Comparison of visual and topographic outcomes of deep-anterior lamellar keratoplasty and penetrating keratoplasty in keratoconus

AIM：To compare visual,surgical and topographic outcomes of deep anterior lamellar keratoplasty（DALK）and penetrating keratoplasty（PK）for keratoconus（KC）.METHODS：In this multicenter,prospective,randomized clinical trial 76 eyes of 71 KC patients operated between January 2011 and July 2014 in 2 tertiary referral hospitals were included. Consecutive patients were alternately selected to receive one of the two surgical methods. Thirty eight eyes underwent DALK with the big-bubble technique and 38 eyes underwent PK.RESULTS：Mean best spectacle corrected visual acuity（BSCVA）at the first postoperative week（P=0.012）and the first postoperative month（P〈0.001）was statistically significantly higher in DALK group. The mean BSCVA at12 mo was not significantly different for DALK（0.30±1.99 log MAR）versus PK（0.40±0.33 log MAR）（P=0.104）. The76.3% of the eyes had a BSCVA over 0.5 in DALK and 47.4%in PK group（P=0.009）. The 7.9% of the eyes had a BSCVA of 1.0 in DALK and 5.3% in PK group（P=0.644）. Mean spherical equivalent was-2.94 D in DALK and-3.09 D in PK group.Mean topographic astigmatism was 4.62 D and 4.18 D respectively. Regular topographic patterns were observed in 31（81.6%）of DALK and 29（76.3%）of PK（P=0.574）. The most frequent topographic pattern was oblate asymmetric bow tie,seen in 39.5% in DALK and 23.7% in PK. CONCLUSION：Big bubble DALK provides an earlier visual improvement compare to PK. However,visual and topographic outcomes are similar to those in PK at 1y. Postoperative complications including rejection and intraocular pressure elevation are more frequent in PK. DALK is a safer alternative to PK for KC. However,intraoperativeperforation of the Descemet＇s membrane is a significant complication.

Numerical simulation of temperature field in deep penetration laser welding of 5A06 aluminum cylinder

Deep penetration laser welding temperature field of 5A06 aluminum alloy canister structure was simulated using the surface-body combination heat source model by ANSYS, which was made up of Gauss surface heat source model and Gauss revolved body heat source model. Convection, radiation and conduction were all con,sidereal during the simulation process. The thermal cycle curves of the points both on the shell outer surface and in the seam thickness direction were calculated. Simulated results agreed well with the experiment results. It concluded that the surface-body combination heat source model was fit for the temperature field simulation of deep penetration laser welding of the aluminum alloy canister structure. This method was proved to be an efficient way to predict the shape and dimension of welded joint for deep penetration laser welding of the aluminum alloy canister structure.

Critical power of keyhole formation in CW Nd:YAG laser deep penetration welding

The energy model was founded to calculate the critical power of keyhole formation by using the limit principle in CW （ continuous wave ） Nd： YAG laser deep penetration welding process. The model was validated by experiments. The results show that ＇.there are two errors between the calculated critical power of keyhole formation and that of experiments ： one is that the calculated results is less than those of experiments, which is caused by not considering the energy loss by heat conduction in the model of keyhole formation. The other is that there is 0. 9 mm error between the axis of the calculated curve of critical power with location of laser focus and that of experimental curve, which is induced by the excursion of laser focus in laser deep penetration welding. At last, the two errors were revised according to the analyses of the errors.

Relation between welding parameter and acoustic emission information during laser deep penetration welding

In laser non penetration deep penetration welding process, welding material will vaporize, metal vapor and ambient gas will produce a higher degree ionization, which forms plasma of high concentration. In the case of forming a small hole, plasma will eject from the hole, and form acoustic emission (AE) signals. Because AE information has many advantages such as non contact measuring, fast response, and high ratio of signal to noise, it can be used as a monitor variable for in process control. By studying AE information, information of welding pool and small hole can be obtained. According to characteristic of AE information, this paper reveals the correlation between welding parameters and AE signals, and provides a good base for further quality control.

