2D Ruthenium-Chromium Oxide with Rich Grain Boundaries Boosts Acidic Oxygen Evolution Reaction Kinetics.

Ruthenium oxide is currently considered as the promising alternative to Ir-based catalysts employed for proton exchange membrane water electrolyzers but still faces the bottlenecks of limited durability and slow kinetics. Herein, a 2D amorphous/crystalline heterophase ac-Cr0.53 Ru0.47 O2-δ substitutional solid solution with pervasive grain boundaries (GBs) is developed to accelerate the kinetics of acidic oxygen evolution reaction (OER) and extend the long-term stability simultaneously. The ac-Cr0.53 Ru0.47 O2-δ shows a super stability with a slow degradation rate and a remarkable mass activity of 455 A gRu -1 at 1.6 V vs RHE, which is ≈3.6- and 5.9-fold higher than those of synthesized RuO2 and commercial RuO2 , respectively. The strong interaction of Cr-O-Ru local units in synergy with the specific 2D structural characteristics of ac-Cr0.53 Ru0.47 O2-δ dominates its enhanced stability. Meanwhile, high-density GBs and the shortened Ru-O bonds tailored by amorphous/crystalline structure and Cr-O-Ru interaction regulate the adsorption and desorption rates of oxygen intermediates, thus accelerating the overall acidic OER kinetics.

Synergistic Effect of Grain Boundaries and Oxygen Vacancies on Enhanced Selectivity for Electrocatalytic CO2 Reduction.

Dual-engineering involved of grain boundaries (GBs) and oxygen vacancies (VO) efficiently engineers the material's catalytic performance by simultaneously introducing favorable electronic and chemical properties. Herein, a novel SnO2 nanoplate is reported with simultaneous oxygen vacancies and abundant grain boundaries (V,G-SnOx/C) for promoting the highly selective conversion of CO2 to value-added formic acid. Attributing to the synergistic effect of employed dual-engineering, the V,G-SnOx/C displays highly catalytic selectivity with a maximum Faradaic efficiency (FE) of 87% for HCOOH production at -1.2 V versus RHE and FEs > 95% for all C1 products (CO and HCOOH) within all applied potential range, outperforming current state-of-the-art electrodes and the amorphous SnOx/C. Theoretical calculations combined with advanced characterizations revealed that GB induces the formation of electron-enriched Sn site, which strengthens the adsorption of *HCOO intermediate. While GBs and VO synergistically lower the reaction energy barrier, thus dramatically enhancing the intrinsic activity and selectivity toward HCOOH.

Multi-Scale Engineered 2D Carbon Polyhedron Array with Enhanced Electrocatalytic Performance.

Electrocatalyst engineering from the atomic to macroscopic level of electrocatalysts is one of the most powerful routes to boost the performance of electrochemical devices. However, multi-scale structure engineering mainly focuses on the range of atomic-to-particle scale such as hierarchical porosity engineering, while catalyst engineering at the macroscopic level, such as the arrangement configuration of nanoparticles, is often overlooked. Here, a 2D carbon polyhedron array with a multi-scale engineered structure via facile chemical etching, ice-templating induced self-assembly, and high-temperature pyrolysis processes is reported. Controlled phytic acid etching of the carbon precursor introduces homogeneous atomic phosphorous and nitrogen doping, as well as a well-defined mesoporous structure. Subsequent ice-templated self-assembly triggers the formation of a 2D particle array superstructure. The atomic-level doping gives rise to high intrinsic activity, while the well-engineered porous structure and particle arrangement addresses the mass transport limitations at the microscopic particle level and macroscopic electrode level. As a result, the as-prepared electrocatalyst delivers outstanding performance toward oxygen reduction reaction in both acidic and alkaline media, which is better than recently reported state-of-the-art metal-free electrocatalysts. Molecular dynamics simulation together with extensive characterizations indicate that the performance enhancement originates from multi-scale structural synergy.

Bridged Pt-OH-Mn Mediator in N-coordinated Mn Single Atoms and Pt Nanoparticles for Electrochemical Biomolecule Oxidation and Discrimination.

