Aerosol deposition technology and its applications in batteries

Aerosol deposition(AD)method is a kind of additive manufacturing technology for fabricating dense films such as metals and ceramics at room temperature.It resolves the challenge of integrating ceramic films onto temperaturesensitive substrates,including metals,glasses,and polymers.It should be emphasized that the AD is a spray coating technology that uses powder without thermal assistance to generate films with high density.Compared to the traditional sputter-based approach,the AD shows several advantages in efficiency,convenience,better interfacial bonding and so on.Therefore,it opens some possibilities to the field of batteries,especially all-solidstate batteries(ASSBs)and draws much attention not only for research but also for large scale applications.The purpose of this work is to provide a critical review on the science and technology of AD as well as its applications in the field of batteries.The process,mechanism and effective parameters of AD,and recent developments in AD applications in the field of batteries will be systematically reviewed so that a trend for AD will be finally provided.

Low-energy spin dynamics in a Kitaev material Na_(3)Ni_(2)BiO_(6) investigated by nuclear magnetic resonance

We perform ^(23)Na nuclear magnetic resonance(NMR) and magnetization measurements on an S=1,quasi-2D honeycomb lattice antiferromagnet Na_(3)Ni_(2)BiO_(6).A large positive Curie-Weiss constant of 22.9 K is observed.The NMR spectra at low fields are consistent with a zigzag magnetic order,indicating a large easy-axis anisotropy.With the field applied along the c*axis,the NMR spectra confirm the existence of a 1/3-magnetization plateau phase between 5.1 T and 7.1 T.The transition from the zigzag order to the 1/3-magnetization plateau phase is also found to be a first-order type.A monotonic decrease of the spin gap is revealed in the 1/3-magnetization plateau phase,which reaches zero at a quantum critical field H_(C)≈8.35 T before entering the fully polarized phase.These data suggest the existence of exchange frustration in the system along with strong ferromagnetic interactions,hosting the possibility for Kitaev physics.Besides,well below the ordered phase,the 1/T_(1) at high fields shows either a level off or an enhancement upon cooling below 3 K,which suggests the existence of low-energy fluctuations.

转录组分析在血液样本时间和供体特征刻画中的应用研究

案件现场生物物证信息深度挖掘与刻画,可以为案件侦查、涉案人员查找提供丰富可靠线索,是当前法医DNA检验的有效补充,也是国内外法庭科学的研究热点之一。本研究以血液样本为研究对象,证实了0~168天内离体血液样本转录组变化的时间相关性,并建立随机森林模型实现不同离体时间血液样本分类。同时,进一步证实相同离体时间段内,不同吸烟习惯和不同性别供体来源的血液样本转录本具有显著差异,HLA-DRB1、HLA-DQB1和HLA-DQA2可以作为供体吸烟习惯判别标志,Y染色体非重组区(non-recombining Y,NRY)的转录本RPS4Y1和EIF1AY可以作为供体性别特征判别标志。本研究为法庭科学领域建立基于转录组分析的血液样本遗留时间和供体特征刻画方法提供了理论基础和实验依据。

Thin NASICON Electrolyte to Realize High Energy Density Solid-State Sodium Metal Battery

The solid-state electrolyte in a solid-state battery acts as an electrons'barrier and an ions'bridge between the two electrodes.As solid-state electrolyte does not store the mobile ions,it is necessary to achieve a thin solid-state electrolyte to reduce the internal resistance and enhance the energy density.In this work,a thin NASICON solid-state electrolyte,with a stoichiometry of Na_(3)Zr_(2)Si_(2)PO_(12),is fabricated by the tape-casting method and its thickness can be easily controlled by the gap between substrate and scraper.The areal-specific resistance and the flexural strength increase with the electrolyte thickness.A solid-state sodium metal battery with 86 pm thick Na_(3)Zr_(2)Si_(2)PO_(12)exhibits a reversible specific capacity of 73-78 mAh g^(-1)with a redox potential of 3.4 V at 0.2 C.This work presents the importance of electrolyte thickness to reduce internal resistance and achieve a high energy density for sodium batteries.

