Three-dimensional(3D)nanoprinting via two-photon polymerization offers unparalleled design flexibility and precision,thereby enabling rapid prototyping of advanced micro-optical elements and systems that have found im...Three-dimensional(3D)nanoprinting via two-photon polymerization offers unparalleled design flexibility and precision,thereby enabling rapid prototyping of advanced micro-optical elements and systems that have found important applications in endomicroscopy and biomedical imaging.The potential of this versatile tool for monolithic manufacturing of dynamic micro-opto-electro-mechanical systems(MOEMSs),however,has not yet been sufficiently explored.This work introduces a 3D-nanoprinted lens actuator with a large optical aperture,optimized for remote focusing in miniaturized imaging systems.The device integrates orthoplanar linear motion springs,a self-aligned sintered micro-magnet,and a monolithic lens,actuated by dual microcoils for uniaxial motion.The use of 3D nanoprinting allows complete design freedom for the integrated optical lens,whereas the monolithic fabrication ensures inherent alignment of the lens with the mechanical elements.With a lens diameter of 1.4 mm and a compact footprint of 5.74 mm,it achieves high mechanical robustness at resonant frequencies exceeding 300 Hz while still providing a large displacement range of 200μm(±100μm).A comprehensive analysis of optical and mechanical performance,including the effects of coil temperature and polymer viscoelasticity,demonstrates its advantages over conventional micro-electro-mechanical system actuators,showcasing its potential for next-generation imaging applications.展开更多
Measurement of optical properties of skin is an expanding and growing field of research.Recent studies have shown that the biological tissue,especially skin,changes the polarization state of the incident light.Using t...Measurement of optical properties of skin is an expanding and growing field of research.Recent studies have shown that the biological tissue,especially skin,changes the polarization state of the incident light.Using this property will enable the study of abnormalities and diseases that alter not only the light intensity but also its polarization state.In this paper we report an experimental study for measuring changes of polarization state of the light scattered from a phantom similar to a sample model of scattering skin.Using the notation of Stokes vector for the polarized light and Mueller matrix for the sample with its polarization properties,we have shown that some elements of the matrix were particularly sensitive to the changes of the polarization-altering physical properties of the scatterers within the phantom.展开更多
AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of ...AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of equal genders underwent two times of abdominal surgery.First,their common bile duct(CBD)was ligated to cause cholestasis by total biliary obstruction(TBO).On day 0,1,3,7,14,21 and 28 after TBO,magnetic resonance imaging(MRI)was conducted to monitor the dilatation of the CBD,and blood was sampled to analyze total serum bilirubin(TSB).Secondly,on day 30,the abdomen was re-opened and gallstone(s)collected from human patients were implanted in the dilated CBD asa virtual gallbladder(VGB),which was closed by suture ligation.This rat cholelithiasis model was examined by MRI,clinical observation,microcholangiography and histology.RESULTS:All rats survived two laparotomies.After ligation,the CBD was dilated to a stable size of 4 to30 mm in diameter on day 21-28,which became a VGB.The rats initially showed signs of jaundice that diminished over time,which paralleled with the evolving TSB levels from 0.6±0.3 mg/d L before ligation,through a peak of 10.9±1.9 mg/dL on day 14,until a nearly normalized value after day 28.The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter.The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology.CONCLUSION:A rat model cholelithiasis with human gallstones has been established,which proves feasible,safe,reliable,nontoxic and cost-effective.Given the gallstones of human origin,applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration.展开更多
Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceut...Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceutical research has played an importantrole in multiple disciplines,particularly in translational oncology.Based on the natural phenomenon of necrosis avidity,Onco Ci Dia has emerged as a novel generic approach for treating solid malignancies.Under this systemic dual targeting strategy,a vascular disrupting agent first selectively causes massive tumor necrosis that is followed by iodine-131 labeled-hypericin(123IHyp),a necrosis-avid compound that kills the residual cancer cells by crossfire effect of beta radiation.In this review,by emphasizing the potential clinical applicability of Onco Ci Dia,we summarize our research activities including optimization of radioiodinated hypericin Hyp preparations and recent studies on the biodistribution,dosimetry,pharmacokinetic and,chemical and radiochemical toxicities of the preparations.Myocardial infarction is a global health problem.Although cardiac scintigraphy using radioactive perfusion tracers is used in the assessment of myocardial viability,searching for diagnostic imaging agents with authentic necrosis avidity is pursued.Therefore,a comparative study on the biological profiles of the necrosis avid 123I-Hyp and the commercially available 99mTc-Sestamibi was conducted and the results are demonstrated.Cholelithiasis or gallstone disease may cause gallbladder inflammation,infection and other severe complications.While studying the mechanisms underlying the necrosis avidity of Hyp and derivatives,their naturally occurring fluorophore property was exploited for targeting cholesterol as a main component of gallstones.The usefulness of Hyp as an optical imaging agent for cholelithiasis was studied and the results are presented.Multiple uses of automatic contrast injectors may reduce costs and save resources.However,cross-contaminations with bloodborne pathogens of infectious diseases may occur.We developed a radioactive method for safety evaluation of a new replaceable patient-delivery system.By mimicking pathogens with a radiotracer,we assessed the feasibility of using the system repeatedly without septic risks.This overview is deemed to be interesting to those involvedin the related fields for translational research.展开更多
Different causative factors acting on the pancreas can result in diseases such as pancreatitis, diabetes and pancreatic tumors. The high incidence and mortality of pancreatic diseases have placed diagnostic imaging in...Different causative factors acting on the pancreas can result in diseases such as pancreatitis, diabetes and pancreatic tumors. The high incidence and mortality of pancreatic diseases have placed diagnostic imaging in a crucial position in daily clinical practice. In this minireview article different pancreatic imaging techniques are discussed, from the standard clinical imaging modalities and state of the art clinical magnetic resonance imaging techniques to current situations in pre-clinical pancreatic imaging studies. In particular, the challenges of pre-clinical rodent pancreatic imaging are addressed, with both the image acquisition techniques and the post-processing methods for rodent pancreatic imaging elaborated.展开更多
