Effectiveness of Butorphanol in alleviating intra- and post-operative visceral pain following microwave ablation for hepatic tumor: a dual-central, randomized, controlled trial.

Many patients who underwent hepatic percutaneous microwave ablation (MWA) reported experiencing pain during the procedure. This study utilized a well-designed multicentral, randomized, and placebo-controlled format to investigate the effects of Butorphanol. Patients who underwent MWA were randomly assigned to either Butorphanol or normal saline group. The primary outcomes of the study were assessed by measuring the patients' intraoperative pain levels using a 10-point visual analog scale (VAS). Secondary outcomes included measuring postoperative pain levels at the 6-h mark (VAS) and evaluating comprehensive pain assessment outcomes. A total of 300 patients were divided between the control group (n = 100) and the experimental group (n = 200). Butorphanol showed statistically significant reductions in intraoperative pain levels compared to the placebo during surgery (5.00 ± 1.46 vs. 3.54 ± 1.67, P < 0.001). Significant differences were observed in postoperative pain levels at the 6-h mark and in the overall assessment of pain (1.39 + 1.21 vs. 0.65 + 0.81, P < 0.001). Butorphanol had a significant impact on reducing the heart rate of patients. The empirical evidence supports the effectiveness of Butorphanol in reducing the occurrence of visceral postoperative pain in patients undergoing microwave ablation for hepatic tumor. Furthermore, the study found no noticeable impact on circulatory and respiratory dynamics.

Construction of MXene-mediated inorganic-organic quaternary ammonium salt-hybrid coating for fire safety and multi-mode synergistic antibacterial of cotton fabric.

With the continuous development of the society, there is a growing demand for the durability, versatility and multifunction of cott fabrics. In this work, the cotton fabric is coated with multifunctional coating via dip-coating of transition metal carbide (MXene) and then encapsulation of dimethyloctadecyl [3-trimethoxysilopropyl] ammonium chloride (QAS). In view of MXene with excellent light absorption and photothermal conversion efficiency, the controllable antibacterial performance of the cotton fabric is further improved. Benefiting from the encapsulation of QAS, CF@P@M@QAS fabric shows mechanical stability (24 h washing, 1000 cycles folding test and 100 cyclic abrasion) and hydrophobicity. Meantime, the QAS on the surface of multifunctional cotton fabric significantly increases antibacterial activity, and the antibacterial rate can reach to 100 % against Staphylococcus aureus (S. aureus) and 98 % Escherichia coli (E. coli). Besides, CF@P@M@QAS cotton fabric also integrates functions of fire safety and physical therapy. Thus, this multifunctional cotton fabric based MXene offers a novel solution for extending its application in medical electronics and physical therapy.

Self-Supplied Reactive Oxygen Species-Responsive Mitoxantrone Polyprodrug for Chemosensitization-Enhanced Chemotherapy under Moderate Hyperthermia.

Currently, the secondary development and modification of clinical drugs has become one of the research priorities. Researchers have developed a variety of TME-responsive nanomedicine carriers to solve certain clinical problems. Unfortunately, endogenous stimuli such as reactive oxygen species (ROS), as an important prerequisite for effective therapeutic efficacy, are not enough to achieve the expected drug release process, therefore, it is difficult to achieve a continuous and efficient treatment process. Herein, a self-supply ROS-responsive cascade polyprodrug (PMTO) is designed. The encapsulation of the chemotherapy drug mitoxantrone (MTO) in a polymer backbone could effectively reduce systemic toxicity when transported in vivo. After PMTO is degraded by endogenous ROS of the TME, another part of the polyprodrug backbone becomes cinnamaldehyde (CA), which can further enhance intracellular ROS, thereby achieving a sustained drug release process. Meanwhile, due to the disruption of the intracellular redox environment, the efficacy of chemotherapy drugs is enhanced. Finally, the anticancer treatment efficacy is further enhanced due to the mild hyperthermia effect of PMTO. In conclusion, the designed PMTO demonstrates remarkable antitumor efficacy, effectively addressing the limitations associated with MTO.

Balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution in postoperative liver regeneration.

