To reduce the cost and increase the efficiency of plant genetic marker fingerprinting for variety discrimination,it is desirable to identify the optimal marker combinations.We describe a marker combination screening m...To reduce the cost and increase the efficiency of plant genetic marker fingerprinting for variety discrimination,it is desirable to identify the optimal marker combinations.We describe a marker combination screening model based on the genetic algorithm(GA)and implemented in a software tool,Loci Scan.Ratio-based variety discrimination power provided the largest optimization space among multiple fitness functions.Among GA parameters,an increase in population size and generation number enlarged optimization depth but also calculation workload.Exhaustive algorithm afforded the same optimization depth as GA but vastly increased calculation time.In comparison with two other software tools,Loci Scan accommodated missing data,reduced calculation time,and offered more fitness functions.In large datasets,the sample size of training data exerted the strongest influence on calculation time,whereas the marker size of training data showed no effect,and target marker number had limited effect on analysis speed.展开更多
This study was conducted with non-English sophomore students,aiming to explore the effects of different interaction combinations and language levels on continuous writing in an online environment,and compare the diffe...This study was conducted with non-English sophomore students,aiming to explore the effects of different interaction combinations and language levels on continuous writing in an online environment,and compare the differences in lexical alignments and composition quality of learners with different interaction combinations and language levels in the same continuous writing task through experiments.The results show that the mean values of the word-phrase alignment of the paired group were higher than those of the individual group in different interaction combinations,and the two groups showed significant differences;in terms of composition quality,the individual group was better than the paired group,but there was no significant difference between the two groups in terms of task continuation.Secondly,the word-phrase alignment and composition scores of the different language-level groups were higher than those of the same language-level groups,and there was a significant difference between the two groups in terms of word-phrase alignments,but not in terms of composition scores.The results of this study can be useful and informative for second language teachers in future continuous teaching in online environments.展开更多
Through the comprehensive analysis of the connotation and logic,inheritance and innovation and the value of social governance,and the dialectical relationship of“two combination”,the inheritance of the idea of Marxi...Through the comprehensive analysis of the connotation and logic,inheritance and innovation and the value of social governance,and the dialectical relationship of“two combination”,the inheritance of the idea of Marxism,the inheritance of excellent traditional culture and the governance of contemporary society.展开更多
Sucrose nonfermenting-related protein kinase 1(SnRK1)is one of the critical serine/threonine protein kinases.It commonly mediates plant growth and development,cross-talks with metabolism processes and physiological re...Sucrose nonfermenting-related protein kinase 1(SnRK1)is one of the critical serine/threonine protein kinases.It commonly mediates plant growth and development,cross-talks with metabolism processes and physiological responses to biotic or abiotic stresses.It plays a key role in distributing carbohydrates and sugar signal transporting.In the present study,eight SnRK1 coding genes were identified in sorghum(Sorghum bicolor L.)via sequences alignment,with three forαsubunits(SnRK1α1 to SnRK1α3),three forβ(SnRK1β1 to SnRK1β3),and one for bothγ(SnRK1γ)andβγ(SnRK1βγ).These eight corresponding genes located on five chromosomes(Chr)of Chr1–3,Chr7,and Chr9 and presented collinearities to SnRK1s from maize and rice,exhibiting highly conserved domains within the same subunits from the three kinds of cereals.Expression results via qRT-PCR showed that different coding genes of SnRK1s in sorghum possessed similar expression patterns except for SnRK1α3 with a low expression level in grains and SnRK1β2 with a relatively high expression level in inflorescences.Results of subcellular localization in sorghum leaf protoplast showed that SnRK1α1/α2/α3/γmainly located on organelles,while the rest four of SnRK1β1/β2/β3/βγlocated on both membranes and some organelles.Besides,three combinations were discovered among eight SnRK1 subunits in sorghum through yeast two hybrid,includingα1-β2-βγ,α2-β3-γ,andα3-β3-γ.These results provide informative references for the following functional dissection of SnRK1 subunits in sorghum.展开更多
A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the mol...A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the molten salt reactor and power system.This model considers the impact of thermal properties of fluid variation on accuracy and has been validated with Simulink.This study reveals the capability of the control system to compensate for anomalous situations and maintain shaft stability in the event of perturbations occurring in high-temperature molten salt tank outlet parameters.Meanwhile,the control system’s impact on the system’s dynamic characteristics under molten salt disturbance is also analyzed.The results reveal that after the disturbance occurs,the controlled system benefits from the action of the control,and the overshoot and disturbance amplitude are positively correlated,while the system power and frequency eventually return to the initial values.This simulation model provides a basis for utilizing molten salt reactors for power generation and maintaining grid stability.展开更多
Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a com...Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.展开更多
The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to...The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.展开更多
BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erl...BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.展开更多
Simultaneous stresses of salinity and drought often coincide during rice-growing seasons in saline lands,primarily due to insufficient water resources and inadequate irrigation facilities.Consequently,combined salinit...Simultaneous stresses of salinity and drought often coincide during rice-growing seasons in saline lands,primarily due to insufficient water resources and inadequate irrigation facilities.Consequently,combined salinity-drought stress poses a major threat to rice production.In this study,two salinity levels(NS,non-salinity;HS,high salinity)along with three drought treatments(CC,control condition;DJ,drought stress imposed at jointing;DH,drought stress imposed at heading)were performed to investigate their combined influences on leaf photosynthetic characteristics,biomass accumulation,and rice yield formation.Salinity,drought,and their combination led to a shortened growth period from heading to maturity,resulting in a reduced overall growth duration.Grain yield was reduced under both salinity and drought stress,with a more substantial reduction under the combined salinity-drought stress.The combined stress imposed at heading caused greater yield losses in rice compared with the stress imposed at jointing.Additionally,the combined salinity-drought stress induced greater decreases in shoot biomass accumulation from heading to maturity,as well as in shoot biomass and nonstructural carbohydrate(NSC)content in the stem at heading and maturity.However,it increased the harvest index and NSC remobilization reserve.Salinity and drought reduced the leaf area index and SPAD value of flag leaves and weakened the leaf photosynthetic characteristics as indicated by lower photosynthetic rates,transpiration rates,and stomatal conductance.These reductions were more pronounced under the combined stress.Salinity,drought,and especially their combination,decreased the activities of ascorbate peroxidase,catalase,and superoxide dismutase,while increasing the contents of malondialdehyde,hydrogen peroxide,and superoxide radical.Our results indicated a more significant yield loss in rice when subjected to combined salinity-drought stress.The individual and combined stresses of salinity and drought diminished antioxidant enzyme activities,inhibited leaf photosynthetic functions,accelerated leaf senescence,and subsequently lowered assimilate accumulation and grain yield.展开更多
In this paper, we explore the linear combinations of right half-plane mappings and vertical strip mappings. We demonstrate that the combinations of these harmonic mappings are convex in the vertical direction provided...In this paper, we explore the linear combinations of right half-plane mappings and vertical strip mappings. We demonstrate that the combinations of these harmonic mappings are convex in the vertical direction provided they are locally univalent and sense-preserving. Furthermore, we extend this analysis to a more general case by setting specific conditions. Additionally, we take some common parameters such as as the dilatation of these harmonic mappings, and prove the sufficient conditions that their combinations are locally univalent and convex in the vertical direction. Several examples are constructed by the Mathematica software to demonstrate our main results.展开更多
BACKGROUND Preschoolers become anxious when they are about to undergo anesthesia and surgery,warranting the development of more appropriate and effective interventions.AIM To explore the effect of static cartoons comb...BACKGROUND Preschoolers become anxious when they are about to undergo anesthesia and surgery,warranting the development of more appropriate and effective interventions.AIM To explore the effect of static cartoons combined with dynamic virtual environments on preoperative anxiety and anesthesia induction compliance in preschool-aged children undergoing surgery.METHODS One hundred and sixteen preschool-aged children were selected and assigned to the drug(n=37),intervention(n=40),and control(n=39)groups.All the children received routine preoperative checkups and nursing before being transferred to the preoperative preparation room on the day of the operation.The drug group received 0.5 mg/kg midazolam and the intervention group treatment consisting of static cartoons combined with dynamic virtual environments.The control group received no intervention.The modified Yale Preoperative Anxiety Scale was used to evaluate the children’s anxiety level on the day before surgery(T0),before leaving the preoperative preparation room(T1),when entering the operating room(T2),and at anesthesia induction(T3).Compliance during anesthesia induction(T3)was evaluated using the Induction Compliance Checklist(ICC).Changes in mean arterial pressure(MAP),heart rate(HR),and respiratory rate(RR)were also recorded at each time point.RESULTS The anxiety scores of the three groups increased variously at T1 and T2.At T3,both the drug and intervention groups had similar anxiety scores,both of which were lower than those in the control group.At T1 and T2,MAP,HR,and RR of the three groups increased.The drug and control groups had significantly higher MAP and RR than the intervention group at T2.At T3,the MAP,HR,and RR of the drug group decreased and were significantly lower than those in the control group but were comparable to those in the intervention group.Both the drug and intervention groups had similar ICC scores and duration of anesthesia induction(T3),both of which were higher than those of the control group.CONCLUSION Combining static cartoons with dynamic virtual environments as effective as medication,specifically midazolam,in reducing preoperative anxiety and fear in preschool-aged children.This approach also improve their compliance during anesthesia induction and helped maintain their stable vital signs.展开更多
