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Peripheral immune cell-derived matrix metalloprotease 8(MMP8):brain trafficking promotes depression-like behavior

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2357-2358页

作者： Dietmar Spengler Theo Rein Max Planck Institute of Psychiatry Epigenomics of Early-Life Stress80804 MunichGermany Max Planck Institute of Psychiatry Molecular Pathways of Depression80804 MunichGermany

In a study recently published in Nature,Cathomas et al.1 report that social stress in mice increases the levels of matrix metalloprotease(MMP)8 in circulating immune cells,thereby altering extracellular space(ECS)and neuronal activity,and ultimately social behavior in susceptible *** deficits resembled those from major depressive disorder(MDD)raising the prospect of MMP8 as a new druggable target in tailored treatments.

关键词： MMP8 al. behavior

Divergent defluorocarboxylation of α-CF_(3) alkenes with formate via photocatalyzed selective mono-or triple C-F bond cleavage

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Science China Chemistry 2024年第1期67卷 368-373页

作者： Xing-Yu Wang Pei Xu Wen-Wen Liu Hao-Qiang Jiang Song-Lei Zhu Dong Guo Xu Zhu Jiangsu Key Laboratory of New Drug research and clinical Pharmacy School of PharmacyXuzhou Medical UniversityXuzhou 22100China

Unprecedented divergent synthesis of gem-difluorovinylacetic acid and glutaric acid derivatives fromα-CF_(3)alkenes with formate as the carbonyl source was *** reaction can undergo selective mono-or triple C-F bond cleavage by simply switching the photocatalyst and hydrogen atom transfer(HAT)catalyst under visible-light-induced conditions at room *** acts as both the C1 source and the reductant through the generation of CO_(2)^(·-)species,which underwent Giese radical addition to electron-deficient alkenes to trigger the consecutive C-F bond cleavage and carboxylation process.

关键词： C-F bond activation defluorocarboxylation carbon dioxide radical anion visible light

Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

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Journal of Integrative Medicine 2024年第1期22卷 46-53页

作者： Rosemary Arnold Jenifer Murphy-Smith Chee H.Ng David Mischoulon Gerard J.Byrne Chad A.Bousman Con Stough Michael Berk Jerome Sarris Professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia depression clinical and research program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of Medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia Departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Psychiatry the University of MelbourneMelbourne 3052Australia Centre for Human Psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and Physical Health and clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The Centre of Excellence in Youth Mental Health the University of MelbourneParkville 3052Australia Florey Institute of Neuroscience and Mental Health the University of MelbourneParkville 3052Australia NICM Health research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial Placebo depression Nutraceutical Psychiatry

Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients

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Journal of Geriatric Cardiology 2024年第2期21卷 211-218页

作者： Luo-Xi XIAO Zi-Yu WANG Jiang-Tao LI Hai-Mei WANG Yi-Ming HAO Pan ZHOU Yu-Lin HUANG Qiu-Ju DENG Yong-Chen HAO Na YANG Li-Zhen HAN Zhao YANG Ping-Ping JIA Yue QI Jing LIU Center for clinical and Epidemiologic research Beijing Anzhen HospitalCapital Medical UniversityBeijing Institute of HeartLung and Blood Vessel DiseasesBeijing Municipal Key Laboratory of Clinical EpidemiologyBeijingChina

