Quantification accuracy in photon-counting detector CT for coronary artery calcium score: a pilot study.

To validate the accuracy of coronary artery calcium score (CACS) using photon-counting detector (PCD) CT under various scanning settings and explore the optimized scanning settings considering both the accuracy and the radiation dose. A CACS phantom containing six hollow cylindrical hydroxyapatite calcifications of two sizes with three densities and 12 patients underwent CACS scans. For PCD-CT, two scanning modes (sequence and flash [high-pitch spiral mode]) and five tube voltages (90kV, 120kV, 140kV, Sn100kV, and Sn140kV) at different image quality (IQ) levels were set for phantom, and patients were scanned with 120kV at IQ19 using flash mode. All acquisitions from PCD-CT were reconstructed at 70keV. Acquisitions in sequence mode at 120kV on an energy-integrating detector CT (EID-CT) was used as the reference. Agatston, mass, and volume scores were calculated. The CACS from PCD-CT exhibited excellent agreements with the reference (all intraclass correlation coefficient [ICC] > 0.99). The root mean square error (RMSE) between the Agatston score acquired from PCD-CT and the reference (5.4-11.5) was small. A radiation dose reduction (16-75%) from PCD-CT compared with the reference was obtained in all protocols using flash mode, albeit with IQ20 only at sequence mode (22-44%). For the patients, ICC ( all ICC > 0.98) and Bland-Altman analysis of CACS all showed high agreements between PCD-CT and the reference, without reclassifying CACS categories(P = 0.317). PCD-CT yields repeatable and accurate CACS across diverse scanning protocols according to our pilot study. Sn100kV, 90kV, and 120kV using flash mode at IQ20 are recommended for clinical applications considering both accuracy and radiation dose.

White light-driven enhanced cerium-doped carbon dots activity to combat multidrug-resistant bacterial infection.

Infections caused by multidrug-resistant (MDR) bacteria are increasing and becoming an urgent global health crisis. The discovery and development of novel antibacterial agents to combat MDR are highly desirable. Here, we report the fabrication of cerium-doped carbon dots (CeCDs) with a simple hydrothermal method, which exhibit intrinsic broad efficacy against MDR bacteria including clinical isolates while maintaining low cytotoxicity and hemolytic effects. Importantly, the antibacterial activity of CeCDs is dramatically improved owing to the generation of reactive oxygen species (ROS) upon white light irradiation. Comprehensive analyses revealed that the CeCDs can penetrate the bacterial wall, disrupt the cell membrane, and prevent the biofilm formation, possibly hindering the bacterial resistance development. And the interaction of CeCDs with lipopolysaccharide (LPS) may contribute to the higher activity against Gram-negative bacteria strains. The treatment of CeCDs in a murine skin infection model can significantly reduce the number of bacteria on infected sites and accelerate wound healing by irradiation with light. Overall, CeCDs show great promise as low-cost and efficient antibacterial agents for chronic wounds and may be served as a powerful weapon to fight against the growing threat of MDR bacterial infection.

Gene mutations in newly diagnosed multiple myeloma patients detected by next-generation sequencing technology.

Background: Multiple myeloma (MM) is a heterogeneous plasma-derived hematopoietic malignancy with complex genetic mutation contributing to the pathogenesis. Though gene sequencing has been applied in MM, genetic features from Chinese MM patients are reported less. We investigated the genetic mutation of newly diagnosed multiple myeloma (NDMM) patients and explore its correlation with cytogenetic abnormalities detected by fluorescence in situ hybridization (FISH). Methods: A total of 206 patients with NDMM were enrolled. After enriching plasma cells with CD138 magnetic beads, 92 MM-related target gene mutations were detected by the Illumina sequencing platform, and six common genetic abnormalities were detected by FISH. Results: 162 cases (78.6%) had at least one gene mutation detected by NDMM. The top 5 mutated genes were KRAS, NRAS, TRAF3, BRAF, and TP53. Cytogenetic abnormalities detected by FISH have a certain correlation with gene mutations, t(11;14) translocations are often accompanied by CCND1 and TP53 mutations, KLHL6 in t(4;14), SP140, CDKN1B and PRKD2 in t(14;16) and t(14;20) translocations. The mutation ratio was higher for EGR1, while lower of CCND1 in patients with gain 1q21. The TP53 mutation was more likely in patients with 17p deletion. The gene mutation affects the pathway of the RNA process is more frequently occurring in males and age less than 70 years patients. The International Staging System (ISS) Stage III correlated with gene mutations in the NK-κB pathway while Revised ISS (R-ISS) Stage III correlated with the DNA damage repair pathway. Conclusions: There are various gene mutations in NDMM patients, mainly RAS/MAPK and NF-κB pathway gene pathways.

