Dear editor,The scarcity of routinemetastatic biopsies or resection limits the finding of biomarkers of diagnosis and prognosis in patients with brain metastases.Derived from necrosis,apoptosis,and secretion of tumor ...Dear editor,The scarcity of routinemetastatic biopsies or resection limits the finding of biomarkers of diagnosis and prognosis in patients with brain metastases.Derived from necrosis,apoptosis,and secretion of tumor cells,circulating tumor DNA(ctDNA)is widely distributed in various body fluids,including peripheral blood and cerebrospinal fluid(CSF),as an alternative biomarker for tumor-associated analysis[1].Fortunately,genomic alterations of blood ctDNA and CSF ctDNA have been proven as prognostic markers in non-small cell lung cancer(NSCLC)patients with brain metastasis[2,3].展开更多
Because of its high adsorption capacity, biochar has been used to stabilize metals when remediating contaminated soils; to date, however, it has seldom been used to remediate contaminated sediment. A biochar was used ...Because of its high adsorption capacity, biochar has been used to stabilize metals when remediating contaminated soils; to date, however, it has seldom been used to remediate contaminated sediment. A biochar was used as a stabilization agent to remediate Cu-and Pb-contaminated sediments, collected from three locations in or close to Beijing. The sediments were mixed with a palm sawdust gasified biochar at a range of weight ratios(2.5%, 5%, and 10%) and incubated for 10, 30, or 60 days. The performance of the different treatments and the heavy metal fractions in the sediments were assessed using four extraction methods, including diffusive gradients in thin films, the porewater concentration, a sequential extraction, and the toxicity characteristic leaching procedure. The results showed that biochar could enhance the stability of heavy metals in contaminated sediments. The degree of stability increased as both the dose of biochar and the incubation time increased. The sediment p H and the morphology of the metal crystals adsorbed onto the biochar changed as the contact time increased. Our results showed that adsorption,metal crystallization, and the p H were the main controls on the stabilization of metals in contaminated sediment by biochar.展开更多
Petroleum hydrocarbons,mainly consisting of n-alkanes and polycyclic aromatic hydrocarbons(PAHs),are considered as priority pollutants and biohazards in the environment,eventually affecting the ecosystem and human hea...Petroleum hydrocarbons,mainly consisting of n-alkanes and polycyclic aromatic hydrocarbons(PAHs),are considered as priority pollutants and biohazards in the environment,eventually affecting the ecosystem and human health.Though many previous studies have investigated the change of bacterial community and alkane degraders during the degradation of petroleum hydrocarbons,there is still lack of understanding on the impacts of soil alkane contamination level.In the present study,microcosms with different n-alkane contamination(1%,3%and 5%)were set up and our results indicated a complete alkane degradation after 30 and 50 days in 1%-and 3%-alkane treatments,respectively.In all the treatments,alkanes with medium-chain length(C_(11)-C_(14))were preferentially degraded by soil microbes,followed by C27-alkane in 3%and 5%treatments.Alkane contamination level slightly altered soil bacterial community,and the main change was the presence and abundance of dominant alkane degraders.Thermogemmatisporaceae,Gemmataceae and Thermodesulfovibrionaceae were highly related to the degradation of C_(14)-and C_(27)-alkanes in 5%treatment,but linked to alkanes with medium-chain(C11-C18)in 1%treatment and C21-alkane in 3%treatment,respectively.Additionally,we compared the abundance of three alkane-monooxygenase genes,e.g.,alk_A,alk_P and alk_R.The abundance of alk_R gene was highest in soils,and alk_P gene was more correlated with alkane degradation efficiency,especially in 5%treatment.Our results suggested that alkane contamination level showed non-negligible effects on soil bacterial communities to some extents,and particularly shaped alkane degraders and degrading genes significantly.This study provides a better understanding on the response of alkane degraders and bacterial communities to soil alkane concentrations,which affects their biodegradation process.展开更多
Background:Limited by difficulties in early detection and availabilities of effective treatments,pancreatic cancer is a highly malignant disease with poor prognosis.Nuclear receptors are a family of ligand‐dependent ...Background:Limited by difficulties in early detection and availabilities of effective treatments,pancreatic cancer is a highly malignant disease with poor prognosis.Nuclear receptors are a family of ligand‐dependent transcription factors that are highly druggable therapeutic targets playing critical roles in human physiological and pathological development,including cancer.In this study,we explored the therapeutic potential as well as the molecular mechanisms of liver X receptor(LXR)agonist GW3965 in pancreatic cancer.Methods:Soft‐agar colony formation assay,xenograft tumors,Oligonucleotide microarray,Reverse transcription real‐time polymerase chain reaction,Western immunoblotting and Immunohistochemistry were used in