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Anti-steatotic and anti-fibrotic effects of the KCa3.1 channel inhibitor, Senicapoc, in non-alcoholic liver disease

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World Journal of Gastroenterology 2017年第23期23卷 4181-4190页

作者： latha paka david e smith dawoon jung siobhan mccormack ping zhou bin duan jing-song li jiaqi shi yong-jie hao kai jiang michael yamin itzhak d goldberg prakash narayan department of Research and development Angion Biomedica Corp.

To evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLd).METHOdSWe have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide (TAA) and high fat diet (HFd)-induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and *** of KCa3.1 expression was recorded in TAA-induced and high fat diet-induced liver disease. Treatment with Senicapoc decreased palmitic acid-driven HepG2 cell death. (P ding that Senicapoc reduces lipid-driven apoptosis in HepG2 cell cultures. In animals fed a HFd for 6 wk, co-treatment with Senicapoc, (1) reduced non-alcoholic fatty liver disease (NAFLd) activity score (NAS) (0-8 scale), (2) decreased steatosis and (3) decreased hepatic lipid content (Oil Red O, P domization of TAA animals and HFd fed animals to Senicapoc was associated with a decrease in liver fibrosis as evidenced by hydroxyproline and Masson’s trichrome staining (P demonstrated that Senicapoc mitigates both steatosis and fibrosis in liver fibrosis *** data suggest that Senicapoc interrupts more than one node in progressive fatty liver disease by its anti-steatotic and anti-fibrotic activities, serving as a double-edged therapeutic sword.

关键词： High fat diet Liver Steatosis Fibrosis KCa3.1 channel Senicapoc Inflammation

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放射治疗对肾脏的毒性作用

国际泌尿系统杂志 1985年第4期 174-176页

作者： itzhak d goldberg 李肇正

用于治疗肿瘤的各种方法对肾脏有潜在的毒性作用,放射疗法亦然,因此在肿瘤治疗期间要注意保护肾脏正常的功能。本文从临床症状、体征、病理生理及治疗情况来讨论肾脏对放射疗法的耐受性。正常的肾脏对放射治疗的反应可根据组织改变、生... 详细信息

用于治疗肿瘤的各种方法对肾脏有潜在的毒性作用,放射疗法亦然,因此在肿瘤治疗期间要注意保护肾脏正常的功能。本文从临床症状、体征、病理生理及治疗情况来讨论肾脏对放射疗法的耐受性。正常的肾脏对放射治疗的反应可根据组织改变、生理变化以及临床预后来加以分类。虽然大多数在腹部及腹膜后进行放射治疗的患者在临床上并无明显的肾脏损害,但可发生一系列功能上和病理上的变化。组织学改变:大多数动物和人类的实验资料表

关键词：放射性肾炎拉德放射疗法患者肾脏放射治疗恶性高血压毒性作用肾小球内皮细胞分剂量

A small molecule fibrokinase inhibitor in a model of fibropolycystic hepatorenal disease

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World Journal of Nephrology 2018年第5期7卷 96-107页

作者： Prani Paka Brian Huang Bin duan Jing-Song Li Ping Zhou Latha Paka Michael A Yamin Scott L Friedman itzhak d goldberg Prakash Narayan department of Research and development Angion Biomedica Corp.UniondaleNY 11553United States Icahn School of Medicine 1 Gustave L.Levy PlaceNew YorkNY 10029United States

AIM To evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis *** At 6 wk of age, PCK rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and left kidneys were collected and rats were continued on treatment for 4 wk. At 14 wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys were collected for histological evaluation. For Western blot studies, PCK rats were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min after the last *** Compared to the wild-type cohort, the PCK kidney(Vehicle cohort) exhibited a marked increase in kidney and liver mass, hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight, reduced renal cystic volume and reduced total kidney hydroxyproline, indicating significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle cohort. ANG3070 treatment also mitigated several markers of kidney injury, including urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment attenuated key indices of renal dysfunction, including proteinuria, albuminuria and serum blood urea nitrogen and creatinine, and significantly improved renal function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated liver dysfunction compared to the PCK-Vehicle *** These results suggest that ANG3070 has the potential to slow disease, and may serve as a bridge toward hepato-renal transplantation in patients with fibropolycystic disease.

