Objective: Adopting the methods of Evidence-based Medicine research to acquire the dominant prescriptions of Shanghan Zabing Lun in the treatment of Endometriosis, meanwhile to fully dig the value of classical prescri...Objective: Adopting the methods of Evidence-based Medicine research to acquire the dominant prescriptions of Shanghan Zabing Lun in the treatment of Endometriosis, meanwhile to fully dig the value of classical prescriptions. Method: Firstly, we searched and collected the literatures from last three decades in CNKI, Wanfang and VIP databases, which are about classical prescriptions treating endometriosis. Then, by screening all the literatures, we obtained the clinical research literatures and individual case reports. Finally, we went through the internal quality of the two categories of literatures to get the dominant prescriptions. Results: 22 Shanghan Zabing Lun prescriptions have been used in the treatment of endometriosis. According to the clinical research and case literatures, Guizhi Fuling Wan is the prime prescription to treat endometriosis with high quality and high frequency. Conclusions: Through evidence-based medical research and evaluation of evidence, it can be seen that treatment of endometriosis presents a certain tendency that Guizhi Fuling Wan, Wenjing Decoction and Dahuang Zhechong Wan have good clinical effect treating endometriosis and their syndromes are well matched with the symptoms of endometriosis in the present clinical environment.展开更多
Background:Prognosis of multiple myeloma(MM)patients with extramedullary disease(EMD)remains poor.T cell dysfunction and an immunosuppressive environment have been reported in the bone marrow(BM)of MM patients.However...Background:Prognosis of multiple myeloma(MM)patients with extramedullary disease(EMD)remains poor.T cell dysfunction and an immunosuppressive environment have been reported in the bone marrow(BM)of MM patients.However,the immunosuppressive microenvironment and immune checkpoint receptors(ICRs)on CD8^(+)T cells in the EMD tissue of newly diagnosed MM(NDMM)patients have not been thoroughly studied.Methods:We investigated the expression levels of T cell immunoglobulin mucin-domain-containing-3(TIM-3)and T-cell immunoglobulin and ITIM domain(TIGIT)on CD8^(+)T cells and the expression of their ligands(Galectin-9 and CD155)on myeloma cells in EMD tissue of NDMM patients.The expression levels of TIM-3 and TIGIT on T cells and their ligands(Galectin-9 and CD155)on myeloma cells were analyzed by multicolored fluorescent flow cytometry in the peripheral blood(PB),BM,and EMD tissue.Additionally,the expression of ICRs was compared among PB,BM,and EMD tissue.Results:The expression levels of TIGIT and TIM-3 on CD8^(+)T cell subsets,including CD8^(+)Naïve T(T_(N))cells and CD8^(+)terminally differentiated effector memory T(TEMRA)cells,were significantly higher in EMD than in PB(p<0.05 for all).The expression levels of TIGIT and TIM-3 on CD8^(+)T_(N)cells were higher in EMD than in BM(p<0.05 for all).There were no differences in Galectin-9 and CD155 expression on myeloma cells among PB,BM,and EMD tissue.Conclusion:Our data add new evidence that T cells express increased TIGIT and TIM-3,suggesting that there may be T-cell exhaustion in EMD of patients with MM.展开更多
Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties.In this study,we built the recombinant Bacillus subtilis WB800 expressing antimicrobial pepti...Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties.In this study,we built the recombinant Bacillus subtilis WB800 expressing antimicrobial peptide KR32(WB800-KR32)using genetic engineering methods and investigated its protective effects of nuclear factor-E2-related factor 2(Nrf2)-Kelch-like ECH-associated protein 1(Keap1)pathway activation in intestinal oxidative disturbance induced by enterotoxigenic Escherichia coli(ETEC)K88 in weaned piglets.Twenty-eight weaned piglets were randomly distributed into four treatment groups with seven replicates fed with a basal diet.The feed of the control group(CON)was infused with normal sterilized saline;meanwhile,the ETEC,ETEC+WB800,and ETEC+WB800-KR32 groups were orally administered normal sterilized saline,5×10^(10)CFU(CFU:colony forming units)WB800,and 5×10^(10)CFU WB800-KR32,respectively,on Days 1-14 and all infused with ETEC K881×10^(10)CFU on Days 15-17.The results showed that pretreatment with WB800-KR32 attenuated ETEC-induced intestinal disturbance,improved the mucosal activity of antioxidant enzyme(catalase(CAT),superoxide dismutase(SOD),and glutathione peroxidase(GPx))and decreased the content of malondialdehyde(MDA).More importantly,WB800-KR32 downregulated genes involved in antioxidant defense(GPx and SOD1).Interestingly,WB800-KR32 upregulated the protein expression of Nrf2 and downregulated the protein expression of Keap1 in the ileum.WB800-KR32 markedly changed the richness estimators(Ace and Chao)of gut microbiota and increased the abundance of Eubacterium_rectale_ATCC_33656 in the feces.The results suggested that WB800-KR32 may alleviate ETEC-induced intestinal oxidative injury through the Nrf2-Keap1 pathway,providing a new perspective for WB800-KR32 as potential therapeutics to regulate intestinal oxidative disturbance in ETEC K88 infection.展开更多