The ultrashort lasers working in pulse-burst mode reveal great machining performance in recent years. The number of pulses in bursts effects greatly on the removal rate and roughness. To generate a more equal amplitud...The ultrashort lasers working in pulse-burst mode reveal great machining performance in recent years. The number of pulses in bursts effects greatly on the removal rate and roughness. To generate a more equal amplitude of pulses in burst with linear polarization output and time gap adjustable, we propose a new method by the harmonic beam combining(HBC).The beam combining is commonly used in adding pulses into the output beam while maintaining the pulse waveform and beam quality. In the HBC, dichroic mirrors are used to combine laser pulses of fundamental wave(FW) into harmonic wave(HW), and nonlinear crystals are used to convert the FW into HW. Therefore, HBC can add arbitrarily more HW pulses to generate pulse-burst in linear polarization with simple structure. The amplitude of each pulse in bursts can be adjusted the same to increase the stability of the burst, the time gap of each pulse can be adjusted precisely by proper time delay. Because HBC adds pulses sequentially, the peak power density of the burst is the same as each pulse, pulses can be combined without concern of back-conversion which often occurs in high peak power density. In the demonstration, the extendibility of HBC was verified by combining two beams with a third beam. The combined efficiency rates were larger than 99%, and the beam quality of each beam was maintained at M^(2)≈1.4.展开更多
Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combina...Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combination with conventional antituberculosis drugs in treatment of tuberculosis (TB) in Uganda, there is paucity of knowledge on their combination effect. Aim: This research aimed to determine combination activity of standard antituberculosis drugs with extracts of Zanthoxylum leprieurii Guill. & Perr. and Rubia cordifolia L., the two common antituberculosis medicinal plants in Uganda, against pansensitive (H37Rv) and multi-drug resistant (MDR) Mycobacterium tuberculosis strains. Materials and Methods: Two reference MTB strains (H37Rv and MDR strain) were inoculated on Middlebrook 7H11 medium containing a combination of standard antituberculosis drugs and methanol extracts of Z. leprieurii and R. cordifolia at varying concentrations. The number of colonies on the plates was observed and counted weekly for up to 8 weeks. In vitro combination activity was determined using proportion method. Mean percentage inhibition was calculated for the reduction of number of colonies on drug-extract combination medium in relation to drug-extract-free control medium. Results: Drug-extract combinations showed good combination activity against Mycobacterium tuberculosis strains when compared with individual standard anti-TB drugs. This was more exhibited against MDR strain. There was however a reduction in percentage inhibition when extracts were combined with ethambutol and streptomycin against H37Rv strain. Conclusions: Zanthoxylum leprieurii and Rubia cordifolia in combination with standard anti-TB drugs exhibited increased in vitro activity against Mycobacterium tuberculosis, especially MDR-TB strain. This justifies the local use of these plants in traditional treatment of tuberculosis especially in resistant cases in Uganda.展开更多
Single-drug therapies or monotherapies are often inadequate,particularly in the case of life-threatening diseases like cancer.Consequently,combination therapies emerge as an attractive strategy.Cancer nanomedicines ha...Single-drug therapies or monotherapies are often inadequate,particularly in the case of life-threatening diseases like cancer.Consequently,combination therapies emerge as an attractive strategy.Cancer nanomedicines have many benefits in addressing the challenges faced by small molecule therapeutic drugs,such as low water solubility and bioavailability,high toxicity,etc.However,it remains a significant challenge in encapsulating two drugs in a nanoparticle.To address this issue,computational methodologies are employed to guide the rational design and synthesis of dual-drug-loaded polymer nanoparticles while achieving precise control over drug loading.Based on the sequential nanoprecipitation technology,five factors are identified that affect the formulation of drug candidates into dual-drug loaded nanoparticles,and then screened 176 formulations under different experimental conditions.Based on these experimental data,machine learning methods are applied to pin down the key factors.The implementation of this methodology holds the potential to signif-icantly mitigate the complexities associated with the synthesis of dual-drug loaded nanoparticles,and the co-assembly of these compounds into nanoparticulate systems demonstrates a promising avenue for combination therapy.This approach provides a new strategy for enabling the streamlined,high-throughput screening and synthesis of new nanoscale drug-loaded entities.展开更多
Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fastin...Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.展开更多
Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvatio...Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.展开更多
Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in undergroun...Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in underground engineering.To reveal the effect of this way,the uniaxial compression experiments with PSC monitoring were conducted on three types of coal-rock combination samples with different strength combinations.The mechanism explanation of PSCs are investigated by resistivity test,atomic force microscopy(AFM)and computed tomography(CT)methods,and a PSC flow model based on progressive failure process is proposed.The influence of strength combinations on PSCs in the progressive failure process are emphasized.The results show the PSC responses between rock part,coal part and the two components are different,which are affected by multi-scale fracture characteristics and electrical properties.As the rock strength decreases,the progressive failure process changes obviously with the influence range of interface constraint effect decreasing,resulting in the different responses of PSC strength and direction in different parts to fracture behaviors.The PSC flow model is initially validated by the relationship between the accumulated charges of different parts.The results are expected to provide a new reference and method for mining design and roadway quality assessment.展开更多
Triple-negative breast cancer,due to its aggressive nature and lack of targeted treatment,faces serious challenges in breast cancer treatment.Conventional therapies,such as chemotherapy,are encumbered by a range of li...Triple-negative breast cancer,due to its aggressive nature and lack of targeted treatment,faces serious challenges in breast cancer treatment.Conventional therapies,such as chemotherapy,are encumbered by a range of limitations,and there is an urgent need for more effective treatment strategies.Ferroptosis,as an iron-dependent form of cell death,has exhibited promising potential in cancer treatment.Combining ferroptosis with other cancer therapies offers new avenues for treatment.Tetrahedral DNA nanostructure(TDN),a novel DNA-based three-dimensional(3D)nanomaterial,is promising drug delivery vehicle and can be utilized for functionalizing inorganic nanomaterials.In this work,we have demonstrated the preparation of Fe_(3)O_(4)-PEI@TDN-DOX nanocomposites and elucidated their antitumor mechanism.The TDN facilitated the enhanced cellular uptake of polyetherimide(PEI)-modified Fe_(3)O_(4),and the delivery of the chemotherapeutic drug doxorubicin(DOX)further augmented their anti-tumor effect.This novel strategy can destroy the tumor redox homeostasis and produce overwhelming lipid peroxides,consequently sensitizing the tumor to ferroptosis.The integration of ferroptosis with other cancer therapies opens up new possibilities for treatment.This research provides valuable mechanistic insights and practical strategies for leveraging nanotechnology to induce ferroptosis and amplify its impact on tumor cells.展开更多
To solve the problem of data fusion for prior information such as track information and train status in train positioning,an adaptive H∞filtering algorithm with combination constraint is proposed,which fuses prior in...To solve the problem of data fusion for prior information such as track information and train status in train positioning,an adaptive H∞filtering algorithm with combination constraint is proposed,which fuses prior information with other sensor information in the form of constraints.Firstly,the train precise track constraint method of the train is proposed,and the plane position constraint and train motion state constraints are analysed.A model for combining prior information with constraints is established.Then an adaptive H∞filter with combination constraints is derived based on the adaptive adjustment method of the robustness factor.Finally,the positioning effect of the proposed algorithm is simulated and analysed under the conditions of a straight track and a curved track.The results show that the positioning accuracy of the algorithm with constrained filtering is significantly better than that of the algorithm without constrained filtering and that the algorithm with constrained filtering can achieve better performance when combined with track and condition information,which can significantly reduce the train positioning error.The effectiveness of the proposed algorithm is verified.展开更多
BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therap...BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.展开更多
基金supported by the Scientific and Technological Innovation 2030 Major Project(2022ZD04019)the Science and Technology Innovation Capacity Building Project of BAAFS(KJCX20230303)+1 种基金Hainan Province Science and Technology Special Fund(ZDYF2023XDNY077)the Beijing Scholars Program(BSP041)。
文摘To reduce the cost and increase the efficiency of plant genetic marker fingerprinting for variety discrimination,it is desirable to identify the optimal marker combinations.We describe a marker combination screening model based on the genetic algorithm(GA)and implemented in a software tool,Loci Scan.Ratio-based variety discrimination power provided the largest optimization space among multiple fitness functions.Among GA parameters,an increase in population size and generation number enlarged optimization depth but also calculation workload.Exhaustive algorithm afforded the same optimization depth as GA but vastly increased calculation time.In comparison with two other software tools,Loci Scan accommodated missing data,reduced calculation time,and offered more fitness functions.In large datasets,the sample size of training data exerted the strongest influence on calculation time,whereas the marker size of training data showed no effect,and target marker number had limited effect on analysis speed.