The rational design of efficient catalysts for uric acid (UA) electrooxidation, as well as the establishment of structure-activity relationships, remains a critical bottleneck in the field of electrochemical sensing. To address these challenges, herein, a hybrid catalyst that integrates carbon-supported Pt nanoparticles and nitrogen-coordinated Mn single atoms (PtNPs/MnNC) is developed. The metal-metal interaction during annealing affords the construction of metallic-bonded Pt-Mn pairs between PtNPs and Mn single atoms, facilitating the electron transfer from PtNPs to the support and thereby optimizing the electronic structure of catalysts. More importantly, experiments and theoretical calculations provide visual proof for the 'incipient hydrous oxide adatom mediator' mechanism for UA oxidation. The Pt-Mn pairs first adsorb OH* to construct the bridged Pt-OH-Mn mediators to serve as a highly active intermediate for N-H bond dissociation and proton transfer. Benefiting from the unique electronic and geometric structure of the catalytic center and reactive intermediates, PtNPs/MnNC exhibits superior electrooxidation performance. The electrochemical sensor based on PtNPs/MnNC enables sensitive detection and discrimination of UA and dopamine in serum samples. This work offers new insights into the construction of novel electrocatalysts for sensitive sensing platforms.

Asymmetric Ligands of a Metal-Organic Framework on Enhanced Photocatalytic CO2 Reduction.

Metal-organic frameworks (MOFs) have been studied extensively in the catalytic field. However, the role of ligands in catalysis has been less well investigated. Here, an asymmetric ligand photocatalytic strategy for CO2 reduction in MOFs is first proposed. MOF-303(Al) with asymmetric ligands (pyrazolyldicarboxylic acid) exhibits synergistic catalytic effects. Specifically, pyrazoles participate in CO2 activation; i.e., pyrazole and µ2-OH form hydrogen bonds with CO2 to polarize C═O bonds. Furthermore, the lowest unoccupied molecular orbital (LUMO; A pyrazole) and highest occupied molecular orbital (HOMO; B pyrazole) act as the electron donor and acceptor to spatially separate the excited electron-hole, with A and B pyrazoles for CO2 and H2O adsorption to avoid competition, respectively. Owing to its advantages, MOF-303-modified g-C3N4 achieves nonsacrificial and transition-metal-free photocatalytic CO2 reduction to CO of 16.19 µmol·g-1·h-1, significantly higher than that of g-C3N4. This work provides fresh insights into asymmetric ligands in photocatalytic CO2 reduction.

Metal-Free Photocatalytic CO2 Reduction to CH4 and H2 O2 under Non-sacrificial Ambient Conditions.

Photocatalytic CO2 reduction to CH4 requires photosensitizers and sacrificial agents to provide sufficient electrons and protons through metal-based photocatalysts, and the separation of CH4 from by-product O2 has poor applications. Herein, we successfully synthesize a metal-free photocatalyst of a novel electron-acceptor 4,5,9,10-pyrenetetrone (PT), to our best knowledge, this is the first time that metal-free catalyst achieves non-sacrificial photocatalytic CO2 to CH4 and easily separable H2 O2 . This photocatalyst offers CH4 product of 10.6 µmol ⋅ g-1 ⋅ h-1 under non-sacrificial ambient conditions (room temperature, and only water), which is two orders of magnitude higher than that of the reported metal-free photocatalysts. Comprehensive in situ characterizations and calculations reveal a multi-step reaction mechanism, in which the long-lived oxygen-centered radical in the excited PT provides as a site for CO2 activation, resulting in a stabilized cyclic carbonate intermediate with a lower formation energy. This key intermediate is thermodynamically crucial for the subsequent reduction to CH4 product with the electronic selectivity of up to 90 %. The work provides fresh insights on the economic viability of photocatalytic CO2 reduction to easily separable CH4 in non-sacrificial and metal-free conditions.

Targeting NQO1/GPX4-mediated ferroptosis by plumbagin suppresses in vitro and in vivo glioma growth.

