Bexarotene improves motor function after spinal cord injury in mice

Spinal cord injury is a challenge in orthopedics because it causes irreversible damage to the central nervous system.Therefore,early treatment to prevent lesion expansion is crucial for the management of patients with spinal cord injury.Bexarotene,a type of retinoid,exerts therapeutic effects on patients with cutaneous T-cell lymphoma and Parkinson's disease.Bexarotene has been proven to promote autophagy,but it has not been used in the treatment of spinal cord injury.To investigate the effects of bexarotene on spinal cord injury,we established a mouse model of T11–T12 spinal cord contusion and performed daily intraperitoneal injection of bexarotene for 5 consecutive days.We found that bexarotene effectively reduced the deposition of collagen and the number of pathological neurons in the injured spinal cord,increased the number of synapses of nerve cells,reduced oxidative stress,inhibited pyroptosis,promoted the recovery of motor function,and reduced death.Inhibition of autophagy with 3-methyladenine reversed the effects of bexarotene on spinal cord injury.Bexarotene enhanced the nuclear translocation of transcription factor E3,which further activated AMP-activated protein kinase-S-phase kinase-associated protein 2-coactivator-associated arginine methyltransferase 1 and AMP-activated protein kinase-mammalian target of rapamycin signaling pathways.Intravenous injection of transcription factor E3 sh RNA or intraperitoneal injection of compound C,an AMP-activated protein kinase blocker,inhibited the effects of bexarotene.These findings suggest that bexarotene regulates nuclear translocation of transcription factor E3 through the AMP-activated protein kinase-Sphase kinase-associated protein 2-coactivator-associated arginine methyltransferase 1 and AMP-activated protein kinase-mammalian target of rapamycin signal pathways,promotes autophagy,decreases reactive oxygen species level,inhibits pyroptosis,and improves motor function after spinal cord injury.

Functions and mechanisms of cytosolic phospholipase A_(2)in central nervous system trauma

Central nervous system(CNS)trauma,including traumatic brain injury and spinal cord injury,has a high rate of disability and mortality,and effective treatment is currently lacking.Previous studies have revealed that neural inflammation plays a vital role in CNS trauma.As the initial enzyme in neuroinflammation,cytosolic phospholipase A_(2)(cPLA2)can hydrolyze membranous phosphatides at the sn-2 position in a preferential way to release lysophospholipids andω3-polyunsaturated fatty acid dominated by arachidonic acid,thereby inducing secondary injuries.Although there is substantial fresh knowledge pertaining to cPLA2,in-depth comprehension of how cPLA2 participates in CNS trauma and the potential methods to amelio rate the clinical res ults after CNS trauma are still insufficient.The present review summarizes the latest understanding of how cPLA2 participates in CNS trauma,highlighting novel findings pertaining to how cPLA2 activation initiates the potential mechanisms specifically,neuroinflammation,lysosome membrane functions,and autophagy activity,that damage the CNS after trauma.Moreover,we focused on testing a variety of drugs capable of inhibiting cPLA2 or the upstream pathway,and we explored how those agents might be utilized as treatments to improve the results following CNS trauma.This review aimed to effectively understand the mechanism of cPLA2 activation and its role in the pathophysiological processes of CNS trauma and provide clarification and a new referential framework for future research.

A bioartificial transgenic porcine whole liver expressing human proteins alleviates acute liver failure in pigs

