Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may...Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.展开更多
The electrochemical reduction of CO_(2)(eCO_(2)R)under ambient conditions is crucial for reducing carbon emissions and achieving carbon neutrality.Despite progress with alkaline and neutral electrolytes,their efficien...The electrochemical reduction of CO_(2)(eCO_(2)R)under ambient conditions is crucial for reducing carbon emissions and achieving carbon neutrality.Despite progress with alkaline and neutral electrolytes,their efficiency is limited by(bi)carbonates formation.Acidic media have emerged as a solution,addressing the(bi)carbonates challenge but introducing the issue of the hydrogen evolu-tion reaction(HER),which reduces CO_(2) conversion efficiency in acidic environments.This review focuses on enhancing the selectivity of acidic CO_(2) electrolysis.It commences with an overview of the latest advancements in acidic CO_(2) electrolysis,focusing on product selectivity and electrocatalytic activity enhancements.It then delves into the critical factors shaping selectivity in acidic CO_(2) electrolysis,with a special emphasis on the influence of cations and catalyst design.Finally,the research challenges and personal perspectives of acidic CO_(2) electrolysis are suggested.展开更多
Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiven...Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines.Herein,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens.We demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo.Then,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was designed.In combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression.This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.展开更多
We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecu...We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecules to branched polyethylenimine(bPEI),over 70%of them could induce the secretion of interferon-β(IFN-β)from murine dendritic and human leukemia monocytic(DC2.4 and THP-1)cells through activating the stimulator of interferon genes(STING)pathway.We further proved that this kind of innate stimulating activity was dependent on the macromolecular architecture as heterocyclic molecules tethered linear PEI(lPEI)or dendritic polyamidoamine(PAMAM)induced no or much less IFN-βsecretion.Furthermore,we prepared a series of poly-L-lysine(PLL)-derivatives with different branches to tether with heterocyclic molecules and proved that this kind of bPEI-like structure was important in en hancing the binding affinity with STING proteins and for exhibiting innate stimulating activity.展开更多
Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death(ICD),which provides a promising alternative way for cancer immunotherapy.However,the ...Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death(ICD),which provides a promising alternative way for cancer immunotherapy.However,the immunogenic effects of such treatments are still weak and robust systemic antitumor immune responses are rarely seen when these agents were used alone.Herein,we proposed a trinity immune enhancing nanoparticles(TIENs)for boosting antitumor immune responses of chemo agents.The TIENs was constructed with Food and Drug Administration(FDA)approved polylactic acid(PLA),canonical proton-sponging cationic polymer polyethyleneimine(PEI),and Toll-like receptor 9(TLR9)agonist cytosine phosphate guanine oligodeoxynucleotide(CpG-ODN).In in vitro studies,the TIENs was proved to(1)promote antigen capturing,(2)antigen-presenting cells(APCs)activation,and(3)antigen cross-presentation.In in vivo studies,intratumorally injected TIENs greatly enhanced antitumor effect and robust immune responses of oxaliplatin and doxorubicin in murine CT26 and 4T1 tumor models,respectively.Furthermore,after decoration with a detachable shielding,the TIENs was proved to be effective in promoting the antitumor effects of chemo agents after intravenous injection.The combination of TIENs with clinically widely used chemo agents should be meaningful in boosting effective antitumor immune responses and cancer therapy.展开更多
基金supported partly by the National Natural Science Foundation of China,No.82071332the Chongqing Natural Science Foundation Joint Fund for Innovation and Development,No.CSTB2023NSCQ-LZX0041 (both to ZG)。
文摘Some studies have confirmed the neuroprotective effect of remote ischemic conditioning against stroke. Although numerous animal researches have shown that the neuroprotective effect of remote ischemic conditioning may be related to neuroinflammation, cellular immunity, apoptosis, and autophagy, the exact underlying molecular mechanisms are unclear. This review summarizes the current status of different types of remote ischemic conditioning methods in animal and clinical studies and analyzes their commonalities and differences in neuroprotective mechanisms and signaling pathways. Remote ischemic conditioning has emerged as a potential therapeutic approach for improving stroke-induced brain injury owing to its simplicity, non-invasiveness, safety, and patient tolerability. Different forms of remote ischemic conditioning exhibit distinct intervention patterns, timing, and application range. Mechanistically, remote ischemic conditioning can exert neuroprotective effects by activating the Notch1/phosphatidylinositol 3-kinase/Akt signaling pathway, improving cerebral perfusion, suppressing neuroinflammation, inhibiting cell apoptosis, activating autophagy, and promoting neural regeneration. While remote ischemic conditioning has shown potential in improving stroke outcomes, its full clinical translation has not yet been achieved.
