为揭示云南两个品种基于六堡茶工艺加工后的茶叶的香气成分,探讨较为合适制作六堡茶的茶树品种,采用顶空固相微萃取-气相色谱-质谱联用技术(Headspace Solid-Phase Micro Extraction and Gas Chromatography Mass Spectrometry,HS-SPME-...为揭示云南两个品种基于六堡茶工艺加工后的茶叶的香气成分,探讨较为合适制作六堡茶的茶树品种,采用顶空固相微萃取-气相色谱-质谱联用技术(Headspace Solid-Phase Micro Extraction and Gas Chromatography Mass Spectrometry,HS-SPME-GC/MS),结合相对香气活度值(Relative Odor Activity Value,ROAV)法分析云南两个品种茶叶渥堆发酵的挥发性成分。结果表明,共检测出152种挥发性成分,以醇类、酯类挥发性成分种类为主,以芳樟醇、月桂烯醇、壬醛、二氢猕猴桃内酯、亚麻酸甲酯和棕榈酸甲酯相对含量较高。ROAV贡献值分析结果显示:两个品种加工过程中主要香气贡献挥发性成分有19种,两个样品显著(P<0.05)贡献的香气化合物包括苯甲醇、癸醛、壬醛、α-紫罗酮、1-辛烯-3-醇、雪松醇、芳樟醇、反式-芳樟醇氧化物(呋喃型)。壬醛、癸醛、β-紫罗兰酮等3种挥发性有机化合物对云抗10号(Y6)陈香的形成具有较大贡献,α-雪松醇、长叶蒎烯、β-柏木烯、右旋萜二烯、α-紫罗酮等5种挥发性有机化合物对黑龙潭群体种(H6)陈香透参香的形成具有较大贡献。本研究从香气成分的角度明确了云抗10号、黑龙潭群体种均适合作为六堡茶原料,其中黑龙潭群体种在感官审评、关键香气成分种类和含量都高于云抗10号,因此黑龙潭群体种相较于云抗10号更适合做六堡茶。展开更多
Background:Depression is a common,easily ignored,accompanied disease of gastric cancer(GC)patients and is often observed with elevated plasma catecholamine levels.Depression frequently promotes GC progression and lead...Background:Depression is a common,easily ignored,accompanied disease of gastric cancer(GC)patients and is often observed with elevated plasma catecholamine levels.Depression frequently promotes GC progression and leads to poor clinical outcomes;however,the molecular mechanisms underlying depression-induced GC progression remain poorly understood.We aimed to study the effects of depression on GC progression and explore possible mechanisms mediating the action of depression-associated catecholamines on GC.Methods:Depression states of GC patients were graded using the Patient Health Questionnaire-9,and plasma catecholamine levels were examined by high performance liquid chromatography coupled with tandem mass spectrometry.Migrative and invasive GC cells were examined using transwell assays,and metastatic GC niches were imaged using bioluminescence technology in a depression mouse model established with chronic unpredictable mild stress.Mouse depression-like behaviors were assessed through sucrose preference,forced swimming,and tail suspension tests.Characteristics of the neuroendocrine phenotype were observed via RT-PCR,Western blotting,flow cytometry,and transmission electron microscopy.Results:Fifty-one GC patients(age:53.61±1.79 years;cancer duration:3.71±0.33 months;depression duration:2.37±0.38 months;male-to-female ratio:1.55:1)were enrolled in the study.Depression grade was significantly higher in GC patients showing higher plasma levels of catecholamines(epinephrine:P=0.018;noradrenaline:P=0.009),higher oncogene metastasis-associated in colon cancer-1(MACC1)level(P=0.018),and metastasis(P<0.001).Further,depression-associated catecholamine specifically bound to the beta-2 adrenergic receptor(β_(2)-AR)and upregulated MACC1 expression,and thus promoting neuroendocrine phenotypic transformation through direct binding betweenMACC1 and synaptophysin.Eventually,the neuroendocrine phenotypic transformation accelerated GC invasion in vitro and metastasis in vivo.However,β_(2)-AR antagonist ICI-118,551 or MACC1 s展开更多
