BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contribut...BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.展开更多
Interference significantly impacts the performance of the Global Navigation Satellite Systems(GNSS),highlighting the need for advanced interference localization technology to bolster anti-interference and defense capa...Interference significantly impacts the performance of the Global Navigation Satellite Systems(GNSS),highlighting the need for advanced interference localization technology to bolster anti-interference and defense capabilities.The Uniform Circular Array(UCA)enables concurrent estimation of the Direction of Arrival(DOA)in both azimuth and elevation.Given the paramount importance of stability and real-time performance in interference localization,this work proposes an innovative approach to reduce the complexity and increase the robustness of the DOA estimation.The proposed method reduces computational complexity by selecting a reduced number of array elements to reconstruct a non-uniform sparse array from a UCA.To ensure DOA estimation accuracy,minimizing the Cramér-Rao Bound(CRB)is the objective,and the Spatial Correlation Coefficient(SCC)is incorporated as a constraint to mitigate side-lobe.The optimization model is a quadratic fractional model,which is solved by Semi-Definite Relaxation(SDR).When the array has perturbations,the mathematical expressions for CRB and SCC are re-derived to enhance the robustness of the reconstructed array.Simulation and hardware experiments validate the effectiveness of the proposed method in estimating interference DOA,showing high robustness and reductions in hardware and computational costs associated with DOA estimation.展开更多
Lattice distortion of materials has a profound impact on their electronic and magnetic properties,which can generate local magnetic states in intrinsically non-magnetic systems.Here we report on the realization of a o...Lattice distortion of materials has a profound impact on their electronic and magnetic properties,which can generate local magnetic states in intrinsically non-magnetic systems.Here we report on the realization of a one-dimensional(1D)magnetic stripe in monolayer H-NbSe_(2)sustained by strain along the terraces of the graphene/SiC substrates.The strength of this tensile strain is widely tunable by the height-to-width ratio of the terraces.Increasing the tensile strength leads to the shifts and splitting of the Nb 4d bands crossing the Fermi energy,generating spin polarization in a 1D magnetic stripe along the terrace.Simultaneously,the charge-densitywave signature of strained H-NbSe_(2)is significantly suppressed.Such a magnetic stripe can be locally quenched by an individual Se-atom defect via the defect-induced Jahn-Teller distortion and charge density redistribution.These findings provide a different route to achieving and manipulating 1D magnetism in otherwise non-magnetic systems,offering a new way for spintronic devices.展开更多
Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine...Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine preparation used to treat RA.ZF may cause liver injury.In this study,we aimed to develop a prediction model for abnormal liver function caused by ZF.Methods This retrospective study collected data from multiple centers from January 2018 to April 2023.Abnormal liver function was set as the target variable according to the alanine transaminase(ALT)level.Features were screened through univariate analysis and sequential forward selection for modeling.Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data.Results This study included 1,913 eligible patients.The LightGBM model exhibited the best performance(accuracy=0.96)out of the 10 learning models.The predictive metrics of the LightGBM model were as follows:precision=0.99,recall rate=0.97,F1_score=0.98,area under the curve(AUC)=0.98,sensitivity=0.97 and specificity=0.85 for predicting ALT<40 U/L;precision=0.60,recall rate=0.83,F1_score=0.70,AUC=0.98,sensitivity=0.83 and specificity=0.97 for predicting 40≤ALT<80 U/L;and precision=0.83,recall rate=0.63,F1_score=0.71,AUC=0.97,sensitivity=0.63 and specificity=1.00 for predicting ALT≥80 U/L.ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels,the combination of TNF-αinhibitors,JAK inhibitors,methotrexate+nonsteroidal anti-inflammatory drugs,leflunomide,smoking,older age,and females in middle-age(45-65 years old).Conclusion This study developed a model for predicting ZF-induced abnormal liver function,which may help improve the safety of integrated administration of ZF and Western medicine.展开更多
Cu(I)based CO adsorbents are prone to oxidation and deactivation owing to the sensitivity of Cu^(+) ions to oxygen and moisture in the humid air.In this study,in order to improve its antioxidant performance,hydrophobi...Cu(I)based CO adsorbents are prone to oxidation and deactivation owing to the sensitivity of Cu^(+) ions to oxygen and moisture in the humid air.In this study,in order to improve its antioxidant performance,hydrophobic Cu(I)based adsorbents were fabricated using polytetrafluoroethylene(PTFE)for the hydrophobic modification,effectively avoiding the contact of CuCl active species with moisture,thereby inhibiting the oxidation of the Cu(I)based adsorbents.The successful introduction of PTFE into the activated carbon(AC)carrier significantly improves the hydrophobicity of the adsorbent.The optimal adsorbent CuCl(6)@AC-PTFE(0.10%)with the CuCl loading of 6 mmol·g^(-1)and the PTFE mass concentration of 0.10%exhibits an excellent CO adsorption capacity of 3.61 mmol·g^(-1)(303 K,500 kPa)as well as high CO/CO_(2)and CO/N_(2)adsorption selectivities of 29 and 203(303 K,100 kPa).Particularly,compared with the unmodified adsorbents,the antioxidant performance of modified adsorbent CuCl(6)@AC-PTFE(0.10%)is significantly improved,holding 86%of CO adsorption performance of fresh one after 24 h of exposure to humid air with a relative humidity of 70%,making the fabricated composite a promising adsorbent for CO separation.展开更多
This paper explores the reform of ideological and political education in the course“Graphic Creative Design”.Addressing issues such as insufficient integration of ideological and political education into traditional...This paper explores the reform of ideological and political education in the course“Graphic Creative Design”.Addressing issues such as insufficient integration of ideological and political education into traditional courses and rigid teaching models,this paper identifies the advantages of ideological and political education based on the characteristics of the course and proposes reform pathways and methods.By incorporating ideological and political education elements such as Chinese traditional culture,values,red culture,and professional ethics into course instruction;innovating teaching methods to establish a blended learning model;using“case studies+projects”to drive ideological and political education integration;leveraging“competition-driven learning”to strengthen professional ethics cultivation;and leveraging technological and conceptual innovations to expand the dimensions of ideological and political education.In teaching practice,modularized instruction is adopted to deeply integrate ideological and political education elements with the curriculum.Cases from outstanding designers are introduced,and real projects and competition topics are used to drive project-based training.Additionally,AIGC technology is utilized to enrich the carriers of ideological and political education,achieving the synergistic development of“professional skill enhancement”and“value concept shaping”.展开更多
