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Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis

Bone Research 2024年第1期12卷 215-226页

作者： Yuhang Liu Ruihan Hao Jia Lv jie Yuan Xuelei wang Churong Xu Ding Ma Zhouyi Duan Bingjun Zhang Liming Dai Yiyun cheng Wei Lu Xiaoling Zhang Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine(SJTUSM)Shanghai 200092China National Facility for Translational Medicine Shanghai 200240China Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai 200241China Department of Orthopaedic Surgery The Second Hospital of Shanxi Medical UniversityTaiyuan 030001China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China School of Medicine Shanghai UniversityShanghai 200444China

Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat *** attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in *** this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice *** address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in ***,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived ***,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 *** knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient *** by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine ***,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

关键词： osteoarthritis metabolism inhibited

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Subsurface multi-physical characterization of mountain excavation and city construction in loess plateau with a fiber-optic sensing system

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第8期16卷 2935-2946页

作者： jie Liu Bin Shi Kai Gu Meng-Ya Sun Jun-cheng Yao He-Ming Han School of Earth Sciences and Engineering Nanjing UniversityNanjingJiangsu210023China Frontiers Science Center for Critical Earth Material Cycling Nanjing UniversityNanjing210023China School of Earth Sciences and Engineering Hohai UniversityNanjing210098China

Mountain excavation and city construction(MECC)projects being launched in the Loess Plateau in China involve the creation of large-scale artificial *** the subsurface evolution characteristics of the artificial land is essential,yet ***,we use an improved fiber-optic monitoring system for its subsurface multi-physical *** system enables us to gather spatiotemporal distribution of various parameters,including strata deformation,temperature,and ***’an New District was selected as a case study to conduct refined in-situ monitoring through a 77 m-deep borehole and a 30 m-long *** reveal that the ground settlement involves both the deformation of the filling loess and the underlying intact ***,the filling loess exhibits a stronger creep capability compared to underlying intact *** deformation along the profile is unevenly distributed,with a positive correlation with soil *** accumulation has been observed at the interface between the filling loess and the underlying intact loess,leading to a significant ***,the temperature and moisture in the filling loess have reached a new equilibrium state,with their depths influenced by atmospheric conditions measuring at 31 m and 26 m,*** refined investigation allows us to identify critical layers that matter the sustainable development of newly created urban areas,and provide improved insights into the evolution mechanisms of land creation.

关键词： Mountain excavation and city construction Fiber-optic monitoring Multi-physical characterization Compacted loess

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A semi-analytical pressure and rate transient analysis model for inner boundary and propped fractures exhibiting dynamic behavior under long-term production conditions

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Petroleum Science 2024年第4期21卷 2520-2535页

作者： Lin-Song cheng Chong Cao Quan-Yu Pan Pin Jia Ren-Yi Cao Zhi-Kai wang Jun-jie Shi College of Petroleum Engineering China University of Petroleum (Beijing) Sinopec Petroleum Exploration and Production Research Institute CNOOC Research Institute State Key Laboratory of Water Resources Protection and Utilization in Coal Mining

The loss of hydrocarbon production caused by the dynamic behavior of the inner boundary and propped fractures under long-term production conditions has been widely reported in recent studies. However,the quantitative relationships for the variations of the inner boundary and propped fractures have not been determined and incorporated in the semi-analytical models for the pressure and rate transient analysis. This work focuses on describing the variations of the inner boundary and propped fractures and capturing the typical characteristics from the pressure transient curves.A generalized semi-analytical model was developed to characterize the dynamic behavior of the inner boundary and propped fractures under long-term production conditions. The pressure-dependent length shrinkage coefficients, which quantify the length changes of the inner zone and propped fractures, are modified and incorporated into this multi-zone semi-analytical model. With simultaneous numerical iterations and numerical inversions in Laplace and real-time space, the transient solutions to pressure and rate behavior are determined in just a few seconds. The dynamic behavior of the inner boundary and propped fractures on transient pressure curves is divided into five periods: fracture bilinear flow(FR1),dynamic PFs flow(FR2), inner-area linear flow(FR3), dynamic inner boundary flow(FR4), and outer-area dominated linear flow(FR5). The early hump during FR2 period and a positive upward shift during FR4period are captured on the log-log pressure transient curves, reflecting the dynamic behavior of the inner boundary and propped fractures during the long-term production *** transient pressure behavior will exhibit greater positive upward trend and the flow rate will be lower with the shrinkage of the inner boundary. The pressure derivative curve will be upward earlier as the inner boundary shrinks more rapidly. The lower permeability caused by the closure of un-propped fractures in the inner zo