BACKGROUND: Ferroptosis has attracted increasing interest in cancer therapy. Emerging evidences suggest that naturally occurring naphthoquinones exhibit potent anti-glioma effects via various mechanisms. METHODS: The anti-glioma effects of plumbagin were evaluated by in vitro and in vivo experiments. Anti-glioma mechanism of plumbagin was studied by proteomics, flow cytometry, MDA assay, western blot, and RT-PCR. Gene knockdown/overexpression, molecular docking, PharmMappper database, and coimmunoprecipitation were used to study the targets of plumbagin. RESULTS: Plumbagin showed higher blood-brain barrier penetration ability than that of lapachol and shikonin and elicited significant growth inhibitory effects in vitro and in vivo. Ferroptosis was the main mechanism of plumbagin-induced cell death. Mechanistically, plumbagin significantly downregulated the protein and mRNA levels of xCT and decreased GPX4 protein levels. NAD(P)H quinone dehydrogenase 1 (NQO1) was revealed as a plumbagin predictive target using PharmMappper database and molecular docking. Plumbagin enhanced NQO1 activity and decreased xCT expression, resulting in NQO1-dependent cell death. It also induced GPX4 degradation via the lysosome pathway and caused GPX4-dependent cell death. CONCLUSIONS: Plumbagin inhibited in vitro and in vivo glioma growth via targeting NQO1/GPX4-mediated ferroptosis, which might be developed as a novel ferroptosis inducer or anti-glioma candidate.

Single-Atom Iron Enables Strong Low-Triggering-Potential Luminol Cathodic Electrochemiluminescence.

The conventional cathodic electrochemiluminescence (ECL) always requires a more negative potential to trigger strong emission, which inevitably damages the bioactivity of targets and decreases the sensitivity and specificity. In this work, iron single-atom catalysts (Fe-N-C SACs) were employed as an efficient co-reaction accelerator for the first time to achieve the impressively cathodic emission of a luminol-H2O2 ECL system at an ultralow potential. Benefiting from the distinct electronic structure, Fe-N-C SACs exhibit remarkable properties for the activation of H2O2 to produce massive reactive oxygen species (ROS) under a negative scanning potential from 0 to -0.2 V. The ROS can oxidize the luminol anions into luminol anion radicals, avoiding the tedious electrochemical oxidation process of luminol. Then, the in situ-formed luminol anion radicals will directly react with ROS for the strong ECL emission. As a proof of concept, sensitive detection of the carcinoembryonic antigen was realized by glucose oxidase-mediated ECL immunoassay, shedding light on the superiority of SACs to construct efficient cathodic ECL systems with low triggering potential.

Iridium Single-Atomic Site Catalysts with Superior Oxygen Reduction Reaction Activity for Sensitive Monitoring of Organophosphorus Pesticides.

Tremendous efforts have been made in developing single-atomic site catalysts (SASCs) for oxygen reduction reaction (ORR), which is regarded as a pivotal cornerstone in electrochemical energy conversion. However, SASCs for ORR have not been explored for electrochemical sensing. Herein, a template-sacrificed strategy is reported for the synthesis of atomically dispersed Ir SASCs, serving as a sensing platform to detect organophosphorus pesticides (OPs) with high sensitivity and selectivity. Owing to abundant Ir single-atom active sites, Ir SASCs show excellent ORR activity and stability in a neutral medium. It is found that the ORR activity of Ir SASCs can be inhibited by thiocholine, which is the hydrolysate of acetylthiocholine. After being integrated with acetylcholinesterase (AChE), the AChE-Ir SASC-based electrochemical sensor is established and shows a superior sensitivity, which shows a wide detection range of 0.5-500 ng mL-1 with a low detection limit of 0.17 ng mL-1 for OPs. This work exhibits a broad application prospect of ORR for sensitive detection of biomolecules.

Ultra-Low Content Bismuth-Anchored Gold Aerogels with Plasmon Property for Enhanced Nonenzymatic Electrochemical Glucose Sensing.

Effective glucose surveillance provides a strong guarantee for the high-quality development of human health. Au nanomaterials possess compelling applications in nonenzymatic electrochemical glucose biosensors owing to superior catalytic performances and intriguing biocompatibility properties. However, it has been a grand challenge to accurately control the architecture and composition of Au nanomaterials to optimize their optical, electronic, and magnetic properties for further improving the performance of electrocatalytic sensing. Herein, ultra-low content Bi-anchored Au aerogels are synthesized via a one-step reduction strategy. Benefiting from the unique structure of aerogels as well as the synergistic effect between Au and Bi, the optimized Au200Bi aerogels greatly boost the activity of glucose oxidation compared with Au aerogels. Under plasmon resonance excitation, bimetallic Au200Bi aerogels with wider photics-dependent properties further show plasmon-promoted glucose electro-oxidation activity, which is derived from the photothermal and photoelectric effects caused by the local surface plasmon resonance. Thanks to the enhanced performance, a nonenzymatic electrochemical glucose biosensor is constructed to detect glucose with high sensitivity. This plasmon-promoted electrocatalytic activity through the synergetic strategy of bimetallic aerogels has potential applications in various research fields.