BACKGROUND Acute pulmonary thromboembolism is a complication of venous thrombosis.Extracorporeal membrane oxygenation(ECMO),an effective rescue measure for rapid hemodynamic recovery,can be used in patients for whom t...BACKGROUND Acute pulmonary thromboembolism is a complication of venous thrombosis.Extracorporeal membrane oxygenation(ECMO),an effective rescue measure for rapid hemodynamic recovery,can be used in patients for whom thrombolysis therapy has failed.CASE SUMMARY This case report describes an extreme rescue process for a patient with a preset inferior vena cava(IVC)filter in a relatively economically underdeveloped area with an insufficient supply of consumables.In an emergency,veno-arterial ECMO was successfully initiated by intubation through the IVC filter to the right atrial opening without displacement of the filter during the entire process.CONCLUSION This study demonstrates that in resource-limited settings,femoral vein cannulation for veno-arterial ECMO is a feasible and safe option for patients with preimplanted IVC filters.展开更多
Sertoli and granulosa cells,the initial differentiated somatic cells in bipotential gonads,play crucial roles in directing male and female gonad development,respectively.The transcription factor Foxo1 is involved in d...Sertoli and granulosa cells,the initial differentiated somatic cells in bipotential gonads,play crucial roles in directing male and female gonad development,respectively.The transcription factor Foxo1 is involved in diverse cellular processes,and its expression in gonadal somatic cells is sex-dependent.While Foxo1 is abundantly expressed in ovarian granulosa cells,it is notably absent in testicular Sertoli cells.Nevertheless,its function in gonadal somatic cell differentiation remains elusive.In this study,we find that ectopic expression of Foxo1 in Sertoli cells leads to defects in testes development.Further study uncovers that the ectopic expression of Foxo1 induces the abundant expression of Foxl2 in Sertoli cells,along with the upregulation of other female-specific genes.In contrast,the expression of male-specific genes is reduced.Mechanistic studies indicate that Foxo1 directly binds to the promoter region of Foxl2,inducing its expression.Our findings highlight that Foxo1 serves as a key regulator for the lineage maintenance of ovarian granulosa cells.This study contributes valuable insights into understanding the regulatory mechanisms governing the lineage maintenance of gonadal somatic cells.展开更多
Transition metal(oxy)hydroxides are potential oxygen evolution reaction(OER)electrocatalysts;however,simultaneously modulating multiple factors to enhance their performance is a grand challenge.Here,we report an incor...Transition metal(oxy)hydroxides are potential oxygen evolution reaction(OER)electrocatalysts;however,simultaneously modulating multiple factors to enhance their performance is a grand challenge.Here,we report an incorporating heteroatom strategy via one-step hydrothermal approach to adjust more than one factor of Mn-doped NiFe(oxy)hydroxide(Mn-NiFeOOH/LDH)heterojunction.Mn doping regulates heterojunction morphology(reducing nanoparticles and becoming thinner and denser nanosheets),Ni/Fe ratio and valence states(Ni^(2+),Ni^(3+),and Ni^(3+Δ))of Ni ions.The former could effectively increase surface active sites,and the latter two reduce the content of Fe in the Mnx-NiFeOOH/LDH heterojunction,en-abling more Ni^(2+)convert to Ni^(3+/3+Δ)that have higher intrinsic OER activity.As a result,the first-rank Mn-NiFeOOH/LDH with ultra-low overpotential of 185 mV@20 mA cm^(-2) and 296 mV@500 mA cm^(-2),and the improved OER performance are outdo to those of commercial RuO_(2) catalyst for OER.Moreover,the Mn-NiFeOOH/LDH affords the earliest initial potential(1.392 V vs.RHE),corresponds to a recorded low overpotential(162 mV).Based on the density functional theory(DFT),Mn dopants can alter intermedi-ate adsorption energy and effectively decrease∗OOH’s energy barrier.This research exhibits a feasible strategy to design low cost electrocatalysts and provide new possibilities for future industrialization.展开更多
Background : Traditional DNA microinjection methods used in mammals are difficult to apply to avian species due to their unique reproductive characteristics. Genetic manipulation in chickens, particularly involving im...Background : Traditional DNA microinjection methods used in mammals are difficult to apply to avian species due to their unique reproductive characteristics. Genetic manipulation in chickens, particularly involving immature follicles within living ovaries, has not been extensively explored. This study seeks to establish an efficient method for generating transgenic chickens through ovarian injection, potentially bypassing the challenges associated with primordial germ cell (PGC) manipulation and fertilized egg microinjection. Methods : Hens were anesthetized and underwent a surgical procedure to access the ovary for DNA injection into immature follicles. The study used liposomes to deliver GFP- expressing plasmids at various dosages. After injection, hens recovered, and their eggs were fertilized through artificial insemination. Results : Transgenic chickens were successfully generated in one generation without needing G0 founders. The injection of 20 μg plasmid yielded the highest transgenic efficiency at 12.1%. GFP- positive embryos were confirmed through microscopy, and successful transgene expression was validated at the tissue level using immunostaining. TERT and GFP elements introduced in the G1 generation resulted in 4.1% positive transgene rates, as confirmed by PCR and Southern blotting. Conclusion : This ovarian injection method offers a promising alternative for avian genetic manipulation, bypassing complex PGC procedures and enabling direct generation of G1 transgenic chickens. This technique simplifies the transgenic process for chickens and has the potential to be adapted for other avian species, especially those without established PGCs culture systems.展开更多
Battery health evaluation and management are vital for the long-term reliability and optimal performance of lithium-ion batteries in electric vehicles.Electrochemical impedance spectroscopy(EIS)offers valuable insight...Battery health evaluation and management are vital for the long-term reliability and optimal performance of lithium-ion batteries in electric vehicles.Electrochemical impedance spectroscopy(EIS)offers valuable insights into battery degradation analysis and modeling.However,previous studies have not adequately addressed the impedance uncertainties,particularly during battery operating conditions,which can substantially impact the robustness and accuracy of state of health(SOH)estimation.Motivated by this,this paper proposes a comprehensive feature optimization scheme that integrates impedance validity assessment with correlation analysis.By utilizing metrics such as impedance residuals and correlation coefficients,the proposed method effectively filters out invalid and insignificant impedance data,thereby enhancing the reliability of the input features.Subsequently,the extreme gradient boosting(XGBoost)modeling framework is constructed for estimating the battery degradation trajectories.The XGBoost model incorporates a diverse range of hyperparameters,optimized by a genetic algorithm to improve its adaptability and generalization performance.Experimental validation confirms the effectiveness of the proposed feature optimization scheme,demonstrating the superior estimation performance of the proposed method in comparison with four baseline techniques.展开更多
