A homologous membrane-camouflaged self-assembled nanodrug for synergistic antitumor therapy.

Limited success has been achieved in ferroptosis-induced cancer treatment due to the challenges related to low production of toxic reactive oxygen species (ROS) and inherent ROS resistance in cancer cells. To address this issue, a self-assembled nanodrug have been investigated that enhances ferroptosis therapy by increasing ROS production and reducing ROS inhibition. The nanodrug is constructed by allowing doxorubicin (DOX) to interact with Fe2+ through coordination interactions, forming a stable DOX-Fe2+ chelate, and this chelate further interacts with sorafenib (SRF), resulting in a stable and uniform nanoparticle. In tumor cells, overexpressed glutathione (GSH) triggers the disassembly of nanodrug, thereby activating the drug release. Interestingly, the released DOX not only activates nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) to produce abundant H2O2 production for enhanced ROS production, but also acts as a chemotherapeutics agent, synergizing with ferroptosis. To enhance tumor selectivity and improve the blood clearance, the nanodrug is coated with a related cancer cell membrane, which enhances the selective inhibition of tumor growth and metastasis in a B16F10 mice model. Our findings provide valuable insights into the rational design of self-assembled nanodrug for enhanced ferroptosis therapy in cancer treatment. STATEMENT OF SIGNIFICANCE: Ferroptosis is a non-apoptotic form of cell death induced by the iron-regulated lipid peroxides (LPOs), offering a promising potential for effective and safe anti-cancer treatment. However, two significant challenges hinder its clinical application: 1) The easily oxidized nature of Fe2+ and the low concentration of H2O2 leads to a low efficiency of intracellular Fenton reaction, resulting in poor therapeutic efficacy; 2) The instinctive ROS resistance of cancer cells induce drug resistance. Therefore, we developed a simple and high-efficiency nanodrug composed of self-assembling by Fe2+ sources, H2O2 inducer and ROS resistance inhibitors. This nanodrug can effectively deliver the Fe2+ sources into tumor tissue, enhance intracellular concentration of H2O2, and reduce ROS resistance, achieving a high-efficiency, precise and safe ferroptosis therapy.

Ferrocene Derivatives for Photothermal Applications.

Ferrocene (Fc) and Fc derivatives have gained popularity in recent years due to their unique structure and characteristics. Among Fc's diverse performances, photothermal conversion, as a primary source of energy conversion, has sparked substantial study attention. This review summaries Fc and Fc derivatives with photothermal characteristics, as well as their applications developed recently. First, methods for the synthesis of Fc-based materials are systematically discussed. Then, the photothermal conversion mechanism based on nonradiative relaxation is summarized. Furthermore, the most recent advances in Fc-based materials in photothermal applications are described, including photothermal degradation, photothermal antibacterial, photothermal therapies, photothermal catalysis, solar-driven water production, and photothermal CO2 separation. Finally, a summary and insights on the photothermal application of Fc-based materials are provided. This paper seeks to provide researchers with a better knowledge of photothermal behavior while also highlighting the potential of Fc and its derivatives in photothermal fields.

LiCl in situ decorated metal-organic framework (MOF)-derived porous carbon for efficient solar-driven atmospheric water harvesting.

Solar-powered sorption-based atmospheric water harvesting (AWH) technology is a promising solution to the freshwater scarcity in arid regions. Existing adsorbent materials still face challenges in aspects such as cycling stability and adsorption kinetics and require further development. Herein, we presented a strategy for the in situ fabrication of high-performance adsorbents, lithium chloride (LiCl)-decorated metal-organic framework (MOF)-derived porous carbon sorbents (PCl), via high-temperature pyrolysis and hydrogen chloride (HCl) vapor treatment. The sorbents display high adsorption capacity across a wide range of humidity water adsorption capacities in a wide humidity range with the maximum adsorption capacity of 7.87 g g-1, and rapid response to the solar-driven process and excellent cyclic stability. The LiCl nanocrystals in PCl can be utilized efficiently and decorated within the porous framework stably, and demonstrate water adsorption at 20%, 40%, 60% and 80% RH, of 1.34, 1.69, 2.56 and 4.23 gH2O·gLiCl-1, respectively, and significantly higher water uptake and release rates than bulk LiCl. This may provide new guides for designing efficient solar-driven AWH.

