Formulating oil-based drilling fluids(OBDFs)with an ultra-low oil-to-water ratio(OWR≤60:40)presents a formidable stability challenge due to the maximized interfacial area and intensified stress on the interfacial fil...Formulating oil-based drilling fluids(OBDFs)with an ultra-low oil-to-water ratio(OWR≤60:40)presents a formidable stability challenge due to the maximized interfacial area and intensified stress on the interfacial film under high-temperature,high-density conditions.To address this,we engineered a synergistic stabilization system through molecular and colloidal design.A novel hyperbranched polyamide emulsifier(epoxidized soybean oil polyamide)(ESOP),synthesized from epoxidized soybean oil,exhibits superior thermal stability and interfacial activity due to its hyperbranched architecture.Combined with calcium petroleum sulfonate(CPS)and hydrophobic nanosilica(HNs),it enables a high-performance OBDF with an ultra-low OWR of 60:40.The results show that the optimized formula achieves an excellent demulsification voltage of 1290 V,an ultra-low HTHP fluid loss of 1.5 mL,a yield point of 12.9 Pa,and a superior sag factor(SF)of 0.504,outperforming both base and commercial systems.Mechanistic studies reveal a multiscale stabilization strategy involving a dense composite interfacial film,Pickering stabilization,a 3D network,and a unique thermally triggered self-reinforcement effect.This work not only provides a cost-effective OBDF formulation but,more importantly,establishes a molecular topology engineering paradigm for stabilizing complex industrial fluids under extreme conditions.展开更多
Heat processing of food has been well validated as the trigger to generate heat-processing side product of advanced lipoxidation end products(ALEs),which potentially engenders the threat on systemic health or progress...Heat processing of food has been well validated as the trigger to generate heat-processing side product of advanced lipoxidation end products(ALEs),which potentially engenders the threat on systemic health or progression of diseases,especially the accumulated effect after long-term intake.Thus,the study was proposed to evaluate the effect of dietary ALEs on health after long-term ingestion,specifically through simulating the intake of dietary ALE in mice within 9 months to investigate the intervention effect and underlying mechanism.The unexpected observation of renal insufficiency or impairment after long-term intake of dietary ALEs indicated the negative impact on renal health,which has been verified by the pathological analysis.Further studies revealed that a high-ALEs diet disrupted the intestinal barrier,with enhanced impact after disturbing the gut microbiota to potentially lower the abundance of beneficial microbiome through producing nephrotoxic metabolites.Correlation analysis showed that the proliferation of harmful bacteria and the reduction of beneficial bacteria were strongly correlated with intestinal barrier damage and the development of renal insufficiency.Furthermore,the underlying mechanism was unveiled as that ALEs could inhibit AMPK/SIRT1 signaling to fundamentally induce renal inflammation and oxidative stress.Thus,it was revealed that long-term intake of dietary ALE could result in renal impairment,and the results emphasized the control or intervention on dietary ALE to decrease to accumulated impairment on systemic health.展开更多
Intracellular redox homeostasis is of indispensable importance in pathophysiology.In order to maintain the balance of the redox state within the cell,reactive oxygen species(ROS)and reactive sulfur species(RSS)react a...Intracellular redox homeostasis is of indispensable importance in pathophysiology.In order to maintain the balance of the redox state within the cell,reactive oxygen species(ROS)and reactive sulfur species(RSS)react and transform with each other,and their levels also directly reflect the degree of oxidative stress and disease.Hypochlorous acid(HClO)and cysteine(Cys)usually co-exist in organisms,interacting with each other in many important physiological processes and synergistically maintaining the dynamic redox balance in the body.To understand the relevance and pathophysiological effects of these two signaling molecules in oxidative stress,unique fluorescence imaging tools are required.Herein,we designed and developed a dual-channel fluorescent probe HP,for the individual and continuous detection of HClO and Cys.This probe could simultaneously monitor the changes in the concentrations of HClO and Cys in cells,and was characterized by a fast response,high sensitivity and high selectivity,especially compared with glutathione(GSH)and homocysteine(Hcy),the probe had a good specificity for Cys.Importantly,probe HP successfully observed dynamic changes in HCl O-and Cys-mediated redox status in the oxygenglucose deprivation/reperfusion(OGD/R)model of HeLa cells and dynamically monitored fluctuations in endogenous HClO levels in lipopolysaccharides(LPS)-induced peritonitis mice.展开更多
Advanced lipoxidation end products(ALEs)are formed by modifying proteins with lipid oxidation products.ALEs formed in the body have been linked to diabetes and hepatic disease.However,it is not known whether ALEs form...Advanced lipoxidation end products(ALEs)are formed by modifying proteins with lipid oxidation products.ALEs formed in the body have been linked to diabetes and hepatic disease.However,it is not known whether ALEs formed in heat-processed foods can induce metabolic diseases.Our results indicate that dietary ALEs induce lipid accumulation in the liver of mice at an early stage and continuous feeding of ALEs induces inflammation,oxidative stress and hepatic insulin resistance.The core reason for these adverse reactions is the damage to the intestinal barrier caused by ALEs.Due to the damage to the intestinal barrier,there is an increase in lipopolysaccharides(LPS)in the liver that induces hepatic lipid accumulation by modulating hepatic lipid metabolism.Furthermore,ALEs plays a major role in the regulation of metabolic diseases by directly or indirectly inhibiting AMP activated protein kinase(AMPK)/Sirtuin 1(SIRT1)signaling through LPS.展开更多