BACKGROUND & AIMS: Post-hepatectomy liver failure (PHLF) leads to poor prognosis in patients undergoing hepatectomy, with hepatic vascular reconstitution playing a critical role. However, the regulators of hepatic vascular reconstitution remain unclear. In this study, we aimed to investigate the regulatory mechanisms of hepatic vascular reconstitution and identify biomarkers predicting PHLF in patients undergoing hepatectomy. METHODS: Candidate genes that were associated with hepatic vascular reconstitution were screened using adeno-associated virus vectors in Alb-Cre-CRISPR/Cas9 mice subjected to partial hepatectomy. The biological activities of candidate genes were estimated using endothelial precursor transfusion and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) models. The level of candidates was detected in biopsies from patients undergoing ALPPS. Risk factors for PHLF were also screened using retrospective data. RESULTS: Downregulation of Gata3 and upregulation of Ramp2 in hepatocytes promoted the proliferation of liver sinusoidal endothelial cells and hepatic revascularization. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor A (VEGFA) played opposite roles in regulating the migration of endothelial precursors from bone marrow and the formation of new sinusoids after hepatectomy. Gata3 restricted endothelial cell function in patient-derived hepatic organoids, which was abrogated by a Gata3 inhibitor. Moreover, overexpression of Gata3 led to higher mortality in ALPPS mice, which was improved by a PEDF-neutralizing antibody. The expression of Gata3/RAMP and PEDF/VEGFA tended to have a negative correlation in patients undergoing ALPPS. A nomogram incorporating multiple factors, such as serum PEDF/VEGF index, was constructed and could efficiently predict the risk of PHLF. CONCLUSIONS: The balance of Gata3 and Ramp2 in hepatocytes regulates the proliferation of liver sinusoidal endothelial cells and hepatic revascularization via changes in the expression of PEDF and VEGFA, revealing potential targets for the prevention and treatment of PHLF. IMPACT AND IMPLICATIONS: In this study, we show that the balance of Gata3 and Ramp2 in hepatocytes regulates hepatic vascular reconstitution by promoting a shift from pigment epithelium-derived factor (PEDF) to vascular endothelial growth factor A (VEGFA) expression during hepatectomy- or ALLPS (associating liver partition and portal vein ligation for staged hepatectomy)-induced liver regeneration. We also identified serum PEDF/VEGFA index as a potential predictor of post-hepatectomy liver failure in patients who underwent hepatectomy. This study improves our understanding of how hepatocytes contribute to liver regeneration and provides new targets for the prevention and treatment of post-hepatectomy liver failure.

A novel ROS-activable self-immolative prodrug for tumor-specific amplification of oxidative stress and enhancing chemotherapy of mitoxantrone.

Reactive oxygen species (ROS) as well-known endogenous stimuli has been widely used to activate drug delivery systems (DDSs) for tumor-specific therapy. Unfortunately, endogenous ROS in the tumor microenvironment (TME) is not enough to achieve effective therapeutic efficacy and cancer cells have adapted to high oxidative stress by upregulating glutathione (GSH) level. Herein, we devised a novel ROS-activable self-immolative prodrug CASDB with both GSH-depletion ability and ROS self-supply competence. Then, an stimuli-responsive nanoplatform integrating CASDB with clinical chemotherapeutics mitoxantrone (MTO) and PLGA was fabricated (denoted as CMPs) through nanoprecipitation method. The CMPs could achieve desired accumulation at tumor tissues through enhanced permeability and retention (EPR) effects. Then the accumulated CMPs could induce tumor cell apoptosis efficiently. Especially, ROS in tumor sites could trigger the immolation of CASDB to generate CA and quinone methide (QM). Then CA and QM cooperatively promoted damage of mitochondria due to oxidative stress and led to cancer cells more sensitive to MTO. Accordingly, MTO could perturb cellular microenvironment of cancer cells then promote the degradation of CASDB. The experiment results demonstrated that CMPs were ideal for desirable synergetic tumor-specific anticancer therapy with negligible systemic toxicity. The half-maximal inhibitory concentrations (IC50) value of CMPs was 6.53 µM, while the IC50 values of MTO was 14.76 µM. And the CMPs group showed the strongest tumor suppressor effect with the tumor sizes increased to 1.2-fold (Control group: 20.6-fold, MTO only: 3.0-fold). This study should be inspirational for designing efficient prodrugs to overcome the handicaps of traditional chemotherapy.

ITCH facilitates proteasomal degradation of TXNIP in hypoxia- induced lung cancer cells.