Research Review of Principles and Methods for Ultrasonic Measurement of Axial Stress in Bolts

Bolts are important fasteners indispensable in the manufacturing field for their advantages, which include convenient assembly and disassembly, easy maintenance, refastenability to prevent looseness, and the avoidance of a phase change in the connected material composition. The precise control of the tightening force in bolts is closely related to the safety and reliability of the connected equipment or structure. Although there are many methods for estimating the tightening force applied to a bolt during assembly, poor accuracy in controlling the preload during the tightening process and a lack of monitoring to determine the residual axial force in service remain issues in evaluating the safety of bolted assemblies. As a nondestructive testing technology, ultrasonic measurement can be applied to successfully address these issues. In order to help researchers understand the theoretical basis and technological development in this field and to equip them to conduct further in-depth research, in this review, the basic knowledge describing the state of stress and deformation of bolts, as well as conventional testing methods are summarized and analyzed. Then, through a review of recent research of the ultrasonic measurement of the axial stress in bolts, the influence of the e ective stressed length and temperature are analyzed and proposed methods of calibration and compensation are reviewed. In order to avoid coupling errors caused by traditional piezoelectric transducers, two newly proposed ultrasonic coupling technologies, the electromagnetic acoustic transducer(EMAT) and the permanent mounted transducer system(PMTS), are reviewed. Finally, the new direction of research of the detection of residual axial stress in in-service bolts that have been assembled to yield is discussed.

NIR-triggered thermo-responsive biodegradable hydrogel with combination of photothermal and thermodynamic therapy for hypoxic tumor

Hypoxia is a typical feature of solid tumors,which highly limits the application of the oxygen-dependent therapy.Also,the dense and hyperbaric tumor tissues impede the penetration of nanoparticles into the deep tumor.Thereby,we designed a novel localized injectable hydrogel combining the photothermal therapy(PTT)and the thermodynamic therapy(TDT),which is based on the generation of free radicals even in the absence of oxygen for hypoxic tumor therapy.In our study,gold nanorods(Au NRs)and 2,2-Azobis[2-(2-imidazalin-2-yl)propane]dihydrochlaride(AIPH)were incorporated into the hydrogel networks,which were formed by the copolymerization of hydrophobic N-isopropyl acrylamide(NIPAM)and hydrophilic glycidyl methacrylate modified hyaluronic acid(HAGMA)to fabricate an injectable and near-infrared(NIR)responsive hydrogel.The crosslinked in situ forming hydrogel could not only realize PTT upon the NIR laser irradiation,but also generate free radicals even in hypoxic condition.Meanwhile the shrink of hydrogels upon thermal could accelerate the generation of free radicals to further damage the tumors,achieving the controlled drug release on demand.The designed hydrogel with a sufficient loading capacity,excellent biocompatibility and negligible systemic toxicity could serve as a long-acting implant for NIR-triggered thermo-responsive free radical generation.The in vitro cytotoxicity result and the in vivo antitumor activity illustrated the excellent therapeutic effect of hydrogels even in the absence of oxygen.Therefore,this innovative oxygen-independent platform combining the antitumor effects of PTT and TDT would bring a new insight into hypoxic tumor therapy by the application of alkyl free radical.

A high-quality reference genome of wild Cannabis sativa

Cannabis sativa is a well-known plant species that has great economic and ecological significance.An incomplete genome of cloned C.sativa was obtained by using SOAPdenovo software in 2011.To further explore the utilization of this plant resource,we generated an updated draft genome sequence for wild-type varieties of C.sativa in China using PacBio single-molecule sequencing and Hi-C technology.Our assembled genome is approximately 808 Mb,with scaffold and contig N50 sizes of 83.00 Mb and 513.57 kb,respectively.Repetitive elements account for 74.75%of the genome.A total of 38,828 protein-coding genes were annotated,98.20%of which were functionally annotated.We provide the first comprehensive de novo genome of wild-type varieties of C.sativa distributed in Tibet,China.Due to long-term growth in the wild environment,these varieties exhibit higher heterozygosity and contain more genetic information.This genetic resource is of great value for future investigations of cannabinoid metabolic pathways and will aid in promoting the commercial production of C.sativa and the effective utilization of cannabinoids.The assembled genome is also a valuable resource for intensively and effectively investigating the C.sativa genome further in the future.

