Causal relationship between periodontal disease-related phenotype and knee osteoarthritis: A two-sample mendelian randomization analysis.

OBJECTIVE: This study aimed to explore the bidirectional causal relationship between periodontal disease-related phenotype (PDRP) and knee osteoarthritis (KOA) in a European population using a two-sample Mendelian Randomization (MR) approach. METHODS: We leveraged publicly available GWAS summary statistics for PDRP (n = 975) and KOA (n = 403,124), assessing their roles as both exposures and outcomes. Our comprehensive MR analysis employed various methods, including inverse variance weighting (IVW), weighted median, Egger regression, simple mode, and weighted mode, to enhance the robustness of our findings. To ensure the reliability of our instrumental variables, we implemented a rigorous screening process based on p-values and F-values, utilized Phenoscanner to investigate potential confounders, and conducted sensitivity analyses. RESULTS: Our analysis identified five SNPs associated with PDRP and three SNPs with KOA, all surpassing the genome-wide significance threshold, as instrumental variables. The IVW method demonstrated a significant causal relationship from PDRP to KOA (beta = 0.013, SE = 0.007, P = 0.035), without evidence of directional pleiotropy (MR-Egger regression intercept = 0.021, P = 0.706). No support was found for reverse causality from KOA to PDRP, as further MR analyses yielded non-significant P-values. Additionally, funnel plots and Cochran's Q test detected no significant heterogeneity or directional pleiotropy, confirming the robustness of our results. In multivariate analysis, when considering smoking, alcohol consumption, BMI collectively no direct causal relationship between KOA and PDRP. Conversely, smoking and higher BMI were independently associated with an increased risk of KOA. CONCLUSION: In conclusion, our analysis revealed no direct causal relationship from KOA to PDRP. However, a causal relationship from PDRP to KOA was observed. Notably, when adjusting for potential confounders like smoking, alcohol intake, and BMI, both the causal connection from PDRP to KOA and the inverse relationship were not substantiated.

High glucose intake exacerbates experimental autoimmune prostatitis through mitochondrial reactive oxygen species-dependent TGF-ß activation-mediated Th17 differentiation.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common inflammatory immune disease of the urogenital system. High glucose intake is considered to be a potential promoter of autoimmune diseases. However, the influence of high glucose intake on CP/CPPS is unknown. This research aimed to explore the influences of high glucose intake on experimental autoimmune prostatitis (EAP), a valid animal model of CP/CPPS, and the underlying mechanism. NOD mice received 20% glucose water or normal water treatment during EAP induction. EAP severity and Th17 cell responses were evaluated. Then, we explored the effects of an IL-17A neutralizing antibody, an inhibitor of TGF-ß, the reactive oxygen species (ROS) inhibitor NAC, and the mitochondrial ROS (mtROS) antioxidant MitoQ on glucose-fed EAP mice. The results demonstrated that high glucose intake aggravated EAP severity and promoted Th17 cell generation, which could be ameliorated by the neutralization of IL-17A. In vitro experiments showed that high dextrose concentrations promoted Th17 cell differentiation through mtROS-dependent TGF-ß activation. Treatment with TGF-ß blockade, NAC, or MitoQ suppressed Th17 cell generation both in vivo and in vitro, resulting in the amelioration of EAP manifestations caused by high glucose intake. This study revealed that high glucose intake exacerbates EAP through mtROS-dependent TGF-ß activation-mediated Th17 differentiation. Our results may provide insights into the molecular mechanisms underlying the detrimental effects of an environmental factor, such as high glucose intake, on CP/CPPS.

Effects of abiotic stress on chlorophyll metabolism.

