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AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis

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Neural Regeneration Research 2025年第8期20卷 2408-2419页

作者： Ruiqi Qiu Mingzhu Yang Xiuxiu jin jingyang Liu Weiping Wang Xiaoli Zhang jinfeng Han Bo Lei Henan Eye Hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Eye Institute Henan Academy of Innovations in Medical ScienceZhengzhouHenan ProvinceChina Branch of National Clinical Research Center for Ocular Disease Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Academy of Medical Science Zhengzhou UniversityZhengzhouHenan ProvinceChina

Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell ***,there is no effective treatment for retinitis pigmentosa caused by PDE6B ***-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis *** aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal *** do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and ***-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western ***2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 *** expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type *** Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction ***,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B ***,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B *** data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upr

关键词： apoptosis AAV2-PDE6B ERK1/2 gene therapy phototransduction proteomics rd10 retinitis pigmentosa

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Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li Department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

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Physically Constrained Adaptive Deep Learning for Ocean Vertical-Mixing Parameterization

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Advances in Atmospheric Sciences 2025年第1期42卷 165-177页

作者： Junjie FANG Xiaojie LI jin LI Zhanao HUANG Yongqiang YU Xiaomeng HUANG Xi WU Chengdu University of Information Technology Chengdu 610225China Institute of Atmospheric Physics Chinese Academy of SciencesBeijing 100029China Tsinghua University Beijing 100084China

Existing traditional ocean vertical-mixing schemes are empirically developed without a thorough understanding of the physical processes involved,resulting in a discrepancy between the parameterization and forecast *** uncertainty in ocean-mixing parameterization is primarily responsible for the bias in ocean *** from deep-learning technology,we design the Adaptive Fully Connected Module with an Inception module as the baseline to minimize *** adaptively extracts the best features through fully connected layers with different widths,and better learns the nonlinear relationship between input variables and parameterization ***,to obtain more accurate results,we impose KPP(K-Profile Parameterization)and PP(Pacanowski–Philander)schemes as physical constraints to make the network parameterization process follow the basic physical laws more *** model data are calculated with human experience,lacking some unknown physical processes,which may differ from the actual data,we use a decade-long time record of hydrological and turbulence observations in the tropical Pacific Ocean as training *** physical constraints and a nonlinear activation function,our method catches its nonlinear change and better adapts to the oceanmixing parameterization *** use of physical constraints can improve the final results.

关键词： deep learning vertical-mixing parameterization ocean sciences adaptive network

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Curcumin attenuates ochratoxin A and hypoxia co‑induced liver injury in grass carp(Ctenopharyngodon idella)by dual targeting endoplasmic reticulum stress and apoptosis via reducing ROS content

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Journal of Animal Science and Biotechnology 2025年第1期16卷 408-423页

作者： Liangqin Wu Piao Zhao Pei Wu Weidan Jiang Yang Liu Hongmei Ren Xiaowan jin Xiaoqiu Zhou Lin Feng Animal Nutrition Institute Sichuan Agricultural UniversityChengdu 611130China Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province Sichuan Agricultural UniversityChengdu 611130China Key Laboratory of Animal Disease-Resistance Nutrition Ministry of EducationMinistry of Agriculture and Rural AffairsKey Laboratory of Sichuan ProvinceChengduSichuan 611130China

