为了探讨5-甲基胞嘧啶(5-methylcytosine,m5C)相关基因在三阴性乳腺癌(triple negative breast cancer,TNBC)患者治疗及预后中的潜在价值,构建了基于m5C相关基因的预后预测模型,用于评估TNBC患者的预后和生存状况。从基因表达总库(gene ...为了探讨5-甲基胞嘧啶(5-methylcytosine,m5C)相关基因在三阴性乳腺癌(triple negative breast cancer,TNBC)患者治疗及预后中的潜在价值,构建了基于m5C相关基因的预后预测模型,用于评估TNBC患者的预后和生存状况。从基因表达总库(gene expression omnibus,GEO)数据库和癌症基因组图谱(the cancer genome atlas,TCGA)数据库中下载TNBC基因表达谱和相应的临床数据。通过Pearson分析确定了99个m5C相关基因,进一步采用单因素Cox分析鉴定出5个与预后有关的m5C相关基因(SLC6A14、BCL11A、UGT8、LMO4、PSAT1)并构建了风险评分(risk score)预测模型,根据风险评分中位值将患者划分为高风险组和低风险组。使用Kaplan-Meier(K-M)生存分析、受试者工作特征(receiver operating characteristic,ROC)曲线、多变量Cox回归分析、构建列线图和校准曲线评估了模型的预测效能。训练集和验证集的K-M生存曲线、受试者工作特征曲线下面积(area under the curve,AUC)分析均验证了模型具有良好的预测能力。多变量Cox回归分析显示,风险评分可作为独立的预后生物标志物。使用ssGSEA、免疫评分分析和化疗药物对高低风险组患者的半最大抑制浓度(half maximal inhibitory concentration,IC50)值差异分析显示,免疫细胞和免疫检查点基因以及大多数化疗药物的IC50值在不同风险组之间的表达存在显著差异。研究结果构建了基于5个m5C相关基因的风险评分预后预测模型,这将有助于阐明TNBC中m5C相关基因的作用机制,进而提供更有价值的预后及诊断的生物标志物和潜在的治疗靶点,为TNBC患者临床个性化治疗提供理论指导。展开更多
Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(W...Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.展开更多
In practical engineering,due to the noncontinuity characteristics of joints in rock slopes,in addition to plane failure,stepped sliding failure may occur for intermittently jointed rock slopes.Especially for intermitt...In practical engineering,due to the noncontinuity characteristics of joints in rock slopes,in addition to plane failure,stepped sliding failure may occur for intermittently jointed rock slopes.Especially for intermittently bedding jointed rock slopes,the correlation and difference in strength parameters between joints and rock bridges,along with the various failure modes and intermittency of rock bridges,contribute to the complexity of stepped failure modes and the unpredictability of failure regions.Based on the upper-bound limit analysis method and multi-sliders step-path failure mode,considering the shear and tensile failure of rock bridges and the weakened relationship between the strength parameters of rock bridges and jointed surfaces,by introducing the modified M-C failure criterion and the formula for calculating the energy consumption of tensile failure of rock bridges,two failure mechanisms are constructed to obtain the safety factor(F_(s))of intermittently jointed rock slopes.The sequential quadratic programming method is used to obtain the optimal upper-bound solution for F_(s).The influence of multiple key parameters(slope height H,horizontal distance L,Slope angleβ,shear strength parameters of the rock bridgeφr and cr,Dimensionless parameter u,weakening coefficients of the internal friction angle and cohesion between the rock bridges and joint surfaces Kφand Kc)on the stability analysis of intermittently jointed rock slopes under the shear failure mode of rock bridges as well as under the tensile failure mode is also explored.The reliability of the failure mechanisms is verified by comparative analysis with theoretical results,numerical results,and landslide cases,and the variation rules of F_(s)with each key parameter are obtained.The results show that F_(s) varies linearly withφr and cr of the rock bridge and with K_(φ)and K_(c),whereas F_(s)changes nonlinearly with H and L.In particular,with the increase in Kφand Kc,Fs increases by approximately 52.78%and 171.02%on average,respectively.For rock bridge tensile failure,F_(s) shows a nonlinearly positive correlation withφr,cr,Kφand Kc.In particular,with the increase in Kφand Kc,Fs increases by approximately 13%and 61.69%on average,respectively.Fs decreases rapidly with increasing slope gradientβand decreasing dimensionless parameterμ.When Kφand Kc are both less than 1.0,the stepped sliding surface occurs more easily than the plane failure surface,especially in the case of tensile failure of the rock bridge.In addition,rock slopes with higher strength parameters,taller heights,and greater weakening coefficients are prone to rock bridge tension failure with lower Fs,and more attention should be given to the occurrence of such accidents in actual engineering.展开更多
