There are well-established chemical and turbidity anomalies in the plumes occurring vicinity of hydrothermal vents, which are used to indicate their existence and locations. We here develop a small, accurate multi-cha...There are well-established chemical and turbidity anomalies in the plumes occurring vicinity of hydrothermal vents, which are used to indicate their existence and locations. We here develop a small, accurate multi-channel chemical sensor to detect such anomalies which can be used in deep-sea at depths of more than 4 000 m. The design allowed five all-solid-state electrodes to be mounted on it and each (apart from one reference electrode) could be changed according to chemicals to be measured. Two experiments were conducted using the chemical sensors. The first was a shallow-sea trial which included sample measurements and in situ monitoring. pH, Eh, CO3^2- and SO4^2- electrodes were utilized to demonstrate that the chemical sensor was accurate and stable outside the laboratory. In the second experiment, the chemical sensor was integrated with pH, Eh, CO3^2- and H2S electrodes, and was used in 29 scans of the seabed along the Southwest Indian Ridge (SWIR) to detect hydrothermal vents, from which 27 sets of valid data were obtained. Hydrothermal vents were identified by analyzing the chemical anomalies, the primary judging criteria were decreasing voltages of Eh and H2S, matched by increasing voltages of pH and CO3^2- . We proposed that simultaneous detection of changes in these parameters will indicate a hydrothermal vent. Amongst the 27 valid sets of data, five potential hydrothermal vents were targeted using the proposed method. We suggest that our sensors could be widely employed by marine scientists.展开更多
BACKGROUND Although minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)have been described as two separate forms of nephrotic syndrome(NS),they are not completely independent.We report a case of a ...BACKGROUND Although minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)have been described as two separate forms of nephrotic syndrome(NS),they are not completely independent.We report a case of a patient transitioning from MCD to FSGS,review the literature,and explore the relationship between the two diseases.CASE SUMMARY A 42-year-old male welder,presenting with lower extremity edema and elevated serum creatinine,was diagnosed with NS and end-stage kidney disease(ESKD)based on laboratory test results.The patient had undergone a kidney biopsy for NS 20 years previously,which indicated MCD,and a second recent kidney biopsy suggested FSGS.The patient was an electric welder with excessive levels of cadmium and lead in his blood.Consequently,we suspect that his aggravated pathology and occurrence of ESKD were related to metal nephrotoxicity.The patient eventually received kidney replacement therapy and quit his job which involved long-term exposure to metals.During the 1-year follow-up period,the patient was negative for metal elements in the blood and urine and recovered partial kidney function.CONCLUSION MCD and FSGS may be different stages of the same disease.The transition from MCD to FSGS in this case indicates disease progression,which may be related to excessive metal contaminants caused by the patient’s occupation.展开更多
The QRS-T angle,as an index of noninvasive cardioelectric vector,is closely related to the change of heart structure and function.There are different methedologies to measure the QRS-T angle,which can be roughly divid...The QRS-T angle,as an index of noninvasive cardioelectric vector,is closely related to the change of heart structure and function.There are different methedologies to measure the QRS-T angle,which can be roughly dividedinto two types:plane angle and space angle.Studies show that the influence factors include two aspects of physiology and pathology of the angle,in pathological ways,the disease such as myocardial hypertrophy,myocardial ischemia,hypertension,ventricular arrhythmia has larger clinical significance.In recent years,the research on the risk stratification of the QRS-T angle on sudden death has made great progress,but there are still some disputes about whether the space angle can be replaced by the plane angle and the range of normal value and so on.展开更多
CUDC-101,an effective and multi-target inhibitor of epidermal growth factor receptor(EGFR),histone deacetylase(HDAC),and human epidermal growth factor receptor 2(HER2),has been reported to inhibit many kinds of cancer...CUDC-101,an effective and multi-target inhibitor of epidermal growth factor receptor(EGFR),histone deacetylase(HDAC),and human epidermal growth factor receptor 2(HER2),has been reported to inhibit many kinds of cancers,such as acute promyelocytic leukemia and non-Hodgkin's lymphoma.However,no studies have yet investigated whether CUDC-101 is effective against myeloma.Herein,we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma(MM)cell lines and induces cell apoptosis in a time-and dose-dependent manner.Moreover,CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase(PI3K)and HDAC,and regulated the cell cycle G2/M arrest.Moreover,we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug.Bortezomib is one of the important drugs in MM treatment,and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib.The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade.Collectively,our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib,which provides insights into exploring new strategies for MM treatment.展开更多
Tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive. The identi?cation of protein molecules with their expre...Tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive. The identi?cation of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clini- cal management of cancer. Proteomics is a systematic research approach aiming to provide the global characterization of protein expression and function under given conditions. Proteomic technology has been widely used in biomarker discovery and pathogenetic studies including tumor metastasis. This article provides a brief review of the application of proteomics in identifying molecular factors in tumor metastasis process. The combination of proteomics with other experimental ap- proaches in biochemistry, cell biology, molecular genetics and chemistry, together with the development of new technologies and improvements in existing method- ologies will continue to extend its application in studying cancer metastasis.展开更多
Recycling of carbon dioxide(CO_2) into fuels and chemicals is a potential approach to reduce CO_2 emission and fossil-fuel consumption. Autotrophic microbes can utilize energy from light, hydrogen, or sulfur to assimi...Recycling of carbon dioxide(CO_2) into fuels and chemicals is a potential approach to reduce CO_2 emission and fossil-fuel consumption. Autotrophic microbes can utilize energy from light, hydrogen, or sulfur to assimilate atmospheric CO_2 into organic compounds at ambient temperature and pressure. This provides a feasible way for biological production of fuels and chemicals from CO_2 under normal conditions. Recently great progress has been made in this research area, and dozens of CO_2-derived fuels and chemicals have been reported to be synthesized by autotrophic microbes. This is accompanied by investigations into natural CO_2-fixation pathways and the rapid development of new technologies in synthetic biology. This review first summarizes the six natural CO_2-fixation pathways reported to date, followed by an overview of recent progress in the design and engineering of CO_2-fixation pathways as well as energy supply patterns using the concept and tools of synthetic biology. Finally, we will discuss future prospects in biological fixation of CO_2.展开更多
Development of controllable hypermutable cells can greatly benefit understanding and harnessing microbial evolution.However,there have not been any similar sys-tems developed for Clostridium,an important bacterial gen...Development of controllable hypermutable cells can greatly benefit understanding and harnessing microbial evolution.However,there have not been any similar sys-tems developed for Clostridium,an important bacterial genus.Here we report a novel two-step strategy for de-veloping controllable hypermutable cells of Clostridium acetobutylicum,an important and representative indus-trial strain.Firstly,the mutS/L operon essential for methyl-directed mismatch repair(MMR)activity was inactivated from the genome of C.acetobutylicum to generate hy-permutable cells with over 250-fold increased mutation rates.Secondly,a proofreading control system carrying an inducibly expressed mutS/L operon was constructed.The hypermutable cells and the proofreading control system were integrated to form a controllable hypermut-able system SMBMutC,of which the mutation rates can be regulated by the concentration of anhydrotetracycline(aTc).Duplication of the miniPthl-tetR module of the proof-reading control system further signifi cantly expanded the regulatory space of the mutation rates,demonstrating hypermutable Clostridium cells with controllable mutation rates are generated.The developed C.acetobutylicum strain SMBMutC2 showed higher survival capacities than the control strain facing butanol-stress,indicating greatly increased evolvability and adaptability of the controllable hypermutable cells under environmental challenges.展开更多
Cytokines are secreted by various cell types and act as critical mediators in many physiological processes,including immune response and tumor progression.Cytokines production is precisely and timely regulated by mult...Cytokines are secreted by various cell types and act as critical mediators in many physiological processes,including immune response and tumor progression.Cytokines production is precisely and timely regulated by multiple mechanisms at different levels,ranging from transcriptional to post-transcriptional and posttranslational processes.Monocyte chemoattractant protein-1 induced protein 1(MCPIP1),a potent immunosuppressive protein,was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1(MCP-1)and subsequently found to possess intrinsic RNase and deubiquitinase activities.MCPIP1 tightly regulates cytokines expression via various functions.Furthermore,cytokines such as interleukin 1 beta(IL-1B)and MCP-1 and inflammatory cytokines inducer lipopolysaccharide(LPS)strongly induce MCPIP1 expression.Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment.In this review,we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.展开更多
