Advanced natural killer/T cell lymphoma(NKTL)has demonstrated poor prognosis with currently available therapies.Here,we report the efficacy of anti-programmed death 1(PD-1)antibody with the P-GEMOX(pegaspargase,gemcit...Advanced natural killer/T cell lymphoma(NKTL)has demonstrated poor prognosis with currently available therapies.Here,we report the efficacy of anti-programmed death 1(PD-1)antibody with the P-GEMOX(pegaspargase,gemcitabine,and oxaliplatin)regimen in advanced NKTL.Nine patients underwent six 21-day cycles of anti-PD-1 antibody(day 1),pegaspargase 2000 U/m2(day 1),gemcitabine 1 g/m2(days 1 and 8)and oxaliplatin 130 mg/m2(day 1),followed by anti-PD-1 antibody maintenance every 3 weeks.Programmed death-ligand 1(PD-L1)expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing(NGS)analysis.Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography(18FDG-PET)and computed tomography or magnetic resonance imaging.Eight patients exhibited significant responses,comprising of seven complete remissions and one partial remission(overall response rate:88.9%).After a median follow-up of 10.6 months,6/9 patients(66.7%)remained in complete remission.The most common grade 3/4 adverse events were anemia(33.3%),neutropenia(33.3%),and thrombocytopenia(33.3%);all of which were manageable and resolved.Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression(5/6,83.3%).NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy.Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D,TET2,and BCORL1 might indicate a poor response to immunochemotherapy.In conclusion,the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL.PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.展开更多
Aim: To evaluate KAII/CD82 expression in Chinese patients with benign prostatic hyperplasia (BPH) and late-stage carcinoma of prostate (CaP). Methods: Thirty Chinese patients with benign prostatic hyperplasia and 34 w...Aim: To evaluate KAII/CD82 expression in Chinese patients with benign prostatic hyperplasia (BPH) and late-stage carcinoma of prostate (CaP). Methods: Thirty Chinese patients with benign prostatic hyperplasia and 34 withCaP (adenocarcinoma clinical stage C and D) were analyzed by means of immunohistochemical methods. Results:The KAII/CD82 expression in BPH tissue was all positive, which was uniformly located on the glandular cell mem-brane at the cell-to-cell borders, but KAII/CD82 expression in metastasis CaP tissues was either significantly lower thanthat of BPH or negative, and the immunostaining pattern was not continuous. In late-stage CAP KAII/CD82 expressionwas correlated inversely to the pathological grade ( P < 0.05), but not to clinical stage ( P > 0.05). Conclusion:The authors believe that decreased and negative KAII/CD82 expression in late-stage CaP may be related to tumor pro-gression and metastasis, and appears to be a prognostic marker.展开更多
AIM:To study the clinical and epidemiological features of patients with clonorchiasis so as to provide scientific evidences for the diagnosis and prevention of clonorchiasis. METHODS:Stools from 282 subjects suspected...AIM:To study the clinical and epidemiological features of patients with clonorchiasis so as to provide scientific evidences for the diagnosis and prevention of clonorchiasis. METHODS:Stools from 282 subjects suspected of having clonorchiasis were examined for helminth eggs with modified Kato's thick smear and sedimentation methods,and their sera were tested for HAV-DNA,HBV-DNA,HCV-RNA,HDV- RNA and HEV-RNA with polymerase chain reaction (PCR). Clinical symptoms of patients with clonorchiasis only were analyzed,and their blood samples were tested for circulating antigen (CAg) with Dot-ELISA,esoinophilic granulocyte count, and alanine aminotransferase (ALT).Meanwhile,they were asked to provide data of occupation,eating habit,hygienic habit and knowledge of donorchiasis.In addition,the ecosystem of the environment in epidemic areas was surveyed. RESULTS:Among the 282 patients,61 (21.43%) were infected with clonorchis sinensis only,97 (34.64%) were co-infected with clonorchis sinensis and other pathogens, 92 (32.86%) were infected with hepatitis virus only and 31 (11.07%) neither with clonorchis sinensis nor hepatitis virus. Among the 61 patients with clonorchiasis only,there were 14 (22.95%) subjects with discomfort over hepatic region or epigasfrium,12 (19.67%) with general malaise or discomfort and inertia in total body,6 (9.84%) with anorexia,indigestion and nausea,4 (6.56%) with fever,dizziness and headache (6.56%),and 25 (40.98%) without any symptoms;sixty one (100%) with CAg (+),98.33% (59160) with eosinophilic granulocytes increased and 65.00% (39/60) with ALT increased.B-mode ultrasonography revealed 61 cases with dilated and thickened walls of intrahepatic bile duct,and blurred patchy echo acoustic image in liver.Twenty-six cases had stones in the bile duct,39 cases had slightly enlarged liver with diffuse coarse spots in liver parenchyma.Twenty cases had enlarged gallbladder with thickened coarse wall and image of floating plagues,9 cases had slightly enlarged spleen.By analysis of epidemiological data,we f展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19).To halt the pandemic,multiple SARS-CoV-2 vaccines have been developed and several have been allow...