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Analysis of new bone,cartilage,and fibrosis tissue in healing murine allografts using whole slide imaging and a new automated histomorphometric algorithm

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Bone research 2015年第4期3卷 226-234页

作者： Longze Zhang Martin Chang Christopher A Beck Edward M Schwarz Brendan F Boyce Center for musculoskeletal research School of Medicine and DentistryUniversity of Rochester Medical Center

Histomorphometric analysis of histologic sections of normal and diseased bone samples,such as healing allografts and fractures,is widely used in bone ***,the utility of traditional semi-automated methods is limited because they are labor-intensive and can have high interobserver variability depending upon the parameters being assessed,and primary data cannot be re-analyzed *** histomorphometry has long been recognized as a solution for these issues,and recently has become more feasible with the development of digital whole slide imaging and computerized image analysis systems that can interact with digital ***,we describe the development and validation of an automated application（algorithm）using Visiopharm＇s image analysis system to quantify newly formed bone,cartilage,and fibrous tissue in healing murine femoral allografts in high-quality digital images of H＆E/alcian blue-stained decalcified histologic *** validate this algorithm,we compared the results obtained independently using OsteoMeasureTM and Visiopharm image analysis *** intraclass correlation coefficient between Visiopharm and OsteoMeasure was very close to one for all tissue elements tested,indicating nearly perfect reproducibility across *** new algorithm represents an accurate and labor-efficient method to quantify bone,cartilage,and fibrous tissue in healing mouse allografts.

关键词： cartilage slide automated healing fibrous Figure automatically sections segmentation quantify

Unveiling phosphofructokinase as the key target: an innovative strategy combining pull-down assays with optical imaging for snail-killing mechanism exploration

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Science China Chemistry 2025年

作者： Yuxun Lu Weisi Wang Le Yu Yuqiang Zhao Ying Chen Yunhai Guo Bingrong Luo Yuhua Liu Shizhu Li Liping Duan Ying Zhou Yunnan Characteristic Plant Extraction Laboratory College of Chemical Science and Technology Yunnan University College of Biological and Chemical Engineering Guangxi University of Science and Technology National Institute of Parasitic Diseases Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research on Tropical Diseases School of Chemistry and Environment Yunnan Minzu University Dali Institute of Schistosomiasis Control

The Pomacea canaliculata, also known as apple snail, is an invasive species in China, posing a serious threat to agricultural production and public health. To prevent its rampant infestation, we developed a highly efficient snail-killing lead compound, 1-(4-chlorophenyl)-3-(pyridin-3-yl)urea (PBQ). However, the killing mechanism of PBQ remains unclear. To elucidate this, two novel compounds, B-PBQ and J-PBQ, were developed through structural modification of PBQ and were used, through both protein pull-down assay and confocal laser scanning microscopy imaging, to identify and confirm that phosphofructokinase(PFK) in the apple snail is the primary target protein of PBQ. Further studies revealed that PBQ successfully inhibits the activity,content, and expression of PFK in apple snail, disrupting the glycolysis pathway and leading to abnormal energy *** disruptions impair the snail’s tolerance to low oxygen, resulting in its efficient eradication. These findings offer a promising direction for developing next-generation PFK-targeted snail-killing pesticides. Furthermore, the strategy of combining pull-down assays with optical imaging used in this work provides a novel approach for the exploration of mechanisms of other pesticide candidates.

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Dissecting the cell microenvironment of ovarian endometrioma through single-cell RNA sequencing

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Science China Life Sciences 2025年第1期 116-129页

作者： Jiangpeng Wu Siyu Xia Wenting Ye Yan Sun Jing Cai Fubing Yu Haiping Wen Xiuwei Yi Taikang Li Mingwei Chen Jiayun Chen Ge Song Chuanbin Yang Yali Song Jigang Wang Department of Reproductive Medicine Dongguan Maternal and Child Health Care Hospital Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalSouthern University of Science and Technology State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Reproductive Medicine Center Foshan Women and Children Hospital State Key Laboratory of Antiviral Drugs School of PharmacyHenan University

Ovarian endometrioma（OE）, also known as “chocolate cysts,” is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+and KLF2+epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies.

