MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A

BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM To elucidate the role played by microRNA-298(miR-298)in CRC radio-resistance.METHODS To establish a radio-resistant CRC cell line,HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period.The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR,and protein expression determination was realized through Western blotting.Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay.Radio-induced apoptosis was discerned through flow cytometry analysis.RESULTS We observed a marked upregulation of miR-298 in radio-resistant CRC cells.MiR-298 emerged as a key determinant of cell survival following radiation exposure,as its overexpression led to a notable reduction in radiation-induced apoptosis.Intriguingly,miR-298 expression exhibited a strong correlation with CRC cell viability.Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A(DYRK1A)as miR-298’s direct target.CONCLUSION Taken together,our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation,thereby positioning miR-298 as a promising candidate for mitigating radioresistance in CRC.

腹腔镜下经腹膜外入路膀胱癌根治术的初步体会

目的评估腹腔镜下经腹膜外入路膀胱癌根治术的可行性及临床疗效。方法选取2017年5月-2019年5月肌层浸润性膀胱癌患者16例,年龄54~78岁,平均69.4岁。开展腹腔镜下腹膜外入路膀胱癌根治术,术中经腹膜外膀胱切除及淋巴清扫,3例行输尿管皮肤造口术,1例行Studer原位回肠新膀胱术,其余12例行Bricker回肠膀胱术,将回肠通道或回肠新膀胱置于腹膜外腔,完整关闭腹膜,观察术中术后并发症及术后肠道功能恢复情况。结果所有患者均顺利完成手术,无1例中转开放手术或经腹腔入路手术,术中出血量120~360 mL,平均190 mL。3例输尿管皮肤造口患者术后第1天恢复饮食,其余13例术后平均4 d恢复饮食,住院时间7~19 d,平均13.8 d。随访8~32个月,未发现肿瘤复发及转移,无1例发生肠梗阻,1例出现轻度肾积水,随访无进行性加重,所有患者肾功能均正常。结论腹腔镜下经腹膜外入路膀胱癌根治术具有良好的安全性及可行性,术后肠道功能恢复较快,值得临床推广。

基于API 617的离心压缩机转子系统动力学特性研究

本文依据API 617的转子动力学设计要求,对某离心压缩机的转子系统展开动力学特性分析,首先对转子-轴承系统进行建模,再次对其进行临界转速计算,计算结果依据API617的要求进行判定,最后对其开展了稳定性分析。研究结果可以指导压缩机的主机设计。

Effect of NaOH concentration on microstructure and corrosion resistance of MAO coating on cast Al-Li alloy

Ceramic coating was prepared on cast Al-Cu-Li alloy by micro-arc oxidation(MAO) in a silicate electrolyte solution with additives including Na2WO4 and Na OH. The effect of NaOH addition varying from 1 to 9 g/L on the microstructure and corrosion behavior of the coatings was investigated. The coating was characterized by XRD, XPS and SEM with respect to the composition and microstructures. The results show that NaOH promoted the formation of oxides in the reaction of MAO and contributed to the increase of layer thickness. Electrochemical tests(polarization curve and EIS) and mass loss test indicate that the corrosion resistance of the coated Al-Cu-Li alloy was improved with the increased addition of NaOH. Moreover, the results prove that the alumina coating formed in the electrolyte with 7 g/L NaOH showed the best corrosion resistance. The examination of the full immersion corrosion test presents the same result of corrosion resistance.

Effect of refining processes on inclusions and mechanical properties of cast Al-2Li-2Cu-0.2Zr alloy

The effect of different refining processes on inclusions and mechanical properties of cast Al-2Li-2Cu-0.2Zr alloy was investigated, including two-stage hexachloroethane (C2Cl6) refining process, two-stage rotating gas bubbling refining process and two-stage composite refining process. It was found that the two-stage composite refining process, which combined C2Cl6 and rotating gas bubbling, can significantly improve the melt purity and mechanical properties of cast Al-2Li-2Cu-0.2Zr alloy. Compared to the unrefined alloy, the volume fraction of gas porosity defects and slag inclusions decreased from 1.47% to 0.12%, and the yield strength, ultimate tensile strength and elongation of as-quenched alloy increased from 113 MPa,179 MPa and 3.9% to 142 MPa, 293 MPa and 18.1%, respectively. C2Cl6 was first utilized to degas and remove large size slag inclusions before lithium addition, and then the rotating gas bubbling was utilized to do the further degassing and remove the suspended fine inclusions after lithium addition. The two-stage composite refining process can take advantage of two methods and get the remarkable refining effect.