Gradient-doped laser ceramics fabricated via 3D printing have great potential for high-power laser applications.However,it is challenging to produce such types of gain media because it is inconvenient to fabricate dif...Gradient-doped laser ceramics fabricated via 3D printing have great potential for high-power laser applications.However,it is challenging to produce such types of gain media because it is inconvenient to fabricate different component slurries prepared offline using traditional methods precisely.To address these issues,a facile approach for the additive manufacturing of high-power laser ceramics is proposed for gradient structure fabrication.First,a material-extrusion-based 3D printing device with a homemade active mixing module is developed to fabricate gradient-doped Yb:YAG(Y3 Al5 O12)laser ceramics using two slurries with different doping concentrations.Sub-sequently,the active mixing module is systematically investigated to obtain different Yb-doped concentrations of printing slurries with a uniform element distribution.By measuring the switching delay volume between dif-ferent components,a proper volume adjustment enables the Yb concentration distribution of the green bodies to be consistent with the designed profile in the 3D process.Finally,multi-component(0-5-10-5-0 at%Yb:YAG)green bodies are printed,and experimental tests are conducted to evaluate the performance of these gradient-doped laser ceramics.The results show that the gradient-doped ceramic obtained 82.1%in-line transmittance at 1100 nm(4.6 mm thickness,along with the doping concentration gradient)and the average Yb ions diffusion distance across the interface fitted in the 20-30𝜇m range.Furthermore,a 1030 nm laser output with an output power of 4.5 W with a slope efficiency of 41.3%is achieved when pumped with a 940 nm laser diode.This study provides useful insights for developing various gradient rare-earth-doped laser ceramics for high-power laser applications.展开更多
The Janus kinase/signal transducers and activators of transcription(JAK-TAT)control natural killer(NK)cells development and cytotoxic functions,however,whether long non-coding RNAs(lncRNAs)are involved in this pathway...The Janus kinase/signal transducers and activators of transcription(JAK-TAT)control natural killer(NK)cells development and cytotoxic functions,however,whether long non-coding RNAs(lncRNAs)are involved in this pathway remains unknown.We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and inducedpluripotent stem cells(iPSCs)-derived NK(iPSC-NK)cells,without reliance on its derived miR-155 and micropeptide P155.Mechanistically,miR155HG bound to miR-6756 and relieved its repression of JAK3 expression,thereby promoting the JAK-TAT pathway and enhancing NK cell proliferation and function.Further investigations disclosed that upon cytokine stimulation,STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription.Collectively,we identify a miR155HG-mediated positive feedback loop of the JAK-TAT signaling.Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer,especially iPSC-derived NK cells.展开更多
Diabetic wound healing remains a major challenge due to the excess hyperglycemia microenvironment,massively bacterial infections,macrophage dysfunction,and persistent inflammation.To comprehensively solve these proble...Diabetic wound healing remains a major challenge due to the excess hyperglycemia microenvironment,massively bacterial infections,macrophage dysfunction,and persistent inflammation.To comprehensively solve these problems,novel multifunctional materials are highly desirable.Herein,a versatile and intelligent hydrogel(Cu_(2)S@FePPOP_(TPM)@GO_(x)@Gel)is reported.Cu_(2)S@FePPOP_(TPM)@GO_(x)with hollow morphology and controllable size was rationally designed and fabricated by using Cu2S nanocubes as a template,followed by in situ growth of Fe PPOP_(TPM)and loading glucose oxidase(GOx),successively.When infection occurs,the Schiff base bonds in Cu_(2)S@FePPOP_(TPM)@GO_(x)@Gel can controllably release Cu_(2)S@FePPOP_(TPM)@GO_(x)based on its excellent dynamic p H-responsiveness,thereby synergically reducing blood glucose levels and killing bacteria achieved relying on the excellent catalytic activity of GOx towards glucose and its promoted peroxidelike activity of Fe PPOP_(TPM).Further experiments on diabetic wound model in vivo demonstrated that Cu_(2)S@FePPOP_(TPM)@GO_(x)@Gel promoted wound healing and skin regeneration,which was attributed to its antibacterial properties,alleviating inflammation,stimulating vascular regeneration,and encouraging M2 polarization of macrophages.This work provides a novel strategy for the construction of a microenvironment-responsive and antibiotics-free drug delivery platform to treat diabetic wounds,as well as broad prospects of nanomaterials in the clinical treatment of chronic wounds.展开更多
An upwind weak Galerkin finite element scheme was devised and analyzed in this article for convection-dominated Oseen equations. The numerical algorithm was based on the weak Galerkin method enhanced by upwind stabili...An upwind weak Galerkin finite element scheme was devised and analyzed in this article for convection-dominated Oseen equations. The numerical algorithm was based on the weak Galerkin method enhanced by upwind stabilization. The resulting finite element scheme uses equal-order, say k, polynomial spaces on each element for the velocity and the pressure unknowns. With finite elements of order k≥1, the numerical solutions are proved to converge at the rate of O(h^(k+1/2)) in an energy-like norm for convection-dominated Oseen equations. Numerical results are presented to demonstrate the accuracy and effectiveness of the upwind weak Galerkin scheme.展开更多
Radiotherapy is one of the main therapeutic methods for cancers;however,nonselective killing of normal cells and tumor cells by X-ray inevitably results in toxicity and side effects.Developing low-toxicity and high-ef...Radiotherapy is one of the main therapeutic methods for cancers;however,nonselective killing of normal cells and tumor cells by X-ray inevitably results in toxicity and side effects.Developing low-toxicity and high-efficiency radiosensitizers to reduce the practical dose of X-ray is a promising approach to overcoming these side effects.Here,we report the use of carboxylatecontaining organic ligands to construct one-dimensional high-Z lanthanide chains for efficient response to X-ray.The onedimensional lanthanide chains are stacked through weak interactions to form coordination nanoframeworks in the presence of polyethylenimine(PEI).The morphology and activity of the synthesized nanoframeworks can be regulated through selenium atom engineering.This study presents a promising approach for effective radiotherapy through selenium-engineering stable lanthanide nanoframeworks with precise coordination structures as radiosensitizers to mitigate X-ray side effects.展开更多
Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain,leading to neurodegeneration in Alzheimer’s disease(AD).Blocking active recognition of microglia w...Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain,leading to neurodegeneration in Alzheimer’s disease(AD).Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses,but is very challenging.Herein,an engineered macrophage-biomimetic versatile nanoantidote(OT-Lipo@M)is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression.Coating macrophage membranes can not only endow OT-Lipo@M with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain,but also efficiently reduce neurotoxin levels to prevent them from activating microglia.The loaded oxytocin(OT)can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4(TLR4)on microglia,inhibiting TLR4-mediated pro-inflammatory signalling cascade.Benefiting from this two-pronged immunosuppressive strategy,OT-Lipo@M exhibits outstanding therapeutic effects on ameliorating cognitive deficits,inhibiting neuronal apoptosis,and enhancing synaptic plasticity in AD mice,accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging.This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.展开更多
We derived and analyzed a new numerical scheme for the Navier-Stokes equations by using H（div） conforming finite elements. A great deal of effort was given to an establishment of some Sobolev-type inequalities for p...We derived and analyzed a new numerical scheme for the Navier-Stokes equations by using H（div） conforming finite elements. A great deal of effort was given to an establishment of some Sobolev-type inequalities for piecewise smooth functions. In particular, the newly derived Sobolev inequalities were employed to provide a mathematical theory for the H（div） finite element scheme. For example, it was proved that the new finite element scheme has solutions which admit a certain boundedness in terms of the input data. A solution uniqueness was also possible when the input data satisfies a certain smallness condition. Optimal-order error estimates for the corresponding finite element solutions were established in various Sobolev norms. The finite element solutions from the new scheme feature a full satisfaction of the continuity equation which is highly demanded in scientific computing.展开更多
A weak Galerkin(WG)method is introduced and numerically tested for the Helmholtz equation.This method is flexible by using discontinuous piecewise polynomials and retains the mass conservation property.At the same tim...A weak Galerkin(WG)method is introduced and numerically tested for the Helmholtz equation.This method is flexible by using discontinuous piecewise polynomials and retains the mass conservation property.At the same time,the WG finite element formulation is symmetric and parameter free.Several test scenarios are designed for a numerical investigation on the accuracy,convergence,and robustness of the WG method in both inhomogeneous and homogeneous media over convex and non-convex domains.Challenging problems with high wave numbers are also examined.Our numerical experiments indicate that the weak Galerkin is a finite element technique that is easy to implement,and provides very accurate and robust numerical solutions for the Helmholtz problem with high wave numbers.展开更多
The objective of this study was to investigate the molecular regulatory mechanism of 1-methylcyclopropene(1-MCP)treatment on leaf yellowing of pak choi during storage at 20°C.In the present study,compared with th...The objective of this study was to investigate the molecular regulatory mechanism of 1-methylcyclopropene(1-MCP)treatment on leaf yellowing of pak choi during storage at 20°C.In the present study,compared with the control and 10μL/L ethylene-treated pak choi,5.0μL/L 1-MCP fumigation alleviated the yellowing process of pak choi as proved by the maintenance of higher levels of colour,chlorophyll content,and appearance.1-MCP treatment decreased chlorophyll breakdown by downregulating the activity of chlorophyll-degrading enzymes(chlorophyll b reductase(CBR)and pheophytinase(PPH))and the expression of their related genes(BcNYC1 and BcPPH).The application of 1-MCP also inhibited the transcript abundance of ethylene biosynthesis and signal transduction genes(BcACO,BcEIN3,and BcERF)and reduced ethylene production,thus helping to maintain the green colour of pak choi;however,ethylene treatment exerted the opposite function.Meanwhile,three transcription factors(BcNAC055,BcMYB44,and BcOBF1)were successfully cloned.Experiments performed using yeast one-hybrid assay,dual-luciferase reporter system and in vivo bioluminescence imaging assay,confirmed that BcNAC055,BcMYB44,and BcOBF1 directly bound to the BcNYC1 promoter.1-MCP inhibited the expression levels of BcNAC055,BcMYB44,BcOBF1,and BcNYC1 during storage,while the application of ethylene activated their expression.In conclusion,1-MCP downregulated the expression of the key chlorophyll degradation gene BcNYC1 by inhibiting the transcript level of its three positive regulators(BcNAC055,BcMYB44,and BcOBF1)and lowered the activity of chlorophyll-degrading enzyme CBR,thereby helping mitigate chlorophyll breakdown to retard leaf yellowing in pak choi.The results of this work extend our understanding of 1-MCP-delayed yellowing in postharvest pak choi.展开更多
