formula. Kaplan-Meier survival estimates and the log-rank test were used to validate the significance of risk parameters for prognosis prediction. RESULT: Nine genes associated with glycolysis (CLDN9, B4GALT1, GMPPB, B4GALT4, AK4, CHST6, PC, GPC1, and SRD5A3) were found to be significantly related to overall survival. The results of mRNA expression analysis by PCR were consistent with those of bioinformatics analysis. Based on the nine-gene signature, the 548 patients with EC were divided into high/low-risk subgroups. The prognostic ability of the nine-gene signature was not affected by other factors. CONCLUSION: A nine-gene signature associated with cellular glycolysis for predicting the survival of patients with EC was developed. The findings provide insight into the mechanisms of cellular glycolysis and identification of patients with poor prognosis in EC.

Hair follicle miRNAs: a novel biomarker for primary blast Induced-Mild traumatic brain injury.

CONTEXT: Due to the wide use of improvised explosive devices during modern warfare, primary blast-derived mild traumatic brain injury (mTBI) has become a major medical condition in the military. With minimal visually identifiable symptoms, an effective molecular biomarker system is desirable. OBJECTIVE: We assessed the potential of mammalian hair follicle miRNAs as an mTBI biomarker. MATERIALS AND METHODS: Due to their well-established roles in mTBI molecular pathology, the expression level of miR-183, miR-26a, miR-181c, miR-29a, miR-34a and miR-27b was determined using qRT-PCR in whisker hair follicles from rats subject to head-only exposure to a single-pulse shock wave. Based on established transcriptomics profiles, sub-network enrichment analysis (SNEA) was also conducted. RESULTS: The results revealed that molecular networks involving miR-183, miR-26a and miR-181c were enriched in multiple treatments, whereas sub-networks of miR-29a, miR-34a and miR-27b were unique to individual exposure groups. DISCUSSION: Our study showed that all six miRNAs were reflective of the mTBI signature involved in cellular responses. Noteworthy was that the decrease in the transcript levels of miR-181c was correlated with shockwave exposure severity. CONCLUSION: This study demonstrates for the first time that mammalian hair follicles are capable of housing miRNA biomarkers for TBI.