SLC6A14 promotes ulcerative colitis progression by facilitating NLRP3 inflammasome-mediated pyroptosis

BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explore the role of SLC6A14 in UC-associated pyroptosis.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR),immunoblotting,and immunohistochemical were used to assess SLC6A14 in human UC tissues.Lipopolysaccharide(LPS)was used to induce inflammation in FHC and NCM460 cells and model enteritis,and SLC6A14 levels were assessed.Pyroptosis markers were quantified using enzyme-linked immunosorbent assay,Western blotting,and qRT-PCR,and EdU incubation,CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis.Mouse models of UC were used for verification.RESULTS SLC6A14 was increased and correlated with NLRP3 in UC tissues.LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels.Reducing SLC6A14 increased cell proliferation and suppressed apoptosis.Reducing SLC6A14 decreased pyroptosis-associated proteins(ASC,IL-1β,IL-18,NLRP3).NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis.SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis.CONCLUSION SLC6A14 promotes UC pyroptosis by regulating NLRP3,suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.

Bibliometric analysis of research challenges and trends in urban underground space

The utilization and development of urban underground space play a crucial role in optimizing the layout of civic architecture and enhancing the urban ecological environment,which contributes toward increasing the overall carrying capacity and promoting sustainable development in megacities.To delve into the research progress of urban underground space,knowledge maps were created using the information visualization software VOSviewer.The literature was systematically extracted from three prominent databases,namely,Web of Science,Scopus,and China National Knowledge Infrastructure.According to the bibliometric analysis of the co-citation and core words co-occurrence,the trends and challenges of research on urban underground space were identified.As highlighted by the results obtained,it still remains highly challenging to achieve interdisciplinary collaboration in urban underground space research;the research trends of urban underground space consist of collaborative planning and whole life cycle sustainable development,multisource geological data informatization and resource evaluation,infrastructure design optimization,and intelligent construction.The knowledge map,drawn using bibliometric methods,offers a quantitative analysis of literature retrieval across various levels.It is recognized as an essential tool for exploring and identifying challenges and trends in urban underground space.

Glucocorticoid reduces the efficacy of afatinib on the head and neck squamous cell carcinoma

Glucocorticoids(GC)are widely used to counter the adverse events during cancer therapy;nonetheless,previous studies pointed out that GC may reduce the efficacy of chemotherapy on cancer cells,especially in epidermal growth factor receptor(EGFR)-targeted therapy of head and neck squamous cell carcinoma(HNSCC)remaining to be elucidated.The primary aim of the present study was to probe into the GC-induced resistance of EGFR-targeted drug afatinib and the underlying mechanism.HNSCC cell lines(HSC-3,SCC-25,SCC-9,and H-400)and the human oral keratinocyte(HOK)cell lines were assessed for GC receptor(GR)expression.The promoting tumor growth effect of GC was evaluated by the CCK-8 assay and flow cytometry.Levels of signaling pathways participants GR,mTOR,and EGFR were determined by quantitative polymerase chain reaction and western blotting.GC increased the proliferation of HNSCC cells in a GR-dependent manner and promoted AKT/mTOR signaling.But GC failed in counteracting the inhibition of rapamycin in the mTOR signaling pathway.Besides,GC also induced resistance to EGFR-targeted drug afatinib through AKT/mTOR instead of the EGFR/ERK signaling pathway.Thus,GCs reduce the efficacy of afatinib on HNSCC,implicating a cautious use of glucocorticoids in clinical practice.

