五谷虫通过抑制免疫应激-补体活化缓解咪喹莫特诱导的小鼠银屑病样皮肤损伤

目的研究五谷虫通过免疫应激-补体活化途径治疗C57BL/6银屑病样小鼠的药效学及作用机制。方法取36只SPF级雄性C57BL/6小鼠,随机分为正常组、模型组、五谷虫(1.25%,2.5%,5%剂量)组、本维莫德(1%)组,6只/组,咪喹莫特乳膏涂抹造模。MPASI评分检测小鼠皮损的严重程度;游标卡尺检测小鼠耳廓肿胀厚度;HE染色检测小鼠背部皮肤及右耳组织病理学变化;观察小鼠抓挠行为学;称重计算小鼠脾脏指数;甲苯胺蓝染色检测小鼠背部皮肤组织肥大细胞数量;ELISA法检测免疫应激(IgG、IgM)、补体活化(CH50、C1s、C3、C3a、C5、C5a)、炎症反应(IL-23、IL-17A、TNF-α)相关因子水平。结果与正常组相比,模型组小鼠MPASI评分、耳廓肿胀厚度均升高(P<0.001);背部皮肤及右耳组织病理损伤加重;抓挠行为次数,脾脏指数,肥大细胞数量,血清IgG、C1s、C3a、C5a、IL-23、IL-17A、TNF-α,组织C1s、C3、C3a、C5、C5a水平均升高(P<0.05),血清CH50、C3、C5水平降低(P<0.001),血清IgM水平有升高趋势,但差异无统计学意义。与模型组相比,五谷虫低、中、高剂量组小鼠MPASI评分、耳廓肿胀厚度降低(P<0.05);背部皮肤及右耳组织病理损伤减弱;抓挠行为次数、脾脏指数、肥大细胞数量降低(P<0.01),五谷虫高剂量组血清IgG、C1s、C3a、C5a、IL-23、IL-17A、TNF-α,组织C1s、C3、C3a、C5、C5a水平降低(P<0.05),血清CH50、C3、C5水平升高(P<0.01)。五谷虫疗效呈现剂量-效应依赖关系。结论五谷虫通过调控免疫应激-补体活化途径发挥治疗银屑病作用。

Characteristics and Risk Factors for Pediatric Sepsis

Objective Sepsis is considered a major cause of health loss in children and had high mortality and morbidity.Currently,there is no reliable model for predicting the prognosis of pediatric patients with sepsis.This study aimed to analyze the clinical characteristics of sepsis in children and assess the risk factors associated with poor prognosis in pediatric sepsis patients to identify timely interventions and improve their outcomes.Methods This study analyzed the clinical indicators and laboratory results of septic patients hospitalized in the Pediatric Intensive Care Unit of Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from January 1,2019,to December 31,2021.Risk factors for sepsis were identified by logistic regression analyses.Results A total of 355 children with sepsis were enrolled,with 333 children(93.8%)in the good prognosis group,and 22 children(6.2%)in the poor prognosis group.Among them,there were 255 patients(71.8%)in the sepsis group,and 100 patients(28.2%)in the severe sepsis group.The length of hospital stay in the poor prognosis group was longer than that in the good prognosis group(P<0.01).The levels of interleukin 1β(IL-1β)in the poor prognosis group were higher than those in the good prognosis group(P>0.05),and the platelet(PLT),albumin(ALB),and hemoglobin(Hb)levels were lower in the poor prognosis group(P<0.01).The IL-8 levels in the severe sepsis group were higher than those in the sepsis group(P<0.05).Multiple logistic regression analysis suggested that lower Hb levels,ALB levels,peak PLT counts,and higher IL-1βlevels were independent risk factors for poor prognosis in children with sepsis.Conclusion Lower Hb,ALB,and PLT counts and elevated IL-1βare independent risk factors for poor prognosis in children with sepsis.