MM(multiple myeloma)accounts for about 10%of hematological malignancies and 1%of cancer.IgD myeloma is a rare type of MM.It was reported that IgD type accounts for about 1%to 2%of all patients with MM abroad,while 3%t...MM(multiple myeloma)accounts for about 10%of hematological malignancies and 1%of cancer.IgD myeloma is a rare type of MM.It was reported that IgD type accounts for about 1%to 2%of all patients with MM abroad,while 3%to 8.9%in domestic cases.^(1) This immunoglobulin protein was first discovered by Dr.Rowe and Fahey in 1965.^(2) Half of a century had passed,the management of IgD MM remains a challenging field.展开更多
Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclona...Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins(M protein),leading to bone destruction,hypercalcemia,anemia,and renal insufficiency(Alexandrakis et al.,2015;Yang et al.,2018).Since a large number of new drugs,represented by proteasome inhibitors and immunomodulators,have been successfullyused to treat MM.展开更多
This paper briefly introduces the core concepts and major contents of the urban design and planning for the Jiangbei CBD in Chongqing. It presents some important methods and ideas for overall urban design from empiric...This paper briefly introduces the core concepts and major contents of the urban design and planning for the Jiangbei CBD in Chongqing. It presents some important methods and ideas for overall urban design from empirical perspectives, so as to provide certain references and experiences to similar urban design and planning projects.展开更多
基金The Open Foundation of Laboratory of Marine Ecosystem and Biogeochemistry,SOA under contract No.LMEB201701
文摘There are well-established chemical and turbidity anomalies in the plumes occurring vicinity of hydrothermal vents, which are used to indicate their existence and locations. We here develop a small, accurate multi-channel chemical sensor to detect such anomalies which can be used in deep-sea at depths of more than 4 000 m. The design allowed five all-solid-state electrodes to be mounted on it and each (apart from one reference electrode) could be changed according to chemicals to be measured. Two experiments were conducted using the chemical sensors. The first was a shallow-sea trial which included sample measurements and in situ monitoring. pH, Eh, CO3^2- and SO4^2- electrodes were utilized to demonstrate that the chemical sensor was accurate and stable outside the laboratory. In the second experiment, the chemical sensor was integrated with pH, Eh, CO3^2- and H2S electrodes, and was used in 29 scans of the seabed along the Southwest Indian Ridge (SWIR) to detect hydrothermal vents, from which 27 sets of valid data were obtained. Hydrothermal vents were identified by analyzing the chemical anomalies, the primary judging criteria were decreasing voltages of Eh and H2S, matched by increasing voltages of pH and CO3^2- . We proposed that simultaneous detection of changes in these parameters will indicate a hydrothermal vent. Amongst the 27 valid sets of data, five potential hydrothermal vents were targeted using the proposed method. We suggest that our sensors could be widely employed by marine scientists.
文摘BACKGROUND Although minimal change disease(MCD)and focal segmental glomerulosclerosis(FSGS)have been described as two separate forms of nephrotic syndrome(NS),they are not completely independent.We report a case of a patient transitioning from MCD to FSGS,review the literature,and explore the relationship between the two diseases.CASE SUMMARY A 42-year-old male welder,presenting with lower extremity edema and elevated serum creatinine,was diagnosed with NS and end-stage kidney disease(ESKD)based on laboratory test results.The patient had undergone a kidney biopsy for NS 20 years previously,which indicated MCD,and a second recent kidney biopsy suggested FSGS.The patient was an electric welder with excessive levels of cadmium and lead in his blood.Consequently,we suspect that his aggravated pathology and occurrence of ESKD were related to metal nephrotoxicity.The patient eventually received kidney replacement therapy and quit his job which involved long-term exposure to metals.During the 1-year follow-up period,the patient was negative for metal elements in the blood and urine and recovered partial kidney function.CONCLUSION MCD and FSGS may be different stages of the same disease.The transition from MCD to FSGS in this case indicates disease progression,which may be related to excessive metal contaminants caused by the patient’s occupation.
