Peptide drugs: a new direction in cancer immunotherapy

Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.

Modulated-ISRJ rejection using online dictionary learning for synthetic aperture radar imagery

In electromagnetic countermeasures circumstances,synthetic aperture radar(SAR)imagery usually suffers from severe quality degradation from modulated interrupt sampling repeater jamming(MISRJ),which usually owes considerable coherence with the SAR transmission waveform together with periodical modulation patterns.This paper develops an MISRJ suppression algorithm for SAR imagery with online dictionary learning.In the algorithm,the jamming modulation temporal properties are exploited with extracting and sorting MISRJ slices using fast-time autocorrelation.Online dictionary learning is followed to separate real signals from jamming slices.Under the learned representation,time-varying MISRJs are suppressed effectively.Both simulated and real-measured SAR data are also used to confirm advantages in suppressing time-varying MISRJs over traditional methods.

Boosting the cycling stability of all-solid-state lithium metal batteries through MOF-based polymeric protective layers

Solid-state electrolytes(SSEs)play a pivotal role in advancing next-generation lithium metal battery technology.However,they commonly encounter substantial interfacial resistance and poor stability when interfacing with lithium metal,hindering practical applications.Herein,we introduce a flexible metal-organic framework(MOF:NUS-6)-incorporated polymeric layer,denoted as NP,designed to protect the sodium superionic conductor(NASICON)-type Li_(1.3)Al_(0.3)Ti_(1.7)(PO_(4))_(3)(LATP)electrolyte from Li metal anodes.The NP matrix establishes a soft interface with the LATP surface,effectively reducing voids and gaps that may arise between the LATP electrolyte and Li metal.Moreover,the MOF component in NP enhances ionic conductivity,offers abundant Li^(+)transport sites,and provides hierarchical ion channels,ensuring a homogeneous Li^(+)flow and thus effectively inhibiting Li dendrite formation.Utilizing NP,we fabricate Li symmetrical cells cycled for over 1600 h at 0.2 mA cm^(-2)and all-solid-state LiINP-LATPI LiFePO_(4)batteries,achieving a remarkable 99.3%capacity retention after 200 cycles at 0.2 C.This work outlines a general strategy for designing long-lasting and stable solid-state Li metal batteries.

A study of the effect of local scour on the flow field near the spur dike

The flow field near a spur dike such as down flow and horseshoe vortex system(HVS)are susceptible to the topographic changes in the local scouring process,resulting in variation of the sediment transport with time.In this study,large eddy simulations with fixed-bed at different scouring stages were conducted to investigate the changes in flow field.The results imply that the bed deformation leads to an increase in flow rate per unit area,which represent the capability of sediment transportation by water,in the scour hole.Moreover,the intensity of turbulent kinetic energy and bimodal motion near the sand bed induced by the HVS were also varied.However,the peak moments between the two sediment transport mechanisms were different.Hence,understanding the complex feedback mechanism between topography and flow field is essential for the local scour problem.

Giant Magneto-Optical Effect in van der Waals Room-Temperature Ferromagnet Fe_(3)GaTe_(2)

The discovery of ferromagnetic two-dimensional(2D)van der Waals(vdWs)materials provides an opportunity to explore intriguing physics and to develop innovative spin electronic devices.However,the main challenge for practical applications of vd Ws ferromagnetic crystals lies in the weak intrinsic ferromagnetism and small perpendicular magnetic anisotropy(PMA)above room temperature.Here,we report the intrinsic vd Ws ferromagnetic crystal Fe_(3)GaTe_(2),synthesized by the self-flux method,exhibiting a Curie temperature(TC)of 370 K,a high saturation magnetization of 33.47 emu/g,and a large PMA energy density of approximately 4.17×10^(5)J/m^(3).Furthermore,the magneto-optical effect is systematically investigated in Fe_(3)GaTe_(2).The doubly degenerate E_(2g)(Γ)mode reverses the helicity of incident photons,indicating the existence of pseudoangular-momentum(PAM)and chirality.Meanwhile,the non-degenerate non-chiral A_(1g)(Γ)phonon exhibits a significant magneto-Raman effect under an external out-of-plane magnetic field.These results lay the groundwork for studying phonon chirality and magneto-optical phenomena in 2D magnetic materials,providing the feasibility for further fundamental research and applications in spintronic devices.