Background:Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2(HER2)-positive gastric cancer.However,the inevitable occurrence of acquired trastuzumab resistance limits the drug b...Background:Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2(HER2)-positive gastric cancer.However,the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit,and there is currently no effective reversal measure.Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves,while the understanding of the mechanisms of environment-mediated drug resistance is relatively lacking.This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients.Methods:Trastuzumab-sensitive and trastuzumab-resistant HER2-positive tumor tissues and cells were collected for transcriptome sequencing.Bioinformatics were used to analyze cell subtypes,metabolic pathways,and molecular signaling pathways.Changes in microenvironmental indicators(such as macrophage,angiogenesis,and metabolism)were verified by immunofluorescence(IF)and immunohistochemical(IHC)analyses.Finally,a multi-scale agent-based model(ABM)was constructed.The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM.Results:Based on transcriptome sequencing,molecular biology,and in vivo experiments,we found that the level of glutamine metabolism in trastuzumabresistant HER2-positive cells was increased,and glutaminase 1(GLS1)was significantly overexpressed.Meanwhile,tumor-derived GLS1 microvesicles drove M2macrophage polarization.Furthermore,angiogenesis promoted trastuzumab resistance.IHC showed high glutamine metabolism,M2 macrophage polarization,and angiogenesis in trastuzumab-resistant HER2-positive tumor tissues from patients and nudemice.Mechanistically,the cell division cycle 42(CDC42)promoted GLS1 expression in tumor cells by activating nuclear factor kappa-B(NF-κB)p65 and drove GLS1microvesicle secretion through IQmotif-containing GTPase-activating protein 1(IQGAP1).Based on the ABM and in vivo experiments,we confirmed that the combi展开更多
电化学CO_(2)还原(CO_(2)RR)是一种很有前景的技术,可以将二氧化碳转化为多种增值化学品,从而达到减缓温室效应的目的.然而,实现目标产品的高催化活性、选择性和稳定性仍然是一个很大的挑战.本文通过还原Sn掺杂的Bi2S3制备了间隙掺杂的S...电化学CO_(2)还原(CO_(2)RR)是一种很有前景的技术,可以将二氧化碳转化为多种增值化学品,从而达到减缓温室效应的目的.然而,实现目标产品的高催化活性、选择性和稳定性仍然是一个很大的挑战.本文通过还原Sn掺杂的Bi2S3制备了间隙掺杂的Snx-Bi (x为Sn与Bi的原子比,x=1/2,1/16,1/24或1/40)纳米线束(NBs).值得注意的是,Sn1/24-Bi NBs在1400 mV的宽电位窗口内表现出超高的甲酸盐选择性(从-0.5到-1.9 V vs.可逆氢电极(RHE),法拉第效率超过90%),在-1.9 V vs.RHE时,电流密度达到了-319 mA cm^(-2),可满足工业使用需求.此外,还实现了在~-200 mA cm^(-2)条件下超过84 h的超长稳定性.实验结果和密度泛函理论计算表明,间隙掺杂Sn优化了*OCHO中间体的吸附亲和力,降低了铋催化剂的电子转移能垒,从而获得了显著的CO_(2)RR性能.本研究为设计具有优异催化活性、选择性和耐久性的掺杂型电催化剂用于CO_(2)RR为甲酸盐提供了启示.展开更多
Varicella-zoster virus(VZV)is a highly infectious agent responsible for both varicella and herpes zoster disease.Despite high efficacy,there remain safety and accessibility concerns with the licensed vaccines.Here,we ...Varicella-zoster virus(VZV)is a highly infectious agent responsible for both varicella and herpes zoster disease.Despite high efficacy,there remain safety and accessibility concerns with the licensed vaccines.Here,we sought to produce a VZV g E immunogen using an E.coli expression system.We found that the soluble expression and yield of g E protein could be enhanced via C-terminal truncations to the protein,thereby facilitating a robust and scalable purification process for the purpose of vaccine manufacturing.The lead truncated g E(aa 31–358),hereafter referred to as tg E,was a homogenous monomer in solution and showed excellent antigenicity.Finally,we assessed and compared the immunogenicity of tg E with commercial v Oka LAV and Shingrix vaccine.We found that aluminum-adjuvanted tg E was immunogenic as compared with v Oka LAV.When adjuvanted with AS01B,a two-dose immunization of tg E showed comparable or better potency in antibody responses and cell-mediated immunity with those of the Shingrix vaccine at the same dosage,especially in terms of the proportion of IFN-γ-expressing CD4^(+)T cells.In conclusion,this method of E.coli-mediate tg E expression offers a cost-effective and scalable strategy to generate an ideal VZV g E immunogen for the development of both varicella and zoster vaccines.展开更多