Candidiasis, also known as candidiasis vulvovaginitis, is an infection caused by different types of Candida fungi, the most frequent being Candida albicans. The present study reports an effective strategy, which opens...Candidiasis, also known as candidiasis vulvovaginitis, is an infection caused by different types of Candida fungi, the most frequent being Candida albicans. The present study reports an effective strategy, which opens new avenues for the treatment of this public health problem. The MAC<sup>®</sup> Methodology, conventional laser light-emitting (LLLT)/LED) methods are based on the biphasic response demonstrated many times in LLLT research and as with other forms of drugs, a “drug” (irradiation parameters) and a “dose” (irradiation times) and the “Arndt-Schulz Law” is often cited as a suitable model to describe the dose-dependent effects of LLLT. This method uses photopharmaceuticals, cell markers and the use of correct parameters for each case to induce the acceleration of tissue repair. The present study shows a case of a 32-year-old patient diagnosed with recurrent candidiasis 4 years ago. Eighteen sessions were performed (every other day) using a photoactivated component (Methylene blue 1% + Clotrimazole 1%) and LED phototherapy (red, blue and violet) with emission times of 60 - 260 seconds for each applicator, according to the dose recommendations of the scar acceleration method (MAC<sup>®</sup>). At the sixth treatment session there was a noticeable decrease in the itching sensation reported by the patient. In session 11 she reported feeling a great improvement, indicating that she no longer felt itching in any area after 18 sessions. The present case demonstrates new methodologies to treat common problems in the population that have a positive impact on the quality of life. This methodology has a promising future because it is non-invasive and requires a great biological transformation for inflammatory, fungal and viral control.展开更多
本文围绕C2M (Customer to Manufacturer)模式在果蔬类农产品供应链中的应用展开研究。对C2M模式进行了深入分析,探讨了其在其他行业中的成功应用以及在农产品供应链中的潜在优势。对C2M模式在果蔬类农产品供应链中的可行性和有效性进...本文围绕C2M (Customer to Manufacturer)模式在果蔬类农产品供应链中的应用展开研究。对C2M模式进行了深入分析,探讨了其在其他行业中的成功应用以及在农产品供应链中的潜在优势。对C2M模式在果蔬类农产品供应链中的可行性和有效性进行了探讨,包括对最优定价策略、渠道选择策略等方面的分析和建议。展望了未来的研究方向和发展趋势,提出了数字化技术的整合、可持续发展和绿色供应链、供应链风险管理、新兴市场和国际贸易,以及消费者参与和定制化需求等方面的建议。研究方向将有助于推动C2M模式在果蔬类农产品供应链中的应用和发展,促进供应链的优化和创新,以满足不断变化的市场需求。展开更多
The roads in correlation with the traffic linked to their existences are at the origin of the emission of numerous polluting substances likely to induce disturbances of the growth and the behavioral changes in the org...The roads in correlation with the traffic linked to their existences are at the origin of the emission of numerous polluting substances likely to induce disturbances of the growth and the behavioral changes in the organisms living in their vicinities. The purpose of this study is to analyze the growth and capacity accumulation of a common earthworm species (Millsonia omodeoi) in Cu, Cr, Ni, Pb and Zn in soils along a main road called “Autoroute du Nord” in C?te d’Ivoire. Thus, the earthworms were harvested in soils from a distance of 0 m (just after the sidewalk) to a distance of 200 m from the toll highway and in a control soil sampled in Lamto reserve (C?te d’Ivoire). The study was carried out in the soil laboratory at the ecological station of Lamto reserve. The Ford-Walford technique was used to determine the model and parameters most appropriated for describing the growth of earthworms. A pairwise comparison of the growth parameters was carried out using