Risk Factors for Disease Aggravation in Older Patients With Non-communicable Diseases: Interpretive Structural and Hierarchical Holographic Modelling.

AIMS: This study aimed to analyse and determine the risk factors of disease aggravation faced by older patients with non-communicable diseases (NCDs) and their interwoven correlations. DESIGN: We employed a descriptive and cross-sectional study, which followed the STROBE guidelines for reporting. METHODS: We conducted a semi-structured in-depth interview with 26 older patients with NCDs from a hospital in Qingdao, China between July and August 2022 on the basis of the literature review. Then, we analysed data using the directed content analysis and determined risk factors through a focus group discussion and the Delphi consultation. Afterward, we combined interpretive structural modelling and hierarchical holographic modelling to construct a hierarchical structure model and drew relationship framework diagrams to exhibit diversified risk factors and complex interwoven correlations. RESULTS: We identified 30 risk factors from individual, interpersonal, organisational, community and policy levels. The hierarchical structure model constructed by interpretive structural modelling demonstrated a four-layer structure, and the individual and interpersonal levels were at the highest layer. The relationship framework diagrams demonstrated the identification process of risk factors and interwoven correlations at individual and organisational levels. CONCLUSIONS: Risk factors causing disease aggravation amongst older patients with NCDs are diverse. To delay the progression of NCDs, we should comprehensively explore risk factors, interpret the root causes and effects of risks from multiple perspectives and consider the interaction amongst multi-level risk factors to develop precise measures related to risk control. IMPACT: Controlling risk factors is an effective measure to postpone disease aggravation. Through this study, we provide a scientific and comprehensive basis for clinical risk screening so that healthcare providers can sense potential risk factors for disease aggravation in older patients' surroundings and formulate targeted nursing measures according to the risk factors faced by different patients. PATIENT OR PUBLIC CONTRIBUTION: Patients participated in interviews to supplement risk factors included in our study. Experts provided opinions on the inclusion, exclusion and modification of risk factors.

Tailoring Copper Single-Atoms-Stabilized Metastable Transition-Metal-Dichalcogenides for Sustainable Hydrogen Production.

Unconventional 1T' phase transition metal dichalcogenides (TMDs) show great potential for hydrogen evolution reaction (HER). However, they are susceptible to transitioning into the stable 2H phase, which reduces their catalytic activity and stability. Herein, we present a scalable approach for designing thermally stable 1T'-TMDs hollow structures (HSs) by etching Cu1.94S templates from pre-synthesized Cu1.94S@TMDs heterostructures, including 1T'-MoS2, MoSe2, WS2, and WSe2 HSs. Furthermore, taking 1T'-MoS2 HSs as an example, the etched Cu ions can be firmly adsorbed on their surface in the form of single atoms (SAs) through Cu-S bonds, thereby elevating the phase transition temperature from 149 ºC to 373 ºC. Due to the advantages conferred by the 1T' phase, hollow structure, and synergistic effect between Cu SAs and 1T'-MoS2 supports, the fabricated 1T'-MoS2 HSs demonstrate superior HER performance. Notably, their high-phase stability enables continuous operation of designed 1T'-MoS2 HSs for up to 200 hours at an ampere-level current density without significant activity decay. This work provides a universal method for synthesizing highly stable 1T'-TMDs electrocatalysts, with a particular focus on the relationship between their phase and catalytic stability.

Intrinsically bioactive multifunctional Poly(citrate-curcumin) for rapid lung injury and MRSA infection therapy.