Spectral characteristics of laser-plasma instabilities with a broadband laser

Recent experimental progresses regarding broadband laser-plasma instabilities(LPIs)show that a 0.6%laser bandwidth can reduce backscatters of the stimulated Brillouin scattering(SBS)and the stimulated Raman scattering(SRS)at normal incidence[Phys.Rev.Lett.132035102(2024)].In this paper,we present a further discussion of the spectral distributions of the scatters developed by broadband LPIs,in addition to a brief validation of the effectiveness of bandwidth on LPIs mitigation at oblique incidence.SBS backscatter has a small redshift in the broadband case contrary to the blueshift with narrowband laser,which may be explained by the self-cross beam energy transfer between the various frequency components within the bandwidth.SRS backscatter spectrum presents a peak at a longer wavelength in the broadband case compared to the short one in the narrowband case,which is possibly attributed to the mitigation effect of bandwidth on filaments at underdense plasmas.The three-halves harmonic emission(3ω/2)has a one-peak spectral distribution under the broadband condition,which is different from the two-peak distribution under the narrowband condition,and may be related to the spectral mixing of different frequency components within the bandwidth if the main sources of the two are both two-plasmon decays.

Microcavity assisted graphene pressure sensor for single-vessel local blood pressure monitoring

Dynamic monitoring of blood pressure (BP) is beneficial to obtain comprehensive cardiovascular information of patients throughout the day. However, the clinical BP measurement method relies on wearing a bulky cuff, which limits the long-term monitoring and control of BP. In this work, a microcavity assisted graphene pressure sensor (MAGPS) for single-vessel local BP monitoring is designed to replace the cuff. The microcavity structure increases the working range of the sensor by gas pressure buffering. Therefore, the MAGPS achieves a wide linear response of 0–1050 kPa and sensitivity of 15.4 kPa^(−1). The large working range and the microcavity structure enable the sensor to fully meet the requirements of BP detection at the radial artery. A database of 228 BP data (60-s data fragment detected by MAGPS) and 11,804 pulse waves from 9 healthy subjects and 5 hypertensive subjects is built. Finally, the BP was detected and analyzed automatically by combining MAGPS and a two-stage convolutional neural network algorithm. For the BP detection method at local radial artery, the first stage algorithm first determines whether the subject has hypertension by the pulse wave. Then, the second stage algorithm can diagnose systolic and diastolic BP with the accuracy of 93.5% and 97.8% within a 10 mmHg error, respectively. This work demonstrates a new BP detection method based on single vessel, which greatly promotes the efficiency of BP detection.

Unveiling the secrets of gastrointestinal mucous adenocarcinoma survival after surgery with artificial intelligence:A population-based study

BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative survival.AIM To investigate the prognosis of GMA and develop predictive model.METHODS From the Surveillance,Epidemiology,and End Results database,we collected clinical information on patients with GMA.After random sampling,the patients were divided into the discovery(70%of the total,for model training),validation(20%,for model evaluation),and completely blind test cohorts(10%,for further model evaluation).The main assessment metric was the area under the receiver operating characteristic curve(AUC).All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA’s prognosis.RESULTS This model had an AUC of 0.7433[95% confidence intervals(95%CI):0.7424-0.7442]in the discovery cohort,0.7244(GMA:0.7234-0.7254)in the validation cohort,and 0.7388(95%CI:0.7378-0.7398)in the test cohort.We packaged it into Windows software for doctors’use and uploaded it.Mucinous gastric adenocarcinoma had the worst prognosis,and these were protective factors of GMA:Regional nodes examined[hazard ratio(HR):0.98,95%CI:0.97-0.98,P<0.001]and chemotherapy(HR:0.62,95%CI:0.58-0.66,P<0.001).CONCLUSION The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively.Combining surgery,chemotherapy,and adequate lymph node dissection during surgery can improve patient outcomes.

Preliminary Model Study for Forecasting a Hot Weather Process in Guangdong Province Using CMA-TRAMS

In this paper, the CMA-TRAMS tropical high-resolution system was used to forecast a typical hot weather process in Guangdong, China with different horizontal resolutions and surface coverage. The results of resolutions of 0.02° and 0.06° were presented with the same surface coverage of the GlobeLand30 V2020, companies with the results of resolution 0.02° with the USGS global surface coverage. The results showed that, on the overall assessment the 2 km model performed better in forecasting 2 m temperature, while the 6 km model was more accurate in predicting 10 m wind speed. In the evaluation of representative stations, the 2 km model performed better in forecasting 2 m temperature and 2 m relative humidity at the coastal stations, and the 2 km model was also better in forecasting 2 m pressure at the representative stations. However, the 6 km model performed better in forecasting 10 m wind speed at the representative stations. Furthermore, the 2 km model, owing to its higher horizontal resolution, presented a more detailed stratification of various meteorological field maps, allowing for a more pronounced simulation of local meteorological element variations. And the use of the surface coverage data of the GlobeLand30 V2020 improved the forecasting of 2 m temperature, and 10 m wind speed compared to the USGS surface coverage data.

