BIBR1532 inhibits proliferation and metastasis of esophageal squamous cancer cells by inducing telomere dysregulation

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a malignant tumor with high morbidity and mortality,and easy to develop resistance to chemotherapeutic agents.Telomeres are DNA-protein complexes located at the termini of chro-mosomes in eukaryotic cells,which are unreplaceable in maintaining the stability and integrity of genome.Telomerase,an RNA-dependent DNA polymerase,play vital role in telomere length maintain,targeting telomerase is a promising therapeutic strategy for cancer.KYSE150 and KYSE410 cells were cultured and exposed to various concentrations of BIBR1532.Cell viability was assessed at 48 hours and 72 hours to determine the IC50 values.The effects of BIBR1532 on ESCC cell proliferation,migration,and cellular senescence were evaluated using the cell counting kit-8 assay,plate colony formation assay,scratch assay,transwell assay,andβ-galactosidase staining,respectively.Western blotting was performed to detect the expression of RESULTS The IC50 values for KYSE150 and KYSE410 cells after 48 hours of BIBR1532 exposure were 48.53μM and 39.59μM,respectively.These values decreased to 37.22μM and 22.71μM,respectively,following a longer exposure of 72 hours.BIBR1532 exhibited dose-dependent effects on KYSE150 and KYSE410 cells,including decreased hTERT expression,inhibition of proliferation and metastasis,and induction of cellular senescence.Mechanistically,BIBR1532 upregulated the expression of the DDR protein,γ-H2AX,and activated the ataxia telangiectasia and Rad3-related protein(ATR)/check point kinase 1(CHK-1)and ataxia-telangiectasia mutated gene(ATM)/CHK2 pathways.BIBR1532 downregulated the expression of telomere-binding proteins,including telomeric-repeat binding factor 1(TRF1),TRF2,protection of telomeres 1,and TIN2-interacting protein 1.In a nude mouse xenograft model,BIBR1532 significantly suppressed tumor growth,reduced hTERT expression,and increasedγ-H2AX protein levels.Hematoxylin and eosin staining of various organs,including the heart,liver,spleen,lungs,and kidneys,revealed no apparent adverse effects.CONCLUSION BIBR1532 exerts anti-cancer effects on ESCC by inducing DDR through the ATR/CHK1 and ATM/CHK2 pathways and downregulating the expression of telomere-binding proteins.

Small cell lung cancer with peripheral neuropathy as the first symptom:Two case reports

BACKGROUND Small cell lung cancer(SCLC)is the most malignant type of lung cancer.Even in the latent period and early stage of the tumor,SCLC is prone to produce distant metastases with complex and diverse clinical manifestations.SCLC is most closely related to paraneoplastic syndrome,and some cases present as paraneoplastic peripheral neuropathy(PPN).PPN in SCLC appears early,lacks specificity,and often occurs before diagnosis of the primary tumor.It is easy to be misdiagnosed as a primary disease of the nervous system,leading to missed diagnosis and delayed diagnosis and treatment.CASE SUMMARY This paper reports two cases of SCLC with limb weakness as the first symptom.The first symptoms of one patient were rash,limb weakness,and abnormal electromyography.The patient was repeatedly referred to the hospital for limb weakness and rash for>1 year,during which time,treatment with hormones and immunosuppressants did not lead to significant improvement,and the condition gradually aggravated.The patient was later diagnosed with SCLC,and the dyskinesia did not worsen as the dermatomyositis improved after antineoplastic and hormone therapy.The second case presented with limb numbness and weakness as the first symptom,but the patient did not pay attention to it.Later,the patient was diagnosed with SCLC after facial edema caused by tumor thrombus invading the vein.However,he was diagnosed with extensive SCLC and died 1 year after diagnosis.CONCLUSION The two cases had PPN and abnormal electromyography,highlighting its correlation with early clinical indicators of SCLC.