Alzheimers disease(AD)is a chronic neurodegenerative disease.The symptoms include memoryand spatial learning dificulties,language disorders,and loss of motivation,which get worse overtime,eventually ending in death.No...Alzheimers disease(AD)is a chronic neurodegenerative disease.The symptoms include memoryand spatial learning dificulties,language disorders,and loss of motivation,which get worse overtime,eventually ending in death.No ffective treatments are available for AD,currently.Currenttreatments only attenuate symptoms temporarily and are associated with severe side ffects.Nearinfra-red(NIR)light has been studied for a long time.We investigated the effect of NIR on ADusing a transgenic mouse model,which was obtained by co-injecting two vectors carrying ADmutations in amyloid precursor protein(APP)and presenilin-i(PSEN1)into C57BL/6J mice.The irradiation equipment consisted of an accommodating box and an LED array.The wave-length of NIR light emitted from LED was between 1040 nm and 1090 nm.The power densitydelivered at the level of the mice was approximately 15 mW/cm^(2),Firstly,we treated the micewith NIR for 40 days,Then,the irradiation was suspended for 28 days.Finally,another 15 daystreatment was brought to mice.We conducted Morris water maze and immunofluorescenceanalysis to evaluate the effects of treatment.Immunofuorescence analysis was based on mea-suring the quantity of plaques in mouse brain slices,Our results show that NIR light improvesmemory and spatial learning ability and reduces plaques moderately.NIR light represents apotential treatment for AD.展开更多
Pancreatic fibrosis(PF)is primarily distinguished by the stimulation of pancreatic stellate cells(PSCs)and excessive extracellular matrix deposition,which is the main barrier impeding drug delivery and distribution.Re...Pancreatic fibrosis(PF)is primarily distinguished by the stimulation of pancreatic stellate cells(PSCs)and excessive extracellular matrix deposition,which is the main barrier impeding drug delivery and distribution.Recently,nanomedicine,with efficient,targeted,and controllable drug release characteristics,has demonstrated enormous advantages in the regression of pancreas fibrotic diseases.Notably,paracrine signals from parenchymal and immune cells such as pancreatic acinar cells,islet cells,pancreatic cancer cells,and immune cells can directly or indirectly modulate PSC differentiation and activation.The intercellular crosstalk between PSCs and these cells has been a critical event involved in fibrogenesis.However,the connections between PSCs and other pancreatic cells during the progression of diseases have yet to be discussed.Herein,we summarize intercellular crosstalk in the activation of PSCs and its contribution to the development of common pancreatic diseases,including pancreatitis,pancreatic cancer,and diabetes.Then,we also examine the latest treatment strategies of nanomedicine and potential targets for PSCs crosstalk in fibrosis,thereby offering innovative insights for the design of antifibrotic nanomedicine.Ultimately,the enhanced understanding of PF will facilitate the development of more precise intervention strategies and foster individually tailored therapeutic approaches for pancreatic diseases.展开更多
Metabolites and metabolism-related gene expression profiles in skeletal muscle change dramatically under obesity,aging and metabolic disease.Since obese and lean pigs are ideal models for metabolic research.Here,we co...Metabolites and metabolism-related gene expression profiles in skeletal muscle change dramatically under obesity,aging and metabolic disease.Since obese and lean pigs are ideal models for metabolic research.Here,we compared metabolome and transcriptome of Longissimus dorsi(LD)muscle between Taoyuan black(TB,obese)and Duroc(lean)pigs at different ages.We defined the“window phase”of intramuscular fat(IMF)deposition in TB pig,which has significantly higher IMF than Duroc pig.Our results displayed discrepant lipid composition and different expression genes(DEGs)enriched in lipid metabolism,and both metabolome and transcriptome analyses revealed stronger energy expenditure and more active amino acid and protein metabolism in Duroc pig.10 up-and 51 down-regulated biomarker metabolites with age-and breed-specificity were identified.Potential secretory metabolites,including organic acid(fumaric acid,succinate,malic acid,and gamma-aminobutyric acid),amino acid(L-lysine,and L-glutamic acid),lipid(2-hydroxyisovaleric acid,and L-carnitine)were demonstrated a significant correlation with IMF deposition.Our research highlights the huge difference of metabolic spectrum in skeletal muscle between obese and lean model and muscle-derived secretory metabolites might act as an ambassador of intercellular communication to regulate systematic metabolism.展开更多
Meat quality and lean meat percentage are important to pig industry.Muscle and adipose tissues are regarded as secretory organs that release myokines and adipokines to mediate muscle-adipose tissue crosstalk,which reg...Meat quality and lean meat percentage are important to pig industry.Muscle and adipose tissues are regarded as secretory organs that release myokines and adipokines to mediate muscle-adipose tissue crosstalk,which regulates lipid deposition and skeletal muscle development.The Taoyuan Black(TB)pig,a Chinese indigenous breed,exhibits abundant lipid deposition and is known for excellent meat quality.The aim of this study was to explore the dynamics of muscle development and lipid deposition in TB pigs at different ages and to identify myokines and adipokines that contribute to lipid accumulation.Forty TB and 40 Duroc pigs were fed the same diet and slaughtered for analysis at age of 60,120,180,and 210 d.The“window phase”of lipid deposition in TB pigs was defined from 120 to 180 d of age according to carcass traits,intramuscular fat(IMF),and adipocyte area.Comparative transcriptome of the longissimus dorsi(LD)muscle and subcutaneous adipose revealed upregulated energy and lipid metabolism pathways in TB pigs at 180 d compared to 120 d(P<0.05).Many myokines and adipokines associated with IMF and peripheral fat deposition have been identified via database comparison.Myokine IGF2 in TB pigs was downregulated at 180 d compared to 120 d(P<0.05)and had negative correlation with backfat thickness,perirenal fat percentage,and fat percentage(P<0.05),adipokines SFRP5 and AGT were upregulated in TB pigs at 180 d compared to 120 d and different between TB and Duroc pigs(P<0.05).This study provides new insights into the interaction between muscle and adipose tissues,as well as potential targets for nutritional regulation of IMF,lean meat percentage,and meat quality.展开更多
