Advancements of the Fluidized Bed Fenton (FBF) Technology for wastewater treatment: Mechanism, mass and heat transfer.

Fluidized Bed Fenton (FBF) technology, a fusion of the Fenton method and fluidized bed reactor, has emerged as a superior alternative to conventional Fenton technology for treating organic industrial wastewater. This innovative approach has garnered significant attention from researchers in recent years. While earlier studies primarily focused on pollutant degradation in simulated wastewater and catalyst development, there has been a growing interest in examining the alterations in mass or heat transfer performance attributed to fluidized beds. This paper explores the factors that contribute to the effectiveness of Fluidized Bed Fenton technology in efficiently degrading various challenging organic pollutants, while also reducing iron sludge production and expanding the applicable pH range, through an analysis of reaction kinetics. Meanwhile, combined with the related work of fluid dynamics, the research related to mass and heat transfer inside the reactor of Fluidized Bed Fenton technology is summarized, and it is proposed that the use of computers to establish a suitable model of Fluidized Bed Fenton and solve it with the assistance of computational fluid dynamics (CFD) and other software will help to further explore the process of mass and heat transfer inside the fluidized bed, which will provide the basis for the future of the Fluidized Bed Fenton from the laboratory to the actual industrial application.

Predicting anti-trypanosome effect of carbazole-derived compounds by powerful SVM with novel kernel function and comprehensive learning PSO.

In order to predict the anti-trypanosome effect of carbazole-derived compounds by quantitative structure-activity relationship, five models were established by the linear method, random forest, radial basis kernel function support vector machine, linear combination mix-kernel function support vector machine, and nonlinear combination mix-kernel function support vector machine (NLMIX-SVM). The heuristic method and optimized CatBoost were used to select two different key descriptor sets for building linear and nonlinear models, respectively. Hyperparameters in all nonlinear models were optimized by comprehensive learning particle swarm optimization with low complexity and fast convergence. Furthermore, the models' robustness and reliability underwent rigorous assessment using fivefold and leave-one-out cross-validation, y-randomization, and statistics including concordance correlation coefficient (CCC), [Formula: see text] , [Formula: see text] , and [Formula: see text] . Among all the models, the NLMIX-SVM model, which was established by support vector regression using a nonlinear combination of radial basis kernel function, sigmoid kernel function, and linear kernel function as a new kernel function, demonstrated excellent learning and generalization abilities as well as robustness: [Formula: see text] = 0.9581, mean square error (MSE) = 0.0199 for the training set and [Formula: see text] = 0.9528, MSE = 0.0174 for the test set. [Formula: see text] , [Formula: see text] , CCC, [Formula: see text] , [Formula: see text], and [Formula: see text] are 0.9539, 0.8908, 0.9752, 0.9529, 0.9528, and 0.9633, respectively. The NLMIX-SVM method proved to be a promising way in quantitative structure-activity relationship research. In addition, molecular docking experiments were conducted to analyze the properties of new derivatives, and a new potential candidate drug molecule was ultimately found. In summary, this study will provide help for the design and screening of novel anti-trypanosome drugs.

Study of PARP inhibitors for breast cancer based on enhanced multiple kernel function SVR with PSO.

PARP1 is one of six enzymes required for the highly error-prone DNA repair pathway microhomology-mediated end joining (MMEJ) and needs to be inhibited when over-expressed. In order to study the PARP1 inhibitory effect of fused tetracyclic or pentacyclic dihydrodiazepinoindolone derivatives (FTPDDs) by quantitative structure-activity relationship technique, six models were established by four kinds of methods, heuristic method, gene expression programming, random forester, and support vector regression with single, double, and triple kernel function respectively. The single, double, and triple kernel functions were RBF kernel function, the integration of RBF and polynomial kernel functions, and the integration of RBF, polynomial, and linear kernel functions respectively. The problem of multi-parameter optimization introduced in the support vector regression model was solved by the particle swarm optimization algorithm. Among the models, the model established by support vector regression with triple kernel function, in which the optimal R 2 and RMSE of training set and test set were 0.9353, 0.9348 and 0.0157, 0.0288, and R2 cv of training set and test set were 0.9090 and 0.8971, shows the strongest prediction ability and robustness. The method of support vector regression with triple kernel function is a great promotion in the field of quantitative structure-activity relationship, which will contribute a lot to designing and screening new drug molecules. The information contained in the model can provide important factors that guide drug design. Based on these factors, six new FTPDDs have been designed. Using molecular docking experiments to determine the properties of new derivatives, the new drug was ultimately successfully designed.