Chlorophyll, an essential pigment in the photosynthetic machinery of plants, plays a pivotal role in the absorption of light energy and its subsequent transfer to reaction centers. Given that the global production of chlorophyll reaches billions of tons annually, a comprehensive understanding of its biosynthetic pathways and regulatory mechanisms is important. The metabolic pathways governing chlorophyll biosynthesis and catabolism are complex, encompassing a series of interconnected reactions mediated by a spectrum of enzymes. Environmental fluctuations, particularly abiotic stressors such as drought, extreme temperature variations, and excessive light exposure, can significantly perturb these processes. Such disruptions in chlorophyll metabolism have profound implications for plant growth and development. This review delves into the core aspects of chlorophyll metabolism, encompassing both biosynthetic and degradative pathways. It elucidates key genes and enzymes instrumental in these processes and underscores the impact of abiotic stress on chlorophyll metabolism. Furthermore, the review aims to deepen the understanding of the interplay between chlorophyll metabolic dynamics and stress responses, thereby shedding light on potential regulatory mechanisms.

The CXCL10/CXCR3 axis regulates Th1 cell differentiation and migration in experimental autoimmune prostatitis through the PI3K/AKT pathway.

OBJECTIVE: To investigate the mechanism of the CXCL10/CXCR3 axis regulating Th1 cell differentiation and migration through the PI3K/AKT pathway in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Experimental autoimmune prostatitis (EAP) model, a well-described and validated animal model of CP/CPPS, was used in our study. After treatment with CXCL10, the severity of EAP and Th1 cell proportion were respectively measured by HE stains, immunohistochemistry, and flow cytometry. Then, the protein expression of the PI3K/AKT pathway in CXCL10/CXCR3-regulated Th1 cell differentiation and migration was evaluated by western blotting. Additionally, by the CXCR3 antagonist AMG487 and the PI3K inhibitor LY294002 applications, the effects of CXCL10/CXCR3 through PI3K/AKT pathway on the Th1 cell differentiation and migration were further assessed. RESULTS: The EAP model was successfully built. CXCL10 increased the proportion of Th1 cells in EAP mice, accompanied by upregulation of the PI3K/AKT pathway. Additionally, the PI3K/AKT pathway was found to be involved in CXCL10/CXCR3 axis-mediated Th1 cell differentiation and migration. CONCLUSIONS: Our investigations indicate that the CXCL10/CXCR3 axis regulates Th1 cell differentiation and migration in EAP through the PI3K/AKT pathway, which provides a new perspective on the immunological mechanisms of CP/CPPS.

BLCA prognostic model creation and validation based on immune gene-metabolic gene combination.

BACKGROUND: Bladder cancer (BLCA) is a prevalent urinary system malignancy. Understanding the interplay of immunological and metabolic genes in BLCA is crucial for prognosis and treatment. METHODS: Immune/metabolism genes were extracted, their expression profiles analyzed. NMF clustering found prognostic genes. Immunocyte infiltration and tumor microenvironment were examined. Risk prognostic signature using Cox/LASSO methods was developed. Immunological Microenvironment and functional enrichment analysis explored. Immunotherapy response and somatic mutations evaluated. RT-qPCR validated gene expression. RESULTS: We investigated these genes in 614 BLCA samples, identifying relevant prognostic genes. We developed a predictive feature and signature comprising 7 genes (POLE2, AHNAK, SHMT2, NR2F1, TFRC, OAS1, CHKB). This immune and metabolism-related gene (IMRG) signature showed superior predictive performance across multiple datasets and was independent of clinical indicators. Immunotherapy response and immune cell infiltration correlated with the risk score. Functional enrichment analysis revealed distinct biological pathways between low- and high-risk groups. The signature demonstrated higher prediction accuracy than other signatures. qRT-PCR confirmed differential gene expression and immunotherapy response. CONCLUSIONS: The model in our work is a novel assessment tool to measure immunotherapy's effectiveness and anticipate BLCA patients' prognosis, offering new avenues for immunological biomarkers and targeted treatments.

A comparison of visual discomfort experienced by surgeons in wireless versus conventional endoscopy in laparoscopic surgery.