Effect Evaluation of CBL Combined with Rain Classroom Teaching Method in Medical Statistics

Objective: To explore the application effect of CBL combined with rain classroom teaching method in medical statistics courses. Methods: The undergraduate students of medical imaging technology in 2019 and 2020 in a university were selected as the research objects. A cluster sampling method was used to select 79 undergraduate students from 2019 in the control group and 75 undergraduate students from 2020 in the experimental group. Traditional teaching method and CBL combined with rain classroom teaching method was used in the control group and experimental group respectively. The final examination scores of the two groups were compared. In experimental group, the correlation between the average score in the rain classroom and the final examination score was tested, and the teaching effect was evaluated. Results: The average score of final examination in experimental group and control group was 79.13 ± 10.32 points and 71.54 ± 14.752 points, respectively, which had a statistically significant difference (Z = 2.586, P = 0.012);the final examination scores of the students in the experimental group were positively correlated with the average scores of the rain classroom (r = 0.372, P = 0.001), and the proportion of satisfaction in the experimental group was 94.7%. Conclusion: The CBL combined with rain classroom teaching method can improve the teaching effectiveness of medical statistics courses.

Tanshinone ⅡA improves Alzheimer’s disease via RNA nuclearenriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis

BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.

Current Situation and Influencing Factors of Preterm Infants Breastfeeding in Jingzhou 3A Hospital

Background: Breast milk is the best source of nutrition for premature infants and a “good medicine” for disease treatment. However, the rate of exclusive breastfeeding of premature infants in China still needs to be improved at present, and the factors affecting breastfeeding are different in different places. Objective: To investigate the current status and influencing factors of preterm infants breastfeeding in Jingzhou 3A hospitals. Methods: A cross-sectional study was conducted to collect breastfeeding information of premature infants in neonatal intensive care unit (NICU) from May to August in 2019 in Jingzhou 3A Hospital, and 152 premature infants’ related information were collected. A questionnaire survey was conducted among the mothers who failed to breastfeed. Results: The rate of exclusive breastfeeding among premature infants in NICU was 9.87%. The rates of first breastfeeding and exclusive breastfeeding at discharge were 13.16% and 32.89% respectively. Not producing enough milk and knowing the right way to pump breast milk contributed a lot to the failure of exclusive breastfeeding. Conclusion: More attention should be paid to the health education and management to improve the rate of breastfeeding in NICU.

制度差异与制度创新:多元制度互动下的大湾区改革

在一国两制的背景下,香港、澳门与内地之间的制度差异如何影响粤港澳大湾区的发展?学界对此仍关注不足。论文基于制度主义理论,构建了"制度差异-张力-制度创新"的理论框架,以深圳前海自贸区的工程建设管理制度改革为案例,分析了制度差异推动改革创新的机制。研究发现,不同的制度逻辑形塑行动主体的认知与行为,因此多元制度在互动中能够产生张力,进而激发行为主体的能动性,促使其反思、设计新的制度、采取改革行动,最终促成制度创新。中国内地与港澳的制度在"一国两制"方针下得以多元共存,制度差异在粤港澳密切互动中产生的张力是大湾区改革的创新源泉,使大湾区在国家改革与发展大局中发挥重要作用。

一种独特的学习原理——谈钢琴家为什么要“唱”

文章探讨了钢琴教育中钢琴家为什么要“唱”的问题。作者认为,“唱”不仅是钢琴家希望获得钢琴声音的连续性和歌唱性的需要,同时也是钢琴技术教育的一种方法;强调在多声部钢琴音乐的理解和掌握方面“唱-弹”和“听-弹”并举,能够起到重要作用。“唱”是钢琴教育中非常重要的技术问题和学习原理,值得钢琴教师们了解和注意。

Diffusion tensor imaging detects Wallerian degeneration of the corticospinal tract early after cerebral infarction

To investigate the feasibility and time window of early detection of Wallerian degeneration in the corticospinal tract after middle cerebral artery infarction, 23 patients were assessed using magnetic resonance diffusion tensor imaging at 3.0T within 14 days after the infarction. The fractional anisotropy values of the affected corticospinal tract began to decrease at 3 days after onset and decreased in all cases at 7 days. The diffusion coefficient remained unchanged. Experimental findings indicate that diffusion tensor imaging can detect the changes associated with Wallerian degeneration of the corticospinal tract as early as 3 days after cerebral infarction.

