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Cell softness reveals tumorigenic potential via ITGB8/AKT/glycolysis signaling in a mice model of orthotopic bladder cancer

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Chinese Medical Journal 2024年第2期137卷 209-221页

作者： Shi qiu Yaqi qiu Linghui Deng Ling Nie Liming Ge Xiaonan Zheng Di Jin Kun Jin Xianghong Zhou Xingyang Su Boyu Cai Jiakun Li Xiang Tu Lina Gong Liangren Liu Zhenhua Liu Yige Bao Jianzhong Ai Tianhai Lin Lu Yang qiang Wei Department of Urology Institute of UrologyNational Clinical Research Center for Geriatrics and Center of Biomedical Big DataWest China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Molecular Oncology Institute of Oncology Research(IOR)Oncology Institute of Southern Switzerland(IOSI)Bellinzona 6500Switzerland Department of Science and Drug Technology University of TurinTurinItaly National Clinical Research Center of Geriatrics The Center of Gerontology and GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610000China Department of Pathology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pharmaceutics and Bioengineering School of Chemical EngineeringSichuan UniversityChengduSichuan 610000China

Background:Bladder cancer,characterized by a high potential of tumor recurrence,has high lifelong monitoring and treatment *** date,tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer ***,the existence of soft tumor cells in bladder tumors remains ***,our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer ***:The stiffness of bladder cancer cells was determined by atomic force microscopy(AFM).The modified microfluidic chip was utilized to separate soft cells,and the 3D Matrigel culture system was to maintain the softness of tumor *** patterns of integrinβ8(ITGB8),protein kinase B(AKT),and mammalian target of rapamycin(mTOR)were determined by Western *** immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59(TRIM59).The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor ***:Using our newly designed microfluidic approach,we identified a small fraction of soft tumor cells in bladder cancer *** importantly,the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens,in which the number of soft tumor cells was associated with tumor ***,we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor ***,we detected a remarkable up-regulation in ITGB8,TRIM59,and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent ***:The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and ***,the soft tumor cells become more sensitive to chemother

关键词： Soft tumor cells 3D Matrigel Stemness Non-muscle invasive bladder neoplasms Microfluidic analytical techniques

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Clinical efficacy and safety of flexible ureteroscopy and percutaneous nephrolithotomy for large kidney stones:A retrospective comparative study

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World Journal of Clinical Cases 2024年第21期12卷 4483-4490页

作者： qiu-Lian Wang Jun-qiang Liu Juan Cao Jun Ding Department of Urology No.904 Hospital of Joint Logistic Support Force of PLAWuxi 214044Jiangsu ProvinceChina

BACKGROUND Renal stones ranging 20–40 mm are very common in *** no largesample clinical studies have confirmed the clinical efficacy and safety of this method,there is also a lack of comparative data with traditional *** To investigate the clinical efficacy of flexible ureteroscopy(FURS)and percutaneous nephrolithotomy(PCNL)by postoperative stone clearance and changes in soluble vascular cell adhesion molecule 1(sVCAM-1)and kidney injury molecule 1(KIM-1)levels in patients with large kidney stones(>2 cm in diameter).METHODS This single-center observational study was performed at a Chinese hospital between January 1,2021,and October 30,*** 250 enrolled patients were diagnosed with large kidney stones(>2 cm)and divided into a FURS group(n=145)and a PCNL group(n=105)by the surgical *** FURS group was treated with flexible ureteroscopy and the PCNL group was treated with percutaneous *** operation time,time to palinesthesia,intraoperative blood loss,drop in hemoglobin,length of hospital stay,stone clearance rate,and complications were recorded in the two *** and postoperative serum sVCAM-1 levels,erythrocyte sedimentation rate(ESR),urine KIM-1 levels,preoperative and postoperative pain visual analog scale(VAS)and Wisconsin Stone Quality of Life Questionnaire(WISQOL)scores were also *** All 250 eligible patients completed the *** were no significant differences in baseline characteristics between the two groups(P>0.05).The operation time in the FURS group was significantly greater than that in the PCNL *** time to ambulation,intraoperative blood loss,decrease in hemoglobin,and length of hospital stay were significantly lower in the FURS group than in the PCNL *** FURS group also had a significantly higher stone clearance rate and a lower incidence of postoperative *** was no significant difference in antibiotic use between the *** serum