Palmitic acid-capped MIL-101-Al as a nano-adjuvant to amplify immune responses against Pseudomonas aeruginosa.

As a highly contagious opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa) is one of the main causes of healthcare-associated infections. The drug-resistant nature of P. aeruginosa can render antibiotic treatments ineffective, leading to a high morbidity and mortality. Higher specificity and reduced toxicity are features of immunotherapy, which can generate robust immune responses and preserve long-term immunological memory to completely eradicate infections. In this study, we developed a type of P. aeruginosa vaccine based on a metal-organic framework. Specifically, MIL-101-Al nanoparticles were synthesized to encapsulate antigens derived from the bacterial lysate (BL) of PAO1, a drug-resistant P. aeruginosa, and the adjuvant unmethylated cytosine-phosphate-guanine oligonucleotide (CpG), which were then modified with palmitic acid (PAA) to obtain MIL-BC@PAA. The stability and biocompatibility were significantly increased by capping with PAA. Moreover, MIL-BC@PAA showed significantly enhanced uptake by antigen presenting cells (APCs), and promoted their maturation. Importantly, immunity studies revealed the greatly elicited antigen-specific humoral and cellular responses, and a protection rate of about 70% was observed in P. aeruginosa-challenged mice. Overall, these results demonstrate the promising potential of MIL-BC@PAA as an ideal nanovaccine for P. aeruginosa vaccination.

Collagen sponge scaffolds loaded with Trichostatin A pretreated BMSCs-derived exosomes regulate macrophage polarization to promote skin wound healing.

The process of wound healing includes the inflammatory stage, which plays an important role. Macrophages can promote inflammatory response and also promote angiogenesis, wound contraction and tissue remodeling required for wound healing. It is crucial to promote macrophages to polarize from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype at a critical time for the quality of wound healing. Because mesenchymal stem cell-derived exosomes have broad therapeutic prospects in the field of tissue repair and regeneration, in this study, we explored whether trichostatin A pretreated bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (T-Exo) could promote wound healing by binding to biomaterial scaffolds through certain anti-inflammatory effects. In the cell experiment, we established macrophage inflammation model and then treated with T-Exo, and finally detected the expression levels of macrophage polarization proteins CD206, CD86 and TNF-α, iNOS, and Arg-1 by Western Blot and immunofluorescence staining; detected the expression levels of inflammation-related genes TNF-α, iNOS, IL-1ß, IL-10 and anti-inflammatory genes CD206 and Arg-1 by qRT-PCR; explored the promoting ability of T-Exo to promote cell migration and tube formation by cell scratch experiment and angiogenesis experiment. The results showed that T-Exo could promote the polarization of M1 macrophages to M2 macrophages, and promote the migration and angiogenesis of HUVECs. Because TSA pretreatment may bring about changes in the content and function of BMSCs-derived exosomes, proteomic analysis was performed on T-Exo and unpretreated BMSCs-derived exosomes (Exo). The results showed that the differentially expressed proteins in T-Exo were related to some pathways that promote angiogenesis, cell migration, proliferation, and re-epithelialization. Then, exosome/collagen sponge (T-Exo/Col) biological scaffolds were prepared, and the physicochemical properties and biocompatibility of the scaffolds were investigated. Animal skin wound models were established, and the therapeutic effect and anti-inflammatory effect of T-Exo/Col in wound repair were evaluated by small animal in vivo imaging, H&E staining, Masson trichrome staining, immunohistochemical staining, Western Blot, and qRT-PCR. The results showed that T-Exo significantly promoted wound healing by inhibiting inflammation, thereby further promoting angiogenesis and collagen formation in vivo. Moreover, the existence of Col scaffold in T-Exo/Col enabled T-Exo to achieve a certain sustained release effect. Finally, we further explored whether TSA exerts beneficial effects by inhibiting HDAC6 gene of BMSCs, but the results showed that knockdown of HDAC6 gene would cause oxidative stress damage to BMSCs, which means that TSA does not produce these beneficial effects by inhibiting HDAC6 gene. What molecular mechanisms TSA exerts beneficial effects through needs to be further elucidated in the future.