This study was conducted to explore the regulatory mechanism of leucine(Leu)on lipid metabolism of finishing pigs.Twenty-four Duroc×Landrace×Large cross pigs with an average body weight of68.33±0.97 kg ...This study was conducted to explore the regulatory mechanism of leucine(Leu)on lipid metabolism of finishing pigs.Twenty-four Duroc×Landrace×Large cross pigs with an average body weight of68.33±0.97 kg were randomly allocated into 3 treatment groups with 8 replicates per group(1 pig per replicate).The dietary treatments were as follows:control group(CON),0.25%Leu group and 0.50%Leu group.The experimental period was 42 d.The results showed as follows.(1)Compared with the CON,0.25%and 0.50%Leu increased(P<0.01)the average daily gain(ADG),while the average backfat thickness(ABT)and the ratio of feed intake to body weight gain(F:G ratio)were decreased(P<0.05).(2)In the 0.25%Leu group,the relative mRNA expression levels of sterol regulatory element binding protein-1c(SREBP1c),recombinant fatty acid transport protein 1(FATP1),chemerin and peroxisome proliferatoractivated receptorγ(PPARγ)were decreased but the level of fatty acid binding protein 4(FABP4)and fatty acid translocase(FAT/CD36)were increased in backfat tissue.In the 0.25%Leu group,the protein levels of p-Rictor,p-Raptor,p-eIF4E-binding protein 1(p-4EBP1),p-silent mating type information regulator 2homolog 1(p-SIRT1)and acetylation ribosome s6 protein kinase 1(Ac—S6K1)were increased(P<0.05).(3)Compared to the CON,the diversity of gut microbiota in the 0.25%Leu group was increased.Principal component analysis showed that the relative abundance of Bacteroidetes,Lactobacillus and Desulfovibrio was higher in the 0.25%Leu group than the CON,but the relative abundance of Firmicutes,Treponema and Shigella was lower than in the CON(P<0.05).(4)Four different metabolites were screened out from the serum of finishing pigs including allolithocholic acid(alloLCA),isolithocholic acid(isoLCA),ursodeoxycholic acid(UDCA)and hyodeoxycholic acid(HDCA),which correlate to various degrees with the above microorganisms.In conclusion,Leu could promote adipose tissue lipolysis of finishing pigs through the mTOR-SIRT1 signaling pathway,and S6K1 is acetylated at the same time,and the interaction between gut microbiota and bile acid metabolism is also involved.展开更多
Leber’s hereditary optic neuropathy(LHON)is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I,which is an important contributor to blindness among young adults across the globe.H...Leber’s hereditary optic neuropathy(LHON)is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I,which is an important contributor to blindness among young adults across the globe.However,the disorder has no available cures,since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them.Herein,PARKIN mRNA-loaded nanoparticle(mNP)-engineered mitochondria(mNP-Mito)were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria,normalizing the function of complex I for treating LHON.The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer,along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process.In a mouse model induced with a complex I inhibitor(rotenone,Rot),mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity(76.5%)compared to the group exposed to Rot damage(29.5%),which greatly promoted the restoration of ATP generation and mitiga-tion of ocular mitochondrial disease-related phenotypes.This study highlights the significance of nanoen-gineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.展开更多
By intelligently utilizing the odd-even effect existing in the melting points of alkanes as presented in the basic textbook of Organic Chemistry, different alkoxy groups were introduced to modify the structure of comm...By intelligently utilizing the odd-even effect existing in the melting points of alkanes as presented in the basic textbook of Organic Chemistry, different alkoxy groups were introduced to modify the structure of commercial Spiro-OMeTAD to give new Spiro derivatives of Spiro-OEtTAD, Spiro-OPrTAD, Spiro-OiPrTAD and Spiro-OBuTAD, with the aim to adjust the molecular packing status in perovskite solar cells as hole transporting compounds. Excitedly, with the introduction of ethoxy groups instead of the methoxy ones in Spiro-OMeTAD, Spiro-OEtTAD-based perovskite solar cells demonstrated the highest device performance of 20.16%, higher than that of Spiro-OMeTAD(18.64%).展开更多
