赛沃替尼治疗MET基因突变非小细胞肺癌的药物浓度与疗效和不良反应的关系

目的:探讨药物浓度与疗效和不良反应之间的关系,了解赛沃替尼治疗MET14外显子跳跃突变晚期非小细胞肺癌患者的疗效和安全性。方法:回顾性分析2018年4月至2019年9月北京大学肿瘤医院收治的携带MET14外显子跳跃突变,并且接受赛沃替尼治疗的16例局部晚期或转移性非小细胞肺癌患者的临床资料及其血浆药物浓度,评估赛沃替尼治疗的疗效和安全性,分析药物浓度与疗效及不良反应的相关性。随访患者的无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS),采用Kaplan-Meier法计算中位PFS和OS。结果:16例患者中男性9例(56.3%),年龄范围51~84岁。肺癌病理类型包括:腺癌11例,肉瘤样癌5例,鳞癌1例。赛沃替尼的客观缓解率为50.0%(8/16),疾病控制率达到87.5%(14/16)。评效达到部分缓解患者和未达到者相比,赛沃替尼的药物谷浓度分别为77.2 ng/mL和146.7 ng/mL(P=0.06)。治疗中出现过2级以上不良反应的患者和仅出现过1级不良反应者,其药物谷浓度分别为116.5 ng/mL和93.2 ng/mL(P=0.59)。所有患者的中位PFS为8.5个月,中位OS为14.1个月。结论:赛沃替尼治疗MET基因突变非小细胞肺癌的效果较好,不良反应可耐受。常规用药剂量下,赛沃替尼的血浆药物谷浓度与疗效可能存在一定负相关,但药物浓度与不良反应的程度无明显相关性。

中国蚊蝎蛉科三新种记述(长翅目)

本研究发现并描述采自中国贵州省和广东省的蚊蝎蛉属2新种和地蚊蝎蛉属1新种。其中观音山蚊蝎蛉Bittacus guanyinshanicus sp.nov.的主要鉴别特征是雄性载肛突上瓣基部膨大,中部缢缩,阳茎叶较长,侧面近纺锤形。长带蚊蝎蛉Bittacus longifasciatus sp.nov.翅面具1较大暗棕色带状斑。黑毛地蚊蝎蛉Terrobittacus nigrosetus sp.nov.具明显暗黑色背中带,雄性上生殖瓣腹缘基部密生黑色长刚毛。

Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice

Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.

Plant life form determines spatiotemporal variability and climate response of plant seed rain in subtropical forests

Spatiotemporal variation of seed rain reflects the response of plants in terms of their reproductive strategy to environmental gradients.In this study,we collected seeds from four sites in the Dalaoling Nature Reserve,Hubei Province,China,between 2011 and 2014,measured seed output and seed mass as seed rain traits,and compared their interannual and elevational variation.Then,we ran phylogenetic generalized mixed linear models(PGLMMs) to explore the effects of temperature and precipitation as well as interspecific differences on seed rain,and fitted the best regression models for seed rain vs.weather of canopy and understory species.The results showed no correlation between values of seed output and seed mass.However,the variation of the two traits showed significantly positive correlation.Seed output of canopy species generally decreased with increasing elevation,and showed significant interannual difference;however,seed output of understory species and seed mass for both canopy and understory species did not show consistency tends along elevational or in interannual variation.Seed output was significantly affected by temperature and precipitation,while seed mass mainly varied due to interspecific differences.Weather explained more the variation of the seed output of canopy species than that of understory species,with R^(2) values of 43.0%and 29.9%,respectively.These results suggested that canopy plants contributed more to the reproductive dynamics of the whole communities,and the canopy's buffer effect on the underground weakened the response of understory plants to weather variation in terms of their reproductive strategy.