Critical parameters to standardize the size and concentration determination of nanomaterials by nanoparticle tracking analysis.

The size and concentration are critical for the diagnostic and therapeutic applications of nanomaterials but the accurate measurement remains challenging. Nanoparticle tracking analysis (NTA) is widely used for size and concentration determination. However, highly repeatable standard operating procedures (SOPs) are absent. We adopted the "search-evaluate-test" strategy to standardize the measurement by searching the critical parameters. The particles per frame are linearly proportional to the sample concentration and the measured results are more accurate and repeatable when the concentration is 108-109 particles/ml. The optimal detection threshold is around 5. The optimal camera level is such that it allows clear observation of particles without diffractive rings and overexposure. The optimal speed is ≤ 50 in AU and âˆ¼ 10 µl/min in flow rate. We then evaluated the protocol using polydisperse polystyrene particles and we found that NTA could discriminate particles in bimodal mixtures with high size resolution but the performance on multimodal mixtures is not as good as that of resistive pulse sensing (RPS). We further analyzed the polystyrene particles, SiO2 particles, and biological samples by NTA following the SOPs. The size and concentration measured by NTA differentially varies to those determined by RPS and transmission electron microscopy.

Application of exosomes in tumor immunity: recent progresses.

Exosomes are small extracellular vesicles secreted by cells, ranging in size from 30 to 150 nm. They contain proteins, nucleic acids, lipids, and other bioactive molecules, which play a crucial role in intercellular communication and material transfer. In tumor immunity, exosomes present various functions while the following two are of great importance: regulating the immune response and serving as delivery carriers. This review starts with the introduction of the formation, compositions, functions, isolation, characterization, and applications of exosomes, and subsequently discusses the current status of exosomes in tumor immunotherapy, and the recent applications of exosome-based tumor immunity regulation and antitumor drug delivery. Finally, current challenge and future prospects are proposed and hope to demonstrate inspiration for targeted readers in the field.

Anodic Electrodepositing Bioinspired Cu-BDC-NH2@Graphene Oxide Membrane for Efficient Uranium Extraction.

The challenge of removing trace levels of heavy metal ions, particularly uranium, from wastewater is a critical concern in environmental management. Uranium, a key element in long-term nuclear power generation, often poses significant extraction difficulties in wastewater due to its low concentration, interference from other ions, and the complexity of aquatic ecosystems. This study introduces an anodic electrodeposited hierarchical porous 2D metal-organic framework (MOF) Cu-BDC-NH2@graphene oxide (GO) membrane for effective uranium extraction by mimicking the function of the superb-uranyl-binding protein. This membrane is characterized by its hierarchical pillared-layer structures resulting from the controlled orientation of Cu-BDC-NH2 MOFs within the laminated GO layers during the electrodeposition process. The integration of amino groups from 2D Cu-BDC-NH2 and carboxylate groups from GO enables a high affinity to uranyl ions, achieving an unprecedented uranium adsorption capacity of 1078.4 mg/g and outstanding selectivity. Our findings not only demonstrate a breakthrough in uranium extraction technology but also pave the way for advancements in water purification and sustainable energy development, proposing a practical and efficient strategy for creating orientation-tunable 2D MOFs@GO membranes tailored for high-efficiency uranium extraction.

Multifunctional DNA scaffold mediated gap plasmon resonance: Application to sensitive PD-L1 sensor.

The introduction of noble metal nanoparticles with good LSPR characteristics can greatly improve the sensitivity of SPR through resonance coupling effect. The plasma resonance response and optical properties of film coupling nanoparticle systems largely depends on the ingenious design of gap structures. Nucleic acid nanostructures have good stability, flexibility, and high biocompatibility, making them ideal materials for gap construction. 2D MOF (Cu-Tcpp) has a large conjugated surface similar to graphene, which can provide a stable substrate for the directional fixation of nucleic acid nanostructures. However, research on gap coupling plasmon based on nucleic acid nanostructures and 2D MOF is still rarely reported. By integrating the advantages of Cu-Tcpp assembled film and DNA tetrahedron immobilization, a nano gap with porous scaffold structure between the gold film and gold nanorod was build. The rigidity of DNA tetrahedron can precisely control the gap size, and its unique programmability allows us to give the coupling structure greater flexibility through the design of nucleic acid chain. The experimental results and FDTD simulation show that the film coupling nanoparticle systems constructed with DNA tetrahedrons greatly enhance the electric field strength near the chip surface and effectively improve the sensitivity of SPR. This research shows the huge potential of nucleic acid nanomaterials in the construction of SPR chip surface microstructures.