A homogeneous binary matrix assisted laser desorption/ionization time-of-flight mass spectrometry assay for determination of artificial sweeteners in beverages.

Artificial sweeteners have been widely used as additives in various beverages. Due to the safety risks associated with artificial sweeteners, it is essential to develop a simple, rapid, and high-throughput method for the analysis of artificial sweeteners. Here, we report a homogeneous binary matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay for the simultaneous analysis of sweeteners including aspartame (ASP), neotame (NEO), and advantame (ADV) with a simple dilution step. The combination of nanodiamonds with 2,5-dihydroxybenzoic acid effectively improved the signal response of sweeteners, decreased the background noise, and improved the "spot-to-spot" repeatability. After the optimization, the method exhibits low limits of detection (ASP: 20 nΜ; NEO: 10 nΜ; ADV: 5 nΜ), good linearity (r > 0.995), satisfactory accuracy (96.2-103.0%), and lower RSDs (1.5-5.8%). Finally, the target sweeteners in 17 soft beverages were successfully determined with this method, showing the potential for the routine analysis of artificial sweeteners.

R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study.

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

Stability and accuracy of fat quantification on photon-counting detector CT with various scan settings: A phantom study.

OBJECTIVE: Fat deposition is an important marker of many metabolic diseases. As a noninvasive and convenient examination method, CT has been widely used for fat quantification. With the clinical application of photon-counting detector (PCD)-CT, we aimed to investigate the accuracy, stability, and dose level of PCD-CT using various scan settings for fat quantification. MATERIALS AND METHODS: Eleven agar-based lipid-containing phantoms (vials with different fat fractions [FFs]; range: 0 %-100 %) were scanned using PCD-CT. Three scanning types (sequence scan, regular spiral scan with a pitch of 0.8, and high-pitch spiral scan with a pitch of 3.2), four tube voltages (90, 120, 140, and 100 kV with a tin filter), and three image quality (IQ) levels (IQ levels of 20, 40, and 80) were alternated, and each scan setting was used twice. For each scan, a 70-keV image was generated using the same reconstruction parameters. A regular spiral scan at 120 kV with IQ80 was used to transfer the CT numbers of all scans to the FF. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were implemented for accuracy and agreement evaluation, and group differences were compared using analysis of variance. RESULTS: Excellent agreement and accuracy of FF derived by PCD-CT with all scan settings was demonstrated by high ICCs (>0.9; range: 0.929-0.998, p < 0.017) and low bias (<5% range: -2.9 %-5%). The root mean square error (RMSE) between the PCD-CT-acquired FF and the reference standard ranged from 1.0 % to 5.0 %, among which the high-pitch scan at 120 kV with IQ20 accounted for the lowest RMSE (1.0 %). The spiral scan at 120 kV with IQ20 and IQ80 yielded the lowest bias (mean value: 1.19 % and 1.23 %, respectively). CONCLUSION: Fat quantification using PCD-CT reconstructed at 70 keV was accurate and stable under various scan settings. PCD-CT has great potential for fat quantification using ultralow radiation doses.

A Simple and Rapid Quantitative Assay for Gossypol via Reactive Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry.

The development of simple and rapid analytical tools for gossypol (GSP) is important to the food industry and medical field. Here, we report a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) method for the detection of GSP by using a reactive matrix 4-hydrazinoquinazoline (4-HQ). The two aldehyde groups of GSP react with the 4-HQ and therefore improve the detection sensitivity and selectivity of GSP. Moreover, GSP forms homogeneous crystals with the 4-HQ matrix, allowing the quantification of the GSP by the proposed method. With the optimized experimental conditions, GSP could be detected at concentrations as low as 0.1 µM and quantified in a wide linear range (1-500 µM). After a brief extraction with an organic solvent, the GSP contents in cottonseeds and cottonseed kernels from different provinces of China were determined successfully. The spiked recovery of GSP in cottonseed/cottonseed kernel samples was obtained as 97.88-105.80%, showing the reliability of the assay for GSP determination in real samples.