<b>Background: </b>COVID-19 produced by SARS-CoV-2 infection has spread worldwide. There is a growing need for immunological assays to detect viral specific antibodies or viral antigen. Current standard of...<b>Background: </b>COVID-19 produced by SARS-CoV-2 infection has spread worldwide. There is a growing need for immunological assays to detect viral specific antibodies or viral antigen. Current standard of diagnosis is reverse-transcriptase polymerase chain reaction (RT-PCR) in nasopharyngeal swabs. However serological tests can be used to determine previous exposure to the virus and complement the diagnosis. IgM and IgG SARS-CoV-2 specific antibodies can be detected as early as one week after infection and assays can be useful to test large groups of individuals. This work revised the available information concerning assays that detect antibodies and antigens for SARS-CoV-2. <b>Methods:</b> Three sources of information were used: technical data sheets (TDS) web pages of the company’s products and published articles in Pubmed with reference to the use of diagnostic kits. All the information was revised until April 5<sup>th</sup> 2020. <b>Results: </b>There were 226 tests coming from 20 countries mainly from China. TDS were found only in 50 (22.1%). Most assays detect specific antibodies (n 180) based on immunochromatography methods (n 110) and use blood-derived samples (n 105). Assays for antibodies detection measured mainly IgM/IgG (n 112) and the most common procedure time was <20 min (n 83). Internal control referred as sensitivity and specificity was found only in 18.6% (n 42) of the assays. The majority of the tests are currently for<i> in vitro</i> diagnosis (IVD). A total 165 articles were found on PubMed 15 were included and only 4 used the commercial kits reviewed. <b>Conclusions: </b>Due to the urgency of producing diagnostic tests for SARS-CoV-2 there is a broad offer of kits. Many tests need additional information for their application. The data collected may be useful in the selection of assays but more and higher quality information is needed.展开更多
Inflammation plays an essential role in the development of atherosclerosis. The initiation and growth of atherosclerotic plaques is accompanied by recruitment of inflammatory and precursor cells from the bloodstream a...Inflammation plays an essential role in the development of atherosclerosis. The initiation and growth of atherosclerotic plaques is accompanied by recruitment of inflammatory and precursor cells from the bloodstream and their differentiation towards pro-inflammatory phenotypes. This process is orchestrated by the production of a number of pro-inflammatory cytokines and chemokines. Human arterial intima consists of structurally distinct leaflets, with a proteoglycan-rich layer lying immediately below the endothelial lining. Recent studies reveal the important role of stellate pericyte-like cells(intimal pericytes) populating the proteoglycan-rich layer in the development of atherosclerosis. During the pathologic process, intimal pericytes may participate in the recruitment of inflammatory cells by producing signalling molecules and play a role in the antigen presentation. Intimal pericytes are also involved in lipid accumulation and the formation of foam cells. This review focuses on the role of pericytelike cells in the development of atherosclerotic lesions.展开更多
Hepatitis C virus(HCV) is a major health problem worldwide. Early detection of the infection will help better management of the infected cases. The monoclonal antibodies(m Ab) of mice are predominantly used for the im...Hepatitis C virus(HCV) is a major health problem worldwide. Early detection of the infection will help better management of the infected cases. The monoclonal antibodies(m Ab) of mice are predominantly used for the immunodiagnosis of several viral,bacterial,and parasitic antigens. Serological detection of HCV antigens and antibodies provide simple and rapid methods of detection but lack sensitivity specially in the window phase between the infection and antibody development. Human mA b are used in the immunotherapy of several blood malignancies,such as lymphoma and leukemia,as well as for autoimmune diseases. In this review article,we will discuss methods of mouse and human monoclonal antibody production. We will demonstrate the role of mouse mA b in the detection of HCV antigens as rapid and sensitive immunodiagnostic assays for the detection of HCV,which is a major health problem throughout the world,particularly in Egypt. We will discuss the value of HCV-neutralizing antibodies and their roles in the immunotherapy of HCV infections and in HCV vaccine development. We will also discuss the different mechanisms by which the virus escape the effect of neutralizing mA b. Finally,we will discuss available and new trends to produce antibodies,such as egg yolk-based antibodies(Ig Y),production in transgenic plants,and the synthetic antibody mimics approach.展开更多
A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol (PEG) (GEMINI protocol). Previous work provided evidence that this is i...A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol (PEG) (GEMINI protocol). Previous work provided evidence that this is in fact possible. Other fusogens might improve current results. In this study, we aimed to assess the effects of PEGylated graphene nanoribons (PEG-GNR, and called "TexasPEG" when prepared as lwt% dispersion in PEG600) versus placebo (saline) on locomotor function recovery and cellular level in a rat model of spinal cord transection at lumbar segment 1 (L1) level. In vivo and in vitro experiments (n -- 10 per experiment) were designed. In the in vivo experiment, all rats were submitted to full spinal cord transection at L1 level. Five weeks later, behavioral assessment was performed using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Immunohistochemical staining with neuron marker neurofilament 200 (NF200) antibody and astrocyt- ic scar marker glial fibrillary acidic protein (GFAP) was also performed in the injured spinal cord. In the in vitro experiment, the effects of TexasPEG application for 72 hours on the neurite outgrowth of SH-SYSY cells were observed under the inverted microscope. Results of both in vivo and in vitro experiments suggest that TexasPEG reduces the formation of glial scars, promotes the regeneration of neurites, and thereby contributes to the recovery of locomotor function of a rat model of spinal cord transfection.展开更多
AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones fr...AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence(365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography(HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones(VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses(5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct(CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrixassisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS).RESULTS: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10^(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10-6 M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericinglucuronide was detected. CONCLUSION: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition.展开更多
AIM To compare therapeutic responses of a vascular-disrupting-agent, combretastatin-A4-phosphate(CA4 P), among hepatocellular carcinomas(HCCs) and implanted rhabdomyosarcoma(R1) in the same rats by magneticresonance-i...AIM To compare therapeutic responses of a vascular-disrupting-agent, combretastatin-A4-phosphate(CA4 P), among hepatocellular carcinomas(HCCs) and implanted rhabdomyosarcoma(R1) in the same rats by magneticresonance-imaging(MRI), microangiography and histopathology.METHODS Thirty-six HCCs were created by diethylnitrosamine gavage in 14 rats that were also intrahepatically implanted with one R1 per rat as monitored by T2-/T1-weighted images(T2wI/T1wI) on a 3.0 T clinical MRIscanner. Vascular response and tumoral necrosis were detected by dynamic contrast-enhanced(DCE-) and CE-MRI before, 1 h after and 12 h after CA4P iv at 10 mg/kg(treatment group n = 7) or phosphate-buffered saline at 1.0 mL/kg(control group n = 7). Tumor blood supply was calculated by a semiquantitative DCE parameter of area under the time signal intensity curve(AUC30). In vivo MRI findings were verified by postmortem techniques.RESULTS On CE-T1wIs, unlike the negative response in all tumors of control animals, in treatment group CA4P caused rapid extensive vascular shutdown in all R1-tumors, but mildly or spottily in HCCs at 1 h. Consequently, tumor necrosis occurred massively in R1-tumors but patchily in HCCs at 12 h. AUC30 revealed vascular closure(66%) in R1-tumors at 1 h(P < 0.05), followed by further perfusion decrease at 12 h(P < 0.01), while less significant vascular clogging occurred in HCCs. Histomorphologically, CA4P induced more extensive necrosis in R1-tumors(92.6%) than in HCCs(50.2%)(P < 0.01); tumor vascularity heterogeneously scored +^+++ in HCCs but homogeneously scored ++ in R1-tumors.CONCLUSION This study suggests superior performance of CA4P in metastatic over primary liver cancers, which could guide future clinical applications of vascular-disruptingagents.展开更多