文摘This study was conducted with non-English sophomore students,aiming to explore the effects of different interaction combinations and language levels on continuous writing in an online environment,and compare the differences in lexical alignments and composition quality of learners with different interaction combinations and language levels in the same continuous writing task through experiments.The results show that the mean values of the word-phrase alignment of the paired group were higher than those of the individual group in different interaction combinations,and the two groups showed significant differences;in terms of composition quality,the individual group was better than the paired group,but there was no significant difference between the two groups in terms of task continuation.Secondly,the word-phrase alignment and composition scores of the different language-level groups were higher than those of the same language-level groups,and there was a significant difference between the two groups in terms of word-phrase alignments,but not in terms of composition scores.The results of this study can be useful and informative for second language teachers in future continuous teaching in online environments.
文摘Through the comprehensive analysis of the connotation and logic,inheritance and innovation and the value of social governance,and the dialectical relationship of“two combination”,the inheritance of the idea of Marxism,the inheritance of excellent traditional culture and the governance of contemporary society.
基金supported by the National Natural Science Foundation of China(32001607)the Fundamental Research Funds for the Central Universities of Southwest University,China(SWU118087)。
文摘Sucrose nonfermenting-related protein kinase 1(SnRK1)is one of the critical serine/threonine protein kinases.It commonly mediates plant growth and development,cross-talks with metabolism processes and physiological responses to biotic or abiotic stresses.It plays a key role in distributing carbohydrates and sugar signal transporting.In the present study,eight SnRK1 coding genes were identified in sorghum(Sorghum bicolor L.)via sequences alignment,with three forαsubunits(SnRK1α1 to SnRK1α3),three forβ(SnRK1β1 to SnRK1β3),and one for bothγ(SnRK1γ)andβγ(SnRK1βγ).These eight corresponding genes located on five chromosomes(Chr)of Chr1–3,Chr7,and Chr9 and presented collinearities to SnRK1s from maize and rice,exhibiting highly conserved domains within the same subunits from the three kinds of cereals.Expression results via qRT-PCR showed that different coding genes of SnRK1s in sorghum possessed similar expression patterns except for SnRK1α3 with a low expression level in grains and SnRK1β2 with a relatively high expression level in inflorescences.Results of subcellular localization in sorghum leaf protoplast showed that SnRK1α1/α2/α3/γmainly located on organelles,while the rest four of SnRK1β1/β2/β3/βγlocated on both membranes and some organelles.Besides,three combinations were discovered among eight SnRK1 subunits in sorghum through yeast two hybrid,includingα1-β2-βγ,α2-β3-γ,andα3-β3-γ.These results provide informative references for the following functional dissection of SnRK1 subunits in sorghum.
基金This work was supported by the Chinese TMSR Strategic Pioneer Science and Technology Project(No.XDA02010300).
文摘A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the molten salt reactor and power system.This model considers the impact of thermal properties of fluid variation on accuracy and has been validated with Simulink.This study reveals the capability of the control system to compensate for anomalous situations and maintain shaft stability in the event of perturbations occurring in high-temperature molten salt tank outlet parameters.Meanwhile,the control system’s impact on the system’s dynamic characteristics under molten salt disturbance is also analyzed.The results reveal that after the disturbance occurs,the controlled system benefits from the action of the control,and the overshoot and disturbance amplitude are positively correlated,while the system power and frequency eventually return to the initial values.This simulation model provides a basis for utilizing molten salt reactors for power generation and maintaining grid stability.
文摘Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.
文摘The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.
基金Supported by NIH/National Cancer Institute Grant,No.R01CA138441 and No.R01CA269452UW Madison Centene Pancreas Cancer Collaborative Award,No.21-8568.
文摘BACKGROUND Pancreatic cancer is a leading cause of cancer-related deaths.Increased activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug administration.Nevertheless,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic outcomes.We previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell death.Erlotinib has not been tested for this effect.AIM To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell death.METHODSΔψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell lines.The viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive MitoQ.The synergy between erlotinib and MitoQ was then analyzed using SynergyFinder 2.0.The preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line xenografts.RESULTS Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive agents.MitoQ triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of MitoQ.SynergyFinder suggested that these drugs synergistically induced tumor cell lethality.Consistent with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each agent.CONCLUSION Our findings suggest that a combination of erlotinib and MitoQ has the potential to suppress pancreatic tumor cell viability effectively.
