To achieve high efficiency of nitrogen and phosphorus removal and to investigate the rule of simultaneous nitrification and denitrification phosphorus removal （SNDPR）, a whole course of SNDPR damage and recovery was...To achieve high efficiency of nitrogen and phosphorus removal and to investigate the rule of simultaneous nitrification and denitrification phosphorus removal （SNDPR）, a whole course of SNDPR damage and recovery was studied in a pilot-scale, anaerobicanoxic oxidation ditch （OD）, where the volumes of anaerobic zone, anoxic zone, and ditches zone of the OD system were 7, 21, and 280 L, respectively. The reactor was fed with municipal wastewater with a flow rate of 336 L/d. The concept of simultaneous nitrification and denitrification （SND） rate （rSND） was put forward to quantify SND. The results indicate that： （1） high nitrogen and phosphorus removal efficiencies were achieved during the stable SND phase, total nitrogen （TN） and total phosphate （TP） removal rates were 80% and 85%, respectively; （2） when the system was aerated excessively, the stability of SND was damaged, and rSND dropped from 80% to 20% or less; （3） the natural logarithm of the ratio of NOx to NH4^＋ in the effluent had a linear correlation to oxidation-reduction potential （ORP）; （4） when NO3^- was less than 6 mg/L, high phosphorus removal efficiency could be achieved; （5） denitrifying phosphorus removal （DNPR） could take place in the anaerobic-anoxic OD system. The major innovation was that the SND rate was devised and quantified.展开更多
Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin...Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinical展开更多
Due to the sophisticated hierarchical structure and limited reparability of articular cartilage(AC),the ideal regeneration of AC defects has been a major challenge in the field of regenerative medicine.As defects prog...Due to the sophisticated hierarchical structure and limited reparability of articular cartilage(AC),the ideal regeneration of AC defects has been a major challenge in the field of regenerative medicine.As defects progress,they often extend from the cartilage layer to the subchondral bone and ultimately lead to osteoarthritis.Tissue engineering techniques bring new hope for AC regeneration.To meet the regenerative requirements of the heterogeneous and layered structure of native AC tissue,a substantial number of multilayered biomimetic scaffolds have been studied.Ideal multilayered scaffolds should generate zone-specific functional tissue similar to native AC tissue.This review focuses on the current status of multilayered scaffolds developed for AC defect repair,including design strategies based on the degree of defect severity and the zone-specific characteristics of AC tissue,the selection and composition of biomaterials,and techniques for design and manufacturing.The challenges and future perspectives of biomimetic multilayered scaffold strategies for AC regeneration are also discussed.展开更多
The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antige...The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1 (TINAGL1), a newly discovered matricellular protein, in H. pylori infection. Increased TINAGL1 production by gastric epithelial cells (GECs) in the infected gastric mucosa was synergistically induced by H. pylori and IL-1β via the ERK-SP1 pathway in a cagA-dependent manner. Elevated human gastric TINAGL1 correlated with H. pylori colonization and the severity of gastritis, and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Tinagl1−/− and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1. Mechanistically, TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5β1 to inhibit ERK and activate the NF-κB pathway, respectively, which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and, as a direct consequence, reduced the bacterial clearance capacity of the H. pylori-specific Th1 response, thereby promoting H. pylori colonization, but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration. In turn, TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes, promoting H. pylori-associated gastritis. In summary, we identified a model in which TINAGL1 collectively ensures H. pylori persistence and promotes gastritis.展开更多
文摘To achieve high efficiency of nitrogen and phosphorus removal and to investigate the rule of simultaneous nitrification and denitrification phosphorus removal （SNDPR）, a whole course of SNDPR damage and recovery was studied in a pilot-scale, anaerobicanoxic oxidation ditch （OD）, where the volumes of anaerobic zone, anoxic zone, and ditches zone of the OD system were 7, 21, and 280 L, respectively. The reactor was fed with municipal wastewater with a flow rate of 336 L/d. The concept of simultaneous nitrification and denitrification （SND） rate （rSND） was put forward to quantify SND. The results indicate that： （1） high nitrogen and phosphorus removal efficiencies were achieved during the stable SND phase, total nitrogen （TN） and total phosphate （TP） removal rates were 80% and 85%, respectively; （2） when the system was aerated excessively, the stability of SND was damaged, and rSND dropped from 80% to 20% or less; （3） the natural logarithm of the ratio of NOx to NH4^＋ in the effluent had a linear correlation to oxidation-reduction potential （ORP）; （4） when NO3^- was less than 6 mg/L, high phosphorus removal efficiency could be achieved; （5） denitrifying phosphorus removal （DNPR） could take place in the anaerobic-anoxic OD system. The major innovation was that the SND rate was devised and quantified.
