Hierarchical porous carbon nanofibrous membranes with elaborated chemical surfaces for efficient adsorptive removal of volatile organic compounds from air.

Volatile organic compounds (VOCs) in the air pose great health risks to humans and the environment. Adsorptive separation technology has proven effective in mitigating VOC pollution, with the adsorbent being the critical component. Therefore, the development of highly efficient adsorbent materials is crucial. Carbon nanofibers, known for their physical-chemical stability and rapid adsorption kinetics, are promising candidates for removing VOCs from the air. However, the relatively simple porous structures and inert surface chemical properties of traditional carbon nanofibers present challenges in further enhancing their application performance further. Herein, a hierarchical porous carbon nanofibrous membrane was prepared using electrospinning technology and a one-step carbonization & activation method. Phenolic resin and polyacrylonitrile were used as co-precursors, with silica nanoparticles serving as the dopant. The resulting membrane exhibited a specific surface area of up to 1560.83 m2/g and surfaces rich in functional O-/N- groups. With a synergistic effect of developed micro- and meso-pores and active chemical surfaces, the carbon nanofibrous membrane demonstrated excellent adsorption separation performance for various VOCs, with comparable adsorption capacities and fast kinetics. Moreover, the membrane displayed remarkable reusability and dynamic adsorption performance for different VOCs, indicating its potential for practical applications.

Advancements in Thermal Insulation through Ceramic Micro-Nanofiber Materials.

Ceramic fibers have the advantages of high temperature resistance, light weight, favorable chemical stability and superior mechanical vibration resistance, which make them widely used in aerospace, energy, metallurgy, construction, personal protection and other thermal protection fields. Further refinement of the diameter of conventional ceramic fibers to microns or nanometers could further improve their thermal insulation performance and realize the transition from brittleness to flexibility. Processing traditional two-dimensional (2D) ceramic fiber membranes into three-dimensional (3D) ceramic fiber aerogels could further increase porosity, reduce bulk density, and reduce solid heat conduction, thereby improving thermal insulation performance and expanding application areas. Here, a comprehensive review of the newly emerging 2D ceramic micro-nanofiber membranes and 3D ceramic micro-nanofiber aerogels is demonstrated, starting from the presentation of the thermal insulation mechanism of ceramic fibers, followed by the summary of 2D ceramic micro-nanofiber membranes according to different types, and then the generalization of the construction strategies for 3D ceramic micro-nanofiber aerogels. Finally, the current challenges, possible solutions, and future prospects of ceramic micro-nanofiber materials are comprehensively discussed. We anticipate that this review could provide some valuable insights for the future development of ceramic micro-nanofiber materials for high temperature thermal insulation.

Non-destructive strategy to extract sustainable helix and high-strength Musa core fibers for rapid water conduction and evaporation.

The reuse and development of natural waste resources is a hotspots and challenges in the research of new fiber materials and the resolution of environmental concern globally. Herein, this study aimed to develop a simple and direct manual extraction process to extract Musa core fibers (MCFs) for rapid water conduction and evaporation. Through simple processes such as ring cutting and stretching, this green and non-destructive inside-out extraction strategy enabled Musa fibers to be naturally and harmlessly degummed from natural Musa stems, with good maintenance of the fiber structure and highly helical morphology. The extracted fibers are composed of regularly and closely arranged cellulose nanofibrils in the shape of ribbon spirally arranged multi-filaments, and the single filament is about 2.65 µm. The high-purity fibers exhibit ultra-high tensile strength under a non-destructive extraction process, and the ultimate tensile strength in dry state is as high as 742.95 MPa. The tensile strength is affected by the number of fiber bundles, which shows that tensile strength and tensile modulus is higher than those of vascular bundle fibers in dry or wet condition. In addition, the MCFs membrane indicates good water conductivity, with a water absorption height of 50 mm for the sample in only 60 s. Moreover, the water evaporation rate of MCFs reaches 1.37 kg m-2 h-1 in 30 min, which shows that MCFs have excellent water conductivity and evaporation rate compared with ordinary cotton fibers. These results indicate that MCFs have great potential in replacing the use of chemical methods to extract fibers from vascular bundles, providing an effective way to achieve sustainability in quick-drying applications, as well as in the sustainable development of natural waste resources.