The aim of this study was as follows:1)to investigate the effects of graded levels of N-carbamylglutamate(NCG)on performance,blood biochemical indexes,carcass traits and related indicators in growingfinishing pigs,and...The aim of this study was as follows:1)to investigate the effects of graded levels of N-carbamylglutamate(NCG)on performance,blood biochemical indexes,carcass traits and related indicators in growingfinishing pigs,and 2)to determine the optimal supplemental level.The toxicity of high-dose(much higher than recommended levels)NCG was assessed by routine blood tests and blood biochemical and histopathologic examinations of the heart,liver,spleen,lung,kidney and stomach.One hundred and forty-four growing-finishing pigs(DurocLarge WhiteLandrace,32.24±1.03 kg)were used in a 74-d experiment and each treatment was replicated 6 times with 4 pigs(2 barrows and 2 gilts)per replicate.The dietary treatments were a corn-soybean meal basal diet supplemented with 0%(control),0.05%,0.1%,0.15%,0.2%or 1%NCG.The first 5 groups were used to explore the optimal supplemental level of NCG,while the control,0.1%and 1%NCG groups were used to explore the safety of high-dose NCG.Compared with the normal control group,the final body weight and average daily gain tended to be higher in the 0.1%group(P=0.08),the lean percentage tended to be higher in the 0.05%group(P=0.07),the levels of free amino acids in the blood significantly increased in the 0.1%group(P<0.05),both 0.1%and 0.15%NCG supplementation increased the levels of nitric oxide(NO)in serum(P=0.07)and muscle growth-and lipid metabolism-related gene expression(P<0.05)and NCG supplementation improved C18:1N9C monounsaturated fatty acids(MUFA)in a dose-dependent manner(P=0.08).In addition,routine blood tests,blood biochemical indexes and histopathological examination revealed no abnormalities.Overall,increasing the levels of NCG did not linearly improve the above indicators;the 0.1%dose showed the best effect,and a high dose(1%)did not pose a toxicity risk.展开更多
Bright emission of organic luminogens at aggregated state has attracted increasing attention for their potential applications in opto-electronic devices and bio-/chemo-sensors.In this article,upon the introduction of ...Bright emission of organic luminogens at aggregated state has attracted increasing attention for their potential applications in opto-electronic devices and bio-/chemo-sensors.In this article,upon the introduction of different substituents(Br,Ph and TPh)to the large conjugated core of 9-methyl-9H-dibenzo[a,c]carbazole(DBC)moiety,the resultant luminogens demonstrated PL quantum yields in solid state ranging from 4.81%to 47.39%.Through the systematic investigation of molecular packing,together with theory calculation,the strong intermolecular electronic coupling in the dimers is proved as the main factor to the bright emission in the solid state.The results afforded a new avenue to investigate the intrinsic relationship among the molecular structures,packing modes and emission properties.展开更多
A novel floating breakwater-windbreak structure(floating forest)has been designed for the protection of vulnerable coastal areas from extreme wind and wave loadings during storm conditions.The modular arch-shaped conc...A novel floating breakwater-windbreak structure(floating forest)has been designed for the protection of vulnerable coastal areas from extreme wind and wave loadings during storm conditions.The modular arch-shaped concrete structure is positioned perpendicularly to the direction of the prevailing wave and wind.The structure below the water surface acts as a porous breakwater with wave scattering capability.An array of tubular columns on the sloping deck of the breakwater act as an artificial forest-type windbreak.A feasibility study involving hydrodynamic and aerodynamic analyses has been performed,focusing on its capability in reducing wave heights and wind speeds in the lee side.The study shows that the proposed 1 km long floating forest is able to shelter a lee area that stretches up to 600 m,with 40%–60%wave energy reduction and 10%–80%peak wind speed reduction.展开更多
We have observed various polarization domains and a giant self-mode-locked pulse in a 130 m long erbium-doped fiber laser without any mode-locking devices.By adjusting the intracavity polarization controller,we invest...We have observed various polarization domains and a giant self-mode-locked pulse in a 130 m long erbium-doped fiber laser without any mode-locking devices.By adjusting the intracavity polarization controller,we investigated the evolution process of the polarization domain with the varying cavity birefringence.When the birefringence was close to zero,the polarization domains split into multidomains,and finally a giant self-mode-locked pulse formed for the first time.We analyzed that the generation of the self-mode-locked pulse was related to the multiple subdomains ascribed to the strong coherent cross coupling between the orthogonal polarization light components in the long fiber cavity.展开更多
文摘Objective: Adopting the methods of Evidence-based Medicine research to acquire the dominant prescriptions of Shanghan Zabing Lun in the treatment of Endometriosis, meanwhile to fully dig the value of classical prescriptions. Method: Firstly, we searched and collected the literatures from last three decades in CNKI, Wanfang and VIP databases, which are about classical prescriptions treating endometriosis. Then, by screening all the literatures, we obtained the clinical research literatures and individual case reports. Finally, we went through the internal quality of the two categories of literatures to get the dominant prescriptions. Results: 22 Shanghan Zabing Lun prescriptions have been used in the treatment of endometriosis. According to the clinical research and case literatures, Guizhi Fuling Wan is the prime prescription to treat endometriosis with high quality and high frequency. Conclusions: Through evidence-based medical research and evaluation of evidence, it can be seen that treatment of endometriosis presents a certain tendency that Guizhi Fuling Wan, Wenjing Decoction and Dahuang Zhechong Wan have good clinical effect treating endometriosis and their syndromes are well matched with the symptoms of endometriosis in the present clinical environment.