文摘The QRS-T angle,as an index of noninvasive cardioelectric vector,is closely related to the change of heart structure and function.There are different methedologies to measure the QRS-T angle,which can be roughly dividedinto two types:plane angle and space angle.Studies show that the influence factors include two aspects of physiology and pathology of the angle,in pathological ways,the disease such as myocardial hypertrophy,myocardial ischemia,hypertension,ventricular arrhythmia has larger clinical significance.In recent years,the research on the risk stratification of the QRS-T angle on sudden death has made great progress,but there are still some disputes about whether the space angle can be replaced by the plane angle and the range of normal value and so on.
基金supported by the National Natural Science Foundation of China(Nos.81872322,81900209,and 82100213)the Zhejiang Key Research and Development Project(No.2020C03014)。
文摘CUDC-101,an effective and multi-target inhibitor of epidermal growth factor receptor(EGFR),histone deacetylase(HDAC),and human epidermal growth factor receptor 2(HER2),has been reported to inhibit many kinds of cancers,such as acute promyelocytic leukemia and non-Hodgkin's lymphoma.However,no studies have yet investigated whether CUDC-101 is effective against myeloma.Herein,we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma(MM)cell lines and induces cell apoptosis in a time-and dose-dependent manner.Moreover,CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase(PI3K)and HDAC,and regulated the cell cycle G2/M arrest.Moreover,we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug.Bortezomib is one of the important drugs in MM treatment,and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib.The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade.Collectively,our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib,which provides insights into exploring new strategies for MM treatment.
基金supported by Hong Kong Research Grants Council Grants HKU 7227/02M(to Q.Y.H.),HKU 7218/02M and HKU 7395/03M(toJ.F.C.)the Department of Chemistry,and the Areasof Excellence scheme of Hong Kong University GrantsCommittee
文摘Tumor metastasis is the dominant cause of death in cancer patients. However, the molecular and cellular mechanisms underlying tumor metastasis are still elusive. The identi?cation of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clini- cal management of cancer. Proteomics is a systematic research approach aiming to provide the global characterization of protein expression and function under given conditions. Proteomic technology has been widely used in biomarker discovery and pathogenetic studies including tumor metastasis. This article provides a brief review of the application of proteomics in identifying molecular factors in tumor metastasis process. The combination of proteomics with other experimental ap- proaches in biochemistry, cell biology, molecular genetics and chemistry, together with the development of new technologies and improvements in existing method- ologies will continue to extend its application in studying cancer metastasis.
基金We are grateful to Miao Chen, Qiangguo Gao and Yiqi Liu （Second Military Medical University, Shanghai, China） for technical support and offer special thanks to Professor Qing Yi （M.D. Anderson Cancer Center Houston, TX, USA） for helpful guidance in the experiments. We thank Shizuo Akira （Osaka University, Osaka, Japan） for originally providing key mouse strains. This work was supported by grants of the National Natural Science Foundation of China （no. 30772502 and 30973455）, Zhejiang Major Medical and the Health Science and Technology ＆ Ministry of Health of the Chinese Government （no. WKJ2009-2-022）. This work was also supported by the Major Research Plan of the Chinese National Natural Science Foundation （no. 91029740）, Zhejiang Province Science and Technology Department Foundation （no. 2009C03012-2） and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents.
基金supported by the National Basic Research Program of China(31470231)National Natural Science Foundation of China(21106175)
文摘Recycling of carbon dioxide(CO_2) into fuels and chemicals is a potential approach to reduce CO_2 emission and fossil-fuel consumption. Autotrophic microbes can utilize energy from light, hydrogen, or sulfur to assimilate atmospheric CO_2 into organic compounds at ambient temperature and pressure. This provides a feasible way for biological production of fuels and chemicals from CO_2 under normal conditions. Recently great progress has been made in this research area, and dozens of CO_2-derived fuels and chemicals have been reported to be synthesized by autotrophic microbes. This is accompanied by investigations into natural CO_2-fixation pathways and the rapid development of new technologies in synthetic biology. This review first summarizes the six natural CO_2-fixation pathways reported to date, followed by an overview of recent progress in the design and engineering of CO_2-fixation pathways as well as energy supply patterns using the concept and tools of synthetic biology. Finally, we will discuss future prospects in biological fixation of CO_2.