Numerical Simulation of Installation Process and Uplift Resistance for An Integrated Suction Foundation in Deep Ocean

A concept design, named integrated suction foundation, is proposed for a tension leg platform（TLP） in deep ocean. The most important improvement in comparing with the traditional one is that a pressure-resistant storage module is designed. It utilizes the high hydrostatic pressure in deep ocean to drive water into the module to generate negative pressure for bucket suction. This work aims to further approve the feasibility of the concept design in the aspect of penetration installation and the uplift force in-place. Seepage is generated during suction penetration, and can have both positive and negative effects on penetration process. To study the effect of seepage on the penetration process of the integrated suction foundation, finite element analysis（FEA） is carried out in this work. In particular, an improved methodology to calculate the penetration resistance is proposed for the integrated suction foundation with respect to the reduction factor of penetration resistance. The maximum allowable negative pressure during suction penetration is calculated with the critical hydraulic gradient method through FEA. The simulation results of the penetration process show that the integrated suction foundation can be installed safely. Moreover, the uplift resistance of the integrated suction foundation is calculated and the feasibility of the integrated suction foundation working on-site is verified. In all, the analysis in this work further approves the feasibility of the integrated suction foundation for TLPs in deep ocean applications.

Light-activated arginine-rich peptide-modified nanoparticles for deep-penetrating chemo-photo-immunotherapy of solid tumor

Poor permeation of drugs and“immune-cold”tumor microenvironment in solid tumors are the two major challenges which lead to the inefficient therapeutic efficacy for cancer treatment.Here,light-activated penetrable nanoparticles(PEGVAL&DOX&ICG@RNPs)for co-delivery of the chemotherapeutic drug doxorubicin(DOX),the photosensitizer agent indocyanine green(ICG),and the angiotensin II receptor blockers valsartan(VAL)were developed to achieve deep drug penetration and synergistic photo-chemo-immunotherapy of solid tumor.Studies showed that under the first-wave of laser irradiation,the polyethylene glycol(PEG)hydrophilic layer as an“inert”surface could detach from the nanoparticles,release VAL and expose the arginine-rich peptide modified-cores that can facilitate deep drug penetration via a transcytosis pathway.When exposed to the second-wave of laser irradiation,the synergistic chemo-photo-immunotherapy can be achieved.As expected,in 4T1 tumorbearing mice,PEG-VAL&DOX&ICG@RNPs treatment could effectively inhibit the growth of tumors,down-regulateα-smooth muscle actin expression level of cancer-associated fibroblasts cells in tumors,induce dendritic cells(DCs)maturation,and promote intratumoral infiltration of cytotoxic T lymphocytes.Moreover,combination therapy by PEG-VAL&DOX&ICG@RNPs and anti-PD-1 monoclonal antibody can elicit memory T cell response for preventing tumor recurrence and metastasis in vivo.This work provides a promising delivery strategy to overcome the current limitations of nanomedicine for achieving more effective therapeutic index of“immune-cold”solid tumor treatment.

RBC Membrane Camouflaged Semiconducting Polymer Nanoparticles for Near-Infrared Photoacoustic Imaging and Photothermal Therapy

Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.

Welding residual stresses analysis of aluminum alloy cylinder

The laser welding residual stresses in an aluminum alloy thick-wall cylinder is investigated by means of nonlinear finite element method. The article has simulated the residual stresses distribution of the longitudinal weld. The result shows that the temperature is high and temperature gradients are large in the very narrow zone under the laser beam. And the axial residual stress shows the alternate tensile stress and compressive stress. Also the axial residual stress is tensile stress along weld line and the stress peak value appears in the middle of the welded seam. What is more, it is symmetric distribution in the distance from the beginning and the last step welding 20 mm. Good agreements are found between calculated results and measured results indicating the validity of the assumptions made for the development of the model.

Near-infrared-II deep tissue fluorescence microscopy and application

Fluorescence imaging has become an essential tool in biomedical research.However,non-invasive deep-tissue threedimensional optical in vivo imaging with the high spatiotemporal resolution is challenging due to the interaction between photons and tissues.Beam shaping has been used to tailor microscopy techniques to enhance microscope performance.The nearinfrared window(NIR)between 700 and 1,700 nm,generally emphasized as the NIR-II(1,000–1,700 nm)window,has been developed into a promising bio-optical solution chosen as the lower interaction effect in this spectrum,showing potential in basic biological research and clinical application.In this review,we summarize the existing methods to increase penetration depth and extensively describe biological microscopy techniques,NIR-II spectral windows,and fluorophores.Strategies to improve bioimaging performance and NIR-II imaging applications are introduced.Based on the current research achievements,we elucidate the main challenges and provide some recommendations and prospects for deep tissue penetration fluorescence for future biomedical applications.