Advanced Strategies of CAR-T Cell Therapy in Solid Tumors and Hematological Malignancies.

Chimeric antigen receptor T-cells, known as CAR-T cells, represent a promising breakthrough in the realm of adoptive cell therapy. These T-cells are genetically engineered to carry chimeric antigen receptors that specifically target tumors. They have achieved notable success in the treatment of blood-related cancers, breathing new life into this field of medical research. However, numerous obstacles limit chimeric antigen receptors T-cell therapy's efficacy, such as it cannot survive in the body long. It is prone to fatigue and exhaustion, leading to difficult tumor elimination and repeated recurrence, affecting solid tumors and hematological malignancies. The challenges posed by solid tumors, especially in the context of the complex solid-tumor microenvironment, require specific strategies. This review outlines recent advancements in improving chimeric antigen receptors T-cell therapy by focusing on the chimeric antigen receptors protein, modifying T-cells, and optimizing the interaction between T-cells and other components within the tumor microenvironment. This article aims to provide an extensive summary of the latest discoveries regarding CAR-T cell therapy, encompassing its application across various types of human cancers. Moreover, it will delve into the obstacles that have emerged in recent times, offering insights into the challenges faced by this innovative approach. Finally, it highlights novel therapeutic options in treating hematological and solid malignancies with chimeric antigen receptors T-cell therapies.

Recent Advancement in Inhaled Nano-drug Delivery for Pulmonary, Nasal, and Nose-to-brain Diseases.

Pulmonary, nasal, and nose-to-brain diseases involve clinical approaches, such as bronchodilators, inhaled steroids, oxygen therapy, antibiotics, antihistamines, nasal steroids, decongestants, intranasal drug delivery, neurostimulation, and surgery to treat patients. However, systemic medicines have serious adverse effects, necessitating the development of inhaled formulations that allow precise drug delivery to the airways with minimum systemic drug exposure. Particle size, surface charge, biocompatibility, drug capacity, and mucoadhesive are unique chemical and physical features that must be considered for pulmonary and nasal delivery routes due to anatomical and permeability considerations. The traditional management of numerous chronic diseases has a variety of drawbacks. As a result, targeted medicine delivery systems that employ nanotechnology enhancer drug efficiency and optimize the overall outcome are created. The pulmonary route is one of the most essential targeted drug delivery systems because it allows the administering of drugs locally and systemically to the lungs, nasal cavity, and brain. Furthermore, the lungs' beneficial characteristics, such as their ability to inhibit first-pass metabolism and their thin epithelial layer, help treat several health complications. The potential to serve as noninvasive self-administration delivery sites of the lung and nasal routes is discussed in this script. New methods for treating respiratory and some systemic diseases with inhalation have been explored and highlight particular attention to using specialized nanocarriers for delivering various drugs via the nasal and pulmonary pathways. The design and development of inhaled nanomedicine for pulmonary, nasal, and respiratory medicine applications is a potential approach for clinical translation.

Expanding the role of combined immunochemotherapy and immunoradiotherapy in the management of head and neck cancer (Review).

