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National Science Review 2024年第7期11卷 189-204页

作者： Taokun Luo Xiaomin Jiang Yingjie Fan Eric Yuan Jinhong Li Langston Tillman Wenbin Lin department of Chemistry University of Chicago department of Radiation and Cellular Oncology and the Ludwig center for Metastasis Research University of Chicago

Radiotherapy is widely used for cancer treatment, but its clinical utility is limited by radioresistance and its inability to target metastases. Nanoscale metal-organic frameworks(MOFs) have shown promise as high-Z nanoradiosensitizers to enhance radiotherapy and induce immunostimulatory regulation of the tumor microenvironment. We hypothesized that MOFs could deliver small-molecule therapeutics to synergize with radiotherapy for enhanced antitumor efficacy. Herein, we develop a robust nanoradiosensitizer,GA-MOF, by conjugating a STING agonist, 2,3-cyclic guanosine monophosphate–adenosine monophosphate(GA), on MOFs for synergistic radiosensitization and STING activation. GA-MOF demonstrated strong anticancer efficacy by forming immune-cell-rich nodules(artificial leukocytoid structures) and transforming them into immunostimulatory hotspots with radiotherapy. Further combination with an immune checkpoint blockade suppressed distant tumors through systemic immune activation. Our work not only demonstrates the potent radiosensitization of GA-MOF, but also provides detailed mechanisms regarding MOF distribution, immune regulatory pathways and long-term immune effects.

关键词： metal-organic framework radiosensitization STING agonist artificial leukocytoid structures immune hotspots immunotherapy nanomedicine

Apoer2/Lrp8:the undercover cop of synaptic homeostasis

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Neural Regeneration Research 2024年第12期19卷 2563-2564页

作者： Gordon C.Werthmann Joachim Herz department of Molecular Genetics and center for Translational Neurodegeneration Research University of Texas Southwestern Medical Center at DallasDallasTXUSA department of Neuroscience department of Neurology University of Texas Southwestern Medical center at Dallas DallasTXUSA

Apolipoprotein E receptor 2(ApoER2)is a receptor for the protein ApoE,the most common genetic risk factor for late-onset Alzheimer's disease(AD).It is also a key modulator of syna ptic homeostasis,in part through its effect on the expression of neuronal genes including those implicated in AD and other neuropsychiatric *** this perspective,we highlight several genes affected by ApoER2 and its alternatively spliced forms and how aberrant expression can be rescued by the reintroduction of the ApoER2 intracellular domain in the mouse hippocampus.

关键词： homeostasis ApoE Alzheimer

Emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of Emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie department of Emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

Haemorrhage after thrombectomy with adjuvant thrombolysis in unknown onset stroke depends on high early lesion water uptake

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Stroke & Vascular Neurology 2024年第4期9卷 390-398页

作者： Gabriel Broocks Lukas Meyer Uta Hanning Tobias Djamsched Faizy Matthias Bechstein Helge Kniep Noel Van Horn Gerhard Schön Ewgenia Barow Götz Thomalla Jens Fiehler Andre Kemmling department of Diagnostic and Interventional Neuroradiology University Medical Center Hamburg-EppendorfHamburgGermany department of Medical Biometry and Epidemiology University Medical Center Hamburg EppendorfHamburgGermany department of Neurology University Medical Center Hamburg-EppendorfHamburgGermany department of Neuroradiology University MarburgMarburgGermany