Background Ochratoxin A(OTA)is a toxin widely found in aquafeed ingredients,and hypoxia is a common prob-lem in fish *** practice,aquatic animals tend to be more sensitive to hypoxia while feeds are contaminated with OTA,but no studies exist in this *** research investigated the multiple biotoxicities of OTA and hypoxia combined on the liver of grass carp and explored the mitigating effect of curcumin(CUR).Methods A total of 720 healthy juvenile grass carp(11.06±0.05 g)were selected and assigned randomly to 4 experi-mental groups:control group(without OTA and CUR),1.2 mg/kg OTA group,400 mg/kg CUR group,and 1.2 mg/kg OTA+400 mg/kg CUR group with three replicates each for 60 ***,32 fish were selected,divided into nor-moxia(18 fish)and hypoxia(18 fish)groups,and subjected to hypoxia stress for 96 *** CUR can attenuate histopathological damage caused by coming to OTA and hypoxia by reducing vacu-olation and nuclear *** alleviation of this damage was associated with the attenuation of apoptosis in the mitochondrial pathway by decreasing the expression of the pro-apoptotic proteins Caspase 3,8,9,Bax,and Apaf1 while increasing the expression of the anti-apoptotic protein Bcl-2,and attenuation of endoplasmic reticulum stress(ERS)by reducing Grp78 expression and chop *** may be attributed to the fact that the addi-tion of CUR increased the levels of catalase(CAT)and glutathione reductase(GSH),increased antioxidant capacity,and ensured the proper functioning of respiratory chain complexes I and II,which in turn reduced the high produc-tion of reactive oxygen species(ROS),thus alleviating apoptosis and *** In conclusion,our data demonstrate the effectiveness of CUR in attenuating liver injury caused by the combination of OTA and *** study confirms the feasibility and efficacy of adding natural products to mitigate toxic damage to aquatic animals.

关键词： Apoptosis Curcumin Endoplasmic reticulum stress Grass carp Hypoxia Ochratoxin A Oxidative damage

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Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population

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Journal of Environmental Sciences 2025年第1期147卷 332-341页

作者： Haiyan Jiang Simei Zhang Yaoyao Lin Lin Meng Jiayi Li Wenqing Wang Kaixuan Yang Mingjuan jin Jianbing Wang Mengling Tang Kun Chen Department of Public Health Fourth Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Department of Public Health Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310058China Department of Public Health National Clinical Research Center for Child Health of Children’s HospitalZhejiang University School of MedicineHangzhou 310058China

Growing evidences showed that heavy metals exposure may be associated with metabolic ***,themechanism underlying arsenic(As)exposure and metabolic syndrome(MetS)risk has not been fully *** we aimed to prospectively investigate the role of serum uric acid(SUA)on the association between blood As exposure and incident MetS.A sample of 1045 older participants in a community in China was *** determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly *** events were defined according to the criteria of the International Diabetes Federation(IDF).Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident *** investigate the role of SUA in the association between As andMetS,amediation analysiswas *** the fully adjusted log-binominal model,per interquartile range increment of As,the risk of MetS increased *** with the lowest quartile of As,the adjusted relative risk(RR)of MetS in the highest quartile was 1.42(95%confidence interval,CI:1.03,2.00).Additionally,blood As was positively associated with SUA,while SUA had significant association with MetS *** mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA,with the proportion of 15.7%.Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults *** analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

关键词： Arsenic(As)exposure Metabolic syndrome(MetS) Serum uric acid(SUA) Cohort study Mediation effect Older adults

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Multiple liver metastases of unknown origin:A case report

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 233-238页

作者： Ying-jin Wang Ze-Chuan Liu Jian Wang Yin-Mo Yang Department of Hepatobiliary Pancreatic Surgery Peking University First HospitalBeijing 100034China Department of Interventional and Vascular Surgery Peking University First HospitalBeijing 100034China

BACKGROUND The liver is the most common site of digestive system tumor metastasis,but not all liver metastases can be traced back to the primary *** it is unusual,syphilis can impact the liver,manifesting as syphilitic hepatitis with inflammatory nodules,which might be misdiagnosed as *** SUMMARY This case report involves a 46-year-old female who developed right upper abdominal pain and intermittent low fever that persisted for more than three *** definitive diagnosis of a tumor had been made in the past decades,but signs of multiple liver metastases were recognized after a computed tomo-graphy scan without evidence of primary *** positive serological tests for syphilis and a biopsy of the liver nodules,a diagnosis of hepatic syphilis was made and confirmed with follow-up nodule reduction after anti-syphilis *** Clinicians must be aware of the possibility that syphilis can cause hepatic inflam-matory masses,especially when liver metastasis is suspected without evidence of primary lesions.A definitive diagnosis should be established in conjunction with a review of the patient’s medical history for accurate therapeutic intervention.

