Effect of Dopant Concentration on Luminescence Properties of KCaPO4:Sm

KCaPO4 doped with different concentrations of Sm was synthesised by a high-temperature solid-state method, and the crystal structure, morphology, TL and OSL properties of Sm-doped KCaPO4 were systematically investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), thermoluminescence (TL), and optically stimulated luminescence (OSL) techniques. The results show that 0.3 mol% Sm-doped KCaPO4 annealed at 1073 K for 1 h has the highest TL intensity, and thus is expected to be a candidate material for thermoluminescence dosimetry applications.

一款紧致化妆品的功效评价方法研究

通过对以棕榈酰五肽-4为主要功能成分化妆品的功效进行评价,研究建立人体紧致功效评价方法体系。筛选31名20~50岁女性受试者,分别在使用产品0周、4周和8周,通过客观测试数据、图像方法及受试者自我评估方法对皮肤各项指标进行评估,采集受试者脸颊、眼角部位的皮肤弹性、皮肤真皮密度等参数,以及TPEF图像及SHG图像,并进行比较分析。结果显示,8周后皮肤弹性、真皮密度(P<0.001)及真-表皮链接指数(DEJI)(P<0.01)有显著变化,与受试者自我评分结果一致,表明方法之间具有相关性。该研究方法可为建立化妆品紧致功效评价方法体系提供技术支持。

急性耳鸣临床特征和严重程度的影响因素分析

目的分析急性耳鸣患者的临床特征和影响耳鸣严重程度的相关因素。方法回顾性分析319例急性耳鸣患者的基本资料、耳鸣发生部位、病程、耳鸣声学特征、听力下降、合并头痛、头晕、耳闷、耳痛等症状及伴发临床疾病等;均完成耳鸣障碍量表(tinnitus handicap inventory,THI)、广泛性焦虑障碍量表(generalized anxiety disorder,GAD-7)、抑郁筛查量表(patient health questionnaire,PHQ-9)、匹兹堡睡眠质量指数量表(Pittsburgh sleep scale,PSQI)、听觉过敏调查表(hyperacusis questionnaire,HQ)、D型人格量表(type D personality scale-14,DS-14)等评估,THI评分≤36分判定为轻度耳鸣组,38~56分为中度耳鸣组,58~100分为重度-极重度耳鸣组。以THI分组作为应变量,上述各因素作为自变量,采用有序多分类logistic回归分析各因素与急性耳鸣严重程度的相关性。结果319例急性耳鸣患者中轻度耳鸣组158例(49.5%),中度耳鸣组72例(22.6%),重-极重度耳鸣组89例(27.9%)。有序多分类logistic回归分析发现听觉过敏(OR=3.921)、焦虑(OR=2.495)、抑郁(OR=2.921)、D型人格(OR=0.349)与急性耳鸣严重程度有关(P<0.05),伴听觉过敏、焦虑、抑郁、D型人格者耳鸣严重程度更重。结论听觉过敏、焦虑、抑郁、D型人格可能是影响急性耳鸣严重程度的因素,在治疗急性耳鸣患者时应予高度关注。

多光子成像技术及其在化妆品评估中的应用

多光子成像技术是一种观察人体皮肤组织结构的光学成像方法,其原理是利用不同波长的近红外激光使皮肤组织中特定的内源性或外源性荧光物质发出不同的荧光信号,从而观测、区分皮肤不同层的特定组织结构。近年来,该方法开始逐步应用于化妆品的评估中,如评估化妆品紧致抗皱、祛斑美白、透皮吸收的效果等。多光子成像技术能够通过监测皮肤形态或代谢的变化评估化妆品紧致抗皱的作用、定量黑色素分布和含量评估化妆品祛斑美白成分的功效性或判断特定皮肤的类型、可视化化妆品成分透皮吸收的过程评估其功效性或安全性。该方法获得的客观、可视化图像可以为化妆品评估提供定量的数据结果,在皮肤成像领域有着广阔的应用前景,本文综述了这种在体、无创、精准的三维成像方法在化妆品评估中的应用和进展。

