Objective:To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods: In this study,we used gi...Objective:To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods: In this study,we used ginger oil,a phytochemical with potential therapeutic properties,to prepare ginger oil patches.High-performance liquid chromatography(HPLC)was used to quantify the main active component of ginger oil,6-gingerol.Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers,including their type and concentration.Subsequently,the ginger oil patches were optimized and subjected to content determination and property evaluations.A PTSD mouse model was established using the foot-shock method.The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections,behavioral tests,and the evaluation of biomarkers such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),brain-derived neurotrophic factor(BDNF),and melatonin(MT).Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels.Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day,addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy.Conclusions: Ginger oil can be prepared as a transdermal drug patch that meets these requirements,and the bioavailability of the prepared patch is better than that of oral administration.It can improve PTSD with good patient compliance and ease of administration.Therefore,it is a promising therapeutic formulation for the treatment of PTSD.展开更多
Monitoring the status of linear guide rails is essential because they are important components in linear motion mechanical production.Thus,this paper proposes a new method of conducting the fault diagnosis of linear g...Monitoring the status of linear guide rails is essential because they are important components in linear motion mechanical production.Thus,this paper proposes a new method of conducting the fault diagnosis of linear guide rails.First,synchrosqueezing transform(SST)combined with Gaussian high-pass filter,termed as SSTG,is proposed to process vibration signals of linear guide rails and obtain time-frequency images,thus helping realize fault feature visual enhancement.Next,the coordinate attention(CA)mechanism is introduced to promote the DenseNet model and obtain the CA-DenseNet deep learning framework,thus realizing accurate fault classifica-tion.Comparison experiments with other methods reveal that the proposed method has a high classification accuracy of up to 95.0%.The experimental results further demonstrate the effectiveness and robustness of the proposed method for the fault diagnosis of linear guide rails.展开更多
This experiment was conducted to investigate the effects of increased atmospheric temperature and CO2 concentration during crop growth on the chemical composition and in vitro rumen fermentation characteristics of whe...This experiment was conducted to investigate the effects of increased atmospheric temperature and CO2 concentration during crop growth on the chemical composition and in vitro rumen fermentation characteristics of wheat straw. The field experiment was carried out from November 2012 to June 2013 at Changshu （31°32′93″N, 120°41′88″E） agro-ecological experimental station. A total of three treatments were set. The concentration of CO2 was increased to 500 pmol/mol in the first treatment （CO2 group）. The temperature was increased by 2℃ in the second treatment （TEM group） and the concentration of CO2 and temperature were both increased in the third treatment （CO2 ＋ TEM group）. The mean temperature and concentration of CO2 in control group were 10.5 ℃ and 413μmol/mol. At harvesting, the wheat straws were collected and analyzed for chemical composition and in vitro digestibility. Results showed that dry matter was significantly increased in all three treatments. Ether extracts and neutral detergent fiber were significantly increased in TEM and CO2 ＋ TEM groups. Crude protein was significantly decreased in CO2＋TEM group. In vitro digestibility analysis of wheat straw revealed that gas production was significantly decreased in CO2 and CO2 ＋ TEM groups. Methane production was significantly decreased in TEM and CO2 ＋ TEM groups. Ammonia nitrogen and microbial crude protein were significantly decreased in all three treatments. Total volatile fatty acids were significantly decreased in CO2 and CO2 ＋ TEM groups. In conclusion, the chemical composition of the wheat straw was affected by temperature and CO2 and the in vitro digestibility of wheat straw was reduced, especially in the combined treatment of temperature and CO2.展开更多