关键词： Syphilitic hepatitis Liver nodules Liver metastasis Treponema pallidum Case report

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Assessing the corrosion protection property of coatings loaded with corrosion inhibitors using the real-time atmospheric corrosion monitoring technique

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 119-126页

作者： Xiaoxue Wang Lulu jin jinke Wang Rongqiao Wang Xiuchun Liu Kai Gao jingli Sun Yong Yuan Lingwei Ma Hongchang Qian Dawei Zhang School of Energy and Power Engineering Beihang UniversityBeijing 100191China Beijing Institute of Space Long March Vehicle Beijing 100076China National Materials Corrosion and Protection Data Center University of Science and Technology BeijingBeijing 100083China Institute of Materials Intelligent Technology Liaoning Academy of MaterialsShenyang 110004China Shanghai Spaceflight Precision Machinery Institute Shanghai 201600China

The atmospheric corrosion monitoring(ACM)technique has been widely employed to track the real-time corrosion behavior of metal ***,limited studies have applied ACM to the corrosion protection properties of organic *** study compared a bare epoxy coating with one containing zinc phosphate corrosion inhibitors,both applied on ACM sensors,to observe their corrosion protection properties over *** with artificial damage via scratches were exposed to immersion and alternating dry and wet environments,which allowed for monitoring galvanic corrosion currents in *** the corrosion tests,the ACM currents of the zinc phosphate/epoxy coating were considerably lower than those of the blank epoxy *** trend in ACM current variations closely matched the results obtained from regular electrochemical tests and surface *** alignment highlights the potential of the ACM technique in evaluating the corrosion protection capabilities of organic *** with the blank epoxy coating,the zinc phosphate/epoxy coating showed much-decreased ACM current values that confirmed the effective inhibition of zinc phosphate against steel corrosion beneath the damaged coating.

关键词： atmospheric corrosion monitoring technology corrosion inhibitor coating carbon steel corrosion protection

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Antimicrobial resistance crisis:could artificial intelligence be the solution?

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Military Medical Research 2025年第1期12卷 72-95页

作者： Guang-Yu Liu Dan Yu Mei-Mei Fan Xu Zhang Ze-Yu jin Christoph Tang Xiao-Fen Liu Department of Immunology and Pathogen Biology School of Basic Medical SciencesHangzhou Normal UniversityKey Laboratory of Aging and Cancer Biology of Zhejiang ProvinceKey Laboratory of Inflammation and Immunoregulation of HangzhouHangzhou Normal UniversityHangzhou 311121China National Key Discipline of Pediatrics Key Laboratory of Major Diseases in Children Ministry of Education Laboratory of DermatologyBeijing Pediatric Research InstituteBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China Robert and Arlene Kogod Center on Aging Mayo ClinicRochesterMN 55905USA Department of Biochemistry and Molecular Biology Mayo ClinicRochesterMN 55905USA Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Sir William Dunn School of Pathology University of OxfordOxford OX13REUK Institute of Antibiotics Huashan HospitalFudan UniversityKey Laboratory of Clinical Pharmacology of AntibioticsNational Health Commission of the People’s Republic of ChinaNational Clinical Research Centre for Aging and MedicineHuashan HospitalFudan UniversityShanghai 200040China

Antimicrobial resistance is a global public health threat,and the World Health Organization(WHO)has announced a priority list of the most threatening pathogens against which novel antibiotics need to be *** discovery and introduction of novel antibiotics are time-consuming and *** to WHO’s report of antibacterial agents in clinical development,only 18 novel antibiotics have been approved since ***,novel antibiotics are critically *** intelligence(AI)has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel ***,we first summarized recently marketed novel antibiotics,and antibiotic candidates in clinical *** addition,we systematically reviewed the involvement of AI in antibacterial drug development and utilization,including small molecules,antimicrobial peptides,phage therapy,essential oils,as well as resistance mechanism prediction,and antibiotic stewardship.