Welding mode transition and process stability in high power laser welding

For high-power CO2 laser welding, besides two well known stable welding processes, i.e. stable deep penetration welding (DPW) and stable heat conduction welding (HCW), the authors have found the third welding process, i.e. unstable-mode welding (UMW) under the certain condition. UMW has its basic feature that the two welding modes (DPW and HCW) appear intermittently, with jumping of penetration depth and weld width between large and small levels. In this paper, effects of welding parameters (focal position, laser power and traveling speed) on laser welding mode and weld appearance have been comprehensively studied. Double-U curves of laser welding mode transition have been obtained, which indicate the ranges of the three mentioned welding processes. This work affords science foundation for selecting the welding process parameters correctly and obtaining stable laser welding.

Metalloprotein-inspired supramolecular photodynamic nanodrugs by multicomponent coordination for deep penetration and enhanced biofilm eradication

Bacterial infections exacerbate the formation of bacterial biofilms,leading to resistance to traditional drugs,persistent infection,and even threatening patient’s life.Efficient antimicrobial materials against drug-resistant bacterial biofilms are highly desired.In this study,a photodynamic nanodrug with bacterial targeting was constructed by cooperative coordination of zinc ion with an antimicrobial peptide with hydrophobic tripeptides on the side chains and the photosensitizer chlorin e6.The supramolecular nanodrug with a uniform spherical structure possessed high photosensitizer loading capacity and enhanced photodynamic efficacy,which could deep penetrate and eradicate methicillin-resistant Staphylococcus aureus(MRSA)biofilms upon 655 nm laser irradiation.Furthermore,in vivo experiments verified the efficient elimination of MRSA biofilms on implanted catheters.This study provides a novel strategy to fabricate metalloprotein-inspired supramolecular photodynamic nanodrugs against drugresistant bacterial biofilms-associated infections in vivo.

Chemical-NIR dual-powered CuS/Pt nanomotors for tumor hypoxia modulation,deep tumor penetration and augmented synergistic phototherapy

The complex tumor microenvironment(TME)with the characteristics of severe hypoxia,enriched hydro-gen peroxide(H_(2)O_(2))and dense nature significantly restricted the therapeutic efficacy of nanomedicine in cancer treatment.Synthetic micro/nanomotors have shown multiple versatility in modulating the abnor-mal TME and overcoming the limited penetration in solid tumor.Herein,we constructed a chemical-NIR dual-propelled nanomotor based on CuS/Pt Janus nanoparticles with IR820 encapsulation for hypoxia alle-viation,deep tumor penetration and augmented synergistic photodynamic(PDT)and photothermal ther-apy(PTT).The deposited Pt effectively catalyzed tumor endogenous H_(2)O_(2) into oxygen,which extremely relieved the tumor hypoxia state and allowed the chemical propulsion of nanomotors.Under NIR irra-diation,the Janus nanomotors exhibited more obvious movement via efficient photothermal conversion.Such autonomous motion significantly improved the tumoral accumulation of nanomotors and facilitated much deeper penetration inside tumor in vivo.In addition,enriched oxygen also promoted the genera-tion of reactive oxygen species(ROS)for augment of PDT,which achieved satisfied antitumor effect in combination with the PTT treatment.Therefore,this strategy based on CuS/Pt Janus nanomotors would provide an innovative dimension for considerable applications in effective cancer management.