A Single-Sized Metasurface for Image Steganography and Multi-Key Information Encryption

With the escalating flow of information and digital communication,information security has become an increasingly important issue.Traditional cryptographic methods are being threatened by advancing progress in computing,while physical encryption methods are favored as a viable and compelling avenue.Metasurfaces,which are known for their extraordinary ability to manipulate optical parameters at the nanoscale,exhibit significant potential for the revolution of optical devices,making them a highly promising candidate for optical encryption applications.Here,a single-sized metasurface with four independent channels is proposed for conducting steganography and multi-key information encryption.More specifically,plaintext is transformed into a ciphertext image,which is encoded into a metasurface,while the decryption key is discretely integrated into another channel within the same metasurface.Two different keys for steganographic image unveiling are also encoded into the metasurface and can be retrieved with different channels and spatial positions.This distributed multi-key encryption approach can enhance security,while strategically distributing images across distinct spatial zones serves as an additional measure to reduce the risk of information leakage.This minimalist designed metasurface,with its advantages of high information density and robust security,holds promise across applications including portable encryption,high-camouflaged image display,and high-density optical storage.

Bilateral meibomian gland morphological alterations in unilateral herpes simplex keratitis based on artificial intelligence analysis

AIM:To explore whether unilateral herpes simplex keratitis(HSK)can cause morphological changes of bilateral meibomian glands(MGs)based on artificial intelligence(AI)analytical system.METHODS:In the retrospective study,29 patients with unilateral HSK and 29 participants matched in terms of age and sex were included as control group.Meibographic images of the upper eyelid using Keratograph 5M and assessed ocular surface parameters including tear meniscus height and tear break-up time.MG density and vagueness values were automatically analyzed and calculated using an AI analytical system.We compared the differences between the affected and the contralateral unaffected eyes in HSK patients,and the normal control eyes.We employed either the paired t-test or the Wilcoxon signed-rank test to compare significant difference between the affected and unaffected eyes in HSK patients or between the HSK group and control group.RESULTS:The MG density was 0.19±0.09 in the HSKaffected eye and 0.18±0.07 in contralateral unaffected eye,which had no significant difference(P=0.616).The MG density between the affected eye with HSK and the normal control group was statistically significant(P=0.028).There was a significant difference in MG density between the contralateral unaffected eye and the normal control group(P=0.012).However,no significant difference in vagueness value was observed between the eye with HSK and the control group or between HSK eye and contralateral eye.CONCLUSION:The MG density between the HSKaffected eye and the contralateral unaffected eye don’t significantly differ,whereas there is a significant decrease in the HSK group compared to that of the normal participants.Unilateral HSV keratitis may suffer from bilateral changes of MG morphology indicating bilateral dry eye.Therefore,the fellow eye of patients with unilateral HSK should be considered a potential case of MG dysfunction,necessitating early treatment for bilateral dry eye in the clinic.

Artificial intelligence-aided diagnosis and treatment in the field of optometry

With the rapid development of computer technology,the application of artificial intelligence(AI)to ophthalmology has gained prominence in modern medicine.As modern optometry is closely related to ophthalmology,AI research on optometry has also increased.This review summarizes current AI research and technologies used for diagnosis in optometry,related to myopia,strabismus,amblyopia,optical glasses,contact lenses,and other aspects.The aim is to identify mature AI models that are suitable for research on optometry and potential algorithms that may be used in future clinical practice.

直播购物环境中主播信任影响因素及调节效应

直播购物以其强大实时互动性和用户体验丰富性迅速成为消费者新宠。但是,包括知名主播在内的“翻车”事件频发,不仅使主播声誉受损,更让消费者对主播的信任大打折扣。学术界对直播购物信任的研究主要集中在购买意愿方面,很少从主播角度来专门研究信任的影响因素,且忽略了主播和产品因素、情境因素以及消费者个体特征在其中可能扮演的调节作用。为此,本文引入主播与产品匹配度、直播中的在线评论、网购经验三个调节变量,探讨它们在主播声誉、主播知名度与主播信任之间的调节效应。结果显示:主播声誉和知名度对主播信任有显著正向影响;产品匹配度对主播声誉、主播知名度与主播信任之间关系均起正向调节作用;在线评论对主播知名度与主播信任之间关系起正向调节作用;网购经验对主播声誉与主播信任之间关系起正向调节作用。