Aptamer-AuNP-conjugated carboxymethyl chitosan-functionalized graphene oxide for colorimetric identification of Salmonella typhimurium.

A novel aptamer-AuNP-conjugated carboxymethyl chitosan-functionalized graphene oxide (CMC/GO@Apt-Au NP) probe was for the first time developed for the determination of Salmonella typhimurium (S. typhimurium). Owing to the conformational change of the aptamers in the presence of S. typhimurium, the Au NPs, which were pre-adsorbed on the aptamers through van der Waals forces, were released into the solution phase and induced the color change of the solution. As a result, S. typhimurium ranging from 102 to 107 CFU/mL was successfully identified using the designed assay with a limit of detection (LOD) of 10 CFU/mL. This low detection level allowed the sensitive recognition of S. typhimurium in milk samples within 40 min without sample pretreatment, a conclusion that agreed well with the traditional plate counting method. The developed method not only provides a rapid way for the determination of S. typhimurium with simplicity and sensitivity but also shows potential universality in the quantification of other pathogenic microorganisms.

Modulating Oxygen Reduction Behaviors on Nickel Single-Atom Catalysts to Probe the Electrochemiluminescence Mechanism at the Atomic Level.

Luminol-dissolved O2 electrochemiluminescence (ECL)-sensing platforms have been widely developed for sensitive and reliable detection, while their actual ECL mechanisms are still in controversy due to the involved multiple reactive oxygen species (ROS). Different from the structural complexity of nanomaterials, well-defined single-atom catalysts (SACs) as coreaction accelerators will provide great prospects for investigating the ECL mechanism at the atomic level. Herein, two carbon-supported nickel SACs with the active centers of Ni-N4 (Ni-N4/C) and Ni-N2O2 (Ni-N2O2/C) were synthesized as efficient coreaction accelerators to enhance the ECL signals of a luminol-dissolved O2 system. By modulating the surrounding environment of the center metal atoms, their corresponding oxygen reduction behaviors can be well controlled to selectively produce intermediate ROS, giving a great chance to study the following ECL process. According to the experimental and calculated results, the superoxide radical (O2•-) acts as the main radical for the ECL reaction and the Ni-N4/C catalyst with the four-electron pathway to activate dissolved O2 is preferential to enhance ECL emission.

Tuning the Ratio of Pt(0)/Pt(II) in Well-Defined Pt Clusters Enables Enhanced Electrocatalytic Reduction/Oxidation of Hydrogen Peroxide for Sensitive Biosensing.

Rational design and construction of advanced sensing platforms for sensitive detection of H2O2 released from living cells is one of the challenges in the field of physiology and pathology. Noble metal clusters are a kind of nanomaterials with well-defined chemical composition and special atomic structures, which have been widely explored in catalysis, biosensing, and therapy. Compared with noble metal nanoparticles, noble metal clusters exhibit great potential in electrochemical biosensing due to their high atom utilization efficiency and abundant reactive active sites. Herein, Pt nanoclusters anchored on hollow carbon spheres (PtNCS/HCS) were successfully prepared for sensitive detection of H2O2. By tuning the ratio of Pt(0)/Pt(II) at different annealing temperatures, the optimized PtNCS/HCS-550 showed higher H2O2 reduction and oxidation catalytic activities than other control samples. Density functional theory calculations revealed that H2O2*can be better activated and dissociated in the Pt0II model featured with the co-existence of Pt(0)/Pt(II) and the key intermediates OOH*/OH* have a stronger interaction with the Pt0II model. As a concept application, the electrochemical biosensing platform was successfully applied to sensitive detection of H2O2 released from the cells.

Fe3C-Assisted Single Atomic Fe Sites for Sensitive Electrochemical Biosensing.