this study.Results:We demonstrated pleotropic in vitro activities of GW3965 in pancreatic cell lines MIA PaCa‐2 and BXPC3 including reduction of cell viability,inhibition of cell proliferation,stimulation of cell death,and suppression of colony formation,which translated to significant inhibition of xenograft tumor growth in vitro.By mapping the gene expression profiles,we identified the up‐regulations of 188 and the down‐regulations of 92 genes common to both cell lines following GW3965 treatment.Genes responsive to GW3965 represent a variety of biological pathways vital for multiple cellular functions.Specifically,we identified that the activating transcription factor 4/thioredoxin‐interacting protein/regulated in development and DNA damage responses 1/mechanistic target of rapamycin(ATF4/TXNIP/REDD1/mTOR)signaling critically controls GW3965‐mediated regulation of cell proliferation/death.The significance of the ATF4/TXNIP/REDD1/mTOR pathway was further supported by associated expressions in xenograft tumors as well as human pancreatic cancer samples.Conclusions:This study provides the pre‐clinical evidence that LXR agonist is a promising therapy for pancreatic cancer.展开更多
Background: The effect of adrenal replacement therapy (ART) with hydrocortisone on critical endpoints such as infection and mortality in critically ill patients with cirrhosis remains unclear. We evaluated our indicat...Background: The effect of adrenal replacement therapy (ART) with hydrocortisone on critical endpoints such as infection and mortality in critically ill patients with cirrhosis remains unclear. We evaluated our indications for ART in patients with cirrhosis with clinical symptoms of adrenal insufficiency (AI), and examined the rate of peri-transplant fungal colonization and mortality associated with ART. Methods: Seventy-eight patients with cirrhosis admitted to our institution's surgical intensive care unit (ICU) over a 4-year period met criteria for AI by vasopressor requirement and baseline cortisol levels. Outcomes included disposition at 90-days, fungal colonization, and fungal infection in the presence or absence of ART. Results: In total, 56 patients received hydrocortisone (HC+) while 22 did not (HC-). The HC+ and HC- groups had comparable median Model for End-stage Liver Disease (MELD) scores (26.5 vs. 25, respectively;p=0.93), median ICU lengths of stay (23 vs. 20 days, respectively;p=0.54) and median cortisol levels (18μg/dL for both, p=0.87). Fungal cultures (FC) from blood, urine or bronchoalveolar lavage/sputum were positive for 44% of HC+, and 40.9%of HC-(p=0.77) had mortality rates between HC+and HC-groups that were not significantly different (60.7%vs. 50%, respectively;p=0.39;α=0.05). The 90-day outcomes for HC+ vs. HC- (39.3% vs. 50% discharged, respectively;p=0.39;α=0.05) and those surviving to transplant (17.9%vs. 36.4%, respectively;p=0.08;α=0.05) were not signifi-cantly different between the two groups.Conclusion:In this small single-center series, we found that steroid administration for AI does not affect the rate of fungal colonization/infection or mortality. Further prospective stu-dies are required to determine the utility of ART and factors affecting the rate of FC and mortality in these patients.展开更多
文摘Dear editor,The scarcity of routinemetastatic biopsies or resection limits the finding of biomarkers of diagnosis and prognosis in patients with brain metastases.Derived from necrosis,apoptosis,and secretion of tumor cells,circulating tumor DNA(ctDNA)is widely distributed in various body fluids,including peripheral blood and cerebrospinal fluid(CSF),as an alternative biomarker for tumor-associated analysis[1].Fortunately,genomic alterations of blood ctDNA and CSF ctDNA have been proven as prognostic markers in non-small cell lung cancer(NSCLC)patients with brain metastasis[2,3].
基金supported by the Science and Technology Project of Beijing (No. D161100000216001)the National Science Foundation of China (No. 41672227)
文摘Because of its high adsorption capacity, biochar has been used to stabilize metals when remediating contaminated soils; to date, however, it has seldom been used to remediate contaminated sediment. A biochar was used as a stabilization agent to remediate Cu-and Pb-contaminated sediments, collected from three locations in or close to Beijing. The sediments were mixed with a palm sawdust gasified biochar at a range of weight ratios(2.5%, 5%, and 10%) and incubated for 10, 30, or 60 days. The performance of the different treatments and the heavy metal fractions in the sediments were assessed using four extraction methods, including diffusive gradients in thin films, the porewater concentration, a sequential extraction, and the toxicity characteristic leaching procedure. The results showed that biochar could enhance the stability of heavy metals in contaminated sediments. The degree of stability increased as both the dose of biochar and the incubation time increased. The sediment p H and the morphology of the metal crystals adsorbed onto the biochar changed as the contact time increased. Our results showed that adsorption,metal crystallization, and the p H were the main controls on the stabilization of metals in contaminated sediment by biochar.
基金supported by the National Scientific Foundation of China(No.41672227).
