Cancer is a global health problem and one of the leading causes of mortality.Immune checkpoint inhibitors have revolutionized the field of oncology,emerging as a powerful treatment strategy.A key pathway that has garn...Cancer is a global health problem and one of the leading causes of mortality.Immune checkpoint inhibitors have revolutionized the field of oncology,emerging as a powerful treatment strategy.A key pathway that has garnered considerable attention is programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1).The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body’s immune system.Furthermore,it controls the phenotype and functionality of innate and adaptive immune components.A range of monoclonal antibodies,including avelumab,atezolizumab,camrelizumab,dostarlimab,durvalumab,sinitilimab,toripalimab,and zimberelimab,have been developed for targeting the interaction between PD-1 and PD-L1.These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system.Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints.This could contribute to the existing arsenal of anticancer drugs.Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis,promoting tumor cell apoptosis,influencing cell proliferation,and eventually leading to tumor cell death and inhibiting cancer progression.However,there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer.Hence,this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules.Moreover,the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules.Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.展开更多
AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 m...AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.展开更多
The aromatic compounds,including o-xylene,m-xylene,p-xylene,and ethylbenzene,primarily originate from the catalytic reforming of crude oil,and have a wide variety of applications.However,because of similar physical an...The aromatic compounds,including o-xylene,m-xylene,p-xylene,and ethylbenzene,primarily originate from the catalytic reforming of crude oil,and have a wide variety of applications.However,because of similar physical and chemical properties,these compounds are difficult to be identified by gas chromatography(GC)without standard samples.With the development of modern nuclear magnetic resonance(NMR)techniques,NMR has emerged as a powerful and efficient tool for the rapid analysis of complex and crude mixtures without purification.In this study,the parameters of one-dimensional(1D)total correlation spectroscopy(TOCSY)NMR techniques,including 1D selective gradient TOCSY and 1D chemicalshift-selective filtration(CSSF)with TOCSY,were optimized to obtain comprehensive molecular structure information.The results indicate that the overlapped signals in NMR spectra of nonpolar aromatic compounds(including o-xylene,m-xylene,p-xylene and ethylbenzene),polar aromatic compounds(benzyl alcohol,benzaldehyde,benzoic acid),and aromatic compounds with additional conjugated bonds(styrene)can be resolved in 1D TOCSY.More importantly,full molecular structures can be clearly distinguished by setting appropriate mixing time in 1D TOCSY.This approach simplifies the NMR spectra,provides structural information of entire molecules,and can be applied for the analysis of other structural isomers.展开更多
目的系统评价复方苦参注射液联合程序性死亡受体1(programmed death receptor 1,PD-1)/程序性死亡配体1(programmed death ligand 1,PD-L1)抑制剂治疗非小细胞肺癌的临床疗效及安全性。方法文献检索限定时间为从建库至2025年6月23日,在...目的系统评价复方苦参注射液联合程序性死亡受体1(programmed death receptor 1,PD-1)/程序性死亡配体1(programmed death ligand 1,PD-L1)抑制剂治疗非小细胞肺癌的临床疗效及安全性。方法文献检索限定时间为从建库至2025年6月23日,在计算机检索PubMed、Embase、Cochrane library、知网、维普、万方和中国生物医学文献数据库关于复方苦参注射液联合PD-1/PD-L1抑制剂治疗非小细胞肺癌的随机对照试验。根据纳排标准筛选文献后,采用Cochrane偏倚风险评估工具进行质量评价,使用Revman 5.4进行统计学分析。结果共纳入6篇文献,包含患者520例。Meta分析结果显示:在临床疗效方面,相比于PD-1/PD-L1抑制剂治疗方案组,复方苦参注射液联合PD-1/PD-L1抑制剂治疗方案组能有效改善客观缓解率(RR=1.66,95%CI:1.36~2.03,P<0.001)、疾病控制率(RR=1.24,95%CI:1.08~1.42,P=0.002)和卡氏功能状态评分(MD=5.66,95%CI:2.22~9.09,P=0.001),对总生存期、中位无进展生存期、无病生存期、两年生存率也有一定的改善作用。在安全性方面,联合治疗能显著降低非小细胞肺癌患者总体不良反应发生率、消化道反应发生率(RR=0.83,95%CI:0.70~0.98,P=0.03)和骨髓抑制发生率(RR=0.64,95%CI:0.53~0.77,P<0.001)。结论复方苦参注射液联合PD-1/PD-L1抑制剂治疗能提高非小细胞肺癌的临床疗效,且安全性良好。展开更多
A convenient photocatalytic multi-component reaction of alkenes,quinoxalin-2(1H)-ones,and diazo compounds has been developed in the presence of water.A number of ester-containing quinoxalin-2(1H)-ones could be efficie...A convenient photocatalytic multi-component reaction of alkenes,quinoxalin-2(1H)-ones,and diazo compounds has been developed in the presence of water.A number of ester-containing quinoxalin-2(1H)-ones could be efficiently obtained in moderate to good yields at room temperature.This metal-free visiblelight-driven tandem reaction was conducted through proton-coupled electron transfer(PCET)process using water as the hydrogen donor and 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene(4CzIPN)as the photocatalyst.展开更多
基金support provided by the Department of Science and Technology,Science and Engineering Research Board(DST-SERB),the Anusandhan National Research Foundation(ANRF),State University Research Excellence(SERB-SURE),Ministry of Science and Technology,Govt.of India(SUR/2022/001353).