Background:Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor(ICI)treatment.This study aimed to uncover the specific mechanisms...Background:Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor(ICI)treatment.This study aimed to uncover the specific mechanisms underlying the difference in sensitivity to ICI treatment between tumors with high(HTB)and low(LTB)tumor burden.Methods:For in vivo studies,several mouse models of subcutaneous tumors were established,and transcriptome sequencing,immunohistochemistry,and flow cytometry assays were used to detect the immune status in these subcutaneous tumors.For in vitro experiments,co-culture models,cytokine antibody arrays,western blotting,flow cytometry,and enzyme-linked immunosorbent assays were used to explore the underlying molecular mechanisms Results:We found that MC38 or B16 subcutaneous tumors from the HTB group did not show any response to anti-programmed cell death protein-1(PD-1)therapy.Through flow cytometry assays,we found that the infiltration with CD8^(+)T cellswas significantly decreasedwhereasM2-like macrophageswere enriched in subcutaneous tumors of HTB groups compared with those of LTB group.These changes were not affected by the initial number of injected tumor cells or tumor age,nor could they be reversed by surgical tumor reduction.Intraperitoneal colony-stimulating factor 1 receptor(CSF-1R)inhibitor PLX3397 injection at different time points of tumor growth only had an effect when administered in the early tumor stage to maintain the“heat”of the tumor microenvironment during the process of tumor growth,thereby achieving a response to ICI treatment when the tumor grew to a large size.Mechanistically,we found that insulin-like growth factor binding protein 2(IGFBP2)expression levelswere significantly elevated in HTB tumor tissues.IGFBP2 promoted the programmed death-ligand 1(PD-L1)expression in M2-like macrophages by activating signal transducer and activator of transcription 3(STAT3),and PD-L1^(+)M2-likemacrophages exerted an immunosuppressive effect by inhibiting the proliferation and ac展开更多
随着我国医疗卫生事业的发展,优化和改进围手术期流程的“加速康复外科”(enhanced recovery after surgery,ERAS)应运而生。研究表明,应用ERAS可有效减轻患者创伤应激反应,缩短平均住院时间。作为ERAS的实施主体,医护人员只有掌握足够...随着我国医疗卫生事业的发展,优化和改进围手术期流程的“加速康复外科”(enhanced recovery after surgery,ERAS)应运而生。研究表明,应用ERAS可有效减轻患者创伤应激反应,缩短平均住院时间。作为ERAS的实施主体,医护人员只有掌握足够的ERAS理论知识,才能树立ERAS是于患者有益的理念,最终投身于ERAS的临床实践工作。因此,本文致力于描述国内外医护人员ERAS认知现状并分析其相关因素,以期推动ERAS在国内综合性医院的普及与应用,促进人民健康状况的改善。展开更多
Dear editor,The tumor microenvironment(TME)heavily impacts disease biology and may influence responses to systemic treatments,and thereby,affects patients’prognosis.In our previous study,we found that immune features...Dear editor,The tumor microenvironment(TME)heavily impacts disease biology and may influence responses to systemic treatments,and thereby,affects patients’prognosis.In our previous study,we found that immune features could predict prognosis and guide the therapy choices for stage I-III colon cancer[1,2].Increasing evidence shows that therapyinduced TME changes can promote tumor progression,metastasis,and the development of resistance[3,4].However,the TME dynamics in colorectal liver metastases(CRLM)under treatment are still incompletely clear.展开更多