Background and purpose In wake-up stroke,CT-based quantitative net water uptake(NWU)might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase(IVT).An important complication after IVT is symptomatic intracerebral haemorrhage(sICH).As NWU directly implies ischaemic lesion progression,reflecting blood-brain barrier injury,we hypothesised that NWU predicts sICH in patients who had a ischaemic stroke undergoing thrombectomy with unknown *** Consecutive analysis of all patients who had unknown onset anterior circulation ischaemic stroke who underwent CT at baseline and endovascular treatment between December 2016 and October *** NWU was assessed on baseline *** primary endpoint was *** association of NWU and other baseline parameters to sICH was investigated using inverse-probability weighting(IPW)*** A total of 88 patients were included,of which 46 patients(52.3%)received *** median NWU was 10.7%(IQR:5.1–17.7).The proportion of patients with any haemorrhage and sICH were 35.2%and 13.6%.NWU at baseline was significantly higher in patients with sICH(19.1%vs 9.6%,p<0.0001)and the median Alberta Stroke Program Early CT Score(ASPECTS)was lower(5 vs 8,p<0.0001).Following IPW,there was no association between IVT and sICH in unadjusted ***,after adjusting for ASPECTS and NWU,there was a significant association between IVT administration and sICH(14.6%,95%CI:3.3%to 25.6%,p<0.01).Conclusion In patients with ischaemic stroke with unknown onset,the combination of high NWU with IVT is directly linked to higher rates of *** ASPECTS for evaluating the extent of the early infarct lesion,quantitative NWU could be used as an imaging biomarker to assess the degree of blood-brain barrier damage in order to predict the risk of sICH in patients with wake up stroke.

关键词： throm thrombolysis high

The Largest Chinese Cohort Study Indicates Homologous Recombination Pathway Gene Mutations as Another Major Genetic Risk Factor for Colorectal Cancer with Heterogeneous Clinical Phenotypes

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Research 2024年第3期6卷 191-203页

作者： Yun Xu Kai Liu Cong Li Minghan Li Fangqi Liu Xiaoyan Zhou Menghong Sun Megha Ranganathan Liying Zhang Sheng Wang Xin Hu Ye Xu department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China department of Pathology Fudan University Shanghai Cancer CenterShanghaiP.R.China department of Pathology Tissue BankFudan University Shanghai Cancer CenterShanghaiP.R.China department of Medicine Memorial Sloan Kettering Cancer CenterNew YorkNYUSA department of Pathology and Laboratory Medicine David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Precision Cancer Medical center Fudan University Shanghai Cancer CenterShanghaiP.R.China

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

关键词： susceptibility category Major

Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

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Neural Regeneration Research 2024年第9期19卷 2075-2080页

作者： Rui Zong Xuemei Li Chunyu Yin Jianfeng He Dekang Zhang Xiangbing Bian Lichao Huang Jiayou Zhou Zhipei Ling Lin Ma Xin Lou Longsheng Pan Xinguang Yu Seniro department of Neurosurgery The First Medical Center of the PLA General HospitalBeijingChina Clinics of Cadre Department of OutpatientThe First Medical Center of the PLA General HospitalBeijingChina department of Radiology The First Medical Center of the PLA General HospitalBeijingChina

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential *** 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical center of the PLA General *** prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(*** Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local *** 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm *** treatment efficacy was determined using the Clinical Rating Scale for *** was evaluated according to the incidence and severity of adverse *** of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate *** the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as *** most common intraoperative adverse events were nausea and *** most frequent postoperative adverse events were paresthesia and equilibrium *** of the adverse events were mild and usually disappeared within a few *** findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

关键词： efficacy essential tremor magnetic resonance-guided focused ultrasound(MRgFUS) movement disorder safety stereotactic therapy thalamotomy ventral intermediate nucleus

Non-innocent partners:bias distribution between photoanodes and cathodes in photoelectrochemical overall water-splitting cells

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National Science Review 2024年第6期11卷 88-89页

作者： Wei Li Dunwei Wang department of Chemistry Merkert Chemistry Center Boston College

Photoelectrochemical (PEC) overall water splitting (OWS) represents a highly promising strategy to directly harvest solar energy and store it in the form of fuels,offering unique benefits such as mitigating issues con...