基金supported by S&T Program of Hebei,China(Grant Number 21377754D)the 2021 Hebei Provincial Governmentfunded Clinical Medicine Talents Training Project(Grant Number 2021-99)。
文摘Background:Prognosis of multiple myeloma(MM)patients with extramedullary disease(EMD)remains poor.T cell dysfunction and an immunosuppressive environment have been reported in the bone marrow(BM)of MM patients.However,the immunosuppressive microenvironment and immune checkpoint receptors(ICRs)on CD8^(+)T cells in the EMD tissue of newly diagnosed MM(NDMM)patients have not been thoroughly studied.Methods:We investigated the expression levels of T cell immunoglobulin mucin-domain-containing-3(TIM-3)and T-cell immunoglobulin and ITIM domain(TIGIT)on CD8^(+)T cells and the expression of their ligands(Galectin-9 and CD155)on myeloma cells in EMD tissue of NDMM patients.The expression levels of TIM-3 and TIGIT on T cells and their ligands(Galectin-9 and CD155)on myeloma cells were analyzed by multicolored fluorescent flow cytometry in the peripheral blood(PB),BM,and EMD tissue.Additionally,the expression of ICRs was compared among PB,BM,and EMD tissue.Results:The expression levels of TIGIT and TIM-3 on CD8^(+)T cell subsets,including CD8^(+)Naïve T(T_(N))cells and CD8^(+)terminally differentiated effector memory T(TEMRA)cells,were significantly higher in EMD than in PB(p<0.05 for all).The expression levels of TIGIT and TIM-3 on CD8^(+)T_(N)cells were higher in EMD than in BM(p<0.05 for all).There were no differences in Galectin-9 and CD155 expression on myeloma cells among PB,BM,and EMD tissue.Conclusion:Our data add new evidence that T cells express increased TIGIT and TIM-3,suggesting that there may be T-cell exhaustion in EMD of patients with MM.
基金supported by the Zhejiang Provincial Key R&D Program of China(No.2021C02008)the China Agriculture Research System of MOF and MARA(No.CARS-35)+2 种基金the National Natural Science Foundation of China(No.32022079)the Fundamental Research Funds for the Central Universities(No.2022QZJH46)the Taishan Industrial Leading Talents Project.
文摘Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties.In this study,we built the recombinant Bacillus subtilis WB800 expressing antimicrobial peptide KR32(WB800-KR32)using genetic engineering methods and investigated its protective effects of nuclear factor-E2-related factor 2(Nrf2)-Kelch-like ECH-associated protein 1(Keap1)pathway activation in intestinal oxidative disturbance induced by enterotoxigenic Escherichia coli(ETEC)K88 in weaned piglets.Twenty-eight weaned piglets were randomly distributed into four treatment groups with seven replicates fed with a basal diet.The feed of the control group(CON)was infused with normal sterilized saline;meanwhile,the ETEC,ETEC+WB800,and ETEC+WB800-KR32 groups were orally administered normal sterilized saline,5×10^(10)CFU(CFU:colony forming units)WB800,and 5×10^(10)CFU WB800-KR32,respectively,on Days 1-14 and all infused with ETEC K881×10^(10)CFU on Days 15-17.The results showed that pretreatment with WB800-KR32 attenuated ETEC-induced intestinal disturbance,improved the mucosal activity of antioxidant enzyme(catalase(CAT),superoxide dismutase(SOD),and glutathione peroxidase(GPx))and decreased the content of malondialdehyde(MDA).More importantly,WB800-KR32 downregulated genes involved in antioxidant defense(GPx and SOD1).Interestingly,WB800-KR32 upregulated the protein expression of Nrf2 and downregulated the protein expression of Keap1 in the ileum.WB800-KR32 markedly changed the richness estimators(Ace and Chao)of gut microbiota and increased the abundance of Eubacterium_rectale_ATCC_33656 in the feces.The results suggested that WB800-KR32 may alleviate ETEC-induced intestinal oxidative injury through the Nrf2-Keap1 pathway,providing a new perspective for WB800-KR32 as potential therapeutics to regulate intestinal oxidative disturbance in ETEC K88 infection.
基金supported by grants awarded by the National Major Scientic Research Program of China(Grant No.2011CB910404)the National Nature Science Foundation of China(Grant No.61227017)+1 种基金the State Key Basic Research Development Program of China(2012CB518103)National Outstanding Young Scientist Award of China(61425006).