Transition-Metal-Based Nanozymes: Synthesis, Mechanisms of Therapeutic Action, and Applications in Cancer Treatment.

Cancer, as one of the leading causes of death worldwide, drives the advancement of cutting-edge technologies for cancer treatment. Transition-metal-based nanozymes emerge as promising therapeutic nanodrugs that provide a reference for cancer therapy. In this review, we present recent breakthrough nanozymes for cancer treatment. First, we comprehensively outline the preparation strategies involved in creating transition-metal-based nanozymes, including hydrothermal method, solvothermal method, chemical reduction method, biomimetic mineralization method, and sol-gel method. Subsequently, we elucidate the catalytic mechanisms (catalase (CAT)-like activities), peroxidase (POD)-like activities), oxidase (OXD)-like activities) and superoxide dismutase (SOD)-like activities) of transition-metal-based nanozymes along with their activity regulation strategies such as morphology control, size manipulation, modulation, composition adjustment and surface modification under environmental stimulation. Furthermore, we elaborate on the diverse applications of transition-metal-based nanozymes in anticancer therapies encompassing radiotherapy (RT), chemodynamic therapy (CDT), photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), immunotherapy, and synergistic therapy. Finally, the challenges faced by transition-metal-based nanozymes are discussed alongside future research directions. The purpose of this review is to offer scientific guidance that will enhance the clinical applications of nanozymes based on transition metals.

Exploring Intraspecific Trait Variation in a Xerophytic Moss Species Indusiella thianschanica (Ptychomitriaceae) across Environmental Gradients on the Tibetan Plateau.

Investigating intraspecific trait variability is crucial for understanding plant adaptation to various environments, yet research on lithophytic mosses in extreme environments remains scarce. This study focuses on Indusiella thianschanica Broth. Hal., a unique lithophytic moss species in the extreme environments of the Tibetan Plateau, aiming to uncover its adaptation and response mechanisms to environmental changes. Specimens were collected from 26 sites across elevations ranging from 3642 m to 5528 m, and the relationships between 23 morphological traits and 15 environmental factors were analyzed. Results indicated that coefficients of variation (CV) ranged from 5.91% to 36.11%, with gametophyte height (GH) and basal cell transverse wall thickness (STW) showing the highest and lowest variations, respectively. Temperature, elevation, and potential evapo-transpiration (PET) emerged as primary environmental drivers. Leaf traits, especially those of the leaf sheath, exhibited a more pronounced response to the environment. The traits exhibited apparent covariation in response to environmental challenges and indicated flexible adaptive strategies. This study revealed the adaptation and response patterns of different morphological traits of I. thianschanica to environmental changes on the Tibetan Plateau, emphasizing the significant effect of temperature on trait variation. Our findings deepen the understanding of the ecology and adaptive strategies of lithophytic mosses.

A 224-bp Indel in the Promoter of PeMYB114 Accounts for Anthocyanin Accumulation of Skin in Passion Fruit (Passiflora spp.).

Passion fruit (Passiflora spp.) is an important fruit tree in the family Passifloraceae. The color of the fruit skin, a significant agricultural trait, is determined by the content of anthocyanin in passion fruit. However, the regulatory mechanisms behind the accumulation of anthocyanin in different passion fruit skin colors remain unclear. In the study, we identified and characterized a R2R3-MYB transcription factor, PeMYB114, which functions as a transcriptional activator in anthocyanin biosynthesis. Yeast one-hybrid system and dual-luciferase analysis showed that PeMYB114 could directly activate the expression of anthocyanin structural genes (PeCHS and PeDFR). Furthermore, a natural variation in the promoter region of PeMYB114 alters its expression. PeMYB114purple accessions with the 224-bp insertion have a higher anthocyanin level than PeMYB114yellow accessions with the 224-bp deletion. The findings enhance our understanding of anthocyanin accumulation in fruits and provide genetic resources for genome design for improving passion fruit quality.

Mechanism of Peppermint Extract-Induced Delay of 'Packham's Triumph' Pear (Pyrus communis L.) Postharvest Ripening.

