The NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome is an intracellular protein complex containing a nucleotide-binding oligomerization domain,leucine-rich repeats,and a pyrin domain.It i...The NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome is an intracellular protein complex containing a nucleotide-binding oligomerization domain,leucine-rich repeats,and a pyrin domain.It is a key regulator of inflammation in viral pneumonia(VP).Small-molecule inhibitors targeting various NLRP3 binding sites are advancing into early clinical trials,but their therapeutic utility is incompletely established.Xuanfei Baidu Formula(XF),clinically used for VP treatment,attenuates NLRP3 activation by hampering caspase-11 to impede polarization of pro-inflammatory macrophages in a model of lipopolysaccharide(LPS)-induced lung injury inmice.Herein,we demonstrate that XF attenuated influenza A virus(IAV)-induced lung inflammation as well as lung injury in immunocompetent(but not in macrophage-depleted)mice.RNA sequencing of sorted lung macrophages from IAV-infected mice revealed that XF inhibited activation of the NLRP3 inflammation and interleukin(IL)-1βproduction.Quantitative nuclear magnetic resonance of XF enabled us to develop XF-Comb1,a fixed-ratio combination of five bioactive compounds that recapitulated the bioactivity of XF in suppressing NLRP3 activation in macrophages in vitro and in vivo.Interestingly,XF-Comb1 inhibited assembly of the NLRP3 inflammasome through multi-site interactions with functional residues of NLRP3,apoptosis-associated speck-like protein containing caspase recruitment domain(ASC),and caspase-1.Taken together,this work advances the development of NLRP3 inhibitors by translating a complex herbal formula into defined bioactive compounds.展开更多
Aqueous microdroplets are of significant interest in biological fields, while the employment of water-inoil (w/o) emulsion and lack of spatial control precluded its widespread application. Herein a novel microfluidic ...Aqueous microdroplets are of significant interest in biological fields, while the employment of water-inoil (w/o) emulsion and lack of spatial control precluded its widespread application. Herein a novel microfluidic approach is developed to generate water-in-water (w/w) microdroplets embedded in hydrogel microfibers. Aqueous two phase system (ATPS) is applied to generate w/w droplets, and alginate is introduced to continuous phase to form microfibers, which offers spatial restriction and manipulation possibility to droplets. The size and pattern of aqueous droplets can be precisely controlled, and immobilization within hydrogel fiber facilitates easy manipulation and observation. The microdroplets surrounded by hydrophilic environment can act as a cell-cell interaction model, and their potential for biological and environmental applications are demonstrated by long-term culture of encapsulated cells and water remediation of Bacillus subtilis.展开更多
Imparting one-dimensional(1D)ultrafine organic nanowires with tailored ligands and atomically-dispersed central noble metal to craft high-performance hybrid single atom electrocatalysts offers a prospective yet challe...Imparting one-dimensional(1D)ultrafine organic nanowires with tailored ligands and atomically-dispersed central noble metal to craft high-performance hybrid single atom electrocatalysts offers a prospective yet challenging approach for the advancement in hydrogen evolution reactions(HER).Herein,we report the evaporation-induced self-assembly of sequence-defined amphiphilic alternating azopeptoids(AAAPs)to generate photo-responsive and micron-scale ultrafine peptoid nanowires(UFPNWs)with a diameter of~1.8 nm via pendants'hydrophobic conjugate stacking mechanism,exemplifying the finest biomimetic polymers-based nanowires to date.A series of 1D UFPNWs-based single-atom catalysts(SACs)were meticulously fabricated using the chelation interaction between Pt ions and nitrogenous ligands.The photo-controllable electrocatalytic performance was evaluated toward acidic HER,which was highly dependent on the presence of Pt elements,the structural characteristic of supports,and the peripheral coordination microenvironment of the center Pt atoms.Notably,the Pt-based hybrid SACs using terpyridine-modified UFPNWs as support presented favorable electrocatalytic capacity with an overpotential of~20 m V at a current density of 10 m A cm^(-2),and a mass activity of 89.6 times greater than commercial Pt/C catalyst.Our work paves an appealing avenue for the construction of stimuli-responsive 1D organic nanowire-based hybrid catalysts with controllable electrocatalytic HER performance.展开更多
Oxidative stress is associated with many acute and chronic inflammatory diseases.Development of nanomaterial-based enzyme mimetics for reactive oxygen species(ROS)scavenging is challenging,but holds great promise for ...Oxidative stress is associated with many acute and chronic inflammatory diseases.Development of nanomaterial-based enzyme mimetics for reactive oxygen species(ROS)scavenging is challenging,but holds great promise for the treatment of inflammatory diseases.Herein,we report the highly ordered manganese dioxide encapsulated selenium-melanin(Se@Me@MnO_(2))nanozyme with high efficiency for intracellular antioxidation and anti-inflammation.The Se@Me@MnO_(2)nanozyme is sequentially fabricated through the radical polymerization and the in-situ oxidation-reduction.In vitro experimental results demonstrated that the Se@Me@MnO_(2) nanozyme exhibits multiple enzyme activities to scavenge ROS,including catalase(CAT),glutathione peroxidase(GPx)and superoxide dismutase(SOD).Mechanism researches illustrated that the Se core possesses GPx-like catalytic activity,the Me and the MnO_(2) possess both the SOD-like and the CAT-like activities.What’s more,due to the stable unpaired electrons existing in the nanozyme,the Se,Me and MnO_(2) provide synergistic and fast electron transfer effect to achieve the quickly scavenging of hydrogen peroxide,hydroxyl radical,and superoxide anion.Further in vivo experimental results showed that this biocompatible nanozyme exhibits cytoprotective effects by resisting ROS-mediated damage,thereby alleviating the inflammation.This multienzyme mimetics is believed to be an excellent ROS scavenger and have a good potential in clinical therapy for ROS-related diseases.展开更多