Idiopathic Orbital Inflammation Associated with Panuveitis in an Adult and a Review of the Literature

Purpose:To report an unusual case of idiopathic orbital inflammation associated with panuveitis. Case report:We report a case of a 47-year-old female with a history of uveitis who presented with abrupt and painful prop tosis with complete vision loss unresponsive to antibiotic therapy.B-scan ultrasonography and magnetic resonance imaging both showed retinal detachment and an orbital space-occupying mass. The patient underwent orbitotomy and the diagnosis of idiopathic orbital inflammation was confirmed by histopathology. Anterior uveitis is rarely seen in idiopathic orbital inflammation in adults. We report for the first time an unusual case of idiopathic orbital inflammation associated with panuveitis. Conclusion:Inflammation involving both the eye and the orbit is rarely seen in adults. Idiopathic orbital inflammation and panuveitis may share a similar mechanism in this case. (Eye Science 2013; 28:40-43)

Moving target defense of routing randomization with deep reinforcement learning against eavesdropping attack

Eavesdropping attacks have become one of the most common attacks on networks because of their easy implementation. Eavesdropping attacks not only lead to transmission data leakage but also develop into other more harmful attacks. Routing randomization is a relevant research direction for moving target defense, which has been proven to be an effective method to resist eavesdropping attacks. To counter eavesdropping attacks, in this study, we analyzed the existing routing randomization methods and found that their security and usability need to be further improved. According to the characteristics of eavesdropping attacks, which are “latent and transferable”, a routing randomization defense method based on deep reinforcement learning is proposed. The proposed method realizes routing randomization on packet-level granularity using programmable switches. To improve the security and quality of service of legitimate services in networks, we use the deep deterministic policy gradient to generate random routing schemes with support from powerful network state awareness. In-band network telemetry provides real-time, accurate, and comprehensive network state awareness for the proposed method. Various experiments show that compared with other typical routing randomization defense methods, the proposed method has obvious advantages in security and usability against eavesdropping attacks.

Probiotic Medilac-S^(█) for the induction of clinical remission in a Chinese population with ulcerative colitis: A systematic review and meta-analysis

AIM To assess the effects of probiotic Medilac-S~ as adjunctive therapy for the induction of remission of ulcerative colitis(UC) in a Chinese population through a systematic review and meta-analysis. METHODS A systematic literature search was conducted to find randomized, controlled trials in a Chinese population with at least two study arms-a control arm which receives a conventional, oral aminosalicylate drug, and a treatment arm, which administers the same conventional drug in conjunction with the probiotic Medilac-S~ per os. Both English and Chinese databases were searched, including Pub Med, EMBASE, Google Scholar, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Search, and study data was extracted onto standardized abstraction sheets. Meta-analyses were conducted for primary and secondary outcomes of interest using a fixed or random effects model. The primary outcome was the induction of clinical remission and the secondary outcomes included changes in Sutherland index, endoscopic and histological scores, proportion of reported clinical symptoms and adverse events(AEs). For outcomes with sufficient data, the type of conventional drug therapy was also assessed to determine if the effects of combination therapy with Medilac-S~ was influenced by drug type. All tests were conducted using a type Ⅰ error rate of 0.05 and all confidence intervals(CI) were based on a 95% confidence level. Review protocol was uploaded to PROSPERO(CRD42018085658 upon completion).RESULTS Fifty-three clinical trials with a total of 3984 participants were identified and included in the review. Medilac-S~ adjunctive therapy significantly improved induction of clinical remission(RR = 1.21; 95%CI: 1.18-1.24; P < 0.0001) with the estimated likelihood of effective treatment, on average, 21% higher for those consuming the probiotic. Sutherland index scores showed the control mean was on average 3.10(CI: 2.41-3.78; P = 0.0428) units greater than the treatment mean, thereby demonstrating significant improvement in participants taking the probiotic. Similarly, a significant difference was seen between the overall reduction of endoscopic and histological scores of control and treatment arm participants, with score decreases in the control groups 0.71(CI: 0.3537-1.0742) and 1.1(CI: 0.9189-1.2300) units smaller than treatment group score decreases. The proportion of participants reporting clinical symptoms,(abdominal pain, tenesmus, blood and mucous in stool, and diarrhea) was significantly reduced after combination therapy with Medilac-S~(P < 0.0001) and estimated to be on average 44%(RR = 0.44, CI: 0.32-0.59), 53%(RR = 0.53, CI: 0.38-74), 40%(RR = 0.40, CI: 0.28-0.58) and 47%(RR = 0.47 CI: 0.36-0.42) respectively, of the proportion of individuals reporting the aforementioned symptoms after conventional therapy alone. The risk of AEs was also significantly reduced with adjunctive Medilac-S~ therapy. The proportion of individuals in the treatment groups reporting AEs was an estimated 72% of the proportion of individuals in the control groups reporting AEs(RR = 0.72, CI: 0.55-0.94, P = 0.0175). Upon comparing effect means for different drug types in conjunction with Medilac-S~, evidence of significant variability(P < 0.0001) was observed, and sulfasalazine was found to be the most effective drug in both primary and secondary outcomes. CONCLUSION Evidence suggests Medilac-S~ adjunctive therapy should be considered standard care for UC in a Chinese population because it aids in the induction of clinical remission, improves symptoms of the gastrointestinal tract and reduces risk of AEs.