Risk factors and predictive models for early recurrent intussusception in children: a retrospective cohort study.

Background: Early recurrent intussusception (ERI) in children is common and seriously affects the physical and mental health of the children. There are few reports discussing risk factors for ERI in children, and this study aims to identify risk factors for ERI in children and build predictive models. Methods: We conducted a retrospective study of 787 children with no relapse intussusception (NRI) and 82 children with ERI between January 2011 and December 2021. Univariate and multifactorial stepwise logistic regression analysis was used to analyze the correlation between 11 factors and ERI, to determine the independent risk factors for ERI in children. The prediction model was established by independent risk factors and then verified. Results: Age, vomiting, bloody stools, and monocyte ratios were independently correlated with the composite endpoint (P<0.05). A nomogram was constructed and a calibration curve was plotted, using independent risk factors. Based on the disease's diagnostic score, the predictive model's performance was validated by using logistic regression receiver operating characteristic (ROC) curve detection, with area under the curve (AUC) value of 0.883 [95% confidence interval (CI): 0.846-0.920], and the calibration curve was close to the ideal diagonal line. In addition, the decision curve analysis (DCA) showed that the model had significant net benefits. Conclusions: Independent risk factors for ERI in children are age, vomiting, bloody stool, and monocyte ratio. Children older than 1 year in age, who lacked vomiting and bloody stool symptoms, and who exhibited an elevated ratio of monocytes were more likely to relapse early. The predictive model constructed herein can predict the early recurrence of children with ERI, providing a reference for clinicians' individualized judgments.

Prediction of histone deacetylase inhibition by triazole compounds based on artificial intelligence.

A quantitative structure-activity relationship (QSAR) study was conducted to predict the anti-colon cancer and HDAC inhibition of triazole-containing compounds. Four descriptors were selected from 579 descriptors which have the most obvious effect on the inhibition of histone deacetylase (HDAC). Four QSAR models were constructed using heuristic algorithm (HM), random forest (RF), radial basis kernel function support vector machine (RBF-SVM) and support vector machine optimized by particle swarm optimization (PSO-SVM). Furthermore, the robustness of four QSAR models were verified by K-fold cross-validation method, which was described by Q 2. In addition, the R 2 of the four models are greater than 0.8, which indicates that the four descriptors selected are reasonable. Among the four models, model based on PSO-SVM method has the best prediction ability and robustness with R 2 of 0.954, root mean squared error (RMSE) of 0.019 and Q 2 of 0.916 for the training set and R 2 of 0.965, RMSE of 0.017 and Q 2 of 0.907 for the test set. In this study, four key descriptors were discovered, which will help to screen effective new anti-colon cancer drugs in the future.

Quantitative structure-activity relationship study of amide derivatives as xanthine oxidase inhibitors using machine learning.