文摘The electrochemical reduction of CO_(2)(eCO_(2)R)under ambient conditions is crucial for reducing carbon emissions and achieving carbon neutrality.Despite progress with alkaline and neutral electrolytes,their efficiency is limited by(bi)carbonates formation.Acidic media have emerged as a solution,addressing the(bi)carbonates challenge but introducing the issue of the hydrogen evolu-tion reaction(HER),which reduces CO_(2) conversion efficiency in acidic environments.This review focuses on enhancing the selectivity of acidic CO_(2) electrolysis.It commences with an overview of the latest advancements in acidic CO_(2) electrolysis,focusing on product selectivity and electrocatalytic activity enhancements.It then delves into the critical factors shaping selectivity in acidic CO_(2) electrolysis,with a special emphasis on the influence of cations and catalyst design.Finally,the research challenges and personal perspectives of acidic CO_(2) electrolysis are suggested.
基金supported by the National Natural Science Foundation of China (22222509, 52025035, 52103194, and 22105199)The Ministry of Science and Technology of China (2022YFE0110200)+3 种基金Bureau of International Cooperation Chinese Academy of Sciences (121522KYSB20200029)Jilin Province Science and Technology Development Plan (YDZJ202101ZYTS131, 20220402037GH, and 20210508049RQ)Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers (20210504001GH)The Youth Innovation Promotion Association of Chinese Academy of Sciences (2020232)。
文摘Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies.However,identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines.Herein,we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens".This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens.We demonstrated that a poly(2-oxazoline)s(POx) conjugated with OVA_(257-264) peptide through a matrix metalloprotease 2(MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo.Then,a POx-based nanovaccine containing OVA_(257-264) peptides to elicit OVA-specific T cell responses was designed.In combination with this hit-and-run vaccine system,an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression.This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.
基金the Bureau of International Cooperation Chinese Academy of Sciences(grant no.121522KYSB20200029)National Natural Science Foundation of China(grant nos.22222509,52025035,52003268,and 51973215)+3 种基金Jilin Province Science and Technology Development Plan(grant nos.YDZJ202101-ZYTS131 and 20220402037GH)Jilin Provincial International Cooperation Key Laboratory of Biomedical Polymers(grant no.20210504001GH)Changchun Science and Technology Development Plan(grant no.21ZY09)the Youth Innovation Promotion Association of Chinese Academy of Sciences(grant no.2020232).
文摘We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity.When we conjugated a series of five-,six-,or seven-membered heterocyclic molecules to branched polyethylenimine(bPEI),over 70%of them could induce the secretion of interferon-β(IFN-β)from murine dendritic and human leukemia monocytic(DC2.4 and THP-1)cells through activating the stimulator of interferon genes(STING)pathway.We further proved that this kind of innate stimulating activity was dependent on the macromolecular architecture as heterocyclic molecules tethered linear PEI(lPEI)or dendritic polyamidoamine(PAMAM)induced no or much less IFN-βsecretion.Furthermore,we prepared a series of poly-L-lysine(PLL)-derivatives with different branches to tether with heterocyclic molecules and proved that this kind of bPEI-like structure was important in en hancing the binding affinity with STING proteins and for exhibiting innate stimulating activity.
基金supported by the National Natural Science Foundation of China(Nos.51973215,52025035,52003268,51829302,and 51833010)Bureau of International Cooperation Chinese Academy of Sciences(No.121522KYSB20200029)+1 种基金the Jilin Province Science and Technology Development Plan(No.2020122331JC)support from the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2020232).
文摘Certain chemo drugs have been reported to potentially induce tumor-specific immune recognition by triggering immunogenic cell death(ICD),which provides a promising alternative way for cancer immunotherapy.However,the immunogenic effects of such treatments are still weak and robust systemic antitumor immune responses are rarely seen when these agents were used alone.Herein,we proposed a trinity immune enhancing nanoparticles(TIENs)for boosting antitumor immune responses of chemo agents.The TIENs was constructed with Food and Drug Administration(FDA)approved polylactic acid(PLA),canonical proton-sponging cationic polymer polyethyleneimine(PEI),and Toll-like receptor 9(TLR9)agonist cytosine phosphate guanine oligodeoxynucleotide(CpG-ODN).In in vitro studies,the TIENs was proved to(1)promote antigen capturing,(2)antigen-presenting cells(APCs)activation,and(3)antigen cross-presentation.In in vivo studies,intratumorally injected TIENs greatly enhanced antitumor effect and robust immune responses of oxaliplatin and doxorubicin in murine CT26 and 4T1 tumor models,respectively.Furthermore,after decoration with a detachable shielding,the TIENs was proved to be effective in promoting the antitumor effects of chemo agents after intravenous injection.The combination of TIENs with clinically widely used chemo agents should be meaningful in boosting effective antitumor immune responses and cancer therapy.