While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury r...While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be determined.Heterotopicossification(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues.Hypoxia andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote HO.However,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to beelucidated.Here,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell fate.Usingsingle-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in MPCs.Zeugopod mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in vivo.ScRNA-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of HO.Importantly,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1αdeletion.From a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic metabolism.This suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC fate.These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.展开更多
SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression.Aberrant glycosylation has been intricately linked with immune escape and tumor growth.SEMA7A is a highly glycosylated p...SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression.Aberrant glycosylation has been intricately linked with immune escape and tumor growth.SEMA7A is a highly glycosylated protein with five glycosylated sites.The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear.Here,we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma,and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides(Asn 105,157,258,330,and 602)via a direct protein‒protein interaction.A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane.Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8,whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal transition.Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8^(+)T cells along a trajectory toward an exhausted state,thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death.Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy.Finally,we also define RBM4,a splice regulator,as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing.These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.展开更多
Restoration of phase aberrations is crucial for addressing atmospheric turbulence in light propagation.Traditional restoration algorithms based on Zernike polynomials(ZPs)often encounter challenges related to high com...Restoration of phase aberrations is crucial for addressing atmospheric turbulence in light propagation.Traditional restoration algorithms based on Zernike polynomials(ZPs)often encounter challenges related to high computational complexity and insufficient capture of high-frequency phase aberration components,so we proposed a Principal-Component-Analysis-based method for representing phase aberrations.This paper discusses the factors influencing the accuracy of restoration,mainly including the sample space size and the sampling interval of D/r_(0),on the basis of characterizing phase aberrations by Principal Components(PCs).The experimental results show that a larger D/r_(0)sampling interval can ensure the generalization ability and robustness of the principal components in the case of a limited amount of original data,which can help to achieve high-precision deployment of the model in practical applications quickly.In the environment with relatively strong turbulence in the test set of D/r_(0)=24,the use of 34 terms of PCs can improve the corrected Strehl ratio(SR)from 0.007 to 0.1585,while the Strehl ratio of the light spot after restoration using 34 terms of ZPs is only 0.0215,demonstrating almost no correction effect.The results indicate that PCs can serve as a better alternative in representing and restoring the characteristics of atmospheric turbulence induced phase aberrations.These findings pave the way to use PCs of phase aberrations with fewer terms than traditional ZPs to achieve data dimensionality reduction,and offer a reference to accelerate and stabilize the model and deep learning based adaptive optics correction.展开更多
Background To comprehensively evaluate the agreement of component corneal aberrations from the newly updated wavefront analysis software of a swept-source optical coherence tomographer(SS-OcT)and a referential Placido...Background To comprehensively evaluate the agreement of component corneal aberrations from the newly updated wavefront analysis software of a swept-source optical coherence tomographer(SS-OcT)and a referential Placido-topography combined OcT device in elderly cataract patients.Methods Retrospective study including 103 eyes from 103 elderly patients scheduled for cataract surgery that were measured on the same day with a SS-OcT(Heidelberg Engineering,Germany)device and a Placido-topography combined OCT device(CsO,Italy).Anterior,total,and posterior corneal wavefront aberrations were evaluated for their mean differences and limits of agreement(LoA)via Bland-Altman plots.Vector analysis was additionally employed to compare corneal astigmatism measurements in dioptric vector space.Results Mean differences of all corneal aberrometric parameters did not exceed O.05 um.Total corneal aberrations were not significantly different from 0 except for vertical coma(-0.04μm;P=0.003),spherical aberration(-0.01μm,P<0.001),and root mean square(RMS)higher-order aberration(HOA)(0.03μm,P=0.04).The 95%LoA for total corneal aberration parameters between both devices were-0.46 to 0.42μm for horizontal astigmatism,-0.37 to 0.41μm for oblique astigmatism,-0.19 to 0.17μm for oblique trefoil,-0.33 to 0.25μm for vertical coma,-0.20 to 0.22μm for horizontal coma,-0.22 to 0.20 um for horizontal trefoil,-0.11 to 0.08μm for spherical aberration,and-0.22 to 0.28 um for RMs HOA.Vector analysis revealed no statistically significant mean differences for anterior,total,and posterior corneal astigmatism in dioptric vector space.Conclusion In eyes undergoing cataract surgery with a regular elderly cornea,corneal wavefront analysis from the SS-OcT device showed functional equivalency to the reference device.Nevertheless,clinically relevant higher-order aberration parameters should be interpreted with caution for surgical decision-making.展开更多
Centella asiatica L.,a medicinal herb,has attracted substantial interest in research as well as commercial domains due to its bioactive compounds which include the pentacyclic triterpenoid centellosides,and in additio...Centella asiatica L.,a medicinal herb,has attracted substantial interest in research as well as commercial domains due to its bioactive compounds which include the pentacyclic triterpenoid centellosides,and in addition,hydroxy.In addition,hydroxycinnamic acid conjugates as well as flavonoids.The latter is the major class of secondary plant metabolites and comprises various subclasses,including anthocyanidins.Anthocyanins are rarely reported in extracts from C.asiatica and differ structurally due to a flavylium(2-phenylchromenylium)ion that carries a positive charge at the oxygen atom of the C-ring of the basic flavonoid structure.Callus of C.asiatica was initiated and propagated on synthetic media and subjected to different light regimes.White callus resulted from white fluorescent illumination,while purple callus developed in response to white light emitting diode(LED)illumination.To profile the metabolites responsible for the intense purple coloration,methanolic extracts were prepared from the two cell lines.Total phenolic,flavonoid,and anthocyanin content were determined and indicated(i)very low levels of flavonoids and anthocyanins in white callus and(ii)that anthocyanins dominate the flavonoid content of the purple callus.Extracts were subjected to untargeted ultra-high-performance liquid chromatography coupled to high-definition mass spectrometry(UHPLC–MS)to profile newly synthesized anthocyanins.Metabolite annotation was based on accurate mass determination and characteristic fragmentation patterns.Here,the reprogramming of the metabolome of white C.asiatica callus due to LED illumination is reported and the profiles of cryptic anthocyanins as well as putative flavonoid and caffeoylquinic acid co-pigments in purple callus are described.展开更多