关键词： Kidney stones Flexible ureteroscopy Percutaneous nephrolithotomy Clinical effective SCM-1 Erythrocyte sedimentation rate Kidney injury molecule 1

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Incidence and warning signs for complications of human brucellosis: a multi-center observational study from China

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Infectious Diseases of Poverty 2024年第1期13卷 53-62页

作者： Qing-Nan Shi Hui-Jie Qin Qiao-Shan Lu hu Li Zhong-Fa Tao Meng-Guang Fan Mu-Heta Aishan Zeng-qiang Kou qiu-Lan Chen Wen-Wu Yin Yan-Ping Zhang National key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and PreventionChangbai RoadChangping DistrictBejing 102206China School of Public Health Guangxi Medical UniversityNanningChina Nanning Center for Disease Control and Prevention NanningChina Guizhou Center for Disease Control and Prevention GuiyangChina Inner Mongolia Center for Disease Control and Prevention HohhotChina Xinjiang Uighur Autonomous Region Center for Disease Control and Prevention UrumqiChina Shandong Center for Disease Control and Prevention JinanChina

Background Brucellosis is a severe zoonotic disease that is often overlooked, particularly in impoverished countries. Timely identification of focal complications in brucellosis is crucial for improving treatment outcomes. However, there is currently a lack of established indicators or biomarkers for diagnosing these complications. Therefore, this study aimed to investigate potential warning signs of focal complications in human brucellosis, with the goal of providing practical parameters for clinicians to aid in the diagnosis and management of *** A multi-center cross-sectional study was conducted in China from December 2019 to August 2021. The study aimed to investigate the clinical characteristics and complications of patients with brucellosis using a questionnaire survey and medical record system. The presence of warning signs for complications was assessed using univariate and multivariate logistic regression models. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used for variable screening and model *** A total of 880 participants diagnosed with human brucellosis were enrolled. The median age of the patients was 50 years [interquartile range (IQR): 41.5-58.0], and 54.8% had complications. The most common organ system affected by complications was the osteoarticular system (43.1%), with peripheral arthritis (30.0%), spondylitis (16.6%), paravertebral abscess (5.0%), and sacroiliitis (2.7%) being the most prevalent. Complications in other organ systems included the genitourinary system (4.7%), respiratory system (4.7%), and hematologic system (4.6%). Several factors were found to be associated with focal brucellosis. These factors included a long delay in diagnosis [odds ratio (OR) = 3.963, 95% confidence interval(CI): 1.906-8.238 for > 90 days], the presence of underlying disease (OR = 1.675, 95%CI: 1.176-2.384), arthralgia (OR = 3.197, 95%CI: 1.986-5.148), eye bulging pain (OR = 3.482, 95%CI:

关键词： Brucellosis Complications Clinical spectrum Warning signs

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Computer Vision-Based Human Body Posture Correction System

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Mechanical Engineering Science 2024年第1期6卷 1-7页

作者： Yangsen qiu Yukun WANG Yuchen WU Xinyi qiang Yunzuo ZHANG School of Information science and Technology Shijiazhuang Tiedao UniversityShijiazhuangHebei050043China

With the development of technology and the progress of life,more and more people,regardless of entertainment,learning,or work,cannot do without computer desks and cannot put down their mobile *** to prolonged sitting and often neglecting the importance of posture,incorrect posture can often lead to health problems such as hunchback,lumbar muscle strain,and shoulder and neck pain over *** address this issue,we designed a computer vision-based human body posture detection *** system utilizes YOLOv8 technology to accurately locate key points of the human body skeleton,and then analyzes the coordinate positions and depth information of these key points to establish a criterion for distinguishing different *** the assistance of an SVM classifier,the system achieves an average recognition rate of 95%.Finally,we successfully deployed the posture detection system on Raspberry Pi hardware and conducted extensive *** test results demonstrate that the system can effectively detect various postures and provide real-time reminders to users to correct poor posture,demonstrating good practicality and stability.