Nanomedicine Disrupts Stromal Barriers to Augment Drug Penetration for Improved Cancer Therapy

Tumor stroma composing diverse extracellular matrixes(ECM)and stromal cells shapes a condensed physical barrier,which severely hampers the efficient accessibility of nanomedicine to tumor cells,especially these deep-seated in the core of tumor.Such barrier significantly compromises the antitumor effects of drug-loaded nanomedicine,revealing the remarkable importance of disrupting stromal barrier for improved tumor therapy with deep penetration ability.To achieve this goal,various nanoparticle-based strategies have been developed,including direct depleting ECM components via delivering anti-fibrotic agents or targeting stromal cells to suppress ECM expression,dynamic regulation of nanoparticles’physicochemical properties(i.e.,size,surface charge,and morphology),mechanical force-driven deep penetration,natural/biomimetic self-driven nanomedicine,and transcytosis-inducing nanomedicine.All these nanostrategies were systemically summarized in this review,and the design principles for obtaining admirable nanomedicine were included.With the rapid development of nanotechnology,elaborate design of multifunctional nanomedicine provides new opportunities for overcoming the critical stromal barriers to maximize the therapeutic index of various therapies,such as chemotherapy,photodynamic therapy,and immunotherapy.

Thiol-mediated transportation pathway:an approach for improving tumor penetration of nanomedicines in vivo

Abnormal tumor microenvironment imposes barriers to tumor penetration of nanomedicine,which remains a major challenge for effective anti-tumor.Herein,we present disulfide-based nanoparticles that actively penetrate deep tumors in vivo through a thiol-mediated transportation pathway.To achieve active tumor accumulation in vivo,disulfide-based nanoparticles are modified with folic acid units(FA-DBNPs).It is gratifying that FA-DBNPs still enter cells via the thiol-mediated pathway,which facilitates transcellular transportation and tumor penetration both in vitro and in vivo.Besides,FA-DBNPs exhibit GSH concentration-dependent depolymerization characterization,indicating that the GSH level in tumor tissues regulates the penetration depth of FA-DBNPs.Benefiting from these advantages,FA-DBNPs showed potent anti-tumor activity in mouse models,leading to the significant regression of tumors.The current study lays a foundation that thiol-mediated transportation is a promising approach in nanomedicine design for solid tumor therapy.

Construction of a 980 nm laser-activated Pt(Ⅱ)metallacycle nanosystem for efficient and safe photo-induced bacteria sterilization

Although metal-based chemical agents have demonstrated promising bacteriostatic effects in phototherapy,their short excitation/emission wavelengths and inadequate phototherapy efficiencies make their application in vivo difficult.We therefore synthesized a novel Pt(Ⅱ)metallacycle(Pt1110)that can be activated with a 980 nm laser for photodiagnosis/treatment in deep tissue.We found that Pt1110 significantly improved photothermal conversion(95%improvement)and ^(1)O_(2) generation(ΦΔ75%increase)compared to the ligand itself 1 and was well capable of light-induced sterilization under safe laser irradiation(0.72 W/cm^(2)).In addition,Pt1110 has little to no toxicity to cells.After incorporated into liposome,Pt1110 NPs was effective in wound healing in infection and keratitis models upon laser irradiation,which was accurately observed by NIR-Ⅱfluorescence imaging.This novel metal-coordinated supramolecular material has a potential to become a universal platform for phototherapy in deep tissue.

Reversing the PAI-1-induced fibrotic immune exclusion of solid tumor by multivalent CXCR4 antagonistic nano-permeator

Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors.Although degradation of fiber is a promising strategy,its application was still bottlenecked by the side effects of causing metastasis,resulting in the failure of immunotherapy.Here,we developed an antimetastatic polymer(HPA)for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator.Nano-permeator shrank after protonation and deeply penetrated into the tumor core to down-regulate the expression of PAI-1 for antifibrosis,and further promoted the sustained infiltration and activation of T cells for killing tumor cells.Moreover,metastasis after fiber elimination was prevented by multivalent CXCR4 antagonistic HPA to reduce the attraction of CXCL12 secreted by distant organs.The administration of stroma-alleviated immunotherapy increased the infiltration of CD8+T cells to 52.5%in tumor tissues,inhibiting nearly 90%metastasis by HPA in distant organs.The nano-permeator reveals the mechanism and correlation between antifibrosis and antimetastasis and was believed to be the optimizing immunotherapy for solid fibrotic tumors.