文摘Alzheimers disease(AD)is a chronic neurodegenerative disease.The symptoms include memoryand spatial learning dificulties,language disorders,and loss of motivation,which get worse overtime,eventually ending in death.No ffective treatments are available for AD,currently.Currenttreatments only attenuate symptoms temporarily and are associated with severe side ffects.Nearinfra-red(NIR)light has been studied for a long time.We investigated the effect of NIR on ADusing a transgenic mouse model,which was obtained by co-injecting two vectors carrying ADmutations in amyloid precursor protein(APP)and presenilin-i(PSEN1)into C57BL/6J mice.The irradiation equipment consisted of an accommodating box and an LED array.The wave-length of NIR light emitted from LED was between 1040 nm and 1090 nm.The power densitydelivered at the level of the mice was approximately 15 mW/cm^(2),Firstly,we treated the micewith NIR for 40 days,Then,the irradiation was suspended for 28 days.Finally,another 15 daystreatment was brought to mice.We conducted Morris water maze and immunofluorescenceanalysis to evaluate the effects of treatment.Immunofuorescence analysis was based on mea-suring the quantity of plaques in mouse brain slices,Our results show that NIR light improvesmemory and spatial learning ability and reduces plaques moderately.NIR light represents apotential treatment for AD.
基金National Key R&D Program of China(2022YFE0198400)National Natural Science Foundation Major International(Regional)Joint Research Program(Nos.82020108029,82320108003,China)+5 种基金National Natural Science Foundation(Nos.82170845,82073398,82003677,82000740,81970717,China)Project of State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZ202021,China)“111”Project from the Ministry of Education of China,the State Administration of Foreign Experts Affairs of China(B16046)Double First-Rate construction plan of China Pharmaceutical University(CPU2018GY06,CPU2022QZ18,China)Key Research&Development Program(BE2022853,China)Medical Key Discipline(ZDXK202203,China)of Jiangsu Province.
文摘Pancreatic fibrosis(PF)is primarily distinguished by the stimulation of pancreatic stellate cells(PSCs)and excessive extracellular matrix deposition,which is the main barrier impeding drug delivery and distribution.Recently,nanomedicine,with efficient,targeted,and controllable drug release characteristics,has demonstrated enormous advantages in the regression of pancreas fibrotic diseases.Notably,paracrine signals from parenchymal and immune cells such as pancreatic acinar cells,islet cells,pancreatic cancer cells,and immune cells can directly or indirectly modulate PSC differentiation and activation.The intercellular crosstalk between PSCs and these cells has been a critical event involved in fibrogenesis.However,the connections between PSCs and other pancreatic cells during the progression of diseases have yet to be discussed.Herein,we summarize intercellular crosstalk in the activation of PSCs and its contribution to the development of common pancreatic diseases,including pancreatitis,pancreatic cancer,and diabetes.Then,we also examine the latest treatment strategies of nanomedicine and potential targets for PSCs crosstalk in fibrosis,thereby offering innovative insights for the design of antifibrotic nanomedicine.Ultimately,the enhanced understanding of PF will facilitate the development of more precise intervention strategies and foster individually tailored therapeutic approaches for pancreatic diseases.
基金supported by the National Natural Science Foundation of China(31972582)the STI 2030-Major Project(2023ZD04072)+4 种基金the Major Project of Changsha City(kh2401015)the Science and Technology Innovation Program of Hunan Province(2021RC4039)the Key Research and Development Program of Hunan Province(2022NK2026)the Youth Innovation Promotion Association CAS(Y202079)China Agriculture Research System of MOF and MARA(CARS-35)。
文摘Metabolites and metabolism-related gene expression profiles in skeletal muscle change dramatically under obesity,aging and metabolic disease.Since obese and lean pigs are ideal models for metabolic research.Here,we compared metabolome and transcriptome of Longissimus dorsi(LD)muscle between Taoyuan black(TB,obese)and Duroc(lean)pigs at different ages.We defined the“window phase”of intramuscular fat(IMF)deposition in TB pig,which has significantly higher IMF than Duroc pig.Our results displayed discrepant lipid composition and different expression genes(DEGs)enriched in lipid metabolism,and both metabolome and transcriptome analyses revealed stronger energy expenditure and more active amino acid and protein metabolism in Duroc pig.10 up-and 51 down-regulated biomarker metabolites with age-and breed-specificity were identified.Potential secretory metabolites,including organic acid(fumaric acid,succinate,malic acid,and gamma-aminobutyric acid),amino acid(L-lysine,and L-glutamic acid),lipid(2-hydroxyisovaleric acid,and L-carnitine)were demonstrated a significant correlation with IMF deposition.Our research highlights the huge difference of metabolic spectrum in skeletal muscle between obese and lean model and muscle-derived secretory metabolites might act as an ambassador of intercellular communication to regulate systematic metabolism.
基金funded by the National Nature Science Foundation of China(U22A20516)the Biological Breeding-National Science and Technology Major Project(2023ZD04072)the Major Project of Changsha City(kh2401015)and the China Agriculture Research System of MOF and MARA(CARS-35).
