BACKGROUND Fanlian Huazhuo Formula(FLHZF)has the functions of invigorating spleen and resolving phlegm,clearing heat and purging turbidity.It has been identified to have therapeutic effects on type 2 diabetes mellitus...BACKGROUND Fanlian Huazhuo Formula(FLHZF)has the functions of invigorating spleen and resolving phlegm,clearing heat and purging turbidity.It has been identified to have therapeutic effects on type 2 diabetes mellitus(T2DM)in clinical application.Non-alcoholic fatty liver disease(NAFLD)is frequently diagnosed in patients with T2DM.However,the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation.AIM To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro.METHODS HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model.Subsequently,experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours.C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD,and then treated with the different concentrations of FLHZF for 10 weeks.RESULTS FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro.Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress,regulating the AMPKα/SREBP-1C signaling pathway,activating autophagy,and inhibiting hepatocyte apoptosis.CONCLUSION FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species,autophagy,apoptosis,and lipid synthesis signaling pathways,indicating its potential for clinical application in NAFLD.展开更多
Microdamage accumulation in bone is one of the mechanisms for energy dissipation during the fracture process. Changes in the ultrastructure and composition of bone constituents due to aging or diseases could affect mi...Microdamage accumulation in bone is one of the mechanisms for energy dissipation during the fracture process. Changes in the ultrastructure and composition of bone constituents due to aging or diseases could affect microdamage accumulation. Low concentration （1 mM） of sodium fluoride （NaF） has been used in this study to investigate the effect of ultrastructural changes on microdamage accumu- lation in mouse tibias following free-fall impact loadings. Twenty-two tibias were divided randomly into control and NaF-treated groups. Free-fall impact loading was conducted twice on each tibia to produce microdamage. The elas- tic modulus of NaF-treated tibias decreased significantly after the impact loadings, while there was no significant difference in the modulus of untreated samples between pre- and post-damage loadings. Microdamage morphology analysis showed that less and shorter microcracks existed in NaF-treated tibias compared with control bones. Meanwhile, more and longer microcracks were observed in tensile regions in untreated samples compared with that in compressive regions, whereas no significant difference was observed between tensile and compressive regions in NaF-treated bones. The results of this study indicate that more energy is required to generate microcracks in NaF-treated bone than in normal bone. A low concentration of fluoride treatment may increase the toughness of bone under impact loading.展开更多
Carrot(Daucus carota)is an Apiaceae plant with multi-colored fleshy roots that provides a model system for carotenoid research.In this study,we assembled a 430.40 Mb high-quality gapless genome to the telomere-to-telo...Carrot(Daucus carota)is an Apiaceae plant with multi-colored fleshy roots that provides a model system for carotenoid research.In this study,we assembled a 430.40 Mb high-quality gapless genome to the telomere-to-telomere(T2T)level of“Kurodagosun”carrot.In total,36268 genes were identified and 34961 of them were functionally annotated.The proportion of repeat sequences in the genome was 55.3%,mainly long terminal repeats.Depending on the coverage of the repeats,14 telomeres and 9 centromeric regions on the chromosomes were predicted.A phylogenetic analysis showed that carrots evolved early in the family Apiaceae.Based on the T2T genome,we reconstructed the carotenoid metabolic pathway and identified the structural genes that regulate carotenoid biosynthesis.Among the 65 genes that were screened,9 were newly identified.Additionally,some gene sequences overlapped with transposons,suggesting replication and functional differentiation of carotenoid-related genes during carrot evolution.Given that some gene copies were barely expressed during development,they might be functionally redundant.Comparison of 24 cytochrome P450 genes associated with carotenoid biosynthesis revealed the tandem or proximal duplication resulting in expansion of CYP gene family.These results provided molecular information for carrot carotenoid accumulation and contributed to a new genetic resource.展开更多
Over the past 2 decades,cancer stem cells(CSCs)have been identified as the root cause of cancer occurrence,progression,chemoradioresistance,recurrence,and metastasis.Targeting CSCs is a novel therapeutic strategy for ...Over the past 2 decades,cancer stem cells(CSCs)have been identified as the root cause of cancer occurrence,progression,chemoradioresistance,recurrence,and metastasis.Targeting CSCs is a novel therapeutic strategy for cancer management and treatment.Liver cancer(LC)is a malignant disease that can endanger human health.Studies are increasingly suggesting that changes in the liver mechanical microenvironment are a primary driver triggering the occurrence and development of liver cancer.In this review,we summarize current understanding of the roles of the liver mechano-microenvironment and liver cancer stem cells(LCSCs)in liver cancer progression.We also discuss the relationship between the mechanical heterogeneity of liver cancer tissues and LCSC recruitment and metastasis.Finally,we highlight potential mechanosensitive molecules in LCSCs and mechanotherapy in liver cancer.Understanding the roles and regulatory mechanisms of the mechano-microenvironment and LCSCs may provide fundamental insights into liver cancer progression and aid in further development of novel therapeutic strategies.展开更多
Cancer stem cells(CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identificatio...Cancer stem cells(CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identification of CSC subpopulations inside a tumor presents a new understanding of cancer development because it implies that tumors can only be eradicated by targeting CSCs. Although advances in liver cancer detection and treatment have increased the possibility of curing the disease at early stages, unfortunately, most patients will relapse and succumb to their disease. Strategies aimed at efficiently targeting liver CSCs are becoming important for monitoring the progress of liver cancer therapy and for evaluating new therapeutic approaches. Herein, we provide a critical discussion of biological markers described in the literature regarding liver cancer stem cells and the potential of these markers to serve as therapeutic targets.展开更多