The quantum alternating operator ansatz algorithm(QAOA+)is widely used for constrained combinatorial optimization problems(CCOPs)due to its ability to construct feasible solution spaces.In this paper,we propose a prog...The quantum alternating operator ansatz algorithm(QAOA+)is widely used for constrained combinatorial optimization problems(CCOPs)due to its ability to construct feasible solution spaces.In this paper,we propose a progressive quantum algorithm(PQA)to reduce qubit requirements for QAOA+in solving the maximum independent set(MIS)problem.PQA iteratively constructs a subgraph likely to include the MIS solution of the original graph and solves the problem on it to approximate the global solution.Specifically,PQA starts with a small-scale subgraph and progressively expands its graph size utilizing heuristic expansion strategies.After each expansion,PQA solves the MIS problem on the newly generated subgraph using QAOA+.In each run,PQA repeats the expansion and solving process until a predefined stopping condition is reached.Simulation results show that PQA achieves an approximation ratio of 0.95 using only 5.57%(2.17%)of the qubits and 17.59%(6.43%)of the runtime compared with directly solving the original problem with QAOA+on Erd?s-Rényi(3-regular)graphs,highlighting the efficiency and scalability of PQA.展开更多
Objective:To observe and study the actual effects of percutaneous pedicle screw minimally invasive surgery in the treatment of spinal fractures and its impact on spinal function.Methods:This study included 48 patients...Objective:To observe and study the actual effects of percutaneous pedicle screw minimally invasive surgery in the treatment of spinal fractures and its impact on spinal function.Methods:This study included 48 patients with spinal fractures admitted between May 2023 and May 2024.The patients were divided into a control group and an experimental group based on treatment differences,with 24 patients in each group.The control group underwent open internal fixation surgery,while the experimental group received percutaneous pedicle screw minimally invasive surgery.Clinical index improvements,cervical dysfunction index,Japanese Orthopaedic Association scores,and pain level improvements were compared between the two groups.Results:The intraoperative blood loss,incision length,operation time,and hospitalization duration in the experimental group were(88.63±18.85),(6.32±1.05),(73.42±4.05),and(12.58±2.56),respectively,compared to(279.95±17.32),(12.89±1.36),(89.93±4.79),and(22.41±2.87)in the control group.Significant differences were observed between the groups,with the experimental group showing superior improvements across all metrics(P<0.05).Conclusion:Percutaneous pedicle screw minimally invasive surgery shows more significant effects in treating spinal fractures,particularly in improving cervical and lumbar spine function,enhancing treatment efficacy and safety,reducing pain levels,and shortening recovery time.Clinical application and promotion are recommended.展开更多
Objective:To evaluate and analyze the actual efficacy of percutaneous vertebroplasty in the treatment of old unstable osteoporotic spinal fractures.Methods:From March 2023 to March 2024,46 patients with old unstable o...Objective:To evaluate and analyze the actual efficacy of percutaneous vertebroplasty in the treatment of old unstable osteoporotic spinal fractures.Methods:From March 2023 to March 2024,46 patients with old unstable osteoporotic spinal fractures in our hospital were included in this study.They were divided into the conventional group and the observation group based on treatment differences,with 23 patients in each group.The conventional group received conservative drug therapy,while the observation group underwent percutaneous vertebroplasty.The following indicators were compared and analyzed between the two groups:clinical treatment effect and improvement in physical function indicators.Results:The treatment efficiency of the observation group was 95.65%(22/23),while that of the conventional group was 69.57%(16/23).There was a significant difference between the groups,and the treatment effect of the observation group was significantly better(P<0.05).After treatment,the scores of physical status,daily living ability,functional independence,and life obstacles in the observation group were(89.33±4.08),(88.72±4.08),(90.41±2.89),(72.35±3.22),respectively,while those in the conventional group were(68.54±4.21),(67.42±4.11),(73.48±2.75),(72.35±3.22).There was a significant difference between the groups,and the improvement in physical function indicators in the observation group was more pronounced(P<0.05).Conclusion:For patients with old unstable osteoporotic spinal fractures,the basic value of percutaneous vertebroplasty is significant.It can not only improve clinical efficacy and safety but also promote the gradual recovery of patients'physical function indicators.It is recommended for clinical reference and practical application.展开更多
Lithium-ion batteries have extensive usage in various energy storage needs,owing to their notable benefits of high energy density and long lifespan.The monitoring of battery states and failure identification are indis...Lithium-ion batteries have extensive usage in various energy storage needs,owing to their notable benefits of high energy density and long lifespan.The monitoring of battery states and failure identification are indispensable for guaranteeing the secure and optimal functionality of the batteries.The impedance spectrum has garnered growing interest due to its ability to provide a valuable understanding of material characteristics and electrochemical processes.To inspire further progress in the investigation and application of the battery impedance spectrum,this paper provides a comprehensive review of the determination and utilization of the impedance spectrum.The sources of impedance inaccuracies are systematically analyzed in terms of frequency response characteristics.The applicability of utilizing diverse impedance features for the diagnosis and prognosis of batteries is further elaborated.Finally,challenges and prospects for future research are discussed.展开更多