AIM:To compare the visual outcomes and corneal higherorder aberrations(HOAs)of patients with high or low myopic astigmatism after small incision lenticule extraction(SMILE).METHODS:A total of 157 eyes of 157 patients ...AIM:To compare the visual outcomes and corneal higherorder aberrations(HOAs)of patients with high or low myopic astigmatism after small incision lenticule extraction(SMILE).METHODS:A total of 157 eyes of 157 patients who underwent SMILE were included in this retrospective,nonrandomized,comparative study.All the eyes which were with the rule astigmatism were divided into high astigmatism group(HAG;astigmatism≤-2.00 D,73 eyes)and low astigmatism group(LAG;astigmatism≥-1.00 D,84 eyes).Visual and refractive examinations were performed,HOAs of the anterior surface,posterior surface,and total cornea of the eyes were evaluated preoperatively and 6mo postoperatively.RESULTS:At the postoperative 6-month follow-up,uncorrected distance visual acuity of 20/20 or better was achieved in 97%and 100%eyes in HAG and LAG respectively and 74%and 100%eyes were within-0.50 D.Vector analysis revealed no significant differences in the correction index(P=0.066),angle of error(P=0.091)or flattening index(P=0.987)between two groups.The magnitude of error was-0.37±0.31 D in HAG and-0.04±0.19 D in LAG(P<0.001).Index of success(IOS)was 0.22±0.09 in the HAG and 0.50±0.46 in the LAG(P<0.001).HOAs of most anterior,posterior and total cornea significantly increased after SMILE,especially the spherical aberration and coma.For HAG,the SMILE procedure induced significantly higher anterior,posterior and total cornea horizontal coma and total corneal total HOAs compared with LAG(P<0.001)and these surgically induced HOAs predominantly originated from the anterior surface of the cornea.CONCLUSION:SMILE surgery induces more HOAs and a mild under-correction of astigmatism in eyes with high astigmatism.The increment in HOAs after SMILE is related to preoperative astigmatism.展开更多
Over the past few decades,angle-resolved photoemission spectroscopy(ARPES)has been one of the important tools to study electronic structure of crystals.In recent years,the spatial resolution of around 150 nm has been ...Over the past few decades,angle-resolved photoemission spectroscopy(ARPES)has been one of the important tools to study electronic structure of crystals.In recent years,the spatial resolution of around 150 nm has been reached through tight focusing of the light spot(nano-ARPES).At present,the lower limit of the spot size of the light on the sample has been reached.Another way to further improve the spatial resolution is through using apertures to only let electrons from a small area of the sample pass.With both back-focal plane and image apertures,the size of the selected area can be as small as 20 nm.Yet,without aberration correction,the maximum opening angle at the sample for 20 nm spatial resolution is usually smaller than 3°,making this method not suitable for nano-ARPES.As shown in this paper,a conventional aberration corrector,which corrects chromatic and third-order spherical aberrations,is not enough either.Only when the fifth-order spherical aberration is also corrected,the opening angle at the sample is large enough for nano-ARPES.In this paper,the design of a time-of-fight PEEM/ARPES/nano-ARPES instrument,which is currently under development at the Quantum Science Center of Guangdong-Hong Kong-Macao Greater Bay Area,is presented.The main point of innovation is a fiveelectrode electron mirror corrector,which is used to correct simultaneously chromatic,third-order and fifth-order spherical aberrations,resulting in 1 nm spatial resolution with~230 mrad aperture angle in PEEM mode.This makes feasible the method of using apertures to improve the spatial resolution of the nano-ARPES mode.A new design of the magnetic prism array(MPA)is also presented,which preserves the rotational symmetry better than the existing designs.展开更多
AIM:To explore choroidal thickness(CT)and choroidal vascularity index(CVI)changes around the macula and optic nerve head(ONH)using swept-source optical coherence tomography(SS-OCT)after small-incision lenticule extrac...AIM:To explore choroidal thickness(CT)and choroidal vascularity index(CVI)changes around the macula and optic nerve head(ONH)using swept-source optical coherence tomography(SS-OCT)after small-incision lenticule extraction(SMILE)and evaluate their associations with accommodation and aberrations.METHODS:Participants were divided into more myopic group(43 eyes)and less myopic group(33 eyes)according to refractive error.SS-OCT,negative relative accommodation(NRA),and positive relative accommodation(PRA)were analyzed before and 1d,1wk,and 1mo postoperatively.Root mean square higher-order aberrations(RMS HOAs),spherical aberrations(SAs),and coma were compared preoperative,1wk,and 1mo postoperatively.RESULTS:After surgery,RMS(0.29±0.26)and Coma(0.16±0.19)all increased.In the more myopic group,central and T macular CT(247.58±63.81 a n d 276.45±62.52μm)increased.NRA(0.41±0.51)and PRA(0.10±1.30)decreased,and SAs(0.21±0.21)increased.In the less myopic group,all regional and mean macular CT increased.NRA was correlated with mean and inferior CTs and mean ONH CVI.SE was correlated with macular CT,CVI,and ONH CT.Mean macular and ONH CTs were associated with RMS HOA,SA,and coma.Macular T2 CT was a significant predictor of SA.Macular T2 and N1 CT were correlated with coma.CONCLUSION:More variations in accommodation and aberrations and fewer choroid thickens on macular and ONH are found in more myopic eyes after SMILE.Choroidal values are associated with accommodation and aberrations during SMILE.Choroid parameters on SS-OCT varies in eyes with different refractive errors after SMILE and has an association with accommodation and visual quality.展开更多
Transcranial focused ultrasound(tFUS)is an emerging modality with strong potential for non-invasively treating brain disorders.However,the inhomogeneity and complex structure of the skull induce substantial phase aber...Transcranial focused ultrasound(tFUS)is an emerging modality with strong potential for non-invasively treating brain disorders.However,the inhomogeneity and complex structure of the skull induce substantial phase aberrations and pressure attenuation;these can distort and shift the acoustic focus,thus hindering the efficiency of tFUS therapy.To achieve effective treatments,phased array transducers combined with aberration correction algorithms are commonly implemented.The present report aims to provide a comprehensive review of the current methods used for tFUS phase aberration correction.We first searched the PubMed and Web of Science databases for studies on phase aberration correction algorithms,identifying 54 articles for review.Relevant information,including the principles of algorithms and refocusing performances,were then extracted from the selected articles.The phase correction algorithms involved two main steps:acoustic field estimation and transmitted pulse adjustment.Our review identified key benchmarks for evaluating the effectiveness of these algorithms,each of which was used in at least three studies.These benchmarks included pressure and intensity,positioning error,focal region size,peak sidelobe ratio,and computational efficiency.Algorithm performances varied under different benchmarks,thus highlighting the importance of application-specific algorithm selection for achieving optimal tFUS therapy outcomes.The present review provides a thorough overview and comparison of various phase correction algorithms,and may offer valuable guidance to tFUS researchers when selecting appropriate phase correction algorithms for specific applications.展开更多
