Il34拯救甲硝唑导致的斑马鱼中枢神经系统轴突再生障碍

甲硝唑(metronidazole,MTZ)是临床常用的抗感染药物,同时在科学研究中被用作细胞靶向消融系统的前体药物,具有极高的应用价值。但MTZ会引起一定程度的神经毒性症状,目前临床及科研使用过程中也缺乏规避其毒性的有效手段,这在一定程度上限制了其应用。因此,探究MTZ引起神经症状的具体机制并探讨应对措施将更大程度地发挥MTZ的实用价值。本研究利用斑马鱼(Danio rerio)脊髓损伤再生模型确认了MTZ的神经毒性导致斑马鱼中枢神经系统轴突再生障碍,通过在斑马鱼中枢神经系统中过表达il34消除了MTZ对轴突再生的抑制,并证明了这种抗MTZ神经毒性的促再生作用不是由白细胞介素34(interleukin 34,Il34)趋化的过量巨噬细胞/小胶质细胞所介导。通过转录组测序分析组间差异表达基因的GO富集分析发现,Il34通过促进细胞间的黏附和细胞定位等生物学过程抗MTZ神经毒性从而促进脊髓损伤修复。综上所述,本研究揭示了MTZ神经毒性的可能原因,为消除MTZ毒性提供了一个新的视角。

Conceptual carbon-reduction process design and quantitative sustainable assessment for concentrating high purity ethylene from wasted refinery gas

The direct emission of waste refinery gas after combustion will cause a severe greenhouse effect.Recovering high-value-added ethylene from wasted refinery gas has fundamental economic and environmental significance. Due to the complexity of the composition of refinery waste gas, designing and optimizing the whole recovery process is still a challenging task. Herein, a novel process(SCOAS) was proposed to obtain polymer-grade ethylene from wasted refinery gas through a direct separation process,and heat pump-assisted thermal integration optimization(HPSCOAS) was carried out. The unique feature of the novel approach is that a new stripper and ethylene reabsorber follow the dry gas absorber to ensure ethylene recovery and methane content. An industrial model, shallow cooling oil absorption(SCOA), and concentration combined cold separation system of ethylene unit using wasted refinery gas was established to analyze the technology and environment. Based on the detailed process modeling and simulation results, the quantitative sustainability assessment of economy and environment based on product life cycle process is carried out. The results show that compared with the traditional process when the same product is obtained, the total annual cost of the HPSCOAS process is the lowest, which is 15.4% lower than that of the SCOA process and 6.1% lower than that of the SCOAS process. In addition,compared with the SCOA process and the HPSCOAS process, the SCOAS process has more environmental advantages. The non-renewable energy consumed by SCOAS is reduced by about 24.8% and 6.1%, respectively. The CO_(2) equivalent is reduced by about 38.6% and 23.7%.

Optimization of energy consumption structure based on carbon emission reduction target:A case study in Shandong Province,China

It is urgent to significantly reduce greenhouse gas emissions to actively deal with global warming.This paper investigates Shandong Province,a typical province of energy consumption,as the research object,aiming to optimize total energy consumption and consumption structure in the future planning year.This paper constructs a methodological system to optimize energy consumption structure in Shandong Province,using a scenario combination of system dynamics(SD)prediction and analysis based on the coupling of key scenario elements affecting different energy consumption from different perspectives.Structural equation modeling and SD sensitivity analysis indicate an overlap between key factors restricting energy consumption.Pairing the key scenario factors can better reflect the internal mechanism of energy consumption development.Based on this,21 scenarios based on different combinations of the key elements are constructed.Through SD prediction and analysis,the most suitable scenario mode for optimizing energy consumption structure in Shandong Province is selected.This paper provides a suitable development range for the average gross domestic product growth rate,the proportion of secondary industry,energy consumption intensity of secondary industry,and the urbanization rate for Shandong Province.This paper can provide a reference for similar research and the government in formulating the optimization scheme of energy consumption structure.

