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Journal of Thermal Science 2024年第4期33卷 1301-1311页

作者： LI yi zhai Binjiang WANG Junying WANG Weizuo JIN Hui State Key Laboratory of Multiphase Flow in Power Engineering Xi'an Jiaotong University

Understanding the residence time distribution(RTD) of a continuous hydrothermal reactor is of great significance to improve product quality and reaction efficiency.In this work,an on-line measurement system is attached to a continuous reactor to investigate the characteristics of RTD.An approach that can accurately fit and describe the experimental measured RTD curve by finding characteristic values is proposed for analysis and comparison.The RTD curves of three experiment groups are measured and the characteristic values are calculated.Results show that increasing total flow rate and extending effective reactor length have inverse effect on average residence time,but they both cause the reactor to approach a plug flow reactor and improve the materials leading.The branch flow rate fraction has no significant effect on RTD characteristics in the scope of the present work except the weak negative correlation with the average residence time.Besides,the natural convection stirring effect can also increase the average residence time,especially when the forced flow is weak.The analysis reveals that it is necessary to consider the matching of natural convection,forced flow and reactor size to control RTD when designing the hydrothermal reactor and working conditions.

关键词： continuous reactor residence time distribution modelling

Risk factors,prognostic factors,and nomograms for distant metastasis in patients with diagnosed duodenal cancer:A population-based study

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1384-1420页

作者： Jia-Rong Shang Chen-yi Xu Xiao-Xue zhai Zhe Xu Jun Qian Department of Oncology Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina Department of Proctology Nanjing Hospital of Chinese MedicineNanjing 210000Jiangsu ProvinceChina Department of Digestive Cancer Surgery Jiangsu Province Hospital of Chinese MedicineThe Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210000Jiangsu ProvinceChina

BACKGROUND Duodenal cancer is one of the most common subtypes of small intestinal cancer,and distant metastasis(DM)in this type of cancer still leads to poor prognosis.Although nomograms have recently been used in tumor areas,no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer.AIM To develop and evaluate nomograms for predicting the risk of DM and person-alized prognosis in patients with duodenal cancer.METHODS Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer,and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM.Two novel nomograms were established,and the results were evaluated by receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).RESULTS A total of 2603 patients with duodenal cancer were included,of whom 457 cases(17.56%)had DM at the time of diagnosis.Logistic analysis revealed independent risk factors for DM in duodenal cancer patients,including gender,grade,tumor size,T stage,and N stage(P<0.05).Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM,including age,histological type,T stage,tumor grade,tumor size,bone metastasis,chemotherapy,and surgery(P<0.05).The accuracy of the nomograms was validated in the training set,validation set,and expanded testing set using ROC curves,calibration curves,and DCA curves.The results of Kaplan-Meier survival curves(P<0.001)indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer.CONCLUSION The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients

关键词： Duodenal cancer Distant metastasis Nomogram Risk factors Prognostic factors

SENEX-mediated CDK4/6 inhibition promotes senescence and confers apoptosis resistance in B-cell non-Hodgkin lymphoma

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BIOCELL 2024年第3期48卷 453-462页

作者： JIYU WANG LIUyiNG yi KEKE HUANG YANGYANG WANG HUIPING WANG ZHIMIN zhai Department of Hematology The Second Affiliated Hospital of Anhui Medical UniversityHefei230601China Department of Hematology The Fourth Affiliated HospitalZhejiang University School of MedicineYiwu322000China

Background:The primary cause of treatment failure in patients with refractory or relapsed B-cell non-Hodgkin lymphoma(r/r B-NHL)is resistance to current therapies,and therapy-induced senescence(TIS)stands out as a crucial mechanism contributing to tumor drug resistance.Here,we analyzed SENEX/Rho GTPase Activating Protein 18(ARHGAP18)expression and prognostic signiﬁcance in doxorubicin-induced B-NHL-TIS model and r/r B-NHL patients,investigating its target in B-NHL cell senescence and the effect of combining speciﬁc inhibitors on apoptosis resistance in B-NHL-TIS cells.Methods:Raji cells were transfected with the human SENEX shRNA recombinant lentiviral vector(Sh-SENEX)and the empty vector negative(NC)to construct a stable transfection cell line with knockdown of SENEX.Effect of SENEX-silencing on B-NHL-TIS formation,cell function and cell cycle-related pathways was analyzed.Using doxorubicin(DOX)-inducible senescent B-NHL cells combined with the speciﬁc cyclin dependent kinase 4/6(CDK4/6)inhibitor Palbociclib to observe that blocking CDK4/6 effects on TIS formation.SENEX expression of 21 B-NHL patients and 8 healthy controls were analyzed by qRT-PCR,and the correlation between its expression and clinical indicators were evaluated.Results:The downregulation of SENEX expression promotes G1-S phase transition and apoptosis while inhibiting cell proliferation,collectively suppressing the formation of TIS in B-NHL.Blockade of CDK4/6 promotes the DOX-induced G1 phase arrest to enhance TIS formation in B-NHL cells which can reverse the regulatory effect of silencing SENEX on B-NHL cell cycle regulation and senescence.The expression levels of SENEX were notably elevated in B-NHL patients compared to healthy controls,and Elevated expression levels of SENEX were associated with poor prognosis of B-NHL patients.Conclusions:SENEX enhances apoptosis resistance in B-NHL by inhibiting CDK4/6,thereby preventing G1-S phase transition and promoting TIS formation.