Immunotherapy has become one of the most promising approaches in tumor therapy, and there are numerous associated clinical trials in China. As an immunosuppressive tumor, head and neck squamous cell carcinoma (HNSCC) carries a high mutation burden, making immune checkpoint inhibitors promising candidates in this field due to their unique mechanism of action. The present review outlines a comprehensive multidisciplinary cancer treatment approach and elaborates on how combining immunochemotherapy and immunoradiotherapy guidelines could enhance clinical efficacy in patients with HNSCC. Furthermore, the present review explores the immunology of HNSCC, current immunotherapeutic strategies to enhance antitumor activity, ongoing clinical trials and the future direction of the current immune landscape in HNSCC. Advanced-stage HNSCC presents with a poor prognosis, low survival rates and minimal improvement in patient survival trends over time. Understanding the potential of immunotherapy and ways to combine it with surgery, chemotherapy and radiotherapy confers good prospects for the management of human papillomavirus (HPV)-positive HNSCC, as well as other HPV-positive malignancies. Understanding the immune system and its effect on HNSCC progression and metastasis will help to uncover novel biomarkers for the selection of patients and to enhance the efficacy of treatments. Further research on why current immune checkpoint inhibitors and targeted drugs are only effective for some patients in the clinic is needed; therefore, further research is required to improve the overall survival of affected patients.

[Improvement of Preparation Method of Rats Platelet-Rich Plasma and Quality Detection].

OBJECTIVE: To optimize the single centrifugation preparation protocol of rat platelet-rich plasma (PRP). METHODS: The arterial blood of rats obtained by carotid artery intubation was collected by heparin sodium anticoagulant tubes, and then the blood divided into sterile EP tubes, adjusting the red blood cell concentration with normal saline, while rat PRP was prepared by centrifugation under different conditions (the centrifugal force was 200×g-240×g, and the centrifugal time was 8-12 min). Subsequently, the blood cell count and quality evaluation of anticoagulat whole blood and PRP were performed by hematology analyzer and flow cytometry, respectively, and the differences between different groups were compared. RESULTS: The red blood cell concentration to (5.5-6.5)×1012/L after anticoagulation of rat whole blood was good for PRP extraction. When the blood samples was centrifuged at 220×g for 10 min, the platelet recovery rate was the highestï¼»(53.52±0.63)%ï¼½. The level of apoptosis and activation of plateles in PRP were not significantly different compared to whole blood(P>0.05), and the release level of growth factor was significantly increased(P<0.05). CONCLUSION: It is a key to improve the PRP extraction efficiency by reducing the amount of mixed red blood cell, and this study successfully modified the preparation method of rat PRP, with platelets high recovery rate and stable quality.

Antimicrobial agent chloroxylenol targets ß­catenin­mediated Wnt signaling and exerts anticancer activity in colorectal cancer.

Chloroxylenol is the active ingredient of the antibacterial agent Dettol. The anticancer effect and underlying mechanisms of this compound and other common antimicrobial agents have not been clearly elucidated. In the present study, the effects of chloroxylenol, benzalkonium chloride, benzethonium chloride, triclosan and triclocarban on ß­catenin­mediated Wnt signaling in colorectal cancer were evaluated using the SuperTOPFlash reporter assay. It was demonstrated that chloroxylenol, but not the other antimicrobial agents tested, inhibited the Wnt/ß­catenin signaling pathway by decreasing the nuclear translocation of ß­catenin and disrupting ß­catenin/T­cell factor 4 complex, which resulted in the downregulation of the Wnt target genes Axin2, Survivin and Leucine­rich G protein­coupled receptor­5. Chloroxylenol effectively inhibited the viability, proliferation, migration and invasion, and sphere formation, and induced apoptosis in HCT116 and SW480 cells. Notably, chloroxylenol attenuated the growth of colorectal cancer in the MC38 cell xenograft model and inhibited organoid formation by the patient­derived cells. Chloroxylenol also demonstrated inhibitory effects on the stemness of colorectal cancer cells. The results of the present study demonstrated that chloroxylenol could exert anti­tumor activities in colorectal cancer by targeting the Wnt/ß­catenin signaling pathway, which provided an insight into its therapeutic potential as an anticancer agent.

Cryopreserved platelets washed with a dialysis machine for dimethyl sulphoxide removal.