Cancer stem cells(CSCs)are a relatively rare subpopulation of tumor cell with self-renewal and tumorigenesis capabilities.CSCs are associated with cancer recurrence,progression,and chemoradiotherapy resistance.Establi...Cancer stem cells(CSCs)are a relatively rare subpopulation of tumor cell with self-renewal and tumorigenesis capabilities.CSCs are associated with cancer recurrence,progression,and chemoradiotherapy resistance.Establishing a reliable platform for CSC enrichment and study is a prerequisite for understanding the characteristics of CSCs and discovering CSC-related therapeutic strategies.Certain strategies for CSC enrichment have been used in laboratory,particularly fluorescence-activated cell sorting(FACS)and mammosphere culture.However,these methods fail to recapitulate the in vivo chemical and physical conditions in tumors,thus potentially decreasing the malignancy of CSCs in culture and yielding unreliable research results.Accumulating research suggests the promise of a biomaterial-based three-dimensional(3 D)strategy for CSC enrichment and study.This strategy has an advantage over conventional methods in simulating the tumor microenvironment,thus providing a more effective and predictive model for CSC laboratory research.In this review,we first briefly discuss the conventional methods for CSC enrichment and study.We then summarize the latest advances and challenges in biomaterial-based 3 D CSC platforms.Design strategies for materials,morphology,and chemical and physical cues are highlighted to provide direction for the future construction of platforms for CSC enrichment and study.展开更多
Cross-talk between tumor cells and mechanical stress in the tumor microenvironment has been shown to be involved in carcinogenesis.High mechanical stress in tumors can alter the metabolism and behaviors of cancer cell...Cross-talk between tumor cells and mechanical stress in the tumor microenvironment has been shown to be involved in carcinogenesis.High mechanical stress in tumors can alter the metabolism and behaviors of cancer cells and cause cancer cells to attain cancer stem-like cell properties,thus driving tumor progression and promoting metastasis.The mechanical signal is converted into a biochemical signal that activates tumorigenic signaling pathways through mechanotransduction.Herein,we describe the physical changes occurring during reprogramming of cancer cell metabolism,which regulate cancer stem cell functions and promote tumor progression and aggression.Furthermore,we highlight emerging therapeutic strategies targeting mechanotransduction signaling pathways.展开更多
This paper comprehensively reviews the research progress on the pharmacological effects of Ardisia gigantifolia Stapf in recent years,and finds that Ardisia gigantifolia Stapf has good pharmacological effects in many ...This paper comprehensively reviews the research progress on the pharmacological effects of Ardisia gigantifolia Stapf in recent years,and finds that Ardisia gigantifolia Stapf has good pharmacological effects in many aspects,including anti-inflammation,anti-oxidation,anti-thrombosis,anti-tumor and so on.In particular,more than ten saponins have been found to have good anti-tumor activity and have potential research value,which can provide reference for the full development and utilization of Ardisia gigantifolia Stapf resources.展开更多
The resistive random access memory(RRAM)has stimulated a variety of promising applications including programmable analog circuit,massive data storage,neuromorphic computing,etc.These new emerging applications have hug...The resistive random access memory(RRAM)has stimulated a variety of promising applications including programmable analog circuit,massive data storage,neuromorphic computing,etc.These new emerging applications have huge demands on high integration density and low power consumption.The cross-point configuration or passive array,which offers the smallest footprint of cell size and feasible capability of multi-layer stacking,has received broad attention from the research community.In such array,correct operation of reading and writing on a cell relies on effective elimination of the sneaking current coming from the neighboring cells.This target requires nonlinear I-V characteristics of the memory cell,which can be realized by either adding separate selector or developing implicit build-in nonlinear cells.The performance of a passive array largely depends on the cell nonlinearity,reliability,on/off ratio,line resistance,thermal coupling,etc.This article provides a comprehensive review on the progress achieved concerning 3D RRAM integration.First,the authors start with a brief overview of the associative problems in passive array and the category of 3D architectures.Next,the state of the arts on the development of various selector devices and self-selective cells are presented.Key parameters that influence the device nonlinearity and current density are outlined according to the corresponding working principles.Then,the reliability issues in 3D array are summarized in terms of uniformity,endurance,retention,and disturbance.Subsequently,scaling issue and thermal crosstalk in 3D memory array are thoroughly discussed,and applications of 3D RRAM beyond storage,such as neuromorphic computing and CMOL circuit are discussed later.Summary and outlooks are given in the final.展开更多
BACKGROUND Collagen is one of the most commonly used natural biomaterials for tendon tissue engineering.One of the possible practical ways to further enhance tendon repair is to combine a porous collagen sponge scaffo...BACKGROUND Collagen is one of the most commonly used natural biomaterials for tendon tissue engineering.One of the possible practical ways to further enhance tendon repair is to combine a porous collagen sponge scaffold with a suitable growth factor or cytokine that has an inherent ability to promote the recruitment,proliferation,and tenogenic differentiation of cells.However,there is an incomplete understanding of which growth factors are sufficient and optimal for the tenogenic differentiation of rat bone marrow mesenchymal stem cells(BMSCs)in a collagen sponge-based 3D culture system.AIM To identify one or more ideal growth factors that benefit the proliferation and tenogenic differentiation of rat BMSCs in a porous collagen sponge scaffold.METHODS We constructed a 3D culture system based on a type I collagen sponge scaffold.The surface