In the Internet of Things(IoT)environment,user-service interaction data are often stored in multiple distributed platforms.In this situation,recommender systems need to integrate the distributed user-service interacti...In the Internet of Things(IoT)environment,user-service interaction data are often stored in multiple distributed platforms.In this situation,recommender systems need to integrate the distributed user-service interaction data across different platforms for making a comprehensive recommendation decision,during which user privacy is probably disclosed.Moreover,as user-service interaction records accumulate over time,they significantly reduce the efficiency of recommendations.To tackle these issues,we propose a lightweight and privacy-preserving service recommendation approach named SerRec_(L2H).In SerRec_(L2H),we employ Learning to Hash(L2H)to encapsulate sensitive user-service interaction data into less-sensitive user indices,which facilitates identifying users with similar preferences efficiently for accurate recommendations.We then validate the feasibility of our proposed SerRec_(L2H)approach through massive experiments conducted on the popular WS-DREAM dataset.The comparative analysis with other competitive approaches demonstrates that our proposal surpasses other approaches in terms ofrecommendation accuracy and efficiency while protecting user privacy.展开更多
Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is ge...Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is generally preferred for use in practice.Herein,a versatile peptide,(HE)_(10)G_(5)R_(6)GDK(HE-RK),was engineered by integrating several motifs into a single sequence,including a masking segment(HE),a flexible linker(G_(5)),and a tumor-penetrating head(RK)which comprised a cell-penetrating peptide(R_(6))and a C-end Rule peptide(RGDK).The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells.Moreover,in our study,polymer micelles conjugated with the HE-RK peptide(PM-HE-RK)showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro,as well as extended blood circulation time and improved tumor targeting and penetration in vivo.Furthermore,the paclitaxel-loaded micelles(PTX/PM-HERK)demonstrated considerable antitumor efficacy,with an 81.48%tumor inhibition rate in the 4T1 mouse model.Overall,the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.展开更多
The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies;however, the underlying mechanism remains underexplored. In this study, we discovered that impai...The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies;however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stressevoked tumor susceptibility, and the stress hormone glucocorticoid(GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor(low-density lipoprotein receptor-related protein-1, LRP1) and the "don’t eat me" signal receptor(signal regulatory protein alpha, SIRPa). Further analysis revealed that GC led to a direct, glucocorticoid receptor(GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevatedgene level of SIRPa by down-regulating mi RNA-4695-3 p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPa axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPa axis may serve as a potential therapeutic strategy for tumor treatment.展开更多
Mutations in the plant homeodomain-like finger protein 6(PHF6)gene are strongly associated with acute myeloid(AML)and T-cell acute lymphoblastic leukemia(T-ALL).In this study,we demonstrated that PHF6 can bind to H3K9...Mutations in the plant homeodomain-like finger protein 6(PHF6)gene are strongly associated with acute myeloid(AML)and T-cell acute lymphoblastic leukemia(T-ALL).In this study,we demonstrated that PHF6 can bind to H3K9me3 and H3K27me1 on the nucleolar chromatin and recruit histone methyltransferase SUV39H1 to the rDNA locus.The deletion of PHF6 caused a decrease in the recruitment of SUV39H1 to rDNA gene loci,resulting in a reduction in the level of H3K9me3 and the promotion of rDNA transcription.The knockdown of either SUV39H1 or PHF6 significantly attenuated the effects of increase in H3K9me3 and suppressed the transcription of rDNA induced by the overexpression of the other interacting partner,thereby establishing an interdependent relationship between PHF6 and SUV39H1 in their control of rRNA transcription.The PHF6 clinical mutants significantly impaired the ability to bind and recruit SUV39H1 to the rDNA loci,resulting in an increase in rDNA transcription activity,the proliferation of in vitro leukemia cells,and the growth of in vivo mouse xenografts.Importantly,significantly elevated levels of pre-rRNA were observed in clinical AML patients who possessed a mutated version of PHF6.The specific rDNA transcription inhibitor CX5461 significantly reduced the resistance of U937 AML cells deficient in PHF6 to cytarabine,the drug that is most commonly used to treat AML.Collectively,we revealed a novel molecular mechanism by which PHF6 recruits methyltransferase SUV39H1 to the nucleolar region in leukemia and provided a potential therapeutic target for PHF6-mutant leukemia.展开更多
