Mitophagy-regulated Necroptosis plays a vital role in the nephrotoxicity of Fumonisin B1 in vivo and in vitro.

Fumonisin B1 (FB1), one of the most widely distributed mycotoxins found in grains and feeds as contaminants, affects many organs including the kidney once ingested. However, the nephrotoxicity of FB1 remains to be further uncovered. The connection between necroptosis and nephrotoxicity of FB1 has been investigated in this study. The results showed that mice exposed to high doses of FB1 (2.25 mg/kg b.w.) developed kidney damage, with significant increases in proinflammatory cytokines (Il-6, Il-1ß), kidney injury-related markers (Ngal, Ntn-1), and gene expressions linked to necroptosis (Ripk1, Ripk3, Mlkl). The concentration-dependent damage effects of FB1 on PK-15 cells contain cytotoxicity, cellular inflammatory response, and necroptosis. These FB1-induced effects can be neutralized by pretreatment with the necroptosis inhibitor Nec-1. Additionally, FB1 caused mitochondrial damage and mitophagy in vivo and in vitro, whereas Mdivi-1, a mitophagy inhibitor, prevented these effects on PK-15 cells as well as, more crucially, necroptosis. In conclusion, the RIPK1/RIPK3/MLKL signal route of necroptosis, which may be controlled by mitophagy, mediated nephrotoxicity of FB1. Our findings clarify the underlying molecular pathways of FB1-induced nephrotoxicity.

Comparison of the PADUA and IMPROVE scores in assessing venous thromboembolism risk in 42,257 medical inpatients in China.

Venous thromboembolism (VTE) is a major contributor to hospital mortality and disability-adjusted life-year (DALY) loss. Multiple guidelines recommend using the Padua or IMPROVE scores to stratify VTE risk in hospitalized medical patients. However, the IMPROVE score is not recommended in Chinese guidelines, and there is very little evaluation of its clinical application and effectiveness in the Chinese population. The objective of this study is to compare the efficacy of the Padua and IMPROVE scoring models for assessing VTE risk in Chinese medical inpatients. We conducted a retrospective analysis of the clinical characteristics and thrombotic risk of 42,257 medical inpatients at a tertiary hospital in Guangdong, China, between 2021 and 2022. Logistic regression was used to assess thrombotic risk factors. The Receiver Operating Characteristic (ROC) curves, Area Under the Curve (AUC), sensitivity, and specificity were employed to evaluate the performance of the two models. Of the 42,257 patients included, 948 (2.24%) experienced VTE during hospitalization. According to the Padua score, 3,7513 (88.78%) of patients were considered low risk, while 4,744 (18.22%) were classified as high risk. The IMPROVE score identified 20,744 (49.09%) of patients as low risk, 20799(49.22%) as intermediate risk, and 714(1.69%) as high risk. The AUC for the Padua score was 0.735 (95% CI: 0.717-0.753), with a sensitivity of 49.4% and specificity of 89.6%. For the IMPROVE score, the AUC was 0.711 (95% CI: 0.693-0.729), with a sensitivity of 32.5% and specificity of 99.0%. The DeLong test, used to compare the AUCs, yielded a z-value of 1.886 with a P-value of 0.059, indicating no statistical difference. When assessing VTE risk in patients with stroke, cancer, nephrotic syndrome, and critical illness (ICU/CCU stay), both scoring models showed comparable predictive performance with AUCs ranging between 0.7 and 0.8. Both the Padua score and IMPROVE score have good predictive ability for VTE events during hospitalization in medical patients. Among them, the IMPROVE score has objective assessment items, simpler operation, and more detailed risk stratification, which is beneficial for clinicians to take physical and pharmacological preventive measures at different levels.ChiCTR2200056903, February 22, retrospectively registered.

Is the expression of different discrete emotions related to time? Evidence from online Chinese reviews using sentiment analysis and human behavior dynamics.