紫花苜蓿MsUGT73B2基因的克隆及表达

糖基化是植物体蛋白、激素等物质的常见修饰方式,对维持植物正常生长发育具有重要作用,在植物中糖基化反应由糖基转移酶催化。利用蒺藜苜蓿参考序列通过RACE法克隆得到紫花苜蓿基因MsUGT73B2的全长序列,利用生物信息学方法分析其氨基酸序列、二级结构、理化性质等,RT-qPCR分析基因表达情况,构建基因表达载体,研究亚细胞定位。结果表明,MsUGT73B2基因全长1 512bp,编码503个氨基酸,属于稳定的亲水性蛋白,序列比对结果显示其属于UGT家族基因,亚细胞定位于细胞质中。MSOGT73B2主要在紫花苜蓿叶片中表达,且干旱、10μmol/L ABA处理下在2h之前升高,之后下降;在150mmol/L NaCl胁迫处理下表现为4h之前表达水平升高,之后下降的趋势。

Effect of intermetallic phases on the anodic oxidation and corrosion of 5A06 aluminum alloy

Intermetallic phases were found to influence the anodic oxidation and corrosion behavior of 5A06 aluminum alloy. Scattered in- termetallic particles were examined by scanning electron microscopy （SEM） and energy dispersive spectroscopy （EDS） after pretreatment. The anodic film was investigated by transmission electron microscopy （TEM）, and its corrosion resistance was analyzed by electrochemical impedance spectroscopy （EIS） and Tafel polarization in NaC1 solution. The results show that the size of A1-Fe-Mg-Mn particles gradually decreases with the iron content. During anodizing, these intermetallic particles are gradually dissolved, leading to the complex porosity in the anodic film beneath the particles. After anodizing, the residual particles are mainly silicon-containing phases, which are embedded in the an- odic film. Electrochemical measurements indicate that the porous anodic film layer is easily penetrated, and the barrier plays a dominant role in the overall protection. Meanwhile, self-healing behavior is observed during the long immersion time.

热交联结合紫外光表面固化制备聚己内酯形状记忆材料

通过热引发剂引发聚己内酯(PCL)自由基交联,再结合紫外光表面二次固化的协同作用,制备了一系列光引发剂添加量不同的PCL形状记忆材料。通过差示扫描量热分析和热重分析、形状记忆性能测试和力学性能测试研究了Irgacure 2959(Ir2959)对PCL交联材料的结晶度和热稳定性、形状记忆性能、力学性能的影响。结果表明,相较于热交联体系,结合紫外光表面二次固化后明显提高了材料的形状记忆性能和力学性能。当光引发剂Ir2959质量分数为3%时(P/B/I-3),材料的形状记忆性能达到峰值,形状固定率(Rf)和形状回复率(Rr)分别由93.0%和91.4%提升至99.5%和99.8%;拉伸强度和断裂伸长率分别由42.5 MPa和658.1%提升至49.9 MPa和805.0%。

Use of Impella cardiac axial flow pump for cardiogenic shock(A newer alternative)-How good is the evidence?

The adverse outcomes of a ventricular heart failure(left,right or biventricular)caused by cardiogenic shock are aggravated by lung oedema and organ mal perfusion.Despite advances in medical sciences,revascularisation and mechanical hemodynamic support have proved ineffective in reducing the mortality rate in such patients.A thorough study of the data available about cardio-vascular diseases reveals that the application of conventional methods of treatment are least helpful to practically restore normal functions of heart when it experiences end-stage systolic ventricular failure.Thus,to overcome the challenges and find alternatives to address this issue,percutaneous ventricular support devices/machines were designed and successfully introduced.These devices have revolutionized the treatment of ventricular heart failures and are now in use all over the world.In this review paper a newer mechanical circulatory support(MCS)device,Impella,has been discussed and compared with a few other devices like(Intra-aortic Balloon Pump(IABP),Extracorporeal Circulation(ECLS)and Veno-arterial Extracorporeal Membrane Oxygenation(VA-ECMO).This article studies the challenges being faced during the treatment of cardiogenic shock,and thoroughly discusses the use and effectiveness of Impella Cardiac Axial Pump in each emergency.It can be said that mechanical circulatory support(MCS)device use during percutaneous coronary intervention(PCI)should be individualized based on multiple factors with a recommended use in patients with the greatest potential benefit and a relatively low risk of device-related complications.The current literature suggests that the outcomes of use of Impella and other mechanical circulatory support devices like IABP and VA-ECMO are comparable.Though there seem to be a few advantages of Impella over the others,sufficiently powered,multi-centric,randomised control trials are needed to establish its superiority.