Effective treatment for secondary angle-closure glaucoma caused by traumatic lens subluxation:phacoemulsification with capsular-tension-ring implantation combined with ophthalmic endoscope-controlled goniosynechialysis

AIM:To investigate the safety and efficacy of phacoemulsification with capsular-tension-ring implantation and posterior chamber intraocular lens implantation combined with ophthalmic endoscope-controlled goniosynechialysis(Phaco-CTR-IOL-OE-GSL)for treating secondary angle-closure glaucoma induced by traumatic lens subluxation.METHODS:A retrospective and descriptive study was performed on patients with lens subluxation,angle closure,goniosynechia,and evaluated intraocular pressure(IOP)that cannot be controlled with medication,who underwent Phaco-CTR-IOL-OE-GSL.The postoperative best-corrected visual acuity(BCVA),IOP,range of goniosynechia and complications were retrospectively observed.RESULTS:Nine patients with secondary angle-closure glaucoma induced by traumatic lens subluxation were included.The follow-up period was 51.1±8.6 mo.The preoperative range of zonule rupture was 158.2°±33.0°,and the range of goniosynechia was 220.0°±92.5°.The baseline BCVA was 0.9±1.0 logMAR,IOP was 30.7±17.3 mm Hg and number of anti-glaucoma medication was 3.2±1.1.Mild intraoperative hyphaemia with 8 eyes(88.8%)in the anterior chamber,and was absorbed two days postoperatively.One eye(11.1%)had postoperative ciliary body detachment and was recovered after five days of topical drug treatment.BCVA was 0.2±0.2 logMAR at 3 mo postoperatively.The average IOP at the last follow-up was 16.7±2.0 mm Hg,and no anti-glaucoma medications were used.The average range of recurrent goniosynechia was 54.9°±33°at the final postoperative gonioscopic examination.CONCLUSION:Phaco-CTR-IOL-OE-GSL is safe and effective in the treatment of secondary angle-closure glaucoma induced by traumatic lens subluxation.The use of an endoscope provides a more direct and clear examination for GSL,and 360°dissection is easily achieved.

Bilateral retrocorneal hyaline scrolls secondary to asymptomatic congenital syphilis: A case report

BACKGROUND Retrocorneal hyaline scrolls are a rare phenomenon.We report a case of bilateral retrocorneal hyaline scrolls that were likely induced by asymptomatic congenital syphilis.CASE SUMMARY A 71-year-old woman presented with blurred vision due to cataracts.Slit-lamp microscopy revealed bilateral hyaline scrolls with a dichotomous branching pattern extending to the anterior chamber or rods attaching to the rough posterior surface of the cornea.The patient was positive for syphilis-specific antibodies,with no ocular or systemic evidence of congenital or acquired syphilis.Binocular cataract,retrocorneal scroll,and corneal endothelial gutta were considered.The scroll of the right eye was removed during cataract surgery and further observed using hematoxylin–eosin staining and scanning electron microscopy.The cornea of the right eye remained transparent,and the residual scroll seemed stable,however,the corneal endothelial density declined at 13 mo after surgery.In vivo confocal microscopy revealed coalescence of corneal guttae at the level of the corneal endothelium or adhesion to the posterior surface of the endothelium,with enlarged endothelial cells in both eyes.Activated keratocytes in the stroma and a highly reflective acellular structure at the level of the Descemet’s membrane were observed.The removed scroll had a cartilage-like hardness and a circularly arranged fiber-like acellular structure.CONCLUSION Occult congenital syphilis could induce corneal endothelial gutta and theformation of retrocorneal scrolls without other signs of ocular syphilis.