Chemical modification of barite for improving the performance of weighting materials for water-based drilling fluids

With increasing drilling depth and large dosage of weighting materials,drilling fluids with high solid content are characterized by poor stability,high viscosity,large water loss,and thick mud cake,easier leading to reservoir damage and wellbore instability.In this paper,micronized barite(MB)was modified(mMB)by grafting with hydrophilic polymer onto the surface through the free radical polymerization to displace conventional API barite partly.The suspension stability of water-based drilling fluids(WBDFs)weighted with API barite:mMB=2:1 in 600 g was significantly enhanced compared with that with API barite/WBDFs,exhibiting the static sag factor within 0.54 and the whole stability index of 2.The viscosity and yield point reached the minimum,with a reduction of more than 40%compared with API barite only at the same density.Through multi-stage filling and dense accumulation of weighting materials and clays,filtration loss was decreased,mud cake quality was improved,and simultaneously it had great reservoir protection performance,and the permeability recovery rate reached 87%.In addition,it also effectively improved the lubricity of WBDFs.The sticking coefficient of mud cake was reduced by 53.4%,and the friction coefficient was 0.2603.Therefore,mMB can serve as a versatile additive to control the density,rheology,filtration,and stability of WBDFs weighted with API barite,thus regulating comprehensive performance and achieving reservoir protection capacity.This work opened up a new path for the productive drilling of extremely deep and intricate wells by providing an efficient method for managing the performance of high-density WBDFs.

Hyperspectral remote sensing identification of marine oil spills and emulsions using feature bands and double-branch dual-attention mechanism network

The accurate identification of marine oil spills and their emulsions is of great significance for emergency response to oil spill pollution.The selection of characteristic bands with strong separability helps to realize the rapid calculation of data on aircraft or in orbit,which will improve the timeliness of oil spill emergency monitoring.At the same time,the combination of spectral and spatial features can improve the accuracy of oil spill monitoring.Two ground-based experiments were designed to collect measured airborne hyperspectral data of crude oil and its emulsions,for which the multiscale superpixel level group clustering framework(MSGCF)was used to select spectral feature bands with strong separability.In addition,the double-branch dual-attention(DBDA)model was applied to identify crude oil and its emulsions.Compared with the recognition results based on original hyperspectral images,using the feature bands determined by MSGCF improved the recognition accuracy,and greatly shortened the running time.Moreover,the characteristic bands for quantifying the volume concentration of water-in-oil emulsions were determined,and a quantitative inversion model was constructed and applied to the AVIRIS image of the deepwater horizon oil spill event in 2010.This study verified the effectiveness of feature bands in identifying oil spill pollution types and quantifying concentration,laying foundation for rapid identification and quantification of marine oil spills and their emulsions on aircraft or in orbit.

Calcium carbonate promotes the formation and stability of soil macroaggregates in mining areas of China

We studied changes in the concentrations of aggregate-cementing agents after different reclamation times and with different fertilization regimes,as well as the formation mechanism of aggregates in reclaimed soil,to provide a theoretical basis for rapid reclamation of soil fertility in the subsidence area of coal mines in Shanxi Province,China.In this study,soil samples of 0–20 cm depth were collected from four fertilization treatments of a longterm experiment started in 2008:no fertilizer (CK),inorganic fertilizer (NPK),chicken manure compost (M),and50%inorganic fertilizer plus 50%chicken manure compost (MNPK).The concentrations of cementing agents and changes in soil aggregate size distribution and stability were analysed.The results showed that the formation of>2 mm aggregates,the aggregate mean weight diameter (MWD),and the proportion of>0.25 mm water-stable aggregates (WR_(0.25)) increased significantly after 6 and 11 years of reclamation.The concentration of organic cementing agents tended to increase with reclamation time,whereas free iron oxide (Fed) and free aluminium oxide(Ald) concentrations initially increased but then decreased.In general,the MNPK treatment signi?cantly increased the concentrations of organic cementing agents and CaCO_(3),and CaCO_(3) increased by 60.4%at 11 years after reclamation.Additionally,CaCO_(3) had the greatest effect on the stability of aggregates,promoting the formation of>0.25 mm aggregates and accounting for 54.4%of the variance in the proportion and stability of the aggregates.It was concluded that long-term reclamation is bene?cial for improving soil structure.The MNPK treatment was the most effective measure for increasing maize grain yield and concentration of organic cementing agents and CaCO_(3).

Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.