Aberration-corrected focus scanning is crucial for high-precision optics,but the conventional optical systems rely on bulky and complicated dynamic correctors.Recently,Shiyi Xiao's group proposed a method using tw...Aberration-corrected focus scanning is crucial for high-precision optics,but the conventional optical systems rely on bulky and complicated dynamic correctors.Recently,Shiyi Xiao's group proposed a method using two rotating cascaded transmissive metasurfaces for adaptive aberration correction in focus scanning.The optimized phase profiles enable precise control of the focal position for scanning custom-curved surfaces.This concept was experimentally validated by two allsilicon meta-devices in the terahertz regime,paving the way for high-precision and compact optical devices in various applications.展开更多
1.Introduction Microbiologically influenced corrosion(MIC)is the destruction of metal materials caused by the activity of microorganisms and the participation of biofilms[1].Global economic costs caused by marine corr...1.Introduction Microbiologically influenced corrosion(MIC)is the destruction of metal materials caused by the activity of microorganisms and the participation of biofilms[1].Global economic costs caused by marine corrosion come to hundreds of billion dollars per year,with approximately 20% of corrosion losses caused by MIC[2].The MIC poses a serious threat to the integrity and safety of assets in the oil and gas industry,water industry,and nuclear waste storage facili-ties[3-5].展开更多
RNA splicing normally generates stable splice- junction sequences in viruses that are important in the context of virus mimicry. Potential variability in envelop proteins may occur with point-mutations inducing crypti...RNA splicing normally generates stable splice- junction sequences in viruses that are important in the context of virus mimicry. Potential variability in envelop proteins may occur with point-mutations inducing cryptic splice-junctions, which would remain unrecognized by T-memory cells of higher organisms in vaccine trials. Such aberrant splice- junctions result from evolution-specific non-conser- vation of actual splice-junction sites due to mutations;as such, locations of splice-junctions in a test DNA sequence could only be imprecisely specified. Such impreciseness of splice-junction locations (or cryptic sites) in a sequence is evaluated in this study via “noisy” attributes (with associated stochastics) to the mutated subspace;and, relevant fuzzy considerations are invoked with membership attributes expressed in terms of a spatial signal-to-noise ratio (SSNR). That is, SSNR adopted as a membership function expresses the belongingness of a site-region to exon/intron subspaces. An illustrative example with actual (Dengue 1 viral) DNA data is furnished demonstrating the pursuit developed in predicting aberrant splice-junctions at cryptic sites in the test sequence.展开更多
Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic al...Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinomas.Among crucial roles of epigenetic alterations,gene silencing by aberrant DNA methylation of promoter regions is one of the most important epigenetic mechanisms.Recent comprehensive methylation analyses on genome-wide scale revealed that sporadic CRC can be classified into distinct epigenotypes.Each epigenotype cooperates with specific genetic alterations,suggesting that they represent different molecular carcinogenic pathways.Precursor lesions of CRC,such as conventional and serrated adenomas,already show similar methylation accumulation to CRC,and can therefore be classified into those epigenotypes of CRC.In addition,specific DNA methylation already occurs in the normal colonic mucosa,which might be utilized for prediction of the personal CRC risk.DNA methylation is suggested to occur at an earlier stage than carcinoma formation,and may predict the molecular basis for future development of CRC.Here,we review DNA methylation and CRC classification,and discuss the possible clinical usefulness of DNA methylation as biomarkers for the diagnosis,prediction of the prognosis and the response to therapy of CRC.展开更多
AIM:To analyze the differences in outcomes and the clinical impact following pancreatoduodenectomy(PD)in patients with and without aberrant right hepatic artery(aRHA).METHODS:All patients undergoing PD between January...AIM:To analyze the differences in outcomes and the clinical impact following pancreatoduodenectomy(PD)in patients with and without aberrant right hepatic artery(aRHA).METHODS:All patients undergoing PD between January 2008 and December 2012 were divided into two groups,one with aRHA and the other without.These groups were compared to identify differences in the intraoperative variables,the oncological clearance and the postoperative morbidity,mortality and hospital stay.RESULTS:A total of 225 patients underwent PD,of which 43(19.1%)patients were found to have eitheraccessory or replaced right hepatic arteries(aRHA group).The aRHA was preserved in 79%of the patients.There was no significant difference in the intraoperative blood loss but operative time was prolonged,reflecting the complexity of the procedure[420±44(240-540)min vs 480±45(300-600)min,P<0.05)].There were no differences in the incidence of postoperative complications(pancreatic leak,pancreatic fistula,delayed gastric emptying and mortality)and hospital stay.Oncological clearance in the form of positive resection margins[13(7.1%)vs 3(6.9%)]and lymph node yield were also similar in the two groups.CONCLUSION:An aRHA is found in approximately one fifth of patients undergoing PD.Preservation is technically possible in most patients and can increase the operative complexity but does not negatively affect the safety or oncological outcomes of the procedure.展开更多
Objective: To investigate the incidence of aberrant bile duct and its management during laparoscopic cholecystectomy (LC). Methods: In 10 000 patients undergoing laparoscopic cholecystectomy from 1992 to July 2001, 3 ...Objective: To investigate the incidence of aberrant bile duct and its management during laparoscopic cholecystectomy (LC). Methods: In 10 000 patients undergoing laparoscopic cholecystectomy from 1992 to July 2001, 3 had the involvement of the right accessory hepatic duct. In patient 1, the aberrant duct drained into the cystic duct was confirmed by open operation. In patient 2, the aberrant duct, which drained to the common bile duct (CBD), was injured and treated with suture and ligature under laparoscopy. In patient 3, the ab- errant duct, which also drained to the CBD, was confirmed and preserved. Results: All patients recovered well except patient 1 who had a transient elevation of ALT. No bile leak- age or other complication occurred. Conclusions: Only variation near the confluence and the entrance of the cystic duct into the bile duct is discovered during laparoscopic cholecystectomy. Right accessory hepatic duct is common and should be preserved during the operation. The accidentally injured small accessory hepatic duct can be treated with ligature without severe disturbance to liver func- tion.展开更多