The Role of Occipitotemporal Network for Speed-Reading:An fMRI Study

The activity of occipitotemporal regions involved in linguistic reading processes,such as the ventral occipitotemporal cortex(vOT),is believed to exhibit strong interactions during higher-order language processing,specifically in the connectivity between the occipital gyrus and the temporal gyrus.In this study,we utilized functional magnetic resonance imaging(fMRI)with psychophysiological interaction(PPI)and dynamic causal modeling(DCM)to investigate the functional and effective connectivity in the occipitotemporal network during speed reading.We conducted the experiment with native Japanese speakers who underwent and without speed-reading training and subsequently performed established reading tasks at different speeds(slow,medium,and fast)while undergoing 3-Tesla Siemens fMRI.Our activation analyses revealed significant changes in occipital and temporal regions as reading speed increased,indicating functional connectivity within the occipitotemporal network.DCM results further demonstrated more intricate effective connections and high involvement within the occipitotemporal pathway:(1)reading signals originated from the inferior occipital gyrus(iO),distributed to the vOT and the posterior superior temporal sulcus(pSTS),and then gathered in the anterior superior temporal sulcus(aSTS);(2)reading speed loads had modulation effects on the pathways from the aSTS to vOT and from the iO to vOT.These findings highlight the complex connectivity and dynamic interactions within the occipitotemporal network during speed-reading processes.

Single-celled metasurface for labeled vortex beam generator

Vortex light is a unique beam characterized by a spiral phase as it propagates. A fundamental parameter of vortex light is the topological charge, which determines the amount of angular momentum and plays a crucial role in tailoring its behavior. However, conventional measurement methods for determining the topological charge, such as those based on interference and phase modulation, tend to be intricate and complex. In this regard, a labeled vortex beam generator is proposed, composed of a metasurface with a single-celled configuration. When the metasurface is illuminated by light of the designed wavelength, the outgoing light exhibits a vortex structure. Furthermore, the topological charge numbers can be directly observed with distinct labeled patterns when the metasurface is placed in an orthogonal-polarized optical path. With advantages such as ultra-compactness, high robustness, and exceptional precision, the proposed metasurface exhibits significant potential for applications in optical communication, light manipulation, optical sensing, etc.

The aromatic peptide protected gold nanoclusters with significant Stokes shift:Ligand-mediated two-step FRET

During the last decade,a great variety of ligand protected gold nanoclusters(AuNCs)have been synthesized,and their broad applications have been intensively reported.Although the spectroscopic properties of AuNCs have been comprehensively explored,the mechanism of the significant Stokes shift(>200 nm)and the specific role played by surface ligands have not been clearly explained yet.In this study,a series of fluorescent AuNCs with huge Stokes shift(up to 530 nm)were successfully prepared by employing the rationally designed tri-peptides as the protecting ligands,and their spectroscopic properties were systematically investigated.The detailed measurements on the example product,YCY-AuNCs(Tyr-Cys-Tyr liganded AuNCs),showed that the energy absorbed by the tyrosine(~250 nm)can be effectively transferred through the ligand-mediated two-step Förster resonance energy transfer(FRET)process and released as fluorescence emission in the near-infrared fluorescence(NIR)range(~780 nm),which resulted in the significant apparent Stokes shift.The YCY ligands play a critical role by offering the tyrosine groups(donor of the first FRET pair),generating the dityrosine-like structure on the AuNCs surface(acceptor of the first FRET pair and donor of the second FRET pair),and protecting the cores(acceptor of the second acceptor).The additional ligand exchange experiments and the investigation on the other AuNCs further demonstrated that the sufficient high density of the aromatic groups is also essential to mediate the two-step FRET and achieve the remarkable Stokes shift.We believe that the aromatic ligand-mediated FRET mechanism not only offers a new theoretical explanation for the huge Stokes shift exhibited in AuNCs,but also provides a general strategy for the construction of new materials with large Stokes shift.