Improved algorithms and coupled neutron-photon transport for auto-importance sampling method

The Auto-Importance Sampling（AIS） method is a Monte Carlo variance reduction technique proposed for deep penetration problems, which can significantly improve computational efficiency without pre-calculations for importance distribution. However, the AIS method is only validated with several simple examples, and cannot be used for coupled neutron-photon transport. This paper presents improved algorithms for the AIS method, including particle transport, fictitious particle creation and adjustment, fictitious surface geometry, random number allocation and calculation of the estimated relative error. These improvements allow the AIS method to be applied to complicated deep penetration problems with complex geometry and multiple materials. A Completely coupled Neutron-Photon Auto-Importance Sampling（CNP-AIS） method is proposed to solve the deep penetration problems of coupled neutron-photon transport using the improved algorithms. The NUREG/CR-6115 PWR benchmark was calculated by using the methods of CNP-AIS, geometry splitting with Russian roulette and analog Monte Carlo, respectively. The calculation results of CNP-AIS are in good agreement with those of geometry splitting with Russian roulette and the benchmark solutions. The computational efficiency of CNP-AIS for both neutron and photon is much better than that of geometry splitting with Russian roulette in most cases, and increased by several orders of magnitude compared with that of the analog Monte Carlo.

Cooperative coordination-mediated multi-component self-assembly of“all-in-one”nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation,high drug-loading efficiency,and excellent therapeutic efficacy.Herein,MnAs-ICG nanospike was generated by self-assembly of indocyanine green(ICG),manganese ions(Mn^(2+)),and arsenate(AsO_(4)^(3−))based on electrostatic and coordination interactions,effectively integrating the bimodal imaging ability of magnetic resonance imaging(MRI)and fluorescence(FL)imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an“all-in-one”theranostic nano-platform.The as-prepared MnAs-ICG nanospike had a uniform size,well-defined nanospike morphology,and impressive loading capacities.The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability,enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components.In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect,prolonged blood circulation and increased tumor accumulation compared to their individual components,effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect.Taken together,this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

Similarities in the penetration depth of concrete impacted by rigid projectiles

Similarity can reflect common laws in the mechanism of rigid-body penetration.In this paper,the similarities in rigid-body penetration depth are demonstrated by three non-dimensional but physically meaningful quantities,i.e.,ρkinetic,I∗ln and N′1.These three quantities represent the non-dimensional areal density of projectile kinetic energy,the effect of nose geometry,and the friction at the interactive cross section between projectile and target respectively.It is shown that experimental data of rigid projectile penetration,from shallow to deep penetration,can be uniquely unified by these three similarity quantities and their relationships.Furthermore,for ogival nose projectiles,their penetration capacities are dominated byρkinetic,which is consisted by non-dimensional effective length Leff and non-dimensional quantity Dpn=ρpv20AY which has the same form as Johnson’s damage number.On the sacrifice of minor theoretical accuracy,the non-dimensional penetration depth P/d can be understood as directly controlled by Dpn,enhanced by projectile effective length Leff under a multiplication relation,and optimized by projectile nose geometry in the formation of I∗ln.

Intelligent nanogels with self-adaptive responsiveness for improved tumor drug delivery and augmented chemotherapy

For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid tumors.Here,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs)for enhanced tumor delivery and augmented chemotherapy.CH was first grafted with PPy to form CH-PPy polymers that were used to form CH-PPy NGs through glutaraldehyde cross-linking via a miniemulsion method.The CH-PPy NGs could be finely treated with an alkaline solution to generate ultrafast charge-reversible CH-PPy-OH-4 NGs(R-NGs)with a negative charge at a physiological pH and a positive charge at a slightly acidic pH.The R-NGs display good cytocompatibility,excellent protein resistance,and high doxorubicin(DOX)loading efficiency.Encouragingly,the prepared R-NGs/DOX have prolonged blood circulation time,enhanced tumor accumulation,penetration and tumor cell uptake due to their self-adaptive charge switching to be positively charged,and responsive drug delivery for augmented chemotherapy of ovarian carcinoma in vivo.Notably,the tumor accumulation of R-NGs/DOX(around 4.7%)is much higher than the average tumor accumulation of other nanocarriers(less than 1%)reported elsewhere.The developed self-adaptive PPy-grafted CH NGs represent one of the advanced designs of nanomedicine that could be used for augmented antitumor therapy with low side effects.