Objectives: The online behavior of online users has taken on complex and diverse characteristics, and posting product reviews on e-commerce platforms is no exception. In fact, reviews contain rich and multi-dimensional discrete emotional information, and whether there is a relationship between the expression of these different discrete emotions and the time interval between product purchase and review posting as well as their related characteristics are the issues that this study needs to analyze and solve in depth. Methods: Based on the OCC model (named after three proposers) of psychological emotional cognitive evaluation theory as the basis for emotion classification, the study used the massive amounts of Chinese reviews of mobile phones on the Chinese e-commerce platform Jingdong Mall as the research object, applied supervised machine learning methods to classify discrete emotions, and constructed a large corpus containing satisfaction, disappointment, admiration, reproach, love, and hate; then the study delved into the distribution and behavioral dynamics characteristics of consumers' comments containing the different discrete emotions at different "purchase-comment" time intervals. Results: The results showed that the first peak of the distribution curves of the six discrete emotions at different "purchase-comment" time intervals occurs on the first day after purchase and then decreases gradually but at different rates. The three curves for satisfaction, love, and hate emotions also show a second peak on the eleventh day, which is more similar to the bimodal distribution, implying that the corresponding product reviews are more objective. In addition, the distribution of reviews containing the six discrete emotions at different "purchase-comment" time intervals follows a power-law distribution and has the temporal characteristics of human behavioral dynamics, that is, "strong paroxysms and weak memory". However, the reviews containing the admiration and reproach emotions were most intensively written by consumers after the purchase, indicating that the service provided by the seller, logistics, and e-commerce platform stimulates more consumers to give quick responses and detailed reviews. Conclusion: This study is not only of great significance for exploring the internal mechanisms of consumer discrete emotional expression but also provides important decision-making references for potential consumer purchasing decisions, product updates for developers, marketing strategy formulation for marketing teams, and service improvement for sellers, logistics companies, and e-commerce platforms.

3D-printed near-infrared-light-responsive on-demand drug-delivery scaffold for bone regeneration.

Although several bioactive 3D-printed bone scaffolds loaded with multiple kinds of biomolecules for enhanced bone regeneration have been recently developed, the manipulation of on-demand release profiles of different biomolecules during bone regeneration remains challenging. Herein, a 3D-printed dual-drug-loaded biomimetic scaffold to regulate the host stem cell recruitment and osteogenic differentiation in a two-stage process for bone regeneration was successfully fabricated. First, a chemotactic small-molecule drug, namely, simvastatin (SIM) was directly incorporated into the hydroxyapatite/collagen bioink for printing and could be rapidly released during the early stage of bone regeneration. Further, near-infrared (NIR)-light-responsive polydopamine-coated hydroxyapatite nanoparticles were designed to deliver the osteogenic drug, i.e., pargyline (PGL) in a controllable manner. Together, our scaffold displayed an on-demand sequential release of those two drugs and could optimize their therapeutic effects to align with the stem cell recruitment and osteoblastic differentiation, thereby promoting bone regeneration. The results confirmed the suitable mechanical strength, high photothermal conversion efficiency, good biocompatibility of our scaffold. The scaffold loaded with SIM could efficiently accelerate the migration of stem cells. In addition, the scaffold with on-demand sequential release promoted alkaline phosphatase (ALP) activity, significantly upregulated gene expression levels of osteogenesis-related markers, and enhanced new-bone-formation capabilities in rabbit cranial defect models. Altogether, this scaffold not only offers a promising strategy to control the behavior of stem cells during bone regeneration but also provides an efficient strategy for controllable sequential release of different biomolecule in bone tissue engineering.

Glycolic acid-based deep eutectic solvents boosting co-production of xylo-oligomers and fermentable sugars from corncob and the related kinetic mechanism.

BACKGROUND: Xylo-oligomers are a kind of high value-added products in biomass fractionation. Although there are several chemical methods to obtain xylo-oligomers from biomass, the reports about the deep eutectic solvents (DESs)-mediated co-production of xylo-oligomers and fermentable sugars and the related kinetic mechanism are limited. RESULTS: In this work, glycolic acid-based DESs were used to obtain xylo-oligomers from corncob. The highest xylo-oligomers yield of 65.9% was achieved at 120 °C for 20 min, of which the functional xylo-oligosaccharides (XOSs, DP 2-5) accounted for up to 31.8%. Meanwhile, the enzymatic digestion of cellulose and xylan in residues reached 81.0% and 95.5%, respectively. Moreover, the addition of metal inorganic salts significantly accelerated the hydrolysis of xylan and even the degradation of xylo-oligomers in DES, thus resulting in higher selectivity of xylan removal. AlCl3 showed the strongest synergistic effect with DES on accelerating the processes, while FeCl2 is best one for xylo-oligomers accumulation, affording the highest xylo-oligomers yield of 66.1% for only 10 min. Furthermore, the kinetic study indicates that the 'potential hydrolysis degree' model could well describe the xylan hydrolysis processes and glycolic acid/lactic acid (3:1) is a promising solvent for xylo-oligomers production, in particular, it worked well with FeCl2 for the excellent accumulation of xylo-oligomers. CONCLUSIONS: Glycolic acid-based deep eutectic solvents can be successfully applied in corncob fractionation with excellent xylo-oligomers and fermentable sugars yields on mild conditions, and the large amount of xylo-oligosaccharides accumulation could be achieved by specific process controlling. The strategies established here can be useful for developing high-valued products from biomass.