The target of the study is to predict the inhibitory effect of amide derivatives on xanthine oxidase (XO) by building several models, which are based on the theory of the quantitative structure-activity relationship (QSAR). The heuristic method (HM) was used to linearly select descriptors and build a linear model. XGBoost was used to non-linearly select descriptors, and radial basis kernel function support vector regression (RBF SVR), polynomial kernel function SVR (poly SVR), linear kernel function SVR (linear SVR), mix-kernel function SVR (MIX SVR), and random forest (RF) were adopted to establish non-linear models, in which the MIX-SVR method gives the best result. The kernel function of MIX SVR has strong abilities of learning and generalization of established models simultaneously, which is because it is a combination of the linear kernel function, the radial basis kernel function, and the polynomial kernel function. In order to test the robustness of the models, leave-one-out cross validation (LOOCV) was adopted. In a training set, R2 = 0.97 and RMSE = 0.01; in a test set, R2 = 0.95, RMSE = 0.01, and Rcv2 = 0.96. This result is in line with the experimental expectations, which indicate that the MIX-SVR modeling approach has good applications in the study of amide derivatives.

Association between urinary biomarkers of polycyclic aromatic hydrocarbons and severe abdominal aortic calcification in adults: data from the National Health and Examination Nutrition Survey.

OBJECTIVE: Recent studies have found that polycyclic aromatic hydrocarbons (PAHs) exposure may increase the risk of cardiovascular disease. The present study aimed to explore the association between PAHs exposure and severe abdominal aortic calcification (AAC) in adults. METHODS: Data were collected from the 2013-2014 National Health and Nutrition Examination Survey. PAHs exposure was analyzed from urinary mono hydroxylated metabolites of PAHs. Logistic regression models and subgroup analysis were performed to explore the association of PAHs exposure with severe AAC prevalence. RESULTS: A total of 1,005 eligible individuals were recruited into the study. After adjusting for confounding factors, those with the highest quartiles of 1-hydroxynaphthalene (1-NAP: OR 2.19, 95% CI 1.03-4.68, Pfor trend < 0.001), 2-hydroxynaphthalene (2-NAP: OR 2.22, 95% CI 1.04-4.64, Pfor trend < 0.001) and 1-hydroxypyrene (1-PYR: OR 2.15, 95% CI 1.06-4.33, Pfor trend < 0.001) were associated with an increased prevalence of severe AAC in the adults compared to those who in the lowest quartile. CONCLUSION: This study found that urinary 1-NAP, 2-NAP and 1-PYR were positively associated with severe AAC prevalence in adults.

Transverse testicular ectopia with persistent Mullerian duct syndrome: Report and review of two cases.

Transverse testicular ectopia is a rare anomaly characterized by both testes descending through a single inguinal canal. The objective of this study was to investigate the pathogenesis, diagnosis, and treatment of transverse testicular ectopia (TTE) with persistent Mullerian duct syndrome (PMDS), and to deepen the understanding of the disease in clinical. A retrospective analysis of the clinical manifestation, diagnosis, and treatment of two children suffering from TTE with PMDS was conducted. Previous studies on the characteristics, diagnosis, and treatment of this disease were reviewed. The two patients were treated with laparoscopy-assisted transseptal orchidopexy-inguinal evaluation. After the surgery, the two patients recovered well. The follow-up visits were done 3 months after the operation. An ultrasound examination confirmed that the two patients had testes in the orthotopic position and normal size. TTE with PMDS is an exceedingly rare disease. The patients manifested cryptorchidism on one side; contralateral inguinal hernia was suspected. Detailed physical and ultrasound examinations before the operation are the key to the early diagnosis of TTE. Laparoscopic evaluation is helpful for the diagnosis and finding of other abnormalities. Surgical treatment is the only method to cure the disease; long-term follow-up is needed after TTE operation.

CD36 accelerates the progression of hepatocellular carcinoma by promoting FAs absorption.

