A novel molecular classification method for osteosarcoma based on tumor cell differentiation trajectories

Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients.However,the highly complex cell origin involved in osteosarcoma(OS)limits the utility of traditional bulk RNA sequencing for OS subclassification.Single-cell RNA sequencing(sc RNA-seq)holds great promise for identifying cell heterogeneity.However,this technique has rarely been used in the study of tumor subclassification.By analyzing sc RNA-seq data for six conventional OS and nine cancellous bone(CB)samples,we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell(CSC)-like subset,which allowed us to classify OS samples into three groups.The classification model was further examined using the TARGET dataset.Each subgroup of OS had different prognoses and possible drug sensitivities,and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment.In addition,we verified the classification model through IHC staining in 138 OS samples,revealing a worse prognosis for Group B patients.Furthermore,we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS.These findings provide a novel subclassification method based on sc RNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.

“智慧党建”在民办职教本科大学生党员教育中的难点突破研究

互联网的高速发展改变了基层组织党建工作环境,对基层党建工作提出了更高的要求,传统的党建方式已经不能完全满足党建创新的需要。“智慧党建”在信息传播模式、信息资源共享、智能化分析等方面发挥着重要作用,许多高校利用“智慧党建”加强对党员的教育,提高党员的政治思想意识。在此背景下,民办职教本科也应围绕“智慧党建”对大学生党员教育开展一系列的改革创新。对此,本研究总结了“智慧党建”在民办职教本科大学生党员教育中的重要意义,凝练“智慧党建”在教育统筹力、引领力、创新力方面的价值功效;并针对民办职教本科“智慧党建”在信息资源、供给模式、互动渠道三个方面存在的现实问题,提出“智慧党建”赋能大学生党员教育理念、教育基础、教育能力、教育制度等方面的难点突破,以期为推动民办职教本科党建工作理论和民办职教本科大学生党员教育理论的发展提供借鉴。

Effects of Pyridoxine on Selected Appetite Regulating Peptides mRNA Expression in Hypothalamic PVN/ARC Nuclei and Gastrointestinal Tract Tissues

An experiment was conducted to investigate the effect of dietary pyridoxine on the gene expression of appetite-regulating peptides in the hypothalamus and gastrointestinal tract of rabbits. Thirty-two rabbits were randomly divided into 2 treatments for 8 weeks (16 replicates/group and 1 rabbit/replicate). The treatments were fed a basal diet (control, measured pyridoxine content is 4.51 mg/kg) and the basal diet with a pyridoxine supplementation at 10 mg/kg (pyridoxine, measured pyridoxine content is 14.64 mg/kg). The results showed that dietary pyridoxine did not significantly alter the mRNA levels of neuropeptide Y, agouti related peptide, pro-opiomelanocortin and cocaine, amphetamine regulated transcript, peptide YY and cholecystokinin in arcuate nucleus, peptide YY in jejunum and ileum, and cholecystokinin in duodenum, jejunum and ileum (P > 0.05). Compared with the control, the mRNA levels of corticotropin-releasing hormone and melanocortin 4 receptor in paraventricular nuclei and peptide YY in duodenum were significantly decreased after pyridoxine treatment (P 0.05). In conclusion, the appetite genes of melanocortin 4 receptor and corticotropin-releasing hormone in paraventricular nuclei and peptide YY in duodenum are involved in the pyridoxine-caused hyperphagia.