AIM:To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67. METHODS:ACF was identified grossly and classified hi...AIM:To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67. METHODS:ACF was identified grossly and classified histologically in 75 resected specimens. ACF was typed into hyperplastic ACF (HACF) and dysplastic ACF (DACF). Sections of ACF, carcinoma and normal colonic mucosa as control were studied for Fhit and Ki67 expressions by immunohistochemistry and were grouped according to staining intensity and the number of positive stained cells observed in different histological groups. Comparison was done between the different groups by Pearson's χ 2 test and γ test for the ordinal data. P value < 0.05 was considered as significant.RESULTS:Age range was 40 to 86 years in males (mean = 43.36) and 45 to 70 years in females (mean = 56). HACF was identified in all cases studied in the non-tumorous colonic mucosa; ACF was observed as non-contiguous scattered foci, which supports the hypothesis of acquisition of single focus monoclonality by colonic epithelial cells in tumor generation. Twenty-four (32%) had DACF and were observed as closure to carcinoma foci. Intensity of Fhit expression:(1) HACF 40% exhibited strong intensity, similar to normal, moderate in 36% and weak in 24%; (2) DACF strong in 25%, moderate in 37.5% and weak in 37.5%; and (3) carcinoma negative in 16%, strong in 43% and moderate and weak in 28.5% each. Significant difference was observed in intensity of the Fhit protein expressions by HACF and DACF (P < 0.05). Tumor in older patients showed a stronger Fhit intensity compared to younger patients (P = 0.036). Vegetarian diet intake and nonsmokers showed stronger Fhit intensities. Advanced stage tumor, non-vegetarian diet and younger age was associated with loss of Fhit protein. Ki67 positivity was an extended crypt pattern in HACF and DACF showed extension up to the neck region of the crypts and surface epithelium. Carcinomas showed a marked increase in Ki67 expression (P < 0.05). Fhit protein had an inverse association with Ki67 expression. CONCLUSION:Weaker Fhit intensity was associated with smoking, non-vegetarian diet intake and increasing Ki67 expression. Loss of Fhit protein expression is possibly influenced by environmental factors like smoking and non-vegetarian diet intake.展开更多
The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries. Aberrant crypt foci （ACF） represent the ear...The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries. Aberrant crypt foci （ACF） represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans. ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis. For over two decades, since its first discovery, azoxymethane （AOM）-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens. Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system. There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up, and extensive research in this field is currently in progress. In chemoprevention studies, AOM-induced rat ACF have been very successful as biomarkers, and have provided several standardized analyses of data. There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome, however, and hence there has been an ambiguity about their role as biomarkers. The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies. The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.展开更多
DNA methylation, one of the best-characterized epigenetic modifications, plays essential roles in diseases, including human cancers. In recent years, our understanding on DNA methylation with human cancers has made si...DNA methylation, one of the best-characterized epigenetic modifications, plays essential roles in diseases, including human cancers. In recent years, our understanding on DNA methylation with human cancers has made significant progress, which was facilitated by stunning development in the analysis of the human methylome of multiple cancer types. In this review, recent developments in the characterization of aberrant DNA methylation involved in human cancers development were discussed with special emphasis on the mechanisms of aberrant DNA methylation in human cancers. We also summarize the recent treatment strategy for human cancers with de-methylation drugs.展开更多
AIM:To clarify the relationship of human rectal aberrant crypt foci and formation of colorectal polyp.METHODS:Eighty-nine subjects were recruited from the population of Japanese individuals who underwent polypectomy a...AIM:To clarify the relationship of human rectal aberrant crypt foci and formation of colorectal polyp.METHODS:Eighty-nine subjects were recruited from the population of Japanese individuals who underwent polypectomy at Yokohama City University Hospital.All patients had baseline adenomas removed at year 0 colonoscopy.Aberrant crypt foci(ACF) were defined as lesions in which the crypts were more darkly stained with methylene blue than normal crypts and had larger diameters,often with oval or slit-like lumens and a thicker epithelial lining.RESULTS:A total of 366 ACFs were identified in 89 patients;all had baseline adenomas removed at the first examination(year 0) colonoscopy and returned for the second(year 1).ACF in the lower rectum were assessed at year 0 and study group were divided into two groups depend on ACF numbers,0-3 or over 3.All participants were examined in the number and maximum size of adenoma.There was no statistical difference in number and maximum size of ACF at year 0,however,maximum size of adenoma was larger in over 3 group than 0-3 group at year 1.CONCLUSION:The number of ACF may be a predictive factor of relatively large adenoma incidence in the pilot phase study.展开更多
The functional interdependence of nerves and blood vessels is a well-established concept during tissue morphogenesis, yet the role of neurovascular coupling in proper and aberrant tissue repair is an emerging field of...The functional interdependence of nerves and blood vessels is a well-established concept during tissue morphogenesis, yet the role of neurovascular coupling in proper and aberrant tissue repair is an emerging field of interest. Here, we sought to define the regulatory relationship of peripheral nerves on vasculature in a severe extremity trauma model in mice, which results in aberrant cell fate and heterotopic ossification(HO). First, a high spatial degree of neurovascular congruency was observed to exist within extremity injury associated heterotopic ossification. Vascular and perivascular cells demonstrate characteristic responses to injury,as assessed by single cell RNA sequencing. This vascular response to injury was blunted in neurectomized mice, including a decrease in endothelial proliferation and type H vessel formation, and a downregulation of key transcriptional networks associated with angiogenesis. Independent mechanisms to chemically or genetically inhibit axonal ingrowth led to similar deficits in HO site angiogenesis, a reduction in type H vessels, and heterotopic bone formation. Finally, a combination of single cell transcriptomic approaches within the dorsal root ganglia identified key neural-derived angiogenic paracrine factors that may mediate neuron-to-vascular signaling in HO. These data provide further understanding of nerve-to-vessel crosstalk in traumatized soft tissues, which may reflect a key determinant of mesenchymal progenitor cell fate after injury.展开更多
文摘While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be determined.Heterotopicossification(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues.Hypoxia andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote HO.However,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to beelucidated.Here,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell fate.Usingsingle-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in MPCs.Zeugopod mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in vivo.ScRNA-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of HO.Importantly,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1αdeletion.From a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic metabolism.This suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC fate.These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.