Diagenetic evolution and reservoir quality of the Oligocene sandstones in the Baiyun Sag, Pearl River Mouth Basin, South China Sea

The Oligocene Zhuhai sandstones are significant reservoirs for hydrocarbons in the Baiyun Sag, South China Sea.For effective appraisal, exploration and exploitation of such a deep-water hydrocarbon sandstone, samples of five wells from depths of 850 m to 3 000 m were studied. A series of comprehensive petrographic and geochemical analyses were performed to unravel the diagenetic features and their impact on the reservoir quality.Petrographically, the sandstones are dominated by feldspathic litharenites and lithic arenites with fine to medium grain sizes and moderate to good sorting. The reservoir quality varies greatly with a range of porosity from 0.2% to 36.1% and permeability from 0.016 ×10~(–3) μm~2 to 4 301 ×10~(–3) μm~2, which is attributed to complex diagenetic evolution related to sedimentary facies;these include compaction, cementation of calcite, dolomite, siderite and framboidal pyrite in eogenetic stage;further compaction, feldspar dissolution, precipitation of ferrocalcite and ankerite, quartz cements, formation of kaolinite and its illitization, precipitation of albite and nodular pyrite, as well as hydrocarbon charge in mesogenetic stage. The dissolution of feldspar and illitization of kaolinite provide internal sources for the precipitation of quartz cement, while carbonate cements are derived from external sources related to interbedded mudstones and deep fluid. Compaction is the predominant factor in reducing the total porosity, followed by carbonate cementation that leads to strong heterogeneity. Feldspar dissolution and concomitant quartz and clay cementation barely changes the porosity but significantly reduces the permeability.The high-quality reservoirs can be concluded as medium-grained sandstones lying in the central parts of thick underwater distributary channel sandbodies(>2 m) with a high content of detrital quartz but low cement.

Foodborne toxin Aflatoxin B_(1)induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.

Optimized nitrogen application for maximizing yield and minimizing nitrogen loss in film mulching spring maize production on the Loess Plateau,China

Excessive use of N fertilizers(driven by high-yield goals)and its consequent environmental problems are becoming increasingly acute in agricultural systems.A 2-year field experiment was conducted to investigate the effects of three N application methods(application of solid granular urea once(OF)or twice(TF),application of solid granular urea mixed with controlled-release urea once(MF),and six N rates(0,60,120,180,240,and 300 kg N ha^(-1))on maize yield,economic benefits,N use efficiency,and soil N balance in the maize(Zea mays L.)film mulching system on the Loess Plateau,China.The grain yield and economic return of maize were significantly affected by the N rate and application method.Compared with the OF treatment,the MF treatment not only increased the maize yield(increased by 9.0-16.7%)but also improved the economic return(increased by 10.9-25.8%).The agronomic N use efficiency(NAE),N partial factor productivity(NPFP)and recovery N efficiency(NRE)were significantly improved by 19.3-66.7,9.0-16.7 and 40.2-71.5%,respectively,compared with the OF treatment.The economic optimal N rate(EONR)of the OF,TF,and MF was 145.6,147.2,and 144.9 kg ha^(-1) in 2019,and 206.4,186.4,and 146.0 kg ha^(-1) in 2020,respectively.The apparent soil N loss at EONR of the OF,TF,and MF were 97.1-100.5,78.5-79.3,and 50.5-68.1 kg ha^(-1),respectively.These results support MF as a one-time N application method for delivering high yields and economic benefits,with low N input requirements within film mulching spring maize system on the Loess Plateau.

Simulation of deuterium pellet ablation and deposition in the EAST tokamak with HPI2 code

Pellet injection is a primary method for fueling the plasma in magnetic confinement devices.For that goal the knowledges of pellet ablation and deposition profiles are critical.In the present study,the pellet fueling code HPI2 was used to predict the ablation and deposition profiles of deuterium pellets injected into a typical H-mode discharge on the EAST tokamak.Pellet ablation and deposition profiles were evaluated for various pellet injection locations,with the aim at optimizing the pellet injection to obtain a deep fueling depth.In this study,we investigate the effect of the injection angle on the deposition depth of the pellet at different velocities and sizes.The ablation and deposition of the injected pellet are mainly studied at each injection position for three different injection angles:0°,45°,and 60°.The pellet injection on the high field side(HFS)can achieve a more ideal deposition depth than on the low field side(LFS).Among these angles,horizontal injection on the middle plane is relatively better on either the HFS or the LFS.When the injection location is 0.468 m below the middle plane on the HFS or 0.40 m above the middle plane of the LFS,it can achieve a similar deposition depth to the one of its corresponding side.When the pre-cooling effect is taken into account,the deposition depth is predicted to increase only slightly when the pellet is launched from the HFS.The findings of this study will serve as a reference for the update of pellet injection systems for the EAST tokamak.

