LA-D-B1,a novel Abemaciclib derivative,exerts anti-breast cancer effects through CDK4/6

Background:Regulatory proteins involved in human cellular division and proliferation,cyclin-dependent kinases 4 and 6(CDK4/6)are overexpressed in numerous cancers,including triple-negative breast cancer(TNBC).TNBC is a common pathological subtype of breast cancer that is prone to recurrence and metastasis,and has a single treatment method.As one of the CDK4/6 inhibitors,abemaciclib can effectively inhibit the growth of breast tumors.In this study,we synthesized LA-D-B1,a derivative of Abemaciclib,and investigated its anti-tumor effects in breast cancer.Methods:Cellular viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Cell cloning and migration abilities were determined by colony formation assay and wound healing assay.Cell invasion abilities and adhesion were determined by cell invasion assay and cell adhesion assay.The impact of compound LA-D-B1 on cell proliferation and the cell cycle was analyzed through Western blotting,which quantified the levels of proteins associated with the cyclin-dependent kinase(CDK)4/6-cyclin D-Rb-E2F pathway.The in vivo anti-tumor activity of compound LA-D-B1 was investigated using a chick chorioallantoic membrane(CAM)model.Results:The study demonstrated that LA-D-B1 effectively suppressed breast cancer cell proliferation,induced apoptosis,and caused cell cycle arrest.Furthermore,LA-D-B1 reduced the expression of key proteins in the CDK4/6-cyclin D-Rb-E2F pathway,including CDK4,CDK6 and E2F1.The results also indicated significant antitumor activity of LA-D-B1 in a transplanted tumor model.Conclusion:In this study,LA-D-B1 demonstrated a potent anti-tumor effect by effectively suppressing cell proliferation and inhibiting cell cycle progression in breast cancer.These findings highlight the potential of LA-D-B1 as a valuable compound for enhancing therapeutic outcomes and controlling the progression of breast cancer.

皖江城市带产业结构与土地利用结构的国土空间耦合

综合运用熵值法和耦合协调度模型,在分析产业结构与土地利用结构之间的关系的基础上,以皖江城市带为例,对研究区2010年产业结构和土地利用结构及其空间格局差异进行测算、分析,以期为产业结构调整及土地利用结构优化提供依据。研究结果表明:(1)目前皖江城市带的城市产业结构信息熵值高于土地利用结构信息熵值,说明产业结构的有序程度低于土地利用结构;(2)产业结构调整和土地利用结构优化耦合基本处在颉颃时期,且协调度大部分处于初级协调发展类,协调关系提升空间很大;(3)皖江城市带产业结构和土地利用结构的耦合协调度的区域分布与区域经济发展水平之间未形成空间上的关联,其互动关系表现为受多种因素影响;(4)皖江城市带城市协调度基本高于耦合度,说明产业结构和土地利用结构耦合作用良好。

耕地轮作休耕对农业土地利用变化的影响研究综述

耕地轮作休耕是新时代实施乡村振兴战略的重要举措之一,随着其在全国逐步试点和展开,将对我国农业土地利用产生重大影响。本文通过对耕地轮作休耕的实施模式、农业经营主体行为响应、对与土地利用变化的影响和研究方式四个方面进行综述,指出:(1)轮作休耕制度对农业土地利用变化的影响是推进轮作休耕制度过程中出现的全新的、重要的、迫切的理论与现实问题;(2)多元经营主体行为响应视角可以揭示耕地轮作休耕制度对农业土地利用变化的微观作用过程、机理和效应;(3)轮作休耕制度对农业土地利用变化影响具有多样性和复杂性;(4)耕地轮作休耕制度的主体土地利用行为响应具有明显的时空差异。

Laparoscopic vs.open surgery for gastrointestinal stromal tumors of esophagogastric junction:A multicenter,retrospective cohort analysis with propensity score weighting

