A novel relationship between elastic modulus and void ratio associated with principal stress for coral calcareous sand

Elastic moduli,e.g.shear modulus G and bulk modulus K,are important parameters of geotechnical materials,which are not only the indices for the evaluation of the deformation ability of soils but also the important basic parameters for the development of the constitutive models of geotechnical materials.In this study,a series of triaxial loading-unloading-reloading shear tests and isotropic loading-unloadingreloading tests are conducted to study several typical mechanical properties of coral calcareous sand(CCS),and the void ratio evolution during loading,unloading and reloading.The test results show that the stress-strain curves during multiple unloading processes are almost parallel,and their slopes are much greater than the deformation modulus at the initial stage of loading.The relationship between the confining pressure and the volumetric strain can be defined approximately by a hyperbolic equation under the condition of monotonic loading of confining pressure.Under the condition of confining pressure unloading,the evolution of void ratio is linear in the e-lnp0 plane,and these lines are a series of almost parallel lines if there are multiple processes of unloading.Based on the experimental results,it is found that the modified Hardin formulae for the elastic modulus estimation have a significant deviation from the tested values for CCS.Based on the experimental results,it is proposed that the elastic modulus of soils should be determined by the intersection line of two spatial surfaces in the G/K-e-p’/pa space(pa:atmosphere pressure).“Ye formulation”is further proposed for the estimation of the elastic modulus of CCS.This new estimation formulation for soil elastic modulus would provide a new method to accurately describe the mechanical behavior of granular soils.

Horizontal well spacing optimization and gas injection simulation for the ultra-low-permeability Yongjin reservoir

Optimal spacing for vertical wells can be effectively predicted with several published methods,but methods suitable for assessing the proper horizontal well spacing are rare.This work proposes a method for calculating the optimal horizontal well spacing for an ultra-low permeability reservoir e the Yongjin reservoir in the Juggar Basin,northwestern China.The result shows that a spacing of 640m is the most economical for the development of the reservoir.To better develop the reservoir,simulation approaches are used and a new model is built based on the calculated well spacing.Since the reservoir has an ultralow permeability,gas injection is regarded as the preferred enhanced oil recovery(EOR)method.Injection of different gases including carbon dioxide,methane,nitrogen and mixed gas are modelled.The results show that carbon dioxide injection is the most efficient and economical for the development of the reservoir.However,if the reservoir produces enough methane,reinjecting methane is even better than injecting carbon dioxide.

Association of frailty and malnutrition with overall survival in adults with gastrointestinal cancer:A prospective cohort study

Background:Themortality burden of patients with gastrointestinalmalignancies is increasing worldwide,suggesting the need formore effective prognostic indicators.This study utilized a prospective cohort to(1)analyze the relationship between frailty and malnutrition and their association with the overall survival(OS)in adults with gastrointestinal cancer and(2)explore which specific frailty-related factors most significantly affect the OS.Methods:Participants diagnosed with gastrointestinal cancer from 2013 to 2018 who were enrolled in the Investigation on Nutrition Status and Clinical Outcome of Common Cancers study were identified.Malnutrition was determined using the Patient-Generated Subjective Global Assessment,whereas frailty was assessed using the FRAIL scale.The main outcome measured was the all-cause mortality.Multivariable-adjusted logistic regression was used to analyze the cross-sectional link between the nutritional status and frailty.Univariate and multivariate Cox regression analyses were conducted to explore the longitudinal association of these with the OS.Results:Among the 4,361 patients enrolled in the study,1,136 deaths were observed over a median follow-up of 43.4 months.Malnourished patients had a significantly higher risk of frailty than well-nourished patients(OR=6.25,95%CI=5.23–7.51).Frailty and malnutrition independently predicted the OS,with frailty showing an HR of 1.50(95%CI=1.33–1.69)and malnutrition showing an HR of 1.51(95%CI=1.31–1.74).Patientswith both frailty andmalnutrition had the highest all-causemortality risk(HR=1.82,95%CI=1.55–2.14)compared with patients with neither risk factor.Mortality rates rose with the accumulation of additional frailty-related factors.Conclusions:Malnutrition and frailty are interrelated prognostic factors in patients with gastrointestinalmalignancies,and their simultaneous presence worsens the patient outcomes.Higher scores for resistance and ambulation are major factors associated with a poorer outcome.Future large-scale prospective studies with repeated measurements are necessary to further explore the complex associations among frailty,malnutrition,and the prognosis in patients with gastrointestinal cancer.

