Overexpression pattern,function,and clinical value of proteasome 26S subunit non-ATPase 6 in hepatocellular carcinoma

BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.

Oxidative Esterification of Methacrolein to Methyl Methacrylate over Supported Palladium Catalyst

Supported palladium catalysts, which were used in the oxidative esterification of methacrolein to methyl methacrylate, have been prepared with different carriers and Pd precursors. Experimental results revealed that Pd catalysts with r-Al2O3 support and Na2PdC14 precursor showed good performance. Pd catalyst modified with Pb and Mg indicated that Pd-Mg bimetallic catalyst exhibited considerably higher activity and Pd-Pb exhibited both higher activity and selectivity. 92.27% methacrolein conversion and 90.57% methyl methacrylate selectivity were obtained on Pd-Pb-Mg catalyst.

ATFF: Advanced Transformer with Multiscale Contextual Fusion for Medical Image Segmentation

Deep convolutional neural network (CNN) greatly promotes the automatic segmentation of medical images. However, due to the inherent properties of convolution operations, CNN usually cannot establish long-distance interdependence, which limits the segmentation performance. Transformer has been successfully applied to various computer vision, using self-attention mechanism to simulate long-distance interaction, so as to capture global information. However, self-attention lacks spatial location and high-performance computing. In order to solve the above problems, we develop a new medical transformer, which has a multi-scale context fusion function and can be used for medical image segmentation. The proposed model combines convolution operation and attention mechanism to form a u-shaped framework, which can capture both local and global information. First, the traditional converter module is improved to an advanced converter module, which uses post-layer normalization to obtain mild activation values, and uses scaled cosine attention with a moving window to obtain accurate spatial information. Secondly, we also introduce a deep supervision strategy to guide the model to fuse multi-scale feature information. It further enables the proposed model to effectively propagate feature information across layers, Thanks to this, it can achieve better segmentation performance while being more robust and efficient. The proposed model is evaluated on multiple medical image segmentation datasets. Experimental results demonstrate that the proposed model achieves better performance on a challenging dataset (ETIS) compared to existing methods that rely only on convolutional neural networks, transformers, or a combination of both. The mDice and mIou indicators increased by 2.74% and 3.3% respectively.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension

BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver diseases.The GM composition is diverse and associated with different etiologies of liver diseases.Notably,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in China.Thus,understanding the role of GM alterations in patients with HBV infection-related PH is essential.AIM To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)placement.METHODS This was a prospective,observational clinical study.There were 30 patients(with a 100%technical success rate)recruited in the present study.Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled.Stool samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon sequencing.RESULTS One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE group.There was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group.CONCLUSION Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated PH.Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.

Intelligent Small Sample Defect Detection of Concrete Surface Using Novel Deep Learning Integrating Improved YOLOv5

Dear Editor,This letter presents an intelligent small sample defect detection of concrete surface using novel deep learning integrating the improved YOLOv5 based on the Wasserstein GAN(WGAN)enhancement algorithm.The proposed method is capable of producing top-notch data sets to address the issues of insufficient samples and substandard quality.

Effect of long reaction distance on gas composition from organic-rich shale pyrolysis under high-temperature steam environment

When high-temperature steam is used as a medium to pyrolyze organic-rich shale,water steam not only acts as heat transfer but also participates in the chemical reaction of organic matter pyrolysis,thus affecting the generation law and release characteristics of gas products.In this study,based on a long-distance reaction system of organic-rich shale pyrolysis via steam injection,the effects of steam temperature and reaction distance on gas product composition are analyzed in depth and compared with other pyrolysis processes.The advantages of organic-rich shale pyrolysis via steam injection are then evaluated.The volume concentration of hydrogen in the gas product obtained via the steam injection pyrolysis of organic-rich shale is the highest,which is more than 60%.The hydrogen content increases as the reaction distance is extended;however,the rate of increase changes gradually.Increasing the reaction distance from 800 to 4000 mm increases the hydrogen content from 34.91%to 69.68%and from 63.13%to 78.61%when the steam temperature is 500℃ and 555℃,respectively.However,the higher the heat injection temperature,the smaller the reaction distance required to form a high concentration hydrogen pyrolysis environment(hydrogen concentration>60%).When the steam pyrolysis temperature is increased from 500℃ to 555℃,the reaction distance required to form a high concentration of hydrogen is reduced from 3800 to 800 mm.Compared with the direct retorting process,the volume concentration of hydrogen obtained from high-temperature steam pyrolysis of organic-rich shale is 8.82 and 10.72 times that of the commonly used Fushun and Kivite furnaces,respectively.The pyrolysis of organic-rich shale via steam injection is a pyrolysis process in a hydrogen-rich environment.