文摘Cancer is a global health problem and one of the leading causes of mortality.Immune checkpoint inhibitors have revolutionized the field of oncology,emerging as a powerful treatment strategy.A key pathway that has garnered considerable attention is programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1).The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body’s immune system.Furthermore,it controls the phenotype and functionality of innate and adaptive immune components.A range of monoclonal antibodies,including avelumab,atezolizumab,camrelizumab,dostarlimab,durvalumab,sinitilimab,toripalimab,and zimberelimab,have been developed for targeting the interaction between PD-1 and PD-L1.These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system.Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints.This could contribute to the existing arsenal of anticancer drugs.Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis,promoting tumor cell apoptosis,influencing cell proliferation,and eventually leading to tumor cell death and inhibiting cancer progression.However,there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer.Hence,this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules.Moreover,the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules.Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.
基金Supported by Shenzhen Science and Technology Program,Shenzhen,China(No.JCYJ20200109145001814,No.SGDX20211123120001001)the National Natural Science Foundation of China(No.81970790)Sanming Project of Medicine in Shenzhen(No.SZSM202011015).
文摘AIM:To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1.METHODS:Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy.Targeted sequence capture array technique was used to screen potential pathologic variants.Polymerase chain reaction and Sanger sequencing were used to confirm the screening results.RESULTS:Fundus examination showed round macular lesions appeared in both eyes.Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye,but it was uneven and slightly elevated in the right eye.Fundus autofluorescence showed patchy hyper-autofluorescence in the macula.Visual field examination indicates central defects in both eyes.Electroretinogram(ERG)and multifocal ERG showed no obvious abnormalities.Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye.We found that the proband carried a missense variant(c.1972C>T)and a deletion variant(c.4717_4718del)of RP1L1,which were originated from the parents and formed compound heterozygous variants.Both variants are likely pathogenic according to the ACMG criteria.Multimodal imaging,ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders.CONCLUSION:A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family,which expands the understanding of phenotype and genotype in RP1L1 maculopathy.
基金We thank the Natural Science Foundation of Shanxi Province(202103021224439)National Natural Science Foundation of China(22075308)for financial support.
文摘The aromatic compounds,including o-xylene,m-xylene,p-xylene,and ethylbenzene,primarily originate from the catalytic reforming of crude oil,and have a wide variety of applications.However,because of similar physical and chemical properties,these compounds are difficult to be identified by gas chromatography(GC)without standard samples.With the development of modern nuclear magnetic resonance(NMR)techniques,NMR has emerged as a powerful and efficient tool for the rapid analysis of complex and crude mixtures without purification.In this study,the parameters of one-dimensional(1D)total correlation spectroscopy(TOCSY)NMR techniques,including 1D selective gradient TOCSY and 1D chemicalshift-selective filtration(CSSF)with TOCSY,were optimized to obtain comprehensive molecular structure information.The results indicate that the overlapped signals in NMR spectra of nonpolar aromatic compounds(including o-xylene,m-xylene,p-xylene and ethylbenzene),polar aromatic compounds(benzyl alcohol,benzaldehyde,benzoic acid),and aromatic compounds with additional conjugated bonds(styrene)can be resolved in 1D TOCSY.More importantly,full molecular structures can be clearly distinguished by setting appropriate mixing time in 1D TOCSY.This approach simplifies the NMR spectra,provides structural information of entire molecules,and can be applied for the analysis of other structural isomers.
文摘目的系统评价复方苦参注射液联合程序性死亡受体1(programmed death receptor 1,PD-1)/程序性死亡配体1(programmed death ligand 1,PD-L1)抑制剂治疗非小细胞肺癌的临床疗效及安全性。方法文献检索限定时间为从建库至2025年6月23日,在计算机检索PubMed、Embase、Cochrane library、知网、维普、万方和中国生物医学文献数据库关于复方苦参注射液联合PD-1/PD-L1抑制剂治疗非小细胞肺癌的随机对照试验。根据纳排标准筛选文献后,采用Cochrane偏倚风险评估工具进行质量评价,使用Revman 5.4进行统计学分析。结果共纳入6篇文献,包含患者520例。Meta分析结果显示:在临床疗效方面,相比于PD-1/PD-L1抑制剂治疗方案组,复方苦参注射液联合PD-1/PD-L1抑制剂治疗方案组能有效改善客观缓解率(RR=1.66,95%CI:1.36~2.03,P<0.001)、疾病控制率(RR=1.24,95%CI:1.08~1.42,P=0.002)和卡氏功能状态评分(MD=5.66,95%CI:2.22~9.09,P=0.001),对总生存期、中位无进展生存期、无病生存期、两年生存率也有一定的改善作用。在安全性方面,联合治疗能显著降低非小细胞肺癌患者总体不良反应发生率、消化道反应发生率(RR=0.83,95%CI:0.70~0.98,P=0.03)和骨髓抑制发生率(RR=0.64,95%CI:0.53~0.77,P<0.001)。结论复方苦参注射液联合PD-1/PD-L1抑制剂治疗能提高非小细胞肺癌的临床疗效,且安全性良好。
基金supported by Sichuan Science and Technology Program(No.2023NSFSC0101)the 2024 Provincial platform project of Chengdu Normal University(No.GNFZ202404)+1 种基金Natural Science Foundation of Shandong Province(No.ZR2021MB065)National Natural Science Foundation of China(No.22101237)。
文摘A convenient photocatalytic multi-component reaction of alkenes,quinoxalin-2(1H)-ones,and diazo compounds has been developed in the presence of water.A number of ester-containing quinoxalin-2(1H)-ones could be efficiently obtained in moderate to good yields at room temperature.This metal-free visiblelight-driven tandem reaction was conducted through proton-coupled electron transfer(PCET)process using water as the hydrogen donor and 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene(4CzIPN)as the photocatalyst.