Structure Optimization of Wheel Force Transducer Based on Natural Frequency and Comprehensive Sensitivity

The current research of wheel force transducer （WFT） mainly focuses on test signal processing and decoupling methods based on signal itself, while the WFT structure optimization research related to decreasing the mass and increase the natural frequency and comprehen- sive sensitivity is not enough. In order to improve the WFT test accuracy, a structure optimization method based on natural frequency and comprehensive sensitivity indicators is put forward. The WPT with 8-beam elastic body is used for the finite element modeling （FEM）, in which the fol- lowing variations are taken into consideration： the con- nection type of elastic body with modified rim, the number of connection holes, and the respects of strain beam including the shape, the cross sectional area and the length, etc.. The test results shows that the natural frequency of the connecting block type is increased by 65.5% compared with the connecting seat type of elastic body ＆ modified rim, and the main channel sensitivity is improved as well. The results show that the connecting block type will achieve the best comprehensive performance when the number of connecting holes between the elastic body and the modified rim is 20. And the thinner and longer strain beam with smaller cross section area is preferable within the scope of elastic body mechanical strength. This research proposes a novel structure optimization method for WFT which contributes to improve the measurement performance of WFT.

Microstructural evolution and mechanical performance of cast Mg−3Nd−0.2Zn−0.5Zr alloy with Y additions

This work investigated the effects of different Y additions(0,1.5,3.0 and 4.5 wt.%)on the microstructural evolution and mechanical performance of cast Mg−3Nd−0.2Zn−0.5Zr alloy.The results show that as the Y content increases,the key secondary phases in as-cast alloys change from the Mg_(12)Nd type to the Mg_(24)Y_(5) type.Meanwhile,the number density of Zn−Zr particles in the grains of as-quenched alloys gradually decreases.HAADF-STEM observations of peak-aged samples reveal that element Y is greatly enriched in the globularβ¢precipitates,leading to a significantly increased volume fraction and promoted precipitation kinetics ofβ¢precipitates,resulting in enhanced strength of the alloy.Tensile tests reveal that,with the addition of 4.5 wt.%Y,the yield strength of the base alloy is substantially increased by 88 and 61 MPa after being aged at 200 and 225°C under peak-aged conditions,respectively.

Claudin 18.2 is a potential therapeutic target for zolbetuximab in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is frequently diagnosed and treated in advanced tumor stages with poor prognosis.More effective screening programs and novel therapeutic means are urgently needed.Recent studies have regarded tight junction protein claudin 18.2(CLDN18.2)as a candidate target for cancer treatment,and zolbetuximab(formerly known as IMAB362)has been developed against CLDN18.2.However,there are few data reported thus far related to the clinicopathological characteristics of CLDN18.2 expression for PDAC.AIM To investigate the expression of CLDN18.2 in PDAC patients and subsequently propose a new target for the treatment of PDAC.METHODS The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Omnibus,and European Genome-phenome Archive databases were first employed to analyze the CLDN18 gene expression in normal pancreatic tissue compared to that in pancreatic cancer tissue.Second,we analyzed the expression of CLDN18.2 in 93 primary PDACs,86 para-cancer tissues,and 13 normal pancreatic tissues by immunohistochemistry.Immunostained tissues were assessed applying the histoscore.subsequently,they fell into two groups according to the expression state of CLDN18.2.Furthermore,the correlations between CLDN18.2 expression and diverse clinicopathological characteristics,including survival,were investigated.RESULTS The gene expression of CLDN18 was statistically higher(P<0.01)in pancreatic tumors than in normal tissues.However,there was no significant correlation between CLDN18 expression and survival in pancreatic cancer patients.CLDN18.2 was expressed in 88(94.6%)of the reported PDACs.Among these tumors,50(56.8%)cases showed strong immunostaining.The para-cancer tissues were positive in 81(94.2%)cases,among which 32(39.5%)of cases were characterized for strong staining intensities.Normal pancreatic tissue was identified solely via weak immunostaining.Finally,CLDN18.2 expression significantly correlated with lymph node metastasis,distant metastasis,nerve invasion,stage,and survival of PDAC patients,while there was no correlation between CLDN18.2 expression and localization,tumor size,patient age and sex,nor any other clinicopathological characteristic.CONCLUSION CLDN18.2 expression is frequently increased in PDAC patients.Thus,it may act as a potential therapeutic target for zolbetuximab in PDAC.