关键词： Congenital hepatic fibrosis Cyst Fibrosis Autosomal recessive polycystic kidney disease Kidney Liver Therapy

Spatial and seasonal variation in soil respiration along a slope in a rubber plantation and a natural forest in Xishuangbanna, Southwest China

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Journal of Mountain Science 2018年第4期15卷 695-707页

作者： ZHAO Yong-li Stefanie d.goldberg XU Jian-chu Rhett d.HARRISON Center for Mountain Ecosystem Studies Kunming Institute of Botany Chinese Academy of Sciences Kunming 650201 China University of Chinese Academy of Sciences Beijing 100039 China World Agroforestry Centre East and Central Asia Kunming 650201 China World Agroforestry Centre East & Southern Africa Region 13 Elm Road Woodlands Lusaka Zambia

Soil respiration is a key component of the global carbon cycle, and even small changes in soil respiration rates could result in significant changes in atmospheric CO_2 levels. The conversion of tropical forests to rubber plantations in SE Asia is increasingly common, and there is a need to understand the impacts of this land-use change on soil respiration in order to revise CO_2 budget calculations. This study focused on the spatial variability of soil respiration along a slope in a natural tropical rainforest and a terraced rubber plantation in Xishuangbanna, Southwest(SW) China. In each land-use type, we inserted 105 collars for soil respiration *** was conducted over one year in Xishuangbanna during May, June, July and October 2015(wet season) and January and March 2016(dry season). The mean annual soil respiration rate was 30% higher in natural forest than in rubber plantation and mean fluxes in the wet and dry season were 15.1 and 9.5 Mg C ha^(-1) yr^(-1) in natural forest and 11.7 and 5.7 Mg C ha^(-1) yr^(-1) in rubber plantation. Using a linear mixedeffects model to assess the effect of changes in soil temperature and moisture on soil respiration, we found that soil temperature was the main driver of variation in soil respiration, explaining 48% of its seasonal variation in rubber plantation and 30% in natural forest. After including soil moisture, the model explained 70% of the variation in soil respiration in natural forest and 76% in rubber plantation. In the natural forest slope position had a significant effect on soil respiration, and soil temperature and soil moisture gradients only partly explained this correlation. In contrast, soil respiration in rubber plantation was not affected by slope position, which may be due to the terrace structure that resulted in more homogeneous environmental conditions along the slope. Further research is needed to determine whether or not these findings hold true at a landscape level.

关键词： Soil respiration Tropical rain forest Rubber plantation Land-use change Carbon cycle Transect

Seedling survival after simulating grazing and drought for two species from the Pamirs,northwestern China

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Plant diversity 2022年第6期44卷 607-616页

作者： Fiona R.Worthy Stefanie d.goldberg Sailesh Ranjitkar Jian-Chu Xu CAS Key Laboratory for Plant diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of SciencesKunming 650201YunnanChina CIFOR-ICRAF China Program World Agroforestry(ICRAF)Kunming 650201YunnanChina Honghe Center for Mountain Futures(CMF) Kunming Institute of BotanyChinese Academy of SciencesHonghe County 654400YunnanChina Faculty of Agroforestry Lumbini Buddhist UniversityLumbiniNepal

For plant populations to persist,seedling recruitment is essential,requiring seed germination,seedling survival and *** and grazing potentially reduce seedling recruitment via increased mortality and reduced *** studied these seederelated processes for two species indigenous to the Pamir Mountains of Xinjiang in northwestern China:Saussurea glacialis and Plantago *** collected from Taxkorgan,Xinjiang,had a viability rate of 15.8%for *** but 100%for *** the viable seeds,the highest germination rates were 62.9%for *** and 45.6%for *** a greenhouse experiment,we imposed a series of stressful conditions,involving a combination of simulated grazing and drought *** had the most severe impact on younger *** showed that 89%of *** mortality was due to early simulated grazing,whereas 80%of *** mortality was due to early simulated *** differences could contribute to their differing *** may rely on water storage in leaves to survive drought events,but showed no shifts in biomass allocation that would improve grazing *** appears more reliant on its root system to survive grazing,but the root reserves of younger plants could be insufficient to grow deeper in response to *** applying all mortality factors,17.7 seedlings/parent of *** survived,while onlydlings/parent of *** survived,raising concerns for its capacity to persist in the *** genetic differences may underlie the two species’contrasting grazing and drought ***,differing conservation strategies are required for their utilization and protection.

关键词： Medicinal plant Pastoralist Plantago lessingii Saussurea glacialis Soil moisture Water deficit

Incident frailty and cognitive impairment by heart failure status in older patients with atrial fibrillation: the SAGE-AF study

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Journal of Geriatric Cardiology 2020年第11期17卷 653-658页

作者： Wei-Jia WANG darleen Lessard Jane Saczynski Robert J goldberg Alan S.Go Tenes Paul Ely Gracia david d McManus department of Medicine University of Massachusetts Medical SchoolWorcesterMAUSA department of Population and Quantitative Health Sciences University of Massachusetts Medical SchoolWorcesterMAUSA department of Pharmacy and Health System Sciences Northeastern UniversityBostonMAUSA division of Research Kaiser Permanente Northern CaliforniaOaklandCAUSA