基金supported by the National Natural Science Foundation of China(NSFC:82173451)Project of Biobank(YBKB202105)from Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai Municipal Health Commission(No.2022LJ001)+1 种基金the Natural Science Foundation of Shanghai(22ZR1437600)Shanghai’s Top Priority Research Center(2022ZZ01017).
文摘SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression.Aberrant glycosylation has been intricately linked with immune escape and tumor growth.SEMA7A is a highly glycosylated protein with five glycosylated sites.The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear.Here,we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma,and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides(Asn 105,157,258,330,and 602)via a direct protein‒protein interaction.A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane.Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8,whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal transition.Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8^(+)T cells along a trajectory toward an exhausted state,thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death.Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy.Finally,we also define RBM4,a splice regulator,as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing.These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.
文摘Restoration of phase aberrations is crucial for addressing atmospheric turbulence in light propagation.Traditional restoration algorithms based on Zernike polynomials(ZPs)often encounter challenges related to high computational complexity and insufficient capture of high-frequency phase aberration components,so we proposed a Principal-Component-Analysis-based method for representing phase aberrations.This paper discusses the factors influencing the accuracy of restoration,mainly including the sample space size and the sampling interval of D/r_(0),on the basis of characterizing phase aberrations by Principal Components(PCs).The experimental results show that a larger D/r_(0)sampling interval can ensure the generalization ability and robustness of the principal components in the case of a limited amount of original data,which can help to achieve high-precision deployment of the model in practical applications quickly.In the environment with relatively strong turbulence in the test set of D/r_(0)=24,the use of 34 terms of PCs can improve the corrected Strehl ratio(SR)from 0.007 to 0.1585,while the Strehl ratio of the light spot after restoration using 34 terms of ZPs is only 0.0215,demonstrating almost no correction effect.The results indicate that PCs can serve as a better alternative in representing and restoring the characteristics of atmospheric turbulence induced phase aberrations.These findings pave the way to use PCs of phase aberrations with fewer terms than traditional ZPs to achieve data dimensionality reduction,and offer a reference to accelerate and stabilize the model and deep learning based adaptive optics correction.
文摘Background To comprehensively evaluate the agreement of component corneal aberrations from the newly updated wavefront analysis software of a swept-source optical coherence tomographer(SS-OcT)and a referential Placido-topography combined OcT device in elderly cataract patients.Methods Retrospective study including 103 eyes from 103 elderly patients scheduled for cataract surgery that were measured on the same day with a SS-OcT(Heidelberg Engineering,Germany)device and a Placido-topography combined OCT device(CsO,Italy).Anterior,total,and posterior corneal wavefront aberrations were evaluated for their mean differences and limits of agreement(LoA)via Bland-Altman plots.Vector analysis was additionally employed to compare corneal astigmatism measurements in dioptric vector space.Results Mean differences of all corneal aberrometric parameters did not exceed O.05 um.Total corneal aberrations were not significantly different from 0 except for vertical coma(-0.04μm;P=0.003),spherical aberration(-0.01μm,P<0.001),and root mean square(RMS)higher-order aberration(HOA)(0.03μm,P=0.04).The 95%LoA for total corneal aberration parameters between both devices were-0.46 to 0.42μm for horizontal astigmatism,-0.37 to 0.41μm for oblique astigmatism,-0.19 to 0.17μm for oblique trefoil,-0.33 to 0.25μm for vertical coma,-0.20 to 0.22μm for horizontal coma,-0.22 to 0.20 um for horizontal trefoil,-0.11 to 0.08μm for spherical aberration,and-0.22 to 0.28 um for RMs HOA.Vector analysis revealed no statistically significant mean differences for anterior,total,and posterior corneal astigmatism in dioptric vector space.Conclusion In eyes undergoing cataract surgery with a regular elderly cornea,corneal wavefront analysis from the SS-OcT device showed functional equivalency to the reference device.Nevertheless,clinically relevant higher-order aberration parameters should be interpreted with caution for surgical decision-making.
文摘Centella asiatica L.,a medicinal herb,has attracted substantial interest in research as well as commercial domains due to its bioactive compounds which include the pentacyclic triterpenoid centellosides,and in addition,hydroxy.In addition,hydroxycinnamic acid conjugates as well as flavonoids.The latter is the major class of secondary plant metabolites and comprises various subclasses,including anthocyanidins.Anthocyanins are rarely reported in extracts from C.asiatica and differ structurally due to a flavylium(2-phenylchromenylium)ion that carries a positive charge at the oxygen atom of the C-ring of the basic flavonoid structure.Callus of C.asiatica was initiated and propagated on synthetic media and subjected to different light regimes.White callus resulted from white fluorescent illumination,while purple callus developed in response to white light emitting diode(LED)illumination.To profile the metabolites responsible for the intense purple coloration,methanolic extracts were prepared from the two cell lines.Total phenolic,flavonoid,and anthocyanin content were determined and indicated(i)very low levels of flavonoids and anthocyanins in white callus and(ii)that anthocyanins dominate the flavonoid content of the purple callus.Extracts were subjected to untargeted ultra-high-performance liquid chromatography coupled to high-definition mass spectrometry(UHPLC–MS)to profile newly synthesized anthocyanins.Metabolite annotation was based on accurate mass determination and characteristic fragmentation patterns.Here,the reprogramming of the metabolome of white C.asiatica callus due to LED illumination is reported and the profiles of cryptic anthocyanins as well as putative flavonoid and caffeoylquinic acid co-pigments in purple callus are described.