topography of the collagen sponge scaffold was observed by scanning electron microscopy.Primary BMSCs were isolated from Sprague-Dawley rats.Cell survival on the surfaces of the scaffolds with different growth factors was assessed by live/dead assay and CCK-8 assay.The mRNA and protein expression levels were confirmed by quantitative real-time polymerase chain reaction and Western blot,respectively.The deposited collagen was assessed by Sirius Red staining.RESULTS Transforming growth factorβ1(TGF-β1)showed great promise in the tenogenic differentiation of BMSCs compared to growth differentiation factor 7(GDF-7)and insulin-like growth factor 1(IGF-1)in both the 2D and 3D cultures,and the 3D culture enhanced the differentiation of BMSCs into tenocytes well beyond the level of induction in the 2D culture after TGF-β1 treatment.In the 2D culture,the proliferation of the BMSCs showed no significant changes compared to the control group after TGF-β1,IGF-1,or GDF-7 treatment.However,TGF-β1 and GDF-7 could increase the cell proliferation in the 3D culture.Strangely,we also found more dead cells in the BMSC-collagen sponge constructs that were treated with TGF-β1.Moreover,TGF-β1 promoted more collagen deposition in both the 2D and 3D cultures.CONCLUSION Collagen sponge-based 3D culture with TGF-β1 enhances the responsiveness of the proliferation and tenogenic differentiation of rat BMSCs.展开更多
The tail bits of intermediate resistance states（IRSs） achieved in the SET process（IRSS） and the RESET process（IRSR） of conductive-bridge random-access memory were investigated. Two types of tail bits were observ...The tail bits of intermediate resistance states（IRSs） achieved in the SET process（IRSS） and the RESET process（IRSR） of conductive-bridge random-access memory were investigated. Two types of tail bits were observed, depending on the filament morphology after the SET/RESET operation.（i） Tail bits resulting from lateral diffusion of Cu ions introduced an abrupt increase of device resistance from IRS to ultrahigh-resistance state, which mainly happened in IRSS.（ii） Tail bits induced by the vertical diffusion of Cu ions showed a gradual shift of resistance toward lower value. Statistical results show that more than 95% of tail bits are generated in IRSS. To achieve a reliable IRS for multilevel cell（MLC） operation, it is desirable to program the IRS in RESET operation. The mechanism of tail bit generation that is disclosed here provides a clear guideline for the data retention optimization of MLC resistive random-access memory cells.展开更多
To reveal the sterility characteristics of Lycium barbarum haploids, cytological observations were made on the anthers of Ningqi No.1 and its haploids obtained from anther culture. The results showed that there were n...To reveal the sterility characteristics of Lycium barbarum haploids, cytological observations were made on the anthers of Ningqi No.1 and its haploids obtained from anther culture. The results showed that there were no significant differences in anther development between Ningqi No.1 and its haploids at the stage of pollen mother cell, and tetrads were formed successfully after the meiosis stage. The tetrads of Ningqi No.1 could release microspores. At the same time, the tapetal cells can provide nutrition for the development of the microspores, which eventually developed into mature pollen grains. Although the haploids could also release microspores at the tetrad stage, the tapetal cells degraded in advance, which made the released microspores unable to develop into mature pollen grains, resulting in pollen abortion of haploids.展开更多
The spiking neural network(SNN),closely inspired by the human brain,is one of the most powerful platforms to enable highly efficient,low cost,and robust neuromorphic computations in hardware using traditional or emerg...The spiking neural network(SNN),closely inspired by the human brain,is one of the most powerful platforms to enable highly efficient,low cost,and robust neuromorphic computations in hardware using traditional or emerging electron devices within an integrated system.In the hardware implementation,the building of artificial spiking neurons is fundamental for constructing the whole system.However,with the slowing down of Moore’s Law,the traditional complementary metal-oxide-semiconductor(CMOS)technology is gradually fading and is unable to meet the growing needs of neuromorphic computing.Besides,the existing artificial neuron circuits are complex owing to the limited bio-plausibility of CMOS devices.Memristors with volatile threshold switching(TS)behaviors and rich dynamics are promising candidates to emulate the biological spiking neurons beyond the CMOS technology and build high-efficient neuromorphic systems.Herein,the state-of-the-art about the fundamental knowledge of SNNs is reviewed.Moreover,we review the implementation of TS memristor-based neurons and their systems,and point out the challenges that should be further considered from devices to circuits in the system demonstrations.We hope that this review could provide clues and be helpful for the future development of neuromorphic computing with memristors.展开更多
Objective: To explore the effect of Daine-35 on serum hormone and antral follicle count of different subtypes of polycystic ovarian syndrome (PCOS). Methods: 138 cases of PCOS were recruited and typed according to Rot...Objective: To explore the effect of Daine-35 on serum hormone and antral follicle count of different subtypes of polycystic ovarian syndrome (PCOS). Methods: 138 cases of PCOS were recruited and typed according to Rotterdam diagnostic criteria;78 cases of tubal infertility without hyperandrogenism and menstrual disorders during the same period were collected as control. Serum reproductive hormones including follicle-stimulating hormone (FSH), luteotropic hormone (LH), prolactin (PRL), estradiol (E2), dehydroepiandrosterone (DHEAS), total testosterone (TT) and fast insulin (INS) were determined by chemiluminescent immunoassay. Ovarian antral follicle count was determined by ultrasonography. The effects on above indexes were evaluated for different subtypes of PCOS after 3 cycles of treatment with Daine-35. Results: The cases of Type A and Type B were respectively 43 (31.2%) and 73 (52.9%). They were the most common clinical phenotypes of PCOS in the central region ofChina. Total testosterone (TT) and DHEAS levels of Types A, C and D were higher than those of the control group (p < 0.05). The LH, LH/FSH, INS and HOMA-IR levels in all types of PCOS were higher than those of the control group (p < 0.05). Antral follicle counts of Types A, B and D were more than those of Type C and the control group (p < 0.05). After treatment with Daine-35 for 3 cycles, the serum TT levels of Types A, C and D decreased (p < 0.05). DHEAS values also decreased, but not significantly (p > 0.05). The serum LH and LH/FSH as well as the antral follicle count of all the PCOS types significantly decreased (p < 0.01). Conclusion: Type A and Type B are the most common clinical phenotypes of PCOS in the central region of China. Taking Daine-35 for 3 cycles can significantly reduce the serum androgen, serum LH, LH/FSH ratio, and antral follicle count of different PCOS types.展开更多