Although DNA mutation drives stem cell aging,how mutation-accumulated stem cells obtain clonal advantage during aging remains poorly understood.Here,using a mouse model of irradiation-induced premature aging and middl...Although DNA mutation drives stem cell aging,how mutation-accumulated stem cells obtain clonal advantage during aging remains poorly understood.Here,using a mouse model of irradiation-induced premature aging and middle-aged mice,we show that DNA mutation accumulation in hematopoietic stem cells(HSCs)during aging upregulates their surface expression of major histocompatibility complex class II(MHCII).MHCII upregulation increases the chance for recognition by bone marrow(BM)-resident regulatory T cells(Tregs),resulting in their clonal expansion and accumulation in the HSC niche.On the basis of the establishment of connexin 43(Cx43)-mediated gap junctions,BM Tregs transfer cyclic adenosine monophosphate(cAMP)to aged HSCs to diminish apoptotic priming and promote their survival via activation of protein kinase A(PKA)signaling.Importantly,targeting the HSC–Treg interaction or depleting Tregs effectively prevents the premature/physiological aging of HSCs.These findings show that aged HSCs use an active self-protective mechanism by entrapping local Tregs to construct a prosurvival niche and obtain a clonal advantage.展开更多
Hematopoietic system is one of the main target organs of irradiation injury.Exposure to radiation can cause acute myelosuppression and long-term hematopoietic injury due to the direct and indirect damage of hematopoie...Hematopoietic system is one of the main target organs of irradiation injury.Exposure to radiation can cause acute myelosuppression and long-term hematopoietic injury due to the direct and indirect damage of hematopoietic stem cells(HSCs)that can self-renew and differentiate into all types of blood cells.So far,many factors in the modulation of HSC biology at steady status have been revealed,while how to orchestrate HSCs in the context of radiation has not been well established.Recently,an increasing number of studies focus on the underlying mechanisms involved in regulating HSC fate after radiation exposure by affecting DNA damage response(DDR),including DNA-damage repair,cell-cycle arrest,apoptosis and senescence,or bone marrow(BM)microenvironment.In this review,we summarize recent findings on intrinsic and extrinsic factors in the regulation of HSC fate after radiation exposure,which may further deepen our understanding of the radioprotection of HSCs.展开更多
Polycyclic musks are widely used for cos- metics and other personal care and household cleaning products. The occurrence and removal of two representa- tive polycyclic musks, galaxolide （HHCB） and tonalide （AHTN） ...Polycyclic musks are widely used for cos- metics and other personal care and household cleaning products. The occurrence and removal of two representa- tive polycyclic musks, galaxolide （HHCB） and tonalide （AHTN） were investigated in three different processes of two sewage treatment plants （STPs） in Xi＇an, China. The samples were preconcentrated by solid phase extraction procedure and analyzed using a gas chromatography mass spectrometry （GC/MS） by a modified procedure. The HHCB was in the range of 82.8 to 182.5 ng.L1 in the influents and 22.6 to 103.9ng.L-1 in the effluents. The AHTN ranged from 11.0 to 19.3 ng. L-1 in the influents and 2.2 to 8.8 ng. I_~1 in the effluents. The removal efficiency of the two musks varied in the ranges of 43.1%-70.4% for HHCB and 54.2%-84.4% for AHTN. Concentrations of the two musks in aqueous phase of three processes slightly increased along the primary process, and significantly removed during the biologic treatment processes, revealing that the selected musks could be remarkably removed in varied activated sludge processes. Advanced processes of activated sludge did not show a significant superiority on selected musk removal compared to the conventional process. The selected musk removal mainly resulted from the adsorption function of activated sludge. There was no significant change of HHCB/AHTN ratios along the treatment flow, indicating that each sewage treatment structure had a similar removal efficiency for the two musks.展开更多
The search of highly efficient drugs for overcoming cancer drug resistance continues to be a challenge for scientists.Constructing a metal drug based in situ oxidation-state transition system to disturb the redox bala...The search of highly efficient drugs for overcoming cancer drug resistance continues to be a challenge for scientists.Constructing a metal drug based in situ oxidation-state transition system to disturb the redox balance in cancer cells is a promising approach for overcoming cancer drug resistance.Inspired by natural redox-active copper enzyme centers,we developed a Cu(Ⅰ)-Cu(Ⅱ) in situ transition system in this work.Through atom engineering,we fine-tuned the thermodynamic stability of this system to investigate its anticancer activity.The results indicated that the synthetic Cu(Ⅰ)-Cu(Ⅱ) system could under-go in situ transition in vitro and in vivo,to disrupt the intracellular redox balance and trigger mitochondrial dysfunction and G2/M arrest,leading to apoptosis and overcoming cancer drug resistance.This study presents a feasible way to overcome cancer drug resistance by designing an in situ oxidation-state transition metal drug system.展开更多
As the technology scales advancing into the nanometer region,the concept of yield has become an increasingly important design metric.To reduce the yield loss caused by local defects,layout optimization can play a crit...As the technology scales advancing into the nanometer region,the concept of yield has become an increasingly important design metric.To reduce the yield loss caused by local defects,layout optimization can play a critical role.In this paper,we propose a new open sensitivity-based model with consideration of the blank space around the net,and study the corresponding net optimization.The proposed new model not only has a high practicability in the selection of nets to be optimized but also solves the issue of the increase in short critical area brought during the open optimization,which means to reduce the open critical area with no new short critical area produced,and thereby this model can ensure the decrease of total critical area and finally achieves an integrative optimization.Compared with the models available,the experimental results show that our sensitivity model not only consumes less time with concise algorithm but also can deal with irregular layout,which is out of the scope of other models.At the end of this paper,the effectiveness of the new model is verified by the experiment on the randomly selected five metal layers from the synthesized OpenSparc circuit layout.展开更多
基金supported by the Key Research and Development Program Project of Hubei Province(2023BCB070).