Postharvest ripening is correlated to the quality and shelf life of European pear fruit. In this study, the effects of peppermint extract on fruit phenotype, related physiological activities, and aroma components during postharvest ripening of the European pear variety 'Packham's Triumph' were examined. Fruit treated with 2.0 g L-1 peppermint extract for 12 h showed delayed softening by 4 d compared with that of the untreated control group. The peak values of ethylene and respiratory rate in fruit were reduced to a certain extent after peppermint extract treatment; however, the peppermint extract did not delay the occurrence of the respiratory climacteric peak. Peppermint extract treatment also did not significantly increase the content of the characteristic peppermint aroma in pear fruit. Further, widely targeted metabolome analysis revealed 298 significantly different metabolites, with flavonoids (40%) and lipid compounds (15%) accounting for the highest proportion on the first day after treatment. The Kyoto Encyclopedia of Genes and Genomes pathway result showed significant enrichment in the metabolic pathways of biosynthesis of flavonoid, isoflavonoid, flavone and flavonol, linoleic acid, and alpha-linolenic acid metabolism following peppermint extract treatment. The combined analysis of transcriptome and metabolome data showed significant enrichment in linoleic acid metabolism and alpha-linolenic acid metabolism on the first, third, and fifth days after peppermint extract treatment. This study indicates that peppermint extract mainly affects the pear fruit softening process in the early stage after treatment.

Magneto-optical nanosystems for tumor multimodal imaging and therapy in-vivo.

Multimodal imaging, which combines the strengths of two or more imaging modalities to provide complementary anatomical and molecular information, has emerged as a robust technology for enhancing diagnostic sensitivity and accuracy, as well as improving treatment monitoring. Moreover, the application of multimodal imaging in guiding precision tumor treatment can prevent under- or over-treatment, thereby maximizing the benefits for tumor patients. In recent years, several intriguing magneto-optical nanosystems with both magnetic and optical properties have been developed, leading to significant breakthroughs in the field of multimodal imaging and image-guided tumor therapy. These advancements pave the way for precise tumor medicine. This review summarizes various types of magneto-optical nanosystems developed recently and describes their applications as probes for multimodal imaging and agents for image-guided therapeutic interventions. Finally, future research and development prospects of magneto-optical nanosystems are discussed along with an outlook on their further applications in the biomedical field.

Validation of the IMPEDE VTE score for prediction of venous thromboembolism in Chinese patients with multiple myeloma: A single-center retrospective cohort study.

Multiple myeloma (MM) significantly increases the risk of venous thromboembolism (VTE) within 6 months of treatment initiation. The IMPEDE VTE score is a VTE risk prediction model which is recently incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, but it lacks validation among Asians, including Chinese MM patients. We performed a retrospective chart review of 405 Chinese with newly diagnosed MM who started therapy at Beijing Jishuitan Hospital between April 2013 to October 2022. The 6-month cumulative incidence of VTE was 3.8 % (95 % CI:1.6-7.6), 8.6 % (95 % CI: 5.3-21.9) and 40.5 % (95 % CI: 24.9-55.7) in the low-, intermediate- and high-risk groups (P < 0.001), respectively. The C-statistic of the IMPEDE VTE scores for predicting VTE within 6 months of treatment initiation was 0.74 (95 % CI: 0.65-0.83). Of note, in this single-center cohort study, we propose that the anticoagulant LMWH may be more effective than the antiplatelet aspirin in potentially preventing VTE in newly diagnosed MM patients. Our findings suggest that the IMPEDE VTE score is a valid evidence-based risk stratification tool in Chinese patients with newly diagnosed MM.

Engineered Bacterial Biomimetic Vesicles Reprogram Tumor-Associated Macrophages and Remodel Tumor Microenvironment to Promote Innate and Adaptive Antitumor Immune Responses.

