Owing to the extreme rainfall and evaporation events under the changing climate,coastal zones are experiencing salinity fluctuations that stress aquatic organisms.However,the biological consequences of ongoing alterat...Owing to the extreme rainfall and evaporation events under the changing climate,coastal zones are experiencing salinity fluctuations that stress aquatic organisms.However,the biological consequences of ongoing alteration in salinity levels on euryhaline organisms remain inconclusive.Herein,we sought to uncover how variation in salinity level adversely alters the bacterioplankton community,the gut microbiota of euryhaline shrimp Penaeus monodon,and subsequent shrimp disease risk.To mimic the extreme weather that induces abrupt changes in coastal water salinity,three salinity levels(10,20,and 30)were selected to investigate the differences in shrimp gut microbiota using bacterial 16S rRNA gene sequencing.Results shows that salinity level and days post experiment(dpe)respectively constrained 45.9%and 13.0%of the variance in the gut bacterial communities.Particularly,abnormal salinity levels accelerated temporal turnover rate,disrupted gut network stability,augmented average variation degree,and increased pathogenic potential in the gut microbiota of shrimp reared at 10 and 30 salinities compared with 20 salinity controls.These changes were accompanied with the shifts in the gut microbiota-mediated functions,especially the compromised immunity and elevated infectious diseases potentials,thereby increasing shrimp disease risk.In addition,abnormal salinity levels increased the role of homogeneous selection governing the gut microbiota.After excluding the dpe-effect,we screened 35 gut salinity-discriminatory taxa that quantitatively discriminated the salinity levels where shrimp were reared,with overall accuracy of 91.1%.Collectively,abnormal salinity levels profoundly disrupt the structure,stability,assembly,and functions of the gut microbiota,which in turn increased disease risk in shrimp.In addition,gut symbionts sensitively responded to the changes in external salinity level.These findings deepened our understanding on the biological consequence of abnormal salinity levels on shrimp health.展开更多
Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Ho...Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.展开更多
基金Supported by the National Natural Science Foundation of China(Nos.32371596,32071549)the Zhejiang Provincial Key Natural Science Foundation of China(No.Z25C030002)+2 种基金the Science and Technology Innovation Yongjiang 2035 Key Research and Development Project of Ningbo(No.2024Z279)the One Health Interdisciplinary Research Project(No.HZ202404)the K.C.Wong Magna Fund in Ningbo University。
文摘Owing to the extreme rainfall and evaporation events under the changing climate,coastal zones are experiencing salinity fluctuations that stress aquatic organisms.However,the biological consequences of ongoing alteration in salinity levels on euryhaline organisms remain inconclusive.Herein,we sought to uncover how variation in salinity level adversely alters the bacterioplankton community,the gut microbiota of euryhaline shrimp Penaeus monodon,and subsequent shrimp disease risk.To mimic the extreme weather that induces abrupt changes in coastal water salinity,three salinity levels(10,20,and 30)were selected to investigate the differences in shrimp gut microbiota using bacterial 16S rRNA gene sequencing.Results shows that salinity level and days post experiment(dpe)respectively constrained 45.9%and 13.0%of the variance in the gut bacterial communities.Particularly,abnormal salinity levels accelerated temporal turnover rate,disrupted gut network stability,augmented average variation degree,and increased pathogenic potential in the gut microbiota of shrimp reared at 10 and 30 salinities compared with 20 salinity controls.These changes were accompanied with the shifts in the gut microbiota-mediated functions,especially the compromised immunity and elevated infectious diseases potentials,thereby increasing shrimp disease risk.In addition,abnormal salinity levels increased the role of homogeneous selection governing the gut microbiota.After excluding the dpe-effect,we screened 35 gut salinity-discriminatory taxa that quantitatively discriminated the salinity levels where shrimp were reared,with overall accuracy of 91.1%.Collectively,abnormal salinity levels profoundly disrupt the structure,stability,assembly,and functions of the gut microbiota,which in turn increased disease risk in shrimp.In addition,gut symbionts sensitively responded to the changes in external salinity level.These findings deepened our understanding on the biological consequence of abnormal salinity levels on shrimp health.
基金supported in part by Chinese National Major Project for New Drug Innovation (2008ZX09312-020,2009ZX09503-014,2012ZX09303012 and 2013ZX09402301)National Key Technology Support Program (2014BAI09B12)+1 种基金Beijing Municipal Science and Technology Commission Major Project for New Drug Innovation (Z111102071011001)Beijing Municipal Science and Technology Commission Project for Beijing Key Laboratory (Z121102009212055)
文摘Objective： This study was designed to determine the safety, pharmacokinetics and biologic effects of a humanmouse chimeric anti-CD20 monoclonal antibody （SCT400） in Chinese padents with CD20-positive B-cell non- Hodgkin＇s lymphoma （CD20 B-cell NHL）. SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians. Methods： Fifteen patients with CD20＋ B-cell NHL received dose-escalating SCT400 infusions （250 mg/m2： n=3; 375 mg/m2： n=9; 500 mg/m2： n=3） once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacoklnetics and pharmacodynamics analyses. Results： No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 ncutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer （NK） cell count or immunoglobulin levels. No patient developed anti- SCT400 antibodies during the course of the study. SCT400 serum half-life （Tin）, maximum concentration （Cmax and area under the curve （AUC） generally increased between the first and fourth infusions （P〈0.05）. At the 375 mg/m2 dose, the T1/2 was 122.5±46.7 h vs. 197.0,75.0 11, respectively, and the Cmax was 200.6±20.2 pg/mL vs. 339.1±71.0 ng/mL, respectively. From 250 mg/m2 to 500 mg/m2, the Cmax and AUC increased significantly in a dose-dependent manner （P〈0.05）. Patients with a high tumor burden had markedly lower serum SCT400 concenmations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses. Conclusions; SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20＋ B-cell NHL.