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19).To halt the pandemic,multiple SARS-CoV-2 vaccines have been developed and several have been allowed for emergency use and rollout worldwide.With novel SARS-CoV-2 variants emerging and circulating widely,whether the original vaccines that were designed based on the wild-type SARS-CoV-2 were effective against these variants has been a contentious discussion.Moreover,some studies revealed the long-term changes of immune responses post SARS-CoV-2 infection or vaccination and the factors that might impact the vaccine-induced immunity.Thus,in this review,we have summarized the influence of mutational hotspots on the vaccine efficacy and characteristics of variants of interest and concern.We have also discussed the reasons that might result in discrepancies in the efficacy of different vaccines estimated in different trials.Furthermore,we provided an overview of the duration of immune responses after natural infection or vaccination and shed light on the factors that may affect the immunity induced by the vaccines,such as special disease conditions,sex,and pre-existing immunity,with the aim of aiding in combating COVID-19 and distributing SARS-CoV-2 vaccines under the prevalence of diverse SARS-CoV-2 variants.展开更多
Mode-division multiplexing(MDM)technology enables high-bandwidth data transmission using orthogonal waveguide modes to construct parallel data streams.However,few demonstrations have been realized for generating and s...Mode-division multiplexing(MDM)technology enables high-bandwidth data transmission using orthogonal waveguide modes to construct parallel data streams.However,few demonstrations have been realized for generating and supporting high-order modes,mainly due to the intrinsic large material groupvelocity dispersion(GVD),which make it challenging to selectively couple different-order spatial modes.We show the feasibility of on-chip GVD engineering by introducing a gradient-index metamaterial structure,which enables a robust and fully scalable MDM process.We demonstrate a record-high-order MDM device that supports TE_(0)–TE_(15)modes simultaneously.40-GBaud 16-ary quadrature amplitude modulation signals encoded on 16 mode channels contribute to a 2.162 Tbit∕s net data rate,which is the highest data rate ever reported for an on-chip single-wavelength transmission.Our method can effectively expand the number of channels provided by MDM technology and promote the emerging research fields with great demand for parallelism,such as high-capacity optical interconnects,high-dimensional quantum communications,and large-scale neural networks.展开更多
Developing low-priced,yet effective and robust catalysts for the nitrogen reduction reaction(NRR) is of vital importance for scalable and renewable electrochemical NH3 synthesis.Herein,we provide the first demonstrati...Developing low-priced,yet effective and robust catalysts for the nitrogen reduction reaction(NRR) is of vital importance for scalable and renewable electrochemical NH3 synthesis.Herein,we provide the first demonstration of MoS_3 as an efficient and durable NRR catalyst in neutral media.The prepared amorphous MoS_3 naturally possessed enriched S vacancies and delivered an NH3 yield of 51.7 μg h^(-1) mg^(-1)and a Faradaic efficiency of 12.8% at-0.3 V(RHE) in 0.5 M LiClO_4,considerably exceeding those of MoS_2 and most reported NRR catalysts.Density functional theory calculations unraveled that S vacancies involved in MoS_3 played a crucial role in activating the NRR via a consecutive mechanism with a low energetics barrier and simultaneously suppressing the hydrogen evolution reaction.展开更多