Background: Osteoarthritis is one of the most common bone diseases, triggered by bone destruction stemming from the inflammatory response of chondrocytes. The disease progresses slowly, but halting its progression or ...Background: Osteoarthritis is one of the most common bone diseases, triggered by bone destruction stemming from the inflammatory response of chondrocytes. The disease progresses slowly, but halting its progression or finding a cure remains elusive. The treatment of pain associated with osteoarthritis has yielded unsatisfactory results. In recent years, mesenchymal stem cells (MSCs) have emerged as a potential avenue for addressing the condition. In this study, we used MSCs to treat companion dogs with osteoarthritis. Methods: For this study, 26 animals were included in this study to assess the pain and mobility one month after treatment. The pain scores were obtained from owners using a questionnaire based on the Helsinki Chronic Pain Index, and the Liverpool Osteoarthritis in Dogs (LOAD) Owner questionnaire to assess the mobility of the dogs from stem cell infusion. Results: Questionnaires were administered to dog owners before and one month after treatment, and we found that dogs treated with MSCS experienced an 81.2% ± 6.8% reduction in pain and a 77.9% ± 10.1% increase in mobility, whereas most of the dogs in the untreated control group experienced disease progression. Conclusions: The transplantation of stem cells into companion pets is a promising and expanding opportunity for pet owners with aging and arthritic dogs. MSCs may play an important role in the treatment of OA without complications in companion pets.展开更多
The evaluation of the microcirculatory bed functional state and the identification of angiospastic disorders with related complications,when the pathological changes are reversible,have an important role in medical pr...The evaluation of the microcirculatory bed functional state and the identification of angiospastic disorders with related complications,when the pathological changes are reversible,have an important role in medical practice.The aim of this study was to evaluate the possibility of using optical noninvasive methods and the cold pressor test to solve this problem.A total of 33 patients with rheumatological diseases and 32 healthy volunteers were included in the study.Laser Doppler flowmetry,tissue reflectance oximetry and pulse oximetry were used as optical noninvasive methods.The parameters were recorded before,immediately after and 20 min after the cold pressor test.Based on the measured parameters,the complex parameters of the microcirculatory bed were calculated.A detailed statistical analysis of the parameter changes for each individual in the two groups displayed diverse microcirculatory bed parameter responses upon cold exposure,with differing recovery of parameters after CPT.New diagnostic criteria were proposed for the identification of angiospastic disorders.According to the proposed criteria,27 people of the volunteers group were confirmed to not display any disorders.In the patient group,however,18 people were observed to have a relatively normal functional state of the microcirculatory bed,while 15 people were observed to have a possible tendency to angiospasm.To highlight the diferences between a relatively normal state and presence of angiospastic disorders,statistical analysis of experimental data was carried out,which revealed significant differences.Further analysis of data with angiospastic disorders identified a relationship between their diagnoses and the results of labo-ratory studies.Thus,the evaluation of combined noninvasive optical diagnostic method use,the cold pressor test and proposed diagnostic criteria showed a positive result.This approach can be used to detect the presence of possible angiospastic disorders and related complications,as well as mi-crocirculatory bed disorders against the background of other diseases.展开更多
Heparin has been considered to be a potentially useful ligand for low-density lipoprotein(LDL) detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LD...Heparin has been considered to be a potentially useful ligand for low-density lipoprotein(LDL) detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LDL,heparin-modified gold surface(GS-Hep) was fabricated by a self-assembling method and hydrophobic-modified gold surfaces(GS-Hydro) was used as a control.The morphologies of the modified gold surfaces were investigated by atomic force microscopy(AFM) and the quantity of heparin bound to gold surface was assayed by the toluidine blue(TB) colorimetric method.Water contact angles were determined to investigate wettability on GS-Hep and GS-Hydro.Surface plasmon resonance(SPR) technique was used subsequently to detect the selective binding of LDL with heparin.And the investigation on the effect of pH on LDL adsorption suggests that lower pH lead to higher quantities of LDL adsorption on GS-Hep.Compared with GS-Hydro,GS-Hep is selective for LDL from both single and binary protein solutions.Moreover,adsorbed LDL on GS-Hep could be washed off by injecting elution solution,such as NaCl solution,for the purpose of the regeneration of GS-Hep for further LDL adsorption.展开更多
AIM: To develop a method for studying myocardial area at risk(AAR) in ischemic heart disease in correlation with cardiac magnetic resonance imaging(c MRI). METHODS: Nine rabbits were anesthetized, intubated and subjec...AIM: To develop a method for studying myocardial area at risk(AAR) in ischemic heart disease in correlation with cardiac magnetic resonance imaging(c MRI). METHODS: Nine rabbits were anesthetized, intubated and subjected to occlusion and reperfusion of the left circumflex coronary artery(LCx) to induce myocardial infarction(MI). ECG-triggered c MRI with delayed en-hancement was performed at 3.0 T. After euthanasia, the heart was excised with the LCx re-ligated. Bifunctional staining was performed by perfusing the aorta with a homemade red-iodized-oil(RIO) dye. The heart was then agar-embedded for ex vivo magnetic resonance imaging and sliced into 3 mm-sections. The AAR was defined by RIO-staining and digital radiography(DR). The perfusion density rate(PDR) was derived from DR for the AAR and normal myocardium. The MI was measured by in vivo delayed enhancement(i DE) and ex vivo delayed enhancement(e DE) c MRI. The AAR and MI were compared to validate the bifunctional straining for cardiac imaging research. Linear regression with Bland-Altman agreement, one way-ANOVA with Bonferroni's multiple comparison, and paired t tests were applied for statistics.RESULTS: All rabbits tolerated well the surgical procedure and subsequent c MRI sessions. The openchest occlusion and close-chest reperfusion of the LCx, double suture method and bifunctional staining were successfully applied in all animals. The percentage MI volumes globally(n = 6) and by slice(n = 25) were 36.59% ± 13.68% and 32.88% ± 12.38% on i DE, and 35.41% ± 12.25% and 32.40% ± 12.34% on e DE. There