Burden of COPD in China and the global from 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019.

OBJECTIVE: To investigate the current disease burden of chronic obstructive pulmonary disease (COPD) in China and globally using the Global Burden of Disease (GBD) data in 2019, as well as to analyse the changes in its risk factors, providing a scientific basis for the formulation of a comprehensive prevention and control strategy for COPD in China. STUDY DESIGN: An observational study based on the GBDs. METHODS: Based on the GBD 2019 database, we obtained data on incidence, prevalence, mortality, disability-adjusted life years (DALYs) and corresponding age-standardised rates of COPD in China and the global, and analysed and described the changing trends of COPD burden in China and the global from 1990 to 2019. RESULTS: In 2019, the total number of COPD deaths in China was 1.04 (95% uncertainty intervals (95% UI): 0.89-1.27) million cases, the number of patients with COPD was 45.16 (95% UI: 41.13-49.62) million cases, and the number of new cases was 4.0 (95% UI: 3.6-4.4) million cases. DALYs were 74.4 (95% UI: 68.2-80.2) million years. Compared with 1990, the number of new incident cases and the overall prevalence of COPD in China in 2019 increased by 66.20% and 66.76%, respectively, which is lower than the overall global level. CONCLUSION: From 1990 to 2019, the age-standardized prevalence rate (ASPR), the age-standardized incidence rate (ASIR) and the age-standardized death rate (ASDR) in China and the global all showed a downward trend, and the rate of decline in China was much higher than the overall level of the world, indicating that China has made specific achievements in the prevention and treatment of COPD, but overall the disease burden of COPD is still hefty, and the number of affected individuals is still increasing.

Cascading effects of seed-stem-individual spatial patterns along a grazing gradient.

Studying the seed trait-stem trait-individual spatial pattern system is helpful for understanding the developmental direction of plant dynamics and populations under grazing disturbance as well as the antagonistic relationship between animals and plants, but few systematic analyses of this spatial pattern system have been carried out. Kobresia humilis is the dominant species in alpine grasslands. We studied K. humilis seed traits and their relationship with K. humilis reproductive individuals, the relationship between reproductive and vegetative stems, and the weights and spatial patterns of reproductive and nonreproductive individuals under four grazing treatments: no grazing (control), light grazing, moderate grazing and heavy grazing. We explored the relationship among seed size and seed number with reproductive stems and vegetative stems along the grazing gradient and assessed the spatial pattern changes between reproductive and nonreproductive individuals. The results showed the following: (1) Seed size increased with increasing grazing intensity, and the coefficient of variation for seed size and seed number in the heavy grazing treatment was greater than 0.6. (2) The structural equation model showed that grazing treatment had a positive effect on seed number, seed size and reproductive stem number and a negative effect on reproductive stem weight. (3) Grazing treatment did not affect the resource allocation to reproductive stems and vegetative stems per unit length of reproductive K. humilis individuals. (4) Compared with the number of reproductive individuals in the no grazing treatment, the number in the heavy grazing treatment decreased significantly, and the negative correlation between reproductive individuals and nonreproductive individuals changed from a full-scale negative correlation to a small-scale negative correlation and a large-scale positive correlation. Our study showed that grazing could activate and change the resource allocation pattern of dominant species in a grassland and have significant positive effects on reproductive stem number, reproductive stem weight, seed number and seed size. Along a grazing intensity gradient, with the increase in distance between reproductive and nonreproductive individuals, the transformation of intraspecific relationships from a negative correlation to a positive correlation is an ecological strategy conducive to population survival.

Oxidative Stress and Pyroptosis in Doxorubicin-Induced Heart Failure and Atrial Fibrillation.