文摘为揭示云南两个品种基于六堡茶工艺加工后的茶叶的香气成分,探讨较为合适制作六堡茶的茶树品种,采用顶空固相微萃取-气相色谱-质谱联用技术(Headspace Solid-Phase Micro Extraction and Gas Chromatography Mass Spectrometry,HS-SPME-GC/MS),结合相对香气活度值(Relative Odor Activity Value,ROAV)法分析云南两个品种茶叶渥堆发酵的挥发性成分。结果表明,共检测出152种挥发性成分,以醇类、酯类挥发性成分种类为主,以芳樟醇、月桂烯醇、壬醛、二氢猕猴桃内酯、亚麻酸甲酯和棕榈酸甲酯相对含量较高。ROAV贡献值分析结果显示:两个品种加工过程中主要香气贡献挥发性成分有19种,两个样品显著(P<0.05)贡献的香气化合物包括苯甲醇、癸醛、壬醛、α-紫罗酮、1-辛烯-3-醇、雪松醇、芳樟醇、反式-芳樟醇氧化物(呋喃型)。壬醛、癸醛、β-紫罗兰酮等3种挥发性有机化合物对云抗10号(Y6)陈香的形成具有较大贡献,α-雪松醇、长叶蒎烯、β-柏木烯、右旋萜二烯、α-紫罗酮等5种挥发性有机化合物对黑龙潭群体种(H6)陈香透参香的形成具有较大贡献。本研究从香气成分的角度明确了云抗10号、黑龙潭群体种均适合作为六堡茶原料,其中黑龙潭群体种在感官审评、关键香气成分种类和含量都高于云抗10号,因此黑龙潭群体种相较于云抗10号更适合做六堡茶。
文摘Background:Depression is a common,easily ignored,accompanied disease of gastric cancer(GC)patients and is often observed with elevated plasma catecholamine levels.Depression frequently promotes GC progression and leads to poor clinical outcomes;however,the molecular mechanisms underlying depression-induced GC progression remain poorly understood.We aimed to study the effects of depression on GC progression and explore possible mechanisms mediating the action of depression-associated catecholamines on GC.Methods:Depression states of GC patients were graded using the Patient Health Questionnaire-9,and plasma catecholamine levels were examined by high performance liquid chromatography coupled with tandem mass spectrometry.Migrative and invasive GC cells were examined using transwell assays,and metastatic GC niches were imaged using bioluminescence technology in a depression mouse model established with chronic unpredictable mild stress.Mouse depression-like behaviors were assessed through sucrose preference,forced swimming,and tail suspension tests.Characteristics of the neuroendocrine phenotype were observed via RT-PCR,Western blotting,flow cytometry,and transmission electron microscopy.Results:Fifty-one GC patients(age:53.61±1.79 years;cancer duration:3.71±0.33 months;depression duration:2.37±0.38 months;male-to-female ratio:1.55:1)were enrolled in the study.Depression grade was significantly higher in GC patients showing higher plasma levels of catecholamines(epinephrine:P=0.018;noradrenaline:P=0.009),higher oncogene metastasis-associated in colon cancer-1(MACC1)level(P=0.018),and metastasis(P<0.001).Further,depression-associated catecholamine specifically bound to the beta-2 adrenergic receptor(β_(2)-AR)and upregulated MACC1 expression,and thus promoting neuroendocrine phenotypic transformation through direct binding betweenMACC1 and synaptophysin.Eventually,the neuroendocrine phenotypic transformation accelerated GC invasion in vitro and metastasis in vivo.However,β_(2)-AR antagonist ICI-118,551 or MACC1 s
基金National Natural Science Foundation of China,Grant/Award Number:82073325。
文摘Background:Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2(HER2)-positive gastric cancer.However,the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit,and there is currently no effective reversal measure.Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves,while the understanding of the mechanisms of environment-mediated drug resistance is relatively lacking.This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients.Methods:Trastuzumab-sensitive and trastuzumab-resistant HER2-positive tumor tissues and cells were collected for transcriptome sequencing.Bioinformatics were used to analyze cell subtypes,metabolic pathways,and molecular signaling pathways.Changes in microenvironmental indicators(such as macrophage,angiogenesis,and metabolism)were verified by immunofluorescence(IF)and immunohistochemical(IHC)analyses.Finally,a multi-scale agent-based model(ABM)was