Background: This study was performed to introduce a new wireless endoscopic system. Research and development were based on fifth-generation transmission technology. Eye symptoms and visual discomfort induced by the novel endoscopic system were compared with those induced by the conventional endoscopic system before and during laparoscopic pelvic surgery. Materials and methods: Twenty surgeons successfully conducted laparoscopic pelvic surgeries using a conventional endoscopic system and a wireless endoscopic system. Subjective and objective data were measured to evaluate visual discomfort before and 2 hours after surgery. Results: In the conventional endoscopic and wireless endoscopic system groups, no significant differences were found in the presurgical or postsurgical questionnaires. In both groups, tear film breakup times significantly decreased after surgery. However, after comparing the 2 groups, no statistically significant difference was found. Conclusions: Compared with the conventional endoscopic system, the novel wireless endoscopic system does not cause additional visual discomfort for experienced surgeons.

Contrast-enhanced and conventional ultrasound images of renal wounds after partial nephrectomy.

OBJECTIVES: To observe the features of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) images of renal wounds after minimally-invasive partial nephrectomy (MIPN) and evaluate their severity using these two modalities. METHODS: This prospective, observational study included 120 patients who underwent MIPN from April to December 2019 in our hospital. The postoperative US images were evaluated and classified, and contrast extravasation characteristics of CEUS were recorded. The correlation between the classification system and perioperative factors was analyzed. RESULTS: Eighty-five patients underwent US and CEUS after MIPN. Conventional US images were classified into three grades according to the surface morphology of renal wounds and overall shape of the kidney around the incision. Univariable and multivariable analyses indicated that the N component of the R.E.N.A.L. score and the resection range were preoperative and intraoperative factors, respectively, related to the US image grades (UIGs). A deep location and expanded excision contributed to an increased UIG. The extravasation rate increased with the UIG (Spearman correlation rho=0.247, P=0.022), and a higher UIG prolonged the length of extravasation. The depth of the tumor and resection range were related to the UIG. CONCLUSIONS: US and CEUS were feasible and repeatable methods that reflect the morphologic changes of renal wounds after MIPN and may be useful for evaluating their severity.

Cancer Patients with Venous Access Device Status and Influencing Factors of Path Analysis Decision Conflicts.

Objective: The study aims to investigate the status of decision-making and the influencing factors of venous access devices in cancer patients and to explore their action path. Methods: A retrospective analysis was conducted on the clinical data of 360 inpatients in the oncology department from July 2022 to October 2022 in Hebei, Shandong, and Shanxi provinces. The patients were assessed with a general information questionnaire, decision conflict scale, general self-efficacy scale, patient version of doctor-patient decision-making questionnaire, and medical version of social support scale. Further analysis was conducted on the influencing factors of decision conflict on cancer patients' status and access to venous access devices. Results: A total of 345 valid questionnaires were acquired, showing the total score of decision-making conflict regarding venous access devices in cancer patients to be 34.72 ± 12.13. A total of 245 patients exhibited decision-making conflict, with a high level in 119 patients. A negative correlation was found between the total score of decision-making conflict with that of self-efficacy, doctor-patient joint decision-making, and social support (r = 0.766, -0.816, -0.74, P < .001). The joint decision-making between doctor and patient directly negatively affected decision-making conflict (ß = -0.587, P < .001). Self-efficacy was found to exert a direct positive and negative predictive effect on the doctor-patient joint decision-making and decision-making conflict, respectively (ß = 0.415, 0.277, P < .001). Social support can contribute to decision-making conflict in a direct or indirect way through multiple modulations of self-efficacy and joint decision-making between doctors and patients (ß = -0.296, -0.237, -0.185, P < .001). Conclusion: Decisional conflicts are existing among cancer patients in intravenous access device selection, the degree of joint decisional involvement of doctors and patients makes a negative predictive effect on intravenous access device selection, and self-efficacy and social support exert direct or indirect effects. Accordingly, enhancing patients' self-efficacy and improving patients' social support from multiple perspectives could contribute to decision-making of intravenous access devices for cancer patients, which could be achieved by developing decision support programs to elevate decision quality, block related paths early, and reduce the level of patients' decision conflicts.

