Single-cell analysis of tumor microenvironment and cell adhesion reveals that interleukin-1 beta promotes cancer cell proliferation in breast cancer

Background: Triple-negative breast cancer(TNBC), which is so called because of the lack of estrogen receptors(ER), progesterone receptors(PR), and human epidermal growth factor receptor 2(HER2) receptors on the cancer cells, accounts for 10%–15% of all breast cancers. The heterogeneity of the tumor microenvironment is high.However, the role of plasma cells controlling the tumor migration progression in TNBC is still not fully understood.Methods: We analyzed single-cell RNA sequencing data from five HER2 positive, 12ER positive/PR positive, and nine TNBC samples. The potential targets were validated by immunohistochemistry.Results: Plasma cells were enriched in TNBC samples, which was consistent with validation using data from The Cancer Genome Atlas. Cell communication analysis revealed that plasma cells interact with T cells through the intercellular adhesion molecule 2–integrin–aLb2 complex, and then release interleukin 1 beta(IL1B), as verified by immunohistochemistry, ultimately promoting tumor growth.Conclusion: Our results revealed the role of plasma cells in TNBC and identified IL1B as a new prognostic marker for TNBC.

Basic helix-loop-helix(bHLH)transcription factor MdbHLH3 negatively affects the storage performance of postharvest apple fruit

The storage period of fleshy fruits greatly affects their quality and selection,and is largely controlled by genetic factors.Therefore,it is imperative to elucidate how genetic factors affect fruit ripening and its storage.Here,we evaluated the postharvest storage properties of the basic helix-loop-helix(bHLH)transcription factor MdbHLH3-overexpressing transgenic Royal gala apple fruits.During storage,the contents of starch,malic acid,fructose,glucose,and sucrose in fruits of three MdbHLH3 transgenic lines were always higher than those of the wild-type(WT)control.Interestingly,the sugar-acid ratio also showed the same trend during fruit storage.Additionally,the fruit firmness decreased with increasing storage time,and the contents of cell wall components such as water-soluble pectin and cellulose in transgenic fruits were higher than those in control fruits,while the firmness of transgenic fruits was lower than that in WT control fruits.Though the ethylene release rate in both showed the same trend(firstly increasing,then decreasing,and finally peaking)in 90-day stored fruits,transgenic apples had higher ethylene levels than the WT control throughout storage.Furthermore,the activities of membrane peroxidase,antioxidant enzymes,and fruit ripening enzymes in all transgenic fruits were significantly higher than those in the WT control.Thus,our findings show how MdbHLH3 negatively regulates and reduces apple storage time.This may prove useful for not only developing biotechnological strategies,but also support traditional breeding programs,to help improve the storage time of fleshy fruits.

Effect of Fluid Electrical Property Changes on Surface Transverse Wave Sensors

A fluid sensor based on the surface transverse wave (STW) delay line on ST-cut quartz has been developed and tested in a large number of fluids with different viscosity and permittivity levels.Influence of fluid mechanical and electrical properties on the sensor's response has been determined and the sensor's performance has been compared with a bulk acoustic wave (BAW) viscosity sensor.The result shows that the viscosity sensitivity of the developed STW sensor represented by the signal to noise ratio is lower than that of a 5 MHz BAW sensor.Applications of the sensor in detecting the quality of industrial fluids are discussed.

Discussion on the Theoretical Basis of Banxia Xiexin Decoction in the Treatment of Insulin Resistance Obesity

Through reading Chinese ancient book Huangdi Nejing,and summarizing and analyzing related literature,the basic pathogenesis of obesity have been found to be the stomach preponderance and spleen weakness,and the imbalance of ascending and descending.Banxia Xiexin Decoction not only has the functions of relieving heat to inhibit stomach intake,supplementing deficiency to assist spleen transport,regulate the ascending and descending,but also has the effects of improving insulin resistance and regulating glucolipid metabolism.Therefore,it is suggested that Banxia Xiexin Decoction can be used in the treatment of insulin resistant obesity,which provides ideas and methods for its treatment.

Prediction of Online Consumers’Repeat Purchase Behavior via BERT-MLP Model

It is an effective means for merchants to carry out precision marketing and improve ROI by using historical user behavior data obtained from promotional activities in order to build a model to predict the repeat purchase behavior of users after promotional activities.Most of the existing prediction models are supervised learning,which does not work well with a small amount of labeled data.This paper proposes a BERT-MLP prediction model that uses“large-scale data unsupervised pre-training+small amount of labeled data fine-tuning.”The experimental results on Alibaba real dataset show that the accuracy of the BERT-MLP model is better than the baseline model.