The rational construction of advanced sensing platforms to sensitively detect H2O2 produced by living cells is one of the challenges in both physiological and pathological fields. Owing to the extraordinary catalytic performances and similar metal coordination to natural metalloenzymes, single atomic site catalysts (SASCs) with intrinsic peroxidase (POD)-like activity have shown great promise for H2O2 detection. However, there still exists an obvious gap between them and natural enzymes because of the great challenge in rationally modulating the electronic and geometrical structures of central atoms. Note that the deliberate modulation of the metal-support interaction may give rise to the promising catalytic activity. In this work, an extremely sensitive electrochemical H2O2 biosensor based on single atomic Fe sites coupled with carbon-encapsulated Fe3C crystals (Fe3C@C/Fe-N-C) is proposed. Compared with the conventional Fe SASCs (Fe-N-C), Fe3C@C/Fe-N-C exhibits superior POD-like activity and electrochemical H2O2 sensing performance with a high sensitivity of 1225 µA/mM·cm2, fast response within 2 s, and a low detection limit of 0.26 µM. Significantly, sensitive monitoring of H2O2 released from living cells is also achieved. Moreover, the density functional theory calculations reveal that the incorporated Fe3C nanocrystals donate electrons to single atomic Fe sites, endowing them with improved activation ability of H2O2 and further enhancing the overall activity. This work provides a new design of synergistically enhanced single atomic sites for electrochemical sensing applications.

Cell density-dependent regulation of microcystin synthetase genes (mcy) expression and microcystin-LR production in Microcystis aeruginosa that mimics quorum sensing.

As the secondary metabolites of cyanobacterial harmful algal blooms (Cyano-HABs), microcystins (MCs) were generated under various environmental and cellular conditions. The understanding of the causes of MCs generation is of great interest in the field of water treatment and environmental science. In this work, we studied how Microcystis aeruginosa (FACHB-905) cell densities affect the MCs synthetase genes (mcy) expression, microcystin-LR (MC-LR) and quorum sensing molecules (Acyl-homoserine lactones (AHLs)) production. An electrochemical sensor was developed here for sensitive and quantitative detection of MC-LR that cultured at different cell densities. The results showed that mcy expression and MC-LR concentration started to increase when the cell density reached ca. 22 × 106 cells/mL, and was significantly increased with increasing cell densities. Moreover, the up-regulation of AHLs with increasing cell densities revealed that MC-LR is quorum sensing-mediated. Our results undoubtedly confirmed that MC-LR was produced in a cell density-dependent way that mimics quorum sensing, and the minimum cell density (ca. 22 × 106 cells/mL) that was required to produce MC-LR was provided and offered a reference standard for the prevention and control of MCs pollution in the actual water environment.

Cascade Reaction System Integrating Single-Atom Nanozymes with Abundant Cu Sites for Enhanced Biosensing.

Single-atom nanozymes (SAzymes), as novel nanozymes with atomically dispersed active sites, are of great importance in the development of nanozymes for their high catalytic activities, the maximum utilization efficiency of metal atoms, and the simple model of active sites. Herein, the peroxidase-like SAzymes with high-concentration Cu sites on carbon nanosheets (Cu-N-C) were synthesized through a salt-template strategy. With the densely distributed active Cu atoms (∼5.1 wt %), the Cu-N-C SAzymes exhibit remarkable activity to mimic natural peroxidase. Integrating Cu-N-C SAzymes with natural acetylcholinesterase and choline oxidase, three-enzyme-based cascade reaction system was constructed for the colorimetric detection of acetylcholine and organophosphorus pesticides. This work not only provides a strategy to synthesize SAzymes with abundant active sites but also gives some new insights for robust nanozyme biosensing systems.

Oxidase-Like Fe-N-C Single-Atom Nanozymes for the Detection of Acetylcholinesterase Activity.

Single-atom catalysts (SACs) have attracted extensive attention in the catalysis field because of their remarkable catalytic activity, gratifying stability, excellent selectivity, and 100% atom utilization. With atomically dispersed metal active sites, Fe-N-C SACs can mimic oxidase by activating O2 into reactive oxygen species, O2- • radicals. Taking advantages of this property, single-atom nanozymes (SAzymes) can become a great impetus to develop novel biosensors. Herein, the performance of Fe-N-C SACs as oxidase-like nanozymes is explored. Besides, the Fe-N-C SAzymes are applied in biosensor areas to evaluate the activity of acetylcholinesterase based on the inhibition toward nanozyme activity by thiols. Moreover, this SAzymes-based biosensor is further used for monitoring the amounts of organophosphorus compounds.