文摘Formulating oil-based drilling fluids(OBDFs)with an ultra-low oil-to-water ratio(OWR≤60:40)presents a formidable stability challenge due to the maximized interfacial area and intensified stress on the interfacial film under high-temperature,high-density conditions.To address this,we engineered a synergistic stabilization system through molecular and colloidal design.A novel hyperbranched polyamide emulsifier(epoxidized soybean oil polyamide)(ESOP),synthesized from epoxidized soybean oil,exhibits superior thermal stability and interfacial activity due to its hyperbranched architecture.Combined with calcium petroleum sulfonate(CPS)and hydrophobic nanosilica(HNs),it enables a high-performance OBDF with an ultra-low OWR of 60:40.The results show that the optimized formula achieves an excellent demulsification voltage of 1290 V,an ultra-low HTHP fluid loss of 1.5 mL,a yield point of 12.9 Pa,and a superior sag factor(SF)of 0.504,outperforming both base and commercial systems.Mechanistic studies reveal a multiscale stabilization strategy involving a dense composite interfacial film,Pickering stabilization,a 3D network,and a unique thermally triggered self-reinforcement effect.This work not only provides a cost-effective OBDF formulation but,more importantly,establishes a molecular topology engineering paradigm for stabilizing complex industrial fluids under extreme conditions.
基金supported by grants from the National Natural Science Foundation of China(32030083)。
文摘Heat processing of food has been well validated as the trigger to generate heat-processing side product of advanced lipoxidation end products(ALEs),which potentially engenders the threat on systemic health or progression of diseases,especially the accumulated effect after long-term intake.Thus,the study was proposed to evaluate the effect of dietary ALEs on health after long-term ingestion,specifically through simulating the intake of dietary ALE in mice within 9 months to investigate the intervention effect and underlying mechanism.The unexpected observation of renal insufficiency or impairment after long-term intake of dietary ALEs indicated the negative impact on renal health,which has been verified by the pathological analysis.Further studies revealed that a high-ALEs diet disrupted the intestinal barrier,with enhanced impact after disturbing the gut microbiota to potentially lower the abundance of beneficial microbiome through producing nephrotoxic metabolites.Correlation analysis showed that the proliferation of harmful bacteria and the reduction of beneficial bacteria were strongly correlated with intestinal barrier damage and the development of renal insufficiency.Furthermore,the underlying mechanism was unveiled as that ALEs could inhibit AMPK/SIRT1 signaling to fundamentally induce renal inflammation and oxidative stress.Thus,it was revealed that long-term intake of dietary ALE could result in renal impairment,and the results emphasized the control or intervention on dietary ALE to decrease to accumulated impairment on systemic health.
基金the National Natural Science Foundation of China(Nos.22207069,22325703,22377071,22074084)Research Project Supported by Shanxi Scholarship Council of China(No.2022-002)+2 种基金the Shanxi Province Science Foundation(Nos.20210302124012,202203021221009)Key R&D and transformation plan of Qinghai Province(No.2020-GX-101)2023 Graduate Innovation Project of Shanxi University。
文摘Intracellular redox homeostasis is of indispensable importance in pathophysiology.In order to maintain the balance of the redox state within the cell,reactive oxygen species(ROS)and reactive sulfur species(RSS)react and transform with each other,and their levels also directly reflect the degree of oxidative stress and disease.Hypochlorous acid(HClO)and cysteine(Cys)usually co-exist in organisms,interacting with each other in many important physiological processes and synergistically maintaining the dynamic redox balance in the body.To understand the relevance and pathophysiological effects of these two signaling molecules in oxidative stress,unique fluorescence imaging tools are required.Herein,we designed and developed a dual-channel fluorescent probe HP,for the individual and continuous detection of HClO and Cys.This probe could simultaneously monitor the changes in the concentrations of HClO and Cys in cells,and was characterized by a fast response,high sensitivity and high selectivity,especially compared with glutathione(GSH)and homocysteine(Hcy),the probe had a good specificity for Cys.Importantly,probe HP successfully observed dynamic changes in HCl O-and Cys-mediated redox status in the oxygenglucose deprivation/reperfusion(OGD/R)model of HeLa cells and dynamically monitored fluctuations in endogenous HClO levels in lipopolysaccharides(LPS)-induced peritonitis mice.
基金supported by grants from the National Natural Science Foundation of China(32030083)。
文摘Advanced lipoxidation end products(ALEs)are formed by modifying proteins with lipid oxidation products.ALEs formed in the body have been linked to diabetes and hepatic disease.However,it is not known whether ALEs formed in heat-processed foods can induce metabolic diseases.Our results indicate that dietary ALEs induce lipid accumulation in the liver of mice at an early stage and continuous feeding of ALEs induces inflammation,oxidative stress and hepatic insulin resistance.The core reason for these adverse reactions is the damage to the intestinal barrier caused by ALEs.Due to the damage to the intestinal barrier,there is an increase in lipopolysaccharides(LPS)in the liver that induces hepatic lipid accumulation by modulating hepatic lipid metabolism.Furthermore,ALEs plays a major role in the regulation of metabolic diseases by directly or indirectly inhibiting AMP activated protein kinase(AMPK)/Sirtuin 1(SIRT1)signaling through LPS.
基金supported by National Key Research and Develop-ment Program of China(Grant No.2023YFB3812000)Jiangsu Provin-cial Key Research and Development Program(Grant No.BE2022069-2),National Natural Science Foundation of China(Grant No.52130207)+1 种基金National Basic Science Research Program of China(Grant No.JCKY2021203B032)the Unveiling and Hanging Project of Nantong(Grant No.JB2022001).