文摘Meat quality and lean meat percentage are important to pig industry.Muscle and adipose tissues are regarded as secretory organs that release myokines and adipokines to mediate muscle-adipose tissue crosstalk,which regulates lipid deposition and skeletal muscle development.The Taoyuan Black(TB)pig,a Chinese indigenous breed,exhibits abundant lipid deposition and is known for excellent meat quality.The aim of this study was to explore the dynamics of muscle development and lipid deposition in TB pigs at different ages and to identify myokines and adipokines that contribute to lipid accumulation.Forty TB and 40 Duroc pigs were fed the same diet and slaughtered for analysis at age of 60,120,180,and 210 d.The“window phase”of lipid deposition in TB pigs was defined from 120 to 180 d of age according to carcass traits,intramuscular fat(IMF),and adipocyte area.Comparative transcriptome of the longissimus dorsi(LD)muscle and subcutaneous adipose revealed upregulated energy and lipid metabolism pathways in TB pigs at 180 d compared to 120 d(P<0.05).Many myokines and adipokines associated with IMF and peripheral fat deposition have been identified via database comparison.Myokine IGF2 in TB pigs was downregulated at 180 d compared to 120 d(P<0.05)and had negative correlation with backfat thickness,perirenal fat percentage,and fat percentage(P<0.05),adipokines SFRP5 and AGT were upregulated in TB pigs at 180 d compared to 120 d and different between TB and Duroc pigs(P<0.05).This study provides new insights into the interaction between muscle and adipose tissues,as well as potential targets for nutritional regulation of IMF,lean meat percentage,and meat quality.
基金supported by National Natural Science Foundation of China(31972582,U22A20516)Science and Technology Innovation Program of Hunan Province(2021RC4039)+1 种基金Key R&D Program of Hunan Province(2022NK2026)the Youth Innovation Promotion Association CAS(Y202079)
文摘This study was conducted to explore the regulatory mechanism of leucine(Leu)on lipid metabolism of finishing pigs.Twenty-four Duroc×Landrace×Large cross pigs with an average body weight of68.33±0.97 kg were randomly allocated into 3 treatment groups with 8 replicates per group(1 pig per replicate).The dietary treatments were as follows:control group(CON),0.25%Leu group and 0.50%Leu group.The experimental period was 42 d.The results showed as follows.(1)Compared with the CON,0.25%and 0.50%Leu increased(P<0.01)the average daily gain(ADG),while the average backfat thickness(ABT)and the ratio of feed intake to body weight gain(F:G ratio)were decreased(P<0.05).(2)In the 0.25%Leu group,the relative mRNA expression levels of sterol regulatory element binding protein-1c(SREBP1c),recombinant fatty acid transport protein 1(FATP1),chemerin and peroxisome proliferatoractivated receptorγ(PPARγ)were decreased but the level of fatty acid binding protein 4(FABP4)and fatty acid translocase(FAT/CD36)were increased in backfat tissue.In the 0.25%Leu group,the protein levels of p-Rictor,p-Raptor,p-eIF4E-binding protein 1(p-4EBP1),p-silent mating type information regulator 2homolog 1(p-SIRT1)and acetylation ribosome s6 protein kinase 1(Ac—S6K1)were increased(P<0.05).(3)Compared to the CON,the diversity of gut microbiota in the 0.25%Leu group was increased.Principal component analysis showed that the relative abundance of Bacteroidetes,Lactobacillus and Desulfovibrio was higher in the 0.25%Leu group than the CON,but the relative abundance of Firmicutes,Treponema and Shigella was lower than in the CON(P<0.05).(4)Four different metabolites were screened out from the serum of finishing pigs including allolithocholic acid(alloLCA),isolithocholic acid(isoLCA),ursodeoxycholic acid(UDCA)and hyodeoxycholic acid(HDCA),which correlate to various degrees with the above microorganisms.In conclusion,Leu could promote adipose tissue lipolysis of finishing pigs through the mTOR-SIRT1 signaling pathway,and S6K1 is acetylated at the same time,and the interaction between gut microbiota and bile acid metabolism is also involved.
基金supported by the National Natural Science Foundation of China(82020108029,82304416,82073398,82302367,China)supported by the Natural Science Foundation of Jiangsu Province(BK20231016,BK20231019,China)+5 种基金the China Postdoctoral Science Foundation(grant Number:2022M720173,China)Jiangsu Funding Program for Excellent Postdoctoral Talent(2023,China)the Fundamental Research Funds for the Central Universities(2632023GR20,China)State Key Laboratory of Natural Medicines China Pharmaceutical University(SKLNMZZ202021,China)Double First-class University Projects(CPU2018GY06,China)Double First-Rate construction plan of China Pharmaceutical University(CPU2022QZ18,China)。
文摘Leber’s hereditary optic neuropathy(LHON)is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I,which is an important contributor to blindness among young adults across the globe.However,the disorder has no available cures,since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them.Herein,PARKIN mRNA-loaded nanoparticle(mNP)-engineered mitochondria(mNP-Mito)were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria,normalizing the function of complex I for treating LHON.The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer,along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process.In a mouse model induced with a complex I inhibitor(rotenone,Rot),mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity(76.5%)compared to the group exposed to Rot damage(29.5%),which greatly promoted the restoration of ATP generation and mitiga-tion of ocular mitochondrial disease-related phenotypes.This study highlights the significance of nanoen-gineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.