An Integrated Simulation System Based on Digital Human Phantom for 4D Radiation Therapy of Lung Cancer

Purpose: To develop and test an integrated simulation system based on the digital Extended Cardio Torso (XCAT) phantom for 4-dimensional (4D) radiation therapy of lung cancer. Methods: A computer program was developed to facilitate the characterization and implementation of the XCAT phantom for 4D radiation therapy applications. To verify that patient-specific motion trajectories are reproducible with the XCAT phantom, motion trajectories of the diaphragm and chest were extracted from previously acquired MRI scans of five subjects and were imported into the XCAT phantom. The input versus the measured trajectories was compared. Simulation methods of 4D-CT and 4D-cone-beam CT (CBCT) based on the XCAT phantom were developed and tested for regular and irregular respiratory patterns. Simulation of 4D dose delivery was illustrated in a simulated lung stereotactic-body radiation therapy (SBRT) case based on the XCAT phantom. Dosimetric comparison was performed between the planned dose and simulated delivered dose. Result: The overall mean (±standard deviation) difference in motion amplitude between the input and measured trajectories was 1.19 (±0.79) mm for the XCAT phantoms with voxel size of 2 mm. 4D-CT and 4D-CBCT images simulated based on the XCAT phantom were validated using regular respiratory patterns and tested for irregular respiratory patterns. Comparison between simulated 4D dose delivery and planned dose for the lung SBRT case showed comparable results in all dosimetric matrices: the relative differences were 0.3%, 4.0%, 0%, and 2.8%, respectively, for max cord dose, max esophagus dose, mean heart dose, and V20Gy of the lungs. 97.5% of planning target volume (PTV) received prescription dose in the simulated 4D delivery, as compared to 95% of PTV received prescription dose in the plan. Conclusion: We developed an integrated simulation system based on the XCAT digital phantom and illustrated its utility in 4D radiation therapy of lung cancer. This simulation system is potentially a useful tool for quality control and development of imaging and treatment techniques for 4D radiation therapy of lung cancer.

Advanced 4-dimensional cone-beam computed tomography reconstruction by combining motion estimation, motioncompensated reconstruction, biomechanical modeling and deep learning

4-Dimensional cone-beam computed tomography(4D-CBCT)offers several key advantages over conventional 3DCBCT in moving target localization/delineation,structure de-blurring,target motion tracking,treatment dose accumulation and adaptive radiation therapy.However,the use of the 4D-CBCT in current radiation therapy practices has been limited,mostly due to its sub-optimal image quality from limited angular sampling of conebeam projections.In this study,we summarized the recent developments of 4D-CBCT reconstruction techniques for image quality improvement,and introduced our developments of a new 4D-CBCT reconstruction technique which features simultaneous motion estimation and image reconstruction(SMEIR).Based on the original SMEIR scheme,biomechanical modeling-guided SMEIR(SMEIR-Bio)was introduced to further improve the reconstruction accuracy of fine details in lung 4D-CBCTs.To improve the efficiency of reconstruction,we recently developed a U-net-based deformation-vector-field(DVF)optimization technique to leverage a population-based deep learning scheme to improve the accuracy of intra-lung DVFs(SMEIR-Unet),without explicit biomechanical modeling.Details of each of the SMEIR,SMEIR-Bio and SMEIR-Unet techniques were included in this study,along with the corresponding results comparing the reconstruction accuracy in terms of CBCT images and the DVFs.We also discussed the application prospects of the SMEIR-type techniques in image-guided radiation therapy and adaptive radiation therapy,and presented potential schemes on future developments to achieve faster and more accurate 4D-CBCT imaging.