文摘Gradient-doped laser ceramics fabricated via 3D printing have great potential for high-power laser applications.However,it is challenging to produce such types of gain media because it is inconvenient to fabricate different component slurries prepared offline using traditional methods precisely.To address these issues,a facile approach for the additive manufacturing of high-power laser ceramics is proposed for gradient structure fabrication.First,a material-extrusion-based 3D printing device with a homemade active mixing module is developed to fabricate gradient-doped Yb:YAG(Y3 Al5 O12)laser ceramics using two slurries with different doping concentrations.Sub-sequently,the active mixing module is systematically investigated to obtain different Yb-doped concentrations of printing slurries with a uniform element distribution.By measuring the switching delay volume between dif-ferent components,a proper volume adjustment enables the Yb concentration distribution of the green bodies to be consistent with the designed profile in the 3D process.Finally,multi-component(0-5-10-5-0 at%Yb:YAG)green bodies are printed,and experimental tests are conducted to evaluate the performance of these gradient-doped laser ceramics.The results show that the gradient-doped ceramic obtained 82.1%in-line transmittance at 1100 nm(4.6 mm thickness,along with the doping concentration gradient)and the average Yb ions diffusion distance across the interface fitted in the 20-30𝜇m range.Furthermore,a 1030 nm laser output with an output power of 4.5 W with a slope efficiency of 41.3%is achieved when pumped with a 940 nm laser diode.This study provides useful insights for developing various gradient rare-earth-doped laser ceramics for high-power laser applications.
基金supported by funding from the National Key Research and Development Project(2020YFA0113500,China)Hunan Provincial Natural Science Foundation of China(2023JJ40341,2023JJ40352)+6 种基金National Natural Science Foundation of China(82473934,32100616,32100490,81922068,82304510,82304511)Chongqing Science and Technology Commission of China(cstc2021jcyj-jqX0006)Scientific Research Project of Hunan Provincial Health Commission(A202302077875,B202302078452,China)the projects of Army Medical University(2022XJS06,2023XQN20,2023XQN19,China)Chongqing Municipal Education Commission Foundation(KJZD-M202412802,China)the Natural Science Foundation of Changsha,Hunan Province(kq2208087,China)the special fund of the Hunan provincial key laboratory of pediatric orthopedics(No.2023TP1019,China)。
文摘The Janus kinase/signal transducers and activators of transcription(JAK-TAT)control natural killer(NK)cells development and cytotoxic functions,however,whether long non-coding RNAs(lncRNAs)are involved in this pathway remains unknown.We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and inducedpluripotent stem cells(iPSCs)-derived NK(iPSC-NK)cells,without reliance on its derived miR-155 and micropeptide P155.Mechanistically,miR155HG bound to miR-6756 and relieved its repression of JAK3 expression,thereby promoting the JAK-TAT pathway and enhancing NK cell proliferation and function.Further investigations disclosed that upon cytokine stimulation,STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription.Collectively,we identify a miR155HG-mediated positive feedback loop of the JAK-TAT signaling.Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer,especially iPSC-derived NK cells.
基金supported by the National Natural Science Foundation of China(21977064,22325703)。
文摘Diabetic wound healing remains a major challenge due to the excess hyperglycemia microenvironment,massively bacterial infections,macrophage dysfunction,and persistent inflammation.To comprehensively solve these problems,novel multifunctional materials are highly desirable.Herein,a versatile and intelligent hydrogel(Cu_(2)S@FePPOP_(TPM)@GO_(x)@Gel)is reported.Cu_(2)S@FePPOP_(TPM)@GO_(x)with hollow morphology and controllable size was rationally designed and fabricated by using Cu2S nanocubes as a template,followed by in situ growth of Fe PPOP_(TPM)and loading glucose oxidase(GOx),successively.When infection occurs,the Schiff base bonds in Cu_(2)S@FePPOP_(TPM)@GO_(x)@Gel can controllably release Cu_(2)S@FePPOP_(TPM)@GO_(x)based on its excellent dynamic p H-responsiveness,thereby synergically reducing blood glucose levels and killing bacteria achieved relying on the excellent catalytic activity of GOx towards glucose and its promoted peroxidelike activity of Fe PPOP_(TPM).Further experiments on diabetic wound model in vivo demonstrated that Cu_(2)S@FePPOP_(TPM)@GO_(x)@Gel promoted wound healing and skin regeneration,which was attributed to its antibacterial properties,alleviating inflammation,stimulating vascular regeneration,and encouraging M2 polarization of macrophages.This work provides a novel strategy for the construction of a microenvironment-responsive and antibiotics-free drug delivery platform to treat diabetic wounds,as well as broad prospects of nanomaterials in the clinical treatment of chronic wounds.
基金supported by Postdoctoral Research Foundation of China(Grant No.2022M721054)the Natural Science Foundation of Henan Province of China(Grant No.222300420213).
文摘An upwind weak Galerkin finite element scheme was devised and analyzed in this article for convection-dominated Oseen equations. The numerical algorithm was based on the weak Galerkin method enhanced by upwind stabilization. The resulting finite element scheme uses equal-order, say k, polynomial spaces on each element for the velocity and the pressure unknowns. With finite elements of order k≥1, the numerical solutions are proved to converge at the rate of O(h^(k+1/2)) in an energy-like norm for convection-dominated Oseen equations. Numerical results are presented to demonstrate the accuracy and effectiveness of the upwind weak Galerkin scheme.
基金supported by the National Natural Science Foundation of China(Nos.21877049,22177038,and 32171296)Guangdong Natural Science Foundation(Nos.2022A1515012235 and 2020B1515120043)+1 种基金Guangdong Pearl River Talent Program(No.2017GC010354)Innovation Team Project in Guangdong Colleges and Universities(Nos.2019KCXTD008 and 2019KTSCX012).