关键词： ovary high-throughput sequencing transcriptomics gene expression analysis ligand-receptor analysis

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Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts

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Bone research 2016年第3期4卷 164-173页

作者： Allahdad Zarei Alireza Morovat Kassim Javaid Cameron P Brown Botnar research centre Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Science University of Oxford Oxford UK Clinical Biochemistry Oxford University Hospitals NHS Trust Oxford UK

The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor （VDR）, we examined their response to different concentrations of 25-hydroxy vitamin D3 [25（OH）D3] （100 or 500 nmol·L^-1） and 1,25-dihydroxy vitamin D3 [1,25（OH）2D3] （0.1 or 0.5 nmol·L^-1） metabolites in cell cultures. Specifically, CD14＋ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand （RANKL） and macrophage colony-stimulating factor （M-CSF）. Tartrate-resistant acid phosphatase （TRAP） histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue （ex vivo） by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR （qRT-PCR） was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L^-1 of 25（OH）D3 and 0.1-0.5 nmol·L^-1 of 1,25（OH）2D3, upregulating cytochrome P450 family 27 subfamily B member I （CYP27B1） and cytochrome P450 family 24 subfamily A member I （CYP24A1）. Osteoclast fusion transcripts transmembrane 7 subfamily member 4 （tm7sf4） and nuclear factor of activated T-cell cytoplasmic 1 （nfatcl） where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25（OH）D3 and 1,25（OH）2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25（OH）2D3 on osteoclasts in vitro may therefore provide

关键词： Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts bone

Insufficient MIRO1 contributes to declined oocyte quality during reproductive aging

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Science China Life Sciences 2025年

作者： Zhen-Nan Pan Hao-Lin Zhang Kun-Huan Zhang Jia-Qian Ju Jing-Cai Liu Shao-Chen Sun College of Animal Science and Technology Nanjing Agricultural University Reproductive Medicine centre The Affiliated Yantai Yuhuangding Hospital of Qingdao University

Mitochondrial Rho-GTPase 1 (MIRO1) is an outer mitochondrial membrane protein which regulates mitochondrial transport and mitophagy in mitosis. In present study, we reported the crucial roles of MIRO1 in mammalian oocyte meiosis and its potential relationship with aging. We found that MIRO1 expressed in mouse and porcine oocytes, and its expression decreased in aged mice. MIRO1 deficiency caused the failure of meiotic resumption and polar body extrusion in both mouse and porcine oocytes, which could be rescued by exogenous MIRO1supplementation. Mass spectrometry data indicated that MIRO1 associated with several cytoskeleton and cell cycle-related proteins, and MIRO1 regulated motor protein Dynein for microtubule-organizing centers (MTOCs) dynamics at germinal vesicle (GV) stage, which determined meiotic resumption. Furthermore, we found that MIRO1 regulated Aurora A and kinesin family member 11 (KIF11) for meiotic spindle assembly in oocytes. Besides, MIRO1 associated with several mitochondria-related proteins dynamic-related protein 1 (DRP1),Parkin and lysosomal-associated membrane protein 2 (LAMP2) for mitochondrial dynamics and mitophagy during oocyte meiosis. Taken together, our results suggested that MIRO1 played pivotal roles in meiotic resumption, spindle assembly and mitochondrial function in mouse and porcine oocytes, and its insufficiency might contribute to the oocyte maturation defects during aging.

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Orthopaedic tissue engineering and stem cells -an unfulfilled promise

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Biomaterials Translational 2021年第2期2卷 89-90页

作者： James T.Triffitt Botnar research centre Nuffield Department of OrthopaedicsRheumatology and Musculoskeletal SciencesUniversity of OxfordOxfordUK

Despite being over thirty years since there was proof that the hypothetical osteogenic stem cell existed,1 demonstration of any dramatic value for the use of such cells in orthopaedic clinical practice by tissue engineering approaches has not yet been *** is notwithstanding extensive studies concerning the likely nature and potentials of these cells in countless in vitro and in vivo *** part,this is based on the confusion caused by exaggeration of claims by unreliable,or at best naïve,investigators and opportunistic entrepreneurs who have grossly misinterpreted data from many ill-conceived studies.2,3 This pseudo-science has been harmful,especially to the stem cell field,both academically and commercially.