were no significant differences for MI determination with excellent linear regression correspondence(r global = 0.89; r slice = 0.9) between i DE and e DE. The percentage AAR volumes globally(n = 6) and by slice(n = 25) were 44.82% ± 15.18% and 40.04% ± 13.64% with RIO-staining, and 44.74% ± 15.98% and 40.48% ± 13.26% by DR showing high correlation in linear regression analysis(r global = 0.99; r slice = 1.0). The mean differences of the two AAR measurements on BlandAltman were almost zero, indicating RIO-staining and DR were essentially equivalent or inter-replaceable. The AAR was significantly larger than MI both globally and slice-by-slice(P < 0.01). After correction with the background and the blank heart without bifunctional staining(n = 3), the PDR for the AAR and normal myocardium was 32% ± 15% and 35.5% ± 35%, respectively,which is significantly different(P < 0.001), suggesting that blood perfusion to the AAR probably by collateral circulation was only less than 10% of that in the normal myocardium.CONCLUSION: The myocardial area at risk in ischemic heart disease could be accurately determined postmortem by this novel bifunctional staining, which may substantially contribute to translational cardiac imaging research.展开更多
We present what we believe is the first conjugate adaptive optics(AO)extension that can be retrofitted into a commercial microscope by being positioned between the camera port and the image sensor.The extension featur...We present what we believe is the first conjugate adaptive optics(AO)extension that can be retrofitted into a commercial microscope by being positioned between the camera port and the image sensor.The extension features a deformable phase plate(DPP),a refractive wavefront modulator,and indirect wavefront sensing to form a completely in-line architecture.This allows the axial position of the DPP to be optimized by maximizing an image quality metric,which is a cumbersome task with deformable mirrors as the correction element.We demonstrate the performance of the system on a Zeiss AxioVert 200M microscope equipped with a 20×0.75 NA air objective.To simulate sample-induced complex aberrations,transparent custom-made arbitrary phase plates were introduced between the sample and the objective.We demonstrate that the extension can provide high-quality full-field correction even for large aberrations,when the DPP is placed at the conjugate plane of the phase plates.We also demonstrate that both the DPP position and its surface profile can be optimized blindly,which can pave the way for plug-and-play conjugate-AO systems.展开更多
We read with great interest the article by Valentini et al.,which presents a controlled implementation study evaluating an interprofessional evidence-based counseling program for complementary and integrative healthca...We read with great interest the article by Valentini et al.,which presents a controlled implementation study evaluating an interprofessional evidence-based counseling program for complementary and integrative healthcare(CIH)in oncology patients[1].展开更多
Post-translational modifications(PTMs)have key roles in extending the functional diversity of proteins and,as a result,regulating diverse cellular processes in prokaryotic and eukaryotic organisms.Phosphorylation modi...Post-translational modifications(PTMs)have key roles in extending the functional diversity of proteins and,as a result,regulating diverse cellular processes in prokaryotic and eukaryotic organisms.Phosphorylation modification is a vital PTM that occurs in most proteins and plays a significant role in many biological processes.Disorders in the phosphorylation process lead to multiple diseases,including neurological disorders and cancers.The purpose of this review is to organize this body of knowledge associated with phosphorylation site(p-site)prediction to facilitate future research in this field.At first,we comprehensively review all related databases and introduce all steps regarding dataset creation,data preprocessing,and method evaluation in p-site prediction.Next,we investigate p-site prediction methods,which are divided into two computational groups:algorithmic and machine learning(ML).Additionally,it is shown that there are basically two main approaches for p-site prediction by ML:conventional and end-to-end deep learning methods,both of which are given an overview.Moreover,this review introduces the most important feature extraction techniques,which have mostly been used in p-site prediction.Finally,we create three test sets from new proteins related to the released version of the database of protein post-translational modifications(dbPTM)in 2022 based on general and human species.Evaluating online p-site prediction tools on newly added proteins introduced in the dbPTM 2022 release,distinct from those in the dbPTM 2019 release,reveals their limitations.In other words,the actual performance of these online p-site prediction tools on unseen proteins is notably lower than the results reported in their respective research pape.展开更多
Existing shape models with spherical topology are typically designed either in the discrete domain using interpolating polygon meshes or in the continuous domain using smooth but non-interpolating schemes such as subd...Existing shape models with spherical topology are typically designed either in the discrete domain using interpolating polygon meshes or in the continuous domain using smooth but non-interpolating schemes such as subdivision or NURBS. Both polygon models and subdivision methods require a large number of parameters to model smooth surfaces.NURBS need fewer parameters but have a complicated rational expression and non-uniform shifts in their formulation. We present a new method to construct deformable closed surfaces, which includes exact spheres, by combining the best of two worlds: a smooth, interpolating model with a continuously varying tangent plane and well-defined curvature at every point on the surface. Our formulation is considerably simpler than NURBS and requires fewer parameters than polygon meshes. We demonstrate the generality of our method with applications including intuitive user-interactive shape modeling,continuous surface deformation, shape morphing,reconstruction of shapes from parameterized point clouds, and fast iterative shape optimization for image segmentation. Comparisons with discrete methods and non-interpolating approaches highlight the advantages of our framework.展开更多
文摘Three-dimensional(3D)nanoprinting via two-photon polymerization offers unparalleled design flexibility and precision,thereby enabling rapid prototyping of advanced micro-optical elements and systems that have found important applications in endomicroscopy and biomedical imaging.The potential of this versatile tool for monolithic manufacturing of dynamic micro-opto-electro-mechanical systems(MOEMSs),however,has not yet been sufficiently explored.This work introduces a 3D-nanoprinted lens actuator with a large optical aperture,optimized for remote focusing in miniaturized imaging systems.The device integrates orthoplanar linear motion springs,a self-aligned sintered micro-magnet,and a monolithic lens,actuated by dual microcoils for uniaxial motion.The use of 3D nanoprinting allows complete design freedom for the integrated optical lens,whereas the monolithic fabrication ensures inherent alignment of the lens with the mechanical elements.With a lens diameter of 1.4 mm and a compact footprint of 5.74 mm,it achieves high mechanical robustness at resonant frequencies exceeding 300 Hz while still providing a large displacement range of 200μm(±100μm).A comprehensive analysis of optical and mechanical performance,including the effects of coil temperature and polymer viscoelasticity,demonstrates its advantages over conventional micro-electro-mechanical system actuators,showcasing its potential for next-generation imaging applications.