Integrating Multiple Linear Regression and Infectious Disease Models for Predicting Information Dissemination in Social Networks

Social network is the mainstream medium of current information dissemination,and it is particularly important to accurately predict its propagation law.In this paper,we introduce a social network propagation model integrating multiple linear regression and infectious disease model.Firstly,we proposed the features that affect social network communication from three dimensions.Then,we predicted the node influence via multiple linear regression.Lastly,we used the node influence as the state transition of the infectious disease model to predict the trend of information dissemination in social networks.The experimental results on a real social network dataset showed that the prediction results of the model are consistent with the actual information dissemination trends.

Boosting external quantum efficiency of a WSe_(2) photodetector across visible and NIR spectra through harnessing plasmonic hot electrons

The layered two-dimensional material tungsten diselenide(WSe_(2))has triggered tremendous interests in the field of optoelectronic devices due to its exceptional carrier transport property.Nevertheless,the limited absorption of WSe_(2) in the near infrared(NIR)band poses a challenge for the application of WSe_(2) photodetectors in night vision,telecommunication,etc.Herein,the enhanced performance of the WSe_(2) photodetector is demonstrated through the incorporation of titanium nitride nanoparticles(TiN NPs),complemented by an atomically-thick Al_(2)O_(3) layer that aids in suppressing the dark current.It is demonstrated that TiN NPs can dramatically enhance the absorption of light in the proposed WSe_(2) photodetector in the NIR regime.This enhancement boosts photocurrent responses through the generation of plasmonic hot electrons,leading to external quantum efficiency(EQE)enhancement factors of 379.66%at 850 nm and 178.47%at 1550 nm.This work presents,for the first time,to our knowledge,that the WSe_(2) photodetector is capable of detecting broadband light spanning from ultraviolet to the telecommunication range,all achieved without the reliance on additional semiconductor materials.This achievement opens avenues for the advancement of cost-effective NIR photodetectors.

Lead-free perovskite Cs_(2)AgBiBr_(6)photodetector detecting NIR light driven by titanium nitride plasmonic hot holes

Lead-free perovskite Cs_(2)AgBiBr_(6)manifests great potential in developing high-performance,environmentally friendly,solution-processable photodetectors(PDs).However,due to the relatively large energy bandgap,the spectrum responses of Cs_(2)AgBiBr_(6)PDs are limited to the ultraviolet and visible region with wavelengths shorter than 560 nm.In this work,a broadband Cs_(2)AgBiBr_(6)PD covering the ultraviolet,visible,and near infrared(NIR)range is demonstrated by incorporating titanium nitride(TiN)nanoparticles that are prepared with the assistance of self-assembled polystyrene sphere array.In addition,an atomically thick Al2O3layer is introduced at the interface between the Cs_(2)AgBiBr_(6)film and TiN nanoparticles to alleviate the dark current deterioration caused by nanoparticle incorporation.As a result,beyond the spectrum range where Cs_(2)AgBiBr_(6)absorbs light,the external quantum efficiency(EQE)of the TiN nanoparticle incorporated Cs_(2)AgBiBr_(6)PD is enhanced significantly compared with that of the control,displaying enhancement factors as high as 2000 over a broadband NIR wavelength range.The demonstrated enhancement in EQE arises from the photocurrent contribution of plasmonic hot holes injected from TiN nanoparticles into Cs_(2)AgBiBr_(6).This work promotes the development of broadband solution-processable perovskite PDs,providing a promising strategy for realizing photodetection in the NIR region.

贝伐珠单抗治疗放射性脑坏死研究进展

放射性脑坏死是原发性或继发性脑肿瘤以及头颈部肿瘤放疗后的严重晚期、不可逆的并发症,尚无有效的治疗方法。近几年来,贝伐珠单抗越来越多地被用于放射性脑坏死的治疗,并确定有一定疗效,可以改善患者生存,但关于最佳治疗时机、方案等一直存在争议,缺乏基本共识,本文就这方面研究进展进行简要回顾。

FAM19A4 is a novel cytokine ligand of formyl peptide receptor I （FPR 1） and is able to promote the migration and phagocytosis of macrophages