Extending microwave-frequency electric-field detection through single transmission peak method

The strength of microwave(MW)electric field can be observed with high precision by using the standard electromagnetically induced transparency and Aulter–Towns(EIT-AT)technique,when its frequency is resonant or nearly-resonant with the Rydberg transition frequency.As the detuning of MW field increases,one of the transmission peaks(single peak)is easier to measure due to its increased amplitude.It can be found that the central symmetry point of the two transmission peaks f_(1/2)is only related to the detuning of MW field△_(MW)and central symmetry point f_(0)of resonant MW field,satisfying the relation f_(1/2)=△_(MW)/2+f_(0).Thus,we demonstrate a single transmission peak method that the MW E-field can be determined by interval between the position of single peak and f_(1/2).We use this method to measure continuous frequencies in a band from-200 MHz to 200 MHz of the MW field.The experimental results and theoretical analysis are presented to describe the effectiveness of this method.For 50 MHz<△_(MW)<200 MHz,this method solves the problem that the AT splitting cannot be measured by using the standard EIT-AT techniques or multiple atomic-level Rydberg atom schemes.

Enhanced energy density and fast-charging ability via directional particle configuration

The limited energy density of lithium-ion capacitors poses a significant obstacle to their widespread application,primarily stemming from the inability of the electrodes to simultaneously fulfill both high energy density and rapid charging requirements.Experimental data demonstrate that a directional particle configuration can enhance charging speed while maintaining high-capacity density,but it is rarely discussed.Here,we have developed a particle-level electrochemical model capable of reconstructing an electrode with a directional particle configuration.By employing this method,an investigation was conducted to explore how the spatial morphology characteristics of particle configuration impact the energy storage characteristics of electrodes.Results demonstrate that rational particle configuration can effectively enhance the transport of lithium ions and create additional space for lithium-ion storage.With the same particle size distribution,the best electrode can increase the discharge capacity by up to132.4% and increase the charging SOC by 11.3% compared to the ordinary electrode under the condition of 6 C.These findings provide a further understanding of the energy storage mechanism inside the anisotropic particle distribution electrode,which is important for developing high-performance lithium-ion capacitors.

Targeted multi-agent communication algorithm based on state control

As an important mechanism in multi-agent interaction,communication can make agents form complex team relationships rather than constitute a simple set of multiple independent agents.However,the existing communication schemes can bring much timing redundancy and irrelevant messages,which seriously affects their practical application.To solve this problem,this paper proposes a targeted multiagent communication algorithm based on state control(SCTC).The SCTC uses a gating mechanism based on state control to reduce the timing redundancy of communication between agents and determines the interaction relationship between agents and the importance weight of a communication message through a series connection of hard-and self-attention mechanisms,realizing targeted communication message processing.In addition,by minimizing the difference between the fusion message generated from a real communication message of each agent and a fusion message generated from the buffered message,the correctness of the final action choice of the agent is ensured.Our evaluation using a challenging set of Star Craft II benchmarks indicates that the SCTC can significantly improve the learning performance and reduce the communication overhead between agents,thus ensuring better cooperation between agents.

Diagnosis and treatment experience of atypical hepatic cystic echinococcosis type 1 at a tertiary center in China