In recent years,with the modern development of traditional medicine,the research on the treatment of inflammatory bowel disease and bowel cancer is increasingly deep.This paper reviews the pharmacological research pro...In recent years,with the modern development of traditional medicine,the research on the treatment of inflammatory bowel disease and bowel cancer is increasingly deep.This paper reviews the pharmacological research progress of flavonoids,alkaloids,polyphenols,polysaccharides,steroids and saponins in the treatment of inflammatory bowel disease and canceration.展开更多
Heme proteins play various important roles in a variety of physiological and pathological processes.Surfactant assemblies have drawn great attention in fabricating fluorescent sensors to detect and identify proteins.I...Heme proteins play various important roles in a variety of physiological and pathological processes.Surfactant assemblies have drawn great attention in fabricating fluorescent sensors to detect and identify proteins.In this study,an acetylpyrene fluorophore containing imidazole HP-1 was synthesized,and it could be well modulated by an anionic surfactant sodium dodecyl sulfate(SDS).The selected ensemble based on HP-1/SDS assemblies exhibited selective fluorescence sensing performance towards the heme proteins,including neuroglobin(Ngb),myoglobin(Mb)and cytochrome c(Cyt c).Besides,phospholipid DMPC vesicles as membrane models were particularly explored the association process between the heme protein Mb and membrane.The present work showed that Mb induced the lysis of DMPC liposomes visualized by transmission electron microscopy and optical microscope.展开更多
Carbonate rock chemical weathering carbon sinks reduce the rate of increase of the atmospheric CO_(2) concentration and global warming. However, uncertainty still exists in the estimation results of carbonate rock che...Carbonate rock chemical weathering carbon sinks reduce the rate of increase of the atmospheric CO_(2) concentration and global warming. However, uncertainty still exists in the estimation results of carbonate rock chemical weathering carbon sink fluxes(CCSF), and the contributions of climate change and ecological restoration to the CCSF are not clear. To this end, we compiled published site data on ion concentrations in different watersheds in China and used a classical thermodynamic dissolution model to reassess the potential and spatial and temporal patterns of the CCSF in China from 1991 to 2020. We quantified the contributions of temperature(MAT), precipitation(MAP), evapotranspiration(ET), soil water(SM), and the normalized difference vegetation index(NDVI) to the CCSF. The results revealed that(1) China's CCSF was 22.76 t CO_(2)km^(-2)yr^(-1), which was higher than the global average(15.77 t CO_(2)km^(-2)yr^(-1)). The total carbonate rock chemical weathering carbon sink(CCS) was 4772.67×10^(4)t CO_(2), contributing 14.91% of the global CCS through a carbonate rock area of 252.98×10^(4)km^(-2).(2) China's CCSF decreased gradually from southeast to northwest, with values of 33.14, 12.93, and7.27 t CO_(2)km^(-2)yr^(-1)in the southern karst, Qinghai-Tibetan karst, and northern karst regions, respectively.(3) The overall CCSF in China exhibited an increasing trend from 1991 to 2020, with a rate of increase of 0.16 t CO_(2)km^(-2)yr^(-1).(4) The contributions of the MAP, MAT, ET, SM, and NDVI to the CCSF were 63.3%, 3.02%, 27.5%, 3.1%, and 3.05%, respectively. Among them, the increase in precipitation was the main contributor to the increase in the CCSF in China over the last 30 years, while the enhancement of ET offset part of the positive contribution of the increase in precipitation to the CCSF. In conclusion, the results of this study provide a systematic quantification of the magnitude, the patterns, and the influencing factors of CCS over a long time series in China. The results are of great significance and provide a reference for the diagnosis and gap analysis of the national and global carbon neutrality capacities.展开更多
Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been d...Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their targets.Cell differentiation is associated with an increase in mitochondrial content and activity.The metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate pathways.Leucine-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell stemness.We found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and function.Knockdown of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic differentiation.It also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro model.When LETM1 was knocked down in vivo,there was reduced tumor formation and lung metastasis.These data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.展开更多
基金Supported by Basic and Applied Basic Research Found of Guangdong Province,No.2022A1515011307。
文摘BACKGROUND Fanlian Huazhuo Formula(FLHZF)has the functions of invigorating spleen and resolving phlegm,clearing heat and purging turbidity.It has been identified to have therapeutic effects on type 2 diabetes mellitus(T2DM)in clinical application.Non-alcoholic fatty liver disease(NAFLD)is frequently diagnosed in patients with T2DM.However,the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation.AIM To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro.METHODS HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model.Subsequently,experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours.C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD,and then treated with the different concentrations of FLHZF for 10 weeks.RESULTS FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro.Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress,regulating the AMPKα/SREBP-1C signaling pathway,activating autophagy,and inhibiting hepatocyte apoptosis.CONCLUSION FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species,autophagy,apoptosis,and lipid synthesis signaling pathways,indicating its potential for clinical application in NAFLD.