FAM 19A4 is an abbreviation for family with sequence similarity 19 （chemokine （C-C motif）-Iike） member A4, which is a secretory protein expressed in low levels in normal tissues. The biological functions of FAM19A4 remain to be determined, and its potential receptor（s） is unclarified. In this study, we demonstrated that FAM 19A4 was a classical secretory protein and we verified for the first time that its mature protein is composed of 95 amino acids. We found that the expression of this novel cytokine was upregulated in lipopolysaccharide （LPS）-stimulated monocytes and macrophages and was typically in polarized M 1. FAM 19A4 shows chemotactic activities on macrophages and enhances the macrophage phagocytosis of zymosan both in vitro and in vivo with noticeable increases of the phosphorylation of protein kinase B （Akt）. FAM 19A4 can also increase the release of reactive oxygen species （ROS） upon zymosan stimulation. Furthermore, based on receptor internalization, radio ligand binding assays and receptor blockage, we demonstrated for the first time that FAM19A4 is a novel ligand of formyl peptide receptor 1 （FPR1）. The above data indicate that upon inflammatory stimulation, monocyte/macrophage-derived FAM 19A4 may play a crucial role in the migration and activation of macrophages during pathogenic infections.

PCC0208017,a novel small-molecule inhibitor of MARK3/MARK4,suppresses glioma progression in vitro and in vivo

Gliomas are the most common primary intracranial neoplasms among all brain malignancies,and the microtubule affinity regulating kinases(MARKs)have become potential drug targets for glioma.Here,we report a novel dual small-molecule inhibitor of MARK3 and MARK4,designated as PCC0208017.In vitro,PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4,and strongly reduced proliferation in three glioma cell lines.This compound attenuated glioma cell migration,glioma cell invasion,and angiogenesis.Molecular mechanism studies revealed that PCC0208017 decreased the phosphorylation of Tau,disrupted microtubule dynamics,and induced a G2/M phase cell cycle arrest.In an in vivo glioma model,PCC0208017 showed robust anti-tumor activity,blood-brain barrier permeability,and a good oral pharmacokinetic profile.Molecular docking studies showed that PCC0208017 exhibited high binding affinity to MARK3 and MARK4.Taken together,our study describes for the first time that PCC0208017,a novel MARK3/MARK4 inhibitor,might be a promising lead compound for treatment of glioma.

Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy

Background:Pathological complete response(pCR)of axillary lymph nodes(ALNs)is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy(NAC),and ALN status is an important prognostic factor for breast cancer patients.This study aims to develop a new predictive clinical model to assess the ALN pCR rate after NAC.Methods:This was a retrospective series of 467 patients who had biopsy-proven positive ALNs at diagnosis and underwent ALN dissection from 2007 to 2014 at the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences.We analyzed the clinicopathologic features of the patients and developed a nomogram to predict the probability of ALN pCR.A multivariable logistic regression stepwise model was used to construct a nomogram to predict ALN pCR in node-positive patients.The adjusted area under the receiver operating characteristic curve(AUC)was calculated to quantify the ability to rank patients by risk.Internal validation was performed using the 50/50 hold-out validation method.The nomogram was externally validated with prospective cohorts of 167 patients from 2016 to 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences and 114 patients from 2018 to 2020 at Beijing Tiantan Hospital.Results:In this retrospective study,115(24.6%)patients achieved ALN pCR after NAC.Multivariate analysis showed that clinical tumor stage(Odds ratio[OR]:0.321,95%confidence interval[CI]:0.121-0.856;P=0.023);primary tumor response(OR:0.189;95%CI:0.123-0.292;P<0.001),and estrogen receptor status(OR:0.530,95%CI:0.304-0.925;P=0.025)were independent predictors of ALN pCR.The nomogram was constructed based on the result of multivariate analysis.In the internal validation of performance of nomogram,the AUCs for the training and test sets were 0.719 and 0.753,respectively.The nomogram was validated in external cohorts with AUCs of 0.720,which demonstrated good discriminatory power in these data sets.Conclusion:We developed a nomogram to predict the likelihood of axillary pCR in node-positive breast cancer patients after NAC.The predictive model performed well in multicenter prospective external validation.This practical tool could provide information to surgeons regarding whether to perform additional ALN dissection after NAC.Trial registration:ChiCTR.org.cn,ChiCTR1800014968.