关键词： computer vision human posture deep learning image processing

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Chiral quantum heating and cooling with an optically controlled ion

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Light(Science & Applications) 2024年第7期13卷 1393-1400页

作者： Jin-Tao Bu Jian-Qi Zhang Ge-Yi Ding Jia-Chong Li Jia-Wei Zhang Bin Wang Wen-qiang Ding Wen-Fei Yuan Liang Chen Qi Zhong Ali keçebaş Şahin KÖzdemir Fei Zhou Hui Jing Mang Feng State key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Wuhan Institute of Physics and MathematicsInnovation Academy of Precision Measurement Science and TechnologyChinese Academy of Sciences430071 WuhanChina. University of the Chinese Academy of Sciences 100049 BeijingChina. Research Center for Quantum Precision Measurement Guangzhou Institute of Industry Technology511458 GuangzhouChina. Department of Engineering Science and Mechanics and Materials Research InstitutePennsylvania State UniversityUniversity ParkState CollegePA 16802USA. key Laboratory of Low-Dimensional Quantum Structures and Quantum Control of Ministry of Education Department of Physics and Synergetic Innovation Center for Quantum Effects and ApplicationsHunan Normal University410081 ChangshaChina. Department of Physics Zhejiang Normal University321004 JinhuaChina

Quantum heat engines and refrigerators are open quantum systems,whose dynamics can be well understood using a non-Hermitian formalism.A prominent feature of non-Hermiticity is the existence of exceptional points(EPs),which has no counterpart in closed quantum *** has been shown in classical systems that dynamical encirclement in the vicinity of an EP,whether the loop includes the EP or not,could lead to chiral mode ***,we show that this is valid also for quantum systems when dynamical encircling is performed in the vicinity of their Liouvillian EPs(LEPs),which include the effects of quantum jumps and associated noise—an important quantum feature not present in previous *** demonstrate,using a Paul-trapped ultracold ion,the first chiral quantum heating and refrigeration by dynamically encircling a closed loop in the vicinity of an *** witness the cycling direction to be associated with the chirality and heat release(absorption)of the quantum heat engine(quantum refrigerator).Our experiments have revealed that not only the adiabaticity breakdown but also the Landau–Zener–Stückelberg process play an essential role during dynamic encircling,resulting in chiral thermodynamic *** observations contribute to further understanding of chiral and topological features in non-Hermitian systems and pave a way to exploring the relation between chirality and quantum thermodynamics.

关键词： quantum chiral dynamical

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Small molecule deoxynyboquinone triggers alkylation and ubiquitination of keap1 at Cys489 on kelch domain for Nrf2 activation and inflammatory therapy

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Journal of Pharmaceutical Analysis 2024年第3期14卷 401-415页

作者： ke-Gang Linghu Tian Zhang Guang-Tao Zhang Peng Lv Wen-Jun Zhang Guan-Ding Zhao Shi-Hang Xiong qiu-Shuo Ma Ming-Ming Zhao Meiwan Chen Yuan-Jia Hu Chang-Sheng Zhang Hua Yu State key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Macao Centre for Research and Development in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina key Laboratory of Tropical Marine Bio-resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaRNAM Center for Marine MicrobiologySouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou510301China State key Laboratory of Functions and Applications of Medicinal Plants&School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang550025China

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by kelch-like ECH-associated protein 1(keap1)alkylation plays a central role in anti-inflammatory ***,activators of Nrf2 through alkylation of keap1-kelch domain have not been ***(DNQ)is a natural small molecule discovered from marine *** current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of *** exhibited significant anti-inflammatory properties both in vitro and in *** pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be theα,β-unsaturated amides moieties by a chemical reaction between DNQ and *** exerted anti-inflammatory effects through activation of Nrf2/ARE ***1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving *** specific alkylation site of DNQ on keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass *** triggered the ubiquitination and subsequent degradation of keap1 by alkylation of the cysteine residue 489(Cys489)on keap1-kelch domain,ultimately enabling the activation of *** findings revealed that DNQ exhibited potent anti-inflammatory capacity throughα,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of keap1-kelch domain,suggesting the potential values of targeting Cys489 on keap1-kelch domain by DNQ-like small molecules in inflammatory therapies.