Advantageous Interfacial Effects of AgPd/g-C3 N4 for Photocatalytic Hydrogen Evolution: Electronic Structure and H2 O Dissociation.

Bimetallic AgPd nanoparticles have been synthesized before, but the interfacial electronic effects of AgPd on the photocatalytic performance have been investigated less. In this work, the results of hydrogen evolution suggest that the bimetallic AgPd/g-C3 N4 sample has superior activity to Ag/g-C3 N4 and Pd/g-C3 N4 photocatalysts. The UV/Vis diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy, CO adsorption diffuse reflectance FTIR spectroscopy, and FTIR results demonstrate that in the AgPd/g-C3 N4 , the surface electronic structures of Pd and Ag are changed, which is beneficial for faster photogenerated electron transfer and greater H2 O molecule adsorption. In situ ESR spectra suggest that, under visible light irradiation, there is more H2 O dissociation to radical species on the AgPd/g-C3 N4 photocatalyst. Furthermore, DFT calculations confirm the interfacial electronic effects of AgPd/g-C3 N4 , that is, Pdδ- ⋅⋅⋅Agδ+ , and the activation energy of H2 O molecule dissociation on AgPd/g-C3 N4 is the lowest, which is the main contributor to the enhanced photocatalytic H2 evolution.

Panax notoginseng saponins promotes stroke recovery by influencing expression of Nogo-A, NgR and p75NGF, in vitro and in vivo.

The spontaneous recovery of function after injury in the adult central nervous system is limited due to the several proteins, such as Nogo-A that have repulsive or inhibitory effects on growing neuritis. The Chinese herbal medicine extraction Panax notoginseng saponins (PNS) injection has been widely used and effective in repairing the function of impaired nerves, but the mechanism of this herbal medicine is still poorly understood. This project evaluated the effect of Panax notoginseng saponins on neurological functional recovery and on the expression of Nogo-A, NgR and p75 at 7, 14 and 28 d after middle cerebral artery occlusion (MCAO) in rats and also oxygen-glucose deprivation/reperfusion (OGD/R) model on SH-SY5Y cells. We found that the expression of Nogo-A, NgR and p75 of rats receiving MCAO surgery increased on the 7th day, reached a peak on the 14th or 28th day and maintained high levels and Panax notoginseng saponins significantly decreased these expressions. This may be the mechanism of Panax notoginseng saponins that contributes to the recovery of nerve function, which plays an important role in brain protection after cerebral infarction.

Bone marrow adipocytes is a new player in supporting myeloma cells proliferation and survival in myeloma microenvironment.

Multiple myeloma (MM) is a lethal B cell neoplasm characterized by clonal expansion of malignant plasma cells in the bone marrow and remains incurable due to disease relapse and drug resistance. Bone marrow adipocytes (BMAs) are emerging as playing active functions that can support myeloma cell growth and survival. The aim of this study is to investigate myeloma-mesenchymal stem cells (MSCs) interaction and the impact of such interactions on the pathogenesis of MM using in vitro co-culture assay. Here we provide evidence that MM cell up-regulated MSCs to express PPAR-γ and pushes MSCs differentiation toward adipocytes at the expense of osteoblasts in co-culture manner. The increased BMAs can effectively enhance MM cell to proliferation, migration, and chemoresistance via cell-cell contact and/or cytokines release regulated by PPAR-γ signal pathway. This effect was partially reversed in medium containing PPAR-γ antagonist G3335 and indicated that G3335 distorts the maturation of MSC-derived adipocytes and cytokines release by adipocytes through inhibition of PPAR-γ, a key transcriptional factor for the activation of adipogenesis, or cell to cell contact, or both. In meantime, we observed higher expression of adipocyte differentiation associated genes DLK1, DGAT1, FABP4, and FASN both in MSCs and MSC derived adipocytes, but the osteoblast differentiation-associated gene ALP was down regulated in MSCs. These finding mean that direct consequence of MM/MSC interaction that play a role in MM pathogenesis. Consistent with those in vitro results, our primary clinical observation also showed that bone marrow samples from MM patients had significantly higher bone adiposity in comparison with controls and the number of adipocytes decreased in those who were response to anti-MM therapy. Our finding suggested that BMAs may have an important contribution to MM progression, particularly in drugs resistant of MM cells, and plays an important contribution in MM bone disease and treatment failure, but more clinical studies are needed to confirm its role.