Eff ects of thinning on ecosystem carbon storage and tree-shrub-herb diversity of a low-quality secondary forest in NE China

Thinning is a widely used forest management tool but systematic research has not been carried out to verify its eff ects on carbon storage and plant diversity at the ecosystem level.In this study,the eff ect of thinning was assessed across seven thinning intensities(0,10,15,20,25,30 and 35%)in a low-quality secondary forest in NE China over a ten-year period.Thinning aff ected the carbon storage of trees,and shrub,herb,and soil layers(P<0.05).It fi rst increased and then decreased as thinning intensity increased,reaching its maximum at 30%thinning.Carbon storage of the soil accounted for more than 64%of the total carbon stored in the ecosystem.It was highest in the upper 20-cm soil layer.Thinning increased tree species diversity while decreasing shrub and herb diversities(P<0.05).Redundancy analysis and a correlation heat map showed that carbon storage of tree and shrub layers was positively correlated with tree diversity but negatively with herb diversity,indicating that the increase in tree diversity increased the carbon storage of natural forest ecosystems.Although thinning decreased shrub and herb diversities,it increased the carbon storage of the overall ecosystem and tree species diversity of secondary forest.Maximum carbon storage and the highest tree diversity were observed at a thinning intensity of 30%.This study provides evidence for the ecological management of natural and secondary forests and improvement of ecosystem carbon sinks and biodiversity.

Cellular and molecular characteristics of the premetastatic niches

The premetastatic niches(PMN)formed by primary tumor-derived molecules regulate distant organs and tissues to further favor tumor colonization.Targeted PMN therapy may prevent tumor metastasis in the early stages,which is becoming increasingly important.At present,there is a lack of in-depth understanding of the cellular and molecular characteristics of the PMN.Here,we summarize current research advances on the cellular and molecular characteristics of the PMN.We emphasize that PMN intervention is a potential therapeutic strategy for early prevention of tumor metastasis,which provides a promising basis for future research and clinical application.

A novel model to evaluate spatial structure in thinned conifer-broadleaved mixed natural forests

In order to ensure the effective analysis and reconstruction of forests,it is key to ensure the quantitative description of their spatial structure.In this paper,a distance model for the optimal stand spatial structure based on weighted Voronoi diagrams is proposed.In particular,we provide a novel methodological model for the comprehensive evaluation of the spatial structure of forest stands in natural mixed conifer-broadleaved forests and the formulation of management decision plans.The applicability of the rank evaluation and the optimal solution distance model are compared and assessed for different standard sample plots of natural mixed conifer-broadleaved forests.The effect of crown width on the spatial structure unit of the trees is observed to be higher than that of the diameter at breast height.Moreover,the influence of crown length is greater than that of tree height.There are nine possible spatial structure units determined by the weighted Voronoi diagram for the number of neighboring trees in the central tree,with an average intersection of neighboring crowns reaching 80%.The rank rating of natural forest sample plots is correlated with the optimal solution distance model,and their results are generally consistent for natural forests.However,the rank rating is not able to provide a quantitative assessment.The optimal solution distance model is observed to be more comprehensive than traditional methods for the evaluation of the spatial structure of forest stands.It can effectively reflect the trends in realistic stand spatial structure factors close to or far from the ideal structure point,and accurately assesses the forest spatial structure.The proposed optimal solution distance model improves the integrated evaluation of the spatial structure of forest stands and provides solid theoretical and technical support for sustainable forest management.