BACKGROUND AND OBJECTIVES: Cryopreserved platelets (cPLTs) can be stored for years and are mainly used in military settings. However, the commonly used cryoprotectant dimethyl sulphoxide (DMSO) has toxic side effects when utilized in high quantities. We developed a novel method to aseptically remove DMSO from thawed cPLTs by dialysis. MATERIALS AND METHODS: One unit of platelets (N = 6) was mixed with 75 mL of 27% DMSO within 4 days after collection and stored at -80°C for 1 week. The platelet counts, platelet distribution width, mean platelet volume (MPV), platelet activity, platelet release, platelet aggregation, platelet metabolism indicators and platelet ultrastructural features (determined by electron microscopy) of the samples at the pre-freeze, post-thaw wash (post-TW) and 24 h post-thaw wash (24-PTW) stages were determined and compared. RESULTS: The DMSO clearance rate from the post-TW platelets was 95.56 ± 1.3%, and the platelet recovery rate after washing was 74.66 ± 6.34%. The total count, activity, release factors, aggregation and thrombolytic ability of the post-TW platelets were lower, whereas the MPV and apoptosis rates were higher compared with those of the pre-freeze platelets. The lactic acid, glucose and potassium ions released from the platelets during washing were filtered away by the dialyser, which significantly reduced their concentration. However, 24-PTW platelets were metabolically active, resulting in a decrease in pH and glucose content and an increase in lactic acid content. The level of potassium ions remained low after 24 h of storage and washing. The pre-freeze platelets maintained their normal disc shape and exhibited an open canalicular system (OCS) and a dense tubular system. The cPLTs appeared irregular after washing, with protruding pseudopodia and an extensive OCS, which increased the release of their contents. CONCLUSION: We developed a novel dialysis method to effectively remove DMSO from cPLTs under aseptic conditions and maintain platelet quality. The clinical efficacy of our method remains to be determined. However, the function of the platelets declined 24 h after washing, making them unsuitable for transfusion.

YBX1 as an oncogenic factor in T-cell acute lymphoblastic leukemia.

Y-box-binding protein 1 (YBX1), a member of the RNA-binding protein family, is a critical regulator of cell survival in various solid tumors and acute myeloid leukemia. However, the function of YBX1 in T-cell acute lymphoblastic leukemia (T-ALL) remains elusive. Here, we found that YBX1 was upregulated in patients with T-ALL, T-ALL cell lines, and NOTCH1-induced T-ALL mice. Furthermore, depletion of YBX1 dramatically reduced cell proliferation, induced cell apoptosis, and induced G0/G1 phase arrest in vitro. Moreover, YBX1 depletion significantly decreased the leukemia burden in the human T-ALL xenograft and NOTCH1-induced T-ALL mice model in vivo. Mechanistically, downregulation of YBX1 markedly inhibited the expression of total AKT serine/threonine kinase (AKT), p-AKT, total extracellular signal-regulated kinase (ERK), and p-ERK in T-ALL cells. Taken together, our results uncovered a critical role of YBX1 in the leukemogenesis of T-ALL, which may have great potential as a biomarker and therapeutic target in T-ALL.

WDR54 exerts oncogenic roles in T-cell acute lymphoblastic leukemia.

WDR54 has been recently identified as a novel oncogene in colorectal and bladder cancers. However, the expression and function of WDR54 in T-cell acute lymphoblastic leukemia (T-ALL) were not reported. In this study, we investigated the expression of WDR54 in T-ALL, as well as its function in T-ALL pathogenesis using cell lines and T-ALL xenograft. Bioinformatics analysis indicated high mRNA expression of WDR54 in T-ALL. We further confirmed that the expression of WDR54 was significantly elevated in T-ALL. Depletion of WDR54 dramatically inhibited cell viability and induced apoptosis and cell cycle arrest at S phase in T-ALL cells in vitro. Moreover, knockdown of WDR54 impeded the process of leukemogenesis in a Jurkat xenograft model in vivo. Mechanistically, the expression of PDPK1, phospho-AKT (p-AKT), total AKT, phospho-ERK (p-ERK), Bcl-2 and Bcl-xL were downregulated, while cleaved caspase-3 and cleaved caspase-9 were upregulated in T-ALL cells with WDR54 knockdown. Additionally, RNA-seq analysis indicated that WDR54 might regulate the expression of some oncogenic genes involved in multiple signaling pathways. Taken together, these findings suggest that WDR54 may be involved in the pathogenesis of T-ALL and serve as a potential therapeutic target for the treatment of T-ALL.