Dysregulated inflammation after trauma or infection could result in the further disease and delayed tissue reconstruction. The conventional anti-inflammatory drug treatment suffers to the poor bioavailability and side effects. Herein, we developed an amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nano oligomer with the robust anti-inflammatory activity for treating acute lung injury (ALI) and Methicillin-resistant staphylococcus aureus (MRSA) infected wound. PCGC demonstrated the sustained curcumin release, inherent photoluminescence, good cellular compatibility, hemocompatibility, robust antioxidant activity and enhanced cellular uptake. PCGC could efficiently scavenge nitrogen-based free radicals, oxygen-based free radicals, and intracellular oxygen species, enhance the endothelial cell migration and reduce the expression of pro-inflammatory factors through the NF-κB signal pathway. Combined the anti-inflammation and antioxidant properties, PCGC can shortened the inflammatory process. In animal model of ALI, PCGC was able to reduce the pulmonary edema, bronchial cell infiltration, and lung inflammation, while exhibiting rapid metabolic behavior in vivo. The MRSA-infection wound model showed that PCGC significantly reduced the expression of pro-inflammatory factors, promoted the angiogenesis and accelerated the wound healing. The transcriptome sequencing and molecular mechanism studies further demonstrated that PCGC could inhibit multiple inflammatory related pathways including TNFAIP3, IL-15RA, NF-κB. This work demonstrates that PCGC is efficient in resolving inflammation and promotes the prospect of application in inflammatory diseases as the drug-loaded therapeutic system.

Solution-Processable Microstructuring of 1T'-Phase Janus MoSSe Monolayers for Boosted Hydrogen Production.

Janus monolayers of transition metal dichalcogenides (TMDs) offer versatile applications due to their tunable polymorphisms. While previous studies focused on conventional 2H-phase Janus monolayers, the scalable synthesis of an unconventional 1T' phase remains challenging. We present a novel solution strategy for fabricating Janus 1T'-MoOSe and MoSSe monolayers by growing sandwiched Se-Mo-O/S shells onto Au nanocores. The Janus Au@1T'-MoSSe catalyst exhibits superior electrocatalytic hydrogen evolution reaction (HER) activity compared to 1T'-MoS2, -MoSe2, and -MoOSe, attributed to its unique electronic structure and intrinsic strain. Remarkably, photoexciting the nanoplasmonic Au cores further enhances the HER via a localized surface plasmon (LSP) effect that drives hot electron injection into surface sulfur vacancies of 1T'-MoSSe monolayer shells, accelerating proton reduction. This synergistic activation of anion vacancies by internal strain and external light-induced Au LSPs, coupled with our scalable synthesis, provides a pathway for developing tailorable polymorphic Janus TMDs for specific applications.

The risk and survival of multiple myeloma as the second primary malignancy in a single Chinese center.

Background: As the overall survival (OS) of patients with multiple myeloma (MM) improves, the incidence of second primary malignancy (SPM) in long-term complications increases. However, there are limited data regarding MM as a SPM. Therefore, this study aimed to determine the time trends in the incidence of MM, as well as the incidence and survival of patients with MM as the SPM. Methods: Kaplan-Meier survival analysis was performed to determine the survival curve, while a log-rank test was used to determine OS. Results: A total of 794 patients were diagnosed with MM among 7,921 patients with hematologic malignancy between 2009 and 2017. The incidence of MM showed an annual upward trend, increasing from 9.3% [2009-2011] to 10.8% [2015-2017]. Of the 794 patients with MM, 16 were diagnosed as the SPM commonly secondary to cancers of the lung (n=4), colon (n=3), breast (n=3), and other (n=6). The median survival of patients with MM as the SPM was 24.5 months (range, 1-95 months). The patients with MM without multiple malignancies had significantly longer survival (median, 46.5 months; range, 17-132 months; P=0.04). Conclusions: This retrospective study suggests that the incidence of MM may be increasing annually and that the survival of patients with MM as the second primary malignant was significantly shorter than that of those without multiple malignancies.