The brain of the domestic pig(Sus scrofa domesticus)has drawn considerable attention due to its high similarities to that of humans.However,the cellular compositions of the pig brain(PB)remain elusive.Here we investig...The brain of the domestic pig(Sus scrofa domesticus)has drawn considerable attention due to its high similarities to that of humans.However,the cellular compositions of the pig brain(PB)remain elusive.Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB(frontal lobe,parietal lobe,temporal lobe,occipital lobe,and hypothalamus)and identified 21 cell subpopulations.The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution.Furthermore,we identified cell types and molecular pathways closely associated with neurological disorders,bridging the gap between gene mutations and pathogenesis.We reported,to our knowledge,the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species,providing extensive resources for future research regarding neural science,evolutionary developmental biology,and regenerative medicine.展开更多
We propose to use the low-coherence property of amplified spontaneous emission(ASE) noise to mitigate optical crosstalk, such as spatial, polarization, and modal crosstalk, which currently limits the density of photon...We propose to use the low-coherence property of amplified spontaneous emission(ASE) noise to mitigate optical crosstalk, such as spatial, polarization, and modal crosstalk, which currently limits the density of photonic integration and fibers for dense space-division multiplexing. High optical crosstalk tolerance can be achieved by ASE-based low-coherence matched detection, which avoids dedicated optical lasers and uses spectrally filtered ASE noise as the signal carrier and as a matched local oscillator. We experimentally demonstrate spatial and modal crosstalk reduction in multimode fiber(MMF) and realize mode-and wavelength-multiplexed transmission over1.5-km MMF supporting three spatial modes using a single ASE source. Performance degradation due to model dispersion over MMF is experimentally investigated.展开更多
基金supported by the Chinese National Natural Science Funds(82041009,31925013,31671457,91753139,and 31871405)Zhejiang University Joint Pingduoduo“Virus Infectious Disease Prevention and Control funds”,a special program from the Ministry of Science and Technology of China(2016YFA0502500)+2 种基金Jiangsu Provincial Distinguished Young Scholars award(BK20180043)the Zhejiang Natural Science Fund(LD19C070001),the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003)A project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Advanced natural killer/T cell lymphoma(NKTL)has demonstrated poor prognosis with currently available therapies.Here,we report the efficacy of anti-programmed death 1(PD-1)antibody with the P-GEMOX(pegaspargase,gemcitabine,and oxaliplatin)regimen in advanced NKTL.Nine patients underwent six 21-day cycles of anti-PD-1 antibody(day 1),pegaspargase 2000 U/m2(day 1),gemcitabine 1 g/m2(days 1 and 8)and oxaliplatin 130 mg/m2(day 1),followed by anti-PD-1 antibody maintenance every 3 weeks.Programmed death-ligand 1(PD-L1)expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing(NGS)analysis.Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography(18FDG-PET)and computed tomography or magnetic resonance imaging.Eight patients exhibited significant responses,comprising of seven complete remissions and one partial remission(overall response rate:88.9%).After a median follow-up of 10.6 months,6/9 patients(66.7%)remained in complete remission.The most common grade 3/4 adverse events were anemia(33.3%),neutropenia(33.3%),and thrombocytopenia(33.3%);all of which were manageable and resolved.Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression(5/6,83.3%).NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy.Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D,TET2,and BCORL1 might indicate a poor response to immunochemotherapy.In conclusion,the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL.PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.
基金The work was supported by a grant from the Guangdong Scientfic and Technologic Committee(No 970750)
文摘Aim: To evaluate KAII/CD82 expression in Chinese patients with benign prostatic hyperplasia (BPH) and late-stage carcinoma of prostate (CaP). Methods: Thirty Chinese patients with benign prostatic hyperplasia and 34 withCaP (adenocarcinoma clinical stage C and D) were analyzed by means of immunohistochemical methods. Results:The KAII/CD82 expression in BPH tissue was all positive, which was uniformly located on the glandular cell mem-brane at the cell-to-cell borders, but KAII/CD82 expression in metastasis CaP tissues was either significantly lower thanthat of BPH or negative, and the immunostaining pattern was not continuous. In late-stage CAP KAII/CD82 expressionwas correlated inversely to the pathological grade ( P < 0.05), but not to clinical stage ( P > 0.05). Conclusion:The authors believe that decreased and negative KAII/CD82 expression in late-stage CaP may be related to tumor pro-gression and metastasis, and appears to be a prognostic marker.