Photodynamic therapy(PDT)usually shows limited efficacy in solid tumors since traditional PDT is O_(2)^(-)dependent while solid tumors are inherently hypoxic.In addition,hypoxic tumor cells possess antiapoptotic pathw...Photodynamic therapy(PDT)usually shows limited efficacy in solid tumors since traditional PDT is O_(2)^(-)dependent while solid tumors are inherently hypoxic.In addition,hypoxic tumor cells possess antiapoptotic pathways that resist PDT-induced apoptosis.Therefore,developing photosensitizers(PSs)that show low O_(2)^(-)dependency and can induce nonapoptotic cell death pathways is critically needed.Herein,a series of Ru(II)polypyridine complex-based PSs,RuNMe,RuH,and RuCN,were synthesized,and their applications against hypoxic tumor cells through PDT were investigated.All three complexes showthe ability to generate the superoxide anion radical(·O_(2)^(-)),which is the type I photoreaction and less O_(2)^(-)dependent.RuNMe shows the best PDT performance against MCF-7 cells and three-dimensional multicellular spheroids,due to its higher cellular uptake and more reactive oxygen species generation.More importantly,RuNMe-incubated MCF-7 cells show photoinduced ferroptosis as evidenced by glutathione peroxidase 4 downregulation and lipid peroxide accumulation.This work not only develops a novel ferroptosis-inducing Ru(II)complex with the type I PDT process but also offers an effective strategy to solve tumor hypoxia in PDT.展开更多
Bacillus spp.has been proven to be critical for the quality of many fermented foods,but as one of the domain bacteria,its effect on the quality of Yibin Yacai has not been fully addressed.Herein,the effects of inocula...Bacillus spp.has been proven to be critical for the quality of many fermented foods,but as one of the domain bacteria,its effect on the quality of Yibin Yacai has not been fully addressed.Herein,the effects of inoculation of Bacillus subtilis Y4 on the physicochemical properties,flavor metabolism and microbial community changes of Yibin Yacai for three-month solid-state fermentation were investigated.The results showed that inoculation of B.subtilis Y4 could reduce the pH and salinity of Yibin Yacai,accelerate the consumption of nitrite,promote the growth of Lactobacillus and the production of sweet amino acid,and inhibit pathogenic microorganisms at the late fermentation stage.During solid-state fermentation,the dominant fungus Cystofilobasidium was positively correlated with most volatile flavor substances,which were indirectly affected by B.subtilis Y4.Furthermore,compared to spontaneous fermented Yibin Yacai,inoculation of B.subtilis Y4 promoted the production of alkenes and made the peak of ester content appear earlier.These results indicated that inoculation of B.subtilis Y4 for solid-state fermentation could improve the quality and taste of Yibin Yacai,and shorten the fermentation time.展开更多
Over the past few decades,tumor immunotherapy has revolutionized the landscape of cancer clinical treatment.There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immun...Over the past few decades,tumor immunotherapy has revolutionized the landscape of cancer clinical treatment.There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy.However,instead of a straightforward combination of multiple therapeutics,it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies,which are based on a comprehensive understanding of the physiological and pathological features.In this case,the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes.Therefore,the concept of Sequential Drug Delivery System(SDDS)is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions,thus complying with the dynamic disease evolution and the human immunity.This review summarizes the recent advancements inbiomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy.Furthermore,the rationales behind various engineering strategies are discussed.Finally,an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.展开更多
基金supported by the National Natural Scientific Foundation(82172186)Beijing Natural Scientific Foundation(L222126).
文摘Objective:To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder(PTSD),and to improve efficacy and patient compliance.Methods: In this study,we used ginger oil,a phytochemical with potential therapeutic properties,to prepare ginger oil patches.High-performance liquid chromatography(HPLC)was used to quantify the main active component of ginger oil,6-gingerol.Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers,including their type and concentration.Subsequently,the ginger oil patches were optimized and subjected to content determination and property evaluations.A PTSD mouse model was established using the foot-shock method.The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections,behavioral tests,and the evaluation of biomarkers such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),brain-derived neurotrophic factor(BDNF),and melatonin(MT).Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels.Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day,addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy.Conclusions: Ginger oil can be prepared as a transdermal drug patch that meets these requirements,and the bioavailability of the prepared patch is better than that of oral administration.It can improve PTSD with good patient compliance and ease of administration.Therefore,it is a promising therapeutic formulation for the treatment of PTSD.
