Myocardial ischemia-reperfusion injury: The balance mechanism between mitophagy and NLRP3 inflammasome.

Myocardial ischemia-reperfusion injury (MIRI) is an injury to cardiomyocytes due to restoration of blood flow after myocardial infarction (MI). It has recently gained much attention in clinical research with special emphasis on the roles of mitochondrial autophagy and inflammation. A mild inflammatory response promotes recovery of post-ischemic cardiomyocyte function and vascular regeneration, but a severe inflammatory response can cause irreversible and substantial cellular damage. Similarly, moderate mitochondrial autophagy can help inhibit excessive inflammation and protect cardiomyocytes. However, MIRI is aggravated when mitochondrial function is disrupted, such as inadequate clearance of damaged mitochondria or excessive activation of mitophagy. How to moderately control mitochondrial autophagy while promoting its balance with nucleotide-binding oligomerization structural domain receptor protein 3 (NLRP3) inflammasome activation is critical. In this paper, we reviewed the molecular mechanisms of mitochondrial autophagy and NLRP3 inflammasome, described the interaction between NLRP3 inflammasome and mitochondrial autophagy, and the effects of different signaling pathways and molecular proteins on MIRI, to provide a reference for future research.

Integration of Self-Passivated Topological Electrodes for Advanced 2D Optoelectronic Devices.

With the rapid development of two-dimensional semiconductor technology, the inevitable chemical disorder at a typical metal-semiconductor interface has become an increasingly serious problem that degrades the performance of 2D semiconductor optoelectronic devices. Herein, defect-free van der Waals contacts have been achieved by utilizing topological Bi2 Se3 as the electrodes. Such clean and atomically sharp contacts avoid the consumption of photogenerated carriers at the interface, enabling a markedly boosted sensitivity as compared to counterpart devices with directly deposited metal electrodes. Typically, the device with 2D WSe2 channel realizes a high responsivity of 20.5 A W-1 , an excellent detectivity of 2.18 × 1012  Jones, and a fast rise/decay time of 41.66/38.81 ms. Furthermore, high-resolution visible-light imaging capability of the WSe2 device is demonstrated, indicating its promising application prospect in future optoelectronic systems. More inspiringly, the topological electrodes are universally applicable to other 2D semiconductor channels, including WS2 and InSe, suggesting its broad applicability. These results open fascinating opportunities for the development of high-performance electronics and optoelectronics.

Magnetic Molecularly Imprinted Polymers for the Rapid and Selective Extraction and Detection of Methotrexatein Serum by HPLC-UV Analysis.

In this work, novel selective recognition materials, namely magnetic molecularly imprinted polymers (MMIPs), were prepared. The recognition materials were used as pretreatment materials for magnetic molecularly imprinted solid-phase extraction (MSPE) to achieve the efficient adsorption, selective recognition, and rapid magnetic separation of methotrexate (MTX) in the patients' plasma. This method was combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) to achieve accurate and rapid detection of the plasma MTX concentration, providing a new method for the clinical detection and monitoring of the MTX concentration. The MMIPs for the selective adsorption of MTX were prepared by the sol-gel method. The materials were characterized by transmission electron microscopy, Fourier transform-infrared spectrometry, X-ray diffractometry, and X-ray photoelectron spectrometry. The MTX adsorption properties of the MMIPs were evaluated using static, dynamic, and selective adsorption experiments. On this basis, the extraction conditions were optimized systematically. The adsorption capacity of MMIPs for MTX was 39.56 mgg-1, the imprinting factor was 9.40, and the adsorption equilibrium time was 60 min. The optimal extraction conditions were as follows: the amount of MMIP was 100 mg, the loading time was 120 min, the leachate was 8:2 (v/v) water-methanol, the eluent was 4:1 (v/v) methanol-acetic acid, and the elution time was 60 min. MTX was linear in the range of 0.00005-0.25 mg mL-1, and the detection limit was 12.51 ng mL-1. The accuracy of the MSPE-HPLC-UV method for MTX detection was excellent, and the result was consistent with that of a drug concentration analyzer.

A review of key cytokines based on gene polymorphism in the pathogenesis of pre-eclampsia.

Although a number of theories have been suggested, including roles for oxidative stress, an abnormal maternal-fetal interface, and genetic and environmental factors, the etiopathology of pre-eclampsia (PE) remains unclear. Maternal immune tolerance is important for maintaining pregnancy, and researchers have increasingly focused on the critical roles of cytokines in the pathogenesis of PE in recent years. The assessment of candidate genetic polymorphisms in PE could partially elucidate the mechanisms of susceptibility to disease, and contribute to seeking for new diagnosis and treatment methods of PE. PE can lead to severe complications, and even the death of both mother and fetus. Although the complex pathology is not yet clear, some evidence suggested that the occurrence of PE is related to inflammatory factors. We reviewed the current understandings of roles of cytokines in PE, and provided an extensive overview of the role of single nucleotide chain polymorphisms (SNPs) in the genes potentially underlying the pathophysiology of PE.