Membrane fusion reverse micelle platforms as potential oral nanocarriers for efficient internalization of free hydrophilic peptides

Orally administered peptides or proteins are garnering increasing preference owing to their superiority in terms of patient compliance and convenience.However,the development of oral protein formulations has stalled due to the low bioavailability of macromolecules that encounter the aggressive gastrointestinal environment and harsh mucus villi barrier.Herein,we propose an ideal reverse micelle/self-emulsifying drug delivery system(RM/SEDDS)nanoplatform that is capable of improving the oral bioavailability of hydrophilic peptides by preventing enzymatic degradation and enhancing mucosal permeability.Upon the passage through the mucus,the self-emulsifying drug delivery system with optimal surface properties effectively penetrates the viscoelastic mucosal barrier,followed by the exposure of the inner reverse micelle amphipathic vectors,which autonomously form continua with the lipidic cell membrane and facilitate the internalization of drugs.This membrane-fusion mechanism inaugurates a new way for hydrophilic peptide delivery in the free form,circumventing the traditional impediments of the cellular internalization of nanocarriers and subsequent poor release of drugs.And more importantly,reverse micelles are not spatially specific to the laden drugs,which enables their delivery for a myriad of peptide clinical drugs.In conclusion,as an exquisitely designed nanoplatform,RM/SEDDS overcomes multiple physiological barriers and opens a new path for drug cellular entry,providing new prospects for the development of oral drug delivery systems.

Peptidomimetic-liganded gold nanoclusters for controlled iron delivery and synergistic suppression of tumor growth

A novel peptidomimetic-liganded gold nanocluster(CDp-AuNC)is proposed for the synergistic suppression of tumor growth.Taking advantages of the multi-capabilities offered by the surface ligands,including iron chelation,glutathione peroxidases-1(GPx-1)binding,and tumor cells recognition,CDp-AuNCs are able to function as the nanocarriers to deliver iron in a controlled manner for the ferroptosis therapy and as the inhibitors for GPx-1 to induce the apoptosis of tumor cells.The Fe2+@CDp-AuNC nanocomplexes are fabricated through a facile self-assembly method.The experimental data verify that the nanocomplexes are internalized specifically by tumor cells with high efficiency.The acidic microenvironment in endosomes triggers the collapse of the nanocomplexes and thereby releases Fe2+to induce ferroptosis and CDp-AuNCs to inhibit the enzyme activity of GPx-1.Benefiting from the H_(2)O_(2)-depleted pathway inhibition and ferroptosis acceleration,the intracellular reactive oxygen species(ROS)level could be enhanced significantly.As a consequence,the apoptosis/ferroptosis of 4T1 cells as well as the tumor elimination in vivo are observed after treatment with the Fe2+@CDp-AuNC nanocomplexes at a relatively low dose.The facile iron loading method,simple construction procedure,and outstanding tumor suppression performance,provide CDp-AuNCs great application promise.More importantly,the strategy of peptidomimetic ligands design provides a transferable approach to building multifunctional nanomaterials.

Erratum to:Membrane fusion reverse micelle platforms as potential oral nanocarriers for efficient internalization of free hydrophilic peptides

Erratum to Nano Research 2023,16(7):9768-9780 https://doi.org/10.1007/s12274-023-5645-7 The complete affiliations of co-author Yiying Lu is Institute of Pharmaceutics,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China and Department of Pharmacy,Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China.

Full-space Cloud of Random Points with a Scrambling Metasurface

With the rapid progress in computer science,including artificial intelligence,big data and cloud computing,full-space spot generation can be pivotal to many practical applications,such as facial recognition,motion detection,augmented reality,etc.These opportunities may be achieved by using diffractive optical elements(DOEs)or light detection and ranging(LIDAR).However,DOEs suffer from intrinsic limitations,such as demanding depth-controlled fabrication techniques,large thicknesses(more than the wavelength),Lambertian operation only in half space,etc.LIDAR nevertheless relies on complex and bulky scanning systems,which hinders the miniaturization of the spot generator.Here,inspired by a Lambertian scatterer,we report a Hermitian-conjugate metasurface scrambling the incident light to a cloud of random points in full space with compressed information density,functioning in both transmission and reflection spaces.Over 4044 random spots are experimentally observed in the entire space,covering angles at nearly 90°.Our scrambling metasurface is made of amorphous silicon with a uniform subwavelength height,a nearly continuous phase coverage,a lightweight,flexible design,and low-heat dissipation.Thus,it may be mass produced by and integrated into existing semiconductor foundry designs.Our work opens important directions for emerging 3D recognition sensors,such as motion sensing,facial recognition,and other applications.

