Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elu...Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.展开更多
High-resolution transmission electron microscopy(HRTEM)promises rapid atomic-scale dynamic structure imaging.Yet,the precision limitations of aberration parameters and the challenge of eliminating aberrations in Cs-co...High-resolution transmission electron microscopy(HRTEM)promises rapid atomic-scale dynamic structure imaging.Yet,the precision limitations of aberration parameters and the challenge of eliminating aberrations in Cs-corrected transmission electron microscopy constrain resolution.A machine learning algorithm is developed to determine the aberration parameters with higher precision from small,lattice-periodic crystal images.The proposed algorithm is then validated with simulated HRTEM images of graphene and applied to the experimental images of a molybdenum disulfide(MoS_(2))monolayer with 25 variables(14 aberrations)resolved in wide ranges.Using these measured parameters,the phases of the exit-wave functions are reconstructed for each image in a focal series of MoS_(2)monolayers.The images were acquired due to the unexpected movement of the specimen holder.Four-dimensional data extraction reveals time-varying atomic structures and ripple.In particular,the atomic evolution of the sulfur-vacancy point and line defects,as well as the edge structure near the amorphous,is visualized as the resolution has been improved from about 1.75?to 0.9 A.This method can help salvage important transmission electron microscope images and is beneficial for the images obtained from electron microscopes with average stability.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
To realize effective co-phasing adjustment in large-aperture sparse-aperture telescopes,a multichannel stripe tracking approach is employed,allowing simultaneous interferometric measurements of multiple optical paths ...To realize effective co-phasing adjustment in large-aperture sparse-aperture telescopes,a multichannel stripe tracking approach is employed,allowing simultaneous interferometric measurements of multiple optical paths and circumventing the need for pairwise measurements along the mirror boundaries in traditional interferometric methods.This approach enhances detection efficiency and reduces system complexity.Here,the principles of the multibeam interference process and construction of a co-phasing detection module based on direct optical fiber connections were analyzed using wavefront optics theory.Error analysis was conducted on the system surface obtained through multipath interference.Potential applications of the interferometric method were explored.Finally,the principle was verified by experiment,an interferometric fringe contrast better than 0.4 is achieved through flat field calibration and incoherent digital synthesis.The dynamic range of the measurement exceeds 10 times of the center wavelength of the working band(1550 nm).Moreover,a resolution better than one-tenth of the working center wavelength(1550 nm)was achieved.Simultaneous three-beam interference can be achieved,leading to a 50%improvement in detection efficiency.This method can effectively enhance the efficiency of sparse aperture telescope co-phasing,meeting the requirements for observations of 8-10 m telescopes.This study provides a technological foundation for observing distant and faint celestial objects.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
AIM:To compare simultaneous corneal collagen cross-linking(CXL)with intracorneal ring segment(ICRS)implantation versus successive ICRS followed by CXL and detect the impact of the timing of CXL after ICRS implantation...AIM:To compare simultaneous corneal collagen cross-linking(CXL)with intracorneal ring segment(ICRS)implantation versus successive ICRS followed by CXL and detect the impact of the timing of CXL after ICRS implantation in the successive method.METHODS:This is a retrospective study of the records of three groups of patients.Group 1 of 28 patients were operated on with simultaneous ICRS implantation and CXL,group 2 of 32 patients had ICRS implantation followed by CXL after 1mo,and group 3 of 38 patients had ICRS implantation followed by CXL after 3mo.The three groups had follow-up visits after 6,12,and 24mo.RESULTS:The preoperative data,age,and gender differences among 3 groups revealed no significant differences.The postoperative spherical