私人记录中的民间宗教:段正元与三位民国军政人物交往钩沉

从熊斌、何键、蒋介石与民国学者段正元及其创办的民间宗教组织“道德学社”的交往看,维系他们的不仅仅是个人信仰那么简单,更重要的是以此来结成一张关系网,以达到扩充势力的目的。

Comorbidities and high in-hospital mortality of cancer-associated pulmonary embolism:findings from a real-world registry study

To the Editor:Cancer has been recognized as an independent predisposing factor of venous thromboembolism(VTE),including pulmonary embolism(PE)and deep vein thrombosis(DVT).Patients with cancer have a sevenfold increased risk of VTE compared with those without cancer.[1]Evidence from autopsy in cancer patients showed that PE is an important disease complication in patients with cancer.[2]Optimal management of PE patients with cancer has become a major concern that challenges clinicians in daily clinical practice.Understanding the risk factors of all-cause death in PE patients with cancer in the real world may enable optimal management and improve their survival.Therefore,this study was performed to characterize cancerassociated PE and evaluate the clinical predictors of inhospital death based on the data of PE patient population in China.

神经肽Y在人脑局灶性皮层发育不良不同Palmini病理亚型间的表达差异

目的探讨不同Palmini病理亚型局灶性脑皮层发育不良(FCD)与正常人脑中神经肽Y(NPY)表达的差异,以及FCD诱发癫痫的机制。方法收集河北省人民医院神经外科自2007年5月至2011年10月收治的行癫痫手术后病理结果符合FCD的患者58例作为试验组。以Palmini分类标准,按病理亚型分为4组:ⅠA组9例、ⅠB组26例、ⅡA组10例、ⅡB组13例。同时取10例正常人脑组织设为对照组。观察FCD患者癫痫发病临床特点,FCD患者及正常人脑中NPY免疫反应阳性细胞数目差异。结果FCDⅡB组癫痫发作频率明显高于其他病理亚型组。FCDⅡB组NPY免疫反应阳性细胞数目与对照组比较明显增加,差异有统计学意义(P<0.05);FCD组中FCDⅠA、FCDⅠB、FCDⅡA各亚型与对照组比较,差异无统计学意义(P>0.05)。结论FCD各病理亚型中FCDⅡB型的NPY免疫反应阳性细胞反应明显,FCDⅡB致痫机制可能与NPY的表达增高有关。

Epidemiological Data of Work-Related Musculoskeletal Disorders—China,2018–2020

Summary What is already known about this topic?In recent decades,work-related musculoskeletal disorders(WMSDs)have become increasingly prominent and have become an important issue that is of universal concern and an urgent need to be solved in all countries of the world.What is added by this report?The top three industries or occupational groups with the highest standardized prevalence rate of WMSDs were flight attendants,medical staff,and vegetable greenhouses in that order.Women workers were 1.5 times more likely to suffer from WMSDs than men workers.

Investigation on Work-Related Musculoskeletal Disorders--China, 2018−2019

What is already known about this topic?Work-related musculoskeletal disorders(WMSDs)have a high prevalence and seriously harmful,which has attracted extensive attention in various countries in the world.Currently,the occurrence and rules of WMSDs in key industries are not known in China.What is added by this report?The prevalence of WMSDs is relatively high among professional populations in key industries in China,with the most commonly affected body parts concentrated in neck,shoulders,and low back and increasing with age and working years.What are the implications for public health practice?This study determined the prevalence and distribution characteristics of WMSDs in key industries in China and provided scientific evidence to recommend for inclusion of WMSDs in the new revision of the list of occupational diseases in China.

A comparison of next-generation sequencing analysis methods for cancer xenograft samples

The application of next-generation sequencing （NGS） technology in cancer is influenced by the quality and purity of tissue samples. This issue is especially critical for patient-derived xenograft （PDX） models, which have proven to be by far the best preclinical tool for investigating human tumor biology, because the sensitivity and specificity of NGS analysis in xenograft samples would be compromised by the contamination of mouse DNA and RNA. This definitely affects downstream analyses by causing inaccurate mutation calling and gene expression estimates. The reliability of NGS data analysis for cancer xenograft samples is therefore highly dependent on whether the sequencing reads derived from the xenograft could be distinguished from those originated from the host. That is, each sequence read needs to be accurately assigned to its original species. Here, we review currently available methodologies in this field, including Xenome, Disambiguate, bamcmp and pdxBlacklist, and provide guidelines for users.

