Selective hydrogenation is an important industrial catalytic process in chemical upgrading, where Pd-based catalysts are widely used because of their high hydrogenation activities. However, poor selectivity and short ...Selective hydrogenation is an important industrial catalytic process in chemical upgrading, where Pd-based catalysts are widely used because of their high hydrogenation activities. However, poor selectivity and short catalyst lifetime because of heavy coke formation have been major concerns. In this work, atomically dispersed Pd atoms were successfully synthesized on graphitic carbon nitride （g-C3N4） using atomic layer deposition. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy （HAADF-STEM） confirmed the dominant presence of isolated Pd atoms without Pd nanoparticle （NP） formation. During selective hydrogenation of acetylene in excess ethylene, the g-C3N4-supported Pd NP catalysts had strikingly higher ethylene selectivities than the conventional Pd/Al2O3 and Pd/SiO2 catalysts. In-situ X-ray photoemission spectroscopy revealed that the considerable charge transfer from the Pd NPs to g-C3N4 likely plays an important role in the catalytic performance enhancement. More impressively, the single-atom Pd1/C3N4 catalyst exhibited both higher ethylene selectivity and higher coking resistance. Our work demonstrates that the single-atom Pd catalyst is a promising candidate for improving both selectivity and coking-resistance in hydrogenation reactions.展开更多
Prostaglandin E2(PGE2), a major cyclooxygenase-2(COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis(OA) patients. However, NSAIDs, including COX-2 inhibitors,...Prostaglandin E2(PGE2), a major cyclooxygenase-2(COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis(OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts(EP4 Lys M) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in the EP4 Lys M mice, with reduced Netrin-1 secretion and CGRP-positive sensory innervation of the subchondral bone. The expression of plateletderived growth factor-BB(PDGF-BB) was also lower in the EP4 Lys Mmice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in the EP4 Lys Mmice. Finally, we showed that the Gαs/PI3 K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA.展开更多
Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness.Herein,a targeting multifunctional black phosphorus(BP)nanoparticle,modified by PEGylated hyaluronic acid(HA),was ...Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness.Herein,a targeting multifunctional black phosphorus(BP)nanoparticle,modified by PEGylated hyaluronic acid(HA),was designed for photothermal/photodynamic/photo-immunotherapy.In vitro and in vivo assays indicated that HA-BP nanoparticles possess excellent biocompatibility,stability,and sufficient therapeutic efficacy in the combined therapy of photothermal therapy(PTT)and photodynamic therapy(PDT)for cancer therapy.Moreover,the results of in vitro showed that HA-BP down-regulated the expression of CD206(M2 macrophage marker)by 42.3%and up-regulated the ratio of CD86(M1 macrophage marker)by 59.6%,indicating that HABP nanoparticles have functions in remodeling tumor associated macrophages(TAMs)phenotype(from protumor M2 TAMs to anti-tumor M1 macrophages).Fluorescence(FL)and photoacoustic(PA)multimodal imaging confirmed the selective accumulation of HA-BP in tumor site via both CD44^+mediated active targeting and passive EPR effect.In vitro and in vivo studies suggested that the combined therapy of PDT,PTT and immunotherapy using HA-BP could not only significantly inhibit original tumor but also induce immunogenic cell death(ICD)and release Damage-associated molecular patterns(DAMPs),which could induce maturation of dendritic cells(DCs)and activate effector cells that robustly evoke the antitumor immune responses for cancer treatment.This study expands the biomedical application of BP nanoparticles and displays the potential of modified BP as a multifunctional therapeutic platform for the future cancer therapy.展开更多
目的明确骨质疏松女性股骨颈骨折与股骨转子间骨折的髋部骨密度差异,探讨骨质疏松患者发生髋部骨折(股骨颈骨折、股骨转子间骨折)与骨折部位骨密度的相关性。方法回顾性分析2015年1月1日至2016年12月31日期间于福建省某三级甲等医院的...目的明确骨质疏松女性股骨颈骨折与股骨转子间骨折的髋部骨密度差异,探讨骨质疏松患者发生髋部骨折(股骨颈骨折、股骨转子间骨折)与骨折部位骨密度的相关性。方法回顾性分析2015年1月1日至2016年12月31日期间于福建省某三级甲等医院的住院治疗的骨质疏松及髋部骨质疏松性骨折患者172例,其中无病史的原发骨质疏松患者109例、骨质疏松性股骨颈骨折患者39例、骨质疏松性转子间骨折24例。分别统计3组患者年龄、体质指数、糖尿病患病情况、骨折侧别、髋部各部位骨密度、血清I型胶原交联C末端肽(C-terminal crosslinking telopeptide of type I collagen,CTX)、I型原胶原N-端前肽(procollagen type I N propeptide,PINP)、25羟基维生素D(25-OH-D)。分别进行三组间及两两组间比较。结果三组间年龄、体质指数、糖尿病患病率差异无统计学意义(F=2.667,P=0.072;F=0.882,P=0.416;χ^2=3.216,P=0.232),股骨颈骨折组与股骨转子间骨折组组间骨折侧别差异无统计学意义(χ^2=0.958,P=0.328),三组间髋部Ward区骨密度差异无统计学意义(F=2.937,P=0.056),髋部骨密度比较,股骨颈、股骨大转子、股骨转子间、髋部整体差异有统计学意义(F=7.825,P=0.001;F=8.668,P<0.001;F=9.657,P<0.001)。股骨颈骨折组、转子间骨折组股骨颈、股骨大转子、股骨转子间、髋部整体骨密度均小于骨质疏松组,差异均有统计学意义(P<0.05);股骨颈骨折组与转子间骨折组股骨颈、大转子、转子间、髋部整体骨密度差异均无统计学意义(P>0.05)。三组间β-CTX、P1NP、维生素D差异均有统计学意义(P<0.05)。股骨颈骨折组、转子间骨折组β-CTX、维生素D均小于骨质疏松组,差异均有统计学意义(P<0.05);转子间骨折与骨质疏松组P1NP差异无统计学意义,股骨颈骨折组与转子间骨折组股骨颈、大转子、转子间、髋部整体骨密度差异均无统计学意义(P>0.05)。结论女性骨质�展开更多
Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement.Attempts in this area tend to develop new forms to make their applications more convenient and wi...Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement.Attempts in this area tend to develop new forms to make their applications more convenient and wider.Here,we propose a novel Chinese herb microneedle(CHMN)patch by integrating the herbal extracts,Premna microphylla and Centella asiatica,with microstructure of microneedle for wound healing.Such path is composed of sap extracted from the herbal leaves via traditional kneading method and solidified by plant ash derived from the brine induced process of tofu in a well-designed mold.Because the leaves of the Premna microphylla are rich in pectin and various amino acids,the CHMN could be imparted with medicinal efficacy of heat clearing,detoxicating,detumescence and hemostatic.Besides,with the excellent pharmaceutical activity of Asiatic acid extracted from Centella asiatica,the CHMN is potential in promoting relevant growth factor genes expression in fibroblasts and showing excellent performance in anti-oxidant,anti-inflammatory and anti-bacterial activity.Taking advantages of these pure herbal compositions,we have demonstrated that the derived CHMN was with dramatical achievement in anti-bacteria,inhibiting inflammatory,collagen deposition,angiogenesis and tissue reconstruction during the wound closure.These results indicate that the integration of traditional Chinese herbs with progressive technologies will facilitate the development and promotion of traditional Chinese medicine in modern society.展开更多
基金Acknowledgements This work was supported by the Thousand Talents Plan, the National Natural Science Foundation of China （Nos. 21473169, 21673215, and 51402283）, the Fundamental Research Funds for the Central Universities （Nos. WK2060030017 and WK2060190026）, and the startup funds from the University of Science and Technology of China. This work was also supported by Hefei Science Center （No. 2015HSC-UP010）.
文摘Selective hydrogenation is an important industrial catalytic process in chemical upgrading, where Pd-based catalysts are widely used because of their high hydrogenation activities. However, poor selectivity and short catalyst lifetime because of heavy coke formation have been major concerns. In this work, atomically dispersed Pd atoms were successfully synthesized on graphitic carbon nitride （g-C3N4） using atomic layer deposition. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy （HAADF-STEM） confirmed the dominant presence of isolated Pd atoms without Pd nanoparticle （NP） formation. During selective hydrogenation of acetylene in excess ethylene, the g-C3N4-supported Pd NP catalysts had strikingly higher ethylene selectivities than the conventional Pd/Al2O3 and Pd/SiO2 catalysts. In-situ X-ray photoemission spectroscopy revealed that the considerable charge transfer from the Pd NPs to g-C3N4 likely plays an important role in the catalytic performance enhancement. More impressively, the single-atom Pd1/C3N4 catalyst exhibited both higher ethylene selectivity and higher coking resistance. Our work demonstrates that the single-atom Pd catalyst is a promising candidate for improving both selectivity and coking-resistance in hydrogenation reactions.
基金supported by grants from the National Key Research and Development Program of China (2020YFC2002800 to J.L. and 2018YFC1105102 to J.L.)the National Natural Science Foundation of China (91949127, 92168204 to J.L.)the Fundamental Research Funds for the Central Universities (22120210586)
文摘Prostaglandin E2(PGE2), a major cyclooxygenase-2(COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis(OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts(EP4 Lys M) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in the EP4 Lys M mice, with reduced Netrin-1 secretion and CGRP-positive sensory innervation of the subchondral bone. The expression of plateletderived growth factor-BB(PDGF-BB) was also lower in the EP4 Lys Mmice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in the EP4 Lys Mmice. Finally, we showed that the Gαs/PI3 K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA.
基金This work was supported by the National Natural Science Foundation of China(51773231)the Natural Science Foundation of Guangdong Province(2014A030312018,2016A030313315)the Project of Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province(2011A060901013).