Patients undergoing doxorubicin (Dox) chemotherapy often develop new-onset atrial fibrillation and heart failure. Recent studies indicate that the TLR4/MyD88/NLRP3 pyroptosis signaling pathway plays a key role in the occurrence and development of cancer, heart failure, and atherosclerosis. However, few studies investigated the role of oxidative stress and pyroptosis in doxorubicin-induced heart failure and new-onset atrial fibrillation. In this study, we recruited 84 healthy subjects, 112 patients undergoing Dox chemotherapy showing heart failure (HF), and 62 patients undergoing Dox treatment who manifested atrial fibrillation (AF). The mRNA and protein levels of TLR4 expression, several downstream pyroptosis-associated proteins (cleaved caspase-1, NLRP3, GSDMD-N, and HMGB-1), serum inflammatory factors, and oxidative stress were detected at the beginning of chemotherapy and after 3 months of Dox chemotherapy. Oxidative stress and downstream pyroptosis-associated proteins tended to increase in the Dox-baseline group to the Dox-HF group. However, virtually no change in the expression of either oxidative stress or pyroptosis-associated proteins was detected in patients after three months of Dox chemotherapy compared with those at baseline. This study suggests that the prolonged oxidative stress and high levels of pyroptosis-associated proteins contribute to cardiac systolic dysfunction, suggesting TLR4 as a novel biomarker and a potential treatment target for doxorubicin-induced heart failure.

Two new antimicrobial monoterpenoid indole alkaloids from the roots of Rauvolfia yunnanensis.

Two new monoterpenoid indole alkaloids 3-hydroxylochnerine (1) and 10-hydroxyvinorine (2) were isolated from the roots of Rauvolfia yunnanensis. Their structures were elucidated based on the analysis of spectroscopic data and ECD calculation. Both compounds exhibited potent antimicrobial activity against Bacillus subtilis and Escherichia coli, and their activities were comparable to the well-known antibacterial drug berberine.

Development and validation of a noninvasive prediction model for identifying eosinophilic asthma.

BACKGROUND: Identification of eosinophilic asthma (EA) using sputum analysis is important for disease monitoring and individualized treatment. But it is laborious and technically demanding. We aimed to develop and validate an effective model to predict EA with multidimensional assessment (MDA). METHODS: The asthma patients who underwent a successful sputum induction cytological analysis were consecutively recruited from March 2014 to January 2021. The variables assessed by MDA were screened by least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a nomogram and an online web calculator. Validation was performed internally by a bootstrap sampling method and externally in the validation cohort. Diagnostic accuracy of the model in different asthma subgroups were also investigated. RESULTS: In total of 304 patients in the training cohort and 95 patients in the validation cohort were enrolled. Five variables were identified in the EA prediction model: gender, nasal polyp, blood eosinophils, blood basophils and FeNO. The C-index of the model was 0.86 (95% CI: 0.81-0.90) in the training cohort and 0.84 (95% CI: 0.72-0.89) in the validation cohort. The calibration curve showed good agreement between the prediction and actual observation. The decision curve analysis (DCA) also demonstrated that the EA prediction model was clinically beneficial. An online publicly available web calculator was constructed (https://asthmaresearcherlimin.shinyapps.io/DynNomapp/). CONCLUSION: We developed and validated a multivariable model based on MDA to help the diagnosis of EA, which has good diagnostic performance and clinical practicability. This practical tool may be a useful alternative for predicting EA in the clinic.

The growth rates and influencing factors of preterm and full-term infants: A birth cohort study.

This study aimed to explore the growth rates and influencing factors of the length and weight of preterm and full-term infants in the urban areas of Hubei province to provide a reference for child health and related clinical fields. A birth cohort study was used to analyze the growth rates and influencing factors of the length and weight of preterm and full-term infants using a multivariate regression analysis. The growth rates of the length and weight of preterm infants were significantly lower than those of full-term infants from birth to 3 months of age (P < .05), and gradually caught up to the level of full-term infants after 3 months of age (P > .05). Meanwhile, there were some influencing factors that had significant differences by their contribution to the growth rates of the length and weight of preterm and full-term infants. This study proposed that perinatal factors were attached more importance to the growth rates of preterm infants in the urban areas of Hubei province.