equivalent and best-corrected visual acuity were improved significantly in all groups compared to the baseline,which were more evident in groups 1 and 2.The differences between preoperative and postoperative mean values of mean of K readings(Km)and maximum K reading(Kmax)at 6mo were 4.66 and 4.1 D in group 1,4.43 and 4.64 D in group 2,but 3.2 and 3.4 D in group 3,respectively.The spherical aberrations and the vertical coma showed significant postoperative changes in all groups,and trefoil showed nonsignificant changes.CONCLUSION:Simultaneous and sequential ICRS implantation and CXL at 1mo has similar Km and Kmax better postoperative changes than when both surgeries were done at three-month intervals.展开更多
Background:Ethylhexyl triazone(EHT)and diethylhexyl butamido triazone(HEB)both belong to the recently developed class of triazine ultraviolet filters.However,their toxicity profiles remain unclear.Objective:To assess ...Background:Ethylhexyl triazone(EHT)and diethylhexyl butamido triazone(HEB)both belong to the recently developed class of triazine ultraviolet filters.However,their toxicity profiles remain unclear.Objective:To assess the genotoxic and phototoxic effects of EHT and HEB.Methods:The genotoxicity of EHT and HEB was assessed using in vitro bacterial reverse mutation assays,chromosomal aberration assays,and micronucleus assays.Meanwhile,their phototoxicity was evaluated using in vitro 3T3 neutral red uptake(NRU)phototoxicity assays and in vivo skin phototoxicity tests.Results:In the bacterial reverse mutation assay,the number of bacterial colonies was not significantly higher in the EHT and HEB groups than in the solvent control group.Similarly,the chromosomal aberration assay revealed no increase in aberration rates after either EHT or HEB treatment.In the micronucleus assay,the frequency of micronuclei was comparable between the treatment and control groups.Finally,based on the 3T3 NRU phototoxicity assay,both EHT and HEB(photo-irritation factor<2 and mean photo effect value<0.1)were classified as non-phototoxic.The skin phototoxicity test in vivo showed the same results as in vitro.Conclusion:Results from a series of genotoxicity and phototoxicity assays indicate that EHT and HEB possess neither genotoxic nor phototoxic potential.These findings provide experimental evidence supporting the safety of EHT and HEB for topical applications.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
Although metabolic homeostasis disruption,cellular damage,and premature senescence caused by salinity stress are well-documented in the literature,there are few studies investigating cytological changes induced by sal...Although metabolic homeostasis disruption,cellular damage,and premature senescence caused by salinity stress are well-documented in the literature,there are few studies investigating cytological changes induced by salinity stress within the altered metabolic landscape of rice,and this study aims to fill that gap.The cytological characterization of root tips(in terms of mitotic index and chromosomal abnormalities such as stickiness,laggards,fragments,bridges,micronuclei,ring chromosomes,and total mitotic abnormalities)was conducted on 10 experimental rice landraces from coastal Bangladesh,grown under post-imbibitional salinity stress(PISS),while correlating these changes with their metabolic status.The results revealed a strong correlation between salinity-induced cytological changes in root cells(mitotic index and chromosomal abnormalities)and the redox interactome status of all experimental rice landraces.The landraces Kutepatnai,Talmugur,Nonakochi,and Benapol,which exhibited a higher ability to mitigate PISS-induced chromosomal abnormalities and improve mitotic index,also showed lower accumulation of oxidative stress markers(protein carbonylation,lipid peroxidation,prooxidant accumulation,oxidative stress index,reactive oxygen species(ROS)-antioxidative stress index,and efficiency of ROS processing via the Halliwell-Asada pathway)compared with more susceptible landraces(Charobalam,Jotaibalam,Kachra,and Lalmota).These findings underscore the role of redox biology in preventing chromotoxic effects under salinity stress.Hierarchical cluster analysis and principal component analysis,used to determine variations and similarities among the experimental rice landraces based on cytological attributes,redox interactome,and physiological phenotypes,classified the landraces according to their salinity tolerance and sensitivity.This study proposes a novel approach for exploring redox-regulated cytological fingerprints as a tool for identifying salinity-tolerant rice landraces.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
