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.

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.

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.

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.

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.