文摘AIM:To study the clinical and epidemiological features of patients with clonorchiasis so as to provide scientific evidences for the diagnosis and prevention of clonorchiasis. METHODS:Stools from 282 subjects suspected of having clonorchiasis were examined for helminth eggs with modified Kato's thick smear and sedimentation methods,and their sera were tested for HAV-DNA,HBV-DNA,HCV-RNA,HDV- RNA and HEV-RNA with polymerase chain reaction (PCR). Clinical symptoms of patients with clonorchiasis only were analyzed,and their blood samples were tested for circulating antigen (CAg) with Dot-ELISA,esoinophilic granulocyte count, and alanine aminotransferase (ALT).Meanwhile,they were asked to provide data of occupation,eating habit,hygienic habit and knowledge of donorchiasis.In addition,the ecosystem of the environment in epidemic areas was surveyed. RESULTS:Among the 282 patients,61 (21.43%) were infected with clonorchis sinensis only,97 (34.64%) were co-infected with clonorchis sinensis and other pathogens, 92 (32.86%) were infected with hepatitis virus only and 31 (11.07%) neither with clonorchis sinensis nor hepatitis virus. Among the 61 patients with clonorchiasis only,there were 14 (22.95%) subjects with discomfort over hepatic region or epigasfrium,12 (19.67%) with general malaise or discomfort and inertia in total body,6 (9.84%) with anorexia,indigestion and nausea,4 (6.56%) with fever,dizziness and headache (6.56%),and 25 (40.98%) without any symptoms;sixty one (100%) with CAg (+),98.33% (59160) with eosinophilic granulocytes increased and 65.00% (39/60) with ALT increased.B-mode ultrasonography revealed 61 cases with dilated and thickened walls of intrahepatic bile duct,and blurred patchy echo acoustic image in liver.Twenty-six cases had stones in the bile duct,39 cases had slightly enlarged liver with diffuse coarse spots in liver parenchyma.Twenty cases had enlarged gallbladder with thickened coarse wall and image of floating plagues,9 cases had slightly enlarged spleen.By analysis of epidemiological data,we f
基金This work was supported by the National Natural Science Foundation of China(82041009,31871405,31925013,U20A20393,32125016 and 32100699)a special program from the Ministry of Science and Technology of China(2016YFA0502500)+5 种基金the China National Postdoctoral Program for Innovative Talents(BX2021208)the China Postdoctoral Science Foundation(2021M692350)the Zhejiang Natural Science Fund(LD19C070001)the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003)a project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,Zhejiang Provincial Natural Science Foundation under Grant(LBY21H060001)the Medical and the Medical and Health Research Project of Zhejiang Province(2020RC115).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19).To halt the pandemic,multiple SARS-CoV-2 vaccines have been developed and several have been allowed for emergency use and rollout worldwide.With novel SARS-CoV-2 variants emerging and circulating widely,whether the original vaccines that were designed based on the wild-type SARS-CoV-2 were effective against these variants has been a contentious discussion.Moreover,some studies revealed the long-term changes of immune responses post SARS-CoV-2 infection or vaccination and the factors that might impact the vaccine-induced immunity.Thus,in this review,we have summarized the influence of mutational hotspots on the vaccine efficacy and characteristics of variants of interest and concern.We have also discussed the reasons that might result in discrepancies in the efficacy of different vaccines estimated in different trials.Furthermore,we provided an overview of the duration of immune responses after natural infection or vaccination and shed light on the factors that may affect the immunity induced by the vaccines,such as special disease conditions,sex,and pre-existing immunity,with the aim of aiding in combating COVID-19 and distributing SARS-CoV-2 vaccines under the prevalence of diverse SARS-CoV-2 variants.
