Progress on diagnostic and prognostic markers of pancreatic cancer

Pancreatic cancer is a malignant disease characterized by low survival and high recurrence rate,whose patients are mostly at the stage of locally advanced or metastatic disease when first diagnosed.Early diagnosis is particularly important because prognostic/predictive markers help guide optimal individualized treatment regimens.So far,CA19-9 is the only biomarker for pancreatic cancer approved by the FDA,but its effectiveness is limited by low sensitivity and specificity.With recent advances in genomics,proteomics,metabolomics,and other analytical and sequencing technologies,the rapid acquisition and screening of biomarkers is now possible.Liquid biopsy also occupies a significant place due to its unique advantages.In this review,we systematically describe and evaluate the available biomarkers that have the greatest potential as vital tools in diagnosing and treating pancreatic cancer.

SIRT4通过抑制GLS2表达增强肝细胞癌对索拉菲尼敏感性的研究

目的:探索Sirtuin4(SIRT4)调控肿瘤谷氨酰胺代谢的机制,明确SIRT4对肝癌细胞干性及索拉菲尼治疗敏感性的影响。方法:通过实时定量PCR(real-time quantitative reverse transcription PCR,qRT-PCR)和免疫组织化学染色检测SIRT4在肝癌中的m RNA和蛋白表达水平。免疫印迹及细胞成球实验检测肿瘤细胞干性,细胞计数实验(CCK-8)和平板克隆实验检测肝癌细胞索拉菲尼治疗敏感性。免疫共沉淀检测SIRT4对蛋白的去乙酰化作用。结果:在肝癌的临床样本组织和细胞系中,SIRT4的表达显著低于癌旁组织和正常肝细胞。在体外实验中,过表达SIRT4能够明显降低肝癌细胞的成球数量(P<0.01)和干性标志物表达,并使索拉菲尼治疗的肝癌细胞克隆数和OD_(450)值进一步下降(均P<0.01)。机制研究表明,SIRT4通过去乙酰化降低谷氨酰胺合成酶2(glutamine synthase 2,GLS2)的表达,进而抑制肝癌细胞中谷氨酰胺的分解代谢,从而调节肝癌细胞的干性和对索拉菲尼的敏感性。结论:SIRT4在肝癌组织中表达显著降低,能够通过降低谷氨酰胺分解代谢,进而抑制肝癌细胞的干性并增强其对索拉菲尼的敏感性。

Rosiglitazone disrupts pancreatic ductal adenocarcinoma progression by activating the tumor suppressor ESE3/EHF

Pancreatic ductal adenocarcinoma(PDAC),the most common histologic type of pancreatic cancer,is among the most lethal cancers,and is associated with poor prognosis because of its inherent chemoresistant nature and metastatic capacity1.Extensive evidence has shown that cancer stem cells(CSCs),a subpopulation of highly plastic“stem”-like cells within the PDAC,mediate this chemoresistantce and metastatic capacity2.CSCs have unique metabolic,invasive,and chemoresistance properties that enable them to continually self-renew and escape standard chemotherapeutic elimination in PDAC,thus often rendering treatments ineffective3,4.

Scientific Analysis of Adding Weather Heat Capacity &#176Ch in the Weather Forecast

This paper analyzes the current weather forecast in most countries on the defects and deficiencies of temperature forecasts. In addition, weather temperature and weather heat capacity were systematically analyzed in this paper. For this reason, the paper put forward a suggestion for the weather heat capacity (oCh) to be added in weather forecast. If the weather forecast augments the unit (oCh), the weather forecast would upgrade from one-dimensional to two-dimensional, and would make the temperature forecast more scientific, more reasonable and more accurately, which can serve the people and make economic construction better than before.

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Ferroptosis,a unique modality of cell death with mechanistic and morphological differences from other cell death modes,plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug resistance.Aberrant epigenetic modifications and posttranslational modifications(PTMs)promote anticancer drug resistance,cancer progression,and metastasis.Accumulating studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases(NSDs),cardiovascular diseases(CVDs),liver diseases,lung diseases,and kidney diseases.In this review,we first summarize the core molecular mechanisms of ferroptosis.Then,the roles of epigenetic processes,including histone PTMs,DNA methylation,and noncoding RNA regulation and PTMs,such as phosphorylation,ubiquitination,SUMOylation,acetylation,methylation,and ADP-ribosylation,are concisely discussed.The roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases,including cancers,NSD,CVDs,liver diseases,lung diseases,and kidney diseases,as well as the application of epigenetic and PTM modulators in the therapy of these diseases,are then discussed in detail.Elucidating the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other diseases.In addition,these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.

3D Printing Technology for Short-continuous Carbon Fiber Synchronous Reinforced Thermoplastic Composites:A Comparison between Towpreg Extrusion and In Situ Impregnation Processes

Three-dimensional(3D)printing of carbon fiber-reinforced thermoplastic composites(CFRTPs)provides an ef-fective method for manufacturing the CFRTPs parts with complex structures.To increase the mechanical per-formance of these parts,a 3D printing technology for short-continuous carbon fiber synchronous-reinforced thermoplastic composites(S/C-CFRTPs)has been proposed.However,the synchronous reinforcement that ex-isted only at particular positions led to a limited improvement in the mechanical performance of the 3D-printed S/C-CFRTP part,which made it challenging to meet the engineering requirements.To solve this problem,two methods for achieving synchronous reinforcement at all the positions of the 3D-printed S/C-CFRTP part are pro-posed.To determine a suitable printing process for the S/C-CFRTP part,a comprehensive comparison between the two methods was conducted through theoretical analysis and experimental verification,involving the print-ing mechanism,fiber content,impregnation percentage,and mechanical performance.The results indicated that the towpreg extrusion process was suitable for manufacturing the 3D-printed S/C-CFRTP part.Compared with the in situ impregnation process,the towpreg extrusion process led to a fiber content increase of approximately 7%and void rate reduction of approximately 6%,resulting in 19%and 20%increases in the tensile and flexural strengths of the 3D-printed S/C-CFRTPs,respectively.Additionally,an optimized process parameter setting for fabricating an S/C-CFRTP prepreg filament with excellent mechanical performance was proposed.The findings of this study can provide a new approach for further improving the mechanical performance of the 3D-printed advanced composites.

The Two Reemergent Confirmed COVID-19 Cases--Manzhouli City,Inner Mongolia Autonomous Region,China,November 20,2020

On November 20,2020,a 55-year-old male went to the Zhongmeng Hospital of Manzhouli City,Inner Mongolia Autonomous Region for diagnosis and treatment of pain in the waist and lower extremities.His wife,a 55-year-old female,accompanied him to the hospital also feeling unwell.They were first tested for coronavirus disease 2019(COVID-19)in Manzhouli People’s Hospital based on China’s policy of ensuring that“all those in need are tested,isolated,hospitalized,and treated.”