基金supported by the following organizations:National Natural Science Foundation of China(Grant Nos.52375522,52207036,and 62203010)the Anhui Provincial Nat-ural Science Foundation(Grant Nos.2308085Y03 and 2208085QE167)+2 种基金the Project of the Outstanding Young Talents in Colleges and Universities of Anhui Province(Grant No.gxyqZD2022006)the College Natural Science Research Key project of Anhui Education Department(Grant No.KJ2021A0018)the University Outstanding Youth Research Project of Anhui Province(Grant No.2022AH030016)。
文摘Monitoring the status of linear guide rails is essential because they are important components in linear motion mechanical production.Thus,this paper proposes a new method of conducting the fault diagnosis of linear guide rails.First,synchrosqueezing transform(SST)combined with Gaussian high-pass filter,termed as SSTG,is proposed to process vibration signals of linear guide rails and obtain time-frequency images,thus helping realize fault feature visual enhancement.Next,the coordinate attention(CA)mechanism is introduced to promote the DenseNet model and obtain the CA-DenseNet deep learning framework,thus realizing accurate fault classifica-tion.Comparison experiments with other methods reveal that the proposed method has a high classification accuracy of up to 95.0%.The experimental results further demonstrate the effectiveness and robustness of the proposed method for the fault diagnosis of linear guide rails.
基金supported by the Special Fund for Agro-scientific Research in the Public Interest in China(No.200903003)
文摘This experiment was conducted to investigate the effects of increased atmospheric temperature and CO2 concentration during crop growth on the chemical composition and in vitro rumen fermentation characteristics of wheat straw. The field experiment was carried out from November 2012 to June 2013 at Changshu （31°32′93″N, 120°41′88″E） agro-ecological experimental station. A total of three treatments were set. The concentration of CO2 was increased to 500 pmol/mol in the first treatment （CO2 group）. The temperature was increased by 2℃ in the second treatment （TEM group） and the concentration of CO2 and temperature were both increased in the third treatment （CO2 ＋ TEM group）. The mean temperature and concentration of CO2 in control group were 10.5 ℃ and 413μmol/mol. At harvesting, the wheat straws were collected and analyzed for chemical composition and in vitro digestibility. Results showed that dry matter was significantly increased in all three treatments. Ether extracts and neutral detergent fiber were significantly increased in TEM and CO2 ＋ TEM groups. Crude protein was significantly decreased in CO2＋TEM group. In vitro digestibility analysis of wheat straw revealed that gas production was significantly decreased in CO2 and CO2 ＋ TEM groups. Methane production was significantly decreased in TEM and CO2 ＋ TEM groups. Ammonia nitrogen and microbial crude protein were significantly decreased in all three treatments. Total volatile fatty acids were significantly decreased in CO2 and CO2 ＋ TEM groups. In conclusion, the chemical composition of the wheat straw was affected by temperature and CO2 and the in vitro digestibility of wheat straw was reduced, especially in the combined treatment of temperature and CO2.
基金supported by Zhejiang Provincial Natural Science Foundation of China(No.LZ22F020002).
文摘In the Internet of Things(IoT)environment,user-service interaction data are often stored in multiple distributed platforms.In this situation,recommender systems need to integrate the distributed user-service interaction data across different platforms for making a comprehensive recommendation decision,during which user privacy is probably disclosed.Moreover,as user-service interaction records accumulate over time,they significantly reduce the efficiency of recommendations.To tackle these issues,we propose a lightweight and privacy-preserving service recommendation approach named SerRec_(L2H).In SerRec_(L2H),we employ Learning to Hash(L2H)to encapsulate sensitive user-service interaction data into less-sensitive user indices,which facilitates identifying users with similar preferences efficiently for accurate recommendations.We then validate the feasibility of our proposed SerRec_(L2H)approach through massive experiments conducted on the popular WS-DREAM dataset.The comparative analysis with other competitive approaches demonstrates that our proposal surpasses other approaches in terms ofrecommendation accuracy and efficiency while protecting user privacy.
基金funded by the National Natural Science Foundation of China(22478438,32401048,and 82273882)the Science Fund for Distinguished Young Scholars of Jiangsu Province(BK20240098)the Special Research Fund from the State Key Laboratory of Natural Medicines at China Pharmaceutical University(SKLNMZZ2024JS19).