Dynamic Single-Cell RNA-Seq reveals mechanism of Selinexor-Resistance in Chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a type of hematologic malignancies caused by BCR-ABL chimeric oncogene. Resistance to tyrosine kinase inhibitors (TKIs) leads to the progression of CML into advanced stages. Selinexor is a small molecule inhibitor that targets a nuclear transporter called Exportin 1. Combined with imatinib, selinexor has been shown to disrupt nuclear-cytoplasmic transport signal of leukemia stem cells, resulting in cell death. The objective of this study was to investigate the mechanism of drug resistance to selinexor in CML. We established K562 cell line resistant to selinexor and conducted single cell dynamic transcriptome sequencing to analyze the heterogeneity within the parental and selinexor resistant cell populations. We identified specific gene expression changes associated with resistance to selinexor. Our results revealed differential expression patterns in genes such as MT2A, TFPI, MTND3, and HMGCS1 in the total RNA, as well as MT-TW, DNAJB1, and HSPB1 in the newly synthesized RNA, between the parental and drug-resistant groups. By applying pseudo-time analysis, we discovered that a specific cluster of cells exhibited characteristics of tumor stem cells. Furthermore, we observed a gradual decrease in the expression of ferroptosis-related molecules as drug resistance developed. In vitro experiments confirmed that the combination of a ferroptosis inducer called RSL3 effectively overcame drug resistance. In conclusion, this study revealed the resistance mechanism of selinexor in CML. In conclusion, we identified a subgroup of CML cells with tumor stem cell properties and demonstrated that ferroptosis inducer improved the efficacy of selinexor in overcoming drug resistance.

Sprayable self-assembly multifunctional bioactive poly(ferulic acid) hydrogel for rapid MRSA infected wound repair.

The repair of methicillin-resistant staphylococcus aureus (MRSA) infected wounds remains a serious challenge. Development of multifunctional bioactive hydrogels has shown promising potential in treating MRSA wound. Ferulic acid has special bioactivities including antioxidant antiinflammation antibacterial capacities but limited in lack of engineering strategy for efficient treatment of MRSA infected wound. Herein, we developed a multifunctional bioactive poly(ferulic acid) copolymer (FPFA) for treating MRSA infected wound. FPFA could be self-assembled into hydrogel under body temperature and demonstrated the injectable, sprayable, self-healing, anti-inflammatory, antioxidant, and angiogenic activity. FPFA hydrogel also showed the good cytocompatibility, efficiently enhanced the endothelial cell migration, scavenged intracellular reactive oxygen species (ROS), inhibited the expression of inflammatory factors and enhanced the in vitro angiogenesis. The MRSA-infected wound model showed that FPFA could significantly inhibit the MRSA infection and excess inflammation, reinforce the angiogenesis, accelerate wound healing and skin tissue regeneration.

Ultrathin heteroatom-doped CeO2 nanosheet assemblies for durable oxygen evolution: Oxygen vacancy engineering to trigger deprotonation.

The manipulation of oxygen vacancies (OVs) in metal oxides has progressively emerged as a versatile strategy for improving their catalytic performance. In this study, we aim to enhance the oxygen evolution reaction (OER) performance of cerium oxide (CeO2) by doping heteroatoms (Fe, Co, Ni) to generate additional OVs. We systematically analyzed both the morphology and electronic structure of the obtained CeO2 catalysts. The experimental results revealed the self-assembly of two-dimensional (2D) CeO2 nanosheets, with an approximate thickness of ∼1.7 nm, into 2D nanosheet assemblies (NSAs). Moreover, the incorporation of heteroatoms into the CeO2 matrix promoted the formation of OVs, resulting in a significant enhancement of the OER performance of CeO2. Among them, the Co-doped CeO2 NSAs sample displayed the highest activity and durability, with almost negligible activity loss during extended operating periods. The roles of heteroatom doping in improving OER activity were explored by DFT calculations. The produced OVs improve the adsorption of hydroxyl groups (OH-), promote the deprotonation process, and increase more active sites. These findings suggest that doping CeO2 with heteroatoms is a promising strategy for improving electrocatalytic OER activity, with great potential for the development of clean energy technologies, including but not limited to water splitting and fuel cells.

SOX10 deficiency-mediated LAMB3 upregulation determines the invasiveness of MAPKi-resistant melanoma.