关键词： Semi-analytical model Length shrinkage Dynamic behavior Boundary changes Transient behavior

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Synthesis and Properties of Mg-doped ZnO Nanobelts

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Semiconductor Photonics and Technology 2009年第4期15卷 225-228,251页

作者： LIU Hang ZHUANG Hui-zhao XUE cheng-shan wang jie LI Jun-lin Institute of Semiconductors Shandong Normal University Jinan 250014 CHN

The chemical vapor deposition(CVD)growth method is applicable to produce high-yield single-crystalline ZnO *** Mg-doped ZnO nanobelts with a smooth surface have been successfully *** morphology,microstructure and optical properties of the ZnO nanobelts were analyzed by X-ray diffraction(XRD),scanning electron microscope(SEM),transmission electron microscope(TEM),selective area electron diffraction(SAED),energy dispersive X-ray spectroscopy(EDS)and photoluminescence(PL)*** reveal that the ZnO nanobelts possess good crystalline *** special formation mechanism of crystal growth is discussed,emphasizing the effect of polar orientation on the nucleation and growth of the ZnO nanobelts.

关键词： Mg-doped ZnO nanobelts chemical vapour deposition method of crystal growth

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Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis

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World Journal of Gastroenterology 2024年第11期30卷 1588-1608页

作者： Xing-Nian Zhou Quan Zhang Hong Peng Yu-jie Qin Yu-Hong Liu Lu wang Ming-Liang cheng Xin-Hua Luo Hong Li Department of Infectious Diseases The Affiliated Hospital of Guizhou Medical UniversityGuizhou Medical UniversityGuiyang 550004Guizhou ProvinceChina Department of Infectious Diseases Guizhou Provincial People's HospitalGuiyang 550001Guizhou ProvinceChina

BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and *** silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and *** To investigate the association between ferroptosis and pyroptosis and the upstream regulatory *** This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce *** D(GSDMD)^(-/-)mice were used as an experimental *** changes in liver tissue were monitored by hematoxylin and eosin ***,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial ***-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain ***1,p53,and GSDMD were assessed by immunofluorescence *** Serum AST and ALT levels were elevated in patients with ***1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver *** the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was *** mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were *** vitro,knockdown of p53 and overexpression of GPX

关键词： Silent information regulator sirtuin 1 Ferroptosis Pyroptosis p53/glutathione peroxidase 4/gasdermin D Acute liver failure

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Photobiomodulation inhibits the expression of chondroitin sulfate proteoglycans after spinal cord injury via the Sox9 pathway

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Neural Regeneration Research 2024年第1期19卷 180-189页

作者： Zhihao Zhang Zhiwen Song Liang Luo Zhijie Zhu Xiaoshuang Zuo cheng Ju Xuankang wang Yangguang Ma Tingyu Wu Zhou Yao jie Zhou Beiyu Chen Tan Ding Zhe wang Xueyu Hu Department of Orthopedics Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina

Both glial cells and glia scar greatly affect the development of spinal cord injury and have become hot spots in research on spinal cord injury *** cellular deposition of dense extracellular matrix proteins such as chondroitin sulfate proteoglycans inside and around the glial scar is known to affect axonal growth and be a major obstacle to autogenous *** proteins are thus candidate targets for spinal cord injury *** previous studies demonstrated that 810 nm photo biomodulation inhibited the formation of chondroitin sulfate proteoglycans after spinal cord injury and greatly improved motor function in model ***,the specific mechanism and potential targets involved remain to be *** this study,to investigate the therapeutic effect of photo biomodulation,we established a mouse model of spinal cord injury by T9 clamping and irradiated the injury site at a power density of 50 mW/cm~2 for 50 minutes once a day for 7 consecutive *** found that photobiomodulation greatly restored motor function in mice and down regulated chondroitin sulfate proteoglycan expression in the injured spinal *** analysis revealed that photobiomodulation inhibited the expression of proteoglycan-related genes induced by spinal cord injury,and versican,a type of proteoglycan,was one of the most markedly changed *** staining showed that after spinal cord injury,versican was present in astrocytes in spinal cord *** expression of versican in primary astrocytes cultured in vitro increased after inflammation induction,whereas photobiomodulation inhibited the expression of ve ***,we found that the increased levels of p-Smad3,p-P38 and p-Erk in inflammatory astrocytes were reduced after photobiomodulation treatment and after delivery of inhibitors including FR 180204,(E)-SIS3,and SB *** suggests that Sma d 3/Sox9 and MAP K/Sox9 pathways may be involved in the effects of photobiomodulatio