the Kruskal-Wallis test with the STATISTICA 7.1 software. The heavy metals contained in the cultivated soils and earthworms were detected and quantified using a Scanning Electron Micro-scope (MEB FEG Supra 40 VP Zeiss) and an Atomic Absorption Spectrometer SPECTRA 110 (VARIAN). The capacity accumulation of heavy metals in earthworm was determined by the bioaccumulation factor (BAF) calculation. The results of this study showed that Gompertz is the most appropriated model to describe the growth of M. omodeoi. The life cycle of M. omodeoi shows that this earthworm adopts a K type demographic strategy. Cu is the most accumulated heavy metals in M. omodeoi, when Cr is the least accumulated. Concerning heavy metal content in the earthworms, it decreases while moving away from the pavement. These results highlight a possibility of choice of M. omodeoi as 1) indicators of heavy metals pollution and 2) target of biological organisms for environmental impact studies.展开更多
LiFePO_(4),as a prevailing cathode material for lithium-ion batteries(LIBs),still encounters issues such as intrinsic poor electronic conductivity,inferior Li-ion diffusion kinetic,and two-phase transformation mechani...LiFePO_(4),as a prevailing cathode material for lithium-ion batteries(LIBs),still encounters issues such as intrinsic poor electronic conductivity,inferior Li-ion diffusion kinetic,and two-phase transformation mechanism involving substantial structural rearrangements,resulting in unsatisfactory rate performance.Carbon coating,cation doping,and morphological control have been widely employed to reconcile these issues.Inspired by these,we propose a synthetic route with metal–organic frameworks(MOFs)as self-sacrificial templates to simultaneously realize shape modulation,Mn doping,and N-doped carbon coating for enhanced electrochemical performances.The as-synthesized Li MnxFe1–xPO4/C(x=0,0.25,and0.5)deliver tunable electrochemical behaviors induced by the MOF templates,among which LiMn_(0.25)Fe_(0.75)PO_(4)/C outperforms its counterparts in cyclability(164.7 mA h g^(-1)after 200 cycles at 0.5 C)and rate capability(116.3 mA h g^(-1)at 10 C).Meanwhile,the ex-situ XRD reveals a dominant single-phase solid solution mechanism of LiMn_(0.25)Fe_(0.75)PO_(4)/C during delithiation,contrary to the pristine LiFePO_(4),without major structural reconstruction,which helps to explain the superior rate performance.Furthermore,the density functional theory(DFT)calculations verify the effects of Mn doping and embody the superiority of LiMn_(0.25)Fe_(0.75)PO_(4)/C as a LIB cathode,which well supports the experimental observations.This work provides insightful guidance for the design of tunable MOF-derived mixed transitionmetal systems for advanced LIBs.展开更多
文摘为了探讨5-甲基胞嘧啶(5-methylcytosine,m5C)相关基因在三阴性乳腺癌(triple negative breast cancer,TNBC)患者治疗及预后中的潜在价值,构建了基于m5C相关基因的预后预测模型,用于评估TNBC患者的预后和生存状况。从基因表达总库(gene expression omnibus,GEO)数据库和癌症基因组图谱(the cancer genome atlas,TCGA)数据库中下载TNBC基因表达谱和相应的临床数据。通过Pearson分析确定了99个m5C相关基因,进一步采用单因素Cox分析鉴定出5个与预后有关的m5C相关基因(SLC6A14、BCL11A、UGT8、LMO4、PSAT1)并构建了风险评分(risk score)预测模型,根据风险评分中位值将患者划分为高风险组和低风险组。使用Kaplan-Meier(K-M)生存分析、受试者工作特征(receiver operating characteristic,ROC)曲线、多变量Cox回归分析、构建列线图和校准曲线评估了模型的预测效能。训练集和验证集的K-M生存曲线、受试者工作特征曲线下面积(area under the curve,AUC)分析均验证了模型具有良好的预测能力。多变量Cox回归分析显示,风险评分可作为独立的预后生物标志物。使用ssGSEA、免疫评分分析和化疗药物对高低风险组患者的半最大抑制浓度(half maximal inhibitory concentration,IC50)值差异分析显示,免疫细胞和免疫检查点基因以及大多数化疗药物的IC50值在不同风险组之间的表达存在显著差异。研究结果构建了基于5个m5C相关基因的风险评分预后预测模型,这将有助于阐明TNBC中m5C相关基因的作用机制,进而提供更有价值的预后及诊断的生物标志物和潜在的治疗靶点,为TNBC患者临床个性化治疗提供理论指导。
基金supported by the Dengfeng Talent Support Program of Beijing Municipal Administration of Hospitals[Grant No.DFL20221601]the Natural Science Foundation of Beijing[Grant No.7212053]Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[Grant No.ZYYCXTD-C-202006].