基金China National Major Project for New Drug Innovation,Grant/Award Number:2017ZX09304015Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS),Grant/Award Number:2016-I2M-1-001。
文摘Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinical
基金supported by the National Key Research and Development Program of China(No.2019YFA0110600)the National Natural Science Foundation of China(No.81772319).
文摘Due to the sophisticated hierarchical structure and limited reparability of articular cartilage(AC),the ideal regeneration of AC defects has been a major challenge in the field of regenerative medicine.As defects progress,they often extend from the cartilage layer to the subchondral bone and ultimately lead to osteoarthritis.Tissue engineering techniques bring new hope for AC regeneration.To meet the regenerative requirements of the heterogeneous and layered structure of native AC tissue,a substantial number of multilayered biomimetic scaffolds have been studied.Ideal multilayered scaffolds should generate zone-specific functional tissue similar to native AC tissue.This review focuses on the current status of multilayered scaffolds developed for AC defect repair,including design strategies based on the degree of defect severity and the zone-specific characteristics of AC tissue,the selection and composition of biomaterials,and techniques for design and manufacturing.The challenges and future perspectives of biomimetic multilayered scaffold strategies for AC regeneration are also discussed.
基金financially supported by the National Natural Science Foundation of China(32225029,22205240,52073287,22075289,82071552 and 22376006)the National Key R&D Program of China(2023YFC2605003)。
基金supported by grants from the National Natural Science Foundation of China(82070578,81870394,82000530 and 81670510)Chongqing Natural Science Fund for Distinguished Young Scholars(cstc2019jcyjjqX0003)+2 种基金Science Innovation Capacity Promotion Project of Army Medical University(2019XQY03)National Key Research and Development Program of China(2016YFC1302200)Collaborative Innovation Center of Chinese Ministry of Education(2020-39).
文摘The interaction between the gastric epithelium and immune cells plays key roles in H. pylori-associated pathology. Here, we demonstrate a procolonization and proinflammatory role of tubulointerstitial nephritis antigen-like 1 (TINAGL1), a newly discovered matricellular protein, in H. pylori infection. Increased TINAGL1 production by gastric epithelial cells (GECs) in the infected gastric mucosa was synergistically induced by H. pylori and IL-1β via the ERK-SP1 pathway in a cagA-dependent manner. Elevated human gastric TINAGL1 correlated with H. pylori colonization and the severity of gastritis, and mouse TINAGL1 derived from non-bone marrow-derived cells promoted bacterial colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Tinagl1−/− and Tinagl1ΔGEC mice and were increased in mice injected with mouse TINAGL1. Mechanistically, TINAGL1 suppressed CCL21 expression and promoted CCL2 production in GECs by directly binding to integrin α5β1 to inhibit ERK and activate the NF-κB pathway, respectively, which not only led to decreased gastric influx of moDCs via CCL21-CCR7-dependent migration and, as a direct consequence, reduced the bacterial clearance capacity of the H. pylori-specific Th1 response, thereby promoting H. pylori colonization, but also resulted in increased gastric influx of Ly6Chigh monocytes via CCL2-CCR2-dependent migration. In turn, TINAGL1 induced the production of the proinflammatory protein S100A11 by Ly6Chigh monocytes, promoting H. pylori-associated gastritis. In summary, we identified a model in which TINAGL1 collectively ensures H. pylori persistence and promotes gastritis.