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Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan department of Medical Imaging AnatomyRadboud University Medical CenterDonders Institute for BrainCognition&BehaviorCenter for Medical NeurosciencePreclinical Imaging Center PRIMERadboud Alzheimer CenterNijmegenthe Netherlands

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the *** at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of *** signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease *** pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier ***,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel ***,the purpose of this review is to provide a new foundation in the study of small vessel disease ***,we discuss the main structural domains and functions of the blood-brain ***,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel ***,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

Progress and challenges for replacing n-methyl-2-pyrrolidone/polyvinylidene fluoride slurry formulations in lithium-ion battery cathodes

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Progress in Natural Science:Materials International 2024年第1期34卷 194-206页

作者： Sung Cik Mun Yeong Hoon Jeon Jong Ho Won Battery Materials Research center LG Chem department of Energy Engineering Dankook University

With electric vehicles, energy storage systems, and portable electronic devices becoming increasingly popular, the demand for lithium-ion batteries has surged considerably. In the lithium-ion battery industry, n-methyl-2-pyrrolidone(NMP) is widely used as the solvent for cathode slurry, and polyvinylidene fluoride(PVDF) is used as the cathode binder. However, because of the harmful effect of NMP on the environment and human health, the use of NMP and PVDF for lithium-ion batteries will be highly regulated in the future. Therefore, developing eco-friendly alternatives is crucial for formulating systems using new solvents and binders. Despite numerous efforts, these alternatives have not been widely adopted across the lithium-ion battery industry. It is due to their limited ability to compete on price or performance to replace the traditional NMP/PVDF slurry formulations. This review investigates developments in the search for new solvents and binders that can be used in cathode slurry compositions. The new systems can potentially decrease energy consumption and manufacturing costs associated with NMP recovery, energy-intensive drying processes, and material expenses. We discuss key factors and technical challenges from earlier studies and compare them with the current, optimized formulations based on NMP and PVDF.

关键词： Lithium-ion battery Eco-friendly alternative Slurry formulation Chemical regulation Binder performance

Trends in oxycodone and oxycodone-containing analgesics administration for back pain in emergency departments in the USA(2007–2018)

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World Journal of Emergency Medicine 2024年第3期15卷 169-174页

作者： Jonathan Chabon Jemer Garrido Deanna Schreiber-Gregory Jefferson Drapkin Sergey Motov department of Emergency Medicine Maimonides Medical CenterBrooklyn 11219USA

BACKGROUND:To describe trends in oxycodone and oxycodone-containing analgesic prescribing for the treatment of back pain among adults in emergency departments(EDs) in the USA from 2007 to ***:Data were gathered from the National Hospital Ambulatory Medical Care Survey(NHAMCS) from 2007 to *** study population included individuals of all ages presenting to USA *** NHAMCS reasons for visit and oxycodone drug ID codes were used to isolate patients with back *** main outcome was the proportion of oxycodone and oxycodone-containing analgesics prescribed for back pain in the EDs over the specified time ***:There was a relative decrease in the overall administration of oxycodone for back pain in the EDs by 62.3% from 2007(244,000 visits) to 2018(92,000 visits).The proportion of ED patients prescribed with oxycodone-containing analgesics for back pain increased among patients aged 45 years and older(from 43.8% to 57.6%),female patients(from 54.5% to 62.0%),black patients(from 22.5% to 30.4%),and Hispanic/Latino patients(from 9.4% to 19.6%).Oxycodone/acetaminophen was most prescribed and accounted for 90.2% of all oxycodone-containing analgesics in 2007,with a decrease to 68.5% in *** oxycodone was the second most prescribed medication,accounting for 6.1% in 2007 and 31.5% in ***:The overall number of oxycodone-containing analgesics decreased significantly from 2007 to ***,that number trended upward in 45-year-old and older,female,black,or Hispanic/Latino patients from 2007 to *** total amount of pure oxycodone increased significantly from 2007 to 2008.

关键词： Oxycodone Back pain Emergency department