Adaptive Control of Discrete-time Nonlinear Systems Using ITF-ORVFL

Random vector functional ink(RVFL)networks belong to a class of single hidden layer neural networks in which some parameters are randomly selected.Their network structure in which contains the direct links between inputs and outputs is unique,and stability analysis and real-time performance are two difficulties of the control systems based on neural networks.In this paper,combining the advantages of RVFL and the ideas of online sequential extreme learning machine(OS-ELM)and initial-training-free online extreme learning machine(ITFOELM),a novel online learning algorithm which is named as initial-training-free online random vector functional link algo rithm(ITF-ORVFL)is investigated for training RVFL.The link vector of RVFL network can be analytically determined based on sequentially arriving data by ITF-ORVFL with a high learning speed,and the stability for nonlinear systems based on this learning algorithm is analyzed.The experiment results indicate that the proposed ITF-ORVFL is effective in coping with nonparametric uncertainty.

Reaction mechanism of methyl nitrite dissociation during co catalytic coupling to dimethyl oxalate:A density functional theory study

Dissociation of methyl nitrite is the first step during CO catalytic coupling to dimethyl oxalate followed by hydrogenation to ethyl glycol in a typical coal to liquid process. In this work, the first-principle calculations based on density functional theory were performed to explore the reaction mechanism for the non-catalytic dissociation of methyl nitrite in the gas phase and the catalytic dissociation of methyl nitrite on Pd(111) surface since palladium supported on alpha-alumina is the most effective catalyst for the coupling. For the non-catalytic case, the calculated results show that the CH_3O–NO bond will break with a bond energy of 1.91 eV, and the produced CH_3O radicals easily decompose to formaldehyde, while the further dissociation of formaldehyde in the gas phase is difficult due to the strong C–H bond. On the other hand, the catalytic dissociation of methyl nitrite on Pd(111) to the adsorbed CH_3O and NO takes place with a small energy barrier of 0.03 eV. The calculated activation energies along the proposed reaction pathways indicate that(i) at low coverage, a successive dehydrogenation of the adsorbed CH_3O to CO and H is favored while(ii) at high coverage, hydrogenation of CH_3O to methanol and carbonylation of CH_3O to methyl formate are more preferred. On the basis of the proposed reaction mechanism,two meaningful ways are proposed to suppress the dissociation of methyl nitrate during the CO catalytic coupling to dimethyl oxalate.

Combination and distribution of reservoir space in complex carbonate rocks

This paper discusses the reservoir space in carbonate rocks in terms of types,combination features,distribution regularity,and controlling factors,based on core observations and tests of the North Truva Oilfield,Caspian Basin.According to the reservoir space combinations,carbonate reservoirs can be divided into four types,i.e.,pore,fracture-pore,pore-cavity-fracture,and pore-cavity.Formation and distribution of these reservoirs is strongly controlled by deposition,diagenesis,and tectonism.In evaporated platform and restricted platform facies,the reservoirs are predominately affected by meteoric fresh water leaching in the supergene-para-syngenetic period and by uplifting and erosion in the late stage,making both platform facies contain all the above-mentioned four types of reservoirs,with various pores,such as dissolved cavities and dissolved fractures,or structural fractures occasionally in favorable structural locations.In open platform facies,the reservoirs deposited continuously in deeper water,in an environment of alternative high-energy shoals（where pore-fracture-type reservoirs are dominant） and low-energy shoals（where pore reservoirs are dominant）.

基于大数据技术的政府财政收入预测—以贵州省为例

本文结合贵州财政收入的构成内容和结构特点,利用R软件,对收集的数据进行整理分析,找出影响地方财政收入的关键影响因素,使用传统时间序列和多元回归分析方法相结合,建立较为完整的地方财政收入预测模型,对贵州省2015~2016年的财政收入进行预测。

Construction of Position Capacity Modular Curriculum System for Grassroots Agricultural Meteorological Observation

Through the investigation and analysis of the operation status and training needs of the agrometeorological observation work of the grass-roots meteorological department,as well as the evaluation of training effects,the development of a modular curriculum system for agrometeorological observation posts was carried out. Research has shown that the structure and distribution of academic qualifications,age and professional title of the agrometeorological observation personnel currently on the job is basically reasonable,human resources are abundant and the observation work is comprehensive. However,there are problems such as lack of professional knowledge and skills,fewer training opportunities and large training needs. Therefore,the pilot training of agricultural meteorological observation still has room for improvement in terms of training frequency,curriculum arrangement,and quality of remote training.