文摘Measurement of optical properties of skin is an expanding and growing field of research.Recent studies have shown that the biological tissue,especially skin,changes the polarization state of the incident light.Using this property will enable the study of abnormalities and diseases that alter not only the light intensity but also its polarization state.In this paper we report an experimental study for measuring changes of polarization state of the light scattered from a phantom similar to a sample model of scattering skin.Using the notation of Stokes vector for the polarized light and Mueller matrix for the sample with its polarization properties,we have shown that some elements of the matrix were particularly sensitive to the changes of the polarization-altering physical properties of the scatterers within the phantom.
基金Supported by Flanders Research Foundation(FWO-42865)the KU Leuven Molecular Small Animal Imaging Center Mo SAIC(KUL EF/05/08)+3 种基金the center of excellence in vivo molecular imaging research(IMIR),KU Leuven projects IOFHB/08/009 and IOF-HB/12/018the European Union(AsiaLink Cf P 2006-Europe Aid/123738/C/ACT/Multi-Proposal No.128-498/111)the National Natural Science Foundation of China No.81071828Jiangsu Province Natural Science Foundation No.BK2010594
文摘AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of equal genders underwent two times of abdominal surgery.First,their common bile duct(CBD)was ligated to cause cholestasis by total biliary obstruction(TBO).On day 0,1,3,7,14,21 and 28 after TBO,magnetic resonance imaging(MRI)was conducted to monitor the dilatation of the CBD,and blood was sampled to analyze total serum bilirubin(TSB).Secondly,on day 30,the abdomen was re-opened and gallstone(s)collected from human patients were implanted in the dilated CBD asa virtual gallbladder(VGB),which was closed by suture ligation.This rat cholelithiasis model was examined by MRI,clinical observation,microcholangiography and histology.RESULTS:All rats survived two laparotomies.After ligation,the CBD was dilated to a stable size of 4 to30 mm in diameter on day 21-28,which became a VGB.The rats initially showed signs of jaundice that diminished over time,which paralleled with the evolving TSB levels from 0.6±0.3 mg/d L before ligation,through a peak of 10.9±1.9 mg/dL on day 14,until a nearly normalized value after day 28.The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter.The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology.CONCLUSION:A rat model cholelithiasis with human gallstones has been established,which proves feasible,safe,reliable,nontoxic and cost-effective.Given the gallstones of human origin,applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration.
基金Supported by the KU Leuven Molecular Small Animal Imaging Center Mo SAIC(KUL EF/05/08)the center of excellence in vivo molecular imaging research+3 种基金KU Leuven projects IOF-HB/08/009 and IOF-HB/12/018the European Union(AsiaLink Cf P 2006-Europe Aid/123738/C/ACt/Multi-Proposal No.128-498/111)the National Natural Science Foundation of China,No.81071828the Jiangsu Provincial Natural Science Foundation,No.BK2010594
文摘Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceutical research has played an importantrole in multiple disciplines,particularly in translational oncology.Based on the natural phenomenon of necrosis avidity,Onco Ci Dia has emerged as a novel generic approach for treating solid malignancies.Under this systemic dual targeting strategy,a vascular disrupting agent first selectively causes massive tumor necrosis that is followed by iodine-131 labeled-hypericin(123IHyp),a necrosis-avid compound that kills the residual cancer cells by crossfire effect of beta radiation.In this review,by emphasizing the potential clinical applicability of Onco Ci Dia,we summarize our research activities including optimization of radioiodinated hypericin Hyp preparations and recent studies on the biodistribution,dosimetry,pharmacokinetic and,chemical and radiochemical toxicities of the preparations.Myocardial infarction is a global health problem.Although cardiac scintigraphy using radioactive perfusion tracers is used in the assessment of myocardial viability,searching for diagnostic imaging agents with authentic necrosis avidity is pursued.Therefore,a comparative study on the biological profiles of the necrosis avid 123I-Hyp and the commercially available 99mTc-Sestamibi was conducted and the results are demonstrated.Cholelithiasis or gallstone disease may cause gallbladder inflammation,infection and other severe complications.While studying the mechanisms underlying the necrosis avidity of Hyp and derivatives,their naturally occurring fluorophore property was exploited for targeting cholesterol as a main component of gallstones.The usefulness of Hyp as an optical imaging agent for cholelithiasis was studied and the results are presented.Multiple uses of automatic contrast injectors may reduce costs and save resources.However,cross-contaminations with bloodborne pathogens of infectious diseases may occur.We developed a radioactive method for safety evaluation of a new replaceable patient-delivery system.By mimicking pathogens with a radiotracer,we assessed the feasibility of using the system repeatedly without septic risks.This overview is deemed to be interesting to those involvedin the related fields for translational research.
文摘Different causative factors acting on the pancreas can result in diseases such as pancreatitis, diabetes and pancreatic tumors. The high incidence and mortality of pancreatic diseases have placed diagnostic imaging in a crucial position in daily clinical practice. In this minireview article different pancreatic imaging techniques are discussed, from the standard clinical imaging modalities and state of the art clinical magnetic resonance imaging techniques to current situations in pre-clinical pancreatic imaging studies. In particular, the challenges of pre-clinical rodent pancreatic imaging are addressed, with both the image acquisition techniques and the post-processing methods for rodent pancreatic imaging elaborated.