constructed.The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM.Results:Based on transcriptome sequencing,molecular biology,and in vivo experiments,we found that the level of glutamine metabolism in trastuzumabresistant HER2-positive cells was increased,and glutaminase 1(GLS1)was significantly overexpressed.Meanwhile,tumor-derived GLS1 microvesicles drove M2macrophage polarization.Furthermore,angiogenesis promoted trastuzumab resistance.IHC showed high glutamine metabolism,M2 macrophage polarization,and angiogenesis in trastuzumab-resistant HER2-positive tumor tissues from patients and nudemice.Mechanistically,the cell division cycle 42(CDC42)promoted GLS1 expression in tumor cells by activating nuclear factor kappa-B(NF-κB)p65 and drove GLS1microvesicle secretion through IQmotif-containing GTPase-activating protein 1(IQGAP1).Based on the ABM and in vivo experiments,we confirmed that the combi
基金supported by the National Key Research and Development Program of China (2020YFA0710303)the National Natural Science Foundation of China (U1905215, 51672046, 51672047 and 22109025)+3 种基金the Scientific Research Foundation of Fuzhou University (510936)the support from the Fundamental Research Funds for the Central Universities (2020CDJQY-A072)the Venture and Innovation Support Program for Chongqing Overseas Returnees (cx2020107)the Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0945)。
文摘电化学CO_(2)还原(CO_(2)RR)是一种很有前景的技术,可以将二氧化碳转化为多种增值化学品,从而达到减缓温室效应的目的.然而,实现目标产品的高催化活性、选择性和稳定性仍然是一个很大的挑战.本文通过还原Sn掺杂的Bi2S3制备了间隙掺杂的Snx-Bi (x为Sn与Bi的原子比,x=1/2,1/16,1/24或1/40)纳米线束(NBs).值得注意的是,Sn1/24-Bi NBs在1400 mV的宽电位窗口内表现出超高的甲酸盐选择性(从-0.5到-1.9 V vs.可逆氢电极(RHE),法拉第效率超过90%),在-1.9 V vs.RHE时,电流密度达到了-319 mA cm^(-2),可满足工业使用需求.此外,还实现了在~-200 mA cm^(-2)条件下超过84 h的超长稳定性.实验结果和密度泛函理论计算表明,间隙掺杂Sn优化了*OCHO中间体的吸附亲和力,降低了铋催化剂的电子转移能垒,从而获得了显著的CO_(2)RR性能.本研究为设计具有优异催化活性、选择性和耐久性的掺杂型电催化剂用于CO_(2)RR为甲酸盐提供了启示.
基金supported by the National Key Research and Development Program of China(2021YFC2301404)the National Natural Science Foundation of China(81991490)+2 种基金the Industry-University-Academy Cooperation Program of Xiamen(2022CXY0107)the Principal Fund(20720220006 and 20720220004)CAMS Innovation Fund for Medical Sciences(2019RU022)。
文摘Varicella-zoster virus(VZV)is a highly infectious agent responsible for both varicella and herpes zoster disease.Despite high efficacy,there remain safety and accessibility concerns with the licensed vaccines.Here,we sought to produce a VZV g E immunogen using an E.coli expression system.We found that the soluble expression and yield of g E protein could be enhanced via C-terminal truncations to the protein,thereby facilitating a robust and scalable purification process for the purpose of vaccine manufacturing.The lead truncated g E(aa 31–358),hereafter referred to as tg E,was a homogenous monomer in solution and showed excellent antigenicity.Finally,we assessed and compared the immunogenicity of tg E with commercial v Oka LAV and Shingrix vaccine.We found that aluminum-adjuvanted tg E was immunogenic as compared with v Oka LAV.When adjuvanted with AS01B,a two-dose immunization of tg E showed comparable or better potency in antibody responses and cell-mediated immunity with those of the Shingrix vaccine at the same dosage,especially in terms of the proportion of IFN-γ-expressing CD4^(+)T cells.In conclusion,this method of E.coli-mediate tg E expression offers a cost-effective and scalable strategy to generate an ideal VZV g E immunogen for the development of both varicella and zoster vaccines.