文摘AIM:To compare the visual outcomes and corneal higherorder aberrations(HOAs)of patients with high or low myopic astigmatism after small incision lenticule extraction(SMILE).METHODS:A total of 157 eyes of 157 patients who underwent SMILE were included in this retrospective,nonrandomized,comparative study.All the eyes which were with the rule astigmatism were divided into high astigmatism group(HAG;astigmatism≤-2.00 D,73 eyes)and low astigmatism group(LAG;astigmatism≥-1.00 D,84 eyes).Visual and refractive examinations were performed,HOAs of the anterior surface,posterior surface,and total cornea of the eyes were evaluated preoperatively and 6mo postoperatively.RESULTS:At the postoperative 6-month follow-up,uncorrected distance visual acuity of 20/20 or better was achieved in 97%and 100%eyes in HAG and LAG respectively and 74%and 100%eyes were within-0.50 D.Vector analysis revealed no significant differences in the correction index(P=0.066),angle of error(P=0.091)or flattening index(P=0.987)between two groups.The magnitude of error was-0.37±0.31 D in HAG and-0.04±0.19 D in LAG(P<0.001).Index of success(IOS)was 0.22±0.09 in the HAG and 0.50±0.46 in the LAG(P<0.001).HOAs of most anterior,posterior and total cornea significantly increased after SMILE,especially the spherical aberration and coma.For HAG,the SMILE procedure induced significantly higher anterior,posterior and total cornea horizontal coma and total corneal total HOAs compared with LAG(P<0.001)and these surgically induced HOAs predominantly originated from the anterior surface of the cornea.CONCLUSION:SMILE surgery induces more HOAs and a mild under-correction of astigmatism in eyes with high astigmatism.The increment in HOAs after SMILE is related to preoperative astigmatism.
基金supported by Shanghai Tech University and Quantum Science Center of Guangdong-Hong Kong-Macao Greater Bay Area,China(Grant No.SZZX2301006)。
文摘Over the past few decades,angle-resolved photoemission spectroscopy(ARPES)has been one of the important tools to study electronic structure of crystals.In recent years,the spatial resolution of around 150 nm has been reached through tight focusing of the light spot(nano-ARPES).At present,the lower limit of the spot size of the light on the sample has been reached.Another way to further improve the spatial resolution is through using apertures to only let electrons from a small area of the sample pass.With both back-focal plane and image apertures,the size of the selected area can be as small as 20 nm.Yet,without aberration correction,the maximum opening angle at the sample for 20 nm spatial resolution is usually smaller than 3°,making this method not suitable for nano-ARPES.As shown in this paper,a conventional aberration corrector,which corrects chromatic and third-order spherical aberrations,is not enough either.Only when the fifth-order spherical aberration is also corrected,the opening angle at the sample is large enough for nano-ARPES.In this paper,the design of a time-of-fight PEEM/ARPES/nano-ARPES instrument,which is currently under development at the Quantum Science Center of Guangdong-Hong Kong-Macao Greater Bay Area,is presented.The main point of innovation is a fiveelectrode electron mirror corrector,which is used to correct simultaneously chromatic,third-order and fifth-order spherical aberrations,resulting in 1 nm spatial resolution with~230 mrad aperture angle in PEEM mode.This makes feasible the method of using apertures to improve the spatial resolution of the nano-ARPES mode.A new design of the magnetic prism array(MPA)is also presented,which preserves the rotational symmetry better than the existing designs.
基金Supported by the National Natural Science Foundation of China(No.81900910)Natural Science Foundation of Zhejiang Province(No.LQ19H120003)Basic Scientific Research Project of Wenzhou(No.Y20210194,No.Y20190638).
文摘AIM:To explore choroidal thickness(CT)and choroidal vascularity index(CVI)changes around the macula and optic nerve head(ONH)using swept-source optical coherence tomography(SS-OCT)after small-incision lenticule extraction(SMILE)and evaluate their associations with accommodation and aberrations.METHODS:Participants were divided into more myopic group(43 eyes)and less myopic group(33 eyes)according to refractive error.SS-OCT,negative relative accommodation(NRA),and positive relative accommodation(PRA)were analyzed before and 1d,1wk,and 1mo postoperatively.Root mean square higher-order aberrations(RMS HOAs),spherical aberrations(SAs),and coma were compared preoperative,1wk,and 1mo postoperatively.RESULTS:After surgery,RMS(0.29±0.26)and Coma(0.16±0.19)all increased.In the more myopic group,central and T macular CT(247.58±63.81 a n d 276.45±62.52μm)increased.NRA(0.41±0.51)and PRA(0.10±1.30)decreased,and SAs(0.21±0.21)increased.In the less myopic group,all regional and mean macular CT increased.NRA was correlated with mean and inferior CTs and mean ONH CVI.SE was correlated with macular CT,CVI,and ONH CT.Mean macular and ONH CTs were associated with RMS HOA,SA,and coma.Macular T2 CT was a significant predictor of SA.Macular T2 and N1 CT were correlated with coma.CONCLUSION:More variations in accommodation and aberrations and fewer choroid thickens on macular and ONH are found in more myopic eyes after SMILE.Choroidal values are associated with accommodation and aberrations during SMILE.Choroid parameters on SS-OCT varies in eyes with different refractive errors after SMILE and has an association with accommodation and visual quality.
基金supported by Start-Up Grant From ShanghaiTech University,2021F0209-000-09Natural Science Foundation of Shanghai Municipality,23ZR1442000。
文摘Transcranial focused ultrasound(tFUS)is an emerging modality with strong potential for non-invasively treating brain disorders.However,the inhomogeneity and complex structure of the skull induce substantial phase aberrations and pressure attenuation;these can distort and shift the acoustic focus,thus hindering the efficiency of tFUS therapy.To achieve effective treatments,phased array transducers combined with aberration correction algorithms are commonly implemented.The present report aims to provide a comprehensive review of the current methods used for tFUS phase aberration correction.We first searched the PubMed and Web of Science databases for studies on phase aberration correction algorithms,identifying 54 articles for review.Relevant information,including the principles of algorithms and refocusing performances,were then extracted from the selected articles.The phase correction algorithms involved two main steps:acoustic field estimation and transmitted pulse adjustment.Our review identified key benchmarks for evaluating the effectiveness of these algorithms,each of which was used in at least three studies.These benchmarks included pressure and intensity,positioning error,focal region size,peak sidelobe ratio,and computational efficiency.Algorithm performances varied under different benchmarks,thus highlighting the importance of application-specific algorithm selection for achieving optimal tFUS therapy outcomes.The present review provides a thorough overview and comparison of various phase correction algorithms,and may offer valuable guidance to tFUS researchers when selecting appropriate phase correction algorithms for specific applications.