Improvements for Tissue-Chopping-Based Immunofluorescence Staining Method of Chloroplast Proteins.

Immunofluorescence staining is a very common method for the subcellular localization study of proteins. A tissue-chopping-based immunofluorescence staining method for chloroplast proteins overcomes the restriction of plant cell wall, makes the operation simpler, and uses less experimental materials. Here we provide some improvements for this method. We found that the stained tissues can be directly observed with a confocal microscope without tissue lysis. Samples maintained at a low temperature (0-4 °C) throughout the process can reduce the intensity of chlorophyll autofluorescence and the background signal. A low temperature is also good for the storage of the sample. Fluorescence signal of the stained samples can be kept for several weeks if they are stored at -20 °C. FtsZ is an essential component of the chloroplast division apparatus. We demonstrated this method with the immunofluorescence staining of FtsZ1 in wildtype Arabidopsis and some chloroplast division mutants. We also successfully tested this method by the immunofluorescence staining of FtsZ1 in many other plants, including woody plants. With these procedures, the performance of tissue-chopping-based immunofluorescence staining method are further improved.

Fabrication and application of a wireless high-definition endoscopic system in urological surgeries.

OBJECTIVE: To introduce a wireless high-definition endoscopic system (WHES) and compare it with a Storz high-definition (HD) system for image resolution, colour resolution, weight, and costs. MATERIALS AND METHODS: The WHES incorporated a portable light-emitting diode light source and a wireless camera module, which can be compatible with different types of endoscopes. Images were wirelessly transmitted to a monitor or mobile platform such as smartphone through a receiver. The International Standards Organization 12233 resolution chart image was used for the comparison of image resolution and Munsell Colour Checker Chart for colour resolution. In all, 38 endourologists used a Likert questionnaire to blindly evaluate cystoscopic images from a patient with haematuria. The surgical team was asked about the overall performance of the WHES in 20 laparoscopic adrenalectomies using a unvalidated subjective survey. RESULTS: There was no difference in image resolution between the two systems (5.82 vs 5.89 line pairs/mm). Without lens and respective light sources, there were better purple (ΔE = 21.48 vs 28.73), blue (ΔE = 34.88 vs 38.6) and red colour resolution (ΔE = 29.01 vs 35.45) for the WHES camera (P < 0.05), but orange (ΔE = 43.45 vs 36.52) and yellow (ΔE = 52.7 vs 35.93) resolutions were better for the Storz HD camera (P < 0.05). Comparing the WHES to a Storz laparoscopic system, the Storz system still had better resolution of orange and yellow, while the resolution of purple, blue, and red was similar for the two systems. The expert comments on resolution, brightness, and colour for cystoscopy were not statistically different, but the ergonomics score for the WHES was higher (3.7 vs 3.33, P = 0.038). The overall cost of the WHES was $23 000-25 000 compared with $45 000-50 000 for a Storz system. There were 100% general satisfaction for the WHES in the survey. CONCLUSION: We developed a new WHES that provides the same resolution images as a Storz laparoscopic system and acceptable colour resolution with the advantages of wireless connection, small volume, low cost, portability, and high-speed wireless transmission.