pH-activatable oxidative stress amplifying dissolving microneedles for combined chemo-photodynamic therapy of melanoma

Photodynamic therapy(PDT)-mediated oxidation treatment is extremely attractive for skin melanoma ablation,but the strong hydrophobicity and poor tumor selectivity of photosensitizers,as well as the oxygen-consuming properties of PDT,leading to unsatisfactory therapeutic outcomes.Herein,a tumor acidic microenvironment activatable dissolving microneedle(DHA@HPFe-MN)was developed to realize controlled drug release and excellent chemo-photodynamic therapy of melanoma via oxidative stress amplification.The versatile DHA@HPFe-MN was fabricated by crosslinking a self-synthesized protoporphyrin(PpIX)-ADH-hyaluronic acid(HA)conjugate HA-ADH-PpIX with“iron reservoir”PA-Fe 3+complex in the needle tip via acylhydrazone bond formation,and dihydroartemisinin(DHA)was concurrently loaded in the hydrogel network.HA-ADH-PpIX with improved water solubility averted undesired aggregation of PpIX to ensure enhanced PDT effect.DHA@HPFe-MN with sharp needle tip,efficient drug loading and excellent mechanical strength could efficiently inserted into skin and reach the melanoma sites,where the acidic pH triggered the degradation of microneedles,enabling Fe-activated and DHA-mediated oxidation treatment,as evidenced by abundant reactive oxygen species(ROS)generation.Moreover,under light irradiation,a combined chemo-photodynamic therapeutic effect was achieved with amplified ROS generation.Importantly,the Fe-catalyzed ROS production of DHA was oxygen-independent,which work in synergy with the oxygen-dependent PDT to effectively destroy tumor cells.This versatile microneedles with excellent biosafety and biodegradability can be customized as a promising localized drug delivery system for combined chemo-photodynamic therapy of melanoma.

“NIR-triggered ROS storage”photodynamic intraocular implant for high-efficient and safe posterior capsular opacification prevention

Posterior capsular opacification(PCO)is the leading cause of vision loss after cataract,mainly caused by the adhesion,proliferation and trans-differentiation of post-operative residual lens epithelial cells(LECs).Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades.Herein,we developed a“NIR-triggered ROS storage”intraocular implant(CTR-Py-Pp IX)based on capsular tension ring(CTR),which is concurrently linked with photosensitizer protophorphyrin IX(Pp IX)and energy storage2-pyridone derivative(Py),to guarantee instantaneous and sustainable ROS generation for LECs killing,aiming to achieve more efficient and safer photodynamic therapy(PDT)to effectively prevent PCO.The silylated Pp IX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-Pp IX.Results demonstrated that CTR-Py-Pp IX had dual functions of PDT and battery,in which Pp IX could generate ROS extracellularly under irradiation,with one part directly inhibiting LECs by lipid peroxidation(LPO)induction of cell membranes.Meanwhile,the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed.Ultimately,the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions,achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility.This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.

Gp130-dependent STAT3 activation in M-CSF-derived macrophages exaggerates tumor progression

Interleukin-6(IL-6)is a common pluripotent cytokine that is highly expressed in the tumor microenvironment.The IL-6/JAK/STAT3 signaling directly promotes tumor progression,severely hampering antitumor immunity.Macrophages,the richest innate immune cells within the tumor microenvironment,manipulate tumor progression via phenotypic plasticity.