基金supported by the National Natural Science Foundation of China (Grant 10872007)
文摘Microdamage accumulation in bone is one of the mechanisms for energy dissipation during the fracture process. Changes in the ultrastructure and composition of bone constituents due to aging or diseases could affect microdamage accumulation. Low concentration （1 mM） of sodium fluoride （NaF） has been used in this study to investigate the effect of ultrastructural changes on microdamage accumu- lation in mouse tibias following free-fall impact loadings. Twenty-two tibias were divided randomly into control and NaF-treated groups. Free-fall impact loading was conducted twice on each tibia to produce microdamage. The elas- tic modulus of NaF-treated tibias decreased significantly after the impact loadings, while there was no significant difference in the modulus of untreated samples between pre- and post-damage loadings. Microdamage morphology analysis showed that less and shorter microcracks existed in NaF-treated tibias compared with control bones. Meanwhile, more and longer microcracks were observed in tensile regions in untreated samples compared with that in compressive regions, whereas no significant difference was observed between tensile and compressive regions in NaF-treated bones. The results of this study indicate that more energy is required to generate microcracks in NaF-treated bone than in normal bone. A low concentration of fluoride treatment may increase the toughness of bone under impact loading.
基金This article was supported by National Natural Science Foundation of China(32072563,32102369)Natural Science Foundation of Jiangsu Province(BK20211366)+2 种基金Project of Guizhou Provincial Department of Science and Technology(Qiankehe Fuqi[2022005])Project of Guiyang of Science and Technology Bureau(Zhuke contract[2021]5-1)Priority Academic Program Development of Jiangsu Higher Education Institutions Project(PAPD).
文摘Carrot(Daucus carota)is an Apiaceae plant with multi-colored fleshy roots that provides a model system for carotenoid research.In this study,we assembled a 430.40 Mb high-quality gapless genome to the telomere-to-telomere(T2T)level of“Kurodagosun”carrot.In total,36268 genes were identified and 34961 of them were functionally annotated.The proportion of repeat sequences in the genome was 55.3%,mainly long terminal repeats.Depending on the coverage of the repeats,14 telomeres and 9 centromeric regions on the chromosomes were predicted.A phylogenetic analysis showed that carrots evolved early in the family Apiaceae.Based on the T2T genome,we reconstructed the carotenoid metabolic pathway and identified the structural genes that regulate carotenoid biosynthesis.Among the 65 genes that were screened,9 were newly identified.Additionally,some gene sequences overlapped with transposons,suggesting replication and functional differentiation of carotenoid-related genes during carrot evolution.Given that some gene copies were barely expressed during development,they might be functionally redundant.Comparison of 24 cytochrome P450 genes associated with carotenoid biosynthesis revealed the tandem or proximal duplication resulting in expansion of CYP gene family.These results provided molecular information for carrot carotenoid accumulation and contributed to a new genetic resource.
基金supported by grants from National Natural Science Foundation of China(Grant No.11832008)the Natural Scienceof Chongqing(Grant No.cstc2020jcyj-msxm X0545)the Japan Society for the Promotion of Science under grants-in-Aid for Scientific Research(S)(Grant No.17H06146)。
文摘Over the past 2 decades,cancer stem cells(CSCs)have been identified as the root cause of cancer occurrence,progression,chemoradioresistance,recurrence,and metastasis.Targeting CSCs is a novel therapeutic strategy for cancer management and treatment.Liver cancer(LC)is a malignant disease that can endanger human health.Studies are increasingly suggesting that changes in the liver mechanical microenvironment are a primary driver triggering the occurrence and development of liver cancer.In this review,we summarize current understanding of the roles of the liver mechano-microenvironment and liver cancer stem cells(LCSCs)in liver cancer progression.We also discuss the relationship between the mechanical heterogeneity of liver cancer tissues and LCSC recruitment and metastasis.Finally,we highlight potential mechanosensitive molecules in LCSCs and mechanotherapy in liver cancer.Understanding the roles and regulatory mechanisms of the mechano-microenvironment and LCSCs may provide fundamental insights into liver cancer progression and aid in further development of novel therapeutic strategies.
基金Supported by The Natural National Science Foundation of ChinaNo.11272365
文摘Cancer stem cells(CSCs) are a small subpopulation in cancer, have been proposed to be cancer-initiating cells, and have been shown to be responsible for chemotherapy resistance and cancer recurrence. The identification of CSC subpopulations inside a tumor presents a new understanding of cancer development because it implies that tumors can only be eradicated by targeting CSCs. Although advances in liver cancer detection and treatment have increased the possibility of curing the disease at early stages, unfortunately, most patients will relapse and succumb to their disease. Strategies aimed at efficiently targeting liver CSCs are becoming important for monitoring the progress of liver cancer therapy and for evaluating new therapeutic approaches. Herein, we provide a critical discussion of biological markers described in the literature regarding liver cancer stem cells and the potential of these markers to serve as therapeutic targets.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.11832008 and 81703012)the Program of the Postgraduate Tutor Team of Chongqing Education Commission(2018)+1 种基金the Fundamental Research Funds for the Central Universities(Grant No.2019CDXYSG0004)the Visiting Scholar Foundation of the Key Laboratory of Biorheological Science and Technology(Chongqing University),Ministry of Education(Grant No.CQKLBST-2017-005)。
文摘Cancer stem cells(CSCs)are a relatively rare subpopulation of tumor cell with self-renewal and tumorigenesis capabilities.CSCs are associated with cancer recurrence,progression,and chemoradiotherapy resistance.Establishing a reliable platform for CSC enrichment and study is a prerequisite for understanding the characteristics of CSCs and discovering CSC-related therapeutic strategies.Certain strategies for CSC enrichment have been used in laboratory,particularly fluorescence-activated cell sorting(FACS)and mammosphere culture.However,these methods fail to recapitulate the in vivo chemical and physical conditions in tumors,thus potentially decreasing the malignancy of CSCs in culture and yielding unreliable research results.Accumulating research suggests the promise of a biomaterial-based three-dimensional(3 D)strategy for CSC enrichment and study.This strategy has an advantage over conventional methods in simulating the tumor microenvironment,thus providing a more effective and predictive model for CSC laboratory research.In this review,we first briefly discuss the conventional methods for CSC enrichment and study.We then summarize the latest advances and challenges in biomaterial-based 3 D CSC platforms.Design strategies for materials,morphology,and chemical and physical cues are highlighted to provide direction for the future construction of platforms for CSC enrichment and study.