Janus hydrogel/electrospun-membrane dressing enhancing wound healing in rats

Background:Excessive exudate secreted from chronic wounds often leads to overhydration and infection.Although a variety of dressings are currently available in clinical applications,they frequently fail to provide multifunction to promote chronic wound healing.The dressings with a Janus structure,featuring distinct properties on each side,are potential to improve wound healing.Methods:Composite dressings with a Janus structure were fabricated,comprising freeze-dried polycaprolactone(PCL)electrospun membrane and alginate-based hydrogel.The PCL fibrous membrane provided air permeability,while the hydrogel loaded with Deferoxamine,composed of alginate and poly(N-isopropylacrylamide)(PNIPAM),exhibited hygroscopic properties.The inclusion of PNIPAM imparted thermo-responsivity.Results:The hydrogel(thickness of 2.778±0.082 mm)exhibited a robust adhesion to the fiber membrane(thickness of 0.261±0.041 mm).For ANDC(Alginate-PNIPAM hydrogel with Deferoxamine/PCL membrane)samples,the water vapor transmission rate(WVTR)was measured to be 3364.80±23.23 g∙m−2∙day−1 and the swelling ratio at 2 h was determined to be 1179±125%.The thermo-responsivity of ANDC samples manifested in an increased swelling rate,escalating from 797±189%at 37°C to 1132±147%at 4°C.The elastic modulus was assessed for lyophilized and rehydrated ANDC sample.When theωof the rheometer rotor was decreased from 10 rad/s to 0.1 rad/s,the lyophilized dressing exhibited a decrease from 2.65±0.01 MPa to 1.80±0.90 MPa,while the rehydrated dressing demonstrated an increase from 133.65±55.68 Pa to 264.23±141.71 Pa.The pro-healing properties of the dressings were evaluated using full-thickness skin defect model on SD rats,and a circular wound of diameter 10 mm healed completely by day 12.Conclusion:The dressings not only protected the wound and absorbed excess exudate,but also demonstrated nondestructive peelability upon cooling,providing a novel approach for accelerating wound healing and management.

Soft Electronics for Health Monitoring Assisted by Machine Learning

Due to the development of the novel materials,the past two decades have witnessed the rapid advances of soft electronics.The soft electronics have huge potential in the physical sign monitoring and health care.One of the important advantages of soft electronics is forming good interface with skin,which can increase the user scale and improve the signal quality.Therefore,it is easy to build the specific dataset,which is important to improve the performance of machine learning algorithm.At the same time,with the assistance of machine learning algorithm,the soft electronics have become more and more intelligent to realize real-time analysis and diagnosis.The soft electronics and machining learning algorithms complement each other very well.It is indubitable that the soft electronics will bring us to a healthier and more intelligent world in the near future.Therefore,in this review,we will give a careful introduction about the new soft material,physiological signal detected by soft devices,and the soft devices assisted by machine learning algorithm.Some soft materials will be discussed such as two-dimensional material,carbon nanotube,nanowire,nanomesh,and hydrogel.Then,soft sensors will be discussed according to the physiological signal types(pulse,respiration,human motion,intraocular pressure,phonation,etc.).After that,the soft electronics assisted by various algorithms will be reviewed,including some classical algorithms and powerful neural network algorithms.Especially,the soft device assisted by neural network will be introduced carefully.Finally,the outlook,challenge,and conclusion of soft system powered by machine learning algorithm will be discussed.

Hole fertilization in the root zone facilitates maize yield and nitrogen utilization by mitigating potential N loss and improving mineral N accumulation