采用高导热金刚石基底的高效散热钙钛矿激光

具有低温升的高效散热方案是实现电泵浦激光的关键因素之一.高导热金刚石有望克服钙钛矿激光的散热限制.本文中,我们展示了一种可以将光泵浦过程中产生热量高效耗散的金刚石基底钙钛矿纳米片激光.此外,紧密光学束缚可以通过在纳米片和金刚石基底之间引入一层薄SiO_(2)间隔层而实现.该激光的品质因子高达~1962,激光阈值为52.19μJ cm^(-2).受益于金刚石基底,其泵浦能量密度相关温度灵敏度较低(~0.56±0.01 K cm~2μJ^(-1)).本工作有望促进电泵浦钙钛矿激光的发展.

原子级化学反应促进可弱光探测有机光电倍增探测器的外量子效率超过10^(8)%

外量子效率远大于100%、低成本、溶液法制备的倍增型有机光电探测器(PM-OPDs)引起广泛关注.但该类器件因阳极欧姆接触带来暗电流的恶化,使其弱光探测并不理想.基于此,本文提出了原子级化学反应改善PM-OPDs暗电流及弱光探测策略,进而带来器件综合性能的显著提升.具体地,本文利用原子层沉积技术在空穴传输层PEDOT:PSS与活性层P3HT:PC71BM(100:1)之间引入0.8 nm厚的Al_(2)O_(3)界面层,通过对薄膜拉曼、XPS及FT-IR性能进行表征,发现原子级厚度的Al_(2)O_(3)可与PEDOT:PSS的化学基团发生反应,调节PEDOT:PSS的功函数,进而在阳极一侧形成肖特基接触.通过与阴极肖特基接触协同,器件在保持高倍增行为的同时,暗电流显著降低.最终,器件的弱光探测性能有所改善,相比于标准器件(可探测64 nW/cm^(2)弱光),Al_(2)O_(3)修饰器件可探测低至2.5 nW/cm^(2)的弱光,且相应的外量子效率和响应率分别达到4.31×10^(8)%,1.85×10^(6)A/W,达到目前报道PM-OPDs的最优值.此策略在新型柔性电子产品及医学成像领域具有很好的应用前景.

Overexpression of GhPFN2 enhances protection against Verticillium dahliae invasion in cotton

Growing evidence indicates that actin cytoskeleton is involved in plant innate immune responses, but the functional mechanism remains largely unknown. Here, we investigated the behavior of a cotton profilin gene （GhPFN2） in response to Verticillium dahliae invasion, and evaluated its contribution to plant defense against this soil-borne fungal pathogen. GhPFN2 expression was up-regulated when cotton root was inoculated with V. dahliae, and the actin architecture was reorganized in the infected root cells, with a clear increase in the density of filamentous actin and the extent of actin btmdling. Compared to the wild type, GhPFN2-overexpressing cotton plants showed enhanced protection against V. dahliae infection and the actin cytoskeleton organization in root epidermal cells was clearly altered, which phenocopied that of the wild-type （WT） root cells challenged with V. dahliae. These results provide a solid line of evidence important for defense against V. dahliae infection. showing that actin cytoskeleton reorganization involving GhPFN2 is

Influence of Different Al Contents on Microstructure, Tensile and Wear Properties of Zn-based Alloy

The influence of different Al contents on the microstructure, hardness, tensile and wear behavior of Zn-based alloys was investigated in the present study. The test results show that alloy with 27% Al content shows the higher ultimate strength and elongation percent at room and elevated temperatures. It also exhibits the higher wear resistance at all loads in view of the higher tightness of Zn-27Al alloy. Increasing Al content from 33% to 48% results in improvement of ultimate strength and elongation percent at room and elevated temperatures. However, the ultimate strength and elongation percent of the ZA48 alloy are still lower than that of Zn-27Al alloys. The reason can be attributed to the increasing segregation and voids with increasing Al contents.

The impaired development of innate lymphoid cells by preterm birth is associated with the infant disease

Innate lymphoid cells (ILCs) are immune cells newly defined inrecent decades and are recognized as the innate counterpart of theT helper cells, including IFNc-producing group 1 ILCs (ILC1s), IL-5and IL-13-producing group 2 ILCs (ILC2s), and IL-22-producinggroup 3 ILCs (ILC3s). Although with a tiny population, ILCs arenot only required for the host to maintain the tissue homeostasisand defense against pathogen invasion but also actively involvedin various inflammatory and allergic diseases [1]. The immune systemis shaped critically in early life, especially when born preterm.Although the development of the immune system in preterm childrenhas been extensively discussed [2], it is still unknownwhether the development of ILCs is influenced by preterm birth.