Gut Microflora Modulates Th17/Treg Cell Differentiation in Experimental Autoimmune Prostatitis via the Short-Chain Fatty Acid Propionate.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a very common urological disorder and has been gradually regarded as an immune-mediated disease. Multiple studies have indicated that the gut microflora plays a pivotal part in immune homeostasis and autoimmune disorder development. However, whether the gut microflora affects the CP/CPPS, and the underlying mechanism behind them remain unclear. Here, we built an experimental autoimmune prostatitis (EAP) mouse model by subcutaneous immunity and identified that its Th17/Treg frequency was imbalanced. Using fecal 16s rRNA sequencing and untargeted/targeted metabolomics, we discovered that the diversity and relative abundance of gut microflora and their metabolites were obviously different between the control and the EAP group. Propionic acid, a kind of short-chain fatty acid (SCFA), was decreased in EAP mice compared to that in controls, and supplementation with propionic acid reduced susceptibility to EAP and corrected the imbalance of Th17/Treg cell differentiation in vivo and in vitro. Furthermore, SCFA receptor G-protein-coupled receptor 43 and intracellular histone deacetylase 6 regulated by propionic acid in Th17 and Treg cells were also evaluated. Lastly, we observed that fecal transplantation from EAP mice induced the decrease of Treg cell frequency in recipient mice. Our data showed that gut dysbiosis contributed to a Th17/Treg differentiation imbalance in EAP via the decrease of metabolite propionic acid and provided valuable immunological groundwork for further intervention in immunologic derangement of CP/CPPS by targeting propionic acid.

Metabonomic analysis of cerebrospinal fluid in epilepsy.

Background: We sought to explore the relationship between epilepsy and cerebrospinal fluid metabolomics and identify biomarkers for the diagnosis, treatment, and prognosis of epilepsy. Methods: In total, 23 epileptic patients treated at The First Affiliated Hospital of Dalian Medical University from April 2019 to September 2019 were selected for the disease group and 13 non-epileptic patients were selected for the control group. Cerebrospinal fluid samples were collected from both groups, and the metabolites were analyzed by gas chromatography-mass spectrometry. The metabolites differentially expressed in the cerebrospinal fluid samples were identified. A differential metabolite enrichment analysis was performed to determine the metabolic pathways. Results: Using a variable importance in the projection value >1 and a P value <0.05 as the screening criteria, we found that 3 metabolites (i.e., alpha-ketoisocaproic acid 1, xylose 1, and glycine 2) were differentially expressed in the cerebrospinal fluid of the 23 epileptic patients compared to the 13 non-epileptic patients. Alpha-ketoisocaproic acid 1 and xylose 1 were highly expressed in the epileptic cerebrospinal fluid samples, while glycine 2 was lowly expressed in the epileptic cerebrospinal fluid samples. Additionally, the 3 metabolites were significantly enriched in the 5 metabolic pathways of primary bile acid biosynthesis, valine, leucine, and isoleucine degradation, glutathione metabolism, glyoxylate and dicarboxylate metabolism, and glycine, serine, and threonine metabolism. Conclusions: The present study examined the metabolites of the cerebrospinal fluid of epileptic patients and non-epileptic patients. Our findings provide insights that may inform the discovery of therapeutic targets and diagnostic markers for epilepsy.

Chinese medicinal herbs for idiopathic membranous nephropathy in adults with nephrotic syndrome: A systematic review of effectiveness and safety.

ABSTRACT: To assess the benefits and harms of Chinese medicinal herbs formulae for the treatment of idiopathic membranous nephropathy in adult patients with primary nephrotic syndrome.Only randomized controlled trials were included. We searched the Cochrane Central Register of Controlled Trials database, PubMed, EMBASE, Chinese National Knowledge Internet, Chinese Biomedicine Database, and VIP. All studies were analyzed using the criteria of the Cochrane Handbook and were assessed in terms of quality and the risk of bias. Review Manager ver. 5.3.5 software was used for the data analysis, and GRADE profiler software was employed to evaluate quality.Two studies were included (n = 126 Chinese participants). We found that compared with against conventional treatment, one Chinese medicinal herbs formula plus conventional treatment reduced 24-hours urinary total protein (mean differences -3.16 g/24 h, 95% confidence intervals -4.03 to -2.29), and two Chinese medicinal herbs formulae increased serum albumin levels (mean differences 3.18 g/L, 95% confidence intervals 1.12 to 5.52; I2 = 0%).Chinese medicinal herbs formulae may reduce 24-hours urinary total protein and increase serum levels of albumin. However, larger and multicenter studies with high methodological quality are still needed.