基金the National Natural Science Foundation of China(Grant No.11832008 and 11772073)by the Program of the Postgraduate Tutor Team,Chongqing Education Commission(2018).
文摘Cross-talk between tumor cells and mechanical stress in the tumor microenvironment has been shown to be involved in carcinogenesis.High mechanical stress in tumors can alter the metabolism and behaviors of cancer cells and cause cancer cells to attain cancer stem-like cell properties,thus driving tumor progression and promoting metastasis.The mechanical signal is converted into a biochemical signal that activates tumorigenic signaling pathways through mechanotransduction.Herein,we describe the physical changes occurring during reprogramming of cancer cell metabolism,which regulate cancer stem cell functions and promote tumor progression and aggression.Furthermore,we highlight emerging therapeutic strategies targeting mechanotransduction signaling pathways.
基金Project of Guangdong Provincial Bureau of Chinese Medicine(20201371)Guangdong Medical Research Foundation(A2020170)Science and Technology Plan of Zhongshan City,Guangdong Province(2019B1014).
文摘This paper comprehensively reviews the research progress on the pharmacological effects of Ardisia gigantifolia Stapf in recent years,and finds that Ardisia gigantifolia Stapf has good pharmacological effects in many aspects,including anti-inflammation,anti-oxidation,anti-thrombosis,anti-tumor and so on.In particular,more than ten saponins have been found to have good anti-tumor activity and have potential research value,which can provide reference for the full development and utilization of Ardisia gigantifolia Stapf resources.
基金the National Key R&D Program of China(Grant Nos.2018YFB0407501 and 2016YFA0201800)the National Natural Science Foundation of China(Grant Nos.61804173,61922083,61804167,61904200,and 61821091)the fourth China Association for Science and Technology Youth Talent Support Project(Grant No.2019QNRC001).
文摘The resistive random access memory(RRAM)has stimulated a variety of promising applications including programmable analog circuit,massive data storage,neuromorphic computing,etc.These new emerging applications have huge demands on high integration density and low power consumption.The cross-point configuration or passive array,which offers the smallest footprint of cell size and feasible capability of multi-layer stacking,has received broad attention from the research community.In such array,correct operation of reading and writing on a cell relies on effective elimination of the sneaking current coming from the neighboring cells.This target requires nonlinear I-V characteristics of the memory cell,which can be realized by either adding separate selector or developing implicit build-in nonlinear cells.The performance of a passive array largely depends on the cell nonlinearity,reliability,on/off ratio,line resistance,thermal coupling,etc.This article provides a comprehensive review on the progress achieved concerning 3D RRAM integration.First,the authors start with a brief overview of the associative problems in passive array and the category of 3D architectures.Next,the state of the arts on the development of various selector devices and self-selective cells are presented.Key parameters that influence the device nonlinearity and current density are outlined according to the corresponding working principles.Then,the reliability issues in 3D array are summarized in terms of uniformity,endurance,retention,and disturbance.Subsequently,scaling issue and thermal crosstalk in 3D memory array are thoroughly discussed,and applications of 3D RRAM beyond storage,such as neuromorphic computing and CMOL circuit are discussed later.Summary and outlooks are given in the final.
基金Supported by Natural National Science Foundation of China,No.31700810 and No.11772073Science and Technology Research Program of Chongqing Municipal Education Commission,No.KJQN201800601+1 种基金Natural Science Foundation of Chongqing,China,No.cstc2020jcyj-msxmX0760Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology(Chongqing University),Ministry of Education,No.CQKLBST-2018-007.