CD36 is emerging as a potential strategy for cancer treatment because of its function of regulating fatty acid intake. The purpose of this study was to clarify the molecular mechanism of CD36 in the progression of HCC. TCGA database was used to analyze the relationship of CD36 with HCC. The expression of CD36 in HCC clinical samples and cell lines was detected by qRT-PCR and western blot. Huh7 cells and HCCLM3 cells were transfected and treated into different group. CCK-8 and clone formation assay were used to detect the cell proliferation ability. Wound healing and transwell experiment were used to detect the metastatic ability. HCC xenografts were constructed in nude mice by subcutaneous injection of stably transfected Huh7 cells. The expression of CD36 in HCC was detected by immunohistochemistry (IHC). The contents of phospholipids and triglycerides in HCC cells were detected by ELISA. And the content of neutral lipids in HCC cells was detected by staining with BODIPY 493/503 and DAPI dye. Then transcriptional sequencing was used to determine the downstream mechanism of CD36 in HCC, and the differentially expressed genes (DEGs) were analyzed. CD36 was upregulated in HCC. Knockdown of CD36 could suppress the proliferation and metastasis of HCC in vitro and in vivo by regulating FAs intake in HCC. In addition, the expression of AKR1C2 was suppressed by sh-CD36, and which was also involved in the regulation of FAs intake. The molecular mechanism by which CD36 accelerated the progression of HCC was to promote the expression of AKR1C2 and thus enhance fatty acids (FAs) intake.

Prediction of Anti-proliferation Effect of [1,2,3]Triazolo[4,5-d]pyrimidine Derivatives by Random Forest and Mix-Kernel Function SVM with PSO.

In order to predict the anti-gastric cancer effect of [1,2,3]triazolo[4,5-d]pyrimidine derivatives (1,2,3-TPD), quantitative structure-activity relationship (QSAR) studies were performed. Based on five descriptors selected from descriptors pool, four QSAR models were established by heuristic method (HM), random forest (RF), support vector machine with radial basis kernel function (RBF-SVM), and mix-kernel function support vector machine (MIX-SVM) including radial basis kernel and polynomial kernel function. Furthermore, the model built by RF explained the importance of the descriptors selected by HM. Compared with RBF-SVM, the MIX-SVM enhanced the generalization and learning ability of the constructed model simultaneously and the multi parameters optimization problem in this method was also solved by particle swarm optimization (PSO) algorithm with very low complexity and fast convergence. Besides, leave-one-out cross validation (LOO-CV) was adopted to test the robustness of the models and Q2 was used to describe the results. And the MIX-SVM model showed the best prediction ability and strongest model robustness: R2 = 0.927, Q2 = 0.916, mean square error (MSE) = 0.027 for the training set and R2 = 0.946, Q2 = 0.913, MSE = 0.023 for the test set. This study reveals five key descriptors of 1,2,3-TPD and will provide help to screen out efficient and novel drugs in the future.

Monocytes augment inflammatory responses in human aortic valve interstitial cells via ß2-integrin/ICAM-1-mediated signaling.

OBJECTIVE: Inflammatory infiltration in aortic valves promotes calcific aortic valve disease (CAVD) progression. While soluble extracellular matrix (ECM) proteins induce inflammatory responses in aortic valve interstitial cells (AVICs), the impact of monocytes on AVIC inflammatory responses is unknown. We tested the hypothesis that monocytes enhance AVIC inflammatory responses to soluble ECM protein in this study. METHODS: Human AVICs isolated from normal aortic valves were cocultured with monocytes and stimulated with soluble ECM protein (matrilin-2). ICAM-1 and IL-6 productions were assessed. YAP and NF-κB phosphorylation were analyzed. Recombinant CD18, neutralizing antibodies against ß2-integrin or ICAM-1, and inhibitor of YAP or NF-κB were applied. RESULTS: AVIC expression of ICAM-1 and IL-6 was markedly enhanced by the presence of monocytes, although matrilin-2 did not affect monocyte production of ICAM-1 or IL-6. Matrilin-2 up-regulated the expression of monocyte ß2-integrin and AVIC ICAM-1, leading to monocyte-AVIC adhesion. Neutralizing ß2-integrin or ICAM-1 in coculture suppressed monocyte adhesion to AVICs and the expression of ICAM-1 and IL-6. Recombinant CD18 enhanced the matrilin-2-induced ICAM-1 and IL-6 expression in AVIC monoculture. Further, stimulation of coculture with matrilin-2 induced greater YAP and NF-κB phosphorylation. Inhibiting either YAP or NF-κB markedly suppressed the inflammatory response to matrilin-2 in coculture. CONCLUSION: Monocyte ß2-integrin interacts with AVIC ICAM-1 to augment AVIC inflammatory responses to soluble matrilin-2 through enhancing the activation of YAP and NF-κB signaling pathways. Infiltrated monocytes may promote valvular inflammation through cell-cell interaction with AVICs to enhance their sensitivity to damage-associated molecular patterns.