基金supported by the National Natural Science Foundation of China (21734007, 51573140, 51673151, 21773045)the Natural Science Foundation of Hubei Province (2017CFA002)the Fundamental Research Funds for the Central Universities (2042017kf0247, 2042018kf0014)
文摘By intelligently utilizing the odd-even effect existing in the melting points of alkanes as presented in the basic textbook of Organic Chemistry, different alkoxy groups were introduced to modify the structure of commercial Spiro-OMeTAD to give new Spiro derivatives of Spiro-OEtTAD, Spiro-OPrTAD, Spiro-OiPrTAD and Spiro-OBuTAD, with the aim to adjust the molecular packing status in perovskite solar cells as hole transporting compounds. Excitedly, with the introduction of ethoxy groups instead of the methoxy ones in Spiro-OMeTAD, Spiro-OEtTAD-based perovskite solar cells demonstrated the highest device performance of 20.16%, higher than that of Spiro-OMeTAD(18.64%).
基金the Beijing Swine Innovation Team of Modern Agriculture Industry Technological System and Chongqing Rongchang Agricultural and Animal Husbandry High-tech Industry Research and Development Project(cstc2019ngzx0019).
文摘The aim of this study was as follows:1)to investigate the effects of graded levels of N-carbamylglutamate(NCG)on performance,blood biochemical indexes,carcass traits and related indicators in growingfinishing pigs,and 2)to determine the optimal supplemental level.The toxicity of high-dose(much higher than recommended levels)NCG was assessed by routine blood tests and blood biochemical and histopathologic examinations of the heart,liver,spleen,lung,kidney and stomach.One hundred and forty-four growing-finishing pigs(DurocLarge WhiteLandrace,32.24±1.03 kg)were used in a 74-d experiment and each treatment was replicated 6 times with 4 pigs(2 barrows and 2 gilts)per replicate.The dietary treatments were a corn-soybean meal basal diet supplemented with 0%(control),0.05%,0.1%,0.15%,0.2%or 1%NCG.The first 5 groups were used to explore the optimal supplemental level of NCG,while the control,0.1%and 1%NCG groups were used to explore the safety of high-dose NCG.Compared with the normal control group,the final body weight and average daily gain tended to be higher in the 0.1%group(P=0.08),the lean percentage tended to be higher in the 0.05%group(P=0.07),the levels of free amino acids in the blood significantly increased in the 0.1%group(P<0.05),both 0.1%and 0.15%NCG supplementation increased the levels of nitric oxide(NO)in serum(P=0.07)and muscle growth-and lipid metabolism-related gene expression(P<0.05)and NCG supplementation improved C18:1N9C monounsaturated fatty acids(MUFA)in a dose-dependent manner(P=0.08).In addition,routine blood tests,blood biochemical indexes and histopathological examination revealed no abnormalities.Overall,increasing the levels of NCG did not linearly improve the above indicators;the 0.1%dose showed the best effect,and a high dose(1%)did not pose a toxicity risk.
基金supported by the National Natural Science Foundation of China(51673151,51973162,21875174,21734007)the Natural Science Foundation of Hubei Province(2017CFA002)。
文摘Bright emission of organic luminogens at aggregated state has attracted increasing attention for their potential applications in opto-electronic devices and bio-/chemo-sensors.In this article,upon the introduction of different substituents(Br,Ph and TPh)to the large conjugated core of 9-methyl-9H-dibenzo[a,c]carbazole(DBC)moiety,the resultant luminogens demonstrated PL quantum yields in solid state ranging from 4.81%to 47.39%.Through the systematic investigation of molecular packing,together with theory calculation,the strong intermolecular electronic coupling in the dimers is proved as the main factor to the bright emission in the solid state.The results afforded a new avenue to investigate the intrinsic relationship among the molecular structures,packing modes and emission properties.
基金This work was supported by ARC Discovery Project Grant DP170104546.
文摘A novel floating breakwater-windbreak structure(floating forest)has been designed for the protection of vulnerable coastal areas from extreme wind and wave loadings during storm conditions.The modular arch-shaped concrete structure is positioned perpendicularly to the direction of the prevailing wave and wind.The structure below the water surface acts as a porous breakwater with wave scattering capability.An array of tubular columns on the sloping deck of the breakwater act as an artificial forest-type windbreak.A feasibility study involving hydrodynamic and aerodynamic analyses has been performed,focusing on its capability in reducing wave heights and wind speeds in the lee side.The study shows that the proposed 1 km long floating forest is able to shelter a lee area that stretches up to 600 m,with 40%–60%wave energy reduction and 10%–80%peak wind speed reduction.
基金supported by the National Key Research and Development Program of China(No.2018YFE0117400)National Natural Science Foundation of China(No.62275093)China Postdoctoral Science Foundation(No.2018M642823)。
文摘We have observed various polarization domains and a giant self-mode-locked pulse in a 130 m long erbium-doped fiber laser without any mode-locking devices.By adjusting the intracavity polarization controller,we investigated the evolution process of the polarization domain with the varying cavity birefringence.When the birefringence was close to zero,the polarization domains split into multidomains,and finally a giant self-mode-locked pulse formed for the first time.We analyzed that the generation of the self-mode-locked pulse was related to the multiple subdomains ascribed to the strong coherent cross coupling between the orthogonal polarization light components in the long fiber cavity.