基金financed by the National Key Research and Development Program,China(Grant Nos.2022YFE0113400 and 2022YFD1500402)National Natural Science Foundation of China(Grant No.32001466)+3 种基金Scientific and Technological Innovation Fund of Carbon Emissions Peak and Neutrality of Jiangsu Provincial Department of Science and Technology,China(Grant Nos.BE2022304 and BE2022305)Joints Funds of the National Natural Science Foundation of China(Grant No.U20A2022)Postdoctoral Research Foundation of China(Grant No.2020M671628)the Priority Academic Program Development of Jiangsu Higher Education Institutions,China.
文摘Simultaneous stresses of salinity and drought often coincide during rice-growing seasons in saline lands,primarily due to insufficient water resources and inadequate irrigation facilities.Consequently,combined salinity-drought stress poses a major threat to rice production.In this study,two salinity levels(NS,non-salinity;HS,high salinity)along with three drought treatments(CC,control condition;DJ,drought stress imposed at jointing;DH,drought stress imposed at heading)were performed to investigate their combined influences on leaf photosynthetic characteristics,biomass accumulation,and rice yield formation.Salinity,drought,and their combination led to a shortened growth period from heading to maturity,resulting in a reduced overall growth duration.Grain yield was reduced under both salinity and drought stress,with a more substantial reduction under the combined salinity-drought stress.The combined stress imposed at heading caused greater yield losses in rice compared with the stress imposed at jointing.Additionally,the combined salinity-drought stress induced greater decreases in shoot biomass accumulation from heading to maturity,as well as in shoot biomass and nonstructural carbohydrate(NSC)content in the stem at heading and maturity.However,it increased the harvest index and NSC remobilization reserve.Salinity and drought reduced the leaf area index and SPAD value of flag leaves and weakened the leaf photosynthetic characteristics as indicated by lower photosynthetic rates,transpiration rates,and stomatal conductance.These reductions were more pronounced under the combined stress.Salinity,drought,and especially their combination,decreased the activities of ascorbate peroxidase,catalase,and superoxide dismutase,while increasing the contents of malondialdehyde,hydrogen peroxide,and superoxide radical.Our results indicated a more significant yield loss in rice when subjected to combined salinity-drought stress.The individual and combined stresses of salinity and drought diminished antioxidant enzyme activities,inhibited leaf photosynthetic functions,accelerated leaf senescence,and subsequently lowered assimilate accumulation and grain yield.
文摘In this paper, we explore the linear combinations of right half-plane mappings and vertical strip mappings. We demonstrate that the combinations of these harmonic mappings are convex in the vertical direction provided they are locally univalent and sense-preserving. Furthermore, we extend this analysis to a more general case by setting specific conditions. Additionally, we take some common parameters such as as the dilatation of these harmonic mappings, and prove the sufficient conditions that their combinations are locally univalent and convex in the vertical direction. Several examples are constructed by the Mathematica software to demonstrate our main results.
基金Supported by Hangzhou Medical and Health Technology Project,No.OO20191141。
文摘BACKGROUND Preschoolers become anxious when they are about to undergo anesthesia and surgery,warranting the development of more appropriate and effective interventions.AIM To explore the effect of static cartoons combined with dynamic virtual environments on preoperative anxiety and anesthesia induction compliance in preschool-aged children undergoing surgery.METHODS One hundred and sixteen preschool-aged children were selected and assigned to the drug(n=37),intervention(n=40),and control(n=39)groups.All the children received routine preoperative checkups and nursing before being transferred to the preoperative preparation room on the day of the operation.The drug group received 0.5 mg/kg midazolam and the intervention group treatment consisting of static cartoons combined with dynamic virtual environments.The control group received no intervention.The modified Yale Preoperative Anxiety Scale was used to evaluate the children’s anxiety level on the day before surgery(T0),before leaving the preoperative preparation room(T1),when entering the operating room(T2),and at anesthesia induction(T3).Compliance during anesthesia induction(T3)was evaluated using the Induction Compliance Checklist(ICC).Changes in mean arterial pressure(MAP),heart rate(HR),and respiratory rate(RR)were also recorded at each time point.RESULTS The anxiety scores of the three groups increased variously at T1 and T2.At T3,both the drug and intervention groups had similar anxiety scores,both of which were lower than those in the control group.At T1 and T2,MAP,HR,and RR of the three groups increased.The drug and control groups had significantly higher MAP and RR than the intervention group at T2.At T3,the MAP,HR,and RR of the drug group decreased and were significantly lower than those in the control group but were comparable to those in the intervention group.Both the drug and intervention groups had similar ICC scores and duration of anesthesia induction(T3),both of which were higher than those of the control group.CONCLUSION Combining static cartoons with dynamic virtual environments as effective as medication,specifically midazolam,in reducing preoperative anxiety and fear in preschool-aged children.This approach also improve their compliance during anesthesia induction and helped maintain their stable vital signs.