Comparative transcriptomics analysis of contrasting varieties of Eucalyptus camaldulensis reveals wind resistance genes.

BACKGROUND: Wind, an important abiotic stress factor, affects forests in coastal areas, causes tree damage and timber loss. METHODS: Two genotypes of Eucalyptus camaldulensis-strong wind-resistant CA5 and weak wind-resistant C037 were used for RNA-seq analysis to screen for candidate wind-resistance genes and transcription factors (TFs) by comparing the transcriptome analysis of the two varieties in response to wind stress. RESULTS: It showed that 7061 differentially expressed unigenes could be annotated including 4,110 up-regulated unigenes and 2,951 down-regulated unigenes. Gene Ontology (GO) analysis revealed that six cellulose pathways were involved in response to wind stress. The unigenes in phenylpropanoid biosynthesis, phenylalanine metabolism, and flavonoid biosynthesis pathways were found to be differentially expressed based on Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Moreover, 37 differentially expressed genes were functionally annotated to be involved in the secondary metabolism of phenylalanine (ko00940). Seventy-eight TFs related to the regulating cellulose and lignin synthesis were expressed differently from the various treatments. The expressions of C3H, POX, MYB, NAC, Gene008307, and Gene011799 were significantly upregulated in CA5. Overall, the main response of Eucalyptus to wind stress was associated with cell wall biosynthesis; key genes of cellulose and lignin biosynthesis pathways and related TFs were involved in the tree response to wind stress.

Pro-inflammatory mediators released by activated monocytes promote aortic valve fibrocalcific activity.

BACKGROUND: Calcific aortic valve disease (CAVD) is the most prevalent heart valve disorder in the elderly. Valvular fibrocalcification is a characteristic pathological change. In diseased valves, monocyte accumulation is evident, and aortic valve interstitial cells (AVICs) display greater fibrogenic and osteogenic activities. However, the impact of activated monocytes on valular fibrocalcification remains unclear. We tested the hypothesis that pro-inflammatory mediators from activated monocytes elevate AVIC fibrogenic and osteogenic activities. METHODS AND RESULTS: Picro-sirius red staining and Alizarin red staining revealed collagen and calcium depositions in cultured human AVICs exposed to conditioned media derived from Pam3CSK4-stimulated monocytes (Pam3 CM). Pam3 CM up-regulated alkaline phosphatase (ALP), an osteogenic biomarker, and extracellular matrix proteins collagen I and matrix metalloproteinase-2 (MMP-2). ELISA analysis identified high levels of RANTES and TNF-α in Pam3 CM. Neutralizing RANTES in the Pam3 CM reduced its effect on collagen I and MMP-2 production in AVICs while neutralizing TNF-α attenuated the effect on AVIC ALP production. In addition, Pam3 CM induced NF-κB and JNK activation. While JNK mediated the effect of Pam3 CM on collagen I and MMP-2 production, NF-κB was critical for the effect of Pam3 CM on ALP production in AVICs. CONCLUSIONS: This study demonstrates that activated monocytes elevate the fibrogenic and osteogenic activities in human AVICs through a paracrine mechanism. TNF-α and RANTES mediate the pro-fibrogenic effect of activated monocytes on AVICs through activation of JNK, and TNF-α also activates NF-κB to elevate AVIC osteogenic activity. The results suggest that infiltrated monocytes elevate AVIC fibrocalcific activity to promote CAVD progression.