文摘Radiotherapy is one of the main therapeutic methods for cancers;however,nonselective killing of normal cells and tumor cells by X-ray inevitably results in toxicity and side effects.Developing low-toxicity and high-efficiency radiosensitizers to reduce the practical dose of X-ray is a promising approach to overcoming these side effects.Here,we report the use of carboxylatecontaining organic ligands to construct one-dimensional high-Z lanthanide chains for efficient response to X-ray.The onedimensional lanthanide chains are stacked through weak interactions to form coordination nanoframeworks in the presence of polyethylenimine(PEI).The morphology and activity of the synthesized nanoframeworks can be regulated through selenium atom engineering.This study presents a promising approach for effective radiotherapy through selenium-engineering stable lanthanide nanoframeworks with precise coordination structures as radiosensitizers to mitigate X-ray side effects.
基金financially supported by the National Natural Science Foundation of China(Grant No.81871431,82171905 and 81801828)the Tianjin Natural Science Foundation(Grant No.21JCQNJC01570 and 22JCYBJC01340)+2 种基金Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-001A)Tianjin Municipal Education Research Project(20140115)Fund for Distinguished Young Scholars of Tianjin Medical University General Hospital(22ZYYJQ03).
文摘Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain,leading to neurodegeneration in Alzheimer’s disease(AD).Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses,but is very challenging.Herein,an engineered macrophage-biomimetic versatile nanoantidote(OT-Lipo@M)is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression.Coating macrophage membranes can not only endow OT-Lipo@M with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain,but also efficiently reduce neurotoxin levels to prevent them from activating microglia.The loaded oxytocin(OT)can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4(TLR4)on microglia,inhibiting TLR4-mediated pro-inflammatory signalling cascade.Benefiting from this two-pronged immunosuppressive strategy,OT-Lipo@M exhibits outstanding therapeutic effects on ameliorating cognitive deficits,inhibiting neuronal apoptosis,and enhancing synaptic plasticity in AD mice,accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging.This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.
基金the NSF IR/D program,while working at the National Science FoundationThe research of Ye was supported in part by National Science Foundation Grant DMS-0612435
文摘We derived and analyzed a new numerical scheme for the Navier-Stokes equations by using H（div） conforming finite elements. A great deal of effort was given to an establishment of some Sobolev-type inequalities for piecewise smooth functions. In particular, the newly derived Sobolev inequalities were employed to provide a mathematical theory for the H（div） finite element scheme. For example, it was proved that the new finite element scheme has solutions which admit a certain boundedness in terms of the input data. A solution uniqueness was also possible when the input data satisfies a certain smallness condition. Optimal-order error estimates for the corresponding finite element solutions were established in various Sobolev norms. The finite element solutions from the new scheme feature a full satisfaction of the continuity equation which is highly demanded in scientific computing.
基金supported in part by National Science Foundation Grant DMS-1115097supported in part by National Science Foundation Grants DMS-1016579 and DMS-1318898.
文摘A weak Galerkin(WG)method is introduced and numerically tested for the Helmholtz equation.This method is flexible by using discontinuous piecewise polynomials and retains the mass conservation property.At the same time,the WG finite element formulation is symmetric and parameter free.Several test scenarios are designed for a numerical investigation on the accuracy,convergence,and robustness of the WG method in both inhomogeneous and homogeneous media over convex and non-convex domains.Challenging problems with high wave numbers are also examined.Our numerical experiments indicate that the weak Galerkin is a finite element technique that is easy to implement,and provides very accurate and robust numerical solutions for the Helmholtz problem with high wave numbers.
基金the National Natural Science Foundation of China(32202127)the Key Project of Jiangsu Province Modern Agriculture(BE2018382)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China.
文摘The objective of this study was to investigate the molecular regulatory mechanism of 1-methylcyclopropene(1-MCP)treatment on leaf yellowing of pak choi during storage at 20°C.In the present study,compared with the control and 10μL/L ethylene-treated pak choi,5.0μL/L 1-MCP fumigation alleviated the yellowing process of pak choi as proved by the maintenance of higher levels of colour,chlorophyll content,and appearance.1-MCP treatment decreased chlorophyll breakdown by downregulating the activity of chlorophyll-degrading enzymes(chlorophyll b reductase(CBR)and pheophytinase(PPH))and the expression of their related genes(BcNYC1 and BcPPH).The application of 1-MCP also inhibited the transcript abundance of ethylene biosynthesis and signal transduction genes(BcACO,BcEIN3,and BcERF)and reduced ethylene production,thus helping to maintain the green colour of pak choi;however,ethylene treatment exerted the opposite function.Meanwhile,three transcription factors(BcNAC055,BcMYB44,and BcOBF1)were successfully cloned.Experiments performed using yeast one-hybrid assay,dual-luciferase reporter system and in vivo bioluminescence imaging assay,confirmed that BcNAC055,BcMYB44,and BcOBF1 directly bound to the BcNYC1 promoter.1-MCP inhibited the expression levels of BcNAC055,BcMYB44,BcOBF1,and BcNYC1 during storage,while the application of ethylene activated their expression.In conclusion,1-MCP downregulated the expression of the key chlorophyll degradation gene BcNYC1 by inhibiting the transcript level of its three positive regulators(BcNAC055,BcMYB44,and BcOBF1)and lowered the activity of chlorophyll-degrading enzyme CBR,thereby helping mitigate chlorophyll breakdown to retard leaf yellowing in pak choi.The results of this work extend our understanding of 1-MCP-delayed yellowing in postharvest pak choi.
基金supported by the Key Program of the National Natural Science Foundation of China(No.81930090)the National Science Foundation for Distinguished Young Scholars of China(No.81725019)the National Natural Science Foundation of China(Nos.82273571,32171104,U22A20279,81874256,and 81872556),Chongqing Natural Science Foundation(2023NSCQ-JQX0076).