Viromes of Haemaphysalis longicornis reveal different viral abundance and diversity in free and engorged ticks

Haemaphysalis longicornis ticks,commonly found in East Asia,can transmit various pathogenic viruses,includingthe severe fever with thrombocytopenia syndrome virus(SFTSV)that has caused febrile diseases among humansin Hubei Province.However,understanding of the viromes of H.longicornis was limited,and the prevalence ofviruses among H.longicornis ticks in Hubei was not well clarified.This study investigates the viromes of bothengorged(fed)and free(unfed)H.longicornis ticks across three mountainous regions in Hubei Province from 2019to 2020.RNA-sequencing analysis identified viral sequences that were related to 39 reference viruses belonging tounclassified viruses and seven RNA viral families,namely Chuviridae,Nairoviridae,Orthomyxoviridae,Parvoviridae,Phenuiviridae,Rhabdoviridae,and Totiviridae.Viral abundance and diversity in these ticks were analysed,andphylogenetic characteristics of the Henan tick virus(HNTV),Dabieshan tick virus(DBSTV),Okutama tick virus(OKTV),and Jingmen tick virus(JMTV)were elucidated based on their full genomic sequences.Prevalenceanalysis demonstrated that DBSTV was the most common virus found in individual H.longicornis ticks(12.59%),followed by HNTV(0.35%),whereas JMTV and OKTV were not detected.These results improve our understanding of H.longicornis tick viromes in central China and highlight the role of tick feeding status and geographyin shaping the viral community.The findings of new viral strains and their potential impact on public health raisethe need to strengthen surveillance efforts for comprehensively assessing their spillover potentials.

Field assessment of straw pellet combustion in improved heating stoves in rural Northeast China

Straw pellets are widely promoted and expected to be a cleaner alternative fuel to unprocessed crop residues and rawcoal in rural China.However,the effectiveness of these dissemination programs is not well evaluated.In this field study,emission characteristics of burning strawpellets,rawcoal,and unprocessed corn cobs in heating stoveswere investigated in a pilot village in Northeast China.Emission measurements covering the whole combustion cycle(ignition,flaming,and smoldering phases)shows the promotion of improved heating stoves and straw pellets could reduce pollutant emissions(e.g.,SO_(2) and CO),but increase NO_(X) and PM_(2.5) emissions compared to the initial stove-fuel use pattern in the studied area.There is a significant variance in emission characteristics between different combustion phases.The normalized emission concentrations of the different stove-fuel combinations were higher than the limits in the Chinese national standard for heating stoves,indicating that the standard is not met for real-world emissions.Coal consumption was lower than official data.Household surveys were conducted to identify the barriers to fuel and stove access associated with existing promotion strategies,management,and policies.The pilot program was of the typical“subsidy-and-policy-dependence”pattern and was unlikely to be implemented on a large scale.Technological innovation,operational optimization,and proper policies considering the local socioeconomic factors are needed to sustain the promotion of biomass straw pellets and stoves.

Changes in process and outcome for ST elevation myocardial infarction in central China from 2011 to 2018

Background:Limited data are available on the changes in the quality of care for ST elevation myocardial infarction(STEMI)during China’s health system reform from 2009 to 2020.This study aimed to assess the changes in care processes and outcome for STEMI patients in Henan province of central China between 2011 and 2018.Methods:We compared the data from the Henan STEMI survey conducted in 2011-2012(n=1548,a cross-sectional study)and the Henan STEMI registry in 2016-2018(n=4748,a multicenter,prospective observational study).Changes in care processes and in-hospital mortality were determined.Process of care measures included reperfusion therapies,aspirin,P2Y12 antagonists,β-blockers,angiotensin-converting enzyme inhibitors or angiotensin receptor blockers,and statins.Therapy use was analyzed among patients who were considered ideal candidates for treatment.Results:STEMI patients in 2016-2018 were younger(median age:63.1 vs.63.8 years)with a lower proportion of women(24.4%[1156/4748]vs.28.2%[437/1548])than in 2011-2012.The composite use rate for guideline-recommended treatments increased significantly from 2011 to 2018(60.9%[5424/8901]vs.82.7%[22,439/27,129],P<0.001).The proportion of patients treated by reperfusion within 12 h increased from 44.1%(546/1237)to 78.4%(2698/3440)(P<0.001)with a prolonged median onset-to-first medical contact time(from 144 min to 210 min,P<0.001).The use of antiplatelet agents,statins,andβ-blockers increased significantly.The risk of in-hospital mortality significantly decreased over time(6.1%[95/1548]vs.4.2%[198/4748],odds ratio[OR]:0.67,95%confidence interval[CI]:0.50-0.88,P=0.005)after adjustment.Conclusions:Gradual implementation of the guideline-recommended treatments in STEMI patients from 2011 to 2018 has been associated with decreased in-hospital mortality.However,gaps persist between clinical practice and guideline recommendation.Public awareness,reperfusion strategies,and construction of chest pain centers need to be further underscored in central China.