LSG中保留胃窦部及His角完整性对术后胃食管反流病的影响

目的探讨腹腔镜胃袖状切除术中保留胃窦部及His角完整性对术后胃食管反流病的影响。方法回顾性分析首都医科大学附属北京潞河医院2022年1月至2023年8月行腹腔镜胃袖状切除手术的肥胖症患者76例,并完成术后6个月随访的患者。分为A组40例(保留胃窦部及His角周围组织完整性)和B组36例(未保留胃窦结构及His角周围组织的完整性)。对比分析两组患者术后1、3、6个月体质量指数(body mass index,BMI)、多余体质量下降百分比(percent excess weight loss,%EWL)及胃食管反流病问卷(gastroesophageal reflux disease questionnaire,Gerd-Q)量表评分的差异性。结果A、B两组患者术前及术后6个月BMI差异无统计学意义(39.44±6.032 kg/m^(2) vs.41.74±6.677 kg/m^(2);28.99±4.763 kg/m^(2) vs.29.82±4.651 kg/m^(2),P>0.05)。A、B两组患者术前胃食管反流病(gastroesophageal reflux disease,GERD)的发病率分别是27.5%(11例)、27.8%(10例),无明显差异(P>0.05)。术后1、3、6个月时A组患者GERD的发病率(Gerd-Q评分≥8)分别是30.0%(12例)、27.5%(11例)、22.5%(9例),显著低于B组的41.7%(15例)、38.9%(14例)、36.1%(13例),P<0.05。结论保留胃窦部及His角的完整性并不影响减重效果,并且有利于降低胃袖状切除术后GERD的发病率。

Effects of aspirin on colon cancer usingquantitative proteomic analysis

Background:Colon cancer is one of the most prevalent digestive cancers worldwide.Results of epidemiological,experimental,and clinical studies suggest that aspirin inhibits the development of colon cancer.This study aimed to systematically elucidate the molecular mechanisms by which aspirin prevents colon carcinogenesis.Methods:We determined the global protein expression profiles of colorectal cancer and aspirin-treated cells using quantitative proteomic analysis.We analyzed the proteomic results using bioinformatics(including differential pro-teins,protein annotation,Kyoto Encyclopedia of Genes and Genomes[KEGG]pathways,and protein-protein inter-action[PPI]network).The viability of the colon cancer cell line and HT29 cells treated with aspirin was determined using the cell counting kit-8 assay.The differentially expressed proteins,such as p53 and cyclin-dependent kinase 1(CDK1),were quantified using real-time polymerase chain reaction(PCR)and Western blotting.We measured cell cycle distribution and apoptosis in HT29 cells exposed to aspirin using fluorescence-activated cell sorting(FACS).Results:We found that 552 proteins were significantly dysregulated,of which 208 and 334 were upregulated and downregulated,respectively,in colon cancer cells exposed to 10 mmol/L of aspirin(95%confidence interval[CI]:-1.269 to-0.106,P<0.05).Further gene enrichment analysis revealed that cell cycle-related proteins,such as p53 and CDK1,were significantly differentially expressed.Proteomic analysis showed that after 24 h of aspirin exposure,the level of p53 increased by 2.52-fold and CDK1 was downregulated to half that of the controls in HT29 cells(95%CI:-0.619 to-0.364,P<0.05).Real-time PCR and Western blotting results showed that p53 was upregulated(95%CI:-3.088 to-1.912,P<0.001)and CDK1 was significantly downregulated after aspirin exposure in colon cancer cells(95%CI:0.576 to 1.045,P<0.05).We observed that aspirin promoted G1/S cell cycle arrest in HT29 cells.We confirmed that aspirin induces apoptosis in human HT29 colon cancer cells in a concentration-dependent manner.Conclusions:These results indicate that aspirin induces G1 arrest and apoptosis in colorectal cancer cells via the p53-CDK1 pathway.Aspirin may be a promising drug candidate for colon cancer prevention.

电子轴向拉伸提升贫氧环境海水电池性能

长寿命溶解氧海水电池是深远海观测能源网络的重要组成单元,但海水贫氧复杂环境对设计高性能氧还原催化剂提出了重要挑战.本文以酞菁铁为模型催化剂,通过理论计算与实验验证,提出了活性位点电子轴向拉伸可大幅提升催化剂在极端贫氧环境中的氧还原活性和稳定性.该研究为构建高性能海水电池提供了材料学解决方案,同时为极端环境下催化剂的变革性设计提供了新的思路.