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
AIM:To compare the changes in preschool refractive status,ocular biological parameters,and higher-order aberrations in children with retinopathy of prematurity(ROP)after retinal laser photocoagulation or anti-vascular...AIM:To compare the changes in preschool refractive status,ocular biological parameters,and higher-order aberrations in children with retinopathy of prematurity(ROP)after retinal laser photocoagulation or anti-vascular endothelial growth factor(anti-VEGF)treatment and explore their underlying factors.METHODS:This observational study involved 118 eyes of 59 children,aged 3 to 6y,with ROP followed up between March 2023 and October 2024.They were divided into the laser,anti-VEGF,and anti-VEGF+laser groups.The laser group received a single session of laser photocoagulation.The anti-VEGF group received a single anti-VEGF treatment.The anti-VEGF+laser group received a single anti-VEGF treatment after birth followed by supplementary laser treatment within 2wk to 6mo.Ocular biological parameters were measured using IOL Master 700 and Pentacam HR.Right-eye higher-order aberrations were measured using the OPD-Scan III.Best-corrected visual acuities(BCVA),refractive statuses,ocular biological parameters,and higherorder aberrations were assessed and compared.Multiple linear regression analysis was conducted to evaluate the relationships among ocular biological parameters,higherorder aberrations,spherical equivalent(SE),and treatment methods.Pearson’s correlation coefficients were used to assess the relationships between the SE and higher-order aberrations.RESULTS:The laser group had a higher incidence of myopia and a lower SE than the anti-VEGF group.The incidence of astigmatism and cylindrical power were significantly lower for the anti-VEGF than for the laser and anti-VEGF+laser groups(P<0.05).The anterior corneal surface astigmatism was higher for the laser and anti-VEGF+laser groups than for the anti-VEGF group.The anterior corneal surface K2 and lens thickness were higher for the laser and anti-VEGF+laser groups than for the anti-VEGF group.The whole-eye higher-order aberration root mean square(RMS)values for the right eye were significantly higher for the laser and anti-VEGF+laser groups than for the anti-VEGF group.The whole-eye trefoil RMS values for the right eye were also significantly higher for the laser and anti-VEGF+laser groups than for the anti-VEGF group(P<0.05).Laser treatment was significantly associated with SE,anterior corneal surface curvature and astigmatism,lens thickness,whole-eye highorder aberrations,and whole-eye trefoil(all P<0.05).CONCLUSION:Children with ROP who received laser treatment have higher myopia and astigmatism than those who received anti-VEGF treatment.Children treated with laser or supplementary laser treatment have higher anterior corneal astigmatism,anterior corneal curvature,thicker lenses,whole-eye higher-order aberrations,and whole-eye trefoil.The cause of myopia in children with ROP after laser treatment is increased anterior corneal surface curvature and lens thickness.展开更多
Maintaining mitochondrial homeostasis is critical for preserving chondrocyte physiological conditions and increasing resistance against osteoarthritis(OA).However,the underlying mechanisms governing mitochondrial self...Maintaining mitochondrial homeostasis is critical for preserving chondrocyte physiological conditions and increasing resistance against osteoarthritis(OA).However,the underlying mechanisms governing mitochondrial self-renewal and energy production remain elusive.In this study,we demonstrated mitochondrial damage and aberrant mitophagy in OA chondrocytes.Genetically overexpressing PTEN-induced putative kinase 1(PINK1)protects against cartilage degeneration by removing defective mitochondria.PINK1 knockout aggravated cartilage damage due to impaired mitophagy.SIRT3 directly deacetylated PINK1 to promote mitophagy and cartilage anabolism.Specifically,PINK1 phosphorylated PKM2 at the Ser127 site,preserving its active tetrameric form.This inhibited nuclear translocation and the interaction withβ-catenin,resulting in a metabolic shift and increased energy production.Finally,a double-knockout mouse model demonstrated the role of the SIRT3-PINK1-PKM2 axis in safeguarding the structural integrity of articular joints and improving motor functions.Overall,this study provides a novel insight into the regulation of mitochondrial renewal and metabolic switches in OA.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
