RhoA as a target to promote neuronal survival and axon regeneration

Paralysis following spinal cord injury （SCI） is due to failure of axonal regeneration. It is believed that the capacities of neurons to regrow their axons are due partly to their intrinsic characteristics, which in turn are greatly influenced by several types of inhibitory molecules that are present, or even increased in the extracellular environment of the injured spinal cord. Many of these inhibitory molecules have been studied extensively in recent years. It has been suggested that the small GTPase RhoA is an intracellular convergence point for signaling by these extracellular inhibitory molecules, but due to the complexity of the central nervous system （CNS） in mammals, and the limitation of pharmacological tools, the specific roles of RhoA are unclear. By exploiting the anatomical and technical advantages of the lamprey CNS, we recently demonstrated that RhoA knockdown promotes true axon regeneration through the lesion site after SCI. In addition, we found that RhoA knockdown protects the large, identified reticulospinal neurons from apoptosis after their axons were axotomized in spinal cord. Therefore, manipulation of the RhoA signaling pathway may be an important approach in the development of treatments that are both neuroprotective and axon regeneration-promoting, to enhance functional recovery after SCI.

Carbon dioxide conversion to valuable chemical products over composite catalytic systems

This paper reports an experimental study on catalytic conversion of carbon dioxide to methanol, ethanol and acetic acid. Satalysts having different catalytic functions were synthesized and combined in different ways to enhance the selectivity to desired products. The combined catalyst system possessed the following functions： methanol synthesis, Fischer-Tropsch synthesis, water-gas-shift and hydrogenation. Results showed that the methods of integrating these catalytic functions played an important role in achieving the desired product selectivity. We speculate that if methanol synthesis sites were located adjacent to the C--C chain growth sites, the formation rate of C2 oxygenates would be enhanced. The advantage of using a high temperature methanol catalyst PdZnA1 in the combined catalyst system was demonstrated. In the presence of PdZnA1 catalyst, the combined catalyst system was stable at 380 ~C. It was observed that, at high temperature, kinetics favored oxygenate formation. The results implied that the process can be intensified by operating at high temperature using Pd-based methanol synthesis catalyst. Steam reforming of the byproduct organics was demonstrated as a means to provide supplemental hydrogen. Preliminary process design, simulation, and economic analysis of the proposed CO2 conversion process were carded out. Economic analysis indicates how ethanol production cost was affected by the price of CO2 and hydrogen.

Heterogeneity in the regenerative abilities of central nervous system axons within species: why do some neurons regenerate better than others?

Some neurons,especially in mammalian peripheral nervous system or in lower vertebrate or in vertebrate central nervous system(CNS)regenerate after axotomy,while most mammalian CNS neurons fail to regenerate.There is an emerging consensus that neurons have different intrinsic regenerative capabilities,which theoretically could be manipulated therapeutically to improve regeneration.Population-based comparisons between"good regenerating"and"bad regenerating"neurons in the CNS and peripheral nervous system of most vertebrates yield results that are inconclusive or difficult to interpret.At least in part,this reflects the great diversity of cells in the mammalian CNS.Using mammalian nervous system imposes several methodical limitations.First,the small sizes and large numbers of neurons in the CNS make it very difficult to distinguish regenerating neurons from non-regenerating ones.Second,the lack of identifiable neurons makes it impossible to correlate biochemical changes in a neuron with axonal damage of the same neuron,and therefore,to dissect the molecular mechanisms of regeneration on the level of single neurons.This review will survey the reported responses to axon injury and the determinants of axon regeneration,emphasizing non-mammalian model organisms,which are often under-utilized,but in which the data are especially easy to interpret.

Inhibition of central axon regeneration: perspective from chondroitin sulfate proteoglycans in lamprey spinal cord injury

Background:Failure of axon regeneration after spinal cord injury(SCI)underlies the paralysis that so profoundly affects patients’quality of life.Many factors are involved in the regeneration failure.Chondroitin sulfate proteoglycans(CSPGs),normal constituents of the perineuronal nets in central nervous system(CNS),are secreted at the injury site and initially were thought to act as a purely physical barrier.In the past decade,the receptor-like protein tyrosine phosphatases,protein tyrosine phosphatase sigma(PTPσ),and leukocyte common antigen-related phosphatase(LAR),have been identified as transmembrane receptors for CSPGs.The two receptors for myelin-associated growth inhibitors,Nogo receptors 1 and 3(NgR1 and NgR3)also have been found to bind with CSPGs(Sharma et al.,2012).These findings suggest that CSPGs inhibit regeneration by interacting with these receptors,initiating downstream inhibitory signaling(Figure 1).

Glypican-3 versus alpha-fetoprotein as a biomarker for hepatocellular carcinoma: a diagnostic meta-analysis

Objective:To assess the diagnostic accuracy of serum GPC3 versus alpha-fetoprotein(AFP)for HCC by using the method of system review.Methods:PubMed and EMBASE were searched from its inception to 20,April 2014 for studies that compared diagnostic accuracy of serum GPC3 with AFP for HCC.Sensitivity,specificity and other measures were pooled using random-effects models.Summary receiver operating characteristic curve analysis was used to summarize the overall test performance.Results:Fourteen studies were included in this meta-analysis.Summary estimates for serum GPC3 and AFP in diagnosing HCC were as follows:sensitivity,69%(95%confidence interval(CI),56-80%)vs.60%(95%CI,50-69%);specificity,91%(95%CI,76-97%)vs.92%(95%CI,84-98%);diagnostic odds ratio(DOR),22(95%CI,6-83)vs.18(95%CI,8-41);and area under sROC,0.85(95%CI,0.81-0.88)vs.0.80(95%CI,0.76-0.83).The pooled sensitivity and specificity for(GPC3+AFP)and AFP were:sensitivity 80%(95%CI,75-85%)vs.64%(95%CI,53-73%)and specificity 86%(95%CI,74-93%)vs.96%(95%CI,86-99%).A significant heterogeneity was found among the ten studies,and meta-regression and subgroup meta-analysis suggested that race and assay type were probably responsible for the heterogeneity.Conclusions:Serum GPC3 may be a promising diagnostic marker of HCC and it was helpful for early detection of primary hepatocellular carcinoma when combined with AFP.More studies for specific race of patients,and using certain methods for detecting GPC3 are required to further confirm the diagnostic value of GPC3 for HCC.