文摘<b>Background: </b>COVID-19 produced by SARS-CoV-2 infection has spread worldwide. There is a growing need for immunological assays to detect viral specific antibodies or viral antigen. Current standard of diagnosis is reverse-transcriptase polymerase chain reaction (RT-PCR) in nasopharyngeal swabs. However serological tests can be used to determine previous exposure to the virus and complement the diagnosis. IgM and IgG SARS-CoV-2 specific antibodies can be detected as early as one week after infection and assays can be useful to test large groups of individuals. This work revised the available information concerning assays that detect antibodies and antigens for SARS-CoV-2. <b>Methods:</b> Three sources of information were used: technical data sheets (TDS) web pages of the company’s products and published articles in Pubmed with reference to the use of diagnostic kits. All the information was revised until April 5<sup>th</sup> 2020. <b>Results: </b>There were 226 tests coming from 20 countries mainly from China. TDS were found only in 50 (22.1%). Most assays detect specific antibodies (n 180) based on immunochromatography methods (n 110) and use blood-derived samples (n 105). Assays for antibodies detection measured mainly IgM/IgG (n 112) and the most common procedure time was <20 min (n 83). Internal control referred as sensitivity and specificity was found only in 18.6% (n 42) of the assays. The majority of the tests are currently for<i> in vitro</i> diagnosis (IVD). A total 165 articles were found on PubMed 15 were included and only 4 used the commercial kits reviewed. <b>Conclusions: </b>Due to the urgency of producing diagnostic tests for SARS-CoV-2 there is a broad offer of kits. Many tests need additional information for their application. The data collected may be useful in the selection of assays but more and higher quality information is needed.
基金Supported by The Russian Scientific Foundation,Moscow,Russian Federation,No.14-15-00112
文摘Inflammation plays an essential role in the development of atherosclerosis. The initiation and growth of atherosclerotic plaques is accompanied by recruitment of inflammatory and precursor cells from the bloodstream and their differentiation towards pro-inflammatory phenotypes. This process is orchestrated by the production of a number of pro-inflammatory cytokines and chemokines. Human arterial intima consists of structurally distinct leaflets, with a proteoglycan-rich layer lying immediately below the endothelial lining. Recent studies reveal the important role of stellate pericyte-like cells(intimal pericytes) populating the proteoglycan-rich layer in the development of atherosclerosis. During the pathologic process, intimal pericytes may participate in the recruitment of inflammatory cells by producing signalling molecules and play a role in the antigen presentation. Intimal pericytes are also involved in lipid accumulation and the formation of foam cells. This review focuses on the role of pericytelike cells in the development of atherosclerotic lesions.
文摘Hepatitis C virus(HCV) is a major health problem worldwide. Early detection of the infection will help better management of the infected cases. The monoclonal antibodies(m Ab) of mice are predominantly used for the immunodiagnosis of several viral,bacterial,and parasitic antigens. Serological detection of HCV antigens and antibodies provide simple and rapid methods of detection but lack sensitivity specially in the window phase between the infection and antibody development. Human mA b are used in the immunotherapy of several blood malignancies,such as lymphoma and leukemia,as well as for autoimmune diseases. In this review article,we will discuss methods of mouse and human monoclonal antibody production. We will demonstrate the role of mouse mA b in the detection of HCV antigens as rapid and sensitive immunodiagnostic assays for the detection of HCV,which is a major health problem throughout the world,particularly in Egypt. We will discuss the value of HCV-neutralizing antibodies and their roles in the immunotherapy of HCV infections and in HCV vaccine development. We will also discuss the different mechanisms by which the virus escape the effect of neutralizing mA b. Finally,we will discuss available and new trends to produce antibodies,such as egg yolk-based antibodies(Ig Y),production in transgenic plants,and the synthetic antibody mimics approach.
基金supported by a grant from the National Research Foundation(NRF)funded by the Korean government(NRF-2015M3A9C7030091 and NRF-2015R1C1A1A02037047)
文摘A sharply transected spinal cord has been shown to be fused under the accelerating influence of membrane fusogens such as polyethylene glycol (PEG) (GEMINI protocol). Previous work provided evidence that this is in fact possible. Other fusogens might improve current results. In this study, we aimed to assess the effects of PEGylated graphene nanoribons (PEG-GNR, and called "TexasPEG" when prepared as lwt% dispersion in PEG600) versus placebo (saline) on locomotor function recovery and cellular level in a rat model of spinal cord transection at lumbar segment 1 (L1) level. In vivo and in vitro experiments (n -- 10 per experiment) were designed. In the in vivo experiment, all rats were submitted to full spinal cord transection at L1 level. Five weeks later, behavioral assessment was performed using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Immunohistochemical staining with neuron marker neurofilament 200 (NF200) antibody and astrocyt- ic scar marker glial fibrillary acidic protein (GFAP) was also performed in the injured spinal cord. In the in vitro experiment, the effects of TexasPEG application for 72 hours on the neurite outgrowth of SH-SYSY cells were observed under the inverted microscope. Results of both in vivo and in vitro experiments suggest that TexasPEG reduces the formation of glial scars, promotes the regeneration of neurites, and thereby contributes to the recovery of locomotor function of a rat model of spinal cord transfection.
基金Supported by Research Foundation-Flanders(FWO)the KU Leuven Molecular Small Animal Imaging Center Mo SAIC,No.KUL EF/05/08+4 种基金the center of excellence in vivo molecular imaging research(IMIR)KU Leuven projects,No.IOFHB/08/009 and No.IOF-HB/12/018the European Union,AsiaLink Cf P 2006-Europe Aid/123738/C/ACT/Multi-Proposal,No128-498/111National Natural Science Foundation of China,No.81071828Jiangsu Province Natural Science Foundation,No.BK2010594
文摘AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence(365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography(HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones(VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses(5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct(CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrixassisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS).RESULTS: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10^(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10-6 M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericinglucuronide was detected. CONCLUSION: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition.