文摘Aberration-corrected focus scanning is crucial for high-precision optics,but the conventional optical systems rely on bulky and complicated dynamic correctors.Recently,Shiyi Xiao's group proposed a method using two rotating cascaded transmissive metasurfaces for adaptive aberration correction in focus scanning.The optimized phase profiles enable precise control of the focal position for scanning custom-curved surfaces.This concept was experimentally validated by two allsilicon meta-devices in the terahertz regime,paving the way for high-precision and compact optical devices in various applications.
基金supported by the National Natural Science Foun-dation of China(Nos.52371071,51971228,and 51771212).
文摘1.Introduction Microbiologically influenced corrosion(MIC)is the destruction of metal materials caused by the activity of microorganisms and the participation of biofilms[1].Global economic costs caused by marine corrosion come to hundreds of billion dollars per year,with approximately 20% of corrosion losses caused by MIC[2].The MIC poses a serious threat to the integrity and safety of assets in the oil and gas industry,water industry,and nuclear waste storage facili-ties[3-5].
文摘RNA splicing normally generates stable splice- junction sequences in viruses that are important in the context of virus mimicry. Potential variability in envelop proteins may occur with point-mutations inducing cryptic splice-junctions, which would remain unrecognized by T-memory cells of higher organisms in vaccine trials. Such aberrant splice- junctions result from evolution-specific non-conser- vation of actual splice-junction sites due to mutations;as such, locations of splice-junctions in a test DNA sequence could only be imprecisely specified. Such impreciseness of splice-junction locations (or cryptic sites) in a sequence is evaluated in this study via “noisy” attributes (with associated stochastics) to the mutated subspace;and, relevant fuzzy considerations are invoked with membership attributes expressed in terms of a spatial signal-to-noise ratio (SSNR). That is, SSNR adopted as a membership function expresses the belongingness of a site-region to exon/intron subspaces. An illustrative example with actual (Dengue 1 viral) DNA data is furnished demonstrating the pursuit developed in predicting aberrant splice-junctions at cryptic sites in the test sequence.
文摘Despite the recent advances in the therapeutic modalities,colorectal cancer(CRC)remains to be one of the most common causes of cancer-related death.CRC arises through accumulation of multiple genetic and epigenetic alterations that transform normal colonic epithelium into adenocarcinomas.Among crucial roles of epigenetic alterations,gene silencing by aberrant DNA methylation of promoter regions is one of the most important epigenetic mechanisms.Recent comprehensive methylation analyses on genome-wide scale revealed that sporadic CRC can be classified into distinct epigenotypes.Each epigenotype cooperates with specific genetic alterations,suggesting that they represent different molecular carcinogenic pathways.Precursor lesions of CRC,such as conventional and serrated adenomas,already show similar methylation accumulation to CRC,and can therefore be classified into those epigenotypes of CRC.In addition,specific DNA methylation already occurs in the normal colonic mucosa,which might be utilized for prediction of the personal CRC risk.DNA methylation is suggested to occur at an earlier stage than carcinoma formation,and may predict the molecular basis for future development of CRC.Here,we review DNA methylation and CRC classification,and discuss the possible clinical usefulness of DNA methylation as biomarkers for the diagnosis,prediction of the prognosis and the response to therapy of CRC.
文摘AIM:To analyze the differences in outcomes and the clinical impact following pancreatoduodenectomy(PD)in patients with and without aberrant right hepatic artery(aRHA).METHODS:All patients undergoing PD between January 2008 and December 2012 were divided into two groups,one with aRHA and the other without.These groups were compared to identify differences in the intraoperative variables,the oncological clearance and the postoperative morbidity,mortality and hospital stay.RESULTS:A total of 225 patients underwent PD,of which 43(19.1%)patients were found to have eitheraccessory or replaced right hepatic arteries(aRHA group).The aRHA was preserved in 79%of the patients.There was no significant difference in the intraoperative blood loss but operative time was prolonged,reflecting the complexity of the procedure[420±44(240-540)min vs 480±45(300-600)min,P<0.05)].There were no differences in the incidence of postoperative complications(pancreatic leak,pancreatic fistula,delayed gastric emptying and mortality)and hospital stay.Oncological clearance in the form of positive resection margins[13(7.1%)vs 3(6.9%)]and lymph node yield were also similar in the two groups.CONCLUSION:An aRHA is found in approximately one fifth of patients undergoing PD.Preservation is technically possible in most patients and can increase the operative complexity but does not negatively affect the safety or oncological outcomes of the procedure.
文摘Objective: To investigate the incidence of aberrant bile duct and its management during laparoscopic cholecystectomy (LC). Methods: In 10 000 patients undergoing laparoscopic cholecystectomy from 1992 to July 2001, 3 had the involvement of the right accessory hepatic duct. In patient 1, the aberrant duct drained into the cystic duct was confirmed by open operation. In patient 2, the aberrant duct, which drained to the common bile duct (CBD), was injured and treated with suture and ligature under laparoscopy. In patient 3, the ab- errant duct, which also drained to the CBD, was confirmed and preserved. Results: All patients recovered well except patient 1 who had a transient elevation of ALT. No bile leak- age or other complication occurred. Conclusions: Only variation near the confluence and the entrance of the cystic duct into the bile duct is discovered during laparoscopic cholecystectomy. Right accessory hepatic duct is common and should be preserved during the operation. The accidentally injured small accessory hepatic duct can be treated with ligature without severe disturbance to liver func- tion.