Childhood trauma and the plasma levels of IL-6, TNF-α are risk factors for major depressive disorder and schizophrenia in adolescents: A cross-sectional and case-control study.

BACKGROUND: It has been reported that childhood trauma and inflammation are associated with major depressive disorder (MDD) and schizophrenia (SZ), but previous researches were almost aimed at adults. The aim of the present research is to observe the alteration of peripheral interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in adolescents (12-20 years) with MDD and SZ, to investigate the impact of childhood abuse in early-onset MDD and SZ, and to furtherly explore the correlation between childhood maltreatment and plasma IL-6, TNF-α levels. SUBJECTS AND METHODS: Enzyme-linked immunosorbent assay (ELISA) is applied to obtain the plasma concentrations of IL-6 and TNF-α in 55 patients with MDD, 51 patients with SZ and 47 healthy minors. The short form of the Childhood Trauma Questionnaire (CTQ-SF) is used to assess the severity of early trauma. RESULTS: Plasma IL-6 and TNF-α levels are significantly elevated in patients with early-onset MDD and SZ compared with healthy subjects (p <0.01), whose results display that the correlation between IL-6 and TNF-α is significantly positive (γ=0.787, p <0.01) in all participants. Compared with the healthy adolescents, patients with MDD and SZ show more serious childhood trauma, and the plasma IL-6, TNF-α concentrations are closely related to childhood maltreatment. CONCLUSIONS: Early trauma and peripheral inflammatory response play an important role in the pathophysiology of early-onset MDD or SZ. The current findings provide effective targets for the prevention, diagnosis, and treatment of major depressive disorder and schizophrenia in adolescents.

Treatment mode and prognosis of esophageal perforation after radiotherapy in patients with esophageal carcinoma.

Objective: Retrospectively analyzed the esophageal carcinoma (EC) patients with esophageal perforation (EP) after radiotherapy to discuss the treatment and prognosis. Methods: Data of patients with EC who had EP after radiotherapy in Hebei Cancer Hospital were collected from 2001 to 2020 and retrospectively analyzed. All analyses were performed using SPSS Statistics for Windows, version 18. 0 (SPSS Inc., Chicago, Ill., USA). P values less than 0.05 were considered statistically significant. Results: A total of 94 patients with EC were enrolled, among which 72 were males and 22 were females, with a median age of 62 (38-82) years. The tumor was located in the upper thoracic in 45 patients, middle thoracic in 45 patients, and lower thoracic in 4 patients. There were 30 cases of tracheoesophageal fistula (TEF) and 64 cases of esophagomediastinal fistula (EMF). All patients died within 11 months (median: two months) after EP. After EP, 48 patients were treated by tube feeding (include nasal feeding and gastrostomy), 26 patients by esophageal stenting, and 20 patients by fluid infusion therapy, and their one, three, and six months survival rates after EP were 81.3%, 31.3%, and 12.5% (P = 0.000). In the TEF group, the one, three, and six month survival rates after EP of tube feeding, esophageal stenting and fluid infusion groups were 88.2%, 17.6%, 11.8%; 45.5%, 27.3%, 0%; and 50.0%, 50.0%, 0% (P = 0.345). In the EMF group, the one, three, and six months survival rates after EP of this three groups were 77.4%, 38.7%, 12.9%; 26.7%, 20.0%, 6.7%; and 22.2%, 11.1%, 0% (P=0.002), respectively. Conclusion: Most patients with EP after radiotherapy died within six months, with low survival and poor prognosis. Tube feeding therapy can achieve relatively good survival, especially for patients with EMF. The survival of patients treated by tube feeding therapy is significantly better than the survival of those treated by other methods.

Clinical outcomes of salvage radiotherapy in patients with supraclavicular lymph node metastases after esophagectomy.