Successful treatment of an enormous rectal mucosa-associated lymphoid tissue lymphoma by endoscopic full-thickness resection:A case report

BACKGROUND Colorectal mucosa-associated lymphoid tissue lymphoma(MALToma),a rare kind of nongastric MALToma,lacks consensus on its endoscopic features and standard therapies.According to previous studies on the clinical characteristics and outcomes of colorectal MALToma,endoscopic resection remains a good therapeutic strategy.CASE SUMMARY A 71-year-old woman suffered intermittent hematochezia for 1 mo,accompanied with abdominal pains but without weight loss,fever,chills or fatigue.Colonoscopy showed a massive hemispheric mass with rough and hyperemic mucosa in the lower rectum.Narrow-band imaging magnifying endoscopy detected some branching abnormal blood vessels and disappearance of glandular structure,which was similar with the tree-like appearance sign in gastric MALToma.Endoscopic ultrasonography revealed the lesion to be hypoechoic,boundary-defined,and echo uniform inside,originating from the muscularis propria.Abdominal enhanced computed tomography(CT)demonstrated a soft tissue mass with defined boundary.No enlarged superficial lymph nodes were detected by B-mode ultrasound.C13-urea breath test and serum Helicobacter pylori antibody were both negative.The patient underwent endoscopic full-thickness resection.Postoperative pathological analysis indicated colorectal MALToma.The patient remained asymptomatic after discharge,and follow-up positron emission tomography–CT and colonoscopy showed no residual lesion,remnants or lymph node metastasis.CONCLUSION This case provides new information on the specific endoscopic features of colorectal MALToma and an alternative treatment for patients.

Three-Dimensional Ab Initio Potential Energy Surface and Predicted Spectra for the CH_(4)-Ne Complex

We present a new three-dimensional potential energy surface(PES)for CH_(4)-Ne complex.The electronic structure computations were carried out using the coupled-cluster method with singles,doubles,and perturbative triples[CCSD(T)],the augmented correlationconsistent aug-cc-pVXZ(X=T,Q)basis sets were employed with bond functions placed at the mid-point on the intermolecular axis,and the energies obtained were then extrapolated to the complete basis set limit.Analytic intermolecular PES is obtained by least-squares fitting to the Morse/Long-Range(MLR)potential function form.These fits to 664 points have root-mean-square deviations of 0.042 cm^(−1).The bound rovibrational levels are calculated for the first time,and the predicted infrared spectra are in good agreement with the experimental values.The microwave spectra for CH_(4)-Ne dimer have also been predicted for the first time.The analytic PES can be used for modeling the dynamical behavior in CH_(4)-(Ne)N clusters,and it will be useful for future studies of the collision-induced-absorption for the CH_(4)-Ne dimer.

Metallurgy and Solidification Microstructure Control of Fusion-Based Additive Manufacturing Fabricated Metallic Alloys:A Review

The metal-based additive manufacturing(AM),also referred to as metal 3D printing,has drawn particular interest because it enables direct creation,aided by computationally-directed path design,of intricate components with site-specific compositions and geometrical requirements as well as low buy-to-fly ratios.During the last two decades,the objective of this revolutionary technology has been shifting from only“rapid prototyping”to advanced manufacturing of special high-end products or devices,which,in many aspects,outperform conventional manufacturing technologies.For fusion-based AM,significant progress has been achieved in understanding the processing window of macroscopic scales,non-equilibrium metallurgy of mesoscale scales,and grain evolution of microscopic scales.Although the versatile capacity of AM facilitates new avenues for discovering advanced materials and structures,their potential has still not been fully explored.Given the unique non-equilibrium solidification during the AM process,coarse columnar grains with strong textures are usually developed along the build direction,which downgrades the mechanical performance.To push the limits of this digital manufacturing,this review attempts to provide in-depth and comprehensive overviews of the recent progress in understanding the evolution and control of the as-built microstructure that has been made recently and the challenges encountered during the AM process.