文摘BACKGROUND Collagen is one of the most commonly used natural biomaterials for tendon tissue engineering.One of the possible practical ways to further enhance tendon repair is to combine a porous collagen sponge scaffold with a suitable growth factor or cytokine that has an inherent ability to promote the recruitment,proliferation,and tenogenic differentiation of cells.However,there is an incomplete understanding of which growth factors are sufficient and optimal for the tenogenic differentiation of rat bone marrow mesenchymal stem cells(BMSCs)in a collagen sponge-based 3D culture system.AIM To identify one or more ideal growth factors that benefit the proliferation and tenogenic differentiation of rat BMSCs in a porous collagen sponge scaffold.METHODS We constructed a 3D culture system based on a type I collagen sponge scaffold.The surface topography of the collagen sponge scaffold was observed by scanning electron microscopy.Primary BMSCs were isolated from Sprague-Dawley rats.Cell survival on the surfaces of the scaffolds with different growth factors was assessed by live/dead assay and CCK-8 assay.The mRNA and protein expression levels were confirmed by quantitative real-time polymerase chain reaction and Western blot,respectively.The deposited collagen was assessed by Sirius Red staining.RESULTS Transforming growth factorβ1(TGF-β1)showed great promise in the tenogenic differentiation of BMSCs compared to growth differentiation factor 7(GDF-7)and insulin-like growth factor 1(IGF-1)in both the 2D and 3D cultures,and the 3D culture enhanced the differentiation of BMSCs into tenocytes well beyond the level of induction in the 2D culture after TGF-β1 treatment.In the 2D culture,the proliferation of the BMSCs showed no significant changes compared to the control group after TGF-β1,IGF-1,or GDF-7 treatment.However,TGF-β1 and GDF-7 could increase the cell proliferation in the 3D culture.Strangely,we also found more dead cells in the BMSC-collagen sponge constructs that were treated with TGF-β1.Moreover,TGF-β1 promoted more collagen deposition in both the 2D and 3D cultures.CONCLUSION Collagen sponge-based 3D culture with TGF-β1 enhances the responsiveness of the proliferation and tenogenic differentiation of rat BMSCs.
基金Project supported by the Ministry of Science and Technology of China(Grant Nos.2016YFA0203800,2016YFA0201803,and 2018YFB0407502)the National Natural Science Foundation of China(Grant Nos.61522408,61334007,and 61521064)+1 种基金Beijing Municipal Science&Technology Commission Program,China(Grant No.Z161100000216153)Huawei Data Center Technology Laboratory
文摘The tail bits of intermediate resistance states（IRSs） achieved in the SET process（IRSS） and the RESET process（IRSR） of conductive-bridge random-access memory were investigated. Two types of tail bits were observed, depending on the filament morphology after the SET/RESET operation.（i） Tail bits resulting from lateral diffusion of Cu ions introduced an abrupt increase of device resistance from IRS to ultrahigh-resistance state, which mainly happened in IRSS.（ii） Tail bits induced by the vertical diffusion of Cu ions showed a gradual shift of resistance toward lower value. Statistical results show that more than 95% of tail bits are generated in IRSS. To achieve a reliable IRS for multilevel cell（MLC） operation, it is desirable to program the IRS in RESET operation. The mechanism of tail bit generation that is disclosed here provides a clear guideline for the data retention optimization of MLC resistive random-access memory cells.
基金Supported by Natural Science Foundation of Ningxia Hui Autonomous Region(NZ16097)Special Agricultural Breeding Project of Ningxia Hui Autonomous Region(2013NYYZ0105,2018NYYZ01-03)
文摘To reveal the sterility characteristics of Lycium barbarum haploids, cytological observations were made on the anthers of Ningqi No.1 and its haploids obtained from anther culture. The results showed that there were no significant differences in anther development between Ningqi No.1 and its haploids at the stage of pollen mother cell, and tetrads were formed successfully after the meiosis stage. The tetrads of Ningqi No.1 could release microspores. At the same time, the tapetal cells can provide nutrition for the development of the microspores, which eventually developed into mature pollen grains. Although the haploids could also release microspores at the tetrad stage, the tapetal cells degraded in advance, which made the released microspores unable to develop into mature pollen grains, resulting in pollen abortion of haploids.
基金This work was supported in part by the Ministry of Science and Technology of China under Grant No.2017YFA0206102in part by the National Natural Science Foundation of China under Grant No.61922083+2 种基金by the Strategic Priority Research Program of Chinese Academy of Sciences under Grant No.XDB44000000by the European Union’s Horizon 2020 Research and Innovation Program with Grant Agreement No.824164by the German Research Foundation Projects MemCrypto under Grant No.GZ:DU 1896/2-1 and MemDPU under Grant No.GZ:DU 1896/3-1.
文摘The spiking neural network(SNN),closely inspired by the human brain,is one of the most powerful platforms to enable highly efficient,low cost,and robust neuromorphic computations in hardware using traditional or emerging electron devices within an integrated system.In the hardware implementation,the building of artificial spiking neurons is fundamental for constructing the whole system.However,with the slowing down of Moore’s Law,the traditional complementary metal-oxide-semiconductor(CMOS)technology is gradually fading and is unable to meet the growing needs of neuromorphic computing.Besides,the existing artificial neuron circuits are complex owing to the limited bio-plausibility of CMOS devices.Memristors with volatile threshold switching(TS)behaviors and rich dynamics are promising candidates to emulate the biological spiking neurons beyond the CMOS technology and build high-efficient neuromorphic systems.Herein,the state-of-the-art about the fundamental knowledge of SNNs is reviewed.Moreover,we review the implementation of TS memristor-based neurons and their systems,and point out the challenges that should be further considered from devices to circuits in the system demonstrations.We hope that this review could provide clues and be helpful for the future development of neuromorphic computing with memristors.