关键词： Antibiotic Artificial intelligence(AI) Clinical development Machine learning(ML) Antimicrobial peptide Phage therapy Antibiotic stewardship

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Constructing Ti_(3)C_(2)T_(x)-MXene-based gradient woodpile structure by direct ink writing 3D printing for efficient microwave absorption

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International Journal of Minerals,Metallurgy and Materials 2025年第3期32卷 657-667页

作者： Changtian Zhu Pei Liu jin Chen Zixuan Ding Guohui Tang Qingqing Gao Yinxu Ni Kai Xu Zhilei Hao Gaojie Xu Fenghua Liu School of Materials Science and Chemical Engineering Ningbo UniversityNingbo 315211China Ningbo Institute of Materials Technology&Engineering Chinese Academy of SciencesNingbo 315201China

As a novel 2D material,Ti_(3)C_(2)T_(x)-MXene has become a major area of interest in the field of microwave absorption(MA).However,the MA effect of common Ti_(3)C_(2)T_(x)-MXene is not prominent and often requires complex processes or combinations of other ma-terials to achieve enhanced *** this context,a kind of gradient woodpile structure using common Ti_(3)C_(2)T_(x)-MXene as MA ma-terial was designed and manufactured through direct ink writing(DIW)3D *** minimum reflection loss(RL_(min))of the Ti_(3)C_(2)T_(x)-MXene-based gradient woodpile structures with a thickness of less than 3 mm can reach-70 dB,showing considerable improve-ment compared with that of a completely filled *** addition,the effective absorption bandwidth(EAB)reaches 7.73 *** study demonstrates that a Ti_(3)C_(2)T_(x)-MXene material with excellent MA performance and tunable frequency band can be successfully fab-ricated with a macroscopic structural design and through DIW 3D printing without complex material hybridization and modification,of-fering broad application prospects by reducing electromagnetic wave radiation and interference.

关键词： Ti_(3)C_(2)T_(x)-MXene electromagnetic wave absorption macro-design impedance matching 3D printing ink

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A multi-affinity supramolecular nanolayer reinforced PVDF-LLZTO composite polymer electrolyte for stable solid-state lithium batteries

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Nano Research 2025年第2期18卷 317-327页

作者： Changfei Liu Sailong Wang Zhengyi Lu Jiaqing Zhao Yuchen Wu Chaojie Ren Ruizhi Yang Chao jin College of Energy Soochow Institute for Energy and Materials InnovationsSoochow UniversitySuzhou 215006China

Technical breakthrough of composite polymer electrolyte(CPE)is one of the key factors that determines the commercial process of the current solid-state lithium ***,high interface impedance limits its electrochemical *** is crucial to optimize the design of multiphase interfaces among different components in CPE for regulating Li+***,a multi-affinity self-assembled 12-crown-4-TFSI(12C4-TFSI)supramolecular nanolayer is introduced into poly(vinylidene difluoride)-Li_(6.75)La_(3)Zr_(1.75)Ta_(0.25)O_(12)(PVDF-LLZTO)CPE as interface *** a result,enhanced Li+conductivity of 4.29×10^(-4)S·cm^(-1),Li+transfer number of 0.44,and stable electrochemical window voltage of 4.8 V ***/Li+at 30℃ are *** symmetric Li||Li cell exhibits an improved critical current density(CCD)of 1.2 mA·cm^(-2) and steady cycling at 0.2 mA·cm^(-2) for over 850 h without visible voltage *** assembled LiǁLiFePO4 coin solid-state cell delivers a high initial discharge capacity of 172.9 mAh·g^(-1) at 0.1 C,rate capability(up to 5.0 C)and outstanding cycling stability with a capacity retention of 87.2% after over 750 cycles at 1.0 *** associated LiǁLiFePO4 pouch cell presents an initial specific discharge capacity of 112.3 mAh·g−1 and successfully runs 30 cycles with a final capacity of 101.8 mAh·g^(-1).This work offers a facile strategy to optimize multiphase interfaces of PVDF-LLZTO CPE for stable solid-state lithium battery.

关键词： solid-state lithium battery composite polymer electrolyte interface impedance modifier supramolecular

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