Acidosis,regardless of hypoxia involvement,is recognized as a chronic and harsh tumor microenvironment(TME)that educates malignant cells to thrive and metastasize.Although overwhelming evidence supports an acidic envi...Acidosis,regardless of hypoxia involvement,is recognized as a chronic and harsh tumor microenvironment(TME)that educates malignant cells to thrive and metastasize.Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression,the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy.Here,chemical-induced and transgenic mouse models for colon,liver and lung cancer were established,respectively.miR-7 and TGF-β2 expressions were examined in clinical tissues(n=184).RNA-seq,miRNA-seq,proteomics,biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis.Our data show that lung cancer is sensitive to the increased acidification of TME,and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5 p.TGF-β2 is a direct target of miR-7-5 p.The reduced expression of miR-7-5 p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer.Indeed,overexpression of miR-7-5 p reduces the acidic p H-enhanced lung cancer metastasis.Furthermore,the human lung tumor samples also show a reduced miR-7-5 p expression but an elevated level of activated TGF-β2;the expressions of both miR-7-5 p and TGF-β2 are correlated with patients’survival.We are the first to identify the role of the miR-7/TGF-β2 axis in acidic p H-enhanced lung cancer metastasis.Our study not only delineates how acidification directly affects tumorigenesis,but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer(NSCLC)treatment.Our study opens an avenue to explore the p H-sensitive subcellular components as novel therapeutic targets for cancer treatment.展开更多
The weft-knitted reduced graphene oxide(r-GO)textile that is made up of many conductive r-GO coated fibers was successfully prepared dependent on the electrospray deposition technique.Interestingly,the r-GO textile pr...The weft-knitted reduced graphene oxide(r-GO)textile that is made up of many conductive r-GO coated fibers was successfully prepared dependent on the electrospray deposition technique.Interestingly,the r-GO textile presents negative resistance variation not only in axial direction as the pressure increases but also in transverse direction as the lateral stretch increases which makes it has the advantage to fabricate the reliable sensors based on strain-resistance effect.The transverse-strain and pressure sensors based on the r-GO textiles all show the excellent sensing characteristics such as high sensitivity,reliability,and good durability,etc.The maximum gauge factors(GF)of the transverse-sensor are 27.1 and 153.5 in the x-and/-direction,respectively.And the practical detection range can up to 40%in the x-direction and 35%in the y-direction,respectively.The r-GO textile pressure sensor also shows high sensitivity for a broad pressure range that with a GF up to 716.8 kPa-1 for less than 4.5 kPa region and still has more sensitive pressure sensing characteristics even the pressure goes up to 14 kPa.Based on those good performances of r-GO textile sensors,its potential applications in human body states monitoring have been studied.展开更多
We aimed to report real-world longitudinal ambient air pollutants levels compared to WHO Air Quality Guidelines(AQG)and analyze multiple air pollutants’joint effect on longevity,and the modification and confounding f...We aimed to report real-world longitudinal ambient air pollutants levels compared to WHO Air Quality Guidelines(AQG)and analyze multiple air pollutants’joint effect on longevity,and the modification and confounding from the climate and urbanization with a focus on the oldest-old.This study included 13,207 old participants with 73.3%aged 80 and beyond,followed up from 2008 to 2018 in 23 Chinese provinces.We used the Cox-proportional hazards model and quantile-based g-computation model to measure separate and joint effects of the multiple pollutants.We adjusted for climate and area economic factors based on a directed acyclic graph.In 2018,no participants met the WHO AQG for PM_(2.5) and O_(3),and about one-third met the AQG for NO_(2).The hazard ratio(HR)for mortality was 1.07(95%confidence interval-CI:1.05,1.09)per decile increase in all three pollutants,with PM_(2.5) being the dominant contributor according to the quantile-based g-computation model.In the three-pollutant model,the HRs(95%CI)for PM_(2.5) and NO_(2) were 1.27(1.25,1.3)and 1.08(1.05,1.12)per 10μg/m3 increase,respectively.The oldest-old experienced a much lower mortality risk from air pollution compared to the young-old.The mortality risk of PM_(2.5) was higher in areas with higher annual average temperatures.The adjustment of road density considerably intensified the association between NO_(2) and mortality.The ambient PM_(2.5) and O_(3) levels in China exceeded the WHO AQG target substantially.Multiple pollutants coexposure,confounding,and modification of the district economic and climate factors should not be ignored in the association between air pollution and mortality.展开更多
基金supported by the projects of National Natural Science Foundation of China(81874367 and 82074019)Guangdong Key Laboratory for Translational Cancer research of Chinese Medicine(2018B030322011,China)+3 种基金Natural Science Foundation for Distinguished Young Scholars of Guangdong Province,China(2017A030306033)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(2016,China)Project of Educational Commission of Guangdong Province of China(2016KTSCX012)Pearl River Nova Program of Guangzhou,China(201710010108)。
文摘Acidosis,regardless of hypoxia involvement,is recognized as a chronic and harsh tumor microenvironment(TME)that educates malignant cells to thrive and metastasize.Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression,the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy.Here,chemical-induced and transgenic mouse models for colon,liver and lung cancer were established,respectively.miR-7 and TGF-β2 expressions were examined in clinical tissues(n=184).RNA-seq,miRNA-seq,proteomics,biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis.Our data show that lung cancer is sensitive to the increased acidification of TME,and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5 p.TGF-β2 is a direct target of miR-7-5 p.The reduced expression of miR-7-5 p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer.Indeed,overexpression of miR-7-5 p reduces the acidic p H-enhanced lung cancer metastasis.Furthermore,the human lung tumor samples also show a reduced miR-7-5 p expression but an elevated level of activated TGF-β2;the expressions of both miR-7-5 p and TGF-β2 are correlated with patients’survival.We are the first to identify the role of the miR-7/TGF-β2 axis in acidic p H-enhanced lung cancer metastasis.Our study not only delineates how acidification directly affects tumorigenesis,but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer(NSCLC)treatment.Our study opens an avenue to explore the p H-sensitive subcellular components as novel therapeutic targets for cancer treatment.