关键词： SENEX B-cell non-Hodgkin lymphoma CDK4/6 G1-S phase transition Therapy-induced senescence Apoptosis resistance

Retinal vascular morphological characteristics in diabetic retinopathy: an artificial intelligence study using a transfer learning system to analyze ultra-wide field images

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International Journal of Ophthalmology(English edition) 2024年第6期17卷 1001-1006页

作者： Xin-yi Deng Hui Liu Zheng-Xi Zhang Han-Xiao Li Jun Wang yi-Qi Chen Jian-Bo Mao Ming-zhai Sun Li-Jun Shen Center for Rehabilitation Medicine Department of OphthalmologyZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina Department of Precision Machinery and Instrumentation University of Science and Technology of ChinaHefei 230026Anhui ProvinceChina Department of Retina Eye Hospital of Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina

AIM:To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy(DR)and in patients with or without diabetic macular edema(DME).METHODS:The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study.The severity of DR patients was graded as mild,moderate and severe non-proliferative diabetic retinopathy(NPDR)according to the international clinical diabetic retinopathy(ICDR)disease severity scale classification,and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods.The presence of DME was determined by optical coherence tomography(OCT),and differences in vascular morphological characteristics were compared between patients with and without DME.RESULTS:Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99%and a Dice metric of 0.76.Compared with the healthy group,the DR group had smaller vessel angles(33.68±3.01 vs 37.78±1.60),smaller fractal dimension(Df)values(1.33±0.05 vs 1.41±0.03),less vessel density(1.12±0.44 vs 2.09±0.36)and fewer vascular branches(206.1±88.8 vs 396.5±91.3),all P<0.001.As the severity of DR increased,Df values decreased,P=0.031.No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics.CONCLUSION:In this study,an artificial intelligence retinal vessel segmentation system is used with 99%accuracy,thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology.DR patients have a tendency of vascular occlusion and dropout.The presence of DME does not compromise the integral retinal vascular pattern.

关键词： diabetic retinopathy vascular morphology deep learning ultra-wide field imaging diabetic macular edema

Brain Transcriptome Analysis Reveals Metabolic Changes Adapting to Hyperhaline or Hypohaline Environments in Spotted Scat(Scatophagus argus)

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Journal of Ocean University of China 2024年第3期23卷 755-765页

作者： LIN Ting zhai yi TIAN Changxu JIANG Dongneng SHI Hongjuan JIANG Mouyan LI Guangli DENG Siping Fisheries College Guangdong Ocean UniversityZhanjiang 524088China Guangdong Research Center on Reproductive Control and Breeding Technology of Indigenous Valuable Fish Species Zhanjiang 524088China Guangdong Provincial Key Laboratory of Pathogenic Biology and Epidemiology for Aquatic Economic Animals Zhanjiang 524088China

The fish brain is crucial for adjusting to environmental changes.Metabolic changes play a vital role in the adaptation to salinity change in aquatic animals.However,few studies have evaluated the responses of the fish brain to salinity changes.To evaluate the response to various salinities,spotted scat(Scatophagus argus)was cultured in water with salinity levels of 5(low salinity:LS),25(control group:Ctrl),and 35(high salinity group:HS)for 22 days.The brain transcriptome was analyzed.In total,1698 differentially expressed genes(DEGs)were identified between the HS and Ctrl groups,and 841 DEGs were identified between the LS and Ctrl groups.KEGG analysis showed that the DEGs in the HS vs.Ctrl comparison were involved in steroid biosynthesis,terpenoid backbone biosynthesis,fatty acid biosynthesis,ascorbate and aldarate metabolism,other types of O-glycan biosynthesis,and fatty acid metabolism.Glyoxylate and dicarboxylate metabolism,one carbon pool by folate,steroid biosynthesis,and cysteine and methionine metabolism were significantly enriched in the LS vs.Ctrl comparison.Additionally,the genes related to metabolism(acc,fas,hmgcr,hmgcs1,mvd,soat1,nsdhl,sqle,cel,fdft1,dnmt3a and mtr)were significantly up-regulated in the HS vs.Ctrl comparison.The genes related to metabolism(lipa,sqle,acc,fas,bhmt,mpst,dnmt3a,mtr,hao2,LOC111225351 and hmgcs1)were significantly up-regulated,while hmgcr and soat1 were significantly down-regulated in the LS vs.Ctrl compparison.These results suggest that salinity stress affects signaling pathways and genes’expressions involved in metabolic processes in the brain,and the differences in metabolism play an important role in adaptation to hyperhaline or hypohaline environments in spotted scat.This research provides a comprehensive overview of transcriptional changes in the brain under hyperhaline or hypohaline conditions,which is helpful to understand the mechanisms underlying salinity adaptation in euryhaline fishes.