Tumor-associated macrophages (TAMs) are among the most abundant infiltrating leukocytes in the tumor microenvironment (TME). Reprogramming TAMs from protumor M2 to antitumor M1 phenotype is a promising strategy for remodeling the TME and promoting antitumor immunity; however, the development of an efficient strategy remains challenging. Here, a genetically modified bacterial biomimetic vesicle (BBV) with IFN-γ exposed on the surface in a nanoassembling membrane pore structure was constructed. The engineered IFN-γ BBV featured a nanoscale structure of protein and lipid vesicle, the existence of rich pattern-associated molecular patterns (PAMPs), and the costimulation of introduced IFN-γ molecules. In vitro, IFN-γ BBV reprogrammed M2 macrophages to M1, possibly through NF-κB and JAK-STAT signaling pathways, releasing nitric oxide (NO) and inflammatory cytokines IL-1ß, IL-6, and TNF-α and increasing the expression of IL-12 and iNOS. In tumor-bearing mice, IFN-γ BBV demonstrated a targeted enrichment in tumors and successfully reprogrammed TAMs into the M1 phenotype; notably, the response of antigen-specific cytotoxic T lymphocyte (CTL) in TME was promoted while the immunosuppressive myeloid-derived suppressor cell (MDSC) was suppressed. The tumor growth was found to be significantly inhibited in both a TC-1 tumor and a CT26 tumor. It was indicated that the antitumor effects of IFN-γ BBV were macrophage-dependent. Further, the modulation of TME by IFN-γ BBV produced synergistic effects against tumor growth and metastasis with an immune checkpoint inhibitor in an orthotopic 4T1 breast cancer model which was insensitive to anti-PD-1 mAb alone. In conclusion, IFN-γ-modified BBV demonstrated a strong capability of efficiently targeting tumor and tuning a cold tumor hot through reprogramming TAMs, providing a potent approach for tumor immunotherapy.

Construction of Smart DNA-Based Drug Delivery Systems for Cancer Therapy.

Due to the disadvantages of poor targeting, slow action, and low effectiveness of current commonly used cancer treatments, including surgery, chemotherapy, and radiotherapy, researchers have turned to DNA as a biomaterial for constructing drug delivery nanocarriers. DNA is favored for its biocompatibility and programmability. In order to overcome the limitations associated with traditional drug delivery systems (DDSs), researchers have developed smart-responsive DNA DDSs that can control drug release in response to specific physical or chemical stimuli at targeted sites. In this review, a summary of multiple targeted ligand structures is provided, various shapes of stable DNA nanomaterials, and different stimuli-responsive drug release strategies in DNA DDSs. Specifically, targeted cell recognition, in vivo stable transport, and controlled drug release of smart DDSs are focused. Finally, the further development prospects and challenges of clinical application of DNA nanomaterials in the field of smart drug delivery are discussed. The objective of this review is to enhance researchers' comprehension regarding the potential application of DNA nanomaterials in precision drug delivery, with the aim of expediting the clinical implementation of intelligent DDSs.

Activatable Probes for Ratiometric Imaging of Endogenous Biomarkers In Vivo.

Dynamic variations in the concentration and abnormal distribution of endogenous biomarkers are strongly associated with multiple physiological and pathological states. Therefore, it is crucial to design imaging systems capable of real-time detection of dynamic changes in biomarkers for the accurate diagnosis and effective treatment of diseases. Recently, ratiometric imaging has emerged as a widely used technique for sensing and imaging of biomarkers due to its advantage of circumventing the limitations inherent to conventional intensity-dependent signal readout methods while also providing built-in self-calibration for signal correction. Here, the recent progress of ratiometric probes and their applications in sensing and imaging of biomarkers are outlined. Ratiometric probes are classified according to their imaging mechanisms, and ratiometric photoacoustic imaging, ratiometric optical imaging including photoluminescence imaging and self-luminescence imaging, ratiometric magnetic resonance imaging, and dual-modal ratiometric imaging are discussed. The applications of ratiometric probes in the sensing and imaging of biomarkers such as pH, reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), gas molecules, enzymes, metal ions, and hypoxia are discussed in detail. Additionally, this Review presents an overview of challenges faced in this field along with future research directions.

The Unneglectable Disease Burden of Otitis Media Among Children in China: A Systematic Review and Meta-analysis.

BACKGROUND: Otitis media (OM) is one of the most commonly diagnosed infections among children yet with obscure disease burden. METHODS: The literature published from 1980 to 2022 was retrieved in PubMed, Ovid-EMBASE, Web of Science, CNKI, Wanfang and VIP. Literature screening, quality assessment and data extraction were conducted by 2 independent reviewers. Heterogeneity and publication bias were detected by I2 , Egger's and Begg's tests. The data were pooled using the random-effects model. The number of OM cases was estimated by the multiplied model based on pooled results and the 2020 China census data. RESULTS: A total of 28,378 literatures were identified with 67 finally included for data analysis. The OM incidence among children was 7.89% [95% confidence interval (CI): 5.43%-11.33%] and the prevalence of OM was 5.13% (95% CI: 3.49%-7.49%). The most common pathogen of the OM cases was Streptococcus pneumoniae ( S. pneumoniae ), with a positive rate of 33.52% (95% CI: 26.55%-41.29%). The most common serotypes of S. pneumoniae isolated from OM cases were serotypes 19F, 19A, 6B, 23F and 3, with 85.8% covered by the PCV13. We estimated that there were 8,950,797 (95% CI: 6,080,533-12,928,051) OM cases among under-fives in China in 2020, of which 3,374,451 (95% CI: 1,698,901-6,277,862) cases of OM were caused by S. pneumoniae . CONCLUSIONS: The burden of OM in China was considerable yet neglected. To date, S. pneumoniae was the most frequently detected bacterial pathogen of OM. Vaccination may be effective to protect young children from OM.