基金Project supported by Youth Innovation Promotion Association of the Chinese Academy of Sciences (Grant No.2020029)。
文摘The ultrashort lasers working in pulse-burst mode reveal great machining performance in recent years. The number of pulses in bursts effects greatly on the removal rate and roughness. To generate a more equal amplitude of pulses in burst with linear polarization output and time gap adjustable, we propose a new method by the harmonic beam combining(HBC).The beam combining is commonly used in adding pulses into the output beam while maintaining the pulse waveform and beam quality. In the HBC, dichroic mirrors are used to combine laser pulses of fundamental wave(FW) into harmonic wave(HW), and nonlinear crystals are used to convert the FW into HW. Therefore, HBC can add arbitrarily more HW pulses to generate pulse-burst in linear polarization with simple structure. The amplitude of each pulse in bursts can be adjusted the same to increase the stability of the burst, the time gap of each pulse can be adjusted precisely by proper time delay. Because HBC adds pulses sequentially, the peak power density of the burst is the same as each pulse, pulses can be combined without concern of back-conversion which often occurs in high peak power density. In the demonstration, the extendibility of HBC was verified by combining two beams with a third beam. The combined efficiency rates were larger than 99%, and the beam quality of each beam was maintained at M^(2)≈1.4.
文摘Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combination with conventional antituberculosis drugs in treatment of tuberculosis (TB) in Uganda, there is paucity of knowledge on their combination effect. Aim: This research aimed to determine combination activity of standard antituberculosis drugs with extracts of Zanthoxylum leprieurii Guill. & Perr. and Rubia cordifolia L., the two common antituberculosis medicinal plants in Uganda, against pansensitive (H37Rv) and multi-drug resistant (MDR) Mycobacterium tuberculosis strains. Materials and Methods: Two reference MTB strains (H37Rv and MDR strain) were inoculated on Middlebrook 7H11 medium containing a combination of standard antituberculosis drugs and methanol extracts of Z. leprieurii and R. cordifolia at varying concentrations. The number of colonies on the plates was observed and counted weekly for up to 8 weeks. In vitro combination activity was determined using proportion method. Mean percentage inhibition was calculated for the reduction of number of colonies on drug-extract combination medium in relation to drug-extract-free control medium. Results: Drug-extract combinations showed good combination activity against Mycobacterium tuberculosis strains when compared with individual standard anti-TB drugs. This was more exhibited against MDR strain. There was however a reduction in percentage inhibition when extracts were combined with ethambutol and streptomycin against H37Rv strain. Conclusions: Zanthoxylum leprieurii and Rubia cordifolia in combination with standard anti-TB drugs exhibited increased in vitro activity against Mycobacterium tuberculosis, especially MDR-TB strain. This justifies the local use of these plants in traditional treatment of tuberculosis especially in resistant cases in Uganda.
基金Australian National Health and Medical Research Council,Grant/Award Number:APP2008698Australian Research Council,Grant/Award Number:DE230101044。
文摘Single-drug therapies or monotherapies are often inadequate,particularly in the case of life-threatening diseases like cancer.Consequently,combination therapies emerge as an attractive strategy.Cancer nanomedicines have many benefits in addressing the challenges faced by small molecule therapeutic drugs,such as low water solubility and bioavailability,high toxicity,etc.However,it remains a significant challenge in encapsulating two drugs in a nanoparticle.To address this issue,computational methodologies are employed to guide the rational design and synthesis of dual-drug-loaded polymer nanoparticles while achieving precise control over drug loading.Based on the sequential nanoprecipitation technology,five factors are identified that affect the formulation of drug candidates into dual-drug loaded nanoparticles,and then screened 176 formulations under different experimental conditions.Based on these experimental data,machine learning methods are applied to pin down the key factors.The implementation of this methodology holds the potential to signif-icantly mitigate the complexities associated with the synthesis of dual-drug loaded nanoparticles,and the co-assembly of these compounds into nanoparticulate systems demonstrates a promising avenue for combination therapy.This approach provides a new strategy for enabling the streamlined,high-throughput screening and synthesis of new nanoscale drug-loaded entities.