Stabilizing electron-rich Ni single-atoms on black phosphorus nanosheets boosts photocatalytic carbon dioxide reduction.

The development of unique single-atom catalysts with electron-rich feature is essential to promoting the photocatalytic CO2 reduction, yet remains a big challenge. Here, a conceptionally new single-atom catalyst constructed from atomically dispersed Ni-P3 species on black phosphorus (BP) nanosheets (BP-Ni) is synthesized for realizing highly efficient visible-light-driven CO2 reduction when trapping photogenerated electrons from homogeneous light absorbers in the presence of triethanolamine as the sacrificial agent. Both the experimental and theoretical calculation data reveal that the Ni-P3 species on BP nanosheets own the electron-rich feature that can improve the photogenerated charge separation efficiency and lower the activation barrier of CO2 conversion. This unique feature makes BP-Ni exhibit the much higher activity as cocatalyst in the photocatalytic CO2 reduction than BP nanosheets. The BP-Ni can also be applied as a cocatalyst for enhanced photocatalytic CO2 reduction after combining with CdSe/S colloidal crystal photocatalyst. The present study offers valuable inspirations for the design and construction of effective catalytic sites toward photocatalytic CO2 reduction reactions.

Parathyroid hormone treatment partially reverses endplate remodeling and attenuates low back pain in animal models of spine degeneration.

Low back pain (LBP) is one of the most prevalent diseases affecting quality of life, with no disease-modifying therapy. During aging and spinal degeneration, the balance between the normal endplate (EP) bilayers of cartilage and bone shifts to more bone. The aged/degenerated bony EP has increased porosity because of osteoclastic remodeling activity and may be a source of LBP due to aberrant sensory innervation within the pores. We used two mouse models of spinal degeneration to show that parathyroid hormone (PTH) treatment induced osteogenesis and angiogenesis and reduced the porosity of bony EPs. PTH increased the cartilaginous volume and improved the mechanical properties of EPs, which was accompanied by a reduction of the inflammatory factors cyclooxygenase-2 and prostaglandin E2. PTH treatment furthermore partially reversed the innervation of porous EPs and reversed LBP-related behaviors. Conditional knockout of PTH 1 receptors in the nucleus pulposus (NP) did not abolish the treatment effects of PTH, suggesting that the NP is not the primary source of LBP in our mouse models. Last, we showed that aged rhesus macaques with spontaneous spinal degeneration also had decreased EP porosity and sensory innervation when treated with PTH, demonstrating a similar mechanism of PTH action on EP sclerosis between mice and macaques. In summary, our results suggest that PTH treatment could partially reverse EP restructuring during spinal regeneration and support further investigation into this potentially disease-modifying treatment strategy for LBP.

Collagen-EGCG Combination Synergistically Prevents UVB-Induced Skin Photoaging in Nude Mice.

Ultraviolet (UV) radiation is a major cause of skin photoaging through generating excessive oxidative stress and inflammation. One of the strategies is to use photo-chemoprotectors, such as natural products with antioxidant and anti-inflammatory properties, to protect the skin from photo damage. The present study investigates the photoprotective potentials of topical administration of unhydrolyzed collagen, epigallocatechin gallate (EGCG), and their combination against ultraviolet B (UVB)-induced photoaging in nude mice. It is found that both the solo and combined pretreatments could recover UVB-induced depletion of antioxidative enzymes, including superoxide dismutase and glutathione peroxidase (GSH-Px), as well as an increase of lipid peroxide malondialdehyde and inflammatory tumor necrosis factor-α. Meanwhile, the UVB-stimulated skin collagen degradation is attenuated significantly with drug treatments, which is evidenced by expression analysis of matrix metalloproteinase-1 and hydroxyproline. Additionally, the mouse skin histology shows that the drug-pretreated groups possess decreased epidermis thickness and normal collagen fiber structure of the dermis layer. These results demonstrate that both EGCG and collagen can protect the skin against UVB-induced skin photoaging. Synergistically, the combination of them shows the maximum prevention to skin damage, showing its potential in the application of anti-photoaging formulation products.

