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.

Tumorigenic bacteria in colorectal cancer:mechanisms and treatments

Colorectal cancer(CRC)is the third most common and the second most fatal cancer.In recent years,more attention has been directed toward the role of gut microbiota in the initiation and development of CRC.Some bacterial species,such as Fusobacterium nucleatum,Escherichia coli,Bacteroides fragilis,Enterococcus faecalis,and Salmonella sp.have been associated with CRC,based upon sequencing studies in CRC patients and functional studies in cell culture and animal models.These bacteria can cause host DNA damage by genotoxic substances,including colibactin secreted by pks+Escherichia coli,B.fragilis toxin(BFT)produced by Bacteroides fragilis,and typhoid toxin(TT)from Salmonella.These bacteria can also indirectly promote CRC by influencing host-signaling pathways,such as E-cadherin/β-catenin,TLR4/MYD88/NF-κB,and SMO/RAS/p38 MAPK.Moreover,some of these bacteria can contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function,creating a proinflammatory environment,or influencing the autophagy process.Treatments with the classical antibacterial drugs,metronidazole or erythromycin,the antibacterial active ingredients,M13@Ag(electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13),berberine,and zerumbone,were found to inhibit tumorigenic bacteria to different degrees.In this review,we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria,as well as progress in developing effective antibacterial therapies.Specific bacteria have been shown to be active in the oncogenesis and progression of CRC,and some antibacterial compounds have shown therapeutic potential in bacteria-induced CRC.These bacteria may be useful as biomarkers or therapeutic targets for CRC.

PtRuAgCoNi高熵合金纳米颗粒高效电催化氧化5-羟甲基糠醛

5-羟甲基糠醛(HMF)的电催化氧化被认为是合成2,5-呋喃二甲酸(FDCA)最环保、经济和有效的方法之一,它可作为聚呋喃二甲酸乙二醇酯(PEF)的生物基前体。在这项工作中,我们通过低温溶剂热法合成了PtRuAgCoNi高熵合金纳米颗粒,并在不改变颗粒结构和组成的情况下进行了简易的处理以去除表面活性剂。负载在碳载体上的合金纳米催化剂无论是否含有表面活性剂在HMF电催化氧化为FDCA的过程中都表现出比商业Pt/C更好的催化性能。且表面活性剂的去除可以进一步提高其电催化性能,表明高熵合金纳米粒子在电催化和绿色化学中具有广阔的应用前景。

Understanding Differences in Event Attribution Results Arising from Modeling Strategy

While there is high confidence that human activities have increased the likelihood and severity of hot extreme events over many parts of the world,there is notable spread in quantitative estimates of anthropogenic influence even on a single event.To better understand the uncertainty of attribution results,here we compare different event attribution methods using the 2015 July-August record-breaking heat event in northwestern China as a case study.To address the anthropogenic influence on the likelihood of the extreme event,we employ attribution runs with two modeling strategies—atmosphere-only and coupled simulations—with different conditioning.In atmosphere-only attribution runs,given the observed sea surface boundary conditions and external forcings in 2015,it is estimated that anthropogenic forcing has increased the likelihood of hot extremes such as that observed in 2015 in the target region,by approximately 27 and 12 times in MIROC5 and HadGEM3-A-N216,respectively.In Coupled Model Intercomparison Project phase 5(CMIP5)fully coupled attribution runs,given the external forcing at the 1961-2015 level and regardless of sea surface boundary conditions,there is a 21-fold increase in the likelihood of similar heat events due to anthropogenic forcing.The differences in quantitative attribution results can arise from modeling strategies,which are tightly linked to different conditioning in attribution.Specifically,different ocean boundary conditions,external forcings,and air-sea coupling processes contribute to different attribution results between the two modeling strategies.Within each modeling strategy,model uncertainty affects quantitative attribution conclusions.The comparison of different attribution methods provides a better understanding of the uncertainty of attribution results,which is useful in synthesizing and interpreting attribution results.

The biology,function,and applications of exosomes in cancer

Exosomes are cell-derived nano vesicles with diameters from 30 to 150 nm,released upon fusion of multi vesicular bodies with the cell surface.They can transport nucleic acids,proteins,and lipids for intercellular communication and activate signaling pathways in target cells.In cancers,exosomes may participate in growth and metastasis of tumors by regulating the immune response,blocking the epithelial-mesenchymal transition,and promoting angiogenesis.They are also involved in the development of resistance to chemotherapeutic drugs.Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers.Because of their amphipathic structure,exosomes are natural drug delivery vehicles for cancer therapy.

Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway

Glioblastoma multiforme(GBM)in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it.Studies of sinomenine,an alkaloid from the Chinese medicinal plant,Sinomenium acutum,showed that it had inhibitory effects on several kinds of cancer.Here,we synthesized a sinomenine derivative,sino-wcj-33(SW33),tested it for antitumor activity on GBM and explored the underlying mechanism.SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells.It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis.Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3 K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body.SW33 also induced autophagy through the PI3 K/AKT/mTOR and AMPK/mTOR pathways.Thus,SW33 appears to be a promising drug for treating GBM effectively and safely.

Impact of 1.5°C and 2.0°C global warming on aircraft takeoff performance in China

Associated with global warming, climate extremes such as extreme temperature will significantly increase. Understanding how climate change will impact the airflights is important to the planning of future flight operations. In this study, the impacts of 1.5 and 2 degree's global warming on the aircraft takeoff performance in China are investigated using a unique climate projection data from an international collaboration project named HAPPI. It is found that the mean summer daily maximum temperature, which is a major factor that affects the flight through changing the aircraft's takeoff weight, will increase significantly with magnitude less than 1.5℃ over most parts of China except for the Tibetan Plateau. The half a degree additional global warming will lead to higher extreme temperature in the arid and semi-arid western China, the Tibetan Plateau and the northeastern China, while the change in eastern China is weak. Five airports including Beijing, Shanghai, Kunming, Lasa and Urumqi will see ～1.0°-2.0℃(1.4°-3.0℃) higher daily maximum temperature under 1.5℃(2.0℃) scenario. The half-degree additional warming will lead to a shift toward higher extreme temperature in these five sites. For both1.5° and 2.0℃ scenarios, the number of weight-restriction days will increase significantly at 3 airports including Beijing, Shanghai, and Lasa. Urumqi will witness an increase of weight-restriction days only in 2.0℃ future.

3-O-Acetyl-11-keto-β-boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma

Glioblastoma is the most common and aggressive primary tumor in the central nervous system,accounting for 12%-15%of all brain tumors.3-O-Acetyl-11-keto-β-boswellic acid(AKBA),one of the most active ingredients of gum resin from Boswellia carteri Birdw.,was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma.However,whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear.An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA.The effects of AKBA on tumor growth were evaluated using MRI.The effects on the alteration of metabolic landscape were detected by MALDIMSI.The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence,respectively.Transmission electron microscope was used to check morphology of cells treated by AKBA.Our results showed that AKBA(100 mg/kg)significantly inhibited the growth of orthotopic U87-MG gliomas.Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma,while immunoblot assays revealed that AKBA suppressed the expression of ATG5,p62,LC3 B,p-ERK/ERK,and P53,and increased the ratio of p-mTOR/mTOR.Taken together,these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy.AKBA could be a promising chemotherapy drug for glioblastoma.

MELK is an oncogenic kinase essential for metastasis,mitotic progression,and programmed death in lung carcinoma

Lung cancer is the fastest growth rate of morbidity and mortality in nearly a decade,and remains difficult to treat.Furthermore,the molecular mechanisms underlying its development are still unclear.In this study,bioinformatics analysis showed that MELK was highly expressed in lung cancer and negatively correlated to the survival of lung adenocarcinoma(LUAD).Immunohistochemistry analysis of LUAD patient tissues revealed there were a high level of MELK expression in LUAD.Knockdown of MELK expression inhibits the migration and invasion of LUAD cells,which may be mediated by Twist1,Slug,MMP7,and N-catenin.Overexpression of MELK promoted the growth of LUAD cells in medium,3D Matrigel,and nude mice.Inhibition of MELK by OTSSP167 arrested cycle of LUAD cells at G2/M phase via PLK1-CDC25C-CDK1 pathway,and triggered apoptosis-mediated pyroptosis.Together,these data indicate that MELK is critical for metastasis,mitotic progression,and programmed death of LUAD and may be a promising therapeutic target for LUAD.

Sphingosine kinase 1 promotes growth of glioblastoma by increasing inflammation mediated by the NF-κB/IL-6/STAT3 and JNK/PTX3 pathways

Glioblastoma(GBM)is the most challenging malignant tumor of the central nervous system because of its high morbidity,mortality,and recurrence rate.Currently,mechanisms of GBM are still unclear and there is no effective drug for GBM in the clinic.Therefore,it is urgent to identify new drug targets and corresponding drugs for GBM.In this study,in silico analyses and experimental data show that sphingosine kinase 1(SPHK1)is up-regulated in GBM patients,and is strongly correlated with poor prognosis and reduced overall survival.Overexpression of SPHK1 promoted the proliferation,invasion,metastasis,and clonogenicity of GBM cells,while silencing SPHK1 had the opposite effect.SPHK1 promoted inflammation through the NF-κB/IL-6/STAT3 signaling pathway and led to the phosphorylation of JNK,activating the JNK-JUN and JNK-ATF3 pathways and promoting inflammation and proliferation of GBM cells by transcriptional activation of PTX3.SPHK1 interacted with PTX3 and formed a positive feedback loop to reciprocally increase expression,promote inflammation and GBM growth.Inhibition of SPHK1 by the inhibitor,PF543,also decreased tumorigenesis in the U87-MG and U251-MG SPHK1 orthotopic mouse models.In summary,we have characterized the role and molecular mechanisms by which SPHK1 promotes GBM,which may provide opportunities for SPHK1-targeted therapy.