Reducing environmental impacts and improving N utilization are critical to ensuring food security in China.Although root-zone fertilization has been considered an effective strategy to improve nitrogen use efficiency (NUE),the effect of controlled-release urea (CRU) applied in conjunction with normal urea in this mode is unclear.Therefore,a 3-year field experiment was conducted using a no-N-added as a control and two fertilization modes (FF,furrow fertilization by manual trenching,i.e.,farmer fertilizer practice;HF:root-zone hole fertilization by point broadcast manually) at 210 kg N ha^(–1) (controlled-release:normal fertilizer=5:5),along with a 1-year in-situ microplot experiment.Maize yield,NUE and N loss were investigated under different fertilization modes.The results showed that compared with FF,HF improved the average yield and N recovery efficiency by 8.5 and 22.3%over three years,respectively.HF had a greater potential for application than FF treatment,which led to increases in dry matter accumulation,total N uptake,SPAD value and LAI.In addition,HF remarkably enhanced the accumulation of ^(15)N derived from fertilizer by 17.2%compared with FF,which in turn reduced the potential loss of^(15)N by 43.8%.HF increased the accumulation of N in the tillage layer of soils at harvest for potential use in the subsequent season relative to FF.Hence,HF could match the N requirement of summer maize,sustain yield,improve NUE and reduce environmental N loss simultaneously.Overall,root-zone hole fertilization with blended CRU and normal urea can represent an effective and promising practice to achieve environmental integrity and food security on the North China Plain,which deserves further application and investigation.

OsAMT1.1 Expression by Nitrate-Inducible Promoter of OsNAR2.1 Increases Nitrogen Use Efficiency and Rice Yield

Nitrate(NO_(3)^(-))and ammonium(NH_(4)^(+))are two main inorganic nitrogen(N)sources during crop growth.Here,we enhanced the expression of OsAMT1.1,which encodes a NH_(4)^(+)transporter,using the NO_(3)^(-)-inducible promoter of OsNAR2.1 and an ubiquitin promoter in transgenic rice plants.Under field condition of 120 kg/hm2 N,agronomic N use efficiency,N recovery efficiency and N transport efficiency,and grain yield of the pOsNAR2.1:OsAMT1.1 transgenic lines were increased compared with those of the wild type(WT)and the pUbi:OsAMT1.1 transgenic plants.Under 2.0 mmol/L NO_(3)^(-)+0.5 mmol/L NH_(4)^(+)and 0.5 mmol/L NO_(3)^(-)+2.0 mmol/L NH_(4)^(+)conditions of hydroponic culture,compared with the WT,both biomass and total N content were increased in the pOsNAR2.1:OsAMT1.1 transgenic lines.However,biomass was significantly reduced in pUbi:OsAMT1.1 transgenic plants under 0.5 mmol/L NO_(3)^(-)+2.0 mmol/L NH_(4)^(+)condition.The lines expressing pOsNAR2.1:OsAMT1.1 exhibited increased OsAMT1.1 expression and 15NH_(4)^(+)influx in roots under both 2.0 mmol/L NO_(3)^(-)+0.5 mmol/L NH_(4)^(+)and 0.5 mmol/L NO_(3)^(-)+2.0 mmol/L NH_(4)^(+)conditions.Our study showed that expression of OsAMT1.1 can be promoted when driven by the OsNAR2.1 promoter,especially under high-level nitrate condition,leading to enhancement of NH_(4)^(+)uptake,N use efficiency and grain yield.

Identification of Green-Revertible Yellow 3(GRY3),encoding a 4-hydroxy-3-methylbut-2-enyl diphosphate reductase involved in chlorophyll synthesis under high temperature and high light in rice

Chlorophyll,a green pigment in photosynthetic organisms,is generated by two distinct biochemical pathways,the tetrapyrrole biosynthetic pathway(TBP) and the methylerythritol 4-phosphate(MEP)pathway.MEP is one of the pathways for isoprenoid synthesis in plants,with 4-hydroxy-3-methylbut-2-enyl diphosphate reductase(HDR) catalyzing its last step.In this study,we isolated a greenrevertible yellow leaf mutant gry3 in rice and cloned the GRY3 gene,which encodes a HDR participating in geranylgeranyl diphosphate(GGPP) biosynthesis in chloroplast.A complementation experiment confirmed that a missense mutation(C to T) in the fourth exon of LOC_Os03g52170 causes the gry3 phenotype.Under high temperature and high light,transcript and protein abundances of GRY3 were reduced in the gry3 mutant.Transcriptional expression of chlorophyll biosynthesis,chloroplast development,and genes involved in photosynthesis were also affected.Excessive reactive oxygen species accumulation,cell death,and photosynthetic proteins degradation were occurred in the mutant.The content of GGPP was reduced in gry3 compared with Nipponbare,resulting in a stoichiometric imbalance of tetrapyrrolic chlorophyll precursors.These results shed light on the response of chloroplast biogenesis and maintenance in plants to high-temperature and high-light stress.