BACKGROUND Hypertension usually clusters with multiple ***,the association between cardiometabolic multimorbidity(CMM)and mortality in hypertensive patients is *** study aimed to investigate the association between CMM and all-cause and cardiovascular disease(CVD)mortality in Chinese patients with *** The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors(CONSIDER),which comprised 5006 participants aged 19–91 *** was defined as the presence of one or more of the following morbidities:diabetes mellitus,dyslipidemia,chronic kidney disease,coronary heart disease,and *** proportional hazard models were used to calculate the hazard ratios(HR)with 95%CI to determine the association between the number of CMMs and both all-cause and CVD *** Among 5006 participants[mean age:58.6±10.4 years,50%women(2509 participants)],76.4%of participants had at least one *** mortality rate was 4.57,4.76,8.48,and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one,two,and three or more morbidities,*** the fully adjusted model,hypertensive participants with two cardiometabolic diseases(HR=1.52,95%CI:1.09–2.13)and those with three or more cardiometabolic diseases(HR=2.44,95%CI:1.71–3.48)had a significantly elevated risk of all-cause *** findings were similar for CVD mortality but with a greater increase in risk *** In this study,three-fourths of hypertensive patients had *** with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients,suggesting more intensive treatment and control in this high-risk patient group.

关键词： hypertensive patients morbidity

An overview of autophagy in the differentiation of dental stem cells

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BIOCELL 2024年第1期48卷 47-64页

作者： XITONG ZHAO TIANJUAN JU XINWEI LI CHANGFENG LIU LULU WANG LI-AN WU State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China

Dental stem cells(DSCs)have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune *** properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative *** many regulatory factors determine the differentiation trajectory of DSCs,prior research has predominantly been based on genetic,epigenetic,and molecular *** evidence suggests that DSC differentiation can also be influenced by autophagy,a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress *** comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC *** achieve this goal,we dissect the intricacies of autophagy and its ***,we elucidate its pivotal roles in impacting DSC differentiation,including osteo/odontogenic,neurogenic,and angiogenic ***,we reveal the regulatory factors that govern autophagy in DSC lineage commitment,including scaffold materials,pharmaceutical cues,and the extrinsic *** implications of this review are far-reaching,underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine.

关键词： Dental stem cells Cell differentiation Autophagy Mitophagy Autophagy regulation

clinical associations of corneal neuromas with ocular surface diseases

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Neural Regeneration research 2024年第1期19卷 140-147页

作者： Charmaine Jan Li Toh Chang Liu Isabelle Xin Yu Lee Molly Tzu Yu Lin Louis Tong Yu-Chi Liu Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore Singapore Eye research Institute Singapore Department of Cornea and External Eye Disease Singapore National Eye CentreSingapore Ophthalmology and Visual Sciences Academic clinical program Duke-NUS Medical SchoolSingapore

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or *** formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ***,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas *** recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface *** neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and *** this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment *** current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more *** imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

关键词： cornea corneal diseases corneal nerve corneal neuropathy in vivo confocal microscopy microneuroma neuroma ocular surface diseases

Machine learning applications in stroke medicine:advancements,challenges,and future prospectives

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Neural Regeneration research 2024年第4期19卷 769-773页

作者： Mario Daidone Sergio Ferrantelli Antonino Tuttolomondo Internal Medicine and Stroke Care Ward Department of Health PromotionMother and Child CareInternal Medicine and Medical SpecialtiesUniversity of Palermo Molecular and clinical Medicine PhD program University of Palermo

Stroke is a leading cause of disability and mortality worldwide,necessitating the development of advanced technologies to improve its diagnosis,treatment,and patient *** recent years,machine learning techniques have emerged as promising tools in stroke medicine,enabling efficient analysis of large-scale datasets and facilitating personalized and precision medicine *** abstract provides a comprehensive overview of machine learning’s applications,challenges,and future directions in stroke *** introduced machine learning algorithms have been extensively employed in all the fields of stroke *** learning models have demonstrated remarkable accuracy in imaging analysis,diagnosing stroke subtypes,risk stratifications,guiding medical treatment,and predicting patient *** the tremendous potential of machine learning in stroke medicine,several challenges must be *** include the need for standardized and interoperable data collection,robust model validation and generalization,and the ethical considerations surrounding privacy and *** addition,integrating machine learning models into clinical workflows and establishing regulatory frameworks are critical for ensuring their widespread adoption and impact in routine stroke *** learning promises to revolutionize stroke medicine by enabling precise diagnosis,tailored treatment selection,and improved *** research and collaboration among clinicians,researchers,and technologists are essential for overcoming challenges and realizing the full potential of machine learning in stroke care,ultimately leading to enhanced patient outcomes and quality of *** review aims to summarize all the current implications of machine learning in stroke diagnosis,treatment,and prognostic *** the same time,another purpose of this paper is to explore all the future perspectives these techniques can provide in combating this disabling dis