Anomalous{1012}tensile twinning and subsequent detwinning in a friction stir processed carbon fiber-reinforced Mg composite

1.Main text Owing to their low density and high specific strength,magnesium alloys and magnesium-based composites have great potential as structure metal materials in applications where lightweight matters[1–4].Deformation twins[5],especially the{1012}tension twins(also called tensile or extension twins)with a low critical resolved shear stress(CRSS)[6],are commonly observed in Mg alloys.They can provide the much-needed deformation along the c-axis in their hcp structure resulting from the very few easily activated slip systems in this crystal structure[7].The tensile twinning activation usually follows the macroscopic Schmid factor law[2],i.e.,the twin variant with the highest Schmid factor occurs,and it only appears when its Schmid factor is positive.

Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage

BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.

中文版听觉过敏量表的信度和效度评价

目的对中文版听觉过敏量表的信度和效度进行评价,以评估其在中国人群中应用的适用性。方法对2017年6月至2017年12月就诊于西京医院耳鼻咽喉科门诊的患者进行调查,共发放300份问卷,所有被调查者需要完成基本情况调查、纯音测听和中文版听觉过敏量表的填写,对中文版听觉过敏量表的信度和效度进行评价。结果收回有效问卷293份,293例受访者中,合并耳鸣243例(82.93%)。问卷调查示,主观上存在听觉过敏181例(61.77%);量表评估诊断为听觉过敏174例(59.39%),两种方法结果一致性检验的Kappa值为0.81(P<0.001)。信度分析结果显示,该量表的整体Cronbach'sα系数为0.93,各维度Cronbach'sα系数均>0.60,分半信度系数为0.86,各维度分半信度系数均>0.60;效度分析中,探索性因子分析结果显示,25个条目可提取4个因子:功能部分、社交部分、情绪部分和声敏感度部分,4个因子的特征值>1,累计方差贡献率为59.42%,根据旋转后成分矩阵可知,25个条目均可分布到4个维度中,每个条目的因子载荷>0.40;效度分析中,验证性因子分析结果显示,模型拟合参数卡方值与自由度之比(χ^(2)/df)=1.98,拟优合度指数(GFI)=0.91,调整的拟优合度指数(AGFI)=0.83,比较拟合指数(CFI)=0.92,塔克-刘易斯指数(TLI)=0.89,近似误差均方根(RMSEA)=0.08,各条目标准化因子载荷>0.40。结论该中文版听觉过敏量表具有良好的信度和效度,可在中国人群中应用。

Bowel preparation protocol for hospitalized patients ages 50 years or older:A randomized controlled trial

BACKGROUND The incidence and mortality rate of colorectal cancer progressively increase with age and become particularly prominent after the age of 50 years.Therefore,the population that is≥50 years in age requires long-term and regular colonoscopies.Uncomfortable bowel preparation is the main reason preventing patients from undergoing regular colonoscopies.The standard bowel preparation regimen of 4-L polyethylene glycol(PEG)is effective but poorly tolerated.AIM To investigate an effective and comfortable bowel preparation regimen for hospitalized patients≥50 years in age.METHODS Patients were randomly assigned to group 1(2-L PEG+30-mL lactulose+a lowresidue diet)or group 2(4-L PEG).Adequate bowel preparation was defined as a Boston bowel preparation scale(BBPS)score of≥6,with a score of≥2 for each segment.Non-inferiority was prespecified with a margin of 10%.Additionally,the degree of comfort was assessed based on the comfort questionnaire.RESULTS The proportion of patients with a BBPS score of≥6 in group 1 was not significantly different from that in group 2,as demonstrated by intention-to-treat(91.2%vs 91.0%,P=0.953)and per-protocol(91.8%vs 91.0%,P=0.802)analyses.Furthermore,in patients≥75 years in age,the proportion of BBPS scores of≥6 in group 1 was not significantly different from that in group 2(90.9%vs 97.0%,P=0.716).Group 1 had higher comfort scores(8.85±1.162 vs 7.59±1.735,P<0.001),longer sleep duration(6.86±1.204 h vs 5.80±1.730 h,P<0.001),and fewer awakenings(1.42±1.183 vs 2.04±1.835,P=0.026)than group 2.CONCLUSION For hospitalized patients≥50 years in age,the bowel preparation regimen comprising 2-L PEG+30-mL lactulose+a low-residue diet produced a cleanse that was as effective as the 4-L PEG regimen and even provided better comfort.