Background Rosemary extract(RE)has been reported to exert antioxidant property.However,the application of RE in late-phase laying hens on egg quality,intestinal barrier and microbiota,and oviductal function has not be...Background Rosemary extract(RE)has been reported to exert antioxidant property.However,the application of RE in late-phase laying hens on egg quality,intestinal barrier and microbiota,and oviductal function has not been systematically studied.This study was investigated to detect the potential effects of RE on performance,egg quality,serum parameters,intestinal heath,cecal microbiota and metabolism,and oviductal gene expressions in late-phase laying hens.A total of 21065-week-old“Jing Tint 6”laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet(CON)or basal diet supplemented with chlortetracycline at 50 mg/kg(CTC)or RE at 50 mg/kg(RE50),100 mg/kg(RE100),and 200 mg/kg(RE200).Results Our results showed that RE200 improved(P<0.05)Haugh unit and n-6/n-3 of egg yolk,serum superoxide dismutase(SOD)compared with CON.No significant differences were observed for Haugh unit and n-6/n-3 of egg yolk among CTC,RE50,RE100 and RE200 groups.Compared with CTC and RE50 groups,RE200 increased serum SOD activity on d 28 and 56.Compared with CON,RE supplementation decreased(P<0.05)total cholesterol(TC)level.CTC,RE100 and RE200 decreased(P<0.05)serum interleukin-6(IL-6)content compared with CON.CTC and RE200 increased jejunal m RNA expression of ZO-1 and Occludin compared with CON.The biomarkers of cecal microbiota and metabolite induced by RE 200,including Firmicutes,Eisenbergiella,Paraprevotella,Papillibacter,and butyrate,were closely associated with Haugh unit,n-6/n-3,SOD,IL-6,and TC.PICRUSt2 analysis indicated that RE altered carbohydrate and amino acid metabolism of cecal microbiota and increased butyrate synthesizing enzymes,including 3-oxoacid Co A-transferase and butyrate-acetoacetate Co A-transferase.Moreover,transcriptomic analysis revealed that RE200 improved gene expressions and functional pathways related to immunity and albumen formation in the oviductal magnum.Conclusions Dietary supplementation with 200 mg/kg RE could increase egg quality of late-phase laying hens via modulating intestinal barrier,cecal microbiota and metabolism,and oviductal function.Overall,RE could be used as a promising feed additive to improve egg quality of laying hens at late stage of production.展开更多
As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative str...As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.展开更多
MicroRNAs(miRNAs)are versatile regulators of gene expression at both the transcription and posttranscription levels.The microRNA miR396 plays vital roles in growth,development,and resistance to abiotic stresses in man...MicroRNAs(miRNAs)are versatile regulators of gene expression at both the transcription and posttranscription levels.The microRNA miR396 plays vital roles in growth,development,and resistance to abiotic stresses in many plant species.However,the roles and functions of miR396 in soybeans are not well understood.Here,we report that Gm-miR396a influences soybean development and salinity tolerance.We found that soybean miR396a was responsive to salt stress.Gm-miR396a gene-edited lines(miR396a-GEs),created using CRISPR/Cas9,exhibited more branches,higher grain yields,and greater salinity tolerance than control plants.The transcripts in lines with altered abundance of miR396a-GE were significantly enriched for biological processes related to hormone regulation.Overexpression of the Gm-miR396a precursor(pre-miR396a-OE)resulted in developmental deficiencies including dwarfness,abnormal inflorescences and flowers,smaller and fewer seeds,and small leaves with larger and more numerous stomata.Transcriptome analysis indicated photosynthesis-related genes were downregulated in pre-miR396a-OE plants.These results contribute valuable insights into the function of GmmiR396a in soybeans and hold promise for enhancing soybean yield and salinity tolerance through germplasm innovation.展开更多
Osteonecrosis of the femoral head(ONFH)is a common complication of glucocorticoid(GC)therapy.Recent advances demonstrate that sympathetic nerves regulate bone homeostasis,and GCs lower the sympathetic tone.Here,we sho...Osteonecrosis of the femoral head(ONFH)is a common complication of glucocorticoid(GC)therapy.Recent advances demonstrate that sympathetic nerves regulate bone homeostasis,and GCs lower the sympathetic tone.Here,we show that the dramatically decreased sympathetic tone is closely associated with the pathogenesis of GC-induced ONFH.GCs activate the glucocorticoid receptor(GR)but hinder the activation of the mineralocorticoid receptor(MR)on neurons in the hypothalamic paraventricular nucleus(PVN).This disrupts the balance of corticosteroid receptors(GR/MR)and subsequently reduces the sympathetic outflow in the PVN.Vascular endothelial cells rapidly react to inhibition of sympathetic tone by provoking endothelial apoptosis in adult male mice treated with methylprednisolone(MPS)daily for 3 days,and we find substantially reduced H-type vessels in the femoral heads of MPS-treated ONFH mice.Importantly,treatment with a GR inhibitor(RU486)in the PVN promotes the activation of MR and rebalances the ratio of GR and MR,thus effectively boosting sympathetic outflow,as shown by an increase in tyrosine hydroxylase expression in both the PVN and the sympathetic postganglionic neurons and an increase in norepinephrine levels in both the serum and bone marrow of the femoral head of MPS-treated mice.Rebalancing the corticosteroid receptors mitigates GC-induced endothelial impairment and ONFH and promotes angiogenesis coupled with osteogenesis in the femoral head,while these effects are abolished by chemical sympathectomy with 6-OHDA or adrenergic receptor-β2(Adrb2)knockout.Furthermore,activating Adrb2 signaling in vivo is sufficient to rescue the GC-induced ONFH phenotype.Mechanistically,norepinephrine increases the expression of the key glycolytic gene 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)via Adrb2-cyclic AMP response element-binding protein(CREB)signaling.Endothelial-specific overexpression of PFKFB3 attenuates endothelial impairment and prevents severe osteonecrosis in MPS-treated Adrb2 knockout mice.Thus,GC inhibits sympathetic tone via the hypothalamic descending pathway,which,in turn,acts as a mediator of GC-induced ONFH.展开更多
文摘BACKGROUND Tacrolimus(FK506)is a key calcineurin inhibitor used to prevent organ transplant rejection and is effective in improving graft survival.However,it is linked to hyperglycemia and insulin resistance,contributing to new-onset diabetes after transplantation and negatively affecting islet function.AIM To study the effects of tacrolimus on the insulin signaling pathway of hepatocytes.METHODS HL7702 cells were treated with different concentrations of tacrolimus(0.1 mg/L,1 mg/L,5 mg/L)for 24 hours.The proteins involved in insulin signaling were detected by Western blotting.RESULTS Compared with the control group,phosphorylation of insulin receptor substrate(IRS)1 at Ser 307 and Ser 323 were increased significantly when the tacrolimus concentration reached 1 and 5 mg/L.Phosphorylation of IRS1 at Ser 1101 was also increased,although not significantly.However,phosphorylation of Ribosomal protein S6 kinase beta-1 at Thr 389 was decreased significantly.The levels of phosphorylated glycogen synthase kinase 3αSer 21 and Ser 9 were increased.Surprisingly,phosphorylation of glycogen synthase at Ser 641 was increased.There was no significant change in the activity of glycogen phosphorylase.CONCLUSION Tacrolimus has no direct effect on hepatic glucose metabolism,but inhibits IRS1-mediated insulin signaling.This may be one of the underlying mechanisms by which tacrolimus induces insulin resistance.