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
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
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
This study aims to improve the integrated testing of large-aperture telescopes to clarify the fundamental principles of an integrated testing system based on astrophotonics.Our demonstration and analyses focused on el...This study aims to improve the integrated testing of large-aperture telescopes to clarify the fundamental principles of an integrated testing system based on astrophotonics.Our demonstration and analyses focused on element-position sensing and modulation based on spatial near-geometric beams,high-throughput step-difference measurements based on channel spectroscopy,distributed broadband-transmittance testing,and standard spectral tests based on near-field energy regulation.Comprehensive analyses and experiments were conducted to confirm the feasibility of the proposed system in the integrated testing process of large-aperture telescopes.The results demonstrated that the angular resolution of the light rays exceeded 5arcsec,which satisfies the requirements for component-position detection in future large-aperture telescopes.The measurement resolution of the wavefront tilt was better than 0.45μrad.Based on the channel spectral method—which combined a high signal-to-noise ratio and high sensitivity,along with continuous-spectral digital segmentation and narrowband-spectral physical segmentation—a resolution of 0.050μm and a range of 50μm were obtained.After calibration,the measurement resolution of the pupil deviation improved to exceed 4%accuracy,and the transmission measurements achieved a consistency of over 2%accuracy.Regarding fringe-broadband interferometry measurements,the system maintained high stability,ensuring its operation within the coherence length,and robustly detected the energy without unwrapping the phase.The use of a projector for calibrating broadband-spectrum measurements led to a reduction in contrast from 0.8142 to 0.6038,which further validates the system's applicability in the integrated testing process of large-aperture telescopes.This study greatly enhanced the observational capabilities of large-aperture telescopes while reducing the integrated system's volume,weight,and power consumption.展开更多
基金supported by the Anhui Provincial Natural Science Foundation(Grant No.2308085MH250)the Natural Science Research Project of Anhui Educational Committee(Grant No.2023AH053327)the Scientific Research Fund Project of Anhui Medical University(2020xkj039).
文摘Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.
基金financial support from the National Natural Science Foundation of China(Grant No.61971201)。
文摘High-resolution transmission electron microscopy(HRTEM)promises rapid atomic-scale dynamic structure imaging.Yet,the precision limitations of aberration parameters and the challenge of eliminating aberrations in Cs-corrected transmission electron microscopy constrain resolution.A machine learning algorithm is developed to determine the aberration parameters with higher precision from small,lattice-periodic crystal images.The proposed algorithm is then validated with simulated HRTEM images of graphene and applied to the experimental images of a molybdenum disulfide(MoS_(2))monolayer with 25 variables(14 aberrations)resolved in wide ranges.Using these measured parameters,the phases of the exit-wave functions are reconstructed for each image in a focal series of MoS_(2)monolayers.The images were acquired due to the unexpected movement of the specimen holder.Four-dimensional data extraction reveals time-varying atomic structures and ripple.In particular,the atomic evolution of the sulfur-vacancy point and line defects,as well as the edge structure near the amorphous,is visualized as the resolution has been improved from about 1.75?to 0.9 A.This method can help salvage important transmission electron microscope images and is beneficial for the images obtained from electron microscopes with average stability.