BACKGROUND: Lung cancer (LC) is one of the most common cancers and a leading cause of cancer-related deaths worldwide. In many pathological conditions, particularly in the tumor microenvironment, cells and tissues frequently exist in a hypoxic state. Here, we evaluated Itchy E3 ubiquitin protein ligase (ITCH) expression in LC cells following hypoxia treatment. METHODS: LC cell lines were treated with hypoxic condition. Cell migration, invasion, inflammation, reactive oxygen species (ROS) production, and apoptosis of LC cells were determined by wound healing assay, Transwell invasive assay, ELISA, DCFH-DA staining, and flow cytometry, respectively. qPCR and WB were used to determine the expression of ITCH and TXNIP. Co-IP was performed to assess the interaction between ITCH and TXNIP. RESULTS: ITCH expression was downregulated in LC cells under hypoxic conditions. Next, LC cells were subjected to hypoxic conditions and changes in cell viability and metastasis were determined. Hypoxic conditions resulted in increased migration and invasion abilities of LC cells. Intracellular reactive oxygen species (ROS) production, inflammation, and apoptosis were also promoted by hypoxia. We found that ITCH overexpression led to the proteasomal degradation of thioredoxin-interacting protein (TXNIP), whereas the expression of the ITCH C830A mutant did not affect TXNIP levels in LC cells. The gain-of-function experiment demonstrated that migration, invasion, ROS generation, inflammation, and apoptosis of hypoxia-conditioned LC cells were ameliorated by ITCH overexpression, whereas the ITCH C830A mutant did not cause any changes in these phenotypes. Furthermore, the contribution of TXNIP knockdown and ITCH overexpression to the hypoxia-induced features in LC cells with ITCH C830A was found to be similar. CONCLUSION: Our results suggest a novel mechanism underlying the changes in ITCH-mediated malignant phenotypes of hypoxia-conditioned LC cells via TXNIP.

Hierarchical Ti3C2Tx@BPA@PCL for flexible polyurethane foam capable of anti-compression, self-extinguishing and flame-retardant.

It is of great importance to fabricate flexible polyurethane foam (FPUF) with superior mechanical properties and flame retardancy for practical applications. Herein, organosilicon and phenyl phosphorus compounds were synthesized and grafted on the surface of Ti3C2Tx (Ti3C2Tx@BPA@PCL) via in-situ polymerization. Then, the FPUF composites were fabricated, combining intrinsic flame retardancy (9,10-dihydro-9-oxa-10-phosphaphenanthrene 10-oxide-diethanolamine: DH-DOPO) (addition amount: 20 wt%) and Ti3C2Tx@BPA@PCL (addition amount: 4 wt%). Attributed to the rigid structure of Ti3C2Tx@BPA@PCL, the tensile strength and compression strength of FPUF showed 24.0% and 253% increase, respectively. In addition, anti-fatigue properties of FPUF composites during the cyclical test were dramatically enhanced. In contrast to pure FPUF, 36.1% and 44.0% reductions in peak heat release rate (pHRR) and total heat release (THR) were achieved for the FPUF containing Ti3C2Tx@BPA@PCL and DH-DOPO, the production rate of carbon dioxide (CO2) and carbon oxide (CO) also decreased by 40.3% and 52.1%, respectively. FPUF4 showed self-extinguishing behavior, and passed the vertical burning test (VBT). This work provides a facile approach to preparing high-performance FPUF with enhanced mechanical property and flame retardancy.

Functionalizing Ti3C2Tx for enhancing fire resistance and reducing toxic gases of flexible polyurethane foam composites with reinforced mechanical properties.

Flexible polyurethane foam (FPUF) is the most used polyurethane, but the highly flammable characteristic limits its widespread usage. In this work, ZIF-8@Ti3C2Txwas synthesized to reduce the heat and toxic gases of FPUF. Flame-retardant FPUF was characterized by cone calorimeter (Cone), thermogravimetric analysis/fourier-transform infrared spectroscopy (TG-FTIR), tensileand compression tests. Compared with pure FPUF, these results showed that the peak of heat release rate (PHRR), total heat release (THR), CO and HCN of FPUF6 decreased by 46%, 69%, 27% and 43.5%, respectively. Moreover, the tensile and compression strength of FPUF6 demonstrated a 52% and 130% increment, respectively. The superior dual metal catalytical charring-forming effect and physical barrier effect of ZIF-8@Ti3C2Tx were achieved. In summary, a simple and reliable strategy for preparing flame-retardant FPUF with reinforced mechanical and fire safety properties was provided.

Design of copper salt@graphene nanohybrids to accomplish excellent resilience and superior fire safety for flexible polyurethane foam.