Transition from backward to sideward stimulated Raman scattering with broadband lasers in plasmas

Broadband lasers have been proposed as future drivers of inertial confined fusion(ICF)to enhance the laser-target coupling efficiency via the mitigation of various parametric instabilities.The physical mechanisms involved have been explored recently,but are not yet fully understood.Here,stimulated Raman scattering(SRS)as one of the key parametric instabilities is investigated theoretically and numerically for a broadband laser propagating in homogeneous plasma in multidimensional geometry.The linear SRS growth rate is derived as a function of scattering angles for two monochromatic laser beams with a fixed frequency differenceδω.Ifδω/ω_(0)∼1%,withω0 the laser frequency,these two laser beams may be decoupled in stimulating backward SRS while remaining coupled for sideward SRS at the laser intensities typical for ICF.Consequently,side-scattering may dominate over backward SRS for two-color laser light.This finding of SRS transition from backward to sideward SRS is then generalized for a broadband laser with a few-percent bandwidth.Particle-in-cell simulations demonstrate that with increasing laser bandwidth,the sideward SRS gradually becomes dominant over the backward SRS.Since sideward SRS is very efficient in producing harmful hot electrons,attention needs to be paid on this effect if ultra-broadband lasers are considered as next-generation ICF drivers.

Universal,predominant exciton transfer in perovskite nanocrystal solids

Perovskite nanocrystal(PNC)solids are promising materials for optoelectronic applications.Recent studies have shown that exciton diffusion in PNC solids occurs via alternate exciton hopping(EH)and photon recycling(PR).The energy disorder induced by the size distribution is a common factor in PNC solids,and the impact of this energy disorder on the exciton diffusion remains unclear.Here,we investigated the exciton diffusion in CsPbBr3 NC solids with a Gaussian size distribution of 11.2±6.8 nm via steady and time-resolved photoluminescence(PL)spectroscopy with multiple detection bands in transmission mode.Our results indicated that exciton diffusion was controlled by a downhill transfer among the different energy sites through the disordered energy landscape,as confirmed by the accompanying low-temperature PL analysis.A detailed examination revealed that the acceptor distribution in tandem with the reabsorption coefficient determined the contribution of EH and PR to exciton transfer between different energy sites.Consequently,the exciton diffusion mechanism varied in PNC solids of different thicknesses:in a thin solid with a thickness of several hundred nanometers,the exciton transfer was dominated by efficient EH and PR from the high-energy sites to the lower-energy sites;in a few-micrometer-thick solid,transfer from the medium-energy sites toward the lower-energy sites also became prominent and occurred mainly through PR.These findings enhance the understanding of the vital role that the acceptor distribution plays in the exciton diffusion process in PNC solids,providing important insights for optoelectronic applications based on PNC solids.Our work also exploits the use of commonly available tools for in-depth exciton diffusion studies,which reveals the interior diffusion information that is usually hidden in surface sensitive PL imaging methods.

Large Eddy Simulations of Rayleigh-Bénard Convection in a Cubic Cavity

This paper conducts a Large Eddy Simulation (LES) of Rayleigh Bénard convection in a cubic cavity based on the WMLES S-Omega subgrid-scale model. For a cubic cavity with a vertical temperature difference of 6.7°C and 20°C, the velocity pulsation profiles and the mean velocity profiles of the vertical section in the middle of the cubic cavity were simulated, respectively. And they are consistent with the experiment results. Furthermore, the mean velocity field of the vertical cross-section in the middle of the cavity was calculated. Structures of the mean velocity field in the two cases are similar. A counterclockwise large vortex is found to occupy the cavity, and there are two small clockwise vortices in the lower left and upper right corners, and the mean velocity fields at two different temperature differences are consistent with the experimental results. The two-dimensional instantaneous temperature field and mean temperature field with different cross-sections in the z-direction, as well as the three-dimensional instantaneous isothermal surface structure, indicate that the large-scale circulation motion within the cubic cavity is moving diagonally. In addition, the structure of the mean streamline also illustrates this viewpoint. For the reverse vortex formed at two corners in the mean streamline structure, we used the Q criterion to identify and obtain two vortex structures similar to boomerangs. The basic turbulent structure in RB thermal convection includes the rising and falling plumes generated by buoyancy effects.