Construction of FRET-based metallacycles with efficient photosensitization efficiency and photocatalytic activity

The fabrication of highly effective photosensitizers has received considerable attention because of their attractive functions and applications in the fields of photodynamic therapy, photosynthesis, photocatalysis, etc. Thus, it is highly desirable to develop a new approach to enhance photosensitization efficiency.Herein, through coordination-driven self-assembly, a series of metallacycles with efficient fluorescence resonance energy transfer(FRET) were effectively constructed, which displayed higher photosensitization efficiency and photocatalytic activity than their model metallacycles without FRET due to broadband absorption and singlet energy transfer from the energy acceptor to the energy donor. Moreover, iodization of fluorophores induced a significant enhancement of the photosensitization efficiency and photocatalytic activity of the metallacycles. This research provides an efficient strategy for improving photosensitization efficiency and a promising platform for the preparation of effective photosensitizers and photocatalysts.

Furan Donor for NIR-II Molecular Fluorophores with Enhanced Bioimaging Performance

The second near-infrared(NIR-II,1,000 to 1,700 nm)molecular fluorophores containing donor–acceptor–donor conjugated backbone have attracted substantial attention due to their outstanding advantages,such as stable emission and facilely tuned photophysical properties.However,it is still challenging for them to simultaneously achieve high brightness and red-shifted absorption and emission.Herein,furan is adopted as the D unit to construct NIR-II fluorophores,demonstrating red shift of absorption,enhanced absorption coefficient,and fluorescent quantum yield when compared with the generally used thiophene counterparts.The high brightness and desirable pharmacokinetics of the optimized fluorophore,IR-FFCHP,endows improved performance for angiography and tumor-targeting imaging.Furthermore,dual-NIR-II imaging of tumor and sentinel lymph nodes(LNs)has been achieved with IR-FFCHP and PbS/CdS quantum dots,enabling the in vivo imaging navigated LN surgery in tumor-bearing mice.This work demonstrates the potential of furan for constructing bright NIR-II fluorophores for biological imaging.

Pyridoxine regulates hair follicle development via the PI3K/Akt, Wnt and Notch signalling pathways in rex rabbits

This study was conducted to evaluate the effect of pyridoxine on the development of hair follicles in Rex rabbits and the underlying molecular mechanism.Two hundred 3-month-old Rex rabbits were randomly divided into 5 groups and fed diets supplemented with 0,5,10,20,or 40 mg/kg pyridoxine.The hair follicle density on the dorsal skin and the gene and protein expression levels of components of the phosphoinositide 3-kinase(PI3 K)/protein kinase B(PKB or Akt),Wnt,Notch and bone morphogenetic protein(BMP)signalling pathways were measured.In addition,free hair follicles were isolated from Rex rabbits and cultured with pyridoxine in vitro to measure hair shaft growth.Furthermore,dermal papilla cells(DPC)were isolated from the skin of Rex rabbits and cultured with pyridoxine in vitro to measure the gene and protein expression levels of components of the PI3 K/Akt,Wnt,Notch and BMP signalling pathways.The results showed that the addition of dietary pyridoxine significantly increased the total follicle density,secondary follicle density,and secondary-to-primary ratio(S/P,P<0.05),that the growth ratio of hair stems was promoted by pyridoxine in basic culture medium,and that the growth length of tentacle hair follicles cultured in the pyridoxine group was longer than that in the control group(P<0.05).In addition,pyridoxine changed the DPC cycle progression and promoted cell proliferation,and appropriate concentrations of pyridoxine(10 and 20μmol/L)significantly inhibited cell apoptosis(P<0.05).Pyridoxine significantly affected the gene expression of components of the PI3 K/Akt,Wnt and Notch signalling pathways in the skin and DPC of Rex rabbits(P<0.05),increased the levels of phosphorylated catenin beta 1(CTNNB1)and Akt,and decreased the level of phosphorylated glycogen synthase kinase 3 beta(GSK-3β)(P<0.05).Therefore,the molecular mechanism by which pyridoxine promotes hair follicle density in Rex rabbits probably occurs through activation of the PI3 K/Akt,Wnt and Notch signalling pathways,prolonging hair follicle growth and delaying the onset of telogen.