Exploring stool-based microrna-92a as a potential biomarker for colorectal cancer diagnosis

Background:Stool-based molecular markers have shown potential as a strategy for colorectal cancer(CRC)screening.This study aimed to evaluate the feasibility of using microRNA-92a expression as a biomarker for CRC in stool samples.Methods:The level of microRNA-92a was measured in stool samples from 210 CRC patients,29 patients with advanced adenomas,15 patients with other cancers,and 101 healthy controls,using real-time quantitative polymerase chain reaction.Receiver operating characteristic curves were used to evaluate sensitivity and specificity.Results:MicroRNA-92a expression was positive in 70.1%of CRC patients,44.8%of advanced adenomas patients,and 36.6%of healthy controls,using a cut-off value of 31.5.The corresponding sensitivity and specificity for discriminating CRC from advanced adenomas were 66.9%and 63.4%,respectively.Moreover,stool-based microRNA-92a expression was better at detecting CRC cancers in the distal colon(sensitivity 82.1%)than the proximal colon(sensitivity 67.9%).There were no significant differences in clinical stage of CRC when comparing AUCs of each parameter(P>0.05).Conclusion:These findings suggest that microRNA-92a expression in stool samples could serve as a promising non-invasive biomarker for CRC detection.

Reductive stressda common metabolic feature of obesity and cancer

Reductive stress,characterized by rising level of NADH(nicotinamide adenine dinucleotide)for a status of NADH/NAD^(+)ratio elevation,has been reported in obesity and cancer.However,the mech-anism and significance of reductive stress remain to be established in obesity.This perspective is prepared to address the issue with new insights published recently.NADH is used in production of NADPH,gluta-thione,ATP and heat in the classical biochemistry.In obesity,elevation of NADH/NAD^(+)ratio,likely from overproduction due to substrate overloading,has been found in the liver for insulin resistance and gluconeogenesis.New evidence demonstrates that the elevation may induce lipogenesis,purine biosynthesis and gluconeogenesis through activation of transcription factors of ChREBP and NRF2.In cancer cells,NADH/NAD^(+)elevation under the Warburg effect is primarily derived from decreased NADH consumption in the mitochondrial respiration.Alternatively,NRF2 overactivation from gene mu-tation represents another mechanism of NADH/NAD^(+)elevation from NADH production in the cancer cells.The elevation is required for quick proliferation of cancer cells through induction of biosynthesis of the essential molecules.It appears that the causes of reductive stress are different between obesity and cancer,while its impact in anabolism is similar in the two conditions.

miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1- containing AMPA receptors in a mouse model of Alzheimer’s disease

Alzheimer ’s disease(AD) is a leading cause of dementia in the elderly.Mitogen-activated protein kinase phosphatase 1(MKP-1) plays a neuroprotective role in AD.However,the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied.MicroRNAs(miRNAs) regulate gene expression at the post-transcriptional level,thereby repressing mRNA translation.Here,we reported that the microRNA-429-3p(miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPPAD model cells.We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3’-untranslated region(3’ UTR).Inhibition of miR-429-3p by its antagomir(A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation.More importantly,intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase(ERK1/2)-mediated GluAl hyperphosphorylation at Ser831 site,thereby increasing the surface expression of GluAl-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors(AMPARs).Together,these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice,suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