Technology development and cost analysis of multiple pollutant abatement for ultra-low emission coal-fired power plants in China

The implementation of ultra-low emission(ULE)limits(SO_(2):35 mg/m3,NOx:50 mg/m3,PM:10 mg/m3)promoted the development of flue gas treatment technologies in China.Pollutant control technology development for Chinese coal-fired power plants was summarized and an analysis of the applicability and cost of pollutant control technologies was conducted.Detailed data were collected from 30 ultra-low emission coal-fired units across China.Based on a cost analysis model,the average unit power generation incremental costs were 0.0144and 0.0095 CNY/(kW·hr)for SO_(2)and NOx control technologies,respectively.The unit power generation incremental cost of twin spray tower technology was 7.2%higher than that of dual-loop spray tower technology.The effect of key parameters on operating cost was analyzed.The unit power generation incremental cost increased because of increments in the electricity price for SO_(2)control technology and the price of the reductant in NOx control technology.With high sulfur content or NOx concentration,the unit power generation incremental cost caused by pollutant control increased,whereas the unit pollutant abatement cost decreased.However,the annual operating hours or load increased,thereby leading to a decline in unit power generation incremental cost and unit pollutant abatement cost.

Development and Characterization of Nanobody-Derived CD47 Theranostic Pairs in Solid Tumors

Overexpression of CD47 is frequently observed in various types of human malignancies,inhibiting myeloidmediated elimination of tumor cells and affecting the prognosis of cancer patients.By mapping biomarker expression,immuno-positron emission tomography has been increasingly used for patient screening and response monitoring.By immunization alpacas with recombinant human CD47,we prepared a CD47-targeting nanobody C2 and developed[^(68)Ga]Ga-NOTA-C2,followed by an exploration of the diagnostic value in CD47-expressing tumor models including gastric-cancer patient-derived xenograft models.By fusing C2 to an albumin binding domain(ABD),we synthesized ABDC2,which had increased in vivo half-life and improved targeting properties.We further labeled ABDC2 with^(68)Ga/^(89)Zr/177Lu to develop radionuclide theranostic pairs and evaluated the pharmacokinetics and theranostic efficacies of the agents in cell-and patient-derived models.Both C2 and ABDC2 specifically reacted with human CD47 with a high KD value of 23.50 and 84.57 pM,respectively.[^(68)Ga]Ga-NOTA-C2 was developed with high radiochemical purity(99>%,n=4)and visualized CD47 expression in the tumors.In comparison to the rapid renal clearance and short half-life of[^(68)Ga]Ga-NOTA-C2,both[^(68)Ga]Ga-NOTA-ABDC2 and[^(89)Zr]Zr-DFOABDC2 showed prolonged circulation and increased tumor uptake,with the highest uptake of[^(89)Zr]Zr-DFO-ABDC2 occurring at 72 h post-injection.Moreover,[177Lu]Lu-DOTA-ABDC2 radioimmunotherapy suppressed the tumor growth but was associated with toxicity,warranting further optimization of the treatment schedules.Taken together,we reported a series of nanobody-derived CD47-targeted agents,of which[^(68)Ga]Ga-NOTA-C2 and[^(89)Zr]Zr-DFO-ABDC2 are readily translatable.Optimization and translation of CD47-targeted theranostic pair may provide new prospects for CD47-targeted management of solid tumors.