Flexible polyurethane foam (FPUF) is the most commonly used polyurethane, but its highly flammable characteristics makes it ignite easily and release a lot of heat and toxic gases. Here, the effect of different forms of copper salt modified graphene (rGO@CuO, rGO@Cu2O and rGO@CSOH) on improving the fire protection efficiency and mechanical property of FPUF is explored. Hybrid FPUF is characterized by thermogravimetric analysis (TGA), cone calorimeter, thermogravimetric analysis/Fourier transform infrared spectroscopy (TG-IR), tension, compression, and falling ball rebound testing. Compared with pure FPUF, the FPUF/rGO@CSOH show a significant decreasement in reducing the heat release of FPUF, the PHRR and THR are reduced by 36.9% and 29.4%, respectively. While the FPUF/rGO@Cu2O demonstrate excellent smoke and toxic gases suppression in FPUF, the PSPR and TSR are reduced by 24.6% and 51.9%, and the COP and COY are also reduced by 51.9% and 55.3%, respectively. After adding the copper salt hybrid, the buffering performance of FPUF did not change. Fortunately, the tensile and compressive strength increase obviously. The flame retardant and smoke suppression mechanism of hybrid FPUF has also been studied. This article gives a effective strategy for the preparation of FPUF with outstanding mechanical property, flame retardant and smoke suppression properties.

The improvement of fire safety performance of flexible polyurethane foam by Highly-efficient P-N-S elemental hybrid synergistic flame retardant.

Herein, three different phosphorus-containing compounds (methyl phosphoryl dichloride, phenyl phosphoryl dichloride and phenyl dichlorophosphate) were reacted with 2-aminobenzothiazole respectively, and a series of synergistic flame retardants with phosphorus, nitrogen and sulfur elements were synthesized, named MPBT, PPBT and POBT respectively. Then, they were added to prepare flame-retardant flexible polyurethane foam (FPUF). Through the analysis of thermal stability, pyrolysis, heat release and smoke release behavior, the influence of different phosphorus-containing structures on the flame-retardant performance of FPUF was studied, and their flame-retardant mechanism was explored in detail. Among them, MPBT had the highest flame retardant efficiency with the same addition amount (10 wt%). The limiting oxygen index (LOI) value of PU/10.0% MPBT reached 22.5 %, and it successfully passed the vertical burning test. Subsequently, the addition amount of MPBT was increased and the best comprehensive performance of flame-retardant FPUF was explored. The results showed that the LOI value of PU/15.0% MPBT was increased to 23.5%. As for PU/15.0% MPBT, the peak heat release rate (PHRR) was 453 KW/m2, which was reduced by 46.64 %; and the flame retardancy index (FRI) value was also increased to 6.88. At the same time, the mechanical properties of flame-retardant FPUF were studied. The tensile strength of PU/15.0% MPBT reached 170 KPa, and the permanent deformation of FPUF/10% MPBT was only 4 %, showing its excellent resilience. The above results show that this phosphorus-containing element hybrid synergistic flame retardant (MPBT) has a very good application prospect in the field of flame-retardant polymer materials.

Anti-Fogging, Frost-Resistant transparent and flexible silver Nanowire-Ti3C2Tx MXene based composite films for excellent electromagnetic interference shielding ability.

The development of electronics proposes higher requirements for flexible, transparent, and conductive materials with high electromagnetic shielding performance in viewing windows. Flexible transparent films have been fabricated by collaborating one-dimensional silver nanowires (AgNWs) and novel two-dimensional Ti3C2Tx MXene sheets on PET films with an external polymeric coating consisting of poly (vinyl alcohol) (PVA) and poly(styrene sulfonate) (PSS). Especially, the combination of different dimensional nanomaterials effectively establishes a conductive network that exhibits a synergistic effect on excellent electromagnetic interference (EMI) shielding performance, which is superior to that of pure AgNW network or Ti3C2Tx network to some extent. By optimizing the AgNWs content (0.05 mg/cm2) and Ti3C2Tx sheets content (0.01 mg/cm2), the PET/AgNW/Ti3C2Tx/PVA-PSS film exhibits a transmittance of 81% and a desirable EMI SE value of 30.5 dB. In addition, the film shows outstanding anti-fogging and frost-resistant properties due to the remarkable water absorption capacity of PVA and PSS on the external surface. Considering its efficiency and simplicity, this transparent conductive film has promising applications in flexible transparent electronic devices and optical related fields.

The Re2Sn2O7 (Re = Nd, Sm, Gd) on the enhancement of fire safety and physical performance of Polyolefin/IFR cable materials.

