Deletion of Krüppel-like factor-4 promotes axonal regeneration in mammals

Axonal regeneration plays an important role in functional recovery after nervous system damage. However, after axonal injury in mammals, regeneration is often poor. The deletion of Krüppel-like factor-4 (Klf4) has been shown to promote axonal regeneration in retinal ganglion cells. However, the effects of Klf4 deletion on the corticospinal tract and peripheral nervous system are unknown. In this study, using a mouse model of sciatic nerve injury, we show that the expression of Klf4 in dorsal root ganglion sensory neurons was significantly reduced after peripheral axotomy, suggesting that the regeneration of the sciatic nerve is associated with Klf4. In vitro, dorsal root ganglion sensory neurons with Klf4 knockout exhibited significantly enhanced axonal regeneration. Furthermore, the regeneration of the sciatic nerve was enhanced in vivo following Klf4 knockout. Finally, AAV-Cre virus was used to knockout the Klf4 gene in the cortex. The deletion of Klf4 enhanced regeneration of the corticospinal tract in mice with spinal cord injury. Together, our findings suggest that regulating KLF4 activity in neurons is a potential strategy for promoting axonal regeneration and functional recovery after nervous system injury. This study was approved by the Animal Ethics Committee at Soochow University, China (approval No. SUDA20200316A01).

Chinese Library Classification No.R456; R741; Q344+.14     

Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

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路志正调理脾胃治疗胸痹的学术思想浅析

全国著名中医学家路志正教授精通中医典籍,对脾胃学说的研究造诣尤深,行医60余年,形成一套独特的临床经验.路老师善用调理脾胃治疗多种疑难杂症,其中运用调理脾胃法辨治胸痹是其学术思想和临床经验的组成部分.现就笔者学习心得简介如下.     

A Mathematical Model and Experimental Verification of Optimal Nozzle Diameter in Needle-Free Injection

Needle-free injection (NFI), as an alternative drug delivery strategy, owns great potential. It is able to reduce complaints about needle phobia and avoid the occurring of accidental needle stick injuries. The nozzle diameter is inherently important in determining the injection dose, injection depth, and pain associated with NFIs. In this work, needle-free injectors with nozzle diameters of 0.17, 0.20, 0.30, 0.40, and 0.50 mm were studied in the simulation and experiment. This article optimizes the mathematical model for spring-powered NFI by considering the hydraulic loss due to the abrupt change in the nozzle exit area and the friction force between the piston and ampoule. We explore the dispersion pattern in gels with different nozzle diameters. Mice insulin injection was conducted to investigate the pharmacological effect of different injection methods. The experimental results show that there is the best dispersion effect and available injection depth while the nozzle diameter is 0.30 mm, which is in agreement with the result predicted by the mathematical model. Also, there is a satisfactory pharmacological effect on the mice insulin injection under the same injection condition. Undoubtedly, the mathematical model is capable of predicting the suitable nozzle diameter under the given conditions.     

Enzymatic synthesis of glucuronidated metabolites of two neurological active agents using plant glucuronosyltransferases

Abstract

Glucuronidation is an important and popular metabolic reaction in vivo of drugs. The further evaluation of biological activity and toxicity of glucuronides is necessary in the course of the drug research and development. However, the synthesis of glucuronides is limited by the lack of efficient approach. Herein, we have developed a new glucuronide synthesis method using plant uridine diphosphate-dependent glucuronosyltransferases (UGTs), UGT88D4, UGT88D7, and EpGT8, enabling the convenient preparation for corresponding O-glucuronide metabolites (1a, 2a, 3a, and 3b) in milligram scale of two neurological active agents, IMM-H004 (1) and FLZ (2). Their structures were characterized by spectroscopic data analyses.     

Comparative Study of Metal Accumulation in Three Fish Species (<Emphasis Type="Italic">Silurus asotus,Cyprinus carpio</Emphasis>, and <Emphasis Type="Italic">Carassius auratus auratus</Emphasis>) from the Jinsha and Tuo Rivers Located Upstream of the Yangtze River,China

Poland is one of the countries distinguished by a long and colorful past. Undergoing numerous turbulent socio-economic changes forced by the course of history, Poland is now one of the member states of the European Union. Experiencing low water quantity and high contamination levels in surface waters, Poland is following other EU countries in the effort to reach a “good” water status. Herein are presented impacts of changes in Polish history on water legislation, management, and research, as well as explanations for the perceptible split between engineering and scientific approaches to the aquatic issues. Drawbacks caused by unsatisfactory state research funding for the sciences and division of the water related contemporary scientific interests are also discussed.     

The clinical significance of plasma CFHR 1–5 in lupus nephropathy

A deficiency of complement factor H may lead to excessive consumption of C3 and an increase in C3b deposition, which are important pathological characteristics of lupus nephritis. Complement factor H-related proteins (CFHRs), comprising CFHR1 to CFHR5 (CFHR1–5), are members of the wider factor H/CFHR family. Their role in lupus nephritis remains unclear. In this study, we compared circulating levels of CFHR1–5 in 152 patients diagnosed with lupus nephritis and 20 unrelated healthy individuals to explore the relationship between the expression of CFHR1–5 and development of the disease. We found that plasma levels of CFHR3 and CFHR5 were higher in patients with lupus nephritis than in healthy individuals; also, CFHR3 and CFHR5 concentrations increased with increasing systemic lupus erythematosus disease activity index (SLEDAI) values (P < 0.05). Pearson's and Spearman's correlation test results confirmed that plasma CFHR3 and CFHR5 levels in lupus nephritis patients were positively correlated with proteinuria and levels of creatinine (Cr) and anti-dsDNA (correlation coefficients = 0.491–0.717, P < 0.05), while they were negatively correlated with plasma C3 levels and eGFR [correlation coefficients = –(0.706–0.788), P < 0.05]. Receiver operating characteristic (ROC) curve analysis results confirmed that plasma CFHR3 and CFHR5 levels were predictive of SLEDAI values and disease end points (area under the curve = 0.664–0.884, P < 0.05), with patients with both high CFHR3 and high CFHR5 exhibiting the shortest progression-free survival. Thus, both CFHR3 and CFHR5 are of prognostic value in lupus nephritis status.     

Childhood polybrominated diphenyl ether (PBDE) exposure and executive function in children in the HOME Study

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (β = 4.6, 95% CI 0.5, 8.7) and BDE-153 (β = 4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function.