Large-scale chemical screen identifies Gallic acid as a geroprotector for human stem cells

Dear Editor,The interventions that slow aging or promote healthy aging may provide preventative measures for age-related diseases(Zhang et al.,2015).Therefore,it is crucial to identify drugs that target aging-related pathologies and improve health-span in geroscience research.Using model organisms such as C.elegans and rodents,several small molecules capable of alleviating the onset or progression of aging,including rapamycin,nicotinamide mononucleotide,and metformin,have been discovered(Partridge et al.,2020).However,the safety and efficacy of these chemicals still need in-depth evaluation before clinical applications(Partridge et al.,2020).As a result,it is necessary to identify additional compounds with geroprotective effects for human cells to counteract the general trend of populational aging.However,transforming a promising compound into an approved drug requires enormous resources.Alternatively,repurposing previously approved drugs for new clinical applications offers a more efficient and less costly path toward drug develop-ment.Therefore,testing U.S.Food and Drug Administration(FDA)-approved drugs for geroprotective effects may dis-covernew therapeutics that have already been stringently tested in humans for safety.

Impact of COVID-19 Interventions on Respiratory and Intestinal Infectious Disease Notifications-Jiangsu Province,China,2020–2023

Introduction:Many measures implemented to control the coronavirus disease 2019(COVID-19)pandemic have reshaped the epidemic patterns of other infectious diseases.This study estimated the impact of the COVID-19 pandemic on respiratory and intestinal infectious diseases and potential changes following reopening.Methods:The optimal intervention and counterfactual models were selected from the seasonal autoregressive integrated moving average(SARIMA),neural network autoregression(NNAR),and hybrid models based on the minimum mean absolute percentage error(MAPE)in the test set.The relative change rate between the actual notification rate and that predicted by the optimal model was calculated for the entire COVID-19 epidemic prevention period and the“reopening”period.Results:Compared with the predicted notification rate based on the counterfactual model,the total relative change rates for the 9 infectious diseases were−44.24%,respiratory infections(−55.41%),and intestinal infections(−26.59%)during 2020–2022.Compared with the predicted notification rate based on the intervention model,the total relative change rates were+247.98%,respiratory infections(+389.59%),and intestinal infections(+50.46%)in 2023.Among them,the relative increases in influenza(+499.98%)and hand-foot-mouth disease(HFMD)(+70.97%)were significant.Conclusions:Measures taken in Jiangsu Province in response to COVID-19 effectively constrained the spread of respiratory and intestinal infectious diseases.Influenza and HFMD rebounded significantly after the lifting of COVID-19 intervention restrictions.

Trends in disease burden of hepatitis B infection in Jiangsu Province,China,1990-2021

Background:The incidence of hepatitis B virus(HBV)has decreased year by year in China after the expansion of vaccination,but there is still a high disease burden in Jiangsu Province of China.Methods:The year-by-year incidence data of HBV in Jiangsu Province from 1990 to 2021 were collected.The incidence rates of males and females age groups were clustered by systematic clustering,and the incidence rates of each age group were analyzed and studied by using Joinpoint regression model and age-period-cohort effect model(APC).Results:Joinpoint regression model and APC model showed a general decrease in HBV prevalence in both males and females.In addition,the results of the APC model showed that the age,period,and cohort effects of patients all affected the incidence of HBV,and the incidence was higher in males than in females.The incidence is highest in the population between the ages of 15 and 30 years(mean:21.76/100,000),especially in males(mean:31.53/100,000)than in females(mean:11.67/100,000).Another high-risk group is those over 60 years of age(mean:21.40/100,000),especially males(mean:31.17/100,000)than females(mean:11.63/100,000).The period effect of the APC model suggests that HBV vaccination is effective in reducing the incidence of HBV in the population.Conclusions:The incidence of HBV in Jiangsu Province showed a gradual downward trend,but the disease burden in males was higher than that in females.The incidence is higher and increasing rapidly in the population between the ages of 15 and 30 years and people over 60 years of age.More targeted prevention and control measures should be imple-mented for males and the elderly.

Estimating the time interval between transmission generations and the presymptomatic period by contact tracing surveillance data from 31 provinces in the mainland of China

The global pandemic of 2019 coronavirus disease(COVID-19)is a great assault to public health.Presymptomatic transmission cannot be controlled with measures designed for symptomatic persons,such as isolation.This study aimed to estimate the interval of the transmission generation(TG)and the presymptomatic period of COVID-19,and compare the ftting effects of TG and serial interval(S)based on the SEIHR model incorporating the surveillance data of 3453 cases in 31 provinces.These data were allocated into three distributions and the value of AIC presented that the Weibull distribution fitted well.The mean of TG was 5.2 days(95%C:4.6-5.8).The mean of the presymptomatic period was 2.4 days(95%CI:1.5-3.2).The dynamic model using TG as the generation time performed well.Eight provinces exhibited a basic reproduction number from 2.16 to 3.14.Measures should be taken to control presymptomatic transmission in the COVID-19 pandemic.