Cross-modal image-text retrieval is a fundamental task in bridging vision and language. It faces two main challenges that are typically not well addressed in previous works. 1) Generalizability: Existing methods often...Cross-modal image-text retrieval is a fundamental task in bridging vision and language. It faces two main challenges that are typically not well addressed in previous works. 1) Generalizability: Existing methods often assume a strong semantic correlation between each text-image pair, which are thus difficult to generalize to real-world scenarios where the weak correlation dominates. 2) Efficiency: Many latest works adopt the single-tower architecture with heavy detectors, which are inefficient during the inference stage because the costly computation needs to be repeated for each text-image pair. In this work, to overcome these two challenges, we propose a two-tower cross-modal contrastive learning (CMCL) framework. Specifically, we first devise a two-tower architecture, which enables a unified feature space for the text and image modalities to be directly compared with each other, alleviating the heavy computation during inference. We further introduce a simple yet effective module named multi-grid split (MGS) to learn fine-grained image features without using detectors. Last but not the least, we deploy a cross-modal contrastive loss on the global image/text features to learn their weak correlation and thus achieve high generalizability. To validate that our CMCL can be readily generalized to real-world scenarios, we construct a large multi-source image-text dataset called weak semantic correlation dataset (WSCD). Extensive experiments show that our CMCL outperforms the state-of-the-arts while being much more efficient.展开更多
基金supported by the National Natural Science Foundation of China(82141201,82405164,82204878,and 32170872)the Haihe Laboratory of Modern Chinese Medicine(Research and development of a universal treatment formula for respiratory viral infections)+3 种基金the National Key Research and Development Program of China(2021YFC1712905,2021YFC1712904,2020YFA0708004,2021YFE0200300,and 2023YFC2306202)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202002,ZYYCXTD-D-202001)the China Postdoctoral Science Foundation(2023M742626)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(CPSF)(GZC20231927).
文摘The NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome is an intracellular protein complex containing a nucleotide-binding oligomerization domain,leucine-rich repeats,and a pyrin domain.It is a key regulator of inflammation in viral pneumonia(VP).Small-molecule inhibitors targeting various NLRP3 binding sites are advancing into early clinical trials,but their therapeutic utility is incompletely established.Xuanfei Baidu Formula(XF),clinically used for VP treatment,attenuates NLRP3 activation by hampering caspase-11 to impede polarization of pro-inflammatory macrophages in a model of lipopolysaccharide(LPS)-induced lung injury inmice.Herein,we demonstrate that XF attenuated influenza A virus(IAV)-induced lung inflammation as well as lung injury in immunocompetent(but not in macrophage-depleted)mice.RNA sequencing of sorted lung macrophages from IAV-infected mice revealed that XF inhibited activation of the NLRP3 inflammation and interleukin(IL)-1βproduction.Quantitative nuclear magnetic resonance of XF enabled us to develop XF-Comb1,a fixed-ratio combination of five bioactive compounds that recapitulated the bioactivity of XF in suppressing NLRP3 activation in macrophages in vitro and in vivo.Interestingly,XF-Comb1 inhibited assembly of the NLRP3 inflammasome through multi-site interactions with functional residues of NLRP3,apoptosis-associated speck-like protein containing caspase recruitment domain(ASC),and caspase-1.Taken together,this work advances the development of NLRP3 inhibitors by translating a complex herbal formula into defined bioactive compounds.
基金financially supported by the National Natural Science Foundation of China (Nos. 81872835, 21621003)Ministry of Science and Technology (Nos. 2017YFC0906902 and 2017ZX09301032)Macao Science and Technology Development Fund (No. 129/2017/A3)
文摘Aqueous microdroplets are of significant interest in biological fields, while the employment of water-inoil (w/o) emulsion and lack of spatial control precluded its widespread application. Herein a novel microfluidic approach is developed to generate water-in-water (w/w) microdroplets embedded in hydrogel microfibers. Aqueous two phase system (ATPS) is applied to generate w/w droplets, and alginate is introduced to continuous phase to form microfibers, which offers spatial restriction and manipulation possibility to droplets. The size and pattern of aqueous droplets can be precisely controlled, and immobilization within hydrogel fiber facilitates easy manipulation and observation. The microdroplets surrounded by hydrophilic environment can act as a cell-cell interaction model, and their potential for biological and environmental applications are demonstrated by long-term culture of encapsulated cells and water remediation of Bacillus subtilis.