Channel-multiplexing for quasi-distributed acoustic sensing with orthogonal codes.

With the increasing demands for large-scale acoustic sensing in many important fields such as hydrophone, vehicle tracking and pipeline monitoring, optical fiber-based distributed acoustic sensing (DAS) has experienced a rapid development. In recent years, quasi-distributed acoustic sensing (QDAS) based on single mode fiber with enhanced point array has emerged, which is a good approach to improve signal-to-noise ratio and deal with the interference-fading problem in DAS. However, similar to DAS, the performance of QDAS is also limited by the finite frequency domain resources. To break the trade-off between sensing bandwidth and distance, additional frequency domain resources are always needed to multiplex the sensing channel. Multiple-input multiple-output coding technology is an approach to realize QDAS channel-multiplexing with the orthogonal probe waves in the same frequency band. In this paper, the iteration constrain condition of the orthogonal codes is modified, and the generation method of more orthogonal codes with high and consistent suppression ratio for QDAS is provided. In the demonstration experiment, the QDAS has successfully achieved 5 times the sensing bandwidth expansion on a 5.19 km fiber based on 5 new orthogonal codes on the same frequency, with 5 m spatial resolution and 10 p ε/H z strain noise level.

Efficacy and safety of bempedoic acid alone or combining with other lipid-lowering therapies in hypercholesterolemic patients: a meta-analysis of randomized controlled trials.

BACKGROUND: Bempedoic acid is a new drug that reduces cholesterol synthesis via inhibiting ATP citrate lyase. It remains unclear whether the combination of bempedoic acid and other lipid-lowering drugs is better than these drugs alone. This study systematically reviewed the efficacy and safety of bempedoic acid monotherapy or combination togethers in hypercholesterolemic patients. METHODS: Randomized controlled trials were searched across Medline, Embase, Cochrane library, web of science, etc. The net change scores [least squares mean (LSM) percentage change] in LDL-C level were meta-analyzed using weighted mean difference. The reductions in other lipids including total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein (ApoB) and high sensitivity C reactive protein (hsCRP) were also assessed. Odds ratio (OR) of the incidence of adverse events (AEs) were calculated to evaluate the safety of bempedoic acid. RESULTS: A total of 13 trials (4858 participates) were included. Pooled data showed that the combination togethers resulted in greater reductions in LDL-C level than monotherapies (bempedoic acid + statin vs. statin: LSM difference (%), - 18.37, 95% CI, - 20.16 to - 16.57, I2 = 0; bempedoic acid + ezetimibe vs. ezetimibe: LSM difference (%), - 18.89, 95% CI, - 29.66 to - 8.13, I2 = 87%). But the difference in efficacy between bempedoic acid and ezetimibe was not obvious. Meta-regression analysis showed the treatment duration was a source of heterogeneity (adj R2 = 16.92, 95% CI, 0.04 to 0.72). Furthermore, the background therapy of statin before screening decreased the efficacy of bempedoic acid. In addition, bempedoic acid also resulted in a significant reduction in TC, non-HDL-C, ApoB and hsCRP level. The OR of muscle-related AEs by the combination of bempedoic acid and statin was 1.29 (95% CI, 1.00 to 1.67, I2 = 0) when compared with statin alone. CONCLUSION: This study showed the efficacy of combination togethers were similar but stronger than these drugs alone. Of note, a trend of high risk of muscle-related AEs by the combination of bempedoic acid and statin was observed, though it is not statistically significant, such risk is needed to be confirmed by more trials, because it is important for us to determine which is the better combinative administration for statin-intolerant patients.

Exploration of CYP21A2 and CYP17A1 polymorphisms and preeclampsia risk among Chinese Han population: a large-scale case-control study based on 5021 subjects.

BACKGROUND: Several genome-wide association studies have identified single-nucleotide polymorphisms (SNPs), such as rs4409766, rs1004467, and rs3824755 in CYP17A1 and rs2021783 in CYP21A2, as new hypertension susceptibility genetic variants in the Chinese population. This study aimed to look into the relationship between preeclampsia (PE) and these SNPs in Chinese Han women. METHODS: Overall, 5021 unrelated pregnant women were recruited, including 2002 patients with PE and 3019 normal healthy controls. The real-time PCR (TaqMan) method was applied to genotype these four polymorphisms. RESULTS: A statistically obvious difference in the allelic frequencies was observed in CYP21A2 rs2021783 between cases and controls (χ2 = 7.201, Pc = 0.028 by allele), and the T allele was associated with the occurrence and development of PE (OR = 1.151, 95% CI 1.039-1.275). We also found a significant association between rs2021783 and the development of early-onset PE (Pc = 0.008 by genotype, Pc = 0.004 by allele). For rs1004467 and rs3824755, the distribution of allelic frequencies differed markedly between mild PE and control groups (χ2 = 6.843, Pc = 0.036; χ2 = 6.869, Pc = 0.036), and patients with the TT genotype of rs1004467 were less easy to develop mild PE than were those carrying the CT or CC genotype (χ2 = 7.002, Pc = 0.032, OR = 1.306, 95% CI 1.071-1.593). The GG genotype of rs3824755 appeared to a protective effect on the occurrence of mild PE (OR = 0.766, 95% CI 0.629-0.934). CONCLUSIONS: CYP21A2 rs2021783 appears to be closely related to PE susceptibility, and CYP17A1 rs1004467 and rs3824755 seem to be closely associated with mild PE in Han women.