Melanoma that develops adaptive resistance to MAPK inhibitors (MAPKi) through transcriptional reprograming-mediated phenotype switching is associated with enhanced metastatic potential, yet the underlying mechanism of this improved invasiveness has not been fully elucidated. In this study, we show that MAPKi-resistant melanoma cells are more motile and invasive than the parental cells. We further show that LAMB3, a ß subunit of the extracellular matrix protein laminin-332 is upregulated in MAPKi-resistant melanoma cells and that the LAMB3-Integrin α3/α6 signaling mediates the motile and invasive phenotype of resistant cells. In addition, we demonstrate that SOX10 deficiency in MAPKi-resistant melanoma cells drives LAMB3 upregulation through TGF-ß signaling. Transcriptome profiling and functional studies further reveal a FAK/MMPs axis mediates the pro-invasiveness effect of LAMB3. Using a mouse lung metastasis model, we demonstrate LAMB3 depletion inhibits the metastatic potential of MAPKi-resistant cells in vivo. In summary, this study identifies a SOX10low/TGF-ß/LAMB3/FAK/MMPs signaling pathway that determines the migration and invasion properties of MAPKi-resistant melanoma cells and provide rationales for co-targeting LAMB3 to curb the metastasis of melanoma cells in targeted therapy.

Nurses' Colleague Solidarity and Job Performance: Mediating Effect of Positive Emotion and Turnover Intention.

Background: Job performance is known as an essential reflection of nursing quality. Colleague solidarity, positive emotion, and turnover intention play effective roles in a clinical working environment, but their impacts on job performance are unclear. Investigating the association between nurses' colleague solidarity and job performance may be valuable, both directly and through the mediating roles of positive emotion and turnover intention. Methods: In this cross-sectional study, a total of 324 Chinese nurses were recruited by convenience sampling method from July 2016 to January 2017. Descriptive analysis, Spearman's correlation analysis, and the structural equation model were applied for analysis by SPSS 26.0 and AMOS 24.0. Results: A total of 49.69% of participants were under 30 years old, and 90.12% of participants were female. Colleague solidarity and positive emotion were positively connected with job performance. The results indicated the mediating effects of positive emotion and turnover intention in this relationship, respectively, as well as the chain mediating effect of positive emotion and turnover intention. Conclusions: In conclusion, dynamic and multiple supportive strategies are needed for nurse managers to ameliorate nursing job performance by improving colleague solidarity and positive emotion and decreasing turnover intention based on the job demand-resource model.

Liquid extramedullary disease in multiple myeloma strongly predicts a poor prognosis and is associated with bortezomib resistance gene upregulation.

BACKGROUND-AIM: Patients with multiple myeloma (MM) relapse with extramedullary disease (EMD) exhibits an aggressive disease course and poor prognostic features. Myelomatous effusion (ME) is a rare subtype of EMD. METHODS: In this retrospective study, we analyzed the baseline characteristics and therapies of 14 EMD patients relapse with ME and 21 EMD patients relapse without ME. RESULTS: Patients with ME relapse demonstrated higher concentrations of serum lactate dehydrogenase, a higher fraction in the International Staging System stage III, and poorer event-free survival (EFS) (9.3 vs. 36.57 months; P = 0.0013) and overall survival (OS) (12.06 vs. 42.64 months; P < 0.001). The multivariate analysis showed that the presence of ME (hazard ratio [HR] 12.57; P = 0.003) and lack of autologous hematopoietic stem cell transplantation therapy (HR 4.382; P = 0.014) were predictive factors for poor OS. Using single-cell RNA sequencing, we discovered several bortezomib resistance genes were highly expressed in extramedullary malignant plasma cells. CONCLUSIONS: The presence of ME strongly predicts a poor prognosis in patients with MM relapse with EMD, and bortezomib resistance genes are highly expressed in extramedullary malignant plasma cells.

Fine particulate matter exposure disturbs autophagy, redox balance and mitochondrial homeostasis via JNK activation to inhibit proliferation and promote EMT in human alveolar epithelial A549 cells.