High-Q Fabry-Pérot Cavity Based on Micro-Lens Array for Refractive Index Sensing

Fabry-Pérot(FP)microcavities have attracted tremendous attention in recent years due to their favorable optical characteristics of the high quality(Q)factor and small mode volume.In this work,we presented a novel approach that utilized the soft lithography and imprinting technology to incorporate the convex micro-lens array structure into the FP(FP-lens)cavity.A strong mode-profile restriction of the micro-lens simultaneously reduced the mode volume and enhanced the Q factor,exhibiting high tolerance to non-parallelism of mirrors compared with that of the plane-plane FP(PP-FP)microcavities.In the experiment,the Q factor of the FP-lens cavity was measured to be 8.145×10^(4),which exhibited a 5.6-fold increase than that of the PP-FP cavity.Furthermore,we experimentally measured the refractive index sensing performance of the FP-lens cavity with the sensitivity of 594.7 nm/RIU and a detection limit of 4.26×10^(–7)RIU.On the basis of this superior sensing performance,the FP-lens cavity has the great potential for applications in biosensors.

卸去心中沉重包袱:员工可隐藏污名披露的系统回顾与展望

可隐藏污名是一种不可见的属性或特征,它传达了在特定社会背景下被贬低的社会身份。可隐藏污名以明显不同于可见污名的方式塑造着员工的身份管理行为,可隐藏污名承载者不仅受披露决策的相对必要性和潜在收益的驱动,而且也承担着对消极预期的恐惧,因而面临着是否、何时、如何以及向谁披露其可隐藏污名的决定,这对员工的工作方式有着重要的影响。事实上,已有多个理论框架为理解披露决策的前因和结果提供了理论基础,本文的目的是整合和统一现有的文献,促进对具有可隐藏污名身份的员工的持续研究。具体来说,本文系统地综合了多个研究领域,包括管理学、应用心理学和社会学中有关管理可隐藏污名的发现,提出了职场中可隐藏污名的披露机制,并在此基础上概述了未来研究的可能途径。

碱土金属催化的硼氢化反应研究进展

硼氢化反应,即在C=O、C=N、C=C等不饱和双键和C≡C、C≡N不饱和三键上直接引入B–H键,是制备有机硼化合物的主要方法之一.近年来,研究发现碱土金属催化剂可广泛应用于有机硼化合物的合成.本文主要介绍了近几年来碱土金属特别是镁金属催化不饱和有机化合物(醛、酮、酯、胺、吡啶、腈、烯炔和碳酸酯等)硼氢化反应的最新研究进展.

Preparation of double-shell Si@SnO_(2)@C nanocomposite as anode for lithium-ion batteries by hydrothermal method

Silicon is one of the most promising anode materials for lithium-ion batteries(LIBs), but it suffers from pulverization and hence poor cycling stability due to the large volume variation during lithiation/delithiation. The core-shell structure is considered as an effective strategy to solve the expansion problem of silicon-based anodes. In this paper, the double-shell structured Si@SnO_(2) @C nanocomposite with nano-silicon as the core and SnO_(2) , C as the shells is synthesized by a facile hydrothermal method.Structural characterization shows that Si@SnO_(2) @C nanocomposite is composed of crystalline Si, crystalline SnO_(2) and amorphous C, and the contents of them are 42.1wt%, 37.8 wt% and 20.1 wt%, respectively. Transmission electron microscope(TEM) observations confirm the double-shell structure of Si@SnO_(2) @C nanocomposite, and the thicknesses of the SnO_(2) and C layers are 20 and 7 nm. The Si@SnO_(2) @C electrode exhibits a high initial discharge capacity of 2777 mAh·g^(-1)at 100 mA·g^(-1)and an excellent rate capability of 340 mAh·g^(-1)at 1500 mA·g^(-1). The outstanding capacity retention is 50.2% after 300 cycles over a potential of 0.01 to 2.00 V(vs. Li/Li+) at 500 mA·g^(-1). The resistance of solid electrolyte interphase(SEI) film(Rf) and charge transfer resistance(Rct) of Si@SnO_(2) @C are 7.68and 0.82 Ω, which are relatively smaller than those of Si@C(21.64 and 2.62 Ω). It is obviously seen that the SnO_(2) shell can reduce the charge transfer resistance, leading to high ion and electron transport efficiency in the Si@SnO_(2) @C electrode. The incorporation of SnO_(2) shell is attributed to the enhanced rate capability and cycling performance of Si@SnO_(2) @C nanocomposite.