基金the financial support from the National Key Research and Development Program of China(No.2023YFB3907001)the National Natural Science Foundation of China(Nos.U2233217,62371029)the UK Engineering and Physical Sciences Research Council(EPSRC),China(Nos.EP/M026981/1,EP/T021063/1 and EP/T024917/)。
文摘Interference significantly impacts the performance of the Global Navigation Satellite Systems(GNSS),highlighting the need for advanced interference localization technology to bolster anti-interference and defense capabilities.The Uniform Circular Array(UCA)enables concurrent estimation of the Direction of Arrival(DOA)in both azimuth and elevation.Given the paramount importance of stability and real-time performance in interference localization,this work proposes an innovative approach to reduce the complexity and increase the robustness of the DOA estimation.The proposed method reduces computational complexity by selecting a reduced number of array elements to reconstruct a non-uniform sparse array from a UCA.To ensure DOA estimation accuracy,minimizing the Cramér-Rao Bound(CRB)is the objective,and the Spatial Correlation Coefficient(SCC)is incorporated as a constraint to mitigate side-lobe.The optimization model is a quadratic fractional model,which is solved by Semi-Definite Relaxation(SDR).When the array has perturbations,the mathematical expressions for CRB and SCC are re-derived to enhance the robustness of the reconstructed array.Simulation and hardware experiments validate the effectiveness of the proposed method in estimating interference DOA,showing high robustness and reductions in hardware and computational costs associated with DOA estimation.
基金supported by the National Key R&D Program of China(Grant Nos.2022YFA1402602,2022YFA1402502,2021YFA1400103,2020YFA0308802,and 2024YFA1611300)the National Natural Science Foundation of China(Grant Nos.92163206,12274026,12321004,12304205,11934003,12393831,and U2230402)+1 种基金Beijing Association for Science and Technology Youth Talent Lift Program,MCIN/AEI/10.13039/501100011033(Grant No.PID2022-140845OB-C66)FEDER Una manera de hacer Europa。
文摘Lattice distortion of materials has a profound impact on their electronic and magnetic properties,which can generate local magnetic states in intrinsically non-magnetic systems.Here we report on the realization of a one-dimensional(1D)magnetic stripe in monolayer H-NbSe_(2)sustained by strain along the terraces of the graphene/SiC substrates.The strength of this tensile strain is widely tunable by the height-to-width ratio of the terraces.Increasing the tensile strength leads to the shifts and splitting of the Nb 4d bands crossing the Fermi energy,generating spin polarization in a 1D magnetic stripe along the terrace.Simultaneously,the charge-densitywave signature of strained H-NbSe_(2)is significantly suppressed.Such a magnetic stripe can be locally quenched by an individual Se-atom defect via the defect-induced Jahn-Teller distortion and charge density redistribution.These findings provide a different route to achieving and manipulating 1D magnetism in otherwise non-magnetic systems,offering a new way for spintronic devices.
基金supported by the Budgeted Fund of Shanghai University of Traditional Chinese Medicine(Natural Science)(No.2021LK037)the Open Project of Qinghai Province Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation(No.2021-ZY-03).
文摘Objective Rheumatoid arthritis(RA)is a systemic autoimmune disease that affects the small joints of the whole body and degrades the patients’quality of life.Zhengqing Fengtongning(ZF)is a traditional Chinese medicine preparation used to treat RA.ZF may cause liver injury.In this study,we aimed to develop a prediction model for abnormal liver function caused by ZF.Methods This retrospective study collected data from multiple centers from January 2018 to April 2023.Abnormal liver function was set as the target variable according to the alanine transaminase(ALT)level.Features were screened through univariate analysis and sequential forward selection for modeling.Ten machine learning and deep learning models were compared to find the model that most effectively predicted liver function from the available data.Results This study included 1,913 eligible patients.The LightGBM model exhibited the best performance(accuracy=0.96)out of the 10 learning models.The predictive metrics of the LightGBM model were as follows:precision=0.99,recall rate=0.97,F1_score=0.98,area under the curve(AUC)=0.98,sensitivity=0.97 and specificity=0.85 for predicting ALT<40 U/L;precision=0.60,recall rate=0.83,F1_score=0.70,AUC=0.98,sensitivity=0.83 and specificity=0.97 for predicting 40≤ALT<80 U/L;and precision=0.83,recall rate=0.63,F1_score=0.71,AUC=0.97,sensitivity=0.63 and specificity=1.00 for predicting ALT≥80 U/L.ZF-induced abnormal liver function was found to be associated with high total cholesterol and triglyceride levels,the combination of TNF-αinhibitors,JAK inhibitors,methotrexate+nonsteroidal anti-inflammatory drugs,leflunomide,smoking,older age,and females in middle-age(45-65 years old).Conclusion This study developed a model for predicting ZF-induced abnormal liver function,which may help improve the safety of integrated administration of ZF and Western medicine.
基金supported by the Natural Science Foundation of Shandong Province(ZR2021MB135)the Major Scientific and Technological Innovation Project of Shandong Province(2021ZDSYS13).
文摘Cu(I)based CO adsorbents are prone to oxidation and deactivation owing to the sensitivity of Cu^(+) ions to oxygen and moisture in the humid air.In this study,in order to improve its antioxidant performance,hydrophobic Cu(I)based adsorbents were fabricated using polytetrafluoroethylene(PTFE)for the hydrophobic modification,effectively avoiding the contact of CuCl active species with moisture,thereby inhibiting the oxidation of the Cu(I)based adsorbents.The successful introduction of PTFE into the activated carbon(AC)carrier significantly improves the hydrophobicity of the adsorbent.The optimal adsorbent CuCl(6)@AC-PTFE(0.10%)with the CuCl loading of 6 mmol·g^(-1)and the PTFE mass concentration of 0.10%exhibits an excellent CO adsorption capacity of 3.61 mmol·g^(-1)(303 K,500 kPa)as well as high CO/CO_(2)and CO/N_(2)adsorption selectivities of 29 and 203(303 K,100 kPa).Particularly,compared with the unmodified adsorbents,the antioxidant performance of modified adsorbent CuCl(6)@AC-PTFE(0.10%)is significantly improved,holding 86%of CO adsorption performance of fresh one after 24 h of exposure to humid air with a relative humidity of 70%,making the fabricated composite a promising adsorbent for CO separation.