基金National Natural Science Foundation of China,Grant/Award Numbers:82073303,82103335,82102731Science and Technology Planning Project of Guangzhou,Grant/Award Number:202201011560Natural Science Foundation of Guangdong Province of China,Grant/Award Number:2022A1515012418。
文摘Background:Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor(ICI)treatment.This study aimed to uncover the specific mechanisms underlying the difference in sensitivity to ICI treatment between tumors with high(HTB)and low(LTB)tumor burden.Methods:For in vivo studies,several mouse models of subcutaneous tumors were established,and transcriptome sequencing,immunohistochemistry,and flow cytometry assays were used to detect the immune status in these subcutaneous tumors.For in vitro experiments,co-culture models,cytokine antibody arrays,western blotting,flow cytometry,and enzyme-linked immunosorbent assays were used to explore the underlying molecular mechanisms Results:We found that MC38 or B16 subcutaneous tumors from the HTB group did not show any response to anti-programmed cell death protein-1(PD-1)therapy.Through flow cytometry assays,we found that the infiltration with CD8^(+)T cellswas significantly decreasedwhereasM2-like macrophageswere enriched in subcutaneous tumors of HTB groups compared with those of LTB group.These changes were not affected by the initial number of injected tumor cells or tumor age,nor could they be reversed by surgical tumor reduction.Intraperitoneal colony-stimulating factor 1 receptor(CSF-1R)inhibitor PLX3397 injection at different time points of tumor growth only had an effect when administered in the early tumor stage to maintain the“heat”of the tumor microenvironment during the process of tumor growth,thereby achieving a response to ICI treatment when the tumor grew to a large size.Mechanistically,we found that insulin-like growth factor binding protein 2(IGFBP2)expression levelswere significantly elevated in HTB tumor tissues.IGFBP2 promoted the programmed death-ligand 1(PD-L1)expression in M2-like macrophages by activating signal transducer and activator of transcription 3(STAT3),and PD-L1^(+)M2-likemacrophages exerted an immunosuppressive effect by inhibiting the proliferation and ac
文摘随着我国医疗卫生事业的发展,优化和改进围手术期流程的“加速康复外科”(enhanced recovery after surgery,ERAS)应运而生。研究表明,应用ERAS可有效减轻患者创伤应激反应,缩短平均住院时间。作为ERAS的实施主体,医护人员只有掌握足够的ERAS理论知识,才能树立ERAS是于患者有益的理念,最终投身于ERAS的临床实践工作。因此,本文致力于描述国内外医护人员ERAS认知现状并分析其相关因素,以期推动ERAS在国内综合性医院的普及与应用,促进人民健康状况的改善。
基金This work was supported by grants from the National Natural Science Foundation of China(81772580)Natural Science Foundation of Guangdong Province,China(2021A1515011705)the Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education(LC2016ZD014).
文摘Dear editor,The tumor microenvironment(TME)heavily impacts disease biology and may influence responses to systemic treatments,and thereby,affects patients’prognosis.In our previous study,we found that immune features could predict prognosis and guide the therapy choices for stage I-III colon cancer[1,2].Increasing evidence shows that therapyinduced TME changes can promote tumor progression,metastasis,and the development of resistance[3,4].However,the TME dynamics in colorectal liver metastases(CRLM)under treatment are still incompletely clear.