Puromycin A, B and C, cryptic nucleosides identified from Streptomyces alboniger NRRL B-1832 by PPtase-based activation

Natural product discovery is pivot for drug development,however,this endeavor is often challenged by the wide inactivation or silence of natural products biosynthetic pathways.We recently developed a highly efficient approach to activate cryptic/silenced biosynthetic pathways through augmentation of the phosphopantetheinylation of carrier proteins.By applying this approach in the Streptomyces alboniger NRRL B-1832,we herein identified three cryptic nucleosides products,including one known puromycin A and two new derivatives(puromycin B and C).The biosynthesis of these products doesn't require the involvement of carrier protein,indicating the phosphopantetheinyl transferase(PPtase)indeed plays a fundamental regulatory role in metabolites biosynthesis.These results demonstrate that the PPtasebased approach have a much broader effective scope than the previously assumed carrier proteininvolving pathways,which will benefit future natural products discovery and biosynthetic studies.

A one-step specific assay for continuous detection of sirtuin 2 activity

Sirtuins(SIRTs)are nicotinamide adenine dinucleotide(NAD^+)-dependent histone deacetylases with diverse physiological functions.A variety of small molecules have been developed to interrogate the physiological function of SIRTs.Therefore,it is desirable to establish efficient and convenient assays to screen SIRTs modulators.In this study,we designed a series of fluorescent nonapeptide probes derived from substrates of SIRTI-SIRT3.Fluorescence increment of these probes is based on SIRT-mediated removal of the acyl side chain with fluorophore,which makes this system free of lysine-recognizing protease.Comparing the reaction of these fluorescent nonapeptide substrates with SIRT1-SIRT3 and SIRT6,it was confirmed that this assessment system was the most suitable for SIRT2activity detection.Thus,SIRT2 was used to modify substrates by truncating the amino acids or lysine side chain of nonapeptide.Finally,two specific and efficient fluorescent probes for SIRT2,ne-D9 and ne-K4a,were developed.Evaluation of the results revealed that ne-K4a based assay was more suitable for modulators screening in vitro,while the other specific substrate ne-D9 was stable in cell lysate and could detect the activity of SIRT2 in the same.In summary,this study presents a novel strategy for detecting SIRT2 activity in vitro and in cell lysate.

Numerical study on three-dimensional CJ detonation waves interacting with isotropic turbulence

The three-dimensional structures of a cellular detonation wave interacting with different turbulent flows were investigated using a one-step irreversible Arrhenius kinetics model. High-resolution bandwidth-optimized WENO scheme of spatial discretization and total variation diminishing temporal integration are used to solve the three dimensional chemically reactive Navier-Stokes equations. The turbulent vertical and entropic forcing effects on the three dimensional detonation wave structures and dynam- ics are analyzed, as well as the detonation effects on tur- bulent vortex structures. It has been found that the turbulence field imposed has created small scale wrinkles embedded in the detonation front, apart from the large scale features of detonation without turbulence. The deto- nation propagating velocity over the leading shock front varies from 0.8 to 1.6 times of CJ velocity and its proba- bility density function （pdf） skews towards sub-CJ velocity and peaks at about 0.9. The recorded detonation velocity always preferentially decays with time, with very rapid accelerations through triple point interactions. Its pdf also skews to sub-CJ velocity, while its overall shape agrees well with W3. The reaction zone is greatly influenced by the vortex, much more irregular and elongated for the turbulent cases. Distributed burning pockets are more likely to be found there. The turbulent kinetic energy is amplified across the detonation, and periodically oscillates downstream the detonation. The off-diagonal components of Reynolds stress also show a rapid rise across the deto- nation and present to be non-zero downstream of detona- tion. Vortex structures are compound results of the convected vortex and the generated vortex by the collision of triple points. The convection term and baroclinic gen- eration term in the transport equation of enstrophy are compared in detail.