Ca-MOF-Derived Porous Sorbents for High-Yield Solar-Driven Atmosphere Water Harvesting.

The development of high-yield, metal-organic framework (MOF)-based water harvesters in arid areas remains challenging due to the absence of effective strategies for enhancing water sorption capacity and kinetics. Herein, we presented a novel strategy for in situ fabrication of calcium chloride (CaCl2) decorated MOF-derived porous sorbents (PCC-42) through pyrolysis Ca-MOF and subsequently hydrochloric acid (HCl) vapor treatment process. The resulting PCC-42 sorbents exhibited a high water adsorption capacity of 3.04 g g-1 at 100% relative humidity (RH), outstanding photothermal performance, and rapid water uptake-release kinetics, surpassing most reported MOFs adsorbents. At 20, 30, 40, and 50% RH, PCC-42 demonstrated water uptake capacity of 0.45, 0.59, 0.76, and 0.9 g g-1, which represented an increase of 421 and 940% (at 20% RH) and 333 and 351% (at 30% RH) compared to Ca-MOF and CaCl2·2H2O, respectively. Approximately 80% of the adsorbed water in PCC-42 could be released under one sun within 50 min. Indoor water harvesting experiments demonstrated that PCC-42 is a promising adsorbent for various humidity environments. Additionally, outdoor solar-driven atmospheric water harvesting (AWH) tests revealed a high daily water production of 1.13 L/kgadsorbent under typical arid conditions (30-60% RH). The proposed strategy helps the design of high-performance adsorbents for solar-driven AWH in arid environments.

Deep eutectic solvent-infused two-dimensional metal-organic framework membranes as quasi-solid-state electrolytes for wearable micro-supercapacitors.

The burgeoning field of miniaturized and portable electronic devices calls for novel advances in micro-energy storage technology. Micro-supercapacitors (MSC) stand at the forefront of this endeavour, yet unlocking their full potential necessitates the exploration of high-performance electrolytes. Herein, we introduce a strategy that leverages flexible metal-organic framework (MOF, CuTCPP) nanosheet-based membranes to construct quasi-solid-state electrolytes (QSSEs) and enhance the ionic conductivity and electrochemical performance of deep eutectic solvent (DES)-based MSCs. Owing to the multiple nanochannel pathways provided by the porous MOF nanosheets, the ionic conductivity of DES within the nanochannels exhibits a 13-fold increment compared with its bulk counterpart. Furthermore, we engineered MSC harnessing the CuTCPP-DES system, whose performance surpasses that reported for most of the ionic liquid and 2D material-based MSCs. The areal-specific capacitance was 81.3 mF cm-2 at a current density of 0.1 mA cm-2, and the energy density was 45.17 µW h cm-2 at a power density of 8.559 mW cm-2. Notably, the performance of MSCs remains consistent and unaffected, even when subjected to bending. These findings contribute to the exploration and potential optimization of the inherent benefits of MOFs, thereby presenting a paradigm shift in nanoconfined systems for microscale energy storage applications.

Research progress of extracellular vesicles and exosomes derived from mesenchymal stem cells in the treatment of oxidative stress-related diseases.

There is growing evidence that mesenchymal stem cell-derived extracellular vesicles and exosomes can significantly improve the curative effect of oxidative stress-related diseases. Mesenchymal stem cell extracellular vesicles and exosomes (MSC-EVs and MSC-Exos) are rich in bioactive molecules and have many biological regulatory functions. In this review, we describe how MSC-EVs and MSC-Exos reduce the related markers of oxidative stress and inflammation in various systemic diseases, and the molecular mechanism of MSC-EVs and MSC-Exos in treating apoptosis and vascular injury induced by oxidative stress. The results of a large number of experimental studies have shown that both local and systemic administration can effectively inhibit the oxidative stress response in diseases and promote the survival and regeneration of damaged parenchymal cells. The mRNA and miRNAs in MSC-EVs and MSC-Exos are the most important bioactive molecules in disease treatment, which can inhibit the apoptosis, necrosis and oxidative stress of lung, heart, kidney, liver, bone, skin and other cells, and promote their survive and regenerate.