基金supported by the National Key R&D Program of China(Grant No.2021YFB2800103)National Natural Science Foundation of China(NSFC)(Grant Nos.62105202,61835008,61860206001,61975115,62035016,and 62105200).
文摘Mode-division multiplexing(MDM)technology enables high-bandwidth data transmission using orthogonal waveguide modes to construct parallel data streams.However,few demonstrations have been realized for generating and supporting high-order modes,mainly due to the intrinsic large material groupvelocity dispersion(GVD),which make it challenging to selectively couple different-order spatial modes.We show the feasibility of on-chip GVD engineering by introducing a gradient-index metamaterial structure,which enables a robust and fully scalable MDM process.We demonstrate a record-high-order MDM device that supports TE_(0)–TE_(15)modes simultaneously.40-GBaud 16-ary quadrature amplitude modulation signals encoded on 16 mode channels contribute to a 2.162 Tbit∕s net data rate,which is the highest data rate ever reported for an on-chip single-wavelength transmission.Our method can effectively expand the number of channels provided by MDM technology and promote the emerging research fields with great demand for parallelism,such as high-capacity optical interconnects,high-dimensional quantum communications,and large-scale neural networks.
基金supported by the National Natural Science Foundation of China (51761024)the CAS ‘‘Light of West China” Program+1 种基金‘‘Feitian Scholar” Program of Gansu Provincethe Foundation of A Hundred Youth Talents Training Program of Lanzhou Jiaotong University。
文摘Developing low-priced,yet effective and robust catalysts for the nitrogen reduction reaction(NRR) is of vital importance for scalable and renewable electrochemical NH3 synthesis.Herein,we provide the first demonstration of MoS_3 as an efficient and durable NRR catalyst in neutral media.The prepared amorphous MoS_3 naturally possessed enriched S vacancies and delivered an NH3 yield of 51.7 μg h^(-1) mg^(-1)and a Faradaic efficiency of 12.8% at-0.3 V(RHE) in 0.5 M LiClO_4,considerably exceeding those of MoS_2 and most reported NRR catalysts.Density functional theory calculations unraveled that S vacancies involved in MoS_3 played a crucial role in activating the NRR via a consecutive mechanism with a low energetics barrier and simultaneously suppressing the hydrogen evolution reaction.
基金the China Postdoctoral Science Foundation(2017M622795)the Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20180507183628543)the Fundamental Research Funds for the Central Universities(2662018PY025 and 2662017PY105)。
文摘The brain of the domestic pig(Sus scrofa domesticus)has drawn considerable attention due to its high similarities to that of humans.However,the cellular compositions of the pig brain(PB)remain elusive.Here we investigated the single-nucleus transcriptomic profiles of five regions of the PB(frontal lobe,parietal lobe,temporal lobe,occipital lobe,and hypothalamus)and identified 21 cell subpopulations.The cross-species comparison of mouse and pig hypothalamus revealed the shared and specific gene expression patterns at the single-cell resolution.Furthermore,we identified cell types and molecular pathways closely associated with neurological disorders,bridging the gap between gene mutations and pathogenesis.We reported,to our knowledge,the first single-cell atlas of domestic pig cerebral cortex and hypothalamus combined with a comprehensive analysis across species,providing extensive resources for future research regarding neural science,evolutionary developmental biology,and regenerative medicine.
基金National Natural Science Foundation of China(61420106011,61601277,61601279,61635006)Shanghai Science and Technology Development Foundation(16511104100,17010500400,18511103400)
文摘We propose to use the low-coherence property of amplified spontaneous emission(ASE) noise to mitigate optical crosstalk, such as spatial, polarization, and modal crosstalk, which currently limits the density of photonic integration and fibers for dense space-division multiplexing. High optical crosstalk tolerance can be achieved by ASE-based low-coherence matched detection, which avoids dedicated optical lasers and uses spectrally filtered ASE noise as the signal carrier and as a matched local oscillator. We experimentally demonstrate spatial and modal crosstalk reduction in multimode fiber(MMF) and realize mode-and wavelength-multiplexed transmission over1.5-km MMF supporting three spatial modes using a single ASE source. Performance degradation due to model dispersion over MMF is experimentally investigated.