文摘Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness.Herein,a targeting multifunctional black phosphorus(BP)nanoparticle,modified by PEGylated hyaluronic acid(HA),was designed for photothermal/photodynamic/photo-immunotherapy.In vitro and in vivo assays indicated that HA-BP nanoparticles possess excellent biocompatibility,stability,and sufficient therapeutic efficacy in the combined therapy of photothermal therapy(PTT)and photodynamic therapy(PDT)for cancer therapy.Moreover,the results of in vitro showed that HA-BP down-regulated the expression of CD206(M2 macrophage marker)by 42.3%and up-regulated the ratio of CD86(M1 macrophage marker)by 59.6%,indicating that HABP nanoparticles have functions in remodeling tumor associated macrophages(TAMs)phenotype(from protumor M2 TAMs to anti-tumor M1 macrophages).Fluorescence(FL)and photoacoustic(PA)multimodal imaging confirmed the selective accumulation of HA-BP in tumor site via both CD44^+mediated active targeting and passive EPR effect.In vitro and in vivo studies suggested that the combined therapy of PDT,PTT and immunotherapy using HA-BP could not only significantly inhibit original tumor but also induce immunogenic cell death(ICD)and release Damage-associated molecular patterns(DAMPs),which could induce maturation of dendritic cells(DCs)and activate effector cells that robustly evoke the antitumor immune responses for cancer treatment.This study expands the biomedical application of BP nanoparticles and displays the potential of modified BP as a multifunctional therapeutic platform for the future cancer therapy.
文摘目的明确骨质疏松女性股骨颈骨折与股骨转子间骨折的髋部骨密度差异,探讨骨质疏松患者发生髋部骨折(股骨颈骨折、股骨转子间骨折)与骨折部位骨密度的相关性。方法回顾性分析2015年1月1日至2016年12月31日期间于福建省某三级甲等医院的住院治疗的骨质疏松及髋部骨质疏松性骨折患者172例,其中无病史的原发骨质疏松患者109例、骨质疏松性股骨颈骨折患者39例、骨质疏松性转子间骨折24例。分别统计3组患者年龄、体质指数、糖尿病患病情况、骨折侧别、髋部各部位骨密度、血清I型胶原交联C末端肽(C-terminal crosslinking telopeptide of type I collagen,CTX)、I型原胶原N-端前肽(procollagen type I N propeptide,PINP)、25羟基维生素D(25-OH-D)。分别进行三组间及两两组间比较。结果三组间年龄、体质指数、糖尿病患病率差异无统计学意义(F=2.667,P=0.072;F=0.882,P=0.416;χ^2=3.216,P=0.232),股骨颈骨折组与股骨转子间骨折组组间骨折侧别差异无统计学意义(χ^2=0.958,P=0.328),三组间髋部Ward区骨密度差异无统计学意义(F=2.937,P=0.056),髋部骨密度比较,股骨颈、股骨大转子、股骨转子间、髋部整体差异有统计学意义(F=7.825,P=0.001;F=8.668,P<0.001;F=9.657,P<0.001)。股骨颈骨折组、转子间骨折组股骨颈、股骨大转子、股骨转子间、髋部整体骨密度均小于骨质疏松组,差异均有统计学意义(P<0.05);股骨颈骨折组与转子间骨折组股骨颈、大转子、转子间、髋部整体骨密度差异均无统计学意义(P>0.05)。三组间β-CTX、P1NP、维生素D差异均有统计学意义(P<0.05)。股骨颈骨折组、转子间骨折组β-CTX、维生素D均小于骨质疏松组,差异均有统计学意义(P<0.05);转子间骨折与骨质疏松组P1NP差异无统计学意义,股骨颈骨折组与转子间骨折组股骨颈、大转子、转子间、髋部整体骨密度差异均无统计学意义(P>0.05)。结论女性骨质�
基金This work was supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52073060,61927805 and 22002018)+1 种基金the Natural Science Foundation of Jiangsu(BE2018707)the Shenzhen Fundamental Research Program(JCYJ20190813152616459)。
文摘Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement.Attempts in this area tend to develop new forms to make their applications more convenient and wider.Here,we propose a novel Chinese herb microneedle(CHMN)patch by integrating the herbal extracts,Premna microphylla and Centella asiatica,with microstructure of microneedle for wound healing.Such path is composed of sap extracted from the herbal leaves via traditional kneading method and solidified by plant ash derived from the brine induced process of tofu in a well-designed mold.Because the leaves of the Premna microphylla are rich in pectin and various amino acids,the CHMN could be imparted with medicinal efficacy of heat clearing,detoxicating,detumescence and hemostatic.Besides,with the excellent pharmaceutical activity of Asiatic acid extracted from Centella asiatica,the CHMN is potential in promoting relevant growth factor genes expression in fibroblasts and showing excellent performance in anti-oxidant,anti-inflammatory and anti-bacterial activity.Taking advantages of these pure herbal compositions,we have demonstrated that the derived CHMN was with dramatical achievement in anti-bacteria,inhibiting inflammatory,collagen deposition,angiogenesis and tissue reconstruction during the wound closure.These results indicate that the integration of traditional Chinese herbs with progressive technologies will facilitate the development and promotion of traditional Chinese medicine in modern society.
