Many effective pretreatment methods (such as dilute acid, dilute alkali, ionic liquids, etc.) have been developed for lignocellulose upgrading, but several defaults of low working mass, high sugar loss and extra cost ...Many effective pretreatment methods (such as dilute acid, dilute alkali, ionic liquids, etc.) have been developed for lignocellulose upgrading, but several defaults of low working mass, high sugar loss and extra cost of solid-liquid separation and water washing hinder their large-scale applica- tion in industry. Besides, the valorization of lignin-rich residue from pretreated biomass after hy- drolysis or fermentation greatly contributes to the economy and sustainability of lignocellulosic biorefinery, which is usually underestimated. This study developed a densification pretreatment with binary chemicals (densifying lignocellulosic biomass with sulfuric acid (SA) and metal salt (MS) followed by autoclave treatment ((DLCA(SA-MS)), which was conducted under mild con- dition (121 ℃) with a biomass working mass as high as 400 kg/m^(3) . The DLCA(SA-MS) biomass achieved over 95% sugar retention, 90% enzymatic sugar conversion and a high concentration of fermentable sugar (212.3 g/L) with superior fermentability. Furthermore, bio-adsorbent de- rived from DLCA(SA-MS) biomass residue was highly adsorptive and suitable for dyeing wastew- ater treatment, providing a feasible and eco-friendly method for lignin-rich residue valorization. These findings indicated that DLCA(SA-MS) pretreatment enables the full-component utilization of biomass and boosts the economic viability of lignocellulosic biorefinery.展开更多
Spinal cord injury(SCI)is a traumatic condition that results in impaired motor and sensory function.Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord,and f...Spinal cord injury(SCI)is a traumatic condition that results in impaired motor and sensory function.Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord,and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI.Although human umbilical cord mesenchymal stem cells(Huc-MSCs)can ameliorate inflammatory microenvironments and promote neural regeneration in SCI,their efficacy is greatly limited by the local microenvironment after SCI.Therefore,in this study,we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor,in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence,and combined with the reactive oxygen species(ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair.Meanwhile,we also modified the classic ferroptosis inhibitor Ferrostatin-1(Fer-1)and synthesized a new prodrug Feborastatin-1(Feb-1).The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI,and promoted the recovery of neurological function in rats with SCI.This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.展开更多
Spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon regeneration.Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal rege...Spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon regeneration.Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury,as well as the limited systemic drug delivery efficiency caused by blood spinal cord barrier.To develop an effective non-invasive treatment strategy for SCI in clinic,we generated an autologous plasma exosome(AP-EXO)based biological scaffold where AP-EXO was loaded with neuron targeting peptide(RVG)and growth-facilitating peptides(ILP and ISP).This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment,thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in mice.More importantly,in ex vivo,human plasma exosomes(HP-EXO)loaded with combinatory peptides of RVG,ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI mice.Combining the efficacy and safety,the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating SCI.It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.展开更多
Human immunodeficiency virus-1(HIV-1)encodes simply 15 proteins and thus depends on multiple host cellular factors for virus reproduction.Spastin,a microtubule severing protein,is an identified HIV-1 dependency factor...Human immunodeficiency virus-1(HIV-1)encodes simply 15 proteins and thus depends on multiple host cellular factors for virus reproduction.Spastin,a microtubule severing protein,is an identified HIV-1 dependency factor,but the mechanism regulating HIV-1 is unclear.Here,the study showed that knockdown of spastin inhibited the production of the intracellular HIV-1 Gag protein and new virions through enhancing Gag lysosomal degradation.Further investigation showed that increased sodium tolerance 1(IST1),the subunit of endosomal sorting complex required for transport(ESCRT),could interact with the MIT domain of spastin to regulate the intracellular Gag production.In summary,spastin is required for HIV-1 replication,while spastin-IST1 interaction facilitates virus production by regulating HIV-1 Gag intracellular trafficking and degradation.Spastin may serve as new target for HIV-1 prophylactic and therapy.展开更多
基金supported by the National Key R&D Program of China(No.2021YFC2101301).