The long transcript of lncRNA TMPO-AS1 promotes bone metastases of prostate cancer by regulating the CSNK2A1/DDX3X complex in Wnt/ß-catenin signaling.

The second most common male cancer is prostate cancer (PCa), which has a high tendency for bone metastasis. Long non-coding RNAs, including TMPO-AS1, play a crucial role in PCa progression. However, TMPO-AS1's function in PCa bone metastasis (BM) and its underlying molecular mechanisms are unclear. Herein, we found that the long transcript of TMPO-AS1 (TMPO-AS1L) was upregulated in PCa tissues with bone metastasis, and overexpression of TMPO-AS1L correlated with advanced clinicopathological features and reduced BM-free survival in patients with PCa. Upregulated TMPO-AS1L promoted, whereas downregulated TMPO-AS1L inhibited, the PCa cell bone metastatic capacity in vitro and in vivo. Mechanistically, TMPO-AS1L was demonstrated to act as a scaffold, that strengthened the interaction of casein kinase 2 alpha 1 (CSNK2A1) and DEAD-box helicase 3 X-linked (DDX3X), and activated the Wnt/ß-catenin signaling pathway, thus promoting BM of PCa. Moreover, upregulation of TMPO-AS1L in PCa resulted from transcription elongation modulated by general transcription factor IIF subunit 2 (GTF2F2). Collectively, our study provides critical insights into the role of TMPO-AS1L in PCa BM via Wnt/ß-catenin signaling, identifying TMPO-AS1L as a candidate marker of PCa bone metastasis prognosis and therapeutic target.

Proton conducting metal-organic frameworks with light response for multistate logic gates.

The simulation of neurons receiving stimulation and transmitting signals by proton conduction has great potential applications in electrochemistry and biology. In this work, copper tetrakis(4-carboxyphenyl)porphyrin (Cu-TCPP), which is a proton conductive metal organic framework (MOF) with photothermal response, is adopted as the structural framework, with the in situ co-incorporation of polystyrene sulfonate (PSS) and sulfonated spiropyran (SSP) to prepare the composite membranes. The resultant PSS-SSP@Cu-TCPP thin-film membranes were used as the logic gates i.e., NO gate, NOR gate and NAND gate because of the photothermal effect of Cu-TCPP MOFs and the photoinduced conformational changes of SSP. This membrane exhibits the high proton conductivity of 1.37 × 10-4 S cm-1. Under the conditions of 55 °C and 95% relative humidity (RH), using 405 nm laser irradiation with 400 mW cm-2 and 520 nm laser irradiation with 200 mW cm-2 as inputs, the device can be adjusted between various steady states, and the value of the conductivity is regarded as the output with different thresholds in different logic gates. Before and after laser irradiation, the electrical conductivity changes dramatically, and the ON/OFF switching ratio reached 1068. The application of three logic gates is realized by constructing circuits with LED lights. Depending on the convenience of light and the easy measurement of conductivity, this kind of device with light source as input and electrical signal as output provides the possibility to realize the remote control of chemical sensors and complex logic gates devices.

BHLHE22 drives the immunosuppressive bone tumor microenvironment and associated bone metastasis in prostate cancer.