Background Atrial fibrillation(AF) and heart failure(HF) frequently co-occur in older individuals. Among patients with AF, HF increases risks for stroke and death, but the associations between HF and incident cognition and physical impairment remain unknown. We aimed to examine the cross-sectional and prospective associations between HF, cognition, and frailty among older patients with AF. Methods The SAGE-AF(Systematic Assessment of Geriatric Elements in AF) study enrolled 1244 patients with AF(mean age 76 years, 48% women) from five practices in Massachusetts and Georgia. HF at baseline was identified from electronic health records using ICd-9/10 codes. At baseline and 1-year, frailty was assessed by Cardiovascular Health Survey score and cognition was assessed by the Montreal Cognitive Assessment. Results Patients with prevalent HF(n = 463, 37.2%) were older, less likely to be non-Hispanic white, had less education, and had greater cardiovascular comorbidity burden and higher CHA2 dS2 VASC and HAS-BLEd scores than patients without HF(all P's djusted regression models, HF(present vs. absent) was associated with both prevalent frailty(adjusted odds ratio [a OR]: 2.38, 95% confidence interval [CI]: 1.64-3.46) and incident frailty at 1 year(a OR: 2.48, 95% CI: 1.37-4.51). HF was also independently associated with baseline cognitive impairment(a OR: 1.60, 95% CI: 1.22-2.11), but not with developing cognitive impairment at 1 year(a OR 1.04, 95%CI: 0.64-1.70). Conclusions Among ambulatory older patients with AF, the co-existence of HF identifies individuals with physical and cognitive impairments who are at higher short-term risk for becoming frail. Preventive strategies to this vulnerable subgroup merit consideration.

关键词： Atrial fibrillation Cognitive impairment Heart failure Frailty

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一般医疗中心理障碍的发现过程

中国心理卫生杂志 1993年第1期7卷 35-37页

作者： goldberg d. ,许又新

一、心理障碍的发现过程精神障碍的调查可以从5个不同的水平加以考虑:1.随机社区样本;2.基层诊所就诊者的调查;3.基层医生对精神上患病人数的估计;4.向精神疾病机构转诊的人数;5.收住精神科的人数。我们设想,求助于精神卫生专科医生的... 详细信息

一、心理障碍的发现过程精神障碍的调查可以从5个不同的水平加以考虑:1.随机社区样本;2.基层诊所就诊者的调查;3.基层医生对精神上患病人数的估计;4.向精神疾病机构转诊的人数;5.收住精神科的人数。我们设想,求助于精神卫生专科医生的人大多数以前都找过其他保健人员。因此,在社区和精神科病床之间存在一系列的过滤,社区里的人必须通过

关键词：家庭医生精神科病人精神障碍心理障碍

Atmospheric pollution in Beijing, China, as recorded in sediments of the Kunming Lake

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Journal of Environmental Sciences 1991年第1期3卷 109-116页

作者： Kathe K.Bertines Minoru Koide Edward d.goldberg San diego State University San Diego 92182 California USA.Scripps Institution of Oceanography La Jolla 92093 California USA.Scripps Institution of Oceanography La Jolla 92093 California USA.

The fluxes of heavy metals and magnetite, a fly-ash component, from coal burning, to sediments of the Kunming Lake in Beijing have increased measurably over the last fifty years. Ages were introduced to the sediment strata through Pb-210 geochronologies. Even with a doubling of coal usage by the year 2000, the anthropogenic metal fluxes will still be less than those recorded in metropolitan Tokyo and U.S. lakes.

关键词： atmospheric pollution sediment heavy metal geochronology.

TopoBERT:a plug and play toponym recognition module harnessing fine-tuned BERT

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International Journal of digital Earth 2023年第1期16卷 3045-3064页

作者： Bing Zhou Lei Zou Yingjie Hu Yi Qiang daniel goldberg department of Geography Texas A&M UniversityCollege StationUSA department of Geography University at BuffaloBuffaloUSA cSchool of Geoscience University of South Florid1Tamp1USA

Extracting precise geographical information from the textual content,referred to as toponym recognition,is fundamental in geographical information retrieval and crucial in a plethora of spatial analyses,*** location-based information from social media,news reports,and surveys for various ***,the performance of existing toponym recognition methods and tools is deficient in supporting tasks that rely on extracting fine-grained geographic information from texts,*** people sending help requests with addresses through social media during *** emerging pretrained language models have,revolutionized,natural language_processing and understanding by machines,offering a promising pathway to optimize toponym recognition to underpin practical *** this paper,TopoBERT,a uniquely designed toponym recognition module based on a one-dimensional'Convolutional Neural Network(CNN1d)and Bidirectional Encoder Representation from Transformers(BERT),is proposed and *** datasets are leveraged to tune the hyperparameters and discover the best strategy to train the *** seven datasets are used to evaluate the *** achieves state-of-the-art performance(average f1-score=0.854)compared to the seven baseline *** is encapsulated into easy-to-use python scripts and can be seamlessly applied to diverse toponym recognition tasks without additional training.

关键词： Natural language processing geoparser convolutional neural network toponym recognition BERT