Background:Preventing heterologous protein influx in patients is important when using xenogeneic bioartificial livers(BALs)to treat liver failure.The development of transgenic porcine livers synthesizing human proteins is a promising approach in this regard.Here,we evaluated the safety and efficacy of a transgenic porcine liver synthesizing human albumin(h ALB)and coagulation factor VII(h FVII)within a bioartificial system.Methods:Tibetan miniature pigs were randomly subjected to different interventions after surgeryinduced partially ischemic liver failure.Group A(n=4)was subjected to basic treatment;group B(n=4)was to standard medical treatment and wild-type porcine BAL perfusion,and group C(n=2)was to standard medical treatment and transgenic BAL perfusion.Biochemical parameters,coagulation status,survival time,and pathological changes were determined.Expressions of h ALB and h FVII were detected using immunohistochemistry and enzyme-linked immunosorbent assays.Results:The survival time in group A was 9.75±1.26 days;this was shorter than that in both perfused groups,in which all animals reached an endpoint of 12 days(P=0.006).Ammonia,bilirubin,and lactate levels were significantly decreased,whereas albumin and fibrinogen levels were increased after perfusion(all P<0.05).h ALB and h FVII were detected in transgenic BAL-perfused pig serum and ex vivo in the liver tissues.Conclusions:The humanized transgenic pig livers could synthesize and secrete h ALB and h FVII ex vivo in a whole organ-based bioartificial system,while maintaining their metabolism,detoxification,transformation,and excretion functions,which were comparable to those observed in wild-type porcine livers.Therefore,the use of transgenic bioartificial whole livers is expected to become a new approach in treating acute liver failure.

Self-assembly of a quadrangular prismatic covalent cage templated by zinc ions:A selective fluorescent sensor for palladium ions

Herein we report a covalent cage TPE-Zn_(4)based on a tetraphenylethylene molecule via subcomponent self-assembly,which is templated by zinc ions.TPE-Zn_(4)features a quadrangular prismatic cage structure,which is characterized by NMR,mass spectrum,and single-crystal X-ray diffractions.TPE-Zn_(4)emitted orange fluorescence(λ_(em)=620 nm)in DMSO solution under the irradiation of UV light(λ_(ex)=395 nm)and can be applied as a fluorescence sensor for selectively detecting Pd^(2+).The fluorescence of TPE-Zn_(4)was quenched by Pd^(2+)in DMSO solution,and a very low detection limit of 62.3 n M was achieved.Mechanism studies reveal that the Pd^(2+)can replace the Zn^(2+),and the heavy atom effect and chelation-enhanced quenching effect between the Pd^(2+)and the cage probably cause the fluorescence quenching.

Cardiovascular and renal burdens of metabolic associated fatty liver disease from serial US national surveys, 1999–2016

Background:Non-communicable chronic diseases have become the leading causes of disease burden worldwide.The trends and burden of“metabolic associated fatty liver disease”(MAFLD)are unknown.We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease(NAFLD).Methods:Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged≥20years from the cross-sectional US National Health and Nutrition Examination Survey periods,1999 to 2002,2003 to 2006,2007 to 2010,and 2011 to 2016.MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity,type 2 diabetes mellitus,or evidence of metabolic dysregulation.Results:The prevalence of MAFLD increased from 28.4%(95% confidence interval 26.3–30.6)in 1999 to 2002 to 35.8%(33.8–37.9)in 2011 to 2016.In 2011 to 2016,among adults with MAFLD,49.0%(45.8–52.2)had hypertension,57.8%(55.2–60.4)had dyslipidemia,26.4%(23.9–28.9)had diabetes mellitus,88.7%(87.0–80.1)had central obesity,and 18.5%(16.3–20.8)were current smokers.The 10-year cardiovascular risk ranged from 10.5%to 13.1%;19.7%(17.6–21.9)had chronic kidney diseases(CKDs).Throughthe fourperiods,adults withMAFLD showedanincrease in obesity;increase intreatment to lower bloodpressure(BP),lipids,and hemoglobin A1c;and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus.Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs,myocardial infarction,or stroke.Generally,although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD,the prevalence of MAFLD was significantly higher than that of NAFLD.Conclusions:From 1999 to 2016,cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD.The absolute cardiorenal burden may be greater for MAFLD than for NAFLD.These data call for early identification and risk stratification of MAFLD and close collaboration between endocrinologists and hepatologists.

An iterative linear quadratic regulator based trajectory tracking controller for wheeled mobile robot

We present an iterative linear quadratic regulator(ILQR) method for trajectory tracking control of a wheeled mobile robot system.The proposed scheme involves a kinematic model linearization technique,a global trajectory generation algorithm,and trajectory tracking controller design.A lattice planner,which searches over a 3D(x,y,θ) configuration space,is adopted to generate the global trajectory.The ILQR method is used to design a local trajectory tracking controller.The effectiveness of the proposed method is demonstrated in simulation and experiment with a significantly asymmetric differential drive robot.The performance of the local controller is analyzed and compared with that of the existing linear quadratic regulator(LQR) method.According to the experiments,the new controller improves the control sequences(v,ω) iteratively and produces slightly better results.Specifically,two trajectories,'S' and '8' courses,are followed with sufficient accuracy using the proposed controller.