基金support from the National Natural Science Foundation of China(Nos.11604173,61625404,61888102,and 51973100)the China Postdoctoral Science Foundation(No.2017M612195)+1 种基金State Key Laboratory of Bio-Fibers and Eco-Textiles,Qingdao University(No.RZ2000003334)fund from the National Key Research Development Project(No.2019YFC0121402).
文摘The weft-knitted reduced graphene oxide(r-GO)textile that is made up of many conductive r-GO coated fibers was successfully prepared dependent on the electrospray deposition technique.Interestingly,the r-GO textile presents negative resistance variation not only in axial direction as the pressure increases but also in transverse direction as the lateral stretch increases which makes it has the advantage to fabricate the reliable sensors based on strain-resistance effect.The transverse-strain and pressure sensors based on the r-GO textiles all show the excellent sensing characteristics such as high sensitivity,reliability,and good durability,etc.The maximum gauge factors(GF)of the transverse-sensor are 27.1 and 153.5 in the x-and/-direction,respectively.And the practical detection range can up to 40%in the x-direction and 35%in the y-direction,respectively.The r-GO textile pressure sensor also shows high sensitivity for a broad pressure range that with a GF up to 716.8 kPa-1 for less than 4.5 kPa region and still has more sensitive pressure sensing characteristics even the pressure goes up to 14 kPa.Based on those good performances of r-GO textile sensors,its potential applications in human body states monitoring have been studied.
基金supported by the National Key R&D Program of China (2018YFC2000400 to Y.Z.)National Natural Sciences Foundation of China (72061137004,71490732 to Y.Z.)+4 种基金the U.S.National Institute of Aging of National Institute of Health (P01AG031719 to Y.Z.)supported by the National Natural Sciences Foundation of China (82250610230 to J.J.S.)Natural Science Foundation of Beijing (IS23105 to J.J.S.)Tsinghua University Vanke School of Public Health Research Grant (2021PY001 to J.J.S.)Tsinghua University Initiative Scientific Research Program (20233080015 to J.J.S.).
文摘We aimed to report real-world longitudinal ambient air pollutants levels compared to WHO Air Quality Guidelines(AQG)and analyze multiple air pollutants’joint effect on longevity,and the modification and confounding from the climate and urbanization with a focus on the oldest-old.This study included 13,207 old participants with 73.3%aged 80 and beyond,followed up from 2008 to 2018 in 23 Chinese provinces.We used the Cox-proportional hazards model and quantile-based g-computation model to measure separate and joint effects of the multiple pollutants.We adjusted for climate and area economic factors based on a directed acyclic graph.In 2018,no participants met the WHO AQG for PM_(2.5) and O_(3),and about one-third met the AQG for NO_(2).The hazard ratio(HR)for mortality was 1.07(95%confidence interval-CI:1.05,1.09)per decile increase in all three pollutants,with PM_(2.5) being the dominant contributor according to the quantile-based g-computation model.In the three-pollutant model,the HRs(95%CI)for PM_(2.5) and NO_(2) were 1.27(1.25,1.3)and 1.08(1.05,1.12)per 10μg/m3 increase,respectively.The oldest-old experienced a much lower mortality risk from air pollution compared to the young-old.The mortality risk of PM_(2.5) was higher in areas with higher annual average temperatures.The adjustment of road density considerably intensified the association between NO_(2) and mortality.The ambient PM_(2.5) and O_(3) levels in China exceeded the WHO AQG target substantially.Multiple pollutants coexposure,confounding,and modification of the district economic and climate factors should not be ignored in the association between air pollution and mortality.