Extracellular Matrix-Mimetic Peptide Scaffolds Prolonged the Hypothermic Preservation of Stem Cells for Storage and Transportation.

Encouraging advances in both regenerative medicine and tissue engineering with stem cells require a short-term preservation protocol to provide enough time for quality control or the transportation of cell products from manufacturing facilities to clinical destinations. The hypothermic preservation of stem cells under refrigerated conditions (2-8 °C) in their specific culture medium provides an alternative and low-cost method for cryopreservation or commercial preservation fluid for short-term storage. However, most stem cells are vulnerable to hypothermia, which might result in cell damage from the cooling process and the lack of extracellular matrix (ECM). Herein, we report a peptide scaffold cell-culture-medium additive for mimicking in vivo ECM to enhance the storage efficiency of mesenchymal stem cells (MSCs) under hypothermic preservation. Peptide scaffolds exhibit protective effects against hypothermic injury by maintaining the viability, proliferation, migration, and differentiation capabilities of cells. The mechanistic study showed that the peptide scaffold was conducive to maintain mitochondrial function by retaining mitochondrial respiration, mitochondrial membrane potential (ΔΨm), and mass to alleviate intracellular and mitochondrial reactive oxygen species (ROS) production. Moreover, the peptide scaffold also prolonged the survival and retained the multipotency of hematopoietic stem and progenitor cells (HSPCs) under hypothermic conditions. In conclusion, these results demonstrate a feasible and convenient preservation system for stem cells that has the potential to promote the clinical application of hematopoietic stem cell therapy.

The Application of Nanotechnology in Immunotherapy based Combinations for Cancer Treatment.

There has been a great amount of advancement in the early field of nano-immunotherapy and combination therapy. Persistent consideration regarding the clinical challenges and therapeutic hindrance should be tended to achieve therapeutic efficacy and potential. In this review, we will address how nanotechnology could defeat the difficulties resulting from cancer immunotherapy, how nanoparticles' utilization can enhance the efficacy of immune checkpoint blockers, and reconstituting the tumor microenvironment can promote antitumor responses. Moreover, this review discusses how nanoparticles mediate therapeutic modalities like chemotherapy, photodynamic therapy, photothermal therapy, and radiotherapy, which are used to target and destroy cancerous cells, initiate the release of tumor antigens, and can trigger anti-tumor immunity reactions. Furthermore, we analyzed the potential benefits of immunotherapy combinatorial using the nanoparticle delivery system to prevent tumor recurrence, hinder metastases, and decrease systemic toxicity of major organs and healthy cells common with uncontrolled targeting.

Combined Immunotherapy and Targeted Therapies for Cancer Treatment: Recent Advances and Future Perspectives.

The previous year's worldview for cancer treatment has advanced from general to more precise therapeutic approaches. Chemotherapies were first distinguished as the most reliable and brief therapy with promising outcomes in cancer patients. However, patients could also suffer from severe toxicities resulting from chemotherapeutic drug usage. An improved comprehension of cancer pathogenesis has led to new treatment choices, including tumor-targeted therapy and immunotherapy. Subsequently, cancer immunotherapy and targeted therapy give more hope to patients since their combination has tremendous therapeutic efficacy. The immune system responses are also initiated and modulated by targeted therapies and cytotoxic agents, which create the principal basis that when targeted therapies are combined with immunotherapy, the clinical outcomes are of excellent efficacy, as presented in this review. This review focuses on how immunotherapy and targeted therapy are applicable in cancer management and treatment. Also, it depicts promising therapeutic results with more extensive immunotherapy applications with targeted therapy. Further elaborate that immune system responses are also initiated and modulated by targeted therapies and cytotoxic agents, which create the principal basis that this combination therapy with immunotherapy can be of great outcome clinically.

