Nature has shown us that the microstructure of the skin of fast-swimming sharks in the ocean can reduce the skin friction drag due to the well-known shark-skin effect.In the present study,the effect of shark-skin-insp...Nature has shown us that the microstructure of the skin of fast-swimming sharks in the ocean can reduce the skin friction drag due to the well-known shark-skin effect.In the present study,the effect of shark-skin-inspired riblets on coherent vortex structures in a turbulent boundary layer（TBL） is investigated.This is done by means of tomographic particle image velocimetry（TPIV） measurements in channel fl ws over an acrylic plate of drag-reducing riblets at a friction Reynolds number of 190.The turbulent fl ws over drag-reducing riblets are verifie by a planar time-resolved particle image velocimetry（TRPIV） system initially,and then the TPIV measurements are performed.Two-dimensional（2D） experimental results with a dragreduction rate of around 4.81% are clearly visible over triangle riblets with a peak-to-peak spacing s＋of 14,indicating from the drag-reducing performance that the buffer layer within the TBL has thickened;the logarithmic law region has shifted upward and the Reynolds shear stress decreased.A comparison of the spatial topological distributions of the spanwise vorticity of coherent vortex structures extracted at different wall-normal heights through the improved quadrant splitting method shows that riblets weaken the amplitudesof the spanwise vorticity when ejection（Q2） and sweep（Q4） events occur at the near wall,having the greatest effect on Q4 events in particular.The so-called quadrupole statistical model for coherent structures in the whole TBL is verified Meanwhile,their spatial conditional-averaged topological shapes and the spatial scales of quadrupole coherent vortex structures as a whole in the overlying turbulent fl w over riblets are changed,suggesting that the riblets dampen the momentum and energy exchange between the regions of near-wall and outer portion of the TBL by depressing the bursting events（Q2 and Q4）,thereby reducing the skin friction drag.展开更多
Meplazumab,a humanized CD147 antibody,has shown favourable safety and efficacy in our previous clinical studies.In DEFLECT(NCT04586153),167 patients with severe COVID-19 were enroled and randomized to receive three do...Meplazumab,a humanized CD147 antibody,has shown favourable safety and efficacy in our previous clinical studies.In DEFLECT(NCT04586153),167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo.Meplazumab at 0.12 mg/kg,compared to the placebo group,showed clinical benefits in significantly reducing mortality by 83.6%(2.4%vs.14.6%,p=0.0150),increasing the proportion of patients alive and discharged without supplemental oxygen(82.9%vs.70.7%,p=0.0337)and increasing the proportion of patients who achieved sustained clinical improvement(41.5%vs.31.7%).The response rate in the 0.2 mg/kg group was relatively increased by 16.0%compared with the placebo group(53.7%vs.46.3%).Meplazumab also reduced the viral loads and multiple cytokine levels.Compare with the placebo group,the 0.3 mg/kg significantly increased the virus negative rate by 40.6%(p=0.0363)and reduced IL-8 level(p=0.0460);the 0.2 mg/kg increased the negative conversion rate by 36.9%,and reduced IL-4(p=0.0365)and IL-8 levels(p=0.0484).In this study,the adverse events occurred at a comparable rate across the four groups,with no unexpected safety findings observed.In conclusion,meplazumab promoted COVID-19 convalescence and reduced mortality,viral load,and cytokine levels in severe COVID-19 population with good safety profile.展开更多
Dear Editor,Persistent Müllerian duct syndrome(PMDS,MIM 261550)is an autosomal recessive inherent disorder of sex development in normally masculinized subjects with Müllerian duct derivatives,including the u...Dear Editor,Persistent Müllerian duct syndrome(PMDS,MIM 261550)is an autosomal recessive inherent disorder of sex development in normally masculinized subjects with Müllerian duct derivatives,including the uterus,fallopian tubes,and upper part of the vagina.1 PMDS is very rare with presentations of bilateral cryptorchidism(55%),unilateral cryptorchidism with contralateral hernia(20%),or transverse testicular ectopia(25%).展开更多