Application of Contrast-Enhanced Ultrasonography (CEUS) in the Assessment of Kidney Wound Recovery After Nephron-Sparing Surgery.

PURPOSE: To investigate feasibility, repeatability and usefulness of contrast-enhanced ultrasonography (CEUS) in the assessment of kidney wound recovery after laparoscopic nephron-sparing surgery (LNSS) or robot-assisted nephron-sparing surgery (RANSS) and preliminarily research the clinical factors associated with the length of extravasation (LOE). PATIENTS AND METHODS: From April 2019 to January 2020, 130 patients that underwent LNSS or RANSS in our hospital were included, and 90 patients (90/130) received CEUS examinations each one day from the postoperative day 1. The discovery of the cessation of contrast medium extravasation from the renal wound was the primary endpoint named "ultrasonic healing", and LOE ranged from the day of surgery to "ultrasonic healing". Patient, tumor, perioperative factors and LOE were collected. Univariate analysis and multivariate linear regression analysis were applied for the determination of factors associated with LOE. RESULTS: The average postoperative LOE was 1.76 days (standard deviation, 1.115; 95% confidence interval: 1.52-1.99). Ultrasonic healing within three days was observed in 95.6% patients (86/90). Univariable and multivariable analyses showed that R and A components in R.E.N.A.L. nephrometry score were associated with LOE. Anterior location and R component score of 2 (tumor size>4cm) were related to longer LOE than posterior location and R score of 1 (tumor size<4cm). The incidence of complications in patients with LOE over one day was higher than those with LOE of one day. CONCLUSION: CEUS was feasible, repeatable and useful in the assessment of kidney wound recovery. Tumor size and location were related to LOE after minimally invasive nephron-sparing surgery (MINSS). Length of stay after MINSS within three days might be relatively safe.

Cu2O-Ag Tandem Catalysts for Selective Electrochemical Reduction of CO2 to C2 Products.

The electrochemical carbon dioxide reduction reaction (CO2RR) to C2 chemicals has received great attention. Here, we report the cuprous oxide (Cu2O) nanocubes cooperated with silver (Ag) nanoparticles via the replacement reaction for a synergetic CO2RR. The Cu2O-Ag tandem catalyst exhibits an impressive Faradaic efficiency (FE) of 72.85% for C2 products with a partial current density of 243.32 mA·cm-2. The electrochemical experiments and density functional theory (DFT) calculations reveal that the introduction of Ag improves the intermediate CO concentration on the catalyst surface and meanwhile reduces the C-C coupling reaction barrier energy, which is favorable for the synthesis of C2 products.

The Influence of the Different Repair Methods on the Electrical Properties of the Normally off p-GaN HEMT.

The influence of the repair process on the electrical properties of the normally off p-GaN high-electron-mobility transistor (HEMT) is studied in detail in this paper. We find that the etching process will cause the two-dimensional electron gas (2DEG) and the mobility of the p-GaN HEMT to decrease. However, the repair process will gradually recover the electrical properties. We study different repair methods and different repair conditions, propose the best repair conditions, and further fabricate the p-GaN HEMTs devices. The threshold voltage of the fabricated device is 1.6 V, the maximum gate voltage is 7 V, and the on-resistance is 23 Ω·mm. The device has a good performance, which proves that the repair conditions can be successfully applied to the fabricate of the p-GaN HEMT devices.