Single-cell RNA-seq reveals a critical role of novel pro-inflammatory EndMT in mediating adverse remodeling in coronary artery-on-a-chip.

A three-dimensional microengineered human coronary artery-on-a-chip was developed for investigation of the mechanism by which low and oscillatory shear stress (OSS) induces pro-atherogenic changes. Single-cell RNA sequencing revealed that OSS induced distinct changes in endothelial cells (ECs) including pro-inflammatory endothelial-to-mesenchymal transition (EndMT). OSS promoted pro-inflammatory EndMT through the Notch1/p38 MAPK-NF-κB signaling axis. Moreover, OSS-induced EC phenotypic changes resulted in proliferation and extracellular matrix (ECM) protein up-regulation in smooth muscle cells (SMCs) through the RANTES-mediated paracrine mechanism. IL-37 suppressed OSS-induced pro-inflammatory EndMT and thereby abrogated SMC proliferation and ECM protein remodeling. Overall, this study provides insights into endothelial heterogeneity under atheroprone shear stress and identifies the mechanistic role of a novel EC subtype in promoting adverse vascular remodeling. Further, this study demonstrates that anti-inflammatory approach is capable of mitigating vascular pathobiology evoked by atheroprone shear stress.

Alpha-ketoglutarate ameliorates pressure overload-induced chronic cardiac dysfunction in mice.

Increasing evidence indicates the involvement of myocardial oxidative injury and mitochondrial dysfunction in the pathophysiology of heart failure (HF). Alpha-ketoglutarate (AKG) is an intermediate metabolite of the tricarboxylic acid (TCA) cycle that participates in different cellular metabolic and regulatory pathways. The circulating concentration of AKG was found to decrease with ageing and is elevated after acute exercise and resistance exercise and in HF. Recent studies in experimental models have shown that dietary AKG reduces reactive oxygen species (ROS) production and systemic inflammatory cytokine levels, regulates metabolism, extends lifespan and delays the occurrence of age-related decline. However, the effects of AKG on HF remain unclear. In the present study, we explored the effects of AKG on left ventricular (LV) systolic function, the myocardial ROS content and mitophagy in mice with transverse aortic constriction (TAC). AKG supplementation inhibited pressure overload-induced myocardial hypertrophy and fibrosis and improved cardiac systolic dysfunction; in vitro, AKG decreased the Ang II-induced upregulation of ß-MHC and ANP, reduced ROS production and cardiomyocyte apoptosis, and repaired Ang II-mediated injury to the mitochondrial membrane potential (MMP). These benefits of AKG in the TAC mice may have been obtained by enhanced mitophagy, which cleared damaged mitochondria. In summary, our study suggests that AKG improves myocardial hypertrophy remodelling, fibrosis and LV systolic dysfunction in the pressure-overloaded heart by promoting mitophagy to clear damaged mitochondria and reduce ROS production; thus, AKG may have therapeutic potential for HF.

A Study on Mesoporous Silica Loaded With Novel Photosensitizers HCE6 and Oxaliplatin for the Treatment of Cholangiocarcinoma.