关键词： cerebrovascular disease deep learning machine learning reinforcement learning stroke stroke therapy supervised learning unsupervised learning

Transdermal treatment for malignant melanoma by aptamer-modified tetrahedral framework nucleic acid delivery of vemurafenib

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Chinese Chemical Letters 2024年第4期35卷 260-267页

作者： Dexuan Xiao Tianyu Chen Tianxu Zhang Sirong Shi Mei Zhang Xin Qin Yunkun Liu Longjiang Li Yunfeng Lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Sichuan Provincial Engineering research Center of Oral Biomaterials Chengdu 610041China Department of Head and Neck Oncology National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China

Melanoma is one of the most malignant skin tumors, whose high invasion is generally associated with BRAF gene mutation. Although new chemotherapeutic drugs, such as vemurafenib, have been developed to inhibit the growth of melanoma, these drugs are usually administered intravenously or orally, resulting in toxic side effects on major tissues and organs. Tetrahedral framework nucleic acids(tFNAs) are a novel type of DNA nanostructures with excellent biocompatibility and versatility which have been proven to penetrate through skin barrier with ease. In this study, we prepared t FNAs with vemurafenib and connected DNA aptamer AS1411 at the apex of t FNAs(AS1411-tFNAs/vemurafenib). On one hand, AS1411-tFNAs/vemurafenib could kill melanoma cells by blocking the mutated BRAF gene in vitro. Compared with free vemurafenib, AS1411-tFNAs/vemurafenib had no obvious toxicity to normal cells. On the other hand,AS1411-tFNAs could transfer vemurafenib to cross through the skin barrier and permeate into tumor tissues. In vivo, transdermal delivery of AS1411-t FNAs/vemurafenib could inhibit the growth of human A375melanoma, whose inhibiting effect was stronger than intravenous administration of vemurafenib. These results demonstrated the application prospects of tFNAs combined with chemotherapeutic drugs in skin tumors.

关键词： Melanoma Vemurafenib DNA nanostructure Transdermal treatment Side effect

Nutritional and lipid profile status of children with spinal muscular atrophy in China:A retrospective case-control study

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Chinese Medical Journal 2024年第10期137卷 1243-1245页

作者： Yijie Feng Jia Wei Mei Yao Jianing Jin Yiqin Cui Qi Long Fei Chen Yi Hong Dongming Zhou Jingjing Hu Xiao Chen Feng Gao Changzheng Yuan Shanshan Mao Department of Neurology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Department of Infection Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Department of Nutrition Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Children’s Hospital Zhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China School of Public Health Zhejiang University School of MedicineHangzhouZhejiang 310012China Children’s Hospital School of Public HealthZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China

To the Editor:5q spinal muscular atrophy(5qSMA)is an autosomal recessive neuromuscular disorder caused by the lack of the survival motor neuron(SMN)protein encoded by the SMN1 gene,located at 5q11.2-q13.3.[1]The incidence is 1/10,000-1/6000 live births,and the mutation carrier rate in China is 1/42.[1]Spinal muscular atrophy(SMA)is mainly divided into four subtypes:SMA type I,II,III,and IV,based on the motor milestones ever *** I-III occur in children,[1]which often result in progressive muscular atrophy and weakness as well as multi-system dysfunction,including nutritional and metabolic issues.[2]Children with SMA may have hidden nutritional and lipid imbalances,despite normal body appearance and anthropometric measurements,making it difcult to detect early and intervene.

关键词： atrophy muscular children