In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a ...In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.展开更多
Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 rep...Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication.Meplazumab is a humanized anti-CD147 IgG_(2) monoclonal antibody,which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019(COVID-19)patients.Here,we conducted a randomized,double-blinded,placebo-controlled phase 1 trial to evaluate the safety,tolerability,and pharmacokinetics of meplazumab in healthy subjects,and an open-labeled,concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients.In phase 1 study,59 subjects were enrolled and assigned to eight cohorts,and no serious treatment-emergent adverse event(TEAE)or TEAE grade≥3 was observed.The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics.No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort.The biodistribution study indicated that meplazumab reached lung tissue and maintained>14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32.In the exploratory phase 2 study,17 COVID-19 patients were enrolled,and 11 hospitalized patients were involved as concurrent control.The meplazumab treatment significantly improved the discharged(P=0.005)and case severity(P=0.021),and reduced the time to virus negative(P=0.045)in comparison to the control group.These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.展开更多
In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a ...In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.展开更多
基金supported by the National Natural Science Foundation of China (Grants 11332006,11272233,and 11411130150)the foundation from the China Scholarship Council (CSC) (Grant 201306250092)the Foundation Project for Outstanding Doctoral Dissertations of Tianjin University
文摘Nature has shown us that the microstructure of the skin of fast-swimming sharks in the ocean can reduce the skin friction drag due to the well-known shark-skin effect.In the present study,the effect of shark-skin-inspired riblets on coherent vortex structures in a turbulent boundary layer（TBL） is investigated.This is done by means of tomographic particle image velocimetry（TPIV） measurements in channel fl ws over an acrylic plate of drag-reducing riblets at a friction Reynolds number of 190.The turbulent fl ws over drag-reducing riblets are verifie by a planar time-resolved particle image velocimetry（TRPIV） system initially,and then the TPIV measurements are performed.Two-dimensional（2D） experimental results with a dragreduction rate of around 4.81% are clearly visible over triangle riblets with a peak-to-peak spacing s＋of 14,indicating from the drag-reducing performance that the buffer layer within the TBL has thickened;the logarithmic law region has shifted upward and the Reynolds shear stress decreased.A comparison of the spatial topological distributions of the spanwise vorticity of coherent vortex structures extracted at different wall-normal heights through the improved quadrant splitting method shows that riblets weaken the amplitudesof the spanwise vorticity when ejection（Q2） and sweep（Q4） events occur at the near wall,having the greatest effect on Q4 events in particular.The so-called quadrupole statistical model for coherent structures in the whole TBL is verified Meanwhile,their spatial conditional-averaged topological shapes and the spatial scales of quadrupole coherent vortex structures as a whole in the overlying turbulent fl w over riblets are changed,suggesting that the riblets dampen the momentum and energy exchange between the regions of near-wall and outer portion of the TBL by depressing the bursting events（Q2 and Q4）,thereby reducing the skin friction drag.
基金The DEFLECT is supported by grants from National Natural Science Foundation of China(No.92169211).Jiangsu Pacific Meinuoke Biopharmaceuticals provided meplazumab.The views expressed in this article is the authors’opinion,not the opinion or policy of funder.