文摘Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions,such as targeting delivery,tissue penetration and enhanced cellular uptake.However,a single ligand with multiple functions is generally preferred for use in practice.Herein,a versatile peptide,(HE)_(10)G_(5)R_(6)GDK(HE-RK),was engineered by integrating several motifs into a single sequence,including a masking segment(HE),a flexible linker(G_(5)),and a tumor-penetrating head(RK)which comprised a cell-penetrating peptide(R_(6))and a C-end Rule peptide(RGDK).The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells.Moreover,in our study,polymer micelles conjugated with the HE-RK peptide(PM-HE-RK)showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro,as well as extended blood circulation time and improved tumor targeting and penetration in vivo.Furthermore,the paclitaxel-loaded micelles(PTX/PM-HERK)demonstrated considerable antitumor efficacy,with an 81.48%tumor inhibition rate in the 4T1 mouse model.Overall,the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.
基金supported,in part,by National Natural Science Foundation of China(grant numbers 81673709,82004231,U1801284 and 81873209)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(grant number 2017BT01Y036,China)and GDUPS(2019,China)+5 种基金Guangdong Science and Technology Foundation for Distinguished Young Scholars(grant number 2017A030306004,China)Science and Technology Program of Guangzhou(grant numbers 201903010062 and 202102010116,China)Fellowship of China Postdoctoral Science Foundation(grant number 2020M683204,China)Guangdong Basic and Applied Basic Research Fund(grant number 2020A1515110388,China)Fundamental Research Funds for the Central Universities(grant number 21620448,China)support of K.C.Wong Education Foundation。
文摘The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies;however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stressevoked tumor susceptibility, and the stress hormone glucocorticoid(GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor(low-density lipoprotein receptor-related protein-1, LRP1) and the "don’t eat me" signal receptor(signal regulatory protein alpha, SIRPa). Further analysis revealed that GC led to a direct, glucocorticoid receptor(GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevatedgene level of SIRPa by down-regulating mi RNA-4695-3 p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPa axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPa axis may serve as a potential therapeutic strategy for tumor treatment.
基金supported by the National Natural Science Foundation of China (81702750, 81670141, 81970145and 82001698)Natural Science Foundation of Guangdong Province (2020A1515011465and 2020A151501467, China)+5 种基金Science, Technology & Innovation Commission of Shenzhen Municipality ( JCYJ20180307154700308, JCYJ20170818163844015, JCYJ20180307151420045, JCYJ20190807151609464, JCYJ20200109142605909 and JCYJ20210324120007020, China)Sun Yat-sen University (20ykzd17 and 20ykpy122, China)International Collaboration of Science and Technology of Guangdong Province (2020A0505100031, China)Guangdong Provincial Key Laboratory of Digestive Cancer Research (No.2021B1212040006,China)The Social Development Foundation of Jiangsu Province (BE2018691, China)Sigrid Jusélius foundation in Finland for funding the project (Finland)
文摘Mutations in the plant homeodomain-like finger protein 6(PHF6)gene are strongly associated with acute myeloid(AML)and T-cell acute lymphoblastic leukemia(T-ALL).In this study,we demonstrated that PHF6 can bind to H3K9me3 and H3K27me1 on the nucleolar chromatin and recruit histone methyltransferase SUV39H1 to the rDNA locus.The deletion of PHF6 caused a decrease in the recruitment of SUV39H1 to rDNA gene loci,resulting in a reduction in the level of H3K9me3 and the promotion of rDNA transcription.The knockdown of either SUV39H1 or PHF6 significantly attenuated the effects of increase in H3K9me3 and suppressed the transcription of rDNA induced by the overexpression of the other interacting partner,thereby establishing an interdependent relationship between PHF6 and SUV39H1 in their control of rRNA transcription.The PHF6 clinical mutants significantly impaired the ability to bind and recruit SUV39H1 to the rDNA loci,resulting in an increase in rDNA transcription activity,the proliferation of in vitro leukemia cells,and the growth of in vivo mouse xenografts.Importantly,significantly elevated levels of pre-rRNA were observed in clinical AML patients who possessed a mutated version of PHF6.The specific rDNA transcription inhibitor CX5461 significantly reduced the resistance of U937 AML cells deficient in PHF6 to cytarabine,the drug that is most commonly used to treat AML.Collectively,we revealed a novel molecular mechanism by which PHF6 recruits methyltransferase SUV39H1 to the nucleolar region in leukemia and provided a potential therapeutic target for PHF6-mutant leukemia.