Clinical characteristics of sudden hearing loss during pregnancy

Objective:The objective of this study was to explore the clinical characteristics and management of sudden hearing loss(HL)during pregnancy,thus better guiding the clinical practice.Methods:The clinical and follow-up data of 17 patients(17 ears)with sudden HL during pregnancy were analyzed retrospectively(the observe group).Twelve nonpregnant female patients(12 ears)with sudden HL of similar clinical characteristics were selected as the control group.The prognosis of the two groups was compared.All the patients were followed up after delivery,and two of them were readmitted to the hospital 1–2 months after delivery.Results:The observe group had better improvement in hearing and a higher response rate compared to the control group.The pure tone hearing and speech recognition rate of patients could still be improved after the readmitted treatment,and the hearing could partially recover spontaneously during follow-up.The laboratory indicators that affect the inflammatory response and coagulation pathway were significantly different between the two groups.Conclusions:The hearing condition of sudden HL during pregnancy is severe,and the prognosis of these patients is better than nonpregnant patients of similar clinical characteristics.Postpartum treatment is still effective,and some patients showed self-healing with time during follow-up.The inflammatory response and coagulation function may affect the hearing of patients through a metabolic pathway.

Advances on supramolecular assembly of cyclometalated platinum(Ⅱ) complexes

Organoplatinum（Ⅱ） compounds have received enormous attention over the past decades due to their square-planar geometry as well as intriguing photo-physical properties.Self-assembly has emerged as an excellent approach to create well-ordered supramolecular architectures with tunable properties,which underpin the role of solvent-directed approach for the design of functional materials.In this minireview,the recent advances on supramolecular self-assembly of cyclometalated platinum（Ⅱ） complexes have been discussed.During the self-assembly process,non-covalent Pt-Pt and π-π interactions play crucial roles in controlling the structures and functions of the resulting assemblies.

VDR–SOX2 signaling promotes colorectal cancer stemness and malignancy in an acidic microenvironment

The acidic tumor microenvironment provides an energy source driving malignant tumor progression.Adaptation of cells to an acidic environment leads to the emergence of cancer stem cells.The expression of the vitamin D receptor(VDR)is closely related to the initiation and development of colorectal carcinoma(CRC),but its regulatory mechanism in CRC stem cells is still unclear.Our study revealed that acidosis reduced VDR expression by downregulating peroxisome proliferator-activated receptor delta(PPARD)expression.Overexpression of VDR effectively suppressed the stemness and oxaliplatin resistance of cells in acidosis.The nuclear export signal in VDR was sensitive to acidosis,and VDR was exported from the nucleus.Chromatin immunoprecipitation(ChIP)and assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)analyses showed that VDR transcriptionally repressed SRY-box 2(SOX2)by binding to the vitamin D response elements in the promoter of SOX2,impairing tumor growth and drug resistance.We demonstrated that a change in the acidic microenvironment combined with overexpression of VDR substantially restricted the occurrence and development of CRC in vivo.These findings reveal a new mechanism by which acidosis could affect the stemness of CRC cells by regulating the expression of SOX2 and show that abnormal VDR expression leads to ineffective activation of vitamin D signaling,resulting in a lack of efficacy of vitamin D in antineoplastic process.

Towards reliable assessment of hydrogen oxidation electrocatalysts for anion-exchange membrane fuel cells

Recent advancement of proton exchange membrane fuel cells has led to commercial sales of fuel-cell cars but market barrier exists because this technology heavily relies on platinum catalyst.Given the permission of adopting platinum-group-metal-free catalysts,anion-exchange membrane fuel cell has received notable attention.However,the sluggish kinetics of anodic hydrogen oxidation reaction(HOR)largely limit the cell efficiency.Although many high-performance HOR catalysts have been reported,there are analytical uncertainties in the literature concerning the assessment of the catalyst activity.Here we determine the origin of false HOR currents in the recorded polarization curves and propose a rigorous approach to eliminate them.We unveil experimentally the uncertainties of obtaining exchange current densities(j0)using Tafel plot from Bulter–Volmer equation and recommend employing the micro-polarization region method.For bulky catalysts that cannot establish a well-defined diffusion layer,we suggest applying external stirring bar to offer certain level of enforced convection and using j0 to compare the activity.

Parkin Inhibits Static Mechanical Pain by Suppressing Membrane Trafficking of Mechano-transducing Ion Channel TACAN

Dear Editor,Clinical practice shows that harmless mechanical stimulation can cause pain in humans after inflammation or nerve injury,leading to asensation called mechanical allodynia[].Mechanicalallodyniacomesin many forms:dynamic allodynia caused by something as light as a brushstroke,static allodynia caused by stimulation by weak von Frey filaments[2],which seriously disturbs thequalityof life and working abilityofpatients.Parkin,an E3ubiquitin ligase,is linked to neurodegenerative diseases such as Parkinson's disease(PD)and Alzheimer's disease(AD)[3,4].