Bee Colony Optimization Algorithm for Routing and Wavelength Assignment Based on Directional Guidance in Satellite Optical Networks

With the development of satellite communication,in order to solve the problems of shortage of on-board resources and refinement of delay requirements to improve the communication performance of satellite optical networks,this paper proposes a bee colony optimization algorithm for routing and wavelength assignment based on directional guidance(DBCO-RWA)in satellite optical networks.In D-BCORWA,directional guidance based on relative position and link load is defined,and then the link cost function in the path search stage is established based on the directional guidance factor.Finally,feasible solutions are expanded in the global optimization stage.The wavelength utilization,communication success probability,blocking rate,communication hops and convergence characteristic are simulated.The results show that the performance of the proposed algorithm is improved compared with existing algorithms.

Anti-apoptotic protein BCL-XL as a therapeutic vulnerability in gastric cancer

Background: New therapeutic targets are needed to improve the outcomes for gastric cancer(GC) patients with advanced disease. Evasion of programmed cell death(apoptosis) is a hallmark of cancer cells and direct induction of apoptosis by targeting the pro-survival BCL2 family proteins represents a promising therapeutic strategy for cancer treatment. Therefore, understanding the molecular mechanisms underpinning cancer cell survival could provide a molecular basis for potential therapeutic interventions. Method: Here we explored the role of BCL2L1 and the encoded anti-apoptotic BCL-XL in GC. Using Droplet Digital PCR(ddPCR) technology to investigate the DNA amplification of BCL2L1 in GC samples and GC cell lines, the sensitivity of GC cell lines to selective BCL-XL inhibitors A1155463 and A1331852, pan-inhibitor ABT-263, and VHL-based PROTAC-BCL-XL was analyzed using(CellTiter-Glo) CTG assay in vitro. Western Blot(WB) was used to detect the protein expression of BCL2 family members in GC cell lines and the manner in which PROTAC-BCL-XL kills GC cells. Coimmunoprecipitation(Co-IP) was used to investigate the mechanism of A1331852 and ABT-263 kills GC cell lines. DDPCR, WB, and real-time PCR(RTPCR) were used to investigate the correlation between DNA, RNA, protein levels, and drug activity. Results: The functional assay showed that a subset of GC cell lines relies on BCL-XL for survival. In gastric cancer cell lines, BCL-XL inhibitors A1155463 and A1331852 are more sensitive than the pan BCL2 family inhibitor ABT-263, indicating that ABT-263 is not an optimal inhibitor of BCL-XL. VHL-based PROTAC-BCL-XL DT2216 appears to be active in GC cells. DT2216 induces apoptosis of gastric cancer cells in a time-and dose-dependent manner through the proteasome pathway. Statistical analysis showed that the BCL-XL protein level predicts the response of GC cells to BCL-XL targeting therapy and BCL2L1 gene CNVs do not reliably predict BCL-XL expression.Conclusion: We identified BCL-XL as a promising therapeutic target in a subset of GC cases with high levels of BCL-XL protein expression. Functionally, we demonstrated that both selective BCL-XL inhibitors and VHL-based PROTAC BCL-XL can potently kill GC cells that are reliant on BCL-XL for survival. However, we found that BCL2L1 copy number variations(CNVs) cannot reliably predict BCL-XL expression, but the BCL-XL protein level serves as a useful biomarker for predicting the sensitivity of GC cells to BCL-XL-targeting compounds. Taken together, our study pinpointed BCL-XL as potential druggable target for specific subsets of GC.

Screening for urinary markers predicting hematopoietic stem cell injury induced by busulfan using genetically diverse mice