Excitation orthogonalized upconversion nanoprobe for instant visual detection of trinitrotoluene

Excitation-emission orthogonalized luminescent upconversion nanoparticles(OUCNPs),which can respond to changes in external stimuli accordingly,show great promise in many intelligent applications.However,the construction of such materials mostly relies on the selective absorption of Nd3+and Yb3+at different wavelengths and the long-range energy migration between the layers,resulting in complex structures and limited orthogonal luminescence intensity.Herein,we developed a relatively simple structure of OUCNPs(β-NaErF4@NaLuF4@NaYF4:20%Yb,2%Er@NaLuF4),where the fluorescence emission switches from red to green when the excitation wavelength is shifted from 808 to 980 nm.This structure exhibits high-quality,independent,and non-interfering orthogonal luminescence properties without Nd3+sensitization and long-range energy migration.As a proof of concept,we demonstrate the application of the designed OUCNPs in anti-counterfeiting.We also prepared OUCNPs@PEI(PEI=polyethylenimine)self-referencing fluorescent probes to enable quantitative analysis of trinitrotoluene(TNT)in solution with a detection limit of 3.04μM.The probes can be made into test strips for portable on-site visual detection of TNT,and can also be used to image latent fingerprints and detect explosive residues in fingerprints simultaneously.The concept proposed in this work can be extended to the visual detection of a larger range of organic and biological molecules,and is highly promising for practical applications.

Fabrication plate-like BaBi_(4)Ti_(4)O_(15) single-crystalline particles by the molten salt synthesis method

Plate-like single-crystalline BaBi_(4)Ti_(4)O_(15) particles were synthesized by the molten salt synthesis(MSS)method.The effects of sintering temperature,holding time,and NaCl-KCl molten salt content on the phase structure and morphology of plate-like BaBi_(4)-Ti_(4)O_(15) particles were investigated.The results show that plate-like BaBi_(4)Ti_(4)O_(15) particles can be synthesized when the sintering temperature is above 800°C.The size of particles increases with increasing sintering temperature and molten salt content.Largely anisotropic plate-like BaBi_(4)Ti_(4)O_(15) particles with diameter≥10μm and thickness of~0.3μm can be obtained under the optimum process parameters.The crystal structure of BaBi_(4)Ti_(4)O_(15) was determined as A21am by TEM,which should be attributed to the Bi3+and Ba2+diffusing into[TiO6]octahedrons.

Fano resonance-enhanced Si/MoS_(2) photodetector

In this work,a Si∕MoS_(2) heterojunction photodetector enhanced by hot electron injection through Fano resonance is developed.By preparing Au oligomers using capillary-assisted particle assembly(CAPA)on the silicon substrate with a nanohole array and covering few-layer MoS_(2) with Au electrodes on top of the oligomer structures,the Fano resonance couples with a Si∕MoS_(2) heterojunction.With on-resonance excitation,Fano resonance generated many hot electrons on the surface of oligomers,and the hot electrons were injected into MoS_(2),providing an increased current in the photodetector under a bias voltage.The photodetectors exhibited a broadband photoresponse ranging from 450 to 1064 nm,and a large responsivity up to 52 A/W at a wavelength of 785 nm under a bias voltage of 3 V.The demonstrated Fano resonance-enhanced Si∕MoS_(2) heterojunction photodetector provides a strategy to improve the photoresponsivity of two-dimensional materials-based photodetectors for optoelectronic applications in the field of visible and near-infrared detection.

Ultra‑Stable Sodium‑Ion Battery Enabled by All‑Solid‑State Ferroelectric‑Engineered Composite Electrolytes

Symmetric Na-ion cells using the NASICON-structured electrodes could simplify the manufacturing process,reduce the cost,facilitate the recycling post-process,and thus attractive in the field of large-scale stationary energy storage.However,the long-term cycling performance of such batteries is usually poor.This investigation reveals the unavoidable side reactions between the NASICON-type Na_(3)V_(2)(PO_(4))_(3)(NVP)anode and the commercial liquid electrolyte,leading to serious capacity fading in the symmetric NVP//NVP cells.To resolve this issue,an all-solid-state composite electrolyte is used to replace the liquid electrolyte so that to overcome the side reaction and achieve high anode/electrolyte interfacial stability.The ferroelectric engineering could further improve the interfacial ion conduction,effectively reducing the electrode/electrolyte interfacial resistances.The NVP//NVP cell using the ferroelectric-engineered composite electrolyte can achieve a capacity retention of 86.4%after 650 cycles.Furthermore,the electrolyte can also be used to match the Prussianblue cathode NaxFeyFe(CN)_(6−z)·nH_(2)O(NFFCN).Outstanding long-term cycling stability has been obtained in the all-solid-state NVP//NFFCN cell over 9000 cycles at a current density of 500 mA g^(-1),with a fading rate as low as 0.005%per cycle.