Comparative chemical characters of Sparganii Rhizoma from different regions in China

Objective： To compare the chemical characters of Sparganii Rhizoma from different areas via chromatographic analysis and to establish a sensitive LC/MS method for quality assessment of Sparganii Rhizoma.Methods： Under the optimised HPLC-PDA chromatographic conditions,twenty batches of Sparganii Rhizoma were analyzed by HPLC fingerprints.Principal component analysis（PCA）,orthogonal projections to latent structures discriminant analysis（OPLS-DA）and hierarchical cluster analysis（HCA）were performed based on all peak areas of Sparganii Rhizoma fingerprints.Meanwhile,part of common peaks were subsequently quantified by UFLC-QTRAP-MS.Results： The similarity values of HPLC fingerprints fluctuated in a wide range of 0.511–0.973,which showed variable differences of chemical characters among Sparganii Rhizoma from twenty habitats.PCA,OPLS-DA and HCA indicated that samples could be divided into five groups with different chemical characters,which generally corresponded with their geographical distributions.A total of 31 peaks in HPLC fingerprints were marked,and eight of them were identified and quantified.The quantitative result was generally in agreement with the classifications based on HPLC fingerprints,which indicated that Sparganii Rhizoma samples from eastern China mostly contained more contents including phenolic acids and flavonoids.Conclusion： This study not only proved that there were relationships between geographic distributions and internal chemical compositions of plants,which could provide evidence to the traditional Chinese medicine concept ＂geo-authentic＂,but also supplied a sensitive and rapid simultaneous quantitive method for the quality estimation of Sparganii Rhizoma.

Modular divergent creation of dual-cocatalysts integrated semiconducting sulfide nanotriads for enhanced photocatalytic hydrogen evolution

Heteronanostructures(HNs)with precise components and interfaces are important for many applications,such as designing efficient and robust solar-to-fuel catalysts via integrating specific semiconductors with favorable band alignments.However,rationally endowing such features with rigorous framework control remains a synthetic bottleneck.Herein,we report a modular divergent creation of dual-cocatalysts integrated semiconducting sulfide nanotriads(NTds),comprising both isolated Pd_(x)S oxidation(ox)and MoS_(2) reduction(red)domains within each single CdS counterpart,which exhibit superior photocatalytic activity and stability for hydrogen evolution reaction(HER).The stepwise constructed Pd_(x)S_((ox))−CdS−MoS_(2(red)) NTds possess dualinterfaces facilitating continuous charge separation and segregated active sites accelerating redox reactions,respectively,achieving the HER rate up to 9 mmol·h^(−1)·g^(−1),which is about 60 times higher than that of bare CdS,and show no evidence of deactivation after long-term cycling.This design principle and transformation protocol provide predictable retrosynthetic pathways to HNs with increased degree of complexity and more elaborate functionalities that are otherwise inaccessible.

Phase-Controlled 1T Transition-Metal Dichalcogenide-Based Multidimensional Hybrid Nanostructures

Metallic-phase transition-metal dichalcogenides(TMDCs)exhibit unusual physicochemical properties compared with their semiconducting counterparts.However,they are thermodynamically unstable to access and it is even more challenging to construct their metastable-phase heterostructures.Herein,we demonstrate a general solution protocol for phase-controlled synthesis of distorted octahedral 1T WS2-based(1T structure denotes an octahedral coordination for W atom)multidimensional hybrid nanostructures from two-dimensional(2D),one-dimensional(1D),and zero-dimensional(0D)templates.This is realized by tuning the reactivity of tungsten precursor and the interaction between crystal surface and ligands.As a conceptual study on crystal phase-and dimensionality-dependent applications,we find that the three-dimensional(3D)hierarchical architectures achieved,comprising 1T WS2 and 2D Ni3S4,are very active and stable for catalyzing hydrogen evolution.Our results open up a new way to rationally design phase-controlled nanostructures with increased complexity and more elaborate functionalities.

Joint Resource Allocation for Lifetime-aware Cooperative Multi-carrier DF System

In this paper,we study the problem of optimal resource allocation for lifetime maximization in an orthogonal-frequencydivision multiplexing(OFDM)system with decode-and-forward relay.The goal is to minimize total energy cost of the system by jointly optimizing power allocation,subcarrier pairing and relay selection.We present a heuristic solution that is composed of two parts.The first part is an optimal power allocation approach to allocate power to a subcarrier pair of the source and the relay.The second part is a modified Hungarian algorithm to make subcarrier pairing and relay selection.Evaluations show that the presented scheme outperforms other schemes in the total transmitted data and the network lifetime.