关键词： Scatophagus argus brain salinity transcriptome analysis

Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

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Zoological Research 2024年第3期45卷 663-678页

作者： Li-Rong Liang Bing Liu Shu-Hui Cao You-yi Zhao Tian Zeng Mei-Ting zhai Ze Fan Dan-yi He San-Xin Ma Xiao-Tong Shi Yao Zhang Hui Zhang State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Engineering Research Center for Dental Materials and Advanced ManufactureDepartment of AnesthesiologySchool of StomatologyAir Force Medical UniversityXi’anShaanxi 710032China Department of Anesthesiology 986th Air Force HospitalAir Force Medical UniversityXi’anShaanxi 710032China

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment.Davunetide,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive protection.However,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood.In this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice.The neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral analysis.Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane.In adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine density.Furthermore,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane group.Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by sevoflurane.Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic proteins.Suppression of Wnt signaling was restored in the davunetide-treated group.Thus,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics.This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways invo

关键词： Davunetide Sevoflurane Abnormal social behaviors ADNP Neurotoxicity

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military Medical Research 2024年第1期11卷 34-49页

作者： yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong zhai Hai-Li Qian Fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

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High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

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World Journal of Stem Cells 2024年第2期16卷 176-190页

作者： Yu-Su Wang Wen-Hui Chu Jing-Jie zhai Wen-ying Wang Zhong-Mei He Quan-Min Zhao Chun-yi Li Institute of Antler Science and Product Technology Changchun Sci-Tech UniversityChangchun 130000Jilin ProvinceChina College of Chinese Medicinal Materials Jilin Agricultural UniversityChangchun 130118Jilin ProvinceChina School of Life Science Taizhou UniversityTaizhou 318000Zhejiang ProvinceChina Department of Oral Implantology Hospital of StomatologyJilin UniversityChangchun 130000Jilin ProvinceChina

BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

关键词： Osteochondral defect repair Mesenchymal stem cells Extracellular matrix Decellularization Antler stem cells Reserve mesenchymal cells Xenogeneic

Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish

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Zoological Research 2024年第2期45卷 355-366页

作者： Jing-yi Jia Guang-Hui Chen Ting-Ting Shu Qi-Yong Lou Xia Jin Jiang-Yan He Wu-Han Xiao Gang zhai Zhan yin College of Fisheries Huazhong Agriculture UniversityWuhanHubei 430070China State Key Laboratory of Freshwater Ecology and Biotechnology Institute of HydrobiologyChinese Academy of SciencesWuhanHubei 430072China College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijing 100049China Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes Chinese Sturgeon Research InstituteChina Three Gorges CorporationYichangHubei 443100China Hubei Hongshan Laboratory Huazhong Agriculture UniversityWuhanHubei 430070China Innovative Academy of Seed Design Chinese Academy of SciencesBeijing 100049China

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males.However,the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood,especially in teleosts.In this study,cyp17a1-/-zebrafish(Danio rerio)exhibited excessive visceral adipose tissue(VAT),lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis(DNL)enzymes.The assay for transposase accessible chromatinwithsequencing(ATAC-seq)results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/-fish compared to cyp17a1+/+male fish,including stearoyl-CoA desaturase(scd)and fatty acid synthase(fasn).Androgen response element(ARE)motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+male fish but not in cyp17a1-/-fish.Both androgen receptor(ar)-/-and wildtype(WT)zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue,lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis enzymes.The Ar agonist BMS-564929 reduced the content of VAT and lipid content,and down-regulated acetyl-CoA carboxylase a(acaca),fasn,and scd expression.Mechanistically,the rescue effect of testosterone on cyp17a1-/-fish in terms of phenotypes was abolished when ar was additionally depleted.Collectively,these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish,thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.

关键词： Cyp17a1 Testosterone Androgen receptor De novo lipogenesis Fatty acid synthesis

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On P-value Combination Procedures

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Acta Mathematica Sinica,English Series 2024年

作者： Zhen MENG Yu Ke SHI Jin yi LIN Qi zhai LI University of Chinese Academy of Sciences School of Statistics Capital University of Economics and Business Academy of Mathematics and Systems Science Chinese Academy of Sciences

Combining p-values is a well-known issue in statistical inference. When faced with a study involving m p-values, determining how to effectively combine them to arrive at a comprehensive and reliable conclusion becomes a significant concern in various fields, including genetics, genomics, and economics, among others. The literature offers a range of combination strategies tailored to different research objectives and data characteristics. In this work, we aim to provide users with a systematic exploration of the p-value combination problem. We present theoretical results for combining p-values using a logarithmic transformation, which highlights the benefits of this approach. Additionally, we propose a combination strategy together with its statistical properties utilizing the gold section method, showcasing its performance through extensive computer simulations. To further illustrate its effectiveness, we apply this approach to a real-world scenario.

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