Background:Busulfan(BU)is an alkylating agent used as a conditioning agent prior to hematopoietic stem cell(HSC)transplantation as it is known to be cytotoxic to host hematopoietic stem and progenitor cells.The susceptibility of HSCs to BU injury plays an important role in the myeloablative efficacy of BU.Different susceptibilities were demonstrated in genetically diverse(GD)mice in our preliminary research.Methods:Three strains of GD mice with different susceptibilities to BU-i nduced HSC injury were used for screening biological markers of HSC injury susceptibility in urine.The urine proteins were analyzed using liquid chromatography coupled with tandem mass spectrometry to screen for differentially expressed proteins.Screening for possible biomarkers based on differences in protein expression abundance was validated using enzyme-l inked immunoassay(ELISA).Results:Functional analysis showed that the differential proteins were all involved in a series of biological pathways related to cellular senescence,apoptosis,and angiogenesis;whereas the differential proteins of the high-susceptible strain were enriched for the regulation of bone marrow microenvironment pathways,those of low-susceptible strain were enriched for the proapoptotic effect of GTPase pathways.Based on protein abundance differences,several urinary proteins that may be indicative of susceptibility were screened,and ELISA validation results showed that angiotensin-converting enzyme may be a potential biomarker predicting HSC susceptibility for BU conditioning.Conclusions:This study indicates that urinary protein levels can reflect differences in susceptibility to BU-i nduced HSC injury.Using GD mice to construct genetic difference models will provide preclinical data for screening BU-related biological markers.

Structural insights into the Oryza sativa cation transporters HKTs in salt tolerance

The high-affinity potassium transporters(HKTs),selectively permeable to either Na^(+)alone or Na^(+)/K^(+),play pivotal roles in maintaining plant Na^(+)/K^(+)homeostasis.Although their involvement in salt tolerance is widely reported,the molecular underpinnings of Oryza sativa HKTs remain elusive.In this study,we elucidate the structures of OsHKT1;1 and OsHKT2;1,representing two distinct classes of rice HKTs.The dimeric assembled OsHKTs can be structurally divided into four domains.At the dimer interface,a half-helix or a loop in the third domain is coordinated by the C-terminal region of the opposite subunit.Additionally,we present the structures of OsHKT1;5 salt-tolerant and salt-sensitive variants,a key quantitative trait locus associated with salt tolerance.The salt-tolerant variant of OsHKT1;5 exhibits enhanced Na^(+)transport capability and displays a more flexible conformation.These findings shed light on the molecular basis of rice HKTs and provide insights into their role in salt tolerance.

Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

农村地区父亲参与现状及其与幼儿发展的关系

父亲参与对儿童发展的重要性受到越来越多的关注,为考察当前我国农村地区父亲参与现状,探究父亲参与和幼儿发展的关系,本研究以620名农村幼儿及其家长作为调查对象,使用自编问卷从父亲是否缺位、父亲参与时间以及父亲参与活动内容等方面测查农村地区父亲参与状况,运用Achenbach儿童行为量表(CBCL)及相关测试评定幼儿行为、社会性、情绪、认知、动作发展水平,结果发现当前我国农村地区父亲参与现状不容乐观,缺位现象普遍且严重;父亲参与可以显著预测幼儿社交退缩、抑郁、注意力发展水平,父亲参与越积极,幼儿社交退缩越少、抑郁情绪越少、注意力发展越好。农村地区父亲应加强自身参与意识,农村家庭应积极支持父亲参与并提高参与质量,政府在发挥正确引导作用的同时应鼓励社会组织助力父亲参与。

Clinical data analysis reveals the role of OGR1 (GPR68) in head and neck squamous cancer

Background:Head and neck squamous cancer(HNSC)frequently occurs in the clinic.Revealing the role of the genes that correlate with cancer cell outgrowth will contribute to potential treatment target identification and tumor inhibition.Methods:The gene expression profiles and gene ontology of the proton-sensing G-protein-coupled receptor OGR1 were analyzed using the TCGA(The Cancer Genome Atlas)database.The effects of sex,age,race,and degree of malignancy on HNSC were investigated,and the survival times of HNSC patients with high or low/medium expression levels of OGR1 were compared.Methylation of the OGR1 promoter CpG sites was also investigated and OGR1-related genes were analyzed using gene set enrichment analysis.Results:OGR1 is overexpressed in HNSC patients.However,compared with the low/median expression group,the high OGR1 expression group did not have different survival rates.The OGR1 expression level differed across sex,age,race,and degree of malignancy,while the methylation of the OGR1 promoter CpG sites was maintained at a similar level.Gene set enrichment analysis revealed that OGR1 was positively correlated with head and neck cancer,cisplatin resistance,hypoxia,angiogenesis,cell migration,and TGF-β.Conclusion:The expression of OGR1 correlated with HNSC progression and survival and thus can serve as a potential treatment target and prognostic marker.