Objective:Laparoscopic resection is increasingly performed for gastrointestinal stromal tumors(GISTs).However,the laparoscopic approach for GISTs located in the esophagogastric junction(EGJ-GIST)is surgically challenging.This study compares the efficacy of laparoscopic surgery and the open procedure for EGJ-GIST through the propensity score weighting(PSW)method.Methods:Between April 2006 and April 2018,1,824 surgical patients were diagnosed with primary gastric GIST at four medical centers in South China.Of these patients,228 were identified as EGJ-GISTs and retrospectively reviewed clinicopathological characteristics,operative information,and long-term outcomes.PSW was used to create the balanced cohorts.Results:PSW was carried out in laparoscopic and open-surgery cohorts according to year of surgery,sex,age,body mass index(BMI),tumor size,mitotic rates and recurrence risk.After PSW,438 patients consisting of 213 laparoscopic(L group)and 225 open surgery(O group)patients were enrolled.After PSW,the following measures in the L group were superior to those in the O group:median operative time[interquartile range(IQR)]:100.0(64.5-141.5)vs.149.0(104.0-197.5)min,P<0.001;median blood loss(IQR):30.0(10.0-50.0)vs.50.0(20.0-100.0)mL,P=0.002;median time to liquid intake(IQR):3.0(2.0-4.0)vs.4.0(3.0-5.0)d,P<0.001;median hospital stay(IQR):6.0(4.0-8.0)vs.7.0(5.0-12.0)d,P<0.001;and postoperative complications(10.3%vs.22.7%,P=0.001).The median follow-up was 55(range,2-153)months in the entire cohort.No significant differences were detected in either relapse-free survival(RFS)[hazard ratio(HR):0.372,95%confidence interval(95%CI):0.072-1.910,P=0.236]or overall survival(OS)(HR:0.400,95%CI:0.119-1.343,P=0.138)between the two groups.Conclusions:Laparoscopic surgery for EGJ-GIST is associated with the advantages of shorter operative time,reduced blood loss,shorter time to liquid intake,and shorter length of stay,all without compromising postoperative outcomes and long-term survival.

Design and verification of an FPGA programmable logic element based on Sense-Switch pFLASH

This paper proposes a kind of programmable logic element(PLE)based on Sense-Switch pFLASH technology.By programming Sense-Switch pFLASH,all three-bit look-up table(LUT3)functions,partial four-bit look-up table(LUT4)functions,latch functions,and d flip flop(DFF)with enable and reset functions can be realized.Because PLE uses a choice of operational logic(COOL)approach for the operation of logic functions,it allows any logic circuit to be implemented at any ratio of combinatorial logic to register.This intrinsic property makes it close to the basic application specific integrated circuit(ASIC)cell in terms of fine granularity,thus allowing ASIC-like cell-based mappers to apply all their optimization potential.By measuring Sense-Switch pFLASH and PLE circuits,the results show that the“on”state driving current of the Sense-Switch pFLASH is about 245.52μA,and that the“off”state leakage current is about 0.1 pA.The programmable function of PLE works normally.The delay of the typical combinatorial logic operation AND3 is 0.69 ns,and the delay of the sequential logic operation DFF is 0.65 ns,both of which meet the requirements of the design technical index.

Gp130-dependent STAT3 activation in M-CSF-derived macrophages exaggerates tumor progression

Interleukin-6(IL-6)is a common pluripotent cytokine that is highly expressed in the tumor microenvironment.The IL-6/JAK/STAT3 signaling directly promotes tumor progression,severely hampering antitumor immunity.Macrophages,the richest innate immune cells within the tumor microenvironment,manipulate tumor progression via phenotypic plasticity.

Type I interferon signaling facilitates resolution of acute liver injury by priming macrophage polarization

Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment.Here,we identified the function of IFN-I in the myeloid compartment during APAP-ALI.Utilizing single-cell RNA sequencing,we characterized the cellular atlas and dynamic progression of liver CD11b+cells post APAP-ALI in WT and STAT2 T403A mice,which was further validated by immunofluorescence staining,bulk RNA-seq,and functional experiments in vitro and in vivo.We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages,leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+restorative macrophage maturation,contributing to efficient liver repair.Overall,we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.

HucMSC-Ex alleviates inflammatory bowel disease via the lnc78583-mediated miR3202/HOXB13 pathway

As a group of nonspecific inflammatory diseases affecting the intestine,inflammatory bowel disease(IBD)exhibits the characteristics of chronic recurring inflammation,and was proven to be increasing in incidence(Kaplan,2015).IBD induced by genetic background,environmental changes,immune functions,microbial composition,and toxin exposures(Sasson et al.,2021)primarily includes ulcerative colitis(UC)and Crohn's disease(CD)with complicated clinical symptoms featured by abdominal pain,diarrhea,and even blood in stools(Fan et al.,2021;Huang et al.,2021).

Fluoride removal from secondary effluent of the graphite industry using electrodialysis:Optimization with response surface methodology

Response surface methodology was utilized to model and optimize the operational variables for defluoridation using an electrodialysis process as the treatment of secondary effluent of the graphite industry. Experiments were conducted using a Box-Behnken surface statistical design in order to evaluate the effects and the interaction of the influential variables including the operational voltage, initial fluoride concentration and flow rate. The regression models for defluoridation and energy consumption responses were statistically validated using analysis of variance (ANOVA);high coefficient of determination values (R^2 = 0.9772 and R^2 = 0.9814;respectively) were obtained. The quadratic model exhibited high reproducibility and a good fit of the experimental data. The optimum values of the initial fluoride concentration, voltage and flow rate were found to be 13.9 mg/L, 13.4 V, 102.5 L/h, respectively. A fluoride removal efficiency of 99.69% was observed under optimum conditions for the treatment of the secondary effluent of the graphite industry.