文摘Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.
基金supported by the National Natural Science Foundation of China(Nos.52208369,52309138,52209142,51978666)the Department of Science and Technology of Sichuan Province(2023NSFSC0284).
文摘In practical engineering,due to the noncontinuity characteristics of joints in rock slopes,in addition to plane failure,stepped sliding failure may occur for intermittently jointed rock slopes.Especially for intermittently bedding jointed rock slopes,the correlation and difference in strength parameters between joints and rock bridges,along with the various failure modes and intermittency of rock bridges,contribute to the complexity of stepped failure modes and the unpredictability of failure regions.Based on the upper-bound limit analysis method and multi-sliders step-path failure mode,considering the shear and tensile failure of rock bridges and the weakened relationship between the strength parameters of rock bridges and jointed surfaces,by introducing the modified M-C failure criterion and the formula for calculating the energy consumption of tensile failure of rock bridges,two failure mechanisms are constructed to obtain the safety factor(F_(s))of intermittently jointed rock slopes.The sequential quadratic programming method is used to obtain the optimal upper-bound solution for F_(s).The influence of multiple key parameters(slope height H,horizontal distance L,Slope angleβ,shear strength parameters of the rock bridgeφr and cr,Dimensionless parameter u,weakening coefficients of the internal friction angle and cohesion between the rock bridges and joint surfaces Kφand Kc)on the stability analysis of intermittently jointed rock slopes under the shear failure mode of rock bridges as well as under the tensile failure mode is also explored.The reliability of the failure mechanisms is verified by comparative analysis with theoretical results,numerical results,and landslide cases,and the variation rules of F_(s)with each key parameter are obtained.The results show that F_(s) varies linearly withφr and cr of the rock bridge and with K_(φ)and K_(c),whereas F_(s)changes nonlinearly with H and L.In particular,with the increase in Kφand Kc,Fs increases by approximately 52.78%and 171.02%on average,respectively.For rock bridge tensile failure,F_(s) shows a nonlinearly positive correlation withφr,cr,Kφand Kc.In particular,with the increase in Kφand Kc,Fs increases by approximately 13%and 61.69%on average,respectively.Fs decreases rapidly with increasing slope gradientβand decreasing dimensionless parameterμ.When Kφand Kc are both less than 1.0,the stepped sliding surface occurs more easily than the plane failure surface,especially in the case of tensile failure of the rock bridge.In addition,rock slopes with higher strength parameters,taller heights,and greater weakening coefficients are prone to rock bridge tension failure with lower Fs,and more attention should be given to the occurrence of such accidents in actual engineering.
文摘Candidiasis, also known as candidiasis vulvovaginitis, is an infection caused by different types of Candida fungi, the most frequent being Candida albicans. The present study reports an effective strategy, which opens new avenues for the treatment of this public health problem. The MAC<sup>®</sup> Methodology, conventional laser light-emitting (LLLT)/LED) methods are based on the biphasic response demonstrated many times in LLLT research and as with other forms of drugs, a “drug” (irradiation parameters) and a “dose” (irradiation times) and the “Arndt-Schulz Law” is often cited as a suitable model to describe the dose-dependent effects of LLLT. This method uses photopharmaceuticals, cell markers and the use of correct parameters for each case to induce the acceleration of tissue repair. The present study shows a case of a 32-year-old patient diagnosed with recurrent candidiasis 4 years ago. Eighteen sessions were performed (every other day) using a photoactivated component (Methylene blue 1% + Clotrimazole 1%) and LED phototherapy (red, blue and violet) with emission times of 60 - 260 seconds for each applicator, according to the dose recommendations of the scar acceleration method (MAC<sup>®</sup>). At the sixth treatment session there was a noticeable decrease in the itching sensation reported by the patient. In session 11 she reported feeling a great improvement, indicating that she no longer felt itching in any area after 18 sessions. The present case demonstrates new methodologies to treat common problems in the population that have a positive impact on the quality of life. This methodology has a promising future because it is non-invasive and requires a great biological transformation for inflammatory, fungal and viral control.