Epidemiologic studies have demonstrated a direct correlation between fine particulate matter (FPM) exposure and the high risk of respiratory diseases. FPM can penetrate deep into the lung and deposit in the alveoli with breath, where it directly interacts with alveolar epithelial cell (APC). However, we know little about the effects nor mechanisms of FPM on APC. Here, using human APC A549 cells, we found that FPM resulted in blockade of autophagic flux, redox imbalance and oxidative stress, mitochondrial fragmentation, increased mitophagy and impaired mitochondrial respiration. Further we showed that activation of JNK signaling (c-Jun N-terminal kinase) and excessive ROS (reactive oxygen species) release contribute to these adverse effects, with the former being upstream of the latter. More importantly, we found that scavenging ROS or inhibiting JNK activation could restore those effects as well as ameliorate FPM-induced inhibition of cell proliferation, and epithelial-mesenchymal transformation (EMT) in A549 cells. Taken together, our findings indicate that FPM leads to toxicity in alveolar type II cells via JNK activation, and JNK-targeting or antioxidant strategies might be beneficial for prevention or treatment of FPM-related pulmonary diseases.

Identification of evolutionary mechanisms of myelomatous effusion by single-cell RNA sequencing.

Myelomatous effusion (ME) is a rare manifestation of extramedullary multiple myeloma (MM) with limited therapeutic options and poor outcomes. The molecular mechanisms underlying ME are incompletely understood. We profiled transcriptomes of bone marrow, peripheral blood (PB), and pleural effusion/ascites from 3 patients with ME using single-cell RNA sequencing analysis. We found that ME contained a higher percentage of cytotoxic T cells, whereas PB contained a higher proportion of naive T cells. Malignant cells varied within and between sites and patients in their expression of signatures. We identified a gene module highly expressed in intramedullary and extramedullary plasma cell clusters and defined cell clusters expressing this gene set as extramedullary-initiating cells (EMICs). This gene set was associated with increased cellular proliferation, involved in p53 signaling, and related to poor prognosis in MM. The transcriptional regulators E2F1, YY1, and SMAD1 were activated in EMICs. Leukocyte immunoglobulin-like receptor subfamily B4 (LILRB4) was upregulated in extramedullary EMICs. We confirmed that LILRB4 promoted MM cell migration in vitro. This study provided insight into the evolutionary mechanisms of ME and defined EMICs and LILRB4 associated with extramedullary development.

A bionic "Trojan horse"-like gene delivery system hybridized with tumor and macrophage cell membrane for cancer therapy.

MiRNA-based gene therapy as a novel targeted therapy has yielded promising results in experimental cancer treatment, however, the inefficient delivery of miRNA to target tissues has limited its application in vivo. Here a unique dual-membrane-camouflaged miRNA21 antagomir delivery nanoplatform (M@NPs/miR21) with immune escape and homologous targeting properties was constructed by cancer cell membrane and macrophage membrane. Different from the single-cell membrane camouflage strategy, the dual-membrane camouflage miRNA21 antagomir delivery nanoplatform based on modification of CD47 protein with immune escape signal and galectin-3 protein with tumor cell aggregation enables efficient, safe and targeted therapy for colon cancer and lung metastases. Camouflaged with the dual-cell membrane, the "Trojan horse" like "pseudo-tumor cell" and/or "pseudo-macrophage" (M@NPs/miR21) carried the target gene miR21 antagomir to the tumor site and showed significant anti-tumor properties at the periphery and the core of subcutaneous tumor tissues. In addition, M@NPs/miR21 was more likely to penetrate dense tumor tissues and function within the tumor mass than NPs/miR21 without membrane coating. M@NPs/miR21 can deliver miR21 antagomir into MC38 cancer cells and tumor tissues, promote tumor apoptosis, and regulate the expression of Bcl2 and Ki67. Moreover, the M@NPs/miR21 gene delivery system not only can effectively inhibit the progression of subcutaneous tumors and lung metastases, but also showed minimal toxicity and good biosafety, making this delivery system particularly attractive for future translational research.