文摘AIM To compare therapeutic responses of a vascular-disrupting-agent, combretastatin-A4-phosphate(CA4 P), among hepatocellular carcinomas(HCCs) and implanted rhabdomyosarcoma(R1) in the same rats by magneticresonance-imaging(MRI), microangiography and histopathology.METHODS Thirty-six HCCs were created by diethylnitrosamine gavage in 14 rats that were also intrahepatically implanted with one R1 per rat as monitored by T2-/T1-weighted images(T2wI/T1wI) on a 3.0 T clinical MRIscanner. Vascular response and tumoral necrosis were detected by dynamic contrast-enhanced(DCE-) and CE-MRI before, 1 h after and 12 h after CA4P iv at 10 mg/kg(treatment group n = 7) or phosphate-buffered saline at 1.0 mL/kg(control group n = 7). Tumor blood supply was calculated by a semiquantitative DCE parameter of area under the time signal intensity curve(AUC30). In vivo MRI findings were verified by postmortem techniques.RESULTS On CE-T1wIs, unlike the negative response in all tumors of control animals, in treatment group CA4P caused rapid extensive vascular shutdown in all R1-tumors, but mildly or spottily in HCCs at 1 h. Consequently, tumor necrosis occurred massively in R1-tumors but patchily in HCCs at 12 h. AUC30 revealed vascular closure(66%) in R1-tumors at 1 h(P < 0.05), followed by further perfusion decrease at 12 h(P < 0.01), while less significant vascular clogging occurred in HCCs. Histomorphologically, CA4P induced more extensive necrosis in R1-tumors(92.6%) than in HCCs(50.2%)(P < 0.01); tumor vascularity heterogeneously scored +^+++ in HCCs but homogeneously scored ++ in R1-tumors.CONCLUSION This study suggests superior performance of CA4P in metastatic over primary liver cancers, which could guide future clinical applications of vascular-disruptingagents.
文摘Background: Osteoarthritis is one of the most common bone diseases, triggered by bone destruction stemming from the inflammatory response of chondrocytes. The disease progresses slowly, but halting its progression or finding a cure remains elusive. The treatment of pain associated with osteoarthritis has yielded unsatisfactory results. In recent years, mesenchymal stem cells (MSCs) have emerged as a potential avenue for addressing the condition. In this study, we used MSCs to treat companion dogs with osteoarthritis. Methods: For this study, 26 animals were included in this study to assess the pain and mobility one month after treatment. The pain scores were obtained from owners using a questionnaire based on the Helsinki Chronic Pain Index, and the Liverpool Osteoarthritis in Dogs (LOAD) Owner questionnaire to assess the mobility of the dogs from stem cell infusion. Results: Questionnaires were administered to dog owners before and one month after treatment, and we found that dogs treated with MSCS experienced an 81.2% ± 6.8% reduction in pain and a 77.9% ± 10.1% increase in mobility, whereas most of the dogs in the untreated control group experienced disease progression. Conclusions: The transplantation of stem cells into companion pets is a promising and expanding opportunity for pet owners with aging and arthritic dogs. MSCs may play an important role in the treatment of OA without complications in companion pets.
文摘The evaluation of the microcirculatory bed functional state and the identification of angiospastic disorders with related complications,when the pathological changes are reversible,have an important role in medical practice.The aim of this study was to evaluate the possibility of using optical noninvasive methods and the cold pressor test to solve this problem.A total of 33 patients with rheumatological diseases and 32 healthy volunteers were included in the study.Laser Doppler flowmetry,tissue reflectance oximetry and pulse oximetry were used as optical noninvasive methods.The parameters were recorded before,immediately after and 20 min after the cold pressor test.Based on the measured parameters,the complex parameters of the microcirculatory bed were calculated.A detailed statistical analysis of the parameter changes for each individual in the two groups displayed diverse microcirculatory bed parameter responses upon cold exposure,with differing recovery of parameters after CPT.New diagnostic criteria were proposed for the identification of angiospastic disorders.According to the proposed criteria,27 people of the volunteers group were confirmed to not display any disorders.In the patient group,however,18 people were observed to have a relatively normal functional state of the microcirculatory bed,while 15 people were observed to have a possible tendency to angiospasm.To highlight the diferences between a relatively normal state and presence of angiospastic disorders,statistical analysis of experimental data was carried out,which revealed significant differences.Further analysis of data with angiospastic disorders identified a relationship between their diagnoses and the results of labo-ratory studies.Thus,the evaluation of combined noninvasive optical diagnostic method use,the cold pressor test and proposed diagnostic criteria showed a positive result.This approach can be used to detect the presence of possible angiospastic disorders and related complications,as well as mi-crocirculatory bed disorders against the background of other diseases.
基金Supported by the Natural Science Foundation of Zhejiang Province of China(Nos.Y4110606 and Y1090649)the Opening Foundation of Zhejing Provincial Top Key Discipline,China(No.20110915)+1 种基金the Zhejiang Provincial Innovative Research Team,China(No.2009R50004)the Fresenius Medical Care of Deutschland GmbH’s Nephrocore Program,Germany
文摘Heparin has been considered to be a potentially useful ligand for low-density lipoprotein(LDL) detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LDL,heparin-modified gold surface(GS-Hep) was fabricated by a self-assembling method and hydrophobic-modified gold surfaces(GS-Hydro) was used as a control.The morphologies of the modified gold surfaces were investigated by atomic force microscopy(AFM) and the quantity of heparin bound to gold surface was assayed by the toluidine blue(TB) colorimetric method.Water contact angles were determined to investigate wettability on GS-Hep and GS-Hydro.Surface plasmon resonance(SPR) technique was used subsequently to detect the selective binding of LDL with heparin.And the investigation on the effect of pH on LDL adsorption suggests that lower pH lead to higher quantities of LDL adsorption on GS-Hep.Compared with GS-Hydro,GS-Hep is selective for LDL from both single and binary protein solutions.Moreover,adsorbed LDL on GS-Hep could be washed off by injecting elution solution,such as NaCl solution,for the purpose of the regeneration of GS-Hep for further LDL adsorption.