皖西大别山区小麦生产现状及发展对策

本文基于皖西大别山区小麦生产现状,总结分析了该区域小麦生产有待进一步提升的环节,包括优质品种、机械化程度、绿色丰产高效栽培技术体系以及小麦品牌影响力等方面。结合这些环节提出加强品种自主选育、提高机械化作业效率、推广丰产高效栽培技术体系和发展绿色农业品牌等对策,为研究区小麦产业的可持续、高质量发展提供参考。

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases.However,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in vivo.Therefore,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke.Matrix metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ischemia.Herein,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel PA-TIMP-QK.PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro.The results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor function.These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

A new species of Discostella guiyangensis sp.nov.(Bacillariophyta,Stephanodiscales)from Guiyang,China:morphology and phylogeny

We describe a new species of Discostella from Guiyang based on light and scanning electron microscopic observations,as well as molecular analysis.This species is morphologically distinguished from other species by a relatively smooth and slightly recessed central area with marginal striae of unequal lengths forked near the margin.Marginal fultoportulae and a single rimoportula are situated between every two costae or on the costae.Both morphological characters and the concatenated data of rbc L and SSU rDNA indicate that Discostella guiyangensis is a unique and new species.According to divergence time estimation analysis,Discostella guiyangensis is the oldest species among the Discostella species sequenced currently.In addition,we complement molecular data of Discostella asterocostata and Discostella stelligera.

Incombustible solid polymer electrolytes:A critical review and perspective

Since the advent of the solid-state batteries,employing solid polymer electrolytes(SPEs)to replace routine flammable liquid electrolytes is regarded to be one of the most promising solutions in pursing highenergy-density battery systems.SPEs with superior thermal stability,good processability,and high mechanical modulus obtain increasing attentions.However,SPE-based batteries are not impenetrable due to their decomposition and combustibility under extreme conditions.Researchers believe incorporating appropriate flame-retardant additives/solvents/fragments into SPEs can intrinsically reduce their flammability to solve the battery safety issues.In this review,the recent research progress of incombustible SPEs,with special emphasis on flame-retardant structural design,is summarized.Specifically,a brief introduction of flame-retardant mechanism,evaluation index for safety of SPEs,and a detailed overview of the latest advances on diverse-types SPEs in various battery systems are highlighted.The deep insight into thermal ru naway process,the free-standing incombustible GPEs,and the ratio nal design of pouch cell structures may be the main directions to motivate revolutionary next-generation for safety batteries.

Hollow Metal-Organic Framework/MXene/Nanocellulose Composite Films for Giga/Terahertz Electromagnetic Shielding and Photothermal Conversion

With the continuous advancement of communication technology,the escalating demand for electromagnetic shielding interference(EMI)materials with multifunctional and wideband EMI performance has become urgent.Controlling the electrical and magnetic components and designing the EMI material structure have attracted extensive interest,but remain a huge challenge.Herein,we reported the alternating electromagnetic structure composite films composed of hollow metal-organic frameworks/layered MXene/nanocellulose(HMN)by alternating vacuum-assisted filtration process.The HMN composite films exhibit excellent EMI shielding effectiveness performance in the GHz frequency(66.8 dB at Kaband)and THz frequency(114.6 dB at 0.1-4.0 THz).Besides,the HMN composite films also exhibit a high reflection loss of 39.7 dB at 0.7 THz with an effective absorption bandwidth up to 2.1 THz.Moreover,HMN composite films show remarkable photothermal conversion performance,which can reach 104.6℃under 2.0 Sun and 235.4℃under 0.8 W cm^(−2),respectively.The unique micro-and macrostructural design structures will absorb more incident electromagnetic waves via interfacial polarization/multiple scattering and produce more heat energy via the local surface plasmon resonance effect.These features make the HMN composite film a promising candidate for advanced EMI devices for future 6G communication and the protection of electronic equipment in cold environments.

Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential

Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke.The contact-kinin pathway,initiated by plasma kallikrein(PK)and activated factor XII(FXIIa),functions bidirectionally with the coagulation and inflammation cascades,providing a novel target for therapeutic drug development in ischemic stroke.In this study,we identified a bat-derived oligopeptide from Myotis myotis(Borkhausen,1797),designated LE6(Leu-Ser-Glu-Glu-Pro-Glu,702 Da),with considerable potential in stroke therapy due to its effects on the contact kinin pathway.Notably,LE6 demonstrated significant inhibitory effects on PK and FXIIa,with inhibition constants of 43.97μmol/L and 6.37μmol/L,respectively.In vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time.In murine models,LE6 effectively inhibited carrageenan-induced mouse tail thrombosis,FeCl3-induced carotid artery thrombosis,and photochemically induced intracerebral thrombosis.Furthermore,LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models.Notably,the low toxicity,hemolytic activity,and bleeding risk of LE6,along with its synthetic simplicity,underscore its clinical applicability.In conclusion,as an inhibitor of FXIIa and PK,LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.

Interpreting Larix principis-rupprechtii radial growth in northern China based on the Vaganov-Shashkin model

Changes in annual radial growth is an important indication of climate change. Dendroclimatology studies in northern China have focused on linear statistical analysis,but lacking studies based on the process of ring formation to clarify the radial growth of trees. Tree-ring width standard chronology(STD) was established using samples of Larix principis-rupprechtii collected at 2303 m altitude on Luya Mountain. Using the Vaganov-Shashkin(VS) model to simulate growth and development, the internal physiological mechanism of radial growth is identified. It was concluded that:(1) the growing season of L. principis-rupprechtii was May to September;(2) soil moisture was a significant factor in the early and late growing seasons, and temperature was the dominant factor in its main growth period;and(3) formation of narrow ring widths was closely related to drought stress, the development of wide ring widths will be restricted by increasing future temperatures. The VS model is applicable for radial growth simulation of subalpine coniferous forests and for guiding the cultivation of local tree species in the future.

Junshanyinzhen tea extract prevents obesity by regulating gut microbiota and metabolic endotoxemia in high-fat diet fed rats

Obesity is associated with gut dysbiosis and metabolic endotoxin.Junshanyinzhen tea extract(JSTE)reduced fat accumulation and body weight in obese mice.However,the effects and mechanism of JSTE in preventing obesity were unclear.Therefore,we used different doses of JSTE(75,150 and 300 mg/(kg·day))to evaluate the effect on high-fat diet(HFD)-induced rats under 8 weeks of intervention.Here,our results showed that JSTE could significantly reduce body weight gain,blood lipid levels and fat accumulation,improve fatty damage in liver tissue(P<0.05).In addition,JSTE increased the expression of intestinal tight junction proteins(P<0.05),relieved metabolic endotoxemia(P<0.05)and chronic low-grade inflammation in HFD rats.Sequencing of fecal samples showed that JSTE could effectively reverse the microbial diversity and the ratio of Firmicutes to Bacteroidetes to normal levels in HFD-fed rats.Desulfovibrioceae and Erysipelotrichaceae,which are positively related to obesity,were decreased by JSTE intervention(P<0.05).while Bifidobacteriaceae,Bacteroidaceae,Akkermansia,and Clostridium,which are negatively related to obesity,were increased.Together,these results suggested that JSTE might effectively prevent obesity by modulating gut microbiota dysbiosis,intestinal barrier dysfunction,metabolic endotoxemia and chronic low-grade infl ammation in HFD-induced rats.