[Factors Affecting the Preservation of Human Peripheral Blood Mononuclear Cells at 4 ℃].

OBJECTIVE: To analyze the preservation effect and related influencing factors of human peripheral blood mononuclear cells under serum-free condition at 4 ℃. METHODS: Human peripheral blood mononuclear cells were isolated by density gradient centrifugation, and stored at 4 ℃ under different cell concentrations, supplemented with human serum albumin, and glucose. The cell viability, total cell number, viable cell number and cell phenotype were detected during preservation of 72 h. RESULTS: With the prolongation of storage time, the number of human peripheral blood mononuclear cells gradually decreased(r=0.982). Compared with the cell concentration of (5-6)×106 cells/ml, the cell number decreased more slowly when the cell storage concentration was (1-2)×106 cells/ml; Adding human serum albumin and glucose can effectively improve the survival rate of human peripheral blood mononuclear cells, among which 2% human serum albumin has a better preservation effect; Compared with the blank control group, the analysis results of cell subsets showed that the downward trends of NK cells and T cells were significantly slowed after adding albumin and glucose. CONCLUSION: The cell density of (1-2)×106/ml and 2% human serum albumin are more suitable for the preservation of PBMC, and 5% glucose can improve the preservation effect of human peripheral blood mononuclear cells at 4 ℃.

Facile fabrication of composite cellulose fibrous materials for efficient and consecutive dyeing wastewater treatment.

Fabricating dye adsorbents with efficient adsorption properties is of great significance in the treatment of printing and dyeing wastewater. Herein, composite materials of polydopamine decorated cellulose fibrous nonwovens (PDA@CF NWs) were fabricated by constructing a PDA functional layer on the surface of cellulose fibers via in situ polymerization. In addition, a three-dimensional adsorbent of 3D PDA@CF NWs with good hydrophilicity, structural stability, and compression resistance could be obtained using a facilely laminating and traditional loop bonding reinforcing technique. Attributed to the efficient and uniform loading of an active PDA functional layer, the resulting PDA@CF NWs exhibited a relatively large adsorption capacity of around 91 mg g-1 towards the template dye of methylene blue within a fast equilibrium time of 2 h, which was superior to most of the fibrous adsorbents. In addition, the treatment column of 3D PDA@CF NWs exhibited a breakthrough capacity of 40.9 mg g-1, reaching nearly 50% of the static saturated dye-binding capacity. More importantly, the 3D PDA@CF NWs column could effectively and continuously separate the mixture of different dyes under gravity, highlighting an excellent practical performance. Thus, the PDA@CF NWs are expected to provide a promising candidate for environment-friendly, large-scale and efficient treatment of industrial printing and dyeing wastewater.

Negatively Charged Composite Nanofibrous Hydrogel Membranes for High-Performance Protein Adsorption.

Nanofibrous materials are considered as promising candidates for fabricating high-efficiency chromatography media, which are urgently needed in protein pharmaceuticals purification and biological research, yet still face several bottlenecks. Herein, novel negatively charged composite nanofibrous hydrogel membranes (NHMs) are obtained by a facile combination of electrospinning and surface coating modification. The resulting NHMs exhibit controllable morphologies and chemical structures. Benefitting from the combined effect of the stable framework of silicon dioxide (SiO2) nanofiber and the function layer of negatively charged hydrogel, as well as good pore connectivity among nanofibers, NHMs exhibit a high protein adsorption capacity of around 1000 mg g-1, and are superior to the commercial cellulose fibrous adsorbent (Sartobind®) and the reported nanofibrous membranous adsorbents. Moreover, due to their relatively stable physicochemical and mechanical properties, NHMs possess comprehensive adsorption performance, favorable resistance to acid and solvents, good selectivity, and excellent regenerability. The designed NHMs composite adsorbents are expected to supply a new protein chromatography platform for effective protein purification in biopharmaceuticals and biochemical reagents.

Platelet 3D Preservation Using a Novel Biomimetic Nanofiber Peptide for Reduced Apoptosis and Easy Storage.