基金Undergraduate Teaching Research and Reform Project,University of Shanghai for Science and Technology,Exploration of Ideological and Political Education Reform in the“Graphic Creative Design”Course(Project No.:10-23-309-603)。
文摘This paper explores the reform of ideological and political education in the course“Graphic Creative Design”.Addressing issues such as insufficient integration of ideological and political education into traditional courses and rigid teaching models,this paper identifies the advantages of ideological and political education based on the characteristics of the course and proposes reform pathways and methods.By incorporating ideological and political education elements such as Chinese traditional culture,values,red culture,and professional ethics into course instruction;innovating teaching methods to establish a blended learning model;using“case studies+projects”to drive ideological and political education integration;leveraging“competition-driven learning”to strengthen professional ethics cultivation;and leveraging technological and conceptual innovations to expand the dimensions of ideological and political education.In teaching practice,modularized instruction is adopted to deeply integrate ideological and political education elements with the curriculum.Cases from outstanding designers are introduced,and real projects and competition topics are used to drive project-based training.Additionally,AIGC technology is utilized to enrich the carriers of ideological and political education,achieving the synergistic development of“professional skill enhancement”and“value concept shaping”.
文摘BACKGROUND Acute pulmonary thromboembolism is a complication of venous thrombosis.Extracorporeal membrane oxygenation(ECMO),an effective rescue measure for rapid hemodynamic recovery,can be used in patients for whom thrombolysis therapy has failed.CASE SUMMARY This case report describes an extreme rescue process for a patient with a preset inferior vena cava(IVC)filter in a relatively economically underdeveloped area with an insufficient supply of consumables.In an emergency,veno-arterial ECMO was successfully initiated by intubation through the IVC filter to the right atrial opening without displacement of the filter during the entire process.CONCLUSION This study demonstrates that in resource-limited settings,femoral vein cannulation for veno-arterial ECMO is a feasible and safe option for patients with preimplanted IVC filters.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0820000)the National Natural Science Foundation of China(82421003,32270902,32170855)+1 种基金the Faculty Resources Project of the College of Life Sciences,Inner Mongolia University(2022-104)Initiative Scientific Research Program,Institute of Zoology,Chinese Academy of Sciences(20231OZ0102).
文摘Sertoli and granulosa cells,the initial differentiated somatic cells in bipotential gonads,play crucial roles in directing male and female gonad development,respectively.The transcription factor Foxo1 is involved in diverse cellular processes,and its expression in gonadal somatic cells is sex-dependent.While Foxo1 is abundantly expressed in ovarian granulosa cells,it is notably absent in testicular Sertoli cells.Nevertheless,its function in gonadal somatic cell differentiation remains elusive.In this study,we find that ectopic expression of Foxo1 in Sertoli cells leads to defects in testes development.Further study uncovers that the ectopic expression of Foxo1 induces the abundant expression of Foxl2 in Sertoli cells,along with the upregulation of other female-specific genes.In contrast,the expression of male-specific genes is reduced.Mechanistic studies indicate that Foxo1 directly binds to the promoter region of Foxl2,inducing its expression.Our findings highlight that Foxo1 serves as a key regulator for the lineage maintenance of ovarian granulosa cells.This study contributes valuable insights into understanding the regulatory mechanisms governing the lineage maintenance of gonadal somatic cells.
基金funding support by the Changsha Natural Science Foundation(grant no.kq2208023)National Natural Scientific Foundation of China(grant no.12074113).
文摘Transition metal(oxy)hydroxides are potential oxygen evolution reaction(OER)electrocatalysts;however,simultaneously modulating multiple factors to enhance their performance is a grand challenge.Here,we report an incorporating heteroatom strategy via one-step hydrothermal approach to adjust more than one factor of Mn-doped NiFe(oxy)hydroxide(Mn-NiFeOOH/LDH)heterojunction.Mn doping regulates heterojunction morphology(reducing nanoparticles and becoming thinner and denser nanosheets),Ni/Fe ratio and valence states(Ni^(2+),Ni^(3+),and Ni^(3+Δ))of Ni ions.The former could effectively increase surface active sites,and the latter two reduce the content of Fe in the Mnx-NiFeOOH/LDH heterojunction,en-abling more Ni^(2+)convert to Ni^(3+/3+Δ)that have higher intrinsic OER activity.As a result,the first-rank Mn-NiFeOOH/LDH with ultra-low overpotential of 185 mV@20 mA cm^(-2) and 296 mV@500 mA cm^(-2),and the improved OER performance are outdo to those of commercial RuO_(2) catalyst for OER.Moreover,the Mn-NiFeOOH/LDH affords the earliest initial potential(1.392 V vs.RHE),corresponds to a recorded low overpotential(162 mV).Based on the density functional theory(DFT),Mn dopants can alter intermedi-ate adsorption energy and effectively decrease∗OOH’s energy barrier.This research exhibits a feasible strategy to design low cost electrocatalysts and provide new possibilities for future industrialization.
基金National Key Research and Development Program of China,Grant/Award Number:2023YFF1000204National Natural Science Foundation of China,Grant/Award Number:32172715,32230105 and 32330103+2 种基金The Innovative Project of State Key Laboratory of Animal Biotech Breeding,Grant/Award Number:2024SKLAB1-2/9Chinese Universities Scientific Fund,Grant/Award Number:2024TC167The 2115 Talent Development Program of China Agricultural University。
文摘Background : Traditional DNA microinjection methods used in mammals are difficult to apply to avian species due to their unique reproductive characteristics. Genetic manipulation in chickens, particularly involving immature follicles within living ovaries, has not been extensively explored. This study seeks to establish an efficient method for generating transgenic chickens through ovarian injection, potentially bypassing the challenges associated with primordial germ cell (PGC) manipulation and fertilized egg microinjection. Methods : Hens were anesthetized and underwent a surgical procedure to access the ovary for DNA injection into immature follicles. The study used liposomes to deliver GFP- expressing plasmids at various dosages. After injection, hens recovered, and their eggs were fertilized through artificial insemination. Results : Transgenic chickens were successfully generated in one generation without needing G0 founders. The injection of 20 μg plasmid yielded the highest transgenic efficiency at 12.1%. GFP- positive embryos were confirmed through microscopy, and successful transgene expression was validated at the tissue level using immunostaining. TERT and GFP elements introduced in the G1 generation resulted in 4.1% positive transgene rates, as confirmed by PCR and Southern blotting. Conclusion : This ovarian injection method offers a promising alternative for avian genetic manipulation, bypassing complex PGC procedures and enabling direct generation of G1 transgenic chickens. This technique simplifies the transgenic process for chickens and has the potential to be adapted for other avian species, especially those without established PGCs culture systems.