文摘Many effective pretreatment methods (such as dilute acid, dilute alkali, ionic liquids, etc.) have been developed for lignocellulose upgrading, but several defaults of low working mass, high sugar loss and extra cost of solid-liquid separation and water washing hinder their large-scale applica- tion in industry. Besides, the valorization of lignin-rich residue from pretreated biomass after hy- drolysis or fermentation greatly contributes to the economy and sustainability of lignocellulosic biorefinery, which is usually underestimated. This study developed a densification pretreatment with binary chemicals (densifying lignocellulosic biomass with sulfuric acid (SA) and metal salt (MS) followed by autoclave treatment ((DLCA(SA-MS)), which was conducted under mild con- dition (121 ℃) with a biomass working mass as high as 400 kg/m^(3) . The DLCA(SA-MS) biomass achieved over 95% sugar retention, 90% enzymatic sugar conversion and a high concentration of fermentable sugar (212.3 g/L) with superior fermentability. Furthermore, bio-adsorbent de- rived from DLCA(SA-MS) biomass residue was highly adsorptive and suitable for dyeing wastew- ater treatment, providing a feasible and eco-friendly method for lignin-rich residue valorization. These findings indicated that DLCA(SA-MS) pretreatment enables the full-component utilization of biomass and boosts the economic viability of lignocellulosic biorefinery.
基金supported by the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100)Tianjin Key Medical Discipline(Specialty)Construct Project(TJYXZDXK-027A)International Innovation Summit for Academicians and Experts(22JRRCRC00010).We thank the Large Instrument Sharing Platform of Tianjin Medical University for the availability of the instruments.
文摘Spinal cord injury(SCI)is a traumatic condition that results in impaired motor and sensory function.Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord,and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI.Although human umbilical cord mesenchymal stem cells(Huc-MSCs)can ameliorate inflammatory microenvironments and promote neural regeneration in SCI,their efficacy is greatly limited by the local microenvironment after SCI.Therefore,in this study,we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor,in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence,and combined with the reactive oxygen species(ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair.Meanwhile,we also modified the classic ferroptosis inhibitor Ferrostatin-1(Fer-1)and synthesized a new prodrug Feborastatin-1(Feb-1).The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI,and promoted the recovery of neurological function in rats with SCI.This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.
基金This work was supported by the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100),ChinaNational Natural Science Foundation of China(81930070)+3 种基金National Natural Science Foundation of China(82102560)the Natural Science Foundation of Shandong Province,China(ZR2021QH097)the No.69 General Fund of China Postdoctoral Science Foundation(2021M691936)Talent project of Shandong University(22480082063100),China.
文摘Spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon regeneration.Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury,as well as the limited systemic drug delivery efficiency caused by blood spinal cord barrier.To develop an effective non-invasive treatment strategy for SCI in clinic,we generated an autologous plasma exosome(AP-EXO)based biological scaffold where AP-EXO was loaded with neuron targeting peptide(RVG)and growth-facilitating peptides(ILP and ISP).This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment,thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in mice.More importantly,in ex vivo,human plasma exosomes(HP-EXO)loaded with combinatory peptides of RVG,ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI mice.Combining the efficacy and safety,the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating SCI.It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.
基金We greatly appreciate Prof.Charles Wood(University of Nebraska,Lincoln,USA)for the gift of the infectious molecular clones(pNL4.3,pNL4.3ΔEnvEGFP,and pVSV-G).the National Natural Science Foundation of China(81571987)Natural Science Foundation of Tianjin Municipal Science and Technology Commission(20JCQNJC01750,21JCQNJC01600).
文摘Human immunodeficiency virus-1(HIV-1)encodes simply 15 proteins and thus depends on multiple host cellular factors for virus reproduction.Spastin,a microtubule severing protein,is an identified HIV-1 dependency factor,but the mechanism regulating HIV-1 is unclear.Here,the study showed that knockdown of spastin inhibited the production of the intracellular HIV-1 Gag protein and new virions through enhancing Gag lysosomal degradation.Further investigation showed that increased sodium tolerance 1(IST1),the subunit of endosomal sorting complex required for transport(ESCRT),could interact with the MIT domain of spastin to regulate the intracellular Gag production.In summary,spastin is required for HIV-1 replication,while spastin-IST1 interaction facilitates virus production by regulating HIV-1 Gag intracellular trafficking and degradation.Spastin may serve as new target for HIV-1 prophylactic and therapy.