PURPOSE: Cholangiocarcinoma (CCA) is a malignant tumor with a high incidence. The therapeutic effect of conventional chemotherapy and radiotherapy is not obvious. Photodynamic therapy (PDT) is an ideal modality to fight cancer, and the nature of photosensitizer limits its application in clinical therapy. The aim of this study was to explore a novel mode of drug delivery for the intervention of bile duct cancer. METHODS: Oxaliplatin and photosensitizer HCE6 were loaded with mesoporous silica nanoparticles (MSNs) to synthesize Oxaliplatin/HCE6-MSNs (OH-MSNs); the structure of OH-MSNs was characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), the drug release rate was detected by high performance liquid chromatography; the cellular activity, apoptosis level, and the expression levels of intracellular apoptosis and autophagy-related factors of OH-MSNs on cholangiocarcinoma cells were observed by CCK-8, flow cytometry, colony formation assay, and Western blot; the effects of OH-MSNs on cholangioma growth were observed by mouse tumor formation, immunohistochemistry, and tissue Tunel staining. RESULTS: The release of OH-MSNs to Oxaliplatin was enhanced under acidic conditions; compared with Oxaliplatin or O-MSNs, OH-MSNs showed more potent killing effects against cholangiocarcinoma cells (P<0.05), and exerted notably inhibitory effects on the activity of cholangiocarcinoma cells (P<0.05), promoted their apoptosis (P<0.05), and greatly facilitated the expression of pro-apoptotic factors and autophagic factors in cholangiocarcinoma cells (P<0.05), and markedly inhibited the expression of anti-apoptotic factors and autophagic inhibitory factors (P<0.05); moreover, OH-MSNs could significantly suppress the growth of mouse cholangiocarcinoma (P<0.05) and induce apoptosis of tumor cells compared with Oxaliplatin or O-MSNs (P<0.05). CONCLUSION: MSNs loading greatly increases the killing effect of Oxaliplatin on cholangiocarcinoma cells and upgrades the autophagic level of cholangiocarcinoma cells, while OH-MSNs synthesized by further loading HCE6 have a more apparent killing effect on cholangiocarcinoma cells.

Laparoscopic percutaneous extraperitoneal closure with peritoneum reinforcement repair for pediatric inguinal hernia: a single-center experience with over 2,000 patients.

BACKGROUND: Inguinal hernia is one of the common diseases in infants and children that requires operative treatment. Laparoscopic inguinal hernia repair in children has become an alternative to the open procedure. Laparoscopic percutaneous extraperitoneal closure with peritoneum reinforcement (LPECPR) is a safe and effective approach for pediatric inguinal hernia, and has a lower recurrence. This is a retrospective study to present our experience with children who underwent LPECPR. METHODS: A total of 2,018 patients with inguinal hernia who underwent LPECPR in our hospital from July, 2011 to December, 2020 were reviewed. The surgical technique is modified on the basis of laparoscopic percutaneous extraperitoneal closure (LPEC) to close extraperitoneally by circuit suturing twice around the internal inguinal ring. RESULTS: All cases were completed LPECPR without conversion. There were no intraoperative complications. A total of 2,018 patients' laparoscopic procedures were achieved. The mean operative time was 14 and 20 min for unilateral and bilateral operations, respectively. Follow-up to date is 13.4 months (6-36 months), there were no postoperative complications, such as knot reactions, hydrocele formation, testicular atrophy or pain, except 3 recurrences (3/2,018, 0.15%). CONCLUSIONS: This modified LPECPR technique can acquire lower recurrence rate for repair pediatric inguinal hernia. The midterm safety and efficacy of LPECPR are proven and it can be a routine procedure.

Monocytes enhance the inflammatory response to TLR2 stimulation in aortic valve interstitial cells through paracrine up-regulation of TLR2 level.