Novel spontaneous myelodysplastic syndrome mouse model

Background:Myelodysplastic syndrome(MDS)is a group of disorders involving he-mopoietic dysfunction leading to leukemia.Although recently progress has been made in identifying underlying genetic mutations,many questions still remain.Animal models of MDS have been produced by introduction of specific mutations.However,there is no spontaneous mouse model of MDS,and an animal model to simulate natu-ral MDS pathogenesis is urgently needed.Methods:In characterizing the genetically diverse mouse strains of the Collaborative Cross(CC)we observed that one,designated JUN,had abnormal hematological traits.This strain was thus further analyzed for phenotypic and pathological iden-tification,comparing the changes in each cell population in peripheral blood and in bone marrow.Results:In a specific-pathogen free environment,mice of the JUN strain are rela-tively thin,with healthy appearance.However,in a conventional environment,they become lethargic,develop wrinkled yellow hair,have loose and light stools,and are prone to infections.We found that the mice were cytopenic,which was due to abnor-mal differentiation of multipotent bone marrow progenitor cells.These are common characteristics of MDS.Conclusions:A mouse strain,JUN,was found displaying spontaneous myelodysplas-tic syndrome.This strain has the advantage over existing models in that it develops MDS spontaneously and is more similar to human MDS than genetically modified mouse models.JUN mice will be an important tool for pathogenesis research of MDS and for evaluation of new drugs and treatments.

Downregulation of HNRNPK in human cancer cells inhibits lung metastasis

Background: Lung cancer frequently occurs in the clinic, leading to poor prognosis and high mortality. Markers for early diagnosis of lung cancer are scarce, and further potential therapeutic targets are also urgently needed.Method: We established a new mouse model in which the specific gene HNRNPK(heterogeneous nuclear ribonucleoprotein K) was downregulated after administration of doxycycline. The lung metastatic nodules were investigated using bioluminescence imaging, micro-CT, and autopsy quantification.Results: Compared with the short hairpin negative control group, less lung metastatic nodules were formed in the short hairpin RNA group.Conclusion: Downregulation of HNRNPK in cancer cells can inhibit lung metastasis.

Research progress on the structure and function of endomucin

Endomucin is a type I integral membrane glycoprotein,which is expressed in venous and capillary endothelial cells.It consists of 261 amino acids with an extracellular domain that is highly O-glycosylated at serine and threonine residues and has several potential N-glycosylation sites.Endomucin plays an important role in biological processes such as cell interaction,molecular cell signaling,angiogenesis and cell migration,and in recent years it has also been identified as an anti-adhesion molecule and a marker of endothelial cells.While it has been shown to be involved in a number of physiological and pathological mechanisms,many of its functions remain unknown,and further study is needed.This article reviews research progress on the function of endomucin to date,in order to provide guidance for future studies.

The nuclear cytokine IL-37a controls lethal cytokine storms primarily via IL-1R8-independent transcriptional upregulation of PPARγ

Cytokine storms are crucial in the development of various inflammatory diseases,including sepsis and autoimmune disorders.The immunosuppressive cytokine INTERLEUKIN(IL)-37 consists of five isoforms(IL-37a-e).We identified IL-37a as a nuclear cytokine for the first time.Compared to IL-37b,IL-37a demonstrated greater efficacy in protecting against Toll-like receptor-induced cytokine hypersecretion and lethal endotoxic shock.The full-length(FL)form of IL-37a and the N-terminal fragment,which is processed by elastase,could translocate into cell nuclei through a distinctive nuclear localization sequence(NLS)/importin nuclear transport pathway.These forms exerted their regulatory effects independent of the IL-1R8 receptor by transcriptionally upregulating the nuclear receptor peroxisome proliferator-activated receptor(PPARγ).This process involved the recruitment of the H3K4 methyltransferase complex WDR5/MLL4/C/EBPβand H3K4me1/2 to the enhancer/promoter of Pparg.The receptor-independent regulatory pathway of the nuclear IL-37a–PPARγaxis and receptor-dependent signaling by secreted IL-37a maintain homeostasis and are potential therapeutic targets for various inflammatory diseases,including sepsis.