Self-crosslinkable chitosan-hyaluronic acid dialdehyde nanoparticles for CD44-targeted siRNA delivery to treat bladder cancer

Bladder cancer is one of the concerning malignancies worldwide,which is lacking effective targeted therapy.Gene therapy is a potential approach for bladder cancer treatment.While,a safe and effective targeted gene delivery system is urgently needed for prompting the bladder cancer treatment in vivo.In this study,we confirmed that the bladder cancer had CD44 overexpression and small interfering RNAs(siRNA)with high interfere to Bcl2 oncogene were designed and screened.Then hyaluronic acid dialdehyde(HAD)was prepared in an ethanol-water mixture and covalently conjugated to the chitosan nanoparticles(CS-HAD NPs)to achieve CD44 targeted siRNA delivery.The in vitro and in vivo evaluations indicated that the siRNA-loaded CS-HAD NPs(siRNA@CS-HAD NPs)were approximately 100 nm in size,with improved stability,high siRNA encapsulation efficiency and low cytotoxicity.CS-HAD NPs could target to CD44 receptor and deliver the therapeutic siRNA into T24 bladder cancer cells through a ligand-receptor-mediated targeting mechanism and had a specific accumulation capacity in vivo to interfere the targeted oncogene Bcl2 in bladder cancer.Overall,a CD44 targeted gene delivery system based on natural macromolecules was developed for effective bladder cancer treatment,which could be more conducive to clinical application due to its simple preparation and high biological safety.

A rapid and sensitive UPLC–MS/MS method for quantitative determination of arformoterol in rat plasma, lung and trachea tissues

A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry（UPLC–MS/MS） method was developed and fully validated for determination of arformoterol in rat plasma, lung and trachea tissues. The chromatographic separation was performed on an Agilent XDB C8 column with gradient elution by using acetonitrile and 0.1% formic acid water. The method presented high sensitivity（LLOQ of 1.83 pg/mL for plasma and 3.90 pg/mL for lung and trachea tissue homogenates） and great linearity over the range of 1.83–458 pg/mL for plasma, 13.9–1560 pg/mL for lung and trachea tissue homogenates. No carry over effect and matrix effect were observed. The intra-and inter-day precision/accuracy were within ±15% at three quality control concentration levels. This robust method was successfully applied to the pharmacokinetic, lung and trachea tissue distribution study after inhalation administration of arformoterol tartrate inhalation solution（50 m g/kg）. The in vivo information indicate that arformoterol can be rapidly absorbed into blood through respiratory systems, lung and trachea tissue maintain a certain amount of arformoterol in 1 h after dosing.

Bone-seeking nanoplatform co-delivering cisplatin and zoledronate for synergistic therapy of breast cancer bone metastasis and bone resorption

The"vicious cycle"established between tumor growth and osteolysis aggravates the process of breast cancer bone metastasis,leading to life-threatening skeletal-related events that severely reduce survival and quality of life.To effectively interrupt the"vicious cycle",innovative therapeutic strategies that not only reduce osteolysis but also relieve tumor burden are urgently needed.Herein,a bone-seeking moiety,alendronate(ALN),functionalized coordination polymer nanoparticles(DZ@ALN)co-delivering cisplatin prodrug(DSP)and antiresorptive agent zoledronate(ZOL)via Zn2+crosslinking for combination therapy was reported.The versatile DZ@ALN with a diameter of about 40 nm can cross the fissure in the bone marrow sinus capillaries,and possesses an excellent bone-seeking ability both in vitro and in vivo.Additionally,DZ@ALN could synergistically inhibit the proliferation of cancer cells,suppress the formation of osteoclast-like cells and induce the apoptosis of osteoclasts in vitro.Importantly,it could preferentially accumulate in bone affected site,remarkably inhibit the proliferation of tumor cells,relieving bone pain,and significantly inhibit the activation of osteoclasts,protecting the bone from destruction in vivo,eventually leading to the breakdown of"vicious cycle"without inducing obvious systemic toxicity.This innovative nanoagent combines chemotherapy and osteolysis inhibition,exhibiting an inspiring strategy for effective treatment of bone metastasis.