基金the National Natural Science Foundation of China(Grant No.31270107)the National Basic Research Program of China(973 Program)(No.2011CBA00800)+1 种基金the National High Technology Research and Development Program(863 Program)(No.2011AA02A208)the Knowledge Innovation Program of the Chinese Acad-emy of Sciences(No.KSCX2-EW-Q-14).
文摘Development of controllable hypermutable cells can greatly benefit understanding and harnessing microbial evolution.However,there have not been any similar sys-tems developed for Clostridium,an important bacterial genus.Here we report a novel two-step strategy for de-veloping controllable hypermutable cells of Clostridium acetobutylicum,an important and representative indus-trial strain.Firstly,the mutS/L operon essential for methyl-directed mismatch repair(MMR)activity was inactivated from the genome of C.acetobutylicum to generate hy-permutable cells with over 250-fold increased mutation rates.Secondly,a proofreading control system carrying an inducibly expressed mutS/L operon was constructed.The hypermutable cells and the proofreading control system were integrated to form a controllable hypermut-able system SMBMutC,of which the mutation rates can be regulated by the concentration of anhydrotetracycline(aTc).Duplication of the miniPthl-tetR module of the proof-reading control system further signifi cantly expanded the regulatory space of the mutation rates,demonstrating hypermutable Clostridium cells with controllable mutation rates are generated.The developed C.acetobutylicum strain SMBMutC2 showed higher survival capacities than the control strain facing butanol-stress,indicating greatly increased evolvability and adaptability of the controllable hypermutable cells under environmental challenges.
基金This work was supported by the Funds for the National Natural Science Foundation of China(Grant No.81700201)Zhejiang Key Research and Development Project(2020C03014)National Major Scientific and Tech no logical Special Project for"Sig nifica nt New Drug Development"(2018ZX09733-003).
文摘Cytokines are secreted by various cell types and act as critical mediators in many physiological processes,including immune response and tumor progression.Cytokines production is precisely and timely regulated by multiple mechanisms at different levels,ranging from transcriptional to post-transcriptional and posttranslational processes.Monocyte chemoattractant protein-1 induced protein 1(MCPIP1),a potent immunosuppressive protein,was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1(MCP-1)and subsequently found to possess intrinsic RNase and deubiquitinase activities.MCPIP1 tightly regulates cytokines expression via various functions.Furthermore,cytokines such as interleukin 1 beta(IL-1B)and MCP-1 and inflammatory cytokines inducer lipopolysaccharide(LPS)strongly induce MCPIP1 expression.Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment.In this review,we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.
基金This work has been supported by the National Natural Science Foundation of China(81900209,81800202)Natural Science Foundation of Zhejiang Province(LY17H080001).
文摘MM(multiple myeloma)accounts for about 10%of hematological malignancies and 1%of cancer.IgD myeloma is a rare type of MM.It was reported that IgD type accounts for about 1%to 2%of all patients with MM abroad,while 3%to 8.9%in domestic cases.^(1) This immunoglobulin protein was first discovered by Dr.Rowe and Fahey in 1965.^(2) Half of a century had passed,the management of IgD MM remains a challenging field.
基金the National Natural Science Foundation of China(Nos.81800201 and 81872322)the Zhejiang Key Research and Development Project(No.2020C03014)the Key Project of Zhejiang Provincial Natural Science Foundation of China(No.LZ22H160009)。
文摘Multiple myeloma(MM)is a common malignant hematological tumor in adults,which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins(M protein),leading to bone destruction,hypercalcemia,anemia,and renal insufficiency(Alexandrakis et al.,2015;Yang et al.,2018).Since a large number of new drugs,represented by proteasome inhibitors and immunomodulators,have been successfullyused to treat MM.
文摘This paper briefly introduces the core concepts and major contents of the urban design and planning for the Jiangbei CBD in Chongqing. It presents some important methods and ideas for overall urban design from empirical perspectives, so as to provide certain references and experiences to similar urban design and planning projects.