Human platelets (PLTs) are vulnerable to unfavorable conditions, and their adequate supply is limited by strict transportation conditions. We report here that PLTs preserved under three-dimensional (3D) conditions using novel biomimetic nanofiber peptides showed reduced apoptosis compared with classical PLTs stored at 22 °C and facilitated the storage and transportation of PLTs. The mechanism of PLT 3D preservation involves the formation of cross-links and a 3D nanofibrous network by a self-assembled peptide scaffold material at physiological conditions after initiation by triggers in plasma. PLTs adhere to the surface of the nanofibrous network to facilitate the 3D distribution of PLTs. The 3D microstructure, rheological properties, and effect on the inflammatory response and hemolysis were evaluated. Compared to traditional PLTs stored at 22 °C, PLTs subjected to 3D preservation showed similar morphology, number, aggregation activity, and reduced apoptosis. The detection of the reactive oxygen species (ROS) levels demonstrated that both reduced intracellular and mitochondrial ROS levels were correlated with reduced apoptosis. This study reveals a new 3D preservation method for PLTs based on the use of novel biomimetic nanofiber peptides that presents an attractive opportunity for various biomedical applications.

Sulfur-Coordinated Organoiridium(III) Complexes Exert Breast Anticancer Activity via Inhibition of Wnt/ß-Catenin Signaling.

The sulfur-coordinated organoiridium(III) complexes pbtIrSS and ppyIrSS, which contain C,N and S,S (dithione) chelating ligands, were found to inhibit breast cancer tumorigenesis and metastasis by targeting Wnt/ß-catenin signaling for the first time. Treatment with pbtIrSS and ppyIrSS induces the degradation of LRP6, thereby decreasing the protein levels of DVL2, ß-catenin and activated ß-catenin, resulting in downregulation of Wnt target genes CD44 and survivin. Additionally, pbtIrSS and ppyIrSS can suppress cell migration and invasion of breast cancer cells. Furthermore, both complexes show the ability to inhibit sphere formation and mediate the stemness properties of breast cancer cells. Importantly, pbtIrSS exerts potent anti-tumor and anti-metastasis effects in mouse xenograft models through the blockage of Wnt/ß-catenin signaling. Taken together, our results indicate that pbtIrSS has great potential to be developed as a breast cancer therapeutic agent with a novel mechanism.

M1-polarized alveolar macrophages are crucial in a mouse model of transfusion-related acute lung injury.

BACKGROUND: The pathogenesis of transfusion-related acute lung injury (TRALI) progress is incompletely understood, and specific therapies for TRALI are lacking. Alveolar macrophages (AMs) are critical for initiation and resolution of lung inflammation. However, the role of AMs in the pathogenesis of TRALI-associated lung failure is poorly understood. STUDY DESIGN AND METHODS: Mouse model for in vivo imaging of interleukin (IL)-6 activation in AMs was established by intratracheal instillation of a lentiviral vector carrying the luciferase reporter gene. The TRALI mouse model was produced by intraperitoneal lipopolysaccharide plus intravenous major histocompatibility complex Class I monoclonal antibody treatment. We focused on the changes in AMs in the lung during TRALI and examined whether targeting AMs is an effective strategy to alleviate this condition. MEASUREMENTS AND MAIN RESULTS: We confirmed that TRALI progress is accompanied by IL-6 activation in AMs. Further study showed that AMs undergo M1 activation during TRALI progress. AM depletion protected mice from TRALI, and transfusion of M1-polarized AMs into 34-1-2 s-treated mice elevated acute lung injury, indicating that the severity of TRALI was able to be ameliorated by targeting AM polarization. Next, we showed that α1 -antitrypsin (AAT) expression improved lung injury by modulating the production of IL-6 in AMs and decreased polarization of AMs toward the M1 phenotype. CONCLUSIONS: M1-polarized AMs are crucial in a mouse model of TRALI, and AAT may serve as a future treatment for TRALI by regulating the polarization of AMs.