基金This work was financially supported by the National Natural Science Foundation of China(grant nos.22122701,21731004,91953201,92153303,21977044,and 21907050)the Natural Science Foundation of Jiangsu Province(grant nos.BK20202004 and BK20190282)the Excellent Research Program of Nanjing University(grant no.ZYJH004).
文摘Photodynamic therapy(PDT)usually shows limited efficacy in solid tumors since traditional PDT is O_(2)^(-)dependent while solid tumors are inherently hypoxic.In addition,hypoxic tumor cells possess antiapoptotic pathways that resist PDT-induced apoptosis.Therefore,developing photosensitizers(PSs)that show low O_(2)^(-)dependency and can induce nonapoptotic cell death pathways is critically needed.Herein,a series of Ru(II)polypyridine complex-based PSs,RuNMe,RuH,and RuCN,were synthesized,and their applications against hypoxic tumor cells through PDT were investigated.All three complexes showthe ability to generate the superoxide anion radical(·O_(2)^(-)),which is the type I photoreaction and less O_(2)^(-)dependent.RuNMe shows the best PDT performance against MCF-7 cells and three-dimensional multicellular spheroids,due to its higher cellular uptake and more reactive oxygen species generation.More importantly,RuNMe-incubated MCF-7 cells show photoinduced ferroptosis as evidenced by glutathione peroxidase 4 downregulation and lipid peroxide accumulation.This work not only develops a novel ferroptosis-inducing Ru(II)complex with the type I PDT process but also offers an effective strategy to solve tumor hypoxia in PDT.
基金supported by the Sichuan Science and Technology Program(no.2019YFG0164).
文摘Bacillus spp.has been proven to be critical for the quality of many fermented foods,but as one of the domain bacteria,its effect on the quality of Yibin Yacai has not been fully addressed.Herein,the effects of inoculation of Bacillus subtilis Y4 on the physicochemical properties,flavor metabolism and microbial community changes of Yibin Yacai for three-month solid-state fermentation were investigated.The results showed that inoculation of B.subtilis Y4 could reduce the pH and salinity of Yibin Yacai,accelerate the consumption of nitrite,promote the growth of Lactobacillus and the production of sweet amino acid,and inhibit pathogenic microorganisms at the late fermentation stage.During solid-state fermentation,the dominant fungus Cystofilobasidium was positively correlated with most volatile flavor substances,which were indirectly affected by B.subtilis Y4.Furthermore,compared to spontaneous fermented Yibin Yacai,inoculation of B.subtilis Y4 promoted the production of alkenes and made the peak of ester content appear earlier.These results indicated that inoculation of B.subtilis Y4 for solid-state fermentation could improve the quality and taste of Yibin Yacai,and shorten the fermentation time.
基金supported by the National Natural Science Foundation of China(22478438,81972894,82303820,82273882,32401048 and 22278442)the Science Fund for Distinguished Young Scholars of Jiangsu Province(BK20240098,China)+4 种基金the Natural Science Foundation of Jiangsu Province(BK20231017,China)the China Postdoctoral Science Foundation(2023M733891)the Jiangsu Funding Program for Excellent Postdoctoral Talent(317717,China)the Fundamental Research Funds for the Central Universities(2632023GR11,China)the Special Research Fund from the State Key Laboratory of Natural Medicines at China Pharmaceutical University(SKLNMZZ2024JS19).
文摘Over the past few decades,tumor immunotherapy has revolutionized the landscape of cancer clinical treatment.There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy.However,instead of a straightforward combination of multiple therapeutics,it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies,which are based on a comprehensive understanding of the physiological and pathological features.In this case,the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes.Therefore,the concept of Sequential Drug Delivery System(SDDS)is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions,thus complying with the dynamic disease evolution and the human immunity.This review summarizes the recent advancements inbiomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy.Furthermore,the rationales behind various engineering strategies are discussed.Finally,an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.