关键词： chondroitin sulfate proteoglycans Erk MAPK P38 photobiomodulation principal component analysis Smad3 Sox9 spinal cord injury versican

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Impact of minimally invasive surgery on immune function and stress response in gastric cancer patients

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2484-2493页

作者： Rong-Hua Zhu Peng-cheng Li jie Zhang Hua-Hua Song Department of General Surgery Chongming Hospital Affiliated to Shanghai University of Medicine and Health SciencesShanghai 202150China Department of Respiratory Medicine Chongming Hospital Affiliated to Shanghai University of Medicine and Health ScienceShanghai 202150China

BACKGROUND Gastric cancer remains a leading cause of cancer-related mortality *** open surgery for gastric cancer is often associated with significant morbidity and prolonged *** To evaluate the effectiveness of laparoscopic minimally invasive surgery as an alternative to traditional open surgery for gastric cancer,focusing on its potential to reduce trauma,accelerate recovery,and achieve comparable oncological *** This study retrospectively analyzed 203 patients with gastric cancer who underwent surgery at the Shanghai Health Medical College Affiliated Chongming Hospital from January 2020 to December *** patients were divided into two groups:Minimally invasive surgery group(n=102),who underwent laparoscopic gastrectomy,and open surgery group(n=101),who underwent traditional open *** compared surgical indicators(surgical incision size,intraop-erative blood loss,surgical duration,and number of lymph nodes dissected),recovery parameters(time to first flatus,time to start eating,time to ambulation,and length of hospital stay),immune function(levels of IgA,IgG,and IgM),intestinal barrier function(levels of D-lactic acid and diamine oxidase),and stress response(levels of C-reactive protein,interleukin-6,and procalcitonin).RESULTS The minimally invasive surgery group demonstrated significantly better outcomes in terms of surgical indicators,including smaller incisions,less blood loss,shorter surgery time,and more lymph nodes dissected(P<0.05 for all).Recovery was also faster in the minimally invasive surgery group,with earlier return of bowel function,earlier initiation of diet,quicker mobilization,and shorter hospital stays(P<0.05 for all).Furthermore,patients in the minimally invasive surgery group had better preserved immune function,superior intestinal barrier function,and a less pronounced stress response postoperatively(P<0.05 for all).CONCLUSION Laparoscopic minimally invasive surgery for gastric cancer not on

关键词： Gastric cancer Laparoscopic surgery Minimally invasive surgery Immune function Intestinal barrier Stress response

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A compact route for efficient production of high-purity β-Ga2O3 powder

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Rare Metals 2024年第9期43卷 4573-4584页

作者： Xiao-Wei Zhou Gao-jie Chen Liang Xu Zhi-Jun Shao cheng Yang Yong-Pan Tian Zhuo Zhao School of Metallurgical Engineering Anhui University of Technology Low-Carbon Research Institute Anhui University of Technology

The present study has proposed a compact process for the production of high-purity β-Ga2O3powder by simply using gallium metal and water as the raw materials. The process basically consists of two essential steps including hydrothermal synthesis of Ga OOH and calcination of Ga OOH for the production of the target product of β-Ga2O3. Thermodynamic evaluation and systematic experiments were conducted for process parameter optimization. X-ray diffractometer（XRD）, scanning electron microscopy（SEM）, thermogravimetryDdifferential scanning calorimetry（TG-DSC） and X-ray photoelectron spectroscopy（XPS） were utilized to clarify the reaction mechanisms of the hydrothermal synthesis and transformation of Ga OOH to β-Ga2O3by calcination. Chemical analysis of the final product of β-Ga2O3obtained under the optimal conditions was carried out with inductively coupled plasma mass spectrometry（ICP-MS）, and the results showed that the contents of the representative impurities such as Ni, Cu, In, Mn, Co, Zn and Cr are obviously lower than the requirement of 5N β-Ga2O3standard, exhibiting excellent application prospect of the proposed process to produce high-purity β-Ga2O3.