文摘Battery health evaluation and management are vital for the long-term reliability and optimal performance of lithium-ion batteries in electric vehicles.Electrochemical impedance spectroscopy(EIS)offers valuable insights into battery degradation analysis and modeling.However,previous studies have not adequately addressed the impedance uncertainties,particularly during battery operating conditions,which can substantially impact the robustness and accuracy of state of health(SOH)estimation.Motivated by this,this paper proposes a comprehensive feature optimization scheme that integrates impedance validity assessment with correlation analysis.By utilizing metrics such as impedance residuals and correlation coefficients,the proposed method effectively filters out invalid and insignificant impedance data,thereby enhancing the reliability of the input features.Subsequently,the extreme gradient boosting(XGBoost)modeling framework is constructed for estimating the battery degradation trajectories.The XGBoost model incorporates a diverse range of hyperparameters,optimized by a genetic algorithm to improve its adaptability and generalization performance.Experimental validation confirms the effectiveness of the proposed feature optimization scheme,demonstrating the superior estimation performance of the proposed method in comparison with four baseline techniques.
基金supported by the National Natural Science Foundation of China(Grant Nos.62371069,62372048,and 62272056)BUPT Excellent Ph.D.Students Foundation(Grant No.CX2023123)。
文摘The quantum alternating operator ansatz algorithm(QAOA+)is widely used for constrained combinatorial optimization problems(CCOPs)due to its ability to construct feasible solution spaces.In this paper,we propose a progressive quantum algorithm(PQA)to reduce qubit requirements for QAOA+in solving the maximum independent set(MIS)problem.PQA iteratively constructs a subgraph likely to include the MIS solution of the original graph and solves the problem on it to approximate the global solution.Specifically,PQA starts with a small-scale subgraph and progressively expands its graph size utilizing heuristic expansion strategies.After each expansion,PQA solves the MIS problem on the newly generated subgraph using QAOA+.In each run,PQA repeats the expansion and solving process until a predefined stopping condition is reached.Simulation results show that PQA achieves an approximation ratio of 0.95 using only 5.57%(2.17%)of the qubits and 17.59%(6.43%)of the runtime compared with directly solving the original problem with QAOA+on Erd?s-Rényi(3-regular)graphs,highlighting the efficiency and scalability of PQA.
文摘Objective:To observe and study the actual effects of percutaneous pedicle screw minimally invasive surgery in the treatment of spinal fractures and its impact on spinal function.Methods:This study included 48 patients with spinal fractures admitted between May 2023 and May 2024.The patients were divided into a control group and an experimental group based on treatment differences,with 24 patients in each group.The control group underwent open internal fixation surgery,while the experimental group received percutaneous pedicle screw minimally invasive surgery.Clinical index improvements,cervical dysfunction index,Japanese Orthopaedic Association scores,and pain level improvements were compared between the two groups.Results:The intraoperative blood loss,incision length,operation time,and hospitalization duration in the experimental group were(88.63±18.85),(6.32±1.05),(73.42±4.05),and(12.58±2.56),respectively,compared to(279.95±17.32),(12.89±1.36),(89.93±4.79),and(22.41±2.87)in the control group.Significant differences were observed between the groups,with the experimental group showing superior improvements across all metrics(P<0.05).Conclusion:Percutaneous pedicle screw minimally invasive surgery shows more significant effects in treating spinal fractures,particularly in improving cervical and lumbar spine function,enhancing treatment efficacy and safety,reducing pain levels,and shortening recovery time.Clinical application and promotion are recommended.
文摘Objective:To evaluate and analyze the actual efficacy of percutaneous vertebroplasty in the treatment of old unstable osteoporotic spinal fractures.Methods:From March 2023 to March 2024,46 patients with old unstable osteoporotic spinal fractures in our hospital were included in this study.They were divided into the conventional group and the observation group based on treatment differences,with 23 patients in each group.The conventional group received conservative drug therapy,while the observation group underwent percutaneous vertebroplasty.The following indicators were compared and analyzed between the two groups:clinical treatment effect and improvement in physical function indicators.Results:The treatment efficiency of the observation group was 95.65%(22/23),while that of the conventional group was 69.57%(16/23).There was a significant difference between the groups,and the treatment effect of the observation group was significantly better(P<0.05).After treatment,the scores of physical status,daily living ability,functional independence,and life obstacles in the observation group were(89.33±4.08),(88.72±4.08),(90.41±2.89),(72.35±3.22),respectively,while those in the conventional group were(68.54±4.21),(67.42±4.11),(73.48±2.75),(72.35±3.22).There was a significant difference between the groups,and the improvement in physical function indicators in the observation group was more pronounced(P<0.05).Conclusion:For patients with old unstable osteoporotic spinal fractures,the basic value of percutaneous vertebroplasty is significant.It can not only improve clinical efficacy and safety but also promote the gradual recovery of patients'physical function indicators.It is recommended for clinical reference and practical application.
文摘Lithium-ion batteries have extensive usage in various energy storage needs,owing to their notable benefits of high energy density and long lifespan.The monitoring of battery states and failure identification are indispensable for guaranteeing the secure and optimal functionality of the batteries.The impedance spectrum has garnered growing interest due to its ability to provide a valuable understanding of material characteristics and electrochemical processes.To inspire further progress in the investigation and application of the battery impedance spectrum,this paper provides a comprehensive review of the determination and utilization of the impedance spectrum.The sources of impedance inaccuracies are systematically analyzed in terms of frequency response characteristics.The applicability of utilizing diverse impedance features for the diagnosis and prognosis of batteries is further elaborated.Finally,challenges and prospects for future research are discussed.