Purpose: To evaluate the clinical outcomes of salvage radiotherapy in patients with supraclavicular lymph node (SCLN) metastases after esophagectomy. Methods: After initial esophagectomy (R0 resection), clinical outcomes in patients with esophageal squamous cell carcinoma with SCLN metastases during follow-up were retrospectively analyzed. Results: A total of 114 patients were split into two groups: the salvage radiotherapy (SR) (n=89) and the control (NSR) (without salvage radiotherapy, n=25). The overall survival rates of 1 year, 3 years and 5 years were 81.6%, 31.4% and 8.6%, accordingly. The 1-year and 3-year survival after SCLN metastases (SASM) rates were 40.2% and 14.5%, respectively; the median SASM time was 10 months. In the SR group, the SASM rates of 1-year and 3-year were 48.1% and 18.9%, compared to 12.0% and 0% in the NSR group (p<0.001). Patients in the SR group who received combined radiochemotherapy experienced 1-year and 3-year SASM rates of 62.6% and 33.4%, compared to 41.9% and 16.5% with single radiotherapy (p<0.001). The salvage radiation dose revealed that the 1-year and 3-year SASM rates turned out to be 56.5% and 23.4% in group of ≥60 Gy, and 29.2% and 7.5% in group of <60 Gy (p<0.001). According to multivariate analysis, combined visceral metastases (CVM), combined mediastinal failure (CMF), salvage radiotherapy, salvage radiation dose and salvage treatment method possibly were identified as important prognostic variables. After propensity score matching (PSM), the above results were similar to those before PSM, except for that only salvage radiotherapy is possibly independent prognostic variables for survival after SCLN metastases in multivariate analysis. Conclusion: It is possible that salvage radiotherapy can increase the survival rate of patients who receive SCLN metastases following esophagectomy.

ω-3 fatty acid alleviates virus-induced myocardial injury by regulating TLR4 and TLR3 expression.

The specific pathogenesis of viral-induced myocardial injury is unclear. TLR regulation plays an important role in virus-induced myocardial injury. The therapeutic effect and possible mechanism of omega-3 fatty acids in patients with viral-induced myocardial injury must be investigated. The study population was randomly divided into three groups: a healthy control group (n = 50); general treatment group (n = 40); and general treatment with ω-3 polyunsaturated fatty acid group (n = 36). We detected the mRNA levels of TLR3 and TLR4, downstream signal pathway proteins, inflammatory factors, oxidative stress markers, and myocardial enzymes in patients and healthy controls. ω-3 fatty acid therapy in patients with virus-induced myocardial injury significantly regulates the expression of TLR3 and TLR4 and their downstream signal protein, increases antioxidant expression, reduces the secretion of inflammatory factors, alleviates myocardial injury, and improves cardiac function. This provides a new strategy to treat virus-induced myocardial injury.

GAPDH siRNA Regulates SH-SY5Y Cell Apoptosis Induced by Exogenous α-Synuclein Protein.

The transport mechanism of intestinal α-synuclein to the central nervous system has become a new hot topic in Parkinson's disease (PD) research. It is worth noting that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been reported to be involved in the pathogenesis of PD. After silencing GAPDH expression by GAPDH siRNA, the normal human intestinal epithelial crypt-like (HIEC) and human SH-SY5Y neuroblastoma cell lines were co-cultured with Escherichia coli cells which were transfected with an α-synuclein overexpression plasmid. The levels of autophagy-related proteins (BECN1, ATG5, LC3A/B and p62) were determined by Western blot analysis. Changes in pro-apoptosis protein levels and flow cytometry analysis were used to assess cell apoptosis and relative intracellular ATP concentration was measured. Oxidative stress was assessed by measuring the levels of reactive oxygen species (ROS) using 2',7'-dichlorofluorescein diacetate (DCFH-DA), thiobarbituric acid-reactive substances (TBARS), and antioxidant capacity was assessed by measuring the glutathione (GSH) levels and superoxide dismutase (SOD) activity. The silencing of the expression of GAPDH pre-knockdown was found to reduce the intracellular levels of ROS and lipid peroxidation, enhance autophagy activity, thereby reducing the cell injury, apoptosis and necrosis induced by exogenous α-synuclein protein in SH-SY5Y cells. This study identifies a new therapeutic target of exogenous α-synuclein protein induced SH-SY5Y cell injury and improves our understanding of the pathophysiological role of GAPDH in vitro.

A high-throughput cell-based gaussia luciferase reporter assay for measurement of CYP1A1, CYP2B6, and CYP3A4 induction.