文摘Objective: To explore the effect of Daine-35 on serum hormone and antral follicle count of different subtypes of polycystic ovarian syndrome (PCOS). Methods: 138 cases of PCOS were recruited and typed according to Rotterdam diagnostic criteria;78 cases of tubal infertility without hyperandrogenism and menstrual disorders during the same period were collected as control. Serum reproductive hormones including follicle-stimulating hormone (FSH), luteotropic hormone (LH), prolactin (PRL), estradiol (E2), dehydroepiandrosterone (DHEAS), total testosterone (TT) and fast insulin (INS) were determined by chemiluminescent immunoassay. Ovarian antral follicle count was determined by ultrasonography. The effects on above indexes were evaluated for different subtypes of PCOS after 3 cycles of treatment with Daine-35. Results: The cases of Type A and Type B were respectively 43 (31.2%) and 73 (52.9%). They were the most common clinical phenotypes of PCOS in the central region ofChina. Total testosterone (TT) and DHEAS levels of Types A, C and D were higher than those of the control group (p < 0.05). The LH, LH/FSH, INS and HOMA-IR levels in all types of PCOS were higher than those of the control group (p < 0.05). Antral follicle counts of Types A, B and D were more than those of Type C and the control group (p < 0.05). After treatment with Daine-35 for 3 cycles, the serum TT levels of Types A, C and D decreased (p < 0.05). DHEAS values also decreased, but not significantly (p > 0.05). The serum LH and LH/FSH as well as the antral follicle count of all the PCOS types significantly decreased (p < 0.01). Conclusion: Type A and Type B are the most common clinical phenotypes of PCOS in the central region of China. Taking Daine-35 for 3 cycles can significantly reduce the serum androgen, serum LH, LH/FSH ratio, and antral follicle count of different PCOS types.
基金Guangdong Medical Research Foundation(A2020170,A2022479)Project of Guangdong Chinese Medicine Bureau(20201371)Zhongshan Science and Technology Plan(2019B1014).
文摘In recent years,with the modern development of traditional medicine,the research on the treatment of inflammatory bowel disease and bowel cancer is increasingly deep.This paper reviews the pharmacological research progress of flavonoids,alkaloids,polyphenols,polysaccharides,steroids and saponins in the treatment of inflammatory bowel disease and canceration.
基金financially supported by the Scientific Research Fund of Hunan Education Department,China(Nos.21B0421,20C1636)The National Natural Science Foundation of China(No.21977042)。
文摘Heme proteins play various important roles in a variety of physiological and pathological processes.Surfactant assemblies have drawn great attention in fabricating fluorescent sensors to detect and identify proteins.In this study,an acetylpyrene fluorophore containing imidazole HP-1 was synthesized,and it could be well modulated by an anionic surfactant sodium dodecyl sulfate(SDS).The selected ensemble based on HP-1/SDS assemblies exhibited selective fluorescence sensing performance towards the heme proteins,including neuroglobin(Ngb),myoglobin(Mb)and cytochrome c(Cyt c).Besides,phospholipid DMPC vesicles as membrane models were particularly explored the association process between the heme protein Mb and membrane.The present work showed that Mb induced the lysis of DMPC liposomes visualized by transmission electron microscopy and optical microscope.
基金supported by the National Natural Science Foundation(Grant Nos.U22A20619,42077455&42367008)the Western Light Cross-team Program of Chinese Academy of Sciences(Grant No.xbzg-zdsys-202101)+3 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant Nos.XDB40000000&XDA23060100)the Guizhou Provincial Science and Technology Projects(Grant No.2022-198)the High-level Innovative Talents in Guizhou Province(Grant Nos.GCC[2022]015-1&2016-5648)the Guizhou Provincial Science and Technology Subsidies(Grant Nos.GZ2019SIG&GZ2020SIG)。
文摘Carbonate rock chemical weathering carbon sinks reduce the rate of increase of the atmospheric CO_(2) concentration and global warming. However, uncertainty still exists in the estimation results of carbonate rock chemical weathering carbon sink fluxes(CCSF), and the contributions of climate change and ecological restoration to the CCSF are not clear. To this end, we compiled published site data on ion concentrations in different watersheds in China and used a classical thermodynamic dissolution model to reassess the potential and spatial and temporal patterns of the CCSF in China from 1991 to 2020. We quantified the contributions of temperature(MAT), precipitation(MAP), evapotranspiration(ET), soil water(SM), and the normalized difference vegetation index(NDVI) to the CCSF. The results revealed that(1) China's CCSF was 22.76 t CO_(2)km^(-2)yr^(-1), which was higher than the global average(15.77 t CO_(2)km^(-2)yr^(-1)). The total carbonate rock chemical weathering carbon sink(CCS) was 4772.67×10^(4)t CO_(2), contributing 14.91% of the global CCS through a carbonate rock area of 252.98×10^(4)km^(-2).(2) China's CCSF decreased gradually from southeast to northwest, with values of 33.14, 12.93, and7.27 t CO_(2)km^(-2)yr^(-1)in the southern karst, Qinghai-Tibetan karst, and northern karst regions, respectively.(3) The overall CCSF in China exhibited an increasing trend from 1991 to 2020, with a rate of increase of 0.16 t CO_(2)km^(-2)yr^(-1).(4) The contributions of the MAP, MAT, ET, SM, and NDVI to the CCSF were 63.3%, 3.02%, 27.5%, 3.1%, and 3.05%, respectively. Among them, the increase in precipitation was the main contributor to the increase in the CCSF in China over the last 30 years, while the enhancement of ET offset part of the positive contribution of the increase in precipitation to the CCSF. In conclusion, the results of this study provide a systematic quantification of the magnitude, the patterns, and the influencing factors of CCS over a long time series in China. The results are of great significance and provide a reference for the diagnosis and gap analysis of the national and global carbon neutrality capacities.
基金supported by grants from the National Natural Science Foundation of China(No.81172545)the Chongqing Science and Technology Commission,China(No.cstc2020jcyj-msxmX0113).
文摘Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their targets.Cell differentiation is associated with an increase in mitochondrial content and activity.The metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate pathways.Leucine-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell stemness.We found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and function.Knockdown of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic differentiation.It also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro model.When LETM1 was knocked down in vivo,there was reduced tumor formation and lung metastasis.These data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.