关键词： likely concerning spite

Variability of the Southwest Monsoon since the Last 25 000 Years and Their Possible Causes: Role of Northern Hemisphere versus Tibetan Plateau

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Journal of Earth Science 2013年第3期24卷 428-436页

作者： Anju Pandey Ravi Mishra centre for Climate Change research National centre for Antarctic & Ocean research

High-precision, clay sediment oxygen and hydrogen isotopes analyses of Pleistocene-Holocene deep-sea sediments from the Bay of Bengal （BOB） are presented for the first time. Our study shows that the major source of sediments in the study area, since the last-25 000 years, is likely to be the Higher Himalayan crystalline rocks. Further, the study of these stable isotope data displays the variation of southwest monsoon （SWM） in the BOB region since the last-25 000 years and the cause behind the variation has been interpreted. The δ 18 O values of the clay sediments are compared with δ 18 O values of the BOB seawater. This comparison shows that the clay sediment δ 18 O values of the studied sediment cores temporally vary along with the changes in strength of the SWM. Based on the changes in the clay sediment δ 18 O values of the studied sediment, we evaluate the variance in the SWM since the last 25 000 years in the BOB. Our results are consistent with previous work in the region based on other proxies. To evaluate the factors influencing the intensity of the SWM since the last glacial maxima, we conducted comparative analyses of the studied clay sediment δ 18 O values with δ 18 O values in the Greenland ice cores （GISP2） and Tibetan ice cores （Guliya）. The results from this comparative study show that large-scale changes in the intensity of the SWM since 25 000 years are affected by the climate oscillations of the Northern Hemisphere, but rapid and abrupt fluctuations in the SWM seem to be controlled by the amount of snow cover in the Tibetan Plateau.

关键词： southwest monsoon Bay of Bengal Tibetan Plateau clay stable isotope.

Scientific evidence is just the starting point: A generalizable process for developing sports injury prevention interventions

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Journal of Sport and Health Science 2016年第3期5卷 334-341页

作者： Alex Donaldson David G.Lloyd Belinda J.Gabbe Jill Cook Warren Young Peta White Caroline F.Finch Australian centre for research into Injury in Sport and its Prevention (ACRISP) Federation University Australia centre for musculoskeletal research Griffith Health Institute Griffith University Department of Epidemiology and Preventive Medicine Monash University La Trobe Sport and Exercise Medicine research centre La Trobe University School of Health Sciences Federation University Australia

Background: The 2 most cited sports injury prevention research frameworks incorporate intervention development, yet little guidance is available in the sports science literature on how to undertake this complex process. This paper presents a generalizable process for developing implementable sports injury prevention interventions, including a case study applying the process to develop a lower limb injury prevention exercise training program(Footy First) for community Australian ***: The intervention development process is underpinned by 2 complementary premises:(1) that evidence-based practice integrates the best available scientific evidence with practitioner expertise and end user values and(2) that research evidence alone is insufficient to develop implementable ***: The generalizable 6-step intervention development process involves(1) compiling research evidence, clinical experience, and knowledge of the implementation context;(2) consulting with experts;(3) engaging with end users;(4) testing the intervention;(5) using theory; and(6)obtaining feedback from early implementers. Following each step, intervention content and presentation should be revised to ensure that the final intervention includes evidence-informed content that is likely to be adopted, properly implemented, and sustained over time by the targeted intervention deliverers. For Footy First, this process involved establishing a multidisciplinary intervention development group, conducting 2targeted literature reviews, undertaking an online expert consensus process, conducting focus groups with program end users, testing the program multiple times in different contexts, and obtaining feedback from early implementers of the ***: This systematic yet pragmatic and iterative intervention development process is potentially applicable to any injury prevention topic across all sports settings and levels. It will guide researchers wishing to undertake interventio

关键词： Australian football Implementation Intervention development Lower limb injuries research-to-practice Sports injury prevention Translation

Novel neuroprotective and hepatoprorective effects of citric acid in acute malathion intoxication

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Asian Pacific Journal of Tropical Medicine 2016年第12期9卷 1157-1169页

作者： Omar M.E.Abdel-Salam Eman R.Youness Nadia A.Mohammed Noha N.Yassen Yasser A.Khadrawy Safinaz Ebrahim El-Toukhy Amany A.Sleem Department of Toxicology and Narcotics National Research Centre Medical Biochemistry National Research Centre Pathology National Research Centre Physiology National Research Centre Pharmacology National Research Centre

Objective: To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Methods: Rats were received intraperitoneal(i.p.) injection of malathion 150 mg/kg along with citric acid(200 or 400 mg/kg, orally), atropine(1 mg/kg, i.p.) or citric acid 200 mg/kg+atropine 1 mg/kg and euthanized 4 h later. Results: Malathion resulted in increased lipid peroxidation(malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase(GPx) activity, total antioxidant capacity(TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase(ACh E) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The Comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase(i NOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain ACh E increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and i NOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, ACh E and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and i NOS expression in brain and liver. Conclusions: The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure.

关键词： Citric acid Malathion Oxidative stress Paraoxonase 1 Cholinesterase Comet assay