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To realize effective co-phasing adjustment in large-aperture sparse-aperture telescopes,a multichannel stripe tracking approach is employed,allowing simultaneous interferometric measurements of multiple optical paths and circumventing the need for pairwise measurements along the mirror boundaries in traditional interferometric methods.This approach enhances detection efficiency and reduces system complexity.Here,the principles of the multibeam interference process and construction of a co-phasing detection module based on direct optical fiber connections were analyzed using wavefront optics theory.Error analysis was conducted on the system surface obtained through multipath interference.Potential applications of the interferometric method were explored.Finally,the principle was verified by experiment,an interferometric fringe contrast better than 0.4 is achieved through flat field calibration and incoherent digital synthesis.The dynamic range of the measurement exceeds 10 times of the center wavelength of the working band(1550 nm).Moreover,a resolution better than one-tenth of the working center wavelength(1550 nm)was achieved.Simultaneous three-beam interference can be achieved,leading to a 50%improvement in detection efficiency.This method can effectively enhance the efficiency of sparse aperture telescope co-phasing,meeting the requirements for observations of 8-10 m telescopes.This study provides a technological foundation for observing distant and faint celestial objects.
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AIM:To compare simultaneous corneal collagen cross-linking(CXL)with intracorneal ring segment(ICRS)implantation versus successive ICRS followed by CXL and detect the impact of the timing of CXL after ICRS implantation in the successive method.METHODS:This is a retrospective study of the records of three groups of patients.Group 1 of 28 patients were operated on with simultaneous ICRS implantation and CXL,group 2 of 32 patients had ICRS implantation followed by CXL after 1mo,and group 3 of 38 patients had ICRS implantation followed by CXL after 3mo.The three groups had follow-up visits after 6,12,and 24mo.RESULTS:The preoperative data,age,and gender differences among 3 groups revealed no significant differences.The postoperative spherical equivalent and best-corrected visual acuity were improved significantly in all groups compared to the baseline,which were more evident in groups 1 and 2.The differences between preoperative and postoperative mean values of mean of K readings(Km)and maximum K reading(Kmax)at 6mo were 4.66 and 4.1 D in group 1,4.43 and 4.64 D in group 2,but 3.2 and 3.4 D in group 3,respectively.The spherical aberrations and the vertical coma showed significant postoperative changes in all groups,and trefoil showed nonsignificant changes.CONCLUSION:Simultaneous and sequential ICRS implantation and CXL at 1mo has similar Km and Kmax better postoperative changes than when both surgeries were done at three-month intervals.
基金supported by the National Natural Science Foundation of China(No.81600459)National Natural Science Foundation of Hubei Province(No.2016CFB312)+3 种基金Talent Introduction Project of Hubei Polytechnic University(No.15xjz03R)Industry-University Collaboration(No.KY2023-269)Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention Foundation(No.SB202103)Provincial College Student Innovation and Entrepreneurship Training Program(No.S202210920011).
文摘Background:Ethylhexyl triazone(EHT)and diethylhexyl butamido triazone(HEB)both belong to the recently developed class of triazine ultraviolet filters.However,their toxicity profiles remain unclear.Objective:To assess the genotoxic and phototoxic effects of EHT and HEB.Methods:The genotoxicity of EHT and HEB was assessed using in vitro bacterial reverse mutation assays,chromosomal aberration assays,and micronucleus assays.Meanwhile,their phototoxicity was evaluated using in vitro 3T3 neutral red uptake(NRU)phototoxicity assays and in vivo skin phototoxicity tests.Results:In the bacterial reverse mutation assay,the number of bacterial colonies was not significantly higher in the EHT and HEB groups than in the solvent control group.Similarly,the chromosomal aberration assay revealed no increase in aberration rates after either EHT or HEB treatment.In the micronucleus assay,the frequency of micronuclei was comparable between the treatment and control groups.Finally,based on the 3T3 NRU phototoxicity assay,both EHT and HEB(photo-irritation factor<2 and mean photo effect value<0.1)were classified as non-phototoxic.The skin phototoxicity test in vivo showed the same results as in vitro.Conclusion:Results from a series of genotoxicity and phototoxicity assays indicate that EHT and HEB possess neither genotoxic nor phototoxic potential.These findings provide experimental evidence supporting the safety of EHT and HEB for topical applications.
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.