基金Supported by The awarded grants of the KU Leuven Molecular Small Animal Imaging Center Mo SAIC(KUL EF/05/08)the Center of Excellence in vivo Molecular Imaging Research(IMIR)of KU Leuven+1 种基金a EU Project Asia-Link Cf P 2006-Europe Aid/123738/C/ACT/Multi-Proposal,No.128-498/111Jiangsu Province Natural Science Foundation,China,No.BK2010594
文摘AIM: To develop a method for studying myocardial area at risk(AAR) in ischemic heart disease in correlation with cardiac magnetic resonance imaging(c MRI). METHODS: Nine rabbits were anesthetized, intubated and subjected to occlusion and reperfusion of the left circumflex coronary artery(LCx) to induce myocardial infarction(MI). ECG-triggered c MRI with delayed en-hancement was performed at 3.0 T. After euthanasia, the heart was excised with the LCx re-ligated. Bifunctional staining was performed by perfusing the aorta with a homemade red-iodized-oil(RIO) dye. The heart was then agar-embedded for ex vivo magnetic resonance imaging and sliced into 3 mm-sections. The AAR was defined by RIO-staining and digital radiography(DR). The perfusion density rate(PDR) was derived from DR for the AAR and normal myocardium. The MI was measured by in vivo delayed enhancement(i DE) and ex vivo delayed enhancement(e DE) c MRI. The AAR and MI were compared to validate the bifunctional straining for cardiac imaging research. Linear regression with Bland-Altman agreement, one way-ANOVA with Bonferroni's multiple comparison, and paired t tests were applied for statistics.RESULTS: All rabbits tolerated well the surgical procedure and subsequent c MRI sessions. The openchest occlusion and close-chest reperfusion of the LCx, double suture method and bifunctional staining were successfully applied in all animals. The percentage MI volumes globally(n = 6) and by slice(n = 25) were 36.59% ± 13.68% and 32.88% ± 12.38% on i DE, and 35.41% ± 12.25% and 32.40% ± 12.34% on e DE. There were no significant differences for MI determination with excellent linear regression correspondence(r global = 0.89; r slice = 0.9) between i DE and e DE. The percentage AAR volumes globally(n = 6) and by slice(n = 25) were 44.82% ± 15.18% and 40.04% ± 13.64% with RIO-staining, and 44.74% ± 15.98% and 40.48% ± 13.26% by DR showing high correlation in linear regression analysis(r global = 0.99; r slice = 1.0). The mean differences of the two AAR measurements on BlandAltman were almost zero, indicating RIO-staining and DR were essentially equivalent or inter-replaceable. The AAR was significantly larger than MI both globally and slice-by-slice(P < 0.01). After correction with the background and the blank heart without bifunctional staining(n = 3), the PDR for the AAR and normal myocardium was 32% ± 15% and 35.5% ± 35%, respectively,which is significantly different(P < 0.001), suggesting that blood perfusion to the AAR probably by collateral circulation was only less than 10% of that in the normal myocardium.CONCLUSION: The myocardial area at risk in ischemic heart disease could be accurately determined postmortem by this novel bifunctional staining, which may substantially contribute to translational cardiac imaging research.
文摘We present what we believe is the first conjugate adaptive optics(AO)extension that can be retrofitted into a commercial microscope by being positioned between the camera port and the image sensor.The extension features a deformable phase plate(DPP),a refractive wavefront modulator,and indirect wavefront sensing to form a completely in-line architecture.This allows the axial position of the DPP to be optimized by maximizing an image quality metric,which is a cumbersome task with deformable mirrors as the correction element.We demonstrate the performance of the system on a Zeiss AxioVert 200M microscope equipped with a 20×0.75 NA air objective.To simulate sample-induced complex aberrations,transparent custom-made arbitrary phase plates were introduced between the sample and the objective.We demonstrate that the extension can provide high-quality full-field correction even for large aberrations,when the DPP is placed at the conjugate plane of the phase plates.We also demonstrate that both the DPP position and its surface profile can be optimized blindly,which can pave the way for plug-and-play conjugate-AO systems.
文摘We read with great interest the article by Valentini et al.,which presents a controlled implementation study evaluating an interprofessional evidence-based counseling program for complementary and integrative healthcare(CIH)in oncology patients[1].
文摘Post-translational modifications(PTMs)have key roles in extending the functional diversity of proteins and,as a result,regulating diverse cellular processes in prokaryotic and eukaryotic organisms.Phosphorylation modification is a vital PTM that occurs in most proteins and plays a significant role in many biological processes.Disorders in the phosphorylation process lead to multiple diseases,including neurological disorders and cancers.The purpose of this review is to organize this body of knowledge associated with phosphorylation site(p-site)prediction to facilitate future research in this field.At first,we comprehensively review all related databases and introduce all steps regarding dataset creation,data preprocessing,and method evaluation in p-site prediction.Next,we investigate p-site prediction methods,which are divided into two computational groups:algorithmic and machine learning(ML).Additionally,it is shown that there are basically two main approaches for p-site prediction by ML:conventional and end-to-end deep learning methods,both of which are given an overview.Moreover,this review introduces the most important feature extraction techniques,which have mostly been used in p-site prediction.Finally,we create three test sets from new proteins related to the released version of the database of protein post-translational modifications(dbPTM)in 2022 based on general and human species.Evaluating online p-site prediction tools on newly added proteins introduced in the dbPTM 2022 release,distinct from those in the dbPTM 2019 release,reveals their limitations.In other words,the actual performance of these online p-site prediction tools on unseen proteins is notably lower than the results reported in their respective research pape.
基金funded by the Swiss National Science Foundation under Grant 200020-162343
文摘Existing shape models with spherical topology are typically designed either in the discrete domain using interpolating polygon meshes or in the continuous domain using smooth but non-interpolating schemes such as subdivision or NURBS. Both polygon models and subdivision methods require a large number of parameters to model smooth surfaces.NURBS need fewer parameters but have a complicated rational expression and non-uniform shifts in their formulation. We present a new method to construct deformable closed surfaces, which includes exact spheres, by combining the best of two worlds: a smooth, interpolating model with a continuously varying tangent plane and well-defined curvature at every point on the surface. Our formulation is considerably simpler than NURBS and requires fewer parameters than polygon meshes. We demonstrate the generality of our method with applications including intuitive user-interactive shape modeling,continuous surface deformation, shape morphing,reconstruction of shapes from parameterized point clouds, and fast iterative shape optimization for image segmentation. Comparisons with discrete methods and non-interpolating approaches highlight the advantages of our framework.