Understanding mechanisms for differential salinity tissue tolerance between quinoa and spinach:Zooming on ROS-inducible ion channels

Soil salinity is a wo rldwide issue and a major threat to global food security.Salinity tolerance is a complex mechanism that is conferred by numerous molecular,physiological,and biochemical traits.Of critical importance are plant's ability to regulate redox balance without compromising reactive oxygen species(ROS)signalling and maintain cytosolic ion homeostasis.In this study,the mechanistic basis of H^(+) retention ability in leaf mesophyll(an important but highly sensitive plant tissue)was compared between halophytic quinoa and glycophytic spinach.Phenotypic data showed quinoa outperformed spinach under 100 to 500 mmol L^(-1) NaCl salinity.The major difference behind this differential salinity sensitivity was a differential H^(+) uptake in leaf mesophyll.Electrophysiological and molecular experiments revealed that a superior ability of mesophyll H^(+) retention in quinoa was conferred by three complementary mechanisms:(ⅰ)an intrinsically lower H^(+)-ATPase activity in quinoa(potentially as an energy saving strategy);(ⅱ)reduced sensitivity of H^(+) transporters to ROS;and(ⅲ)increased sensitivity of ROS-inducible Ca^(2+)-permeable channels,Moreover,the sensitivity of H^(+)-transport systems to ROS was further examined in NaCl-acclimated quinoa and spinach plants.The key factors differentiating between H^(+) retention in acclimated leaf mesophyll was associated with the reduced sensitivity and gene expression of H^(+)-permeable outward rectifying channel(GORK),Arabidopsis potassium transporter 1(AKT1),and high affinity potassium transporter 5(HAK5)to additional NaCl and ROS stress,along with the upregulation of ROS scavenging system.Taken together,our results showed that the tissue-specific and ROS-specific regulation of H^(+) retention are important for conferring salinity tolerant at least in the halophyte quinoa.

C-O官能团修饰的CaMoO_(4)光催化剂的合成与光催化活性研究

采用溶胶凝胶法制备了对盐酸金霉素具有高效降解活性的CaMoO_(4)光催化剂。通过多种表征手段,研究了CaMoO_(4)光催化剂的相结构、纯度、官能团、表面形貌、光学性质和光催化活性。结果表明,CaMoO_(4)光催化剂为四方相,其样品中存在少量的C-O官能团;颗粒近似呈球形,由大颗粒和细颗粒组成;其具有高的可见光响应能力,光学带隙值为3.21 eV。以盐酸金霉素为目标降解物,在不同的药品质量浓度、催化剂含量、pH值条件研究了CaMoO_(4)光催化剂降解盐酸金霉素的光催化活性。结果表明,盐酸金霉素质量浓度为200 mg/L、催化剂含量1 g/L和pH值为7时,CaMoO_(4)光催化剂的降解百分比达到了94%。结合实验结果和能带理论,提出了CaMoO_(4)光催化剂降解盐酸金霉素的光催化机理。机理研究表明,C-O官能团在反应过程中为电子提供额外的能量使其跃迁到CaMoO_(4)光催化剂的导带,促进电子空穴对的产生;空穴、羟基自由基和超氧自由基是促进盐酸金霉素降解的关键因素。

复杂任务情境中技术如何促进部门协同——基于S市市域社会治理现代化指挥中心的案例研究

已有研究多将技术促进部门协同理解为技术与组织互动视角下,基层政府为应对复杂任务情境采取的一种策略性行为,但对其背后的权力维度关注甚少。论文围绕权力视角下技术如何实现政府部门协同这一核心问题,选取S市市域社会治理现代化指挥中心为案例,探讨技术是否影响,以及如何影响政府部门间的权力关系。研究认为,从案例中析出的分布式治理遵从了“任务情境-技术应用-治理行为”相互适配的行动逻辑,对标复杂性任务情境,通过平台技术的协调功能,能够推动政府部门围绕“高效处置一件事”组建任务共同体。这种任务共同体暗含了以“科层为体、技术为用”的嵌套性组织结构和松散耦合性部门关系互为表里的新型权力结构——分布式权力网络。分布式治理作为根植于中国城市基层治理场景的微观理论,一方面有助于丰富基层治理机制的理论图谱,对传统基层治理机制选择的理论预设以及技术治理与科层治理共生理论进行了部分修正和改进;另一方面,通过反思技术与科层组织关系的传统研究路径,将权力维度重新拉入技术与组织关系研究,在一定程度上扩展了既有研究视域。同时,分布式治理的提出也为回答“优化基层治理数字化转型和技术化创新”之问提供了一个探索性答案。