Conversion of pure Chinese fir plantation to multi-layered mixed plantation enhances the soil aggregate stability by regulating microbial communities in subtropical China

Background:Soil aggregates are the basic units of soil structure,and their stability is a key indicator of soil quality and capacity to support ecosystem functions.The impacts of various environmental factors on soil aggregates have been widely studied.However,there remains elusive knowledge on the synergistic effects of changing forest stand structure on soil aggregate stability(SAS),particularly in subtropical China where soil erosion remains a critical issue.Methods:We investigated variations in the components of soil humus(HS),including humic acids(HAs),fulvic acids(FAs),and humins(HMs),under pure Chinese fir(Cunninghamia lanceolata)plantation(PP)and multilayered mixed plantation(MP)comprising C.lanceolata,Castanopsis hystrix,and Michelia hedyosperma.The state of soil aggregate stability,was determined by three separate methods,i.e.,dry-sieving,wet-sieving,and the Le Bissonnais.High-throughput sequencing was used to determine the diversity and composition of microbial communities under PP and MP.We then built partial least squares path models(PLS-PM)for assessing the responses of SAS to the variations in soil microorganisms and HS components.Results:The MP stands had significantly greater SAS(P<0.05),higher content of HAs and more rapid organic matter humification within aggregates,than the PP stands.High-throughput sequencing confirmed that the Pielou andα-diversity index values(Chao1 and Shannon)for fungi were all significantly higher under MP than under PP,while no marked difference was found in bacterialα-diversity between the two plantation types.Moreover,there were markedly greater abundance of three bacterial phyla(Verrucomicrobia,Chloroflexi,and Gemmatimonadetes)and three fungal phyla(Ascomycota,Kickxellomycota,and Glomeromycota),and significantly less abundance of two bacterial phyla(Planctomycetes and Firmicutes)and four fungal phyla(Basidiomycota,Mortierellomycota,Mucoromycota,and Rozellomycota)under MP than under PP.The Chloroflexi and Ascomycota phyla appeared to be the primary drivers of soil aggregate distribution.Our findings revealed that the promotion of SAS under MP was mainly driven by increased soil organic matter(SOM)content,which altered bacterial communities and enhanced fungal diversity,thereby increasing HAs content and the rate of organic matter humification.Conclusions:Considering the combined effects of enhanced soil quality,productivity,and relevant economic costs,introducing broadleaved tree species into Chinese fir plantations can be an effective strategy for stabilizing soil structure against erosion in subtropical China.Our study elucidated the controls on variations of SAS in Chinese fir-dominated plantations and demonstrated the benefit of converting pure Chinese fir plantation to multi-layered mixed plantations in increasing soil structural stability and improving site quality.

A MXene-Based Bionic Cascaded-Enzyme Nanoreactor for Tumor Phototherapy/Enzyme Dynamic Therapy and Hypoxia-Activated Chemotherapy

The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on Ti_(3)C_(2)nanosheets for combined tumor enzyme dynamic therapy(EDT),phototherapy and deoxygenation-activated chemotherapy.Briefly,glucose oxidase(GOX)and chloroperoxidase(CPO)were chemically conjugated onto Ti_(3)C_(2)nanosheets,where the deoxygenation-activated drug tirapazamine(TPZ)was also loaded,and the Ti_(3)C_(2)-GOX-CPO/TPZ(TGCT)was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47(m_eTGCT).Due to biomimetic membrane camouflage and CD47 overexpression,m_eTGCT exhibited superior immune escape and homologous targeting capacities,which could effectively enhance the tumor preferential targeting and internalization.Once internalized into tumor cells,the cascade reaction of GOX and CPO could generate HClO for efficient EDT.Simultaneously,additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen(~1O_(2)).Furthermore,local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy.Consequently,m_eTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy,EDT and chemotherapy for efficient tumor inhibition.This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy.

Combination therapy of hydrogel and stem cells for diabetic wound healing

Diabetic wounds(DWs)are a common complication of diabetes mellitus;DWs have a low cure rate and likely recurrence,thus affecting the quality of patients’lives.As traditional therapy cannot effectively improve DW closure,DW has become a severe clinical medical problem worldwide.Unlike routine wound healing,DW is difficult to heal because of its chronically arrested inflammatory phase.Although mesenchymal stem cells and their secreted cytokines can alleviate oxidative stress and stimulate angiogenesis in wounds,thereby promoting wound healing,the biological activity of mesenchymal stem cells is compromised by direct injection,which hinders their therapeutic effect.Hydrogels form a three-dimensional network that mimics the extracellular matrix,which can provide shelter for stem cells in the inflammatory microenvironment with reactive oxygen species in DW,and maintains the survival and viability of stem cells.This review summarizes the mechanisms and applications of stem cells and hydrogels in treating DW;additionally,it focuses on the different applications of therapy combining hydrogel and stem cells for DW treatment.