Nanomaterials for Disease Treatment by Modulating the Pyroptosis Pathway.

Pyroptosis differs significantly from apoptosis and cell necrosis as an alternative mode of programmed cell death. Its occurrence is mediated by the gasdermin protein, leading to characteristic outcomes including cell swelling, membrane perforation, and release of cell contents. Research underscores the role of pyroptosis in the etiology and progression of many diseases, making it a focus of research intervention as scientists explore ways to regulate pyroptosis pathways in disease management. Despite numerous reviews detailing the relationship between pyroptosis and disease mechanisms, few delve into recent advancements in nanomaterials as a mechanism for modulating the pyroptosis pathway to mitigate disease effects. Therefore, there is an urgent need to fill this gap and elucidate the path for the use of this promising technology in the field of disease treatment. This review article delves into recent developments in nanomaterials for disease management through pyroptosis modulation, details the mechanisms by which drugs interact with pyroptosis pathways, and highlights the promise that nanomaterial research holds in driving forward disease treatment.

Hypomethylating agents (HMAs) show benefit in AML rather than in intermediate/high-risk MDS based on genetic mutations in epigenetic modification (EMMs): from a retrospective study.

Since HMAs were recommended for treatments in AML and MDS, we wondered whether HMAs could provide similar benefit to AML and intermediate/high-risk MDS under the direction of next-generation sequencing. Here we retrospectively analyzed the prognosis of 176 AML and 128 intermediate/high-risk MDS patients treated with HMAs or non-HMA regimens. For AML, HMAs regimen was related to better CR rate compared with non-HMA regimen in elder cohort, while the situation was the opposite in younger cohort. In consolidation phase, EMM (+) patients could benefit from HMAs regimen. Relapsed AML patients receiving HMAs regimen rather than non-HMA regimen had better post-relapse survival. Multivariate analysis identified HMA regimen as an independent prognostic factor for OS in EMM (+) cohort. For intermediate/high-risk MDS patients not undergoing HSCT, however, HMA regimen showed no survival advantage in EMM (+) cohort and was conversely associated with shorter survival in EMM (-) cohort compared with non-HMA regimen. And among those undergoing HSCT, HMA prior to HSCT predicted poor prognosis compared with upfront HSCT regardless of the existence of EMMs. Therefore, HMAs had better therapeutic value in AML rather than in intermediate/high-risk MDS based on EMMs.

Activating Tumor-Selective Liquid Metal Nanomedicine through Galvanic Replacement.

Advanced chemotherapeutic strategies including prodrug and nanocatalytic medicine have significantly advanced tumor-selective theranostics, but delicate prodrug screening, tedious synthesis, low degradability/biocompatibility of inorganic components, and unsatisfied reaction activity complicate treatment efficacies. Here, the intrinsic anticancer bioactivity of liquid metal nanodroplets (LMNDs) is explored through galvanic replacement. By utilizing a mechano-degradable ligand, the resultant size of the aqueous LMND is unexpectedly controlled as small as ≈20 nm (LMND20). It is demonstrated that LMND20 presents excellent tumor penetration and biocompatibility and activates tumor-selective carrier-to-drug conversion, synchronously depleting Cu2+ ions and producing Ga3+ ions through galvanic replacement. Together with abundant generation of reactive oxygen species, multiple anticancer pathways lead to selective apoptosis and anti-angiogenesis of breast cancer cells. Compared to the preclinical/clinical anticancer drugs of tetrathiomolybdate and Ga(NO3 )3 , LMND20 administration significantly improves the therapeutic efficacy and survival in a BCap-37 xenograft mouse model, yet without obvious side effects.