文摘Although DNA mutation drives stem cell aging,how mutation-accumulated stem cells obtain clonal advantage during aging remains poorly understood.Here,using a mouse model of irradiation-induced premature aging and middle-aged mice,we show that DNA mutation accumulation in hematopoietic stem cells(HSCs)during aging upregulates their surface expression of major histocompatibility complex class II(MHCII).MHCII upregulation increases the chance for recognition by bone marrow(BM)-resident regulatory T cells(Tregs),resulting in their clonal expansion and accumulation in the HSC niche.On the basis of the establishment of connexin 43(Cx43)-mediated gap junctions,BM Tregs transfer cyclic adenosine monophosphate(cAMP)to aged HSCs to diminish apoptotic priming and promote their survival via activation of protein kinase A(PKA)signaling.Importantly,targeting the HSC–Treg interaction or depleting Tregs effectively prevents the premature/physiological aging of HSCs.These findings show that aged HSCs use an active self-protective mechanism by entrapping local Tregs to construct a prosurvival niche and obtain a clonal advantage.
基金This work was supported by grants from the National Natural Science Foundation of China(No.81725019,81930090,81500087)the Scientific Research Project of PLA(AWS16J014).
文摘Hematopoietic system is one of the main target organs of irradiation injury.Exposure to radiation can cause acute myelosuppression and long-term hematopoietic injury due to the direct and indirect damage of hematopoietic stem cells(HSCs)that can self-renew and differentiate into all types of blood cells.So far,many factors in the modulation of HSC biology at steady status have been revealed,while how to orchestrate HSCs in the context of radiation has not been well established.Recently,an increasing number of studies focus on the underlying mechanisms involved in regulating HSC fate after radiation exposure by affecting DNA damage response(DDR),including DNA-damage repair,cell-cycle arrest,apoptosis and senescence,or bone marrow(BM)microenvironment.In this review,we summarize recent findings on intrinsic and extrinsic factors in the regulation of HSC fate after radiation exposure,which may further deepen our understanding of the radioprotection of HSCs.
文摘Polycyclic musks are widely used for cos- metics and other personal care and household cleaning products. The occurrence and removal of two representa- tive polycyclic musks, galaxolide （HHCB） and tonalide （AHTN） were investigated in three different processes of two sewage treatment plants （STPs） in Xi＇an, China. The samples were preconcentrated by solid phase extraction procedure and analyzed using a gas chromatography mass spectrometry （GC/MS） by a modified procedure. The HHCB was in the range of 82.8 to 182.5 ng.L1 in the influents and 22.6 to 103.9ng.L-1 in the effluents. The AHTN ranged from 11.0 to 19.3 ng. L-1 in the influents and 2.2 to 8.8 ng. I_~1 in the effluents. The removal efficiency of the two musks varied in the ranges of 43.1%-70.4% for HHCB and 54.2%-84.4% for AHTN. Concentrations of the two musks in aqueous phase of three processes slightly increased along the primary process, and significantly removed during the biologic treatment processes, revealing that the selected musks could be remarkably removed in varied activated sludge processes. Advanced processes of activated sludge did not show a significant superiority on selected musk removal compared to the conventional process. The selected musk removal mainly resulted from the adsorption function of activated sludge. There was no significant change of HHCB/AHTN ratios along the treatment flow, indicating that each sewage treatment structure had a similar removal efficiency for the two musks.
基金supported by National Natural Science Foundation of China (21877049,22177038,32171296)Guangdong Natural Science Foundation (2020B1515120043,2022A1515012235)+2 种基金the Major Program for Tackling Key Problems of Industrial Technology in Guangzhou (201902020013)Guangdong Pearl River Talent Program(2017GC010354)the Innovation Team Project in Guangdong Colleges and Universities (2019KCXTD008,2019KTSCX012)
文摘The search of highly efficient drugs for overcoming cancer drug resistance continues to be a challenge for scientists.Constructing a metal drug based in situ oxidation-state transition system to disturb the redox balance in cancer cells is a promising approach for overcoming cancer drug resistance.Inspired by natural redox-active copper enzyme centers,we developed a Cu(Ⅰ)-Cu(Ⅱ) in situ transition system in this work.Through atom engineering,we fine-tuned the thermodynamic stability of this system to investigate its anticancer activity.The results indicated that the synthetic Cu(Ⅰ)-Cu(Ⅱ) system could under-go in situ transition in vitro and in vivo,to disrupt the intracellular redox balance and trigger mitochondrial dysfunction and G2/M arrest,leading to apoptosis and overcoming cancer drug resistance.This study presents a feasible way to overcome cancer drug resistance by designing an in situ oxidation-state transition metal drug system.
基金Project supported in part by the National Natural Science Foundation of China(No.61173088)the Science & Technology Program of Xi’an,China(No.CX12485)the 111 Project(No.B08038)
文摘As the technology scales advancing into the nanometer region,the concept of yield has become an increasingly important design metric.To reduce the yield loss caused by local defects,layout optimization can play a critical role.In this paper,we propose a new open sensitivity-based model with consideration of the blank space around the net,and study the corresponding net optimization.The proposed new model not only has a high practicability in the selection of nets to be optimized but also solves the issue of the increase in short critical area brought during the open optimization,which means to reduce the open critical area with no new short critical area produced,and thereby this model can ensure the decrease of total critical area and finally achieves an integrative optimization.Compared with the models available,the experimental results show that our sensitivity model not only consumes less time with concise algorithm but also can deal with irregular layout,which is out of the scope of other models.At the end of this paper,the effectiveness of the new model is verified by the experiment on the randomly selected five metal layers from the synthesized OpenSparc circuit layout.