关键词： Deoxynyboquinone Anti-inflammation Target keap1/Nrf2 Alkylation Ubiquitination

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Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer

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Frontiers of Medicine 2024年第1期18卷 109-127页

作者： Guoqiang Li Peng Pu Mengqiao Pan Xiaoling Weng Shimei qiu Yiming Li Sk Jahir Abbas Lu Zou ke Liu Zheng Wang Ziyu Shao Lin Jiang Wenguang Wu Yun Liu Rong Shao Fatao Liu Yingbin Liu Department of Biliary-Pancreatic Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China State key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteShanghai200127China Shanghai key Laboratory of Biliary Tract Disease Shanghai200082China Department of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai200082China Shanghai Tenth People’s Hospital of Tongji University Shanghai200072China Department of General Surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200082China Department of Pharmacology Shanghai Jiao Tong University School of MedicineShanghai200025China

Altered three-dimensional architecture of chromatin influences various genomic regulators and subsequent gene expression in human ***,knowledge of the topological rearrangement of genomic hierarchical layers in cancer is largely ***,by taking advantage of in situ Hi-C,RNA-sequencing,and chromatin immunoprecipitation sequencing(ChIP-seq),we investigated structural reorganization and functional changes in chromosomal compartments,topologically associated domains(TADs),and CCCTC binding factor(CTCF)-mediated loops in gallbladder cancer(GBC)tissues and cell *** observed that the chromosomal compartment A/B switch was correlated with CTCF binding levels and gene expression *** inter-TAD interactions with weaker TAD boundaries were identified in cancer cell lines relative to normal ***,the chromatin short loops and cancer unique loops associated with chromatin remodeling and epithelial–mesenchymal transition activation were enriched in cancer compared with their control ***-specific enhancer–promoter loops,which contain multiple transcription factor binding motifs,acted as a central element to regulate aberrant gene *** of individual enhancers in each loop anchor that connects with promoters led to the inhibition of their corresponding gene ***,our data offer the landscape of hierarchical layers of cancer genome and functional alterations that contribute to the development of GBC.

关键词： 3D genome cancer TADs loop gene regulation

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Clinical Study of Shentong Zhuyu Decoction Combined with Massage Therapy in the Treatment of Exertional Chronic Lumbar Muscle Strain

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Medicinal Plant 2024年第2期15卷 65-68页

作者： Lijun HAN Pengjun QIN Junbao ke qiang YAO Yongzhi LI Shangluo Hospital of Traditional Chinese Medicine Shangluo 726000China Shanyang County People s Hospital Shangluo 726400China

[Objectives]To explore the effects of Shentong Zhuyu decoction combined with massage therapy in the treatment of exertional chronic lumbar muscle strain.[Methods]Sixty-four cases of exertional chronic lumbar muscle strain were randomly divided into two groups(32 cases each group).The patients in the control group only took celecoxib capsules,and those in the treatment group additionally took Shentong Zhuyu decoction combined with massage *** syndrome score,lumbar function,hemorrheology index and clinical effect were compared between the two groups before and after treatment.[Results]After treatment,the TCM syndrome scores of lumbar distension/dull pain,tingling-like lumbago,adverse lateral turn,body weight loss,dark purple tongue,slow or astringent pulse,and Oswestry disability index(ODI)score in the treatment group were lower than those in the control group,and the levels of plasma viscosity,red blood cell aggregation index,platelet aggregation rate(PAG)and fibrinogen(Fib)were lower than those in the control group,showing statistical significance(P<0.05).The overall clinical effect distribution of the treatment group was better than that of the control group,and the difference was statistically significant(P<0.05).[Conclusions]Shentong Zhuyu decoction combined with massage therapy can effectively relieve the symptoms of patients with lumbago and improve the lumbar mobility function and hemorrheology,with obvious therapeutic effects in the treatment of exertional chronic lumbar muscle strain.