文摘Petroleum hydrocarbons,mainly consisting of n-alkanes and polycyclic aromatic hydrocarbons(PAHs),are considered as priority pollutants and biohazards in the environment,eventually affecting the ecosystem and human health.Though many previous studies have investigated the change of bacterial community and alkane degraders during the degradation of petroleum hydrocarbons,there is still lack of understanding on the impacts of soil alkane contamination level.In the present study,microcosms with different n-alkane contamination(1%,3%and 5%)were set up and our results indicated a complete alkane degradation after 30 and 50 days in 1%-and 3%-alkane treatments,respectively.In all the treatments,alkanes with medium-chain length(C_(11)-C_(14))were preferentially degraded by soil microbes,followed by C27-alkane in 3%and 5%treatments.Alkane contamination level slightly altered soil bacterial community,and the main change was the presence and abundance of dominant alkane degraders.Thermogemmatisporaceae,Gemmataceae and Thermodesulfovibrionaceae were highly related to the degradation of C_(14)-and C_(27)-alkanes in 5%treatment,but linked to alkanes with medium-chain(C11-C18)in 1%treatment and C21-alkane in 3%treatment,respectively.Additionally,we compared the abundance of three alkane-monooxygenase genes,e.g.,alk_A,alk_P and alk_R.The abundance of alk_R gene was highest in soils,and alk_P gene was more correlated with alkane degradation efficiency,especially in 5%treatment.Our results suggested that alkane contamination level showed non-negligible effects on soil bacterial communities to some extents,and particularly shaped alkane degraders and degrading genes significantly.This study provides a better understanding on the response of alkane degraders and bacterial communities to soil alkane concentrations,which affects their biodegradation process.
基金National Natural Science Foundation of China,Grant/Award Numbers:81270868,81472692,81573012。
文摘Background:Limited by difficulties in early detection and availabilities of effective treatments,pancreatic cancer is a highly malignant disease with poor prognosis.Nuclear receptors are a family of ligand‐dependent transcription factors that are highly druggable therapeutic targets playing critical roles in human physiological and pathological development,including cancer.In this study,we explored the therapeutic potential as well as the molecular mechanisms of liver X receptor(LXR)agonist GW3965 in pancreatic cancer.Methods:Soft‐agar colony formation assay,xenograft tumors,Oligonucleotide microarray,Reverse transcription real‐time polymerase chain reaction,Western immunoblotting and Immunohistochemistry were used in this study.Results:We demonstrated pleotropic in vitro activities of GW3965 in pancreatic cell lines MIA PaCa‐2 and BXPC3 including reduction of cell viability,inhibition of cell proliferation,stimulation of cell death,and suppression of colony formation,which translated to significant inhibition of xenograft tumor growth in vitro.By mapping the gene expression profiles,we identified the up‐regulations of 188 and the down‐regulations of 92 genes common to both cell lines following GW3965 treatment.Genes responsive to GW3965 represent a variety of biological pathways vital for multiple cellular functions.Specifically,we identified that the activating transcription factor 4/thioredoxin‐interacting protein/regulated in development and DNA damage responses 1/mechanistic target of rapamycin(ATF4/TXNIP/REDD1/mTOR)signaling critically controls GW3965‐mediated regulation of cell proliferation/death.The significance of the ATF4/TXNIP/REDD1/mTOR pathway was further supported by associated expressions in xenograft tumors as well as human pancreatic cancer samples.Conclusions:This study provides the pre‐clinical evidence that LXR agonist is a promising therapy for pancreatic cancer.
文摘Background: The effect of adrenal replacement therapy (ART) with hydrocortisone on critical endpoints such as infection and mortality in critically ill patients with cirrhosis remains unclear. We evaluated our indications for ART in patients with cirrhosis with clinical symptoms of adrenal insufficiency (AI), and examined the rate of peri-transplant fungal colonization and mortality associated with ART. Methods: Seventy-eight patients with cirrhosis admitted to our institution's surgical intensive care unit (ICU) over a 4-year period met criteria for AI by vasopressor requirement and baseline cortisol levels. Outcomes included disposition at 90-days, fungal colonization, and fungal infection in the presence or absence of ART. Results: In total, 56 patients received hydrocortisone (HC+) while 22 did not (HC-). The HC+ and HC- groups had comparable median Model for End-stage Liver Disease (MELD) scores (26.5 vs. 25, respectively;p=0.93), median ICU lengths of stay (23 vs. 20 days, respectively;p=0.54) and median cortisol levels (18μg/dL for both, p=0.87). Fungal cultures (FC) from blood, urine or bronchoalveolar lavage/sputum were positive for 44% of HC+, and 40.9%of HC-(p=0.77) had mortality rates between HC+and HC-groups that were not significantly different (60.7%vs. 50%, respectively;p=0.39;α=0.05). The 90-day outcomes for HC+ vs. HC- (39.3% vs. 50% discharged, respectively;p=0.39;α=0.05) and those surviving to transplant (17.9%vs. 36.4%, respectively;p=0.08;α=0.05) were not signifi-cantly different between the two groups.Conclusion:In this small single-center series, we found that steroid administration for AI does not affect the rate of fungal colonization/infection or mortality. Further prospective stu-dies are required to determine the utility of ART and factors affecting the rate of FC and mortality in these patients.