Background and Objectives: Chronic valvular inflammation associated with monocyte infiltration promotes calcific aortic valve disease (CAVD) progression. Further, innate immunity in aortic valve interstitial cells (AVICs), mediated by Toll-like receptors (TLRs), up-regulates cellular inflammatory, fibrogenic and osteogenic activities. Currently, the pro-inflammatory communication between monocytes and AVICs and the underlying mechanism are unclear. We hypothesized that monocytes up-regulate AVIC inflammatory activity. This study sought to characterize the interaction between monocytes and AVICs and to elucidate the mechanism underlying cell-to-cell communication. Methods and Results: AVICs, monocytes and co-cultures were exposed to a low concentration of TLR2 activator Pam3CSK4 (0.03 µg/ml). The TLR2 activator at this dose induced a marked increase in AVIC production of ICAM-1 and VCAM-1 only when co-cultured with monocytes. Adding conditioned medium from Pam3CSK4-treated monocytes (Pam3 CM, containing 0.1 µg/ml of Pam3CSK4) to AVIC culture (30% vol/vol; diluting Pam3CSK4 to 0.03 µg/ml) greatly increased the expression of adhesion molecules while adding conditioned medium from untreated monocytes (control CM) had no effect. Inhibition or knockdown of TLR2 in AVICs markedly reduced ICAM-1 and VCAM-1 expression induced by Pam3 CM. Further, Pam3 CM increased TLR2 levels in AVICs. Multiplex-ELISA analysis of Pam3 CM identified greater levels of TNF-α. Neutralization of TNF-α abolished the effect of Pam3 CM on AVIC TLR2 levels, resulting in marked attenuation of its potency in the induction of adhesion molecule expression. Conclusions: This study demonstrates that activated monocytes use paracrine signaling to sensitize AVICs for inflammatory responses to a low level of TLR2 activator. The mechanism of sensitization involves up-regulation of AVIC TLR2 levels by TNF-α from monocytes. Infiltrated monocytes in aortic valve tissue may exacerbate valvular inflammation by rendering AVICs hypersensitive to TLR2 activators.

Mechanistic Roles of Matrilin-2 and Klotho in Modulating the Inflammatory Activity of Human Aortic Valve Cells.

BACKGROUND: Calcific aortic valve disease (CAVD) is a chronic inflammatory disease. Soluble extracellular matrix (ECM) proteins can act as damage-associated molecular patterns and may induce valvular inflammation. Matrilin-2 is an ECM protein and has been found to elevate the pro-osteogenic activity in human aortic valve interstitial cells (AVICs). Klotho, an anti-aging protein, appears to have anti-inflammatory properties. The effect of matrilin-2 and Klotho on AVIC inflammatory responses remains unclear. METHODS AND RESULTS: Isolated human AVICs were exposed to matrilin-2. Soluble matrilin-2 induced the production of ICAM-1, MCP-1, and IL-6. It also induced protein kinase R (PKR) activation via Toll-like receptor (TLR) 2 and 4. Pretreatment with PKR inhibitors inhibited NF-κB activation and inflammatory mediator production induced by matrilin-2. Further, recombinant Klotho suppressed PKR and NF-κB activation and markedly reduced the production of inflammatory mediators in human AVICs exposed to matrilin-2. CONCLUSIONS: This study revealed that soluble matrilin-2 upregulates AVIC inflammatory activity via activation of the TLR-PKR-NF-κB pathway and that Klotho is potent to suppress AVIC inflammatory responses to a soluble ECM protein through inhibiting PKR. These novel findings indicate that soluble matrilin-2 may accelerate the progression of CAVD by inducing valvular inflammation and that Klotho has the potential to suppress valvular inflammation.

Electrochemically triggered degradation of silicon membranes for smart on-demand transient electronic devices.

Transient electronics is an emerging technology that enables unique functional transformation or the physical disappearance of electronic devices, and is attracting increasing attention for potential applications in data secured hardware as an ultimate solution against data breaches. Developing smart triggered degradation modalities of silicon (Si) remain the key challenge to achieve advanced non-recoverable on-demand transient electronics. Here, we present a novel electrochemically triggered transience mechanism of Si by lithiation, allowing complete and controllable destruction of Si devices. The depth and microstructure of the lithiation-affected zone over time is investigated in detail and the results suggest a few hours of lithiation is sufficient to create microcracks and significantly promote lithium penetration. Finite element models are proposed to confirm the mechanism. Electrochemically triggered degradation of thin film Si ribbons and Si integrated circuit chips with metal-oxide-semiconductor field-effect transistors from a commercial 0.35 micrometer complementary metal-oxide-semiconductor technology node is performed to demonstrate the potential applications for commercial electronics. This work opens new opportunities for versatile triggered transience of Si-based devices for critical secured information systems and green consumer electronics.