Anthropogenic influence on extreme Meiyu rainfall in 2020 and its future risk

Eastern China experienced excessive Meiyu rainfall in the summer of 2020,with a long rainy season and frequent extreme rainfall events.Extreme rainfall occurred on daily to monthly time scales.In particular,persistent heavy rainfall events occurred;e.g.,the maximum accumulated rainfall over four consecutive weeks(Rx28day)in the lower reaches of the Yangtze River was 94%greater than climatology,breaking the observational record since 1961.With ongoing anthropogenic climate change,it is vital to understand the anthropogenic influence on this extreme rainfall event and its driving mechanisms.In this study,based on multi-model simulations under different external forcings that participate in the Detection and Attribution Model Intercomparison Project(DAMIP)in the Coupled Model Intercomparison Project-phase 6(CMIP6),we show that anthropogenic forcing has reduced the probability of the Rx28day extreme rainfall as that in observations in the lower reaches of the Yangtze River in 2020,by 46%(22–62%).Specifically,greenhouse gas(GHG)emissions have increased the probability by 44%as a result of atmospheric warming and moistening.However,this effect was offset by anthropogenic aerosols,which reduced the probability by 73%by reducing atmospheric moisture and weakening the East Asian summer monsoon circulation.With the continuous emissions of GHGs and reductions in aerosols in the future,similar persistent heavy rainfall events are projected to occur more frequently.A higher occurrence probability is expected under higher emission scenarios,which is estimated to be 4.6,13.6 and 27.7 times that in the present day under the SSP1-2.6,SSP2-4.5,and SSP5-8.5 emission scenarios,respectively,by the end of the 21st century.Thus,efficient mitigation measures will help to reduce the impacts related to extreme rainfall.

Scientific challenges and instrumentation for the International Meridian Circle Program

Earth’s ecosystems and human activities are threatened by a broad spectrum of hazards of major importance for the safety of ground infrastructures,space systems and space flight:solar activity,earthquakes,atmospheric and climatic disturbances,changes in the geomagnetic field,fluctuations of the global electric circuit.Monitoring and understanding these major hazards to better predict and mitigate their effects is one of the greatest scientific and operational challenges of the 21st century.Though diverse,these hazards share one feature in common:they all leave their characteristic imprints on a critical layer of the Earth’s environment:its ionosphere,middle and upper atmosphere(IMUA).The objective of the International Meridian Circle Program(IMCP),a major international program led by the Chines Academy of Sciences(CAS),is to deploy,integrate and operate a global network of research and monitoring instruments to use the IMUA as a screen on which to detect these imprints.In this article,we first show that the geometry required for the IMCP global observation system leads to a deployment of instruments in priority along the 120°E-60°W great meridian circle,which will cover in an optimal way both the dominant geographic and geomagnetic latitude variations,possibly complemented by a second Great Circle along the 30°E-150°W meridians to capture longitude variations.Then,starting from the Chinese Meridian Project(CMP)network and using it as a template,we give a preliminary and promising description of the instruments to be integrated and deployed along the 120°E-60°W great circle running across China,Australia and the Americas.

MELK is an oncogenic kinase essential for metastasis,mitotic progression,and programmed death in lung carcinoma

Lung cancer is the fastest growth rate of morbidity and mortality in nearly a decade,and remains difficult to treat.Furthermore,the molecular mechanisms underlying its development are still unclear.In this study,bioinformatics analysis showed that MELK was highly expressed in lung cancer and negatively correlated to the survival of lung adenocarcinoma(LUAD).Immunohistochemistry analysis of LUAD patient tissues revealed there were a high level of MELK expression in LUAD.Knockdown of MELK expression inhibits the migration and invasion of LUAD cells,which may be mediated by Twist1,Slug,MMP7,and N-catenin.Overexpression of MELK promoted the growth of LUAD cells in medium,3D Matrigel,and nude mice.Inhibition of MELK by OTSSP167 arrested cycle of LUAD cells at G2/M phase via PLK1-CDC25C-CDK1 pathway,and triggered apoptosis-mediated pyroptosis.Together,these data indicate that MELK is critical for metastasis,mitotic progression,and programmed death of LUAD and may be a promising therapeutic target for LUAD.