Polyolefin (PO) cables used in confined spaces need to have low smoke, low heat release, low toxic gas release and excellent physical properties. In this work, a series of rare earth stannates Re2Sn2O7 (RES, Re = Nd, Sm, Gd) with high temperature catalytic performance were prepared by hydrothermal method for synergistic flame retardant PO/IFR. The flame retardancy, heat release, smoke density, toxic gas release and physical properties of PO composites were thoroughly studied in detail. The RES could enhance the vertical burning rating and the limiting oxygen index (LOI) of PO/IFR composites. Moreover, the residual char of the thermogravimetric analysis increased from 9.7% to 11.4 wt% after the RES added in PO/IFR system. Interestingly, the PO/IFR system containing Gd2Sn2O7 exhibits the lowest peak heat release rate of 233.7 kW/m2. Excellent flame resistance due to the formation of a complete and compact protective char layer. In addition, the toxic release of PO during combustion is also effectively reduced by introducing the RES. The tube furnace combustion test shows that the emission of carbon oxide (CO) and hydrogen cyanide (HCN) of PO/IFR/Gd2Sn2O7 are the lowest. It can be attributed to the catalytic effect of rare earth elements and the blocking effect of the dense char layer. In addition, compared with the PO/IFR composites, the PO/IFR/RES system demonstrate higher mechanical properties and volume resistivity. Therefore, the addition of RES has a positive effect on improving the physical properties and fire safety properties of the PO/IFR cable composites, especially suitable for using in confined spaces.

PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2.

Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS and established PHF5A as potential therapeutic target.

Durable electromagnetic interference (EMI) shielding ramie fabric with excellent flame retardancy and Self-healing performance.

Although more and more attention has been paid to electromagnetic interference (EMI) shielding fabric materials due to increasing electromagnetic waves pollution, little attention to their fire safety behavior and durability in practical use. Herein, durable EMI shielding ramie fabric with flame retardant and self-healing performance were fabricated by depositing ammonium polyphosphate (APP)/polyethyleneimine (PEI) layer, MXene sheets and polycaprolactone (PCL) layer. The resultant multifunctional fabric could self-extinguish and the peak heat release rate (pHRR) value reduced about 74.3% for the modified ramie fabric that contains about 12 wt% of PEI/APP bilayer compared with pure ramie fabric. Furthermore, the ramie fabric coated by a increasing amount of MXene sheets changed from insulating to conductive, thus gradually improving their EMI shielding performance, which exhibit a high electrical conductivity of 900.56 S/m with an outstanding SE value of 35 dB at a 1.2 mg/cm2 content in the X-band. Besides, When the multifunctional fabric was cut off under external force, it could achieve self-healing and the EMI shielding performance can recover to 34 dB due to the low melting point and good fluidity of PCL. Thus, this multifunctional fabric holds great promise for wearable intelligent cloth, EMI shielding and other fields.

A facile strategy for lightweight, anti-dripping, flexible polyurethane foam with low smoke emission tendency and superior electromagnetic wave blocking.

Flexible polyurethane foam (FPUF) has been considered as an excellent material in many fields, such as furniture and electromagnetic interference (EMI) shielding products due to its lightweight and flexibility. However, there is a severe fire hazard problem for FPUF that makes it unsuitable to be used in practical. Herein, a facile method was to prepare anti-dripping FPUF via electroless plating at ambient temperature. The silver nanoparticles (SNPs) were in-situ grown on the surface along with the polydopamine (PDA) as an adhesive and template (SNP@PDA@FPUF). As a result, these FPUFs show outstanding fire safety and anti-dripping capacity, and the heat release rate reduced 80.92%. Furthermore, the amounts of carbon oxide (CO) and carbon dioxide (CO2) decreased 75.01% and 22.4%, respectively. Above all, the EMI shielding effectiveness (SE) accomplished almost 120 dB as the increasing electroless time with a low density of 0.051 g/cm3. Furthermore, the specific EMI SE (SSE) and the absolute EMI SE (SSE/t) accomplished 2630.98 dB·cm3/g and 2434 dB·cm2/g, respectively, which was far beyond the commercial request. Therefore, this work may provide a facile way to prepare low density and EMI shielding products with high fire safety for next generation electronic products.

MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis.

PURPOSE: Lenvatinib is a long-awaited alternative to Sorafenib for first-line targeted therapy of patients with advanced hepatocellular carcinoma (HCC). However, resistance to Lenvatinib results in tumor progression and has become a major obstacle to improving the prognosis of HCC patients. Exploring the mechanisms underlying Lenvatinib resistance is considered essential for the treatment of advanced HCC. METHODS: Lenvatinib resistant HCC (LR-HCC) cells were generated and potential long non-coding RNAs (Lnc-RNAs) upregulated in LR-HCC cells were identified by RNA sequencing. The effects of upregulated Lnc-RNAs were evaluated in vitro in cell models and in vivo in experimental animals using quantitative cell viability and apoptosis assays. RESULTS: We found that Lnc-RNA MT1JP (MT1JP) was upregulated in LR-HCC cells and inhibited the apoptosis signaling pathway. In addition, we found