丁二酸酐改性聚乙烯醇微球对热塑性淀粉性能的影响

为了提高热塑性淀粉(TPS)塑料的力学和耐水等性能,扩大其应用领域。文中以丁二酸酐(SAA)改性的聚乙烯醇微球(PVAMS)为增强体,与玉米淀粉和甘油混合制备复合材料,研究了不同SAA添加量改性的PVAMS对TPS力学性能、热性能、耐水和加工性能的影响。结果表明,SAA质量分数为15%时,SAA-PVAMS/TPS的拉伸强度和断裂伸长率分别为5.01 MPa和66.7%,冲击强度为35.39 kJ/m^(2);转变温度和热稳定性略有提高;吸水率降低,表面疏水性提高,接触角最大为61.2°;平衡和峰值扭矩分别为10.51 N·m和26.35 N·m,相对比较适中,易于加工成型。因此,以SAA改性的PVAMS来增强TPS,能实现复合材料性能的有效提升。

The development and implementation of pathological parameters and molecular testing impact prognosis of colorectal adenocarcinoma

Objective:This study aims to analyze how changes in pathological diagnosis practice and molecular detection technology have affected clinical outcomes for colorectal cancer(CRC)patients in Fudan University Shanghai Cancer Center(FUSCC).Methods:This retrospective cohort study analyzed 21,141 pathologically confirmed CRC cases diagnosed at FUSCC from 2008 to 2020.Patients were divided into five groups for different analytical purposes:(1)the before vs.since 2014 groups to analyze the influence of the changes in the classification criteria of pT3 and pT4 staging on the survival of patients;(2)the partial vs.total mesorectal excision(TME)groups to analyze whether evaluation of completeness of the mesorectum have impact on the survival of patients;(3)the tumor deposit(TD)(+)N0 vs.TD(+)N1c groups to analyze the influence of the changes in the pN staging on the survival of patients with positive TD and negative regional lymph node metastasis(LNM);(4)the before vs.since 2013 groups to analyze the influence of the changes in the testing process of deficient mismatch repair on the survival of patients;and(5)the groups with vs.without RAS/BRAF gene mutation testing to analyze the influence of these testing on the survival of patients.Patients’clinicopathological parameters,including age at diagnosis,sex,tumor size,location,differentiation,mucinous subtype,TD,lymphovascular invasion,perineural invasion,tumor depth,LNM and distant metastasis,and tumor-node-metastasis(TNM)stage,were compared between groups.Kaplan-Meier analysis with log rank method was performed for patients’overall survival(OS)and disease-free survival(DFS)analyses.Results:In pathological reports,there were three parameter changes that impacted patient outcomes.Firstly,changes in the pT staging criteria led to a shift of the ratio of patients with stage pT3 to stage pT4 from 1:110.9 to 1:0.26.In comparison to patients admitted before 2014(n=4,754),a significant difference in prognosis between pT3 and pT4 stages was observed since 2014(n=9,965).Secondly,we began to evaluate the completeness of the mesorectum since 2016.As a result,91.0%of patients with low rectal cancer underwent TME(n=4,111)surgery,and patients with TME had significantly better OS compared with partial mesorectal excision(PME,n=409).Thirdly,we began to stage TD(+)LNM(-)as N1c since 2017.The results showed that N1c(n=127)but not N0(n=39)can improve the prognosis of patients without LNM and distal metastasis.In molecular testing,there have been three and five iterations of updates regarding mismatch repair(MMR)/microsatellite instability(MSI)status and RAS/BRAF gene mutation detection,respectively.The standardization of MMR status testing has sharply decreased the proportion of deficient MMR(dMMR)patients(from 32.5%to 7.4%)since 2013.The prognosis of patients underwent MMR status testing since 2013(n=867)were significantly better than patients before 2013(n=1,313).In addition,detection of RAS/BRAF gene mutation status(n=5,041)resulted in better DFS but not OS,for patients with stage I-III disease(n=16,557).Conclusion:Over the past few decades,updates in elements in pathological reports,as well as the development of standardized tests for MMR/MSI status and RAS/BRAF gene mutations have significantly improved patient outcomes.