Morphology and phylogenetic placement of Mallomonas vietnamica(Synurales,Chrysophyceae)from China

The newly described chrysophyte,Mallomonas vietnamica,is reported for the first time in China from specimens collected in Guizhou Province,SW China.The morphological characteristics were studied using light and scanning electron microscopy.The species was described based on morphological characteristics,including cell size,scale size,dome,V-rib,and bristles.Subsequently,molecular sequencing of M.vietnamica was conducted and a phylogenetic tree was constructed based on concatenated SSU,LSU,and rbc L sequences.The phylogenetic tree led us to suggest raising a new section named Uncatusipedae for this species.This study provides new molecular data from the genus Mallomonas and enriches our understanding of the species diversity and geographical distribution of the genus Mallomonas in China.

^(68)Ga-FAPI-04 PET/CT对胰腺癌的诊断价值及对肿瘤分期的影响

目的:探讨^(68)Ga标记的成纤维细胞激活蛋白抑制剂(fibroblast activation protein inhibitor,FAPI)-04正电子发射断层显像/X线计算机体层成像(positron emission tomography and computed tomography,PET/CT)对初诊胰腺癌的诊断价值及对肿瘤分期的影响。方法:回顾性收集2021年8月至2023年8月于重庆大学附属肿瘤医院就诊的134例因怀疑胰腺占位的患者临床及影像资料。分析^(68)Ga-FAPI-04 PET/CT对胰腺癌原发灶及转移灶的诊断价值;并与传统CT比较,分析^(68)Ga-FAPI-04 PET/CT对胰腺癌肿瘤分期的影响。结果:共计纳入134例患者,其中胰腺癌127例,良性病变7例。^(68)Ga-FAPI-04 PET/CT对胰腺癌原发灶、区域淋巴结及远处转移灶检出率分别为100%(127/127)、68.63%(35/51),95.35%(41/43)。胰腺癌中位最大标准化摄取值(standard uptake value maxium,SUVmax)为14.92,高于胰腺良性病变中位SUVmax(6.1)(Z=−2.921,P=0.003)。与传统CT比较,^(68)Ga-FAPI PET/CT检查后共有32.28%(41/127)胰腺癌患者TNM分期发生改变。3.94%(5/127)患者改变了治疗方案。结论:^(68)Ga-FAPI-04 PET/CT对胰腺癌原发灶诊断具有较高的敏感性,较传统CT可发现更多远处转移病灶,改善患者M分期,有助于全面评估全身肿瘤负荷、制定治疗计划。

Prediction of the Pore-Pressure Built-Up and Temperature of Fire-Loaded Concrete with Pix2Pix

Concrete subjected to fire loads is susceptible to explosive spalling, which can lead to the exposure of reinforcingsteel bars to the fire, substantially jeopardizing the structural safety and stability. The spalling of fire-loaded concreteis closely related to the evolution of pore pressure and temperature. Conventional analytical methods involve theresolution of complex, strongly coupled multifield equations, necessitating significant computational efforts. Torapidly and accurately obtain the distributions of pore-pressure and temperature, the Pix2Pix model is adoptedin this work, which is celebrated for its capabilities in image generation. The open-source dataset used hereinfeatures RGB images we generated using a sophisticated coupled model, while the grayscale images encapsulate the15 principal variables influencing spalling. After conducting a series of tests with different layers configurations,activation functions and loss functions, the Pix2Pix model suitable for assessing the spalling risk of fire-loadedconcrete has been meticulously designed and trained. The applicability and reliability of the Pix2Pix model inconcrete parameter prediction are verified by comparing its outcomes with those derived fromthe strong couplingTHC model. Notably, for the practical engineering applications, our findings indicate that utilizing monochromeimages as the initial target for analysis yields more dependable results. This work not only offers valuable insightsfor civil engineers specializing in concrete structures but also establishes a robust methodological approach forresearchers seeking to create similar predictive models.

Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study

BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality rate.We aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and CAP.METHODS:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April 2020.Patients were allocated to the DM or non-DM group and paired with propensity score matching.Baseline characteristics and clinical outcomes up to 90 days were evaluated.The primary outcome was the 10-day mortality.Receiver operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical analysis.RESULTS:Among 152 enrolled patients,60 pairs were successfully matched.There was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml vs.median 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of 0.747.The cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,respectively.Multivariate Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with DM.CONCLUSION:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.