关键词： Calcination Hydrothermal synthesis Purity Reaction mechanism β-Ga2O3

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Interpretability of Neural Networks Based on Game-theoretic Interactions

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Machine Intelligence Research 2024年第4期21卷 718-739页

作者： Huilin Zhou jie Ren Huiqi Deng Xu cheng Jinpeng Zhang Quanshi Zhang School of Electronic Information and Electrical Engineering Shanghai Jiao Tong UniversityShanghai 200240China XLAB The Second Academy of China Aerospace Science and Industry CorporationBeijing 100854China

This paper introduces the system of game-theoretic interactions,which connects both the explanation of knowledge encoded in a deep neural networks(DNN)and the explanation of the representation power of a *** this system,we define two gametheoretic interaction indexes,namely the multi-order interaction and the multivariate *** crucially,we use these interaction indexes to explain feature representations encoded in a DNN from the following four aspects:(1)Quantifying knowledge concepts encoded by a DNN;(2)Exploring how a DNN encodes visual concepts,and extracting prototypical concepts encoded in the DNN;(3)Learning optimal baseline values for the Shapley value,and providing a unified perspective to compare fourteen different attribution methods;(4)Theoretically explaining the representation bottleneck of ***,we prove the relationship between the interaction encoded in a DNN and the representation power of a DNN(e.g.,generalization power,adversarial transferability,and adversarial robustness).In this way,game-theoretic interactions successfully bridge the gap between“the explanation of knowledge concepts encoded in a DNN”and"the explanation of the representation capacity of a DNN"as a unified explanation.

关键词： Model interpretability and transparency explainable AI game theory interaction deep learning.

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Measurement of the neutron-induced total cross sections of ^(nat)Pb from 0.3 eV to 20 MeV on the Back-n at CSNS

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Nuclear Science and Techniques 2024年第2期35卷 85-93页

作者： jie-Ming Xue Song Feng Yong-Hao Chen Han Yi Min Xiao Pin-Jing cheng Xin-Xiang Li Rong Liu Yi-Wei Yang Zi-jie Han Da-Jun Zhao Hao-Qiang wang Bao-Qian Li Ji-Rong Zhao Lei-Xun Tang Wen Luo Bo Zheng School of Nuclear Science and Technology University of South ChinaHengyang 421001China Institute of High Energy Physics Chinese Academy of Sciences(CAS)Beijing 100049China Spallation Neutron Source Science Center Dongguan 523803China Institute of Nuclear Physics and Chemistry China Academy of Engineering PhysicsMianyang 621900China

The neutron-induced total cross sections of natural lead have been measured in a wide energy range(0.3 eV-20 MeV)on the back-streaming white neutron beamline(Back-n)at the China Spallation Neutron *** energy was determined by the neutron total cross-section spectrometer using the time-of-flight technique.A fast multi-cell fission chamber was used as the neutron detector,and a 10-mm-thick high-purity natural lead sample was employed for the neutron transmission *** on-beam background was determined using Co,In,Ag,and Cd *** excitation function of ^(nat)Pb(n,tot)reaction below 20 MeV was calculated using the TALYS-1.96 nuclear-reaction modeling *** present results were compared with previous results,the evaluated data available in the five major evaluated nuclear data libraries(i.e.,ENDF/B-VIII.0,JEFF-3.3,JENDL-5,CENDL-3.2,and BROND-3.1),and the theoretical calculation *** agreement was found between the new results and those of previous experiments and with the theoretical curves in the corresponding *** measurement obtained the neutron total cross section of natural lead with good accuracy over a wide energy range and added experimental data in the resonance energy *** provides more reliable experimental data for nuclear engineering design and nuclear data evaluation of lead.

关键词： Neutron-induced total cross section Natural lead Time-of-flight TALYS-1.96 CSNS Back-n white neutron beamline

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