Summary of animal models of myelodysplastic syndrome

Myelodysplastic syndrome(MDS)is a malignant tumor of the hematological system characterized by long-term,progressive refractory hemocytopenia.In addition,the risk of leukemia is high,and once it develops,the course of acute leukemia is short with poor curative effect.Animal models are powerful tools for studying human diseases and are highly effective preclinical platforms.Animal models of MDS can accurately show genetic aberrations and hematopoietic clone phenotypes with similar cellular features(such as impaired differentiation and increased apoptosis),and symptoms can be used to assess existing treatments.Animal models are also helpful for understanding the pathogenesis of MDS and its relationship with acute leukemia,which helps with the identification of candidate genes related to the MDS phenotype.This review summarizes the current status of animal models used to research myelodysplastic syndrome(MDS).

Optimization study of spherical tuyere based on BP neural network and new evaluation index

The energy consumption of heating,ventilation,and air conditioning(HVAC)systems holds a significant position in building energy usage,accounting for about 65%of the total energy consumption.Moreover,with the advancement of building automation,the energy consumption of ventilation systems continues to grow.This study focuses on improving the performance of spherical tuyeres in HVAC systems.It primarily utilizes neural networks and multi-island genetic algorithms(MIGA)for multi-parameter optimization.By employing methods such as structural parameterization,accurate and fast computational fluid dynamics(CFD)simulations,a minimized sample space,and a rational optimization strategy,the time cycle of the optimization process is shortened.Additionally,a new comprehensive evaluation index is proposed in this research to describe the performance of spherical tuyeres,which can be used to more accurately assess spherical tuyeres with different structures.The results show that by establishing a neural network prediction model and combining it with the multi-island genetic algorithm,a novel spherical tuyere design was successfully achieved.The optimized novel spherical tuyeres achieved a 27.05%reduction in the spherical tuyeres effective index(STEI)compared to the traditional spherical tuyeres.Moreover,the resistance decreased by 15.68%,and the jet length increased by 7.57%.The experimental results demonstrate that our proposed optimization method exhibits high accuracy,good generalization capability,and excellent agreement at different Reynolds numbers.

1-Pbps orbital angular momentum fibre-optic transmission

Space-division multiplexing(SDM),as a main candidate for future ultra-high capacity fibre-optic communications,needs to address limitations to its scalability imposed by computation-intensive multi-input multi-output(MIMO)digital signal processing(DSP)required to eliminate the crosstalk caused by optical coupling between multiplexed spatial channels.By exploiting the unique propagation characteristics of orbital angular momentum(OAM)modes in ring core fibres(RCFs),a system that combines SDM and C+L band dense wavelength-division multiplexing(DWDM)in a 34 km 7-core RCF is demonstrated to transport a total of 24960 channels with a raw(net)capacity of 1.223(1.02)Peta-bit s−1(Pbps)and a spectral efficiency of 156.8(130.7)bit s−1 Hz−1.Remarkably for such a high channel count,the system only uses fixed-size 4×4 MIMO DSP modules with no more than 25 time-domain taps.Such ultra-low MIMO complexity is enabled by the simultaneous weak coupling among fibre cores and amongst non-degenerate OAM mode groups within each core that have a fixed number of 4 modes.These results take the capacity of OAM-based fibre-optic communications links over the 1 Pbps milestone for the first time.They also simultaneously represent the lowest MIMO complexity and the 2nd smallest fibre cladding diameter amongst reported few-mode multicore-fibre(FM-MCF)SDM systems of>1 Pbps capacity.We believe these results represent a major step forward in SDM transmission,as they manifest the significant potentials for further up-scaling the capacity per optical fibre whilst keeping MIMO processing to an ultra-low complexity level and in a modularly expandable fashion.