文摘Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.
基金the National Natural Science Foundation of China(Grant Nos.:82102767 and 82002655)the 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University,China(Grant No.:2020HXFH036)+2 种基金the Knowledge Innovation Program of the Chinese Academy of Sciences,China(Grant No.:JH2022007)the Cultivation Project of Basic Medical College of Xinxiang Medical University,China(Grant No.:JCYXYKY202112)the Key Project of Science and Technology of Henan Province,China(Grant No.:222102310260).
文摘Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.
基金supported by National Key R&D Program of China(No.2022YFC3004705)the National Natural Science Foundation of China(Nos.52074280,52227901 and 52204249)National Natural Science Foundation of China Youth Fund(No.52104230).
文摘Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in underground engineering.To reveal the effect of this way,the uniaxial compression experiments with PSC monitoring were conducted on three types of coal-rock combination samples with different strength combinations.The mechanism explanation of PSCs are investigated by resistivity test,atomic force microscopy(AFM)and computed tomography(CT)methods,and a PSC flow model based on progressive failure process is proposed.The influence of strength combinations on PSCs in the progressive failure process are emphasized.The results show the PSC responses between rock part,coal part and the two components are different,which are affected by multi-scale fracture characteristics and electrical properties.As the rock strength decreases,the progressive failure process changes obviously with the influence range of interface constraint effect decreasing,resulting in the different responses of PSC strength and direction in different parts to fracture behaviors.The PSC flow model is initially validated by the relationship between the accumulated charges of different parts.The results are expected to provide a new reference and method for mining design and roadway quality assessment.
基金supported by the National Key R&D Program of China(No.2019YFA0110600)the National Natural Science Foundation of China(Nos.82370929 and 81970916)+3 种基金the Sichuan Science and Technology Program(Nos.2022NSFSC0002 and 2023YFG022)Sichuan Province Youth Science and Technology Innovation Team(No.2022JDTD0021)Research and Develop Program,West China Hospital of Stomatology Sichuan University(No.RD03202302)the Research Funding from West China School/Hospital of Stomatology Sichuan University(No.QDJF2022-2)。
文摘Triple-negative breast cancer,due to its aggressive nature and lack of targeted treatment,faces serious challenges in breast cancer treatment.Conventional therapies,such as chemotherapy,are encumbered by a range of limitations,and there is an urgent need for more effective treatment strategies.Ferroptosis,as an iron-dependent form of cell death,has exhibited promising potential in cancer treatment.Combining ferroptosis with other cancer therapies offers new avenues for treatment.Tetrahedral DNA nanostructure(TDN),a novel DNA-based three-dimensional(3D)nanomaterial,is promising drug delivery vehicle and can be utilized for functionalizing inorganic nanomaterials.In this work,we have demonstrated the preparation of Fe_(3)O_(4)-PEI@TDN-DOX nanocomposites and elucidated their antitumor mechanism.The TDN facilitated the enhanced cellular uptake of polyetherimide(PEI)-modified Fe_(3)O_(4),and the delivery of the chemotherapeutic drug doxorubicin(DOX)further augmented their anti-tumor effect.This novel strategy can destroy the tumor redox homeostasis and produce overwhelming lipid peroxides,consequently sensitizing the tumor to ferroptosis.The integration of ferroptosis with other cancer therapies opens up new possibilities for treatment.This research provides valuable mechanistic insights and practical strategies for leveraging nanotechnology to induce ferroptosis and amplify its impact on tumor cells.
基金the National Natural Science Fund of China(61471080)Training Plan for Young Backbone Teachers in Colleges and Universities of Henan Province(2018GGJS171).
文摘To solve the problem of data fusion for prior information such as track information and train status in train positioning,an adaptive H∞filtering algorithm with combination constraint is proposed,which fuses prior information with other sensor information in the form of constraints.Firstly,the train precise track constraint method of the train is proposed,and the plane position constraint and train motion state constraints are analysed.A model for combining prior information with constraints is established.Then an adaptive H∞filter with combination constraints is derived based on the adaptive adjustment method of the robustness factor.Finally,the positioning effect of the proposed algorithm is simulated and analysed under the conditions of a straight track and a curved track.The results show that the positioning accuracy of the algorithm with constrained filtering is significantly better than that of the algorithm without constrained filtering and that the algorithm with constrained filtering can achieve better performance when combined with track and condition information,which can significantly reduce the train positioning error.The effectiveness of the proposed algorithm is verified.
基金Capital Health Development and Scientific Research Special Project,No.2022-2-2175.
文摘BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.