The risk factors related to the severity of pain in patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

BACKGROUND: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a disease with diverse clinical manifestations, such as pelvic pain or perineal pain. Although recent studies found several risk factors related to the pain severity of CP/CPPS patients, results were inconsistent. Here, we aimed to identify novel risk factors that are closely related to the severity of pain in patients with CP/CPPS. METHODS: We retrospectively collected the clinical records from patients with CP/CPPS from March 2019 to October 2019. The questionnaire was used to obtain related parameters, such as demographics, lifestyle, medical history, etc. To identify potential risk factors related to pain severity, we used the methods of univariate and multivariate logistic regression analyses. Further, to confirm the relationship between these confirmed risk factors and CP/CPPS, we randomly divided CP/CPPS patients into the training and the validation cohorts with a ratio of 7:3. According to the co-efficient result of each risk factor calculated by multivariate logistic regression analysis, a predicting model of pain severity was established. The receiver operating characteristic curve (ROC), discrimination plot, calibration plot, and decision curve analyses (DCA) were used to evaluate the clinical usage of the current model in both the training and validation cohorts. RESULTS: A total of 272 eligible patients were enrolled. The univariate and multivariate logistic regression analysis found that age [odds ratio (OR): 2.828, 95% confidence intervals (CI): 1.239-6.648, P = 0.004], holding back urine (OR: 2.413, 95% CI: 1.213-4.915, P = 0.005), anxiety or irritability (OR: 3.511, 95% CI: 2.034-6.186, P < 0.001), contraception (OR: 2.136, 95% CI:1.161-3.014, P = 0.029), and smoking status (OR: 1.453, 95% CI: 1.313-5.127, P = 0.013) were the risk factors of pain severity. We then established a nomogram model, to test whether these factors could be used to predict the pain severity of CP/CPPS patients in turn. Finally, ROC, DCA, and calibration analyses proved the significance and stability of this nomogram, further confirmed that these factors were closely related to the pain severity of CP/CPPS patients. CONCLUSIONS: We identify age, holding back urine, anxiety or irritability, contraception, and smoking are risk factors closely related to the pain severity in patients with CP/CPPS. Our results provide novel inspirations for clinicians to design the personalized treatment plan for individual CP/CPPS patient who has suffered different encounters.

Knockout of Eva1a leads to rapid development of heart failure by impairing autophagy.

EVA1A (Eva-1 homologue A) is a novel lysosome and endoplasmic reticulum-associated protein that can regulate cell autophagy and apoptosis. Eva1a is expressed in the myocardium, but its function in myocytes has not yet been investigated. Therefore, we generated inducible, cardiomyocyte-specific Eva1a knockout mice with an aim to determine the role of Eva1a in cardiac remodelling in the adult heart. Data from experiments showed that loss of Eva1a in the adult heart increased cardiac fibrosis, promoted cardiac hypertrophy, and led to cardiomyopathy and death. Further investigation suggested that this effect was associated with impaired autophagy and increased apoptosis in Eva1a knockout hearts. Moreover, knockout of Eva1a activated Mtor signalling and the subsequent inhibition of autophagy. In addition, Eva1a knockout hearts showed disorganized sarcomere structure and mitochondrial misalignment and aggregation, leading to the lack of ATP generation. Collectively, these data demonstrated that Eva1a improves cardiac function and inhibits cardiac hypertrophy and fibrosis by increasing autophagy. In conclusion, our results demonstrated that Eva1a may have an important role in maintaining cardiac homeostasis.

Heat transfer and friction characteristics of the microfluidic heat sink with variously-shaped ribs for chip cooling.

This paper experimentally and numerically investigated the heat transfer and friction characteristics of microfluidic heat sinks with variously-shaped micro-ribs, i.e., rectangular, triangular and semicircular ribs. The micro-ribs were fabricated on the sidewalls of microfluidic channels by a surface-micromachining micro-electro-mechanical system (MEMS) process and used as turbulators to improve the heat transfer rate of the microfluidic heat sink. The results indicate that the utilizing of micro-ribs provides a better heat transfer rate, but also increases the pressure drop penalty for microchannels. Furthermore, the heat transfer and friction characteristics of the microchannels are strongly affected by the rib shape. In comparison, the triangular ribbed microchannel possesses the highest Nusselt number and friction factor among the three rib types.