[The Risk and Survival Analysis of Multiple Malignancies in Hematologic Malignancy Patients: A Single Chinese Center Retrospective Study, 2009 through 2017].

OBJECTIVE: To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients. METHODS: The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively. RESULTS: A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival. CONCLUSION: In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.

Photoactivated MXene Nanosheets for Integrated Bone-Soft Tissue Therapy: Effect and Potential Mechanism.

The bone defects caused by trauma are inevitably accompanied by soft tissue damage. The development of multifunctional bioactive biomaterials with integrated bone and soft tissue regeneration is necessary and needed urgently in orthopedics. In this work, we found that the photoactivated MXene (Ti3C2Tx) nanosheet showed positive effects on promoting both bone and soft tissue regeneration. We further investigated the detailed effect and potential mechanism of photoactivated MXene on tissue regeneration. Photoactivated MXene shows a good thermal effect and robust antibacterial activity to inhibit the expression of inflammation factors and methicillin-resistant Staphylococcus aureus (MRSA) infection and induces the expression of pro-angiogenic factors and soft tissue wound repair. Photoactivated MXene can also regulate the osteogenic differentiation of adipose-derived stem cells (ADSCs) through the ERK signaling pathway by activating the heat shock protein 70 (HSP70) and enhancing the repair of bone tissue. This work sheds light on the development of bioactive MXene with photothermal activation as an efficient strategy for bone and soft tissue regeneration simultaneously.

Differences in clinical characteristics and chest CT findings between severe and critical H1N1 pneumonia.

INTRODUCTION: Critical H1N1 pneumonia patients usually have one of the symptoms such as respiratory failure, septic shock, multiple organ dysfunction, or other need for intensive care management, which are associated with high risk of mortality. It is essential to differentiate the severity of H1N1 pneumonia and take corresponding target treatments. OBJECTIVES: We aim to investigate the differences in clinical characteristics and chest computed tomography (CT) findings between severe and critical patients with H1N1 pneumonia. METHODS: A total of 27 patients diagnosed with H1N1 pneumonia from October 2018 to March 2019 were retrospectively analyzed, and the differences in clinical manifestations, laboratory tests, and chest CT findings between the severe group (15 patients) and the critical group (12 patients) were compared. RESULTS: Frequency of dyspnea at rest was higher in critical group than that in severe group (P = 0.019). The neutrophil percentage was higher (P = 0.014) and the lymphocyte percentage was lower (P = 0.025) in critical compared with severe group. Bilateral lung involvement was the predominant pattern in both severe and critical patients, whereas the number of involved lobes in critical patients was more than that in severe patients (P = 0.024). Peripheral distribution was the predominant pattern in severe patients (40%), whereas more diffuse involvement of the lungs was observed in critical patients (83.30%). Ground-glass opacities and consolidation were the main CT findings in both groups, and prevalence of consolidation was higher in critical relative to severe group (83.30%). CONCLUSION: Compared with severe patients, those with critical H1N1 pneumonia were more likely to present with dyspnea at rest and decreased lymphocyte percentage. Chest CT showed that diffuse bilateral involvement and higher prevalence of consolidation are associated with critical outcomes.

Engineering Multifunctional Polyether Ether Ketone Implant: Mechanics-Adaptability, Biominerialization, Immunoregulation, Anti-Infection, Osteointegration, and Osteogenesis.