BACKGROUND Some hydatid cysts of cystic echinococcosis type 1(CE1)lack well-defined cyst walls or distinctive endocysts,making them difficult to differentiate from simple hepatic cysts.AIM To investigate the diagnostic methods for atypical hepatic CE1 and the clinical efficacy of laparoscopic surgeries.METHODS The clinical data of 93 patients who had a history of visiting endemic areas of CE and were diagnosed with cystic liver lesions for the first time at the People's Hospital of Xinjiang Uygur Autonomous Region(China)from January 2018 to September 2023 were retrospectively analyzed.Clinical diagnoses were made based on findings from serum immunoglobulin tests for echinococcosis,routine abdominal ultrasound,high-frequency ultrasound,abdominal computed tomography(CT)scan,and laparoscopy.Subsequent to the treatments,these patients underwent reexaminations at the outpatient clinic until October 2023.The evaluations included the diagnostic precision of diverse examinations,the efficacy of surgical approaches,and the incidence of CE recurrence.RESULTS All 93 patients were diagnosed with simple hepatic cysts by conventional abdominal ultrasound and abdominal CT scan.Among them,16 patients were preoperatively diagnosed with atypical CE1,and 77 were diagnosed with simple hepatic cysts by high-frequency ultrasound.All the 16 patients preoperatively diagnosed with atypical CE1 underwent laparoscopy,of whom 14 patients were intraoperatively confirmed to have CE1,which was consistent with the postoperative pathological diagnosis,one patient was diagnosed with a mesothelial cyst of the liver,and the other was diagnosed with a hepatic cyst combined with local infection.Among the 77 patients who were preoperatively diagnosed with simple hepatic cysts,4 received aspiration sclerotherapy of hepatic cysts,and 19 received laparoscopic fenestration.These patients were intraoperatively diagnosed with simple hepatic cysts.During the followup period,none of the 14 patients with CE1 experienced recurrence or implantation of hydatid scolices.One of the 77 patients was finally confirmed to have CE complicated with implantation to the right intercostal space.CONCLUSION Abdominal high-frequency ultrasound can detect CE1 hydatid cysts.The laparoscopic technique serves as a more effective diagnostic and therapeutic tool for CE.

A 16-bit 18-MSPS flash-assisted SAR ADC with hybrid synchronous and asynchronous control logic

This paper presents a 16-bit,18-MSPS(million samples per second)flash-assisted successive-approximation-register(SAR)analog-to-digital converter(ADC)utilizing hybrid synchronous and asynchronous(HYSAS)timing control logic based on an on-chip delay-locked loop(DLL).The HYSAS scheme can provide a longer settling time for the capacitive digital-to-analog converter(CDAC)than the synchronous and asynchronous SAR ADC.Therefore,the issue of incomplete settling or ringing in the DAC voltage for cases of either on-chip or off-chip reference voltage can be solved to a large extent.In addition,the fore-ground calibration of the CDAC’s mismatch is performed with a finite-impulse-response bandpass filter(FIR-BPF)based least-mean-square(LMS)algorithm in an off-chip FPGA(field programmable gate array).Fabricated in 40-nm CMOS process,the proto-type ADC achieves 94.02-dB spurious-free dynamic range(SFDR),and 75.98-dB signal-to-noise-and-distortion ratio(SNDR)for a 2.88-MHz input under 18-MSPS sampling rate.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Monitoring seismicity in the southern Sichuan Basin using a machine learning workflow

Monitoring seismicity in real time provides significant benefits for timely earthquake warning and analyses.In this study,we propose an automatic workflow based on machine learning(ML)to monitor seismicity in the southern Sichuan Basin of China.This workflow includes coherent event detection,phase picking,and earthquake location using three-component data from a seismic network.By combining Phase Net,we develop an ML-based earthquake location model called Phase Loc,to conduct real-time monitoring of the local seismicity.The approach allows us to use synthetic samples covering the entire study area to train Phase Loc,addressing the problems of insufficient data samples,imbalanced data distribution,and unreliable labels when training with observed data.We apply the trained model to observed data recorded in the southern Sichuan Basin,China,between September 2018 and March 2019.The results show that the average differences in latitude,longitude,and depth are 5.7 km,6.1 km,and 2 km,respectively,compared to the reference catalog.Phase Loc combines all available phase information to make fast and reliable predictions,even if only a few phases are detected and picked.The proposed workflow may help real-time seismic monitoring in other regions as well.

面向无人机雷达通信一体化系统的轨迹与资源联合优化

针对灵活高效的区域探测和数据回传任务,研究了时分复用模式下无人机雷达通信一体化系统(IRCS)的时间资源分配、功率资源分配和无人机轨迹的联合优化问题,以达到最大化系统雷达探测链路和通信传输链路的加权总容量的目的。为解决该非凸优化问题,采用了块坐标下降(BCD)算法及逐次凸逼近(SCP)技术,迭代优化时间资源分配、功率资源分配和无人机轨迹。仿真结果表明,所提方案可以得到收敛解,并且可以有效提升系统容量。