Construction of digital 3D magic-cube organization structure for innovation-driven manufacturing

Owing to the heterogeneity between functional units and resource scarcity,manufacturing firms have been struggling with intra-organizational coordination for productivity and innovation.Traditional organizational structures,such as linear-functional and matrix,may cause responsibility division and independent goals(Shahani,2020),and are more difficult to be adopted by large-sized innovative manufacturing firms for quantity production.This is based on a review of several new forms of organization(i.e.,network organization,multiteam system,and platform organization)compared with the traditional forms of organization(i.e.,linear,matrix,and business unit organization,among others).This study proposes a three-dimensional(3D)magic-cube organizational structure,considering the product dimensions,business,and administration.Moreover,the characteristics,propositions of system operation,system dynamic model,and working model of the 3D magic-cube organization are described.Finally,the 3D model is applied in a Chinese manufacturing firm to test its effectiveness.By redesigning the post and pay system,the pilot organization establishes a project-driven and cross-functional coordination mechanism,positively affecting the firm’s financial profit,output value,labor productivity,and income of per capita.The proposed 3D model can be adopted by large-or medium-sized manufacturing firms for product development and innovation.The implications of both practice and theory are also discussed in this study.

Patent Recommendation Based on Boundary-Spanning Technology Search:An Empirical Study from the Robotics Field

A three-dimensional boundary-spanning technology search model including search depth, scope and height is established, and a quantitative calculation method is proposed to dynamically describe an organisation's technology search behaviour and demand characteristics. Organisations are clustered by types as technical, comprehensive, or professional using k-means based on technology search behaviour. Recommendation strategies for various types of organisations are proposed based on this, and the search and supply libraries of each organisation are built by considering their type and search contents. The semantic similarity between patents in different libraries is calculated using a Word2Vec and TextRank model to achieve patent recommendations. An empirical study of the robotics field shows a recommendation accuracy of 0.751, and the accuracy of the technical, comprehensive, and professional types is 0.8282, 0.5389 and 0.7723, respectively. This study considers an organisation's dynamic search behaviour and makes class-based recommendations, with a low computational complexity and strong interpretability.

Slope stability analysis based on big data and convolutional neural network

The Limit Equilibrium Method(LEM)is commonly used in traditional slope stability analyses,but it is time-consuming and complicated.Due to its complexity and nonlinearity involved in the evaluation process,it cannot provide a quick stability estimation when facing a large number of slopes.In this case,the convolutional neural network(CNN)provides a better alternative.A CNN model can process data quickly and complete a large amount of data analysis in a specific situation,while it needs a large number of training samples.It is difficult to get enough slope data samples in practical engineering.This study proposes a slope database generation method based on the LEM.Samples were amplified from 40 typical slopes,and a sample database consisting of 20000 slope samples was established.The sample database for slopes covered a wide range of slope geometries and soil layers’physical and mechanical properties.The CNN trained with this sample database was then applied to the stability prediction of 15 real slopes to test the accuracy of the CNN model.The results show that the slope stability prediction method based on the CNN does not need complex calculation but only needs to provide the slope coordinate information and physical and mechanical parameters of the soil layers,and it can quickly obtain the safety factor and stability state of the slopes.Moreover,the prediction accuracy of the CNN trained by the sample database for slope stability analysis reaches more than 99%,and the comparisons with the BP neural network show that the CNN has significant superiority in slope stability evaluation.Therefore,the CNN can predict the safety factor of real slopes.In particular,the combination of typical actual slopes and generated slope data provides enough training and testing samples for the CNN,which improves the prediction speed and practicability of the CNN-based evaluation method in engineering practice.

HIV-1 exposure triggers autophagic degradation of stathmin and hyperstabilization of microtubules to disrupt epithelial cell junctions

Dear Editor,Human immunodeficiency virus type 1(HIV-1)infection is mainly initiated on mucosal epithelial surfaces.Exposure to HIV-1 impairs the mucosal epithelial barrier,allowing viral transmission across the mucosal epithelium.1 Interaction of HIV-1 envelope glycoprotein gp120 with its primary receptor,cluster of differentiation 4(CD4),and chemokine coreceptors has been implicated in the disruption of epithelial cell junctions upon HIV-1 exposure.1 However,the molecular details and underlying mechanisms of this disruption remain elusive.