Polyether ether ketone (PEEK) has become one of the most promising polymer implants in bone orthopedics, due to the biocompatibility, good processability, and radiation resistance. However, the poor mechanics-adaptability/osteointegration/osteogenesis/antiinfection limits the long-term in vivo applications of PEEK implants. Herein, a multifunctional PEEK implant (PEEK-PDA-BGNs) is constructed through in situ surface deposition of polydopamine-bioactive glass nanoparticles (PDA-BGNs). PEEK-PDA-BGNs exhibit good performance on osteointegration and osteogenesis in vitro and in vivo, due to their multifunctional properties including mechanics-adaptability, biominerialization, immunoregulation, anti-infection, and osteoinductive activity. PEEK-PDA-BGNs can show the bone tissue-adaptable mechanic surface and induce the rapid biomineralization (apatite formation) under a simulated body solution. Additionally, PEEK-PDA-BGNs can induce the M2 phenotype polarization of macrophages, reduce the expression of inflammatory factors, promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), and improve the osseointegration and osteogenesis ability of the PEEK implant. PEEK-PDA-BGNs also show good photothermal antibacterial activity and can kill 99% of Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA), suggesting their potential antiinfection ability. This work suggests that PDA-BGNs coating is probably a facile strategy to construct multifunctional (biomineralization, antibacterial, immunoregulation) implants for bone tissue replacement.

Identification of long noncoding RNA NEAT1 as a key gene involved in the extramedullary disease of multiple myeloma by bioinformatics analysis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) are involved in tumorigenesis and play a key role in cancer progression. To determine whether lncRNAs are involved in extramedullary disease of multiple myeloma (EMD), we analyzed the expression profile of lncRNAs in EMD. METHODS: Three pairs of EMD patients and their intramedullary MM cells were screened by microarray first. We extracted data from gene chips and made an identification of lncRNAs and mRNAs with significant differences between EMD group and non EMD group. WGCNA confirmed the EMD related gene module and drew a heat map to further determine the key gene lncRNA-NEAT1. In the meantime, bone marrow and extramedullary samples (hydrothorax and ascites) were collected from 2 MM patients and subjected to single-cell RNA-seq. Single cell Transcriptome analysis was conducted to verify the gene expression difference of malignant plasma cells derived from intramedullary and extramedullary. Then we verified high expression level of lncRNA-NEAT1 in EMD patients by using quantitative real-time PCR (qRT-PCR) and analyzed the correlation between expression patterns and survival and molecular genetics analysis of the LncRNA (NEAT1) involved in MM patients. At last, cell experiments were conducted to observe the effects of down-regulation of NEAT1on the proliferation, cell cycle and PTEN pathway related proteins of multiple myeloma cell lines U266 and RPMI8226. RESULTS: We identified one of the EMD related key gene is lncRNA-NEAT1. Compared with patients without extramedullary lesions, intramedullary MM cells in EMD patients expressed NEAT1 highly. The outcome of parallel single-cell RNA sequencing (RNA-seq) revealed NEAT1 level of plasma cells came from pleural effusion /ascites increased significantly compared with myeloma-stricken bone marrow. By survival and molecular genetic analysis, NEAT1 gene expression was not associated with OS and PFS in MM patients. However, the expression of NEAT1 is related to adverse therapeutic reactions and the progression of MM. We found that the expressions of NEAT1 were negatively associated with albumin levels and were positively associated with gain of chromosome 1q, IGH-CCND1, IGH@-FGFR3/WHSC1,and IGH-MAF gene fusion, respectively. At the level of cell experiment, CCK-8, soft agar clone formation experiment and CFSE staining showed that down regulating NEAT1 could inhibit the proliferation of U266 and RPMI8226 cells; Cell cycle detection showed that down-regulation of NEAT1 would interfere with the cell cycle process, and RPMI 8226 cells were blocked in G1 phase. Western blot analysis showed that when the expression of NEAT1 was down regulated in U266 and RPMI 8226 cells, the expression of PTEN and p-PTEN (phosphorylated phosphatase and tensin homologue) was up-regulated, and the expression of PI3K, p-PI3K (human phosphorylated inositol 3 kinase), Akt, p-Akt (phosphorylated protein kinase B). DISCUCCION AND CONCLUSION: This study provides novel insights into the lncRNA-NEAT1 and reveals that NEAT1 maybe a potential lncRNA biomarkers in EMD.