Application of geophysical methods in fine detection of urban concealed karst:A case study of Wuhan City,China

The construction of modern livable cities faces challenges in karst areas,including ground collapse and engineering problems.Wuhan,with a population of 13.74×10^(6) and approximately 1161 km^(2)of soluble rocks in the urban area of 8569.15 km^(2),predominantly consists of concealed karst areas where occasional ground collapse events occur,posing significant threats to underground engineering projects.To address these challenges,a comprehensive geological survey was conducted in Wuhan,focusing on major karstrelated issues.Geophysical methods offer advantages over drilling in detecting concealed karst areas due to their efficiency,non-destructiveness,and flexibility.This paper reviewed the karst geological characteristics in Wuhan and the geophysical exploration methods for karst,selected eight effective geophysical methods for field experimentation,evaluated their suitability,and proposed method combinations for different karst scenarios.The results show that different geophysical methods have varying applicability for karst detection in Wuhan,and combining multiple methods enhances detection effectiveness.The specific recommendations for method combinations provided in this study serve as a valuable reference for karst detection in Wuhan.

Experimental study of the effects of a multistage pore-throat structure on the seepage characteristics of sandstones in the Beibuwan Basin:Insights into the flooding mode

To investigate the relationship between grain sizes, seepage capacity, and oil-displacement efficiency in the Liushagang Formation of the Beibuwan Basin, this study identifies the multistage pore-throat structure as a crucial factor through a comparison of oil displacement in microscopic pore-throat experiments. The two-phase flow evaluation method based on the Li-Horne model is utilized to effectively characterize and quantify the seepage characteristics of different reservoirs, closely relating them to the distribution of microscopic pores and throats. It is observed that conglomerate sandstones at different stages exhibit significant heterogeneity and noticeable differences in seepage capacity, highlighting the crucial role played by certain large pore throats in determining seepage capacity and oil displacement efficiency. Furthermore, it was found that the displacement effects of conglomeratic sandstones with strong heterogeneity were inferior to those of conventional homogeneous sandstone, as evidenced by multiple displacement experiments conducted on core samples with varying granularities and flooding systems. Subsequently, core-based experiments on associated gas flooding after water flooding were conducted to address the challenge of achieving satisfactory results in a single displacement mode for reservoirs with significant heterogeneity. The results indicate that the oil recovery rates for associated gas flooding after water flooding increased by 7.3%-16.4% compared with water flooding alone at a gas-oil ratio of approximately 7000 m^(3)/m^(3). Therefore, considering the advantages of gas flooding in terms of seepage capacity, oil exchange ratio, and the potential for two-phase production, gas flooding is recommended as an energy supplement mode for homogeneous reservoirs in the presence of sufficient gas source and appropriate tectonic angle. On the other hand, associated gas flooding after water flooding is suggested to achieve a more favorable development effect compared to a single mode of energy supplementation for strongly heterogeneous sandstone reservoirs.

DPAL-BERT:A Faster and Lighter Question Answering Model

Recent advancements in natural language processing have given rise to numerous pre-training language models in question-answering systems.However,with the constant evolution of algorithms,data,and computing power,the increasing size and complexity of these models have led to increased training costs and reduced efficiency.This study aims to minimize the inference time of such models while maintaining computational performance.It also proposes a novel Distillation model for PAL-BERT(DPAL-BERT),specifically,employs knowledge distillation,using the PAL-BERT model as the teacher model to train two student models:DPAL-BERT-Bi and DPAL-BERTC.This research enhances the dataset through techniques such as masking,replacement,and n-gram sampling to optimize knowledge transfer.The experimental results showed that the distilled models greatly outperform models trained from scratch.In addition,although the distilled models exhibit a slight decrease in performance compared to PAL-BERT,they significantly reduce inference time to just 0.25%of the original.This demonstrates the effectiveness of the proposed approach in balancing model performance and efficiency.

The interaction between temperature and precipitation on the potential distribution range of Betula ermanii in the alpine treeline ecotone on the Changbai Mountain

Alpine treeline ecotones are highly sensitive to climate warming.The low temperature-determined alpine treeline is expected to shift upwards in response to global warming.However,little is known about how temperature interacts with other important factors to influence the distribution range of tree species within and beyond the alpine treeline ecotone.Hence,we used a GF-2 satellite image,along with bioclimatic and topographic variables,to develop an ensemble suitable habitat model based on the species distribution modeling algorithms in Biomod2.We investigated the distribution of suitable habitats for B.ermanii under three climate change scenarios(i.e.,low(SSP126),moderate(SSP370)and extreme(SSP585)future emission trajectories)between two consecutive time periods(i.e.,current-2055,and 2055-2085).By 2055,the potential distribution range of B.ermanii will expand under all three climate scenarios.The medium and high suitable areas will decline under SSP370 and SSP585scenarios from 2055 to 2085.Moreover,under the three climate scenarios,the uppermost altitudes of low suitable habitat will rise to 2,329 m a.s.l.,while the altitudes of medium and high suitable habitats will fall to 2,201 and2,051 m a.s.l.by 2085,respectively.Warming promotes the expansion of B.ermanii distribution range in Changbai Mountain,and this expansion will be modified by precipitation as climate warming continues.This interaction between temperature and precipitation plays a significant role in shaping the potential distribution range of B.ermanii in the alpine treeline ecotone.This study reveals the link between environmental factors,habitat distribution,and species distribution in the alpine treeline ecotone,providing valuable insights into the impacts of climate change on high-elevation vegetation,and contributing to mountain biodiversity conservation and sustainable development.