文摘AIM:To characterize aberrant crypt focus (ACF) in adjoining mucosa in sporadic colorectal carcinoma and to evaluate fragile histidine triad (Fhit) protein and Ki67. METHODS:ACF was identified grossly and classified histologically in 75 resected specimens. ACF was typed into hyperplastic ACF (HACF) and dysplastic ACF (DACF). Sections of ACF, carcinoma and normal colonic mucosa as control were studied for Fhit and Ki67 expressions by immunohistochemistry and were grouped according to staining intensity and the number of positive stained cells observed in different histological groups. Comparison was done between the different groups by Pearson's χ 2 test and γ test for the ordinal data. P value < 0.05 was considered as significant.RESULTS:Age range was 40 to 86 years in males (mean = 43.36) and 45 to 70 years in females (mean = 56). HACF was identified in all cases studied in the non-tumorous colonic mucosa; ACF was observed as non-contiguous scattered foci, which supports the hypothesis of acquisition of single focus monoclonality by colonic epithelial cells in tumor generation. Twenty-four (32%) had DACF and were observed as closure to carcinoma foci. Intensity of Fhit expression:(1) HACF 40% exhibited strong intensity, similar to normal, moderate in 36% and weak in 24%; (2) DACF strong in 25%, moderate in 37.5% and weak in 37.5%; and (3) carcinoma negative in 16%, strong in 43% and moderate and weak in 28.5% each. Significant difference was observed in intensity of the Fhit protein expressions by HACF and DACF (P < 0.05). Tumor in older patients showed a stronger Fhit intensity compared to younger patients (P = 0.036). Vegetarian diet intake and nonsmokers showed stronger Fhit intensities. Advanced stage tumor, non-vegetarian diet and younger age was associated with loss of Fhit protein. Ki67 positivity was an extended crypt pattern in HACF and DACF showed extension up to the neck region of the crypts and surface epithelium. Carcinomas showed a marked increase in Ki67 expression (P < 0.05). Fhit protein had an inverse association with Ki67 expression. CONCLUSION:Weaker Fhit intensity was associated with smoking, non-vegetarian diet intake and increasing Ki67 expression. Loss of Fhit protein expression is possibly influenced by environmental factors like smoking and non-vegetarian diet intake.
基金Supported by Health Canada,Government of Canada,Canada
文摘The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries. Aberrant crypt foci （ACF） represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans. ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis. For over two decades, since its first discovery, azoxymethane （AOM）-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens. Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system. There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up, and extensive research in this field is currently in progress. In chemoprevention studies, AOM-induced rat ACF have been very successful as biomarkers, and have provided several standardized analyses of data. There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome, however, and hence there has been an ambiguity about their role as biomarkers. The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies. The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.
文摘DNA methylation, one of the best-characterized epigenetic modifications, plays essential roles in diseases, including human cancers. In recent years, our understanding on DNA methylation with human cancers has made significant progress, which was facilitated by stunning development in the analysis of the human methylome of multiple cancer types. In this review, recent developments in the characterization of aberrant DNA methylation involved in human cancers development were discussed with special emphasis on the mechanisms of aberrant DNA methylation in human cancers. We also summarize the recent treatment strategy for human cancers with de-methylation drugs.
基金Supported by Grant-in-Aid for Research on the Third Term Comprehensive Control Research for Cancer from the Ministry of Health,Labour and Welfare,Japan to Nakajima Aa grant from the National Institute of Biomedical Innovation (NBIO) to Nakajima Aa grant from the Ministry of Education,Culture,Sports,Science and Technology,Japan (KIBAN-B) to Nakajima A and (KIBAN-C) to Takahashi H
文摘AIM:To clarify the relationship of human rectal aberrant crypt foci and formation of colorectal polyp.METHODS:Eighty-nine subjects were recruited from the population of Japanese individuals who underwent polypectomy at Yokohama City University Hospital.All patients had baseline adenomas removed at year 0 colonoscopy.Aberrant crypt foci(ACF) were defined as lesions in which the crypts were more darkly stained with methylene blue than normal crypts and had larger diameters,often with oval or slit-like lumens and a thicker epithelial lining.RESULTS:A total of 366 ACFs were identified in 89 patients;all had baseline adenomas removed at the first examination(year 0) colonoscopy and returned for the second(year 1).ACF in the lower rectum were assessed at year 0 and study group were divided into two groups depend on ACF numbers,0-3 or over 3.All participants were examined in the number and maximum size of adenoma.There was no statistical difference in number and maximum size of ACF at year 0,however,maximum size of adenoma was larger in over 3 group than 0-3 group at year 1.CONCLUSION:The number of ACF may be a predictive factor of relatively large adenoma incidence in the pilot phase study.
基金JHU microscopy facility.A.W.J.was funded by NIH/NIAMS(R01 AR070773),NIH/NIDCR(R21 DE027922)USAMRAA through the Peer-Reviewed Medical Research Program(W81XWH-18–1–0121,W81XWH-18–1–0336)+7 种基金Broad Agency Announcement(W81XWH-18–10613)American Cancer Society(Research Scholar Grant,RSG-18–027–01-CSM)the Maryland Stem Cell Research Foundation.B.L.funded by the NIH(1R01 AR071379)funded by NIH(R01 AR079171)Do D(W81XWH-20–1–0795)supported by the NIH/NIAMS(R01 AR068934)NIH/NIDCR(R21 DE027922)the VA(Merit Award and Senior Research Career Scientist Award)。
文摘The functional interdependence of nerves and blood vessels is a well-established concept during tissue morphogenesis, yet the role of neurovascular coupling in proper and aberrant tissue repair is an emerging field of interest. Here, we sought to define the regulatory relationship of peripheral nerves on vasculature in a severe extremity trauma model in mice, which results in aberrant cell fate and heterotopic ossification(HO). First, a high spatial degree of neurovascular congruency was observed to exist within extremity injury associated heterotopic ossification. Vascular and perivascular cells demonstrate characteristic responses to injury,as assessed by single cell RNA sequencing. This vascular response to injury was blunted in neurectomized mice, including a decrease in endothelial proliferation and type H vessel formation, and a downregulation of key transcriptional networks associated with angiogenesis. Independent mechanisms to chemically or genetically inhibit axonal ingrowth led to similar deficits in HO site angiogenesis, a reduction in type H vessels, and heterotopic bone formation. Finally, a combination of single cell transcriptomic approaches within the dorsal root ganglia identified key neural-derived angiogenic paracrine factors that may mediate neuron-to-vascular signaling in HO. These data provide further understanding of nerve-to-vessel crosstalk in traumatized soft tissues, which may reflect a key determinant of mesenchymal progenitor cell fate after injury.