Association between blood cadmium and vitamin D levels in the Yangtze Plain of China in the context of rapid urbanization

Background:China has experienced rapid urbanization in the past 30 years.We aimed to report blood cadmium level(BCL)in the rapidly urbanized Yangtze Plain of China,and explore the association between BCL and 25-hydroxyvitamin D(25(OH)D).Methods:Our data source was the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors(SPECT-China)cross-sectional study(ChiCTR-ECS-14005052,www.chictr.org).We enrolled 3234 subjects from 12 villages in the Yangtze Plain.BCLs were measured by atomic absorption spectrometry.25(OH)D was measured with a chemiluminescence assay.Results:A total of 2560(79.2%)subjects were diagnosed with vitamin D deficiency.The median(interquartile range)BCL was 1.80μg/L(0.60-3.42)for men and 1.40μg/L(0.52-3.10)for women.In women,mean 25(OH)D concentrations were inversely associated with BCL(0.401,95%confidence interval:-0.697 to-0.105 nmol/L lower with each doubling of the BCL)after adjustment for age,educational status,current smoking,body mass index,diabetes,and season.However,there was no significant difference in 25(OH)D across the BCL tertiles for men.Conclusions:BCL in Chinese residents in the Yangtze Plain were much higher than that in developed countries.An inverse association between BCL and 25(OH)D was found in general Chinese women after multivariable adjustment.Future prospective cohort and animal studies are warranted to resolve the direction and temporality of these relationships,and to elucidate the exact mechanisms involved.

National trends in insulin resistance andβ-cell dysfunction among adults with prediabetes:NHANES 2001-2016

Background::Insulin resistance is the central abnormality and mechanism underlying the progression of cardiometabolic-based chronic diseases.This study aimed to evaluate the trends in insulin resistance andβ-cell dysfunction from 2001 to 2016 among US adults with undiagnosed diabetes,prediabetes,and normal glucose regulation and to provide sex-specific information using data from National Health and Nutrition Examination Surveys(NHANES)2001-2016.Methods::Data from 14,481 participants aged over 20 years from 8 consecutive 2-year cross-sectional cycles of the NHANES from 2001 to 2016 were used.Updated homoeostasis model assessment 2(HOMA2:HOMA2%B forβ-cell function and HOMA2IR for insulin resistance)was used as a surrogate measure.We defined the upper sex-specific tertile of HOMA2IR as insulin resistance and the lower corresponding tertile of HOMA2%B as lowβ-cell function.Results::In both sexes with undiagnosed diabetes,HOMA2%B(men,Ptrend=0.118;women,Ptrend=0.184)and HOMA2IR(men,Ptrend=0.710;women,Ptrend=0.855)remained stable over time.In the prediabetes group,both sexes exhibited significant increasing trends in HOMA2%B(men,Ptrend<0.010;women,Ptrend<0.010)and HOMA2IR(men,Ptrend<0.010;women,Ptrend<0.050).Adjusting for waist circumference mildly attenuated the trend in HOMA2IR and insulin resistance in men(Ptrend<0.010),but it resulted in no significance in women(Ptrend=0.196).In regard to normal glucose regulation,both sexes presented significant decreasing trends in lowβ-cell function(men,Ptrend<0.050;women<0.010)and attenuated trends in insulin resistance(men,Ptrend=0.196;women,Ptrend=0.121).Conclusions::Over 16 years,insulin resistance demonstrated an increasing trend in adult US population with prediabetes,whileβ-cell function showed a compensatory increasing trend.Identifying people with prediabetes early and focusing on reducing insulin resistance as the intervention core,especially controlling central obesity,might increase the opportunity for cardiovascular and diabetes risk reduction.