The induction of cytochrome P450s can result in reduced drug efficacy and lead to potential drug-drug interactions. The xenoreceptors-aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR)-play key roles in CYP induction by xenobiotics. In order to be able to rapidly screen for the induction of three enzymes (CYP1A1, CYP2B6, and CYP3A4), we generated a stable AhR-responsive HepG2 cell line, a stable CAR-responsive HepG2 cell line, and a stable PXR-responsive HepG2 cell line.To validate these stable xenoreceptor-responsive HepG2 cell lines, we evaluated the induction of the different Gaussia reporter activities, as well as the mRNA and protein expression levels of endogenous CYPs in response to different inducers.The induction of luciferase activity in the stable xenoreceptor-responsive HepG2 cell lines by specific inducers occurred in a concentration dependent manner. There was a positive correlation between the induction of luciferase activities and the induction endogenous CYP mRNA expression levels. These xenoreceptor-responsive HepG2 cell lines were further validated with known CYP1A1, CYP2B6, and CYP3A4 inducers.These stable xenoreceptor-responsive HepG2 cell lines may be used in preclinical research for the rapid and sensitive detection of AhR, CAR, and PXR ligands that induce CYP450 isoforms.

Mercury as a cause of membranous nephropathy and Guillain-Barre syndrome: case report and literature review.

Secondary renal involvement in chronic exposure to metallic mercury is well known. Mercury also causes central nervous system damage and demyelinating polyneuropathy. Here, we describe a case of a patient with daily exposure to mercury in skin lightening cream and hair dyes who was diagnosed with Guillain-Barre syndrome and then developed nephrotic syndrome because of membranous neuropathy. By reviewing the literature describing mercury-associated diseases, we found that mercury components have an immunomodulatory activity, which is also involved in both peripheral neuropathy and glomerulonephritis.

Solutions to stuck tunneled cuffed catheters in patients undergoing maintenance hemodialysis.

OBJECTIVE: To study and discuss treatments for stuck tunneled cuffed catheter in patients undergoing maintenance hemodialysis. METHOD: Retrospectively analyzing clinical data of 13 patients with stuck tunneled cuffed catheter in the Kidney Disease Center of the First Affiliated Hospital, College of Medicine, Zhejiang University in the period between September 2012 and October 2018. All patients failed to remove hemodialysis catheters by regular technique. The stuck catheters were treated by thoracotomy, endoluminal percutaneous transluminal angioplasty with blunt dissection or embedded and left in situ. RESULTS: In 13 patients, one was successfully treated by thoracotomy, one failed to remove the catheter by regular technique and blunt dissection, and the stump of the catheter was clamped and buried in the subcutaneous fascia of the neck, and the other 11 were treated by endoluminal percutaneous transluminal angioplasty with blunt dissection. The average time of catheter removal procedure is 25 min, the overall success rate is 92.3%, and the success rate of percutaneous transluminal angioplasty is 100%. CONCLUSION: Thoracotomy is an efficient way to treat stuck catheter but is limited by its high risk and complications. Leaving part of catheter in situ may increase the risk of central vein stenosis. Comparing to the former two, endoluminal percutaneous transluminal angioplasty is a safe, efficient, and practical way for stuck catheters and should be recommended as the first choice.

Ultracompact optical fiber acoustic sensors based on a fiber-top spirally-suspended optomechanical microresonator.

Acoustic wave sensors with a high sensitivity and small size are highly desired for a wide variety of important and emerging applications such as photoacoustic gas sensing and bio-imaging. Here we present an ultracompact optical fiber acoustic sensor based on an optomechanical resonator that is directly in situ printed on the end face of a standard single-mode optical fiber by using an optical 3D µ-printing technology. The fiber-top optomechanical microresonator is composed of a microscale suspended polymer micro-disk that forms a Fabry-Perot interferometric cavity, together with the optical fiber end face, and acts as the acoustic wave-sensitive micromechanical resonator simultaneously. The microbeams for suspending the micro-disk are devised with a spiral structure to overcome the small-size imposed low deflection amplitude so as to improve its sensitivity to acoustic waves. The sensor with a high sensitivity of 118.3 mV/Pa and low noise equivalent acoustic signal level of 0.328µPa/Hz1/2 at audio frequency is experimentally demonstrated. Moreover, with a resonance amplification mechanism, the sensitivity can be enhanced by 40.1 times when the frequency of the acoustic wave matches with the natural resonance frequency of the optomechanical resonator. Such an ultrasmall fiber-tip acoustic sensor has not only a miniaturization-induced broad bandwidth, but also a structure-enhanced ultrahigh sensitivity and thus is very promising in various acoustic wave-based sensing, imaging, and testing applications.