文摘Meplazumab,a humanized CD147 antibody,has shown favourable safety and efficacy in our previous clinical studies.In DEFLECT(NCT04586153),167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo.Meplazumab at 0.12 mg/kg,compared to the placebo group,showed clinical benefits in significantly reducing mortality by 83.6%(2.4%vs.14.6%,p=0.0150),increasing the proportion of patients alive and discharged without supplemental oxygen(82.9%vs.70.7%,p=0.0337)and increasing the proportion of patients who achieved sustained clinical improvement(41.5%vs.31.7%).The response rate in the 0.2 mg/kg group was relatively increased by 16.0%compared with the placebo group(53.7%vs.46.3%).Meplazumab also reduced the viral loads and multiple cytokine levels.Compare with the placebo group,the 0.3 mg/kg significantly increased the virus negative rate by 40.6%(p=0.0363)and reduced IL-8 level(p=0.0460);the 0.2 mg/kg increased the negative conversion rate by 36.9%,and reduced IL-4(p=0.0365)and IL-8 levels(p=0.0484).In this study,the adverse events occurred at a comparable rate across the four groups,with no unexpected safety findings observed.In conclusion,meplazumab promoted COVID-19 convalescence and reduced mortality,viral load,and cytokine levels in severe COVID-19 population with good safety profile.
基金supported by grant from the National Key Research and Development Project(2021YFC1005300,2021YFC1005304,and 2018YFC1004202)the Natural Science Foundation of Liaoning Province(2022-MS-208)the 345 Talent of Shengjing Hospital of China Medical University(C0101).
文摘Dear Editor,Persistent Müllerian duct syndrome(PMDS,MIM 261550)is an autosomal recessive inherent disorder of sex development in normally masculinized subjects with Müllerian duct derivatives,including the uterus,fallopian tubes,and upper part of the vagina.1 PMDS is very rare with presentations of bilateral cryptorchidism(55%),unilateral cryptorchidism with contralateral hernia(20%),or transverse testicular ectopia(25%).
基金supported by the National Science and Technology Major Project of China(2019ZX09732-001)the Key R&D Plan Projects in Shaanxi Province(2020ZDXM2-SF-01)Young Talent fund of the University Association for Science and Technology in Shaanxi,China(20200304).
文摘In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.
基金the China National Science and Technology Major Project(2019ZX09732-001).
文摘Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication.Meplazumab is a humanized anti-CD147 IgG_(2) monoclonal antibody,which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019(COVID-19)patients.Here,we conducted a randomized,double-blinded,placebo-controlled phase 1 trial to evaluate the safety,tolerability,and pharmacokinetics of meplazumab in healthy subjects,and an open-labeled,concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients.In phase 1 study,59 subjects were enrolled and assigned to eight cohorts,and no serious treatment-emergent adverse event(TEAE)or TEAE grade≥3 was observed.The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics.No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort.The biodistribution study indicated that meplazumab reached lung tissue and maintained>14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32.In the exploratory phase 2 study,17 COVID-19 patients were enrolled,and 11 hospitalized patients were involved as concurrent control.The meplazumab treatment significantly improved the discharged(P=0.005)and case severity(P=0.021),and reduced the time to virus negative(P=0.045)in comparison to the control group.These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.
基金This work was supported by the National Science and Technology Major Project of China(2019ZX09732-001)the Key R&D Plan Projects in Shaanxi Province(2020ZDXM2-SF-01)Young Talent fund of the University Association for Science and Technology in Shaanxi,China(20200304).
文摘In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2,no specific and effective drugs for treating this disease have been reported until today.Angiotensin-converting enzyme 2(ACE2),a receptor of SARS-CoV-2,mediates the virus infection by binding to spike protein.Although ACE2 is expressed in the lung,kidney,and intestine,its expressing levels are rather low,especially in the lung.Considering the great infectivity of COVID-19,we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection.Here,we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein.The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody,Meplazumab,inhibits SARSCoV-2 amplification.Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells,which can be neutralized by CD147 extracellular fragment.Viral loads are detectable in the lungs of human CD147(hCD147)mice infected with SARS-CoV-2,but not in those of virus-infected wild type mice.Interestingly,virions are observed in lymphocytes of lung tissue from a COVID-19 patient.Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dosedependent manner,which is specifically inhibited by Meplazumab.Furthermore,CD147 mediates virus entering host cells by endocytosis.Together,our study reveals a novel virus entry route,CD147-spike protein,which provides an important target for developing specific and effective drug against COVID-19.