基金supported by the National Natural Science Foundation of China(52373114,52073092,22231007,22001071)。
文摘Imparting one-dimensional(1D)ultrafine organic nanowires with tailored ligands and atomically-dispersed central noble metal to craft high-performance hybrid single atom electrocatalysts offers a prospective yet challenging approach for the advancement in hydrogen evolution reactions(HER).Herein,we report the evaporation-induced self-assembly of sequence-defined amphiphilic alternating azopeptoids(AAAPs)to generate photo-responsive and micron-scale ultrafine peptoid nanowires(UFPNWs)with a diameter of~1.8 nm via pendants'hydrophobic conjugate stacking mechanism,exemplifying the finest biomimetic polymers-based nanowires to date.A series of 1D UFPNWs-based single-atom catalysts(SACs)were meticulously fabricated using the chelation interaction between Pt ions and nitrogenous ligands.The photo-controllable electrocatalytic performance was evaluated toward acidic HER,which was highly dependent on the presence of Pt elements,the structural characteristic of supports,and the peripheral coordination microenvironment of the center Pt atoms.Notably,the Pt-based hybrid SACs using terpyridine-modified UFPNWs as support presented favorable electrocatalytic capacity with an overpotential of~20 m V at a current density of 10 m A cm^(-2),and a mass activity of 89.6 times greater than commercial Pt/C catalyst.Our work paves an appealing avenue for the construction of stimuli-responsive 1D organic nanowire-based hybrid catalysts with controllable electrocatalytic HER performance.
基金supported by the Innovation Zone Project(No.18-163-12-ZT-003-077-01)Health Major Project(Nos.BWS17J028 and AWS16J018)National Natural Science Foundation of China(Nos.81872835,21621003,and 21563010).
文摘Oxidative stress is associated with many acute and chronic inflammatory diseases.Development of nanomaterial-based enzyme mimetics for reactive oxygen species(ROS)scavenging is challenging,but holds great promise for the treatment of inflammatory diseases.Herein,we report the highly ordered manganese dioxide encapsulated selenium-melanin(Se@Me@MnO_(2))nanozyme with high efficiency for intracellular antioxidation and anti-inflammation.The Se@Me@MnO_(2)nanozyme is sequentially fabricated through the radical polymerization and the in-situ oxidation-reduction.In vitro experimental results demonstrated that the Se@Me@MnO_(2) nanozyme exhibits multiple enzyme activities to scavenge ROS,including catalase(CAT),glutathione peroxidase(GPx)and superoxide dismutase(SOD).Mechanism researches illustrated that the Se core possesses GPx-like catalytic activity,the Me and the MnO_(2) possess both the SOD-like and the CAT-like activities.What’s more,due to the stable unpaired electrons existing in the nanozyme,the Se,Me and MnO_(2) provide synergistic and fast electron transfer effect to achieve the quickly scavenging of hydrogen peroxide,hydroxyl radical,and superoxide anion.Further in vivo experimental results showed that this biocompatible nanozyme exhibits cytoprotective effects by resisting ROS-mediated damage,thereby alleviating the inflammation.This multienzyme mimetics is believed to be an excellent ROS scavenger and have a good potential in clinical therapy for ROS-related diseases.
文摘Cross-modal image-text retrieval is a fundamental task in bridging vision and language. It faces two main challenges that are typically not well addressed in previous works. 1) Generalizability: Existing methods often assume a strong semantic correlation between each text-image pair, which are thus difficult to generalize to real-world scenarios where the weak correlation dominates. 2) Efficiency: Many latest works adopt the single-tower architecture with heavy detectors, which are inefficient during the inference stage because the costly computation needs to be repeated for each text-image pair. In this work, to overcome these two challenges, we propose a two-tower cross-modal contrastive learning (CMCL) framework. Specifically, we first devise a two-tower architecture, which enables a unified feature space for the text and image modalities to be directly compared with each other, alleviating the heavy computation during inference. We further introduce a simple yet effective module named multi-grid split (MGS) to learn fine-grained image features without using detectors. Last but not the least, we deploy a cross-modal contrastive loss on the global image/text features to learn their weak correlation and thus achieve high generalizability. To validate that our CMCL can be readily generalized to real-world scenarios, we construct a large multi-source image-text dataset called weak semantic correlation dataset (WSCD). Extensive experiments show that our CMCL outperforms the state-of-the-arts while being much more efficient.