文摘Although metabolic homeostasis disruption,cellular damage,and premature senescence caused by salinity stress are well-documented in the literature,there are few studies investigating cytological changes induced by salinity stress within the altered metabolic landscape of rice,and this study aims to fill that gap.The cytological characterization of root tips(in terms of mitotic index and chromosomal abnormalities such as stickiness,laggards,fragments,bridges,micronuclei,ring chromosomes,and total mitotic abnormalities)was conducted on 10 experimental rice landraces from coastal Bangladesh,grown under post-imbibitional salinity stress(PISS),while correlating these changes with their metabolic status.The results revealed a strong correlation between salinity-induced cytological changes in root cells(mitotic index and chromosomal abnormalities)and the redox interactome status of all experimental rice landraces.The landraces Kutepatnai,Talmugur,Nonakochi,and Benapol,which exhibited a higher ability to mitigate PISS-induced chromosomal abnormalities and improve mitotic index,also showed lower accumulation of oxidative stress markers(protein carbonylation,lipid peroxidation,prooxidant accumulation,oxidative stress index,reactive oxygen species(ROS)-antioxidative stress index,and efficiency of ROS processing via the Halliwell-Asada pathway)compared with more susceptible landraces(Charobalam,Jotaibalam,Kachra,and Lalmota).These findings underscore the role of redox biology in preventing chromotoxic effects under salinity stress.Hierarchical cluster analysis and principal component analysis,used to determine variations and similarities among the experimental rice landraces based on cytological attributes,redox interactome,and physiological phenotypes,classified the landraces according to their salinity tolerance and sensitivity.This study proposes a novel approach for exploring redox-regulated cytological fingerprints as a tool for identifying salinity-tolerant rice landraces.
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 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.
基金Supported by Key Research and Development Program of Shaanxi Province(No.2024SF-YBXM-320)the Clinical Research Project of the Fourth Military Medical University(No.2022LC2247)Medical Staff Training Boosting Project of Xijing Hospital,Air Force Medical University(No.XJZT24CY52).
文摘AIM:To compare the changes in preschool refractive status,ocular biological parameters,and higher-order aberrations in children with retinopathy of prematurity(ROP)after retinal laser photocoagulation or anti-vascular endothelial growth factor(anti-VEGF)treatment and explore their underlying factors.METHODS:This observational study involved 118 eyes of 59 children,aged 3 to 6y,with ROP followed up between March 2023 and October 2024.They were divided into the laser,anti-VEGF,and anti-VEGF+laser groups.The laser group received a single session of laser photocoagulation.The anti-VEGF group received a single anti-VEGF treatment.The anti-VEGF+laser group received a single anti-VEGF treatment after birth followed by supplementary laser treatment within 2wk to 6mo.Ocular biological parameters were measured using IOL Master 700 and Pentacam HR.Right-eye higher-order aberrations were measured using the OPD-Scan III.Best-corrected visual acuities(BCVA),refractive statuses,ocular biological parameters,and higherorder aberrations were assessed and compared.Multiple linear regression analysis was conducted to evaluate the relationships among ocular biological parameters,higherorder aberrations,spherical equivalent(SE),and treatment methods.Pearson’s correlation coefficients were used to assess the relationships between the SE and higher-order aberrations.RESULTS:The laser group had a higher incidence of myopia and a lower SE than the anti-VEGF group.The incidence of astigmatism and cylindrical power were significantly lower for the anti-VEGF than for the laser and anti-VEGF+laser groups(P<0.05).The anterior corneal surface astigmatism was higher for the laser and anti-VEGF+laser groups than for the anti-VEGF group.The anterior corneal surface K2 and lens thickness were higher for the laser and anti-VEGF+laser groups than for the anti-VEGF group.The whole-eye higher-order aberration root mean square(RMS)values for the right eye were significantly higher for the laser and anti-VEGF+laser groups than for the anti-VEGF group.The whole-eye trefoil RMS values for the right eye were also significantly higher for the laser and anti-VEGF+laser groups than for the anti-VEGF group(P<0.05).Laser treatment was significantly associated with SE,anterior corneal surface curvature and astigmatism,lens thickness,whole-eye highorder aberrations,and whole-eye trefoil(all P<0.05).CONCLUSION:Children with ROP who received laser treatment have higher myopia and astigmatism than those who received anti-VEGF treatment.Children treated with laser or supplementary laser treatment have higher anterior corneal astigmatism,anterior corneal curvature,thicker lenses,whole-eye higher-order aberrations,and whole-eye trefoil.The cause of myopia in children with ROP after laser treatment is increased anterior corneal surface curvature and lens thickness.