文摘本文围绕C2M (Customer to Manufacturer)模式在果蔬类农产品供应链中的应用展开研究。对C2M模式进行了深入分析,探讨了其在其他行业中的成功应用以及在农产品供应链中的潜在优势。对C2M模式在果蔬类农产品供应链中的可行性和有效性进行了探讨,包括对最优定价策略、渠道选择策略等方面的分析和建议。展望了未来的研究方向和发展趋势,提出了数字化技术的整合、可持续发展和绿色供应链、供应链风险管理、新兴市场和国际贸易,以及消费者参与和定制化需求等方面的建议。研究方向将有助于推动C2M模式在果蔬类农产品供应链中的应用和发展,促进供应链的优化和创新,以满足不断变化的市场需求。
文摘The roads in correlation with the traffic linked to their existences are at the origin of the emission of numerous polluting substances likely to induce disturbances of the growth and the behavioral changes in the organisms living in their vicinities. The purpose of this study is to analyze the growth and capacity accumulation of a common earthworm species (Millsonia omodeoi) in Cu, Cr, Ni, Pb and Zn in soils along a main road called “Autoroute du Nord” in C?te d’Ivoire. Thus, the earthworms were harvested in soils from a distance of 0 m (just after the sidewalk) to a distance of 200 m from the toll highway and in a control soil sampled in Lamto reserve (C?te d’Ivoire). The study was carried out in the soil laboratory at the ecological station of Lamto reserve. The Ford-Walford technique was used to determine the model and parameters most appropriated for describing the growth of earthworms. A pairwise comparison of the growth parameters was carried out using the Kruskal-Wallis test with the STATISTICA 7.1 software. The heavy metals contained in the cultivated soils and earthworms were detected and quantified using a Scanning Electron Micro-scope (MEB FEG Supra 40 VP Zeiss) and an Atomic Absorption Spectrometer SPECTRA 110 (VARIAN). The capacity accumulation of heavy metals in earthworm was determined by the bioaccumulation factor (BAF) calculation. The results of this study showed that Gompertz is the most appropriated model to describe the growth of M. omodeoi. The life cycle of M. omodeoi shows that this earthworm adopts a K type demographic strategy. Cu is the most accumulated heavy metals in M. omodeoi, when Cr is the least accumulated. Concerning heavy metal content in the earthworms, it decreases while moving away from the pavement. These results highlight a possibility of choice of M. omodeoi as 1) indicators of heavy metals pollution and 2) target of biological organisms for environmental impact studies.
基金the financial support from the Research and Development Plan Project in Key Fields of Guangdong Province(2020B0101030005)Applied Special Project of Guangdong Provincial Science and Technology Plan(2017B090917002)+1 种基金Basic and Applied Basic Research Fund of Guangdong Province(2019B1515120027)Key R&D projects in Guangdong Province(2020B0101030005)。
文摘LiFePO_(4),as a prevailing cathode material for lithium-ion batteries(LIBs),still encounters issues such as intrinsic poor electronic conductivity,inferior Li-ion diffusion kinetic,and two-phase transformation mechanism involving substantial structural rearrangements,resulting in unsatisfactory rate performance.Carbon coating,cation doping,and morphological control have been widely employed to reconcile these issues.Inspired by these,we propose a synthetic route with metal–organic frameworks(MOFs)as self-sacrificial templates to simultaneously realize shape modulation,Mn doping,and N-doped carbon coating for enhanced electrochemical performances.The as-synthesized Li MnxFe1–xPO4/C(x=0,0.25,and0.5)deliver tunable electrochemical behaviors induced by the MOF templates,among which LiMn_(0.25)Fe_(0.75)PO_(4)/C outperforms its counterparts in cyclability(164.7 mA h g^(-1)after 200 cycles at 0.5 C)and rate capability(116.3 mA h g^(-1)at 10 C).Meanwhile,the ex-situ XRD reveals a dominant single-phase solid solution mechanism of LiMn_(0.25)Fe_(0.75)PO_(4)/C during delithiation,contrary to the pristine LiFePO_(4),without major structural reconstruction,which helps to explain the superior rate performance.Furthermore,the density functional theory(DFT)calculations verify the effects of Mn doping and embody the superiority of LiMn_(0.25)Fe_(0.75)PO_(4)/C as a LIB cathode,which well supports the experimental observations.This work provides insightful guidance for the design of tunable MOF-derived mixed transitionmetal systems for advanced LIBs.