An overview of the switching parameter variation of RRAM

Resistive random access memory(RRAM) has been considered as one of the most promising candidates for next-generation nonvolatile memory, due to its advantages of simple device structure, excellent scalability, fast operation speed and low power consumption. Deeply understanding the physical mechanism and effectively controlling the statistical variation of switching parameters are the basis of fostering RRAM into commercial application. In this paper, based on the deep understanding on the mechanism of the formation and rupture of conductive filament, we summarize the methods of analyzing and modeling the statistics of switching parameters such as SET/RESET voltage, current, speed or time. Then, we analyze the distributions of switching parameters and the influencing factors. Additionally, we also sum up the analytical model of resistive switching statistics composed of the cell-based percolation model and SET/RESET switching dynamics. The results of the model can successfully explain the experimental distributions of switching parameters of the Ni O- and Hf O2-based RRAM devices. The model also provides theoretical guide on how to improve the uniformity and reliability such as disturb immunity. Finally, some experimental approaches to improve the uniformity of switching parameters are discussed.

High brightness NIR-Ⅱ nanofluorophores based on fused-ring acceptor molecules

It is challenging to develop molecular fluorophores in the second near-infrared(NIR-Ⅱ)window with long wavelength emission and high brightness,which can improve the performance of biological imaging.Herein,we report a molecular engineering approach to afford NIR-Ⅱ fluorophores with these merits based on fused-ring acceptor(FRA)molecules.Dioctyl 3,4-propylenedioxy thiophene(PDOT-C8)is utilized as the bridging donor to replace 3-ethylhexyloxy thiophene(3-EHOT),leading to more than 20 times enhancement of brightness.The nanofluorophores(NFs)based on the optimized CPTIC-4F molecule exhibit an emission peak of 1,110 nm with a fluorescence quantum yield(QY)of 0.39%(QY of IR-26 is 0.050%in dichloroethane as reference)and peak absorption coefficient of 14.5 x 10^4 M^-1·cm^-1 in aqueous solutions,which are significantly higher than those of 3-EHOT based COTIC-4F NFs.It is found that PDOT-C8 can weaken intermolecular aggregation,enhance protection of molecular backbone from water,and decrease backbone distortion,beneficial for the high brightness.Compared with indocyanine green with same injection dose,CPTIC-4F NFs show 10 times higher signal-to-background ratio for whole body vessels imaging at 1,300 nm long pass filters.

Acid-induced tunable white light emission based on triphenylamine derivatives

A series of triphe nylamine(TPA)derivatives with various substituent groups were prepared and showed different absorption and fluorescence characteristics due to the substituent effect.On account of the existence of pyridine units,these TPA derivatives exhibited acid-induced tunable multicolor fluorescence emission including white light emission.In addition,acid-induced fluorescence regulation of these compounds has been also realized in the solid state,which enable them to be successfully constructed the stimuli-responsive fluorescent films and fluorescent inks for inkjet printing.

Engineering naphthalimide-cyanine integrated near-infrared dye into ROS-responsive nanohybrids for tumor PDT/PTT/chemotherapy

Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents.Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT.Herein,we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton.The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820.Furthermore,ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica(RMON)to construct nanomedicine NBD&ML@RMON,which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.

Theoretical predication for transition energies of thermally activated delayed fluorescence molecules

Thermally activated delayed fluorescence（TADF） emitters are primarily comprised of intramolecular charge-transfer（ICT） molecules with small energy difference between the lowest singlet and triplet excited states.They lend extremely favorable electroluminescent performance to organic light-emitting diodes（OLEDs）.This paper summarizes relevant issues and research efforts in the theoretical prediction of singlet- and triplet-transition energies of ICT molecules via time-dependent density functional theory（TDDFT）.The successful application of the descriptor-based optimal Hartree-Fock percentage method and the optimally tuned range-separated functional to many TADF systems represent an interesting approach to the exact prediction of the complex excited-state molecular dynamics within TDDFT.