Electrochemical synthesis of dipyrazolo/dipyrimidine-fused pyridines via oxidative domino cyclization of C(sp^(3))–H bonds

An electrochemically oxidative domino cyclization reaction of methyl azaarenes/ketones with pyrazol-5-amines and 6-amino-pyrimidine-2,4-diones was developed, providing a variety of dipyrazolo[3,4-b:4’,3’-e]pyridines and dipyrimidine-fused pyridines with moderate to good yields. The reaction involved two C–C bond formations and one C–N bond formation in one pot. Moreover, the photoluminescence properties of the representative dipyrazolo[3,4-b:4’,3’-e]pyridines were investigated.

Spatial impacts of climate factors on regional agricultural and forestry biomass resources in north-eastern province of China

The dynamics of agricultural and forestry biomass are highly sensitive to climate change, particularly in high latitude regions. Heilongjiang Province was selected as research area in North-east China. We explored the trend of regional climate warming and distribution feature of biomass resources, and then analyzed on the spatial relationship between climate factors and biomass resources. Net primary productivity （NPP） is one of the key indicators of vegetation productivity, and was simulated as base data to calculate the distribution of agricultural and forestry biomass. The results show that temperatures rose by up to 0.37℃/10a from 1961 to 2013. Spatially, the variation of agricultural biomass per unit area changed from -1.93 to 5.85 t.km^-2.a^-1 during 2000,2013. More than 85% of farmland areas showed a positive relationship be.tween agricultural biomass and precipitation. The results suggest that precipitation exerts an overwhelming climate influence on agricultural biomass. The mean density of forestry biomass varied from 10 to 30 t·km^-2. Temperature had a significant negative effect on forestry biomass in Lesser Khingan and northern Changbai Mountain, because increased temperature leads to decreased Rubisco activity and increased respiration in these areas. Precipitation had a significant positive relationship with forestry biomass in south-western Changbai Mountain, because this area had a wanner climate and stress from insufficient precipitation may induce xylem cavitation. Understanding the effects of climate factors on regional biomass resources is of great significance in improving environmental management and promoting sustainable development of further biomass resource use.

Genomic mutation signatures in primary breast cancer and their axillary metastatic lymph nodes

Breast cancer is one of the most common malignant tumors in women all over the world.Metastasis represents a major adverse progression of breast cancer,resulting in poor survival duration.Axillary lymph node metastasis is often the first step of systemic metastasis process of breast cancer.However,themechanismof lymph node metastasis and the genomic signatures of primary breast tumors and lymph node metastasis are still under exploration.Whole exome sequencing was applied to primary breast cancer,axillary metastatic lymph nodes,andwhite blood cells from10Chinesewomen patients in our study.Single nucleotide variants(SNVs)and copynumber variants(CNVs)were compared between primary tumors and lymph nodes for individual patients.There are somatic SNVs(average 5.58±2.56 per megabase)in primary breast cancers and somatic SNVs(average 5.46±2.66 per megabase)in axillary metastatic lymph nodes were identified,which is corresponding to a semblable mutation burden in two malignant sites(P=0.81).No difference was found in CNVs(P=0.33).In primary breast cancer,somatic SNVs(48.12±13.80%)and CNVs(61.72±35.00%)were overlapping with somatic SNVs(49.43±12.30%)and CNVs(72.01±24.31%)in axillary metastatic lymph nodes.Nine genes were screened for significant specificmutations in primary tumors,and 15 genes were significantly mutated in metastatic lymph nodes.Using MutSigCV screening,it was found that HRNR and AHNAK2 are lymph node metastasis-specific genes.In our study,primary breast tumors are directly related to axillary lymph node metastases together and there are most SNVs and CNVs which were overlapping in primary andmetastatic sites.These variants which are overlapping is closely related to themetastatic process of tumor invasion with early genetic variability.This is the first timeto prove the concept of polyclonalmetastaticmodel and in thismodelmore than one clonemigrates establish the metastases to axillary lymph nodes.This study was approved by the institutional review board(IRB)of the Cancer Hospital,Chinese Academy of Medical Sciences,and Peking Union Medical College,China(approval No.NCC2016G-030)on March 3,2016.