关键词： Chronic lumbar muscle strain Exertional Massage Shentong Zhuyu decoction

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Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

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Bone Research 2024年第2期12卷 334-348页

作者： Ziqian Xiang Pengfei Zhang Chunwang Jia Rongkun Xu Dingren Cao Zhaoning Xu Tingting Lu Jingwei Liu Xiaoxiong Wang Cheng qiu Wenyang Fu Weiwei Li Lei Cheng qiang Yang Shiqing Feng Lianlei Wang Yunpeng Zhao Xinyu Liu Department of Orthopaedics Qilu Hospital of Shandong UniversityJinan 250012China University of Health and Rehabilitation Sciences Qingdao 226000China Xiangya School of Medicine Central South UniversityChangsha 410013China School of Nursing and Rehabilitation Shandong UniversityJinan 250012China Department of Pediatrics Cangzhou Central HospitalCangzhou 061011China Department of Pediatric Surgery Qilu Hospital of Shandong UniversityJinan 250012China Department of Pathology Qilu Hospital of Shandong UniversityJinan 250012China Department of Spine Surgery Tianjin HospitalTianjin UniversityTianjin 30021China The Second Hospital of Shandong University Cheeloo College of MedicineShandong UniversityJinan 250012China

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be ***,Piezo1 channel was identified as a key iron transporter in response to mechanical ***1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron ***,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical ***,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

关键词： stress overload channel

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Antisymmetric planar Hall effect in rutile oxide ﬁlms induced by the Lorentz force

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Science Bulletin 2024年第15期69卷 2362-2369页

作者： Yongwei Cui Zhaoqing Li Haoran Chen Yunzhuo Wu Yue Chen ke Pei Tong Wu Nian Xie Renchao Che Xuepeng qiu Yi Liu Zhe Yuan Yizheng Wu Department of Physics State Key Laboratory of Surface PhysicsFudan UniversityShanghai 200433China Institute for Nanoelectronic Devices and Quantum Computing Fudan UniversityShanghai 200433China Interdisciplinary Center for Theoretical Physics and Information Sciences Fudan UniversityShanghai 200433China Center for Advanced Quantum Studies and Department of Physics Beijing Normal UniversityBeijing 100875China Laboratory of Advanced Materials Shanghai Key Lab of Molecular Catalysis and Innovative MaterialsAcademy for Engineering&TechnologyFudan UniversityShanghai 200438China Shanghai key Laboratory of Special Artiﬁcial Microstructure Materials and Technology School of Physics Science and EngineeringTongji UniversityShanghai 200092China Zhejiang Laboratory Hangzhou 311100China Shanghai Research Center for Quantum Sciences Shanghai 201315China Shanghai key Laboratory of Metasurfaces for Light Manipulation Fudan UniversityShanghai 200433China

The conventional Hall effect is linearly proportional to the field component or magnetization component perpendicular to a film. Despite the increasing theoretical proposals on the Hall effect to the in-plane field or magnetization in various special systems induced by the Berry curvature, such an unconventional Hall effect has only been experimentally reported in Weyl semimetals and in a heterodimensional superlattice. Here, we report an unambiguous experimental observation of the antisymmetric planar Hall effect(APHE) with respect to the in-plane magnetic field in centrosymmetric rutile RuO_(2) and IrO_(2) single-crystal films. The measured Hall resistivity is found to be linearly proportional to the component of the applied in-plane magnetic field along a particular crystal axis and to be independent of the current direction or temperature. Both the experimental observations and theoretical calculations confirm that the APHE in rutile oxide films is induced by the Lorentz force. Our findings can be generalized to ferromagnetic materials for the discovery of anomalous Hall effects and quantum anomalous Hall effects induced by in-plane magnetization. In addition to significantly expanding knowledge of the Hall effect, this work opens the door to explore new members in the Hall effect family.

关键词： Antisymmetric planar Hall effect Lorentz force Rutile oxide films Crystal symmetry

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