基金supported by the China Postdoctoral Science Foundation(2022M723370)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA23080603)。
文摘Background Rosemary extract(RE)has been reported to exert antioxidant property.However,the application of RE in late-phase laying hens on egg quality,intestinal barrier and microbiota,and oviductal function has not been systematically studied.This study was investigated to detect the potential effects of RE on performance,egg quality,serum parameters,intestinal heath,cecal microbiota and metabolism,and oviductal gene expressions in late-phase laying hens.A total of 21065-week-old“Jing Tint 6”laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet(CON)or basal diet supplemented with chlortetracycline at 50 mg/kg(CTC)or RE at 50 mg/kg(RE50),100 mg/kg(RE100),and 200 mg/kg(RE200).Results Our results showed that RE200 improved(P<0.05)Haugh unit and n-6/n-3 of egg yolk,serum superoxide dismutase(SOD)compared with CON.No significant differences were observed for Haugh unit and n-6/n-3 of egg yolk among CTC,RE50,RE100 and RE200 groups.Compared with CTC and RE50 groups,RE200 increased serum SOD activity on d 28 and 56.Compared with CON,RE supplementation decreased(P<0.05)total cholesterol(TC)level.CTC,RE100 and RE200 decreased(P<0.05)serum interleukin-6(IL-6)content compared with CON.CTC and RE200 increased jejunal m RNA expression of ZO-1 and Occludin compared with CON.The biomarkers of cecal microbiota and metabolite induced by RE 200,including Firmicutes,Eisenbergiella,Paraprevotella,Papillibacter,and butyrate,were closely associated with Haugh unit,n-6/n-3,SOD,IL-6,and TC.PICRUSt2 analysis indicated that RE altered carbohydrate and amino acid metabolism of cecal microbiota and increased butyrate synthesizing enzymes,including 3-oxoacid Co A-transferase and butyrate-acetoacetate Co A-transferase.Moreover,transcriptomic analysis revealed that RE200 improved gene expressions and functional pathways related to immunity and albumen formation in the oviductal magnum.Conclusions Dietary supplementation with 200 mg/kg RE could increase egg quality of late-phase laying hens via modulating intestinal barrier,cecal microbiota and metabolism,and oviductal function.Overall,RE could be used as a promising feed additive to improve egg quality of laying hens at late stage of production.
基金National Natural Science Foundation of China[82274366]The National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine:Multi-dimensional Evaluation and Multidisciplinary Innovation Team of Southwest Traditional Chinese Medicine Resources[ZYYCXTD-D-202209]+2 种基金The Youth Talent Promotion Project of China Association of Chinese Medicine[2021-QNRC2-A09]The Major Project of Sichuan Provincial Administration of Traditional Chinese Medicine(2023ZD01)the financial support from the Indian Council of Medical Research(ICMR),New Delhi,India,through Extramural Research Grants.
文摘As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.
基金supported by the National Key Research and Development Program of China (2021YFD1201603,2023YFD1202900)the Key Research and Development Program of Shandong Province (Agricultural Seed Improvement Project) (ZDYF2023LZGC001)+1 种基金the Key Research and Development Program of Hainan Province (ZDYF2022XDNY135)the Agricultural Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences (ASTIP No.CAAS-ZDRW202407,01-ICS-02).
文摘MicroRNAs(miRNAs)are versatile regulators of gene expression at both the transcription and posttranscription levels.The microRNA miR396 plays vital roles in growth,development,and resistance to abiotic stresses in many plant species.However,the roles and functions of miR396 in soybeans are not well understood.Here,we report that Gm-miR396a influences soybean development and salinity tolerance.We found that soybean miR396a was responsive to salt stress.Gm-miR396a gene-edited lines(miR396a-GEs),created using CRISPR/Cas9,exhibited more branches,higher grain yields,and greater salinity tolerance than control plants.The transcripts in lines with altered abundance of miR396a-GE were significantly enriched for biological processes related to hormone regulation.Overexpression of the Gm-miR396a precursor(pre-miR396a-OE)resulted in developmental deficiencies including dwarfness,abnormal inflorescences and flowers,smaller and fewer seeds,and small leaves with larger and more numerous stomata.Transcriptome analysis indicated photosynthesis-related genes were downregulated in pre-miR396a-OE plants.These results contribute valuable insights into the function of GmmiR396a in soybeans and hold promise for enhancing soybean yield and salinity tolerance through germplasm innovation.
基金supported by the National Natural Science Foundation of China (82472439,82270935,81974337,82102627)the Hubei Provincial Natural Science Foundation of China (2021CFB095)+1 种基金the Wuhan Knowledge Innovation Project (2022020801020468)the Project of Scientific Research Plan of Wuhan Municipal Health Commission (WX21Q19)。
文摘Osteonecrosis of the femoral head(ONFH)is a common complication of glucocorticoid(GC)therapy.Recent advances demonstrate that sympathetic nerves regulate bone homeostasis,and GCs lower the sympathetic tone.Here,we show that the dramatically decreased sympathetic tone is closely associated with the pathogenesis of GC-induced ONFH.GCs activate the glucocorticoid receptor(GR)but hinder the activation of the mineralocorticoid receptor(MR)on neurons in the hypothalamic paraventricular nucleus(PVN).This disrupts the balance of corticosteroid receptors(GR/MR)and subsequently reduces the sympathetic outflow in the PVN.Vascular endothelial cells rapidly react to inhibition of sympathetic tone by provoking endothelial apoptosis in adult male mice treated with methylprednisolone(MPS)daily for 3 days,and we find substantially reduced H-type vessels in the femoral heads of MPS-treated ONFH mice.Importantly,treatment with a GR inhibitor(RU486)in the PVN promotes the activation of MR and rebalances the ratio of GR and MR,thus effectively boosting sympathetic outflow,as shown by an increase in tyrosine hydroxylase expression in both the PVN and the sympathetic postganglionic neurons and an increase in norepinephrine levels in both the serum and bone marrow of the femoral head of MPS-treated mice.Rebalancing the corticosteroid receptors mitigates GC-induced endothelial impairment and ONFH and promotes angiogenesis coupled with osteogenesis in the femoral head,while these effects are abolished by chemical sympathectomy with 6-OHDA or adrenergic receptor-β2(Adrb2)knockout.Furthermore,activating Adrb2 signaling in vivo is sufficient to rescue the GC-induced ONFH phenotype.Mechanistically,norepinephrine increases the expression of the key glycolytic gene 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)via Adrb2-cyclic AMP response element-binding protein(CREB)signaling.Endothelial-specific overexpression of PFKFB3 attenuates endothelial impairment and prevents severe osteonecrosis in MPS-treated Adrb2 knockout mice.Thus,GC inhibits sympathetic tone via the hypothalamic descending pathway,which,in turn,acts as a mediator of GC-induced ONFH.