Circulating levels of IFN-γ, IL-1, IL-17 and IL-22 in pre-eclampsia: A systematic review and meta-analysis.

OBJECTIVE: Pre-eclampsia (PE) is a common multi-systemic disease, and the effect of cytokines on PE is not clear. The purpose of this meta-analysis was to evaluate the circulating levels of interferon gamma (IFN-γ), interleukin (IL)-1, IL-17 and IL-22 in patients with PE. STUDY DESIGN: Relevant studies were identified after a preliminary investigation of studies published up to May 2019 using PubMed and Embase. In this study, all 27 included articles underwent quality rating, with a total of 495 patients with PE and 557 controls. Among them, eight papers and 932 subjects contributed to the meta-analysis of IFN-γ, and six papers and 343 subjects contributed to the meta-analysis of IL-17. Based on the inclusion and exclusion criteria, the retrieved papers were screened and evaluated independently. Relevant data for IFN-γ and IL-17 were extracted for meta-analysis and subgroup analysis, and the stability of the results was evaluated by sensitivity analysis. At the same time, a systematic evaluation was carried out for IL-1 and IL-22 with a small number of included papers. RESULTS: Several papers included in the systematic review showed that the circulating levels of IL-22 were higher in patients with severe PE than in controls, while IL-1 levels did not differ significantly between the two groups. The meta-analysis showed that patients with PE had higher circulating levels of IFN-γ than controls [standardized mean difference (SMD) 1.45, 95 % confidence interval (CI) 0.56-2.34]. There was no evidence of a difference in the circulating levels of IL-17 between patients with PE and controls (SMD 0.53, 95 %CI -0.43 to 1.48). CONCLUSION: This meta-analysis suggested that changes in circulating levels of IFN-γ might be associated with PE.

The role of SLITRK6 in the pathogenesis of Tourette syndrome: From the conclusion of a family-based study in the Chinese Han population.

BACKGROUND: Tourette syndrome (TS) is a complex neuropsychiatric disorder coupled with obvious genetic heterogeneity. Studies in recent years have confirmed the association of SLITRK genes with sensory and neuropsychiatric diseases. To detect whether SLITRK6 is involved in the progress of TS, a family-based association study was performed to explore the possible genetic association between SLITRK6 and TS in the Chinese Han population. METHODS: We genotyped 399 TS nuclear families trios, and then analyzed three tag SLITRK6 single nucleotide polymorphisms using the transmission disequilibrium test (TDT) haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods. RESULTS: The TDT showed no statistically significant allele transfer for the three polymorphisms. The HRR and HHRR also showed a negative association. CONCLUSIONS: Despite the results suggesting that these polymorphisms may not be associated with susceptibility to TS in the Chinese Han population, we are still unable to determine the potential role of SLITRK6 in the pathogenesis of TS. Furthermore, the results still need to be confirmed in a larger sample size and in different populations.

Changes in the levels of l-carnitine, acetyl-l-carnitine and propionyl-l-carnitine are involved in perfluorooctanoic acid induced developmental cardiotoxicity in chicken embryo.

Perfluorooctanoic acid (PFOA), a persistent organic pollutant, is associated with developmental toxicity. This study investigated the mechanism of PFOA-induced developmental cardiotoxicity in chicken embryo, focusing on the interactions between developmental exposure to PFOA and the levels of l-carnitine (LC), acetyl-l-carnitine (ALC) and propionyl-l-carnitine (PLC) in the heart. To evaluate the developmental cardiotoxicity, fertile chicken eggs were exposed to 0.1, 0.5, 1, 2 or 5mg/kg PFOA via air cell injection. Furthermore, exposure to 2mg/kg PFOA, with or without 100mg/kg LC were applied to investigate the effects of LC supplement. The results of functional and morphological assessments confirmed PFOA induced developmental cardiotoxicity in chicken embryo, which could be alleviated by co-exposure to LC. LC-MS/MS results also revealed remarkable decrease in LC, ALC and PLC levels in embryonic day six (ED6) chicken embryo hearts as well as LC level in embryonic day fifteen (ED15) chicken embryo hearts following developmental exposure to 2mg/kg PFOA. Meanwhile, co-exposure to 100mg/kg LC significantly elevated the levels of LC, ALC and PLC in chicken embryo hearts. Significantly elevated expression level of carnitine acetyltransferase (CRAT) in PFOA-exposed ED6 chicken embryo hearts was observed via western blotting, while LC co-exposure counteracted such changes. In conclusion, changes in the levels of LC, ALC and PLC in early embryonic stages are associated with PFOA induced developmental cardiotoxicity in chicken embryos.