PAL-BERT:An Improved Question Answering Model

In the field of natural language processing(NLP),there have been various pre-training language models in recent years,with question answering systems gaining significant attention.However,as algorithms,data,and computing power advance,the issue of increasingly larger models and a growing number of parameters has surfaced.Consequently,model training has become more costly and less efficient.To enhance the efficiency and accuracy of the training process while reducing themodel volume,this paper proposes a first-order pruningmodel PAL-BERT based on the ALBERT model according to the characteristics of question-answering(QA)system and language model.Firstly,a first-order network pruning method based on the ALBERT model is designed,and the PAL-BERT model is formed.Then,the parameter optimization strategy of the PAL-BERT model is formulated,and the Mish function was used as an activation function instead of ReLU to improve the performance.Finally,after comparison experiments with traditional deep learning models TextCNN and BiLSTM,it is confirmed that PALBERT is a pruning model compression method that can significantly reduce training time and optimize training efficiency.Compared with traditional models,PAL-BERT significantly improves the NLP task’s performance.

Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

A new type of shale gas reservoir—carbonate-rich shale: From laboratory mechanical characterization to field stimulation strategy

Recently, a new promising type of marine shale gas reservoir, carbonate-rich shale, has been discovered.But the mechanical properties of this type of shale were still unrevealed and the corresponding reservoir stimulation design was lack of guidance. Using the deep downhole cores of an exploratory carbonate-rich shale gas well, the physical and mechanical parameters and failure mechanism of the whole reservoir section were acquired and evaluated systematically, by performing XRD, tri-axial compression, Brazilian splitting, and fracture toughness tests. A new model was established to evaluate the reservoir brittleness based on fracture morphology and stress-strain curve. Recommended strategy for reservoir stimulation was discussed. Results showed that(1) Carbonate-rich shale possessed high compressive strength and high Young's modulus, which were improved by 10.74% and 3.37% compared to that of siliceous shale. It featured high tensile strength and fracture toughness, with insignificant anisotropy.(2) With the content of carbonate minerals increasing, the shear failure morphology transformed from sparse and wide brittle fractures to diffusely distributed and subtle plastic cracks.(3) The brittleness index order was: siliceous shale, clay-rich shale, carbonate-rich shale, and limestone.(4) The special properties of carbonate-rich shale were rooted in the inherent feature of carbonate minerals(high strength, high elastic modulus,and cleavage structure), resulting in greater challenge in reservoirs stimulation. The above findings would promote the understanding of carbonate-rich shale reservoirs and provide reference for the optimum design of reservoir stimulation.

Truncated Gauss-Newton full-waveform inversion of pure quasi-P waves in vertical transverse isotropic media

Full-waveform inversion(FWI) uses the full information of seismic data to obtain a quantitative estimation of subsurface physical parameters. Anisotropic FWI has the potential to recover high-resolution velocity and anisotropy parameter models, which are critical for imaging the long-offset and wideazimuth data. We develop an acoustic anisotropic FWI method based on a simplified pure quasi P-wave(qP-wave) equation, which can be solved efficiently and is beneficial for the subsequent inversion.Using the inverse Hessian operator to precondition the functional gradients helps to reduce the parameter tradeoff in the multi-parameter inversion. To balance the accuracy and efficiency, we extend the truncated Gauss-Newton(TGN) method into FWI of pure qP-waves in vertical transverse isotropic(VTI) media. The inversion is performed in a nested way: a linear inner loop and a nonlinear outer loop.We derive the formulation of Hessian-vector products for pure qP-waves in VTI media based on the Lagrange multiplier method and compute the model update by solving a Gauss-Newton linear system via a matrix-free conjugate gradient method. A suitable preconditioner and the Eisenstat and Walker stopping criterion for the inner iterations are used to accelerate the convergence and avoid prohibitive computational cost. We test the proposed FWI method on several synthetic data sets. Inversion results reveal that the pure acoustic VTI FWI exhibits greater accuracy than the conventional pseudoacoustic VTI FWI. Additionally, the TGN method proves effective in mitigating the parameter crosstalk and increasing the accuracy of anisotropy parameters.