基金supported by grants from National Nature Science Foundation of China(82272494,82472452,82402864)National Key R&D Program of China(2022YFC2502902)+4 种基金Key Project of Jiangsu Health Commission(K2023079)Natural Science Foundation of Jiangsu Province(BK20240368)Basic Research Pilot Project Suzhou(SSD2024062),China Postdoctoral Science Foundation(2024M762313)Boxi Youth Natural Science Foundation(BXQN2023014)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Maintaining mitochondrial homeostasis is critical for preserving chondrocyte physiological conditions and increasing resistance against osteoarthritis(OA).However,the underlying mechanisms governing mitochondrial self-renewal and energy production remain elusive.In this study,we demonstrated mitochondrial damage and aberrant mitophagy in OA chondrocytes.Genetically overexpressing PTEN-induced putative kinase 1(PINK1)protects against cartilage degeneration by removing defective mitochondria.PINK1 knockout aggravated cartilage damage due to impaired mitophagy.SIRT3 directly deacetylated PINK1 to promote mitophagy and cartilage anabolism.Specifically,PINK1 phosphorylated PKM2 at the Ser127 site,preserving its active tetrameric form.This inhibited nuclear translocation and the interaction withβ-catenin,resulting in a metabolic shift and increased energy production.Finally,a double-knockout mouse model demonstrated the role of the SIRT3-PINK1-PKM2 axis in safeguarding the structural integrity of articular joints and improving motor functions.Overall,this study provides a novel insight into the regulation of mitochondrial renewal and metabolic switches in OA.
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.
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].
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(Grant No.12133009)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.2020221)the Science and Technology Development Plan of Jilin Province(Grant No.20220402032GH)。
文摘This study aims to improve the integrated testing of large-aperture telescopes to clarify the fundamental principles of an integrated testing system based on astrophotonics.Our demonstration and analyses focused on element-position sensing and modulation based on spatial near-geometric beams,high-throughput step-difference measurements based on channel spectroscopy,distributed broadband-transmittance testing,and standard spectral tests based on near-field energy regulation.Comprehensive analyses and experiments were conducted to confirm the feasibility of the proposed system in the integrated testing process of large-aperture telescopes.The results demonstrated that the angular resolution of the light rays exceeded 5arcsec,which satisfies the requirements for component-position detection in future large-aperture telescopes.The measurement resolution of the wavefront tilt was better than 0.45μrad.Based on the channel spectral method—which combined a high signal-to-noise ratio and high sensitivity,along with continuous-spectral digital segmentation and narrowband-spectral physical segmentation—a resolution of 0.050μm and a range of 50μm were obtained.After calibration,the measurement resolution of the pupil deviation improved to exceed 4%accuracy,and the transmission measurements achieved a consistency of over 2%accuracy.Regarding fringe-broadband interferometry measurements,the system maintained high stability,ensuring its operation within the coherence length,and robustly detected the energy without unwrapping the phase.The use of a projector for calibrating broadband-spectrum measurements led to a reduction in contrast from 0.8142 to 0.6038,which further validates the system's applicability in the integrated testing process of large-aperture telescopes.This study greatly enhanced the observational capabilities of large-aperture telescopes while reducing the integrated system's volume,weight,and power consumption.