BACKGROUND: The molecular characteristics of prostate cancer (PCa) cells and the immunosuppressive bone tumor microenvironment (TME) contribute to the limitations of immune checkpoint therapy (ICT). Identifying subgroups of patients with PCa for ICT remains a challenge. Herein, we report that basic helix-loop-helix family member e22 (BHLHE22) is upregulated in bone metastatic PCa and drives an immunosuppressive bone TME. METHODS: In this study, the function of BHLHE22 in PCa bone metastases was clarified. We performed immunohistochemical (IHC) staining of primary and bone metastatic PCa samples, and assessed the ability to promote bone metastasis in vivo and in vitro. Then, the role of BHLHE22 in bone TME was determined by immunofluorescence (IF), flow cytometry, and bioinformatic analyses. RNA sequencing, cytokine array, western blotting, IF, IHC, and flow cytometry were used to identify the key mediators. Subsequently, the role of BHLHE22 in gene regulation was confirmed using luciferase reporter, chromatin immunoprecipitation assay, DNA pulldown, co-immunoprecipitation, and animal experiments. Xenograft bone metastasis mouse models were used to assess whether the strategy of immunosuppressive neutrophils and monocytes neutralization by targeting protein arginine methyltransferase 5 (PRMT5)/colony stimulating factor 2 (CSF2) could improve the efficacy of ICT. Animals were randomly assigned to treatment or control groups. Moreover, we performed IHC and correlation analyses to identify whether BHLHE22 could act as a potential biomarker for ICT combination therapies in bone metastatic PCa. RESULTS: Tumorous BHLHE22 mediates the high expression of CSF2, resulting in the infiltration of immunosuppressive neutrophils and monocytes and a prolonged immunocompromised T-cell status. Mechanistically, BHLHE22 binds to the CSF2 promoter and recruits PRMT5, forming a transcriptional complex. PRMT5 epigenetically activates CSF2 expression. In a tumor-bearing mouse model, ICT resistance of Bhlhe22+ tumors could be overcome by inhibition of Csf2 and Prmt5. CONCLUSIONS: These results reveal the immunosuppressive mechanism of tumorous BHLHE22 and provide a potential ICT combination therapy for patients with BHLHE22+ PCa.

Sunlight propelled two-dimensional nanorobots with enhanced mechanical damage of bacterial membrane.

Bacterial pollution in water sources poses a serious threat to human health and causes a water crisis. To treat it efficiently and ecologically, many studies have explored the antibacterial properties of two-dimensional nanomaterials in water, but their static antibacterial modes limit their effectiveness. In this work, we designed a facile and effective antibacterial nanorobots by loading super small gold nanorods (sAuNR) onto the surface of MXene nanosheets (MXene@sAuNR). The plasmon resonance effect of sAuNR can enhance the optical absorption cross section of the nanorobots, thereby improving their motion ability under irradiation and then causing cell membrane mechanical damage to bacteria. Our research proved that nanorobots with good optical driving characteristics displayed gratifying antibacterial properties even at ultra-low concentration as 5 µg/mL within 30 min. Furthermore, the nanorobots showed satisfactory antibacterial efficiency in real river samples under sunlight irradiation. These nanorobots presented in this study provides valuable insights towards designing self-energy collection and self-driving antibacterial materials that overcome the shortcomings of conventional static antibacterial methods. As sunlight is the cheapest and natural light source, these nanorobots have opened an effective and sustainable way for large-scale treatment of bacterial pollution in water.

Electrodeposited MOFs Membrane with In Situ Incorporation of Charged Molecules for Osmotic Energy Harvesting.

Ion-selective membranes are considered as the promising candidates for osmotic energy harvesting. However, the fabrication of highly perm-selective membrane is the major challenge. Metal-organic frameworks (MOFs) with well-defined nanochannels along functional charged groups show great importance to tackle this problem. Here, a series of dense sodium polystyrene sulfonate (PSS) incorporated MOFs composite membranes (PSS@MOFs) on a porous anodic aluminum oxide (AAO) membrane via in situ anodic electrodeposition process are developed. Benefiting to the novel structural design of the confined Ag layer, PSS@MOFs dense composite membrane with less defects formed. The sulfonated nanochannels of the PSS@MOFs composite membrane provided rapid and selective transport of cations due to the enhanced electrostatic interaction between the permeating ions and MOFs. While osmotic energy conversion, 860 nm thick negatively charged PSS@MOFs composite membrane achieves an ultrahigh cation transfer number of 0.993 and energy conversion efficiency of 48.8% at a 100-fold salinity gradient. Moreover, a large output power of 2.90 µW has been achieved with an ultra-low internal resistance of 999 Ω, employing an effective area of 12.56 mm2 . This work presents a promising strategy to construct a high-performance MOFs-based osmotic energy harvesting system for practical applications.