Chemical screening reveals Ronidazole is a superior prodrug to Metronidazole for nitroreductase-induced cell ablation system in zebrafish larvae

The Metronidazole(MTZ)/nitroreductase(NTR)-mediated cell ablation system is the most commonly used chemical-genetic cell ablation method in zebrafish. This system can specifically ablate target cells under spatial and temporal control. The MTZ/NTR system has become a widely used cell ablation system in biological, developmental, and functional studies. However, the inadequate cell-ablation ability of some cell types and the side effects of high concentration MTZ impede extensive applications of the MTZ/NTR system. In the present study, the US drug collection library was searched to extend the NTR system. Six MTZ analogs were found, and the cell-ablation ability of these analogs was tested in zebrafish larvae. The results revealed that two of the NTR substrates, Furazolidone and Ronidazole, ablated target cells more efficiently than MTZ at lower concentrations. Furthermore, the working concentration of Ronidazole, but not Furazolidone and MTZ, did not affect axonal bridge formation during spinal cord regeneration. Our results,taken together, indicate that Ronidazole is a superior prodrug to MTZ for the NTR system, especially for the study of neuron regeneration in zebrafish larvae.

Incidence and Risk Factors of the Upper-Limb Musculoskeletal Disorders Among Occupational Groups in Key Industries—China,2018–2021

What is already known about this topic?The burden of illness and economic losses due to upper-limb work-related musculoskeletal disorders(UL-WMSDs)is high;thus,they have become a major global public health problem.At present,the epidemiological characteristics of UL-WMSDs in China's occupational population are still unknown.What is added by this report?The incidence of UL-WMSDs among key occupational groups in China is 22.5%,with distinct occupational characteristics.What are the implications for public health practice?This study has primarily determined the occurrence and potential risk factors of UL-WMSDs in key industries in China and provided data support for recommending prevention and control of the occurrence of such diseases in key industries in China,and in facilitating the addition into the China’s List of Legal Occupational Diseases.

Gene dysregulation analysis builds a mechanistic signature for prognosis and therapeutic benefit in colorectal cancer

The implementation of cancer precision medicine requires biomarkers or signatures for predicting prognosis and therapeutic benefits.Most of current efforts in this field are paying much more attention to predictive accuracy than to molecular mechanistic interpretability.Mechanism-driven strategy has recently emerged,aiming to build signatures with both predictive power and explanatory power.Driven by this strategy,we developed a robust gene dysregulation analysis framework with machine learning algorithms,which is capable of exploring gene dysregulations underlying carcinogenesis from high-dimensional data with cooperativity and synergy between regulators and several other transcriptional regulation rules taken into consideration.We then applied the framework to a colorectal cancer(CRC)cohort from The Cancer Genome Atlas.The identified CRC-related dysregulations significantly covered known carcinogenic processes and exhibited good prognostic effect.By choosing dysregulations with greedy strategy,we built a four-dysregulation(4-DysReg)signature,which has the capability of predicting prognosis and adjuvant chemotherapy benefit.4-DysReg has the potential to explain carcinogenesis in terms of dysfunctional transcriptional regulation.These results demonstrate that our gene dysregulation analysis framework could be used to develop predictive signature with mechanistic interpretability for cancer precision medicine,and furthermore,elucidate the mechanisms of carcinogenesis.

TGPred:a tumor gene prediction webserver for analyzing structural and functional impacts of variants

With the increasing use of high-throughput sequencing technology in tumor research,a large number of somatic variations are being identified and some of them have proved to be responsible for tumorigenesis(Cancer Genome Atlas Research Network et al.,2013).Investigating structural and functional impacts of tumor somatic variants would greatly help to identify causal variations,understand the mechanisms of carcinogenesis,and develop novel anti-tumor therapies.Therefore,many efforts have recently been made to map genomic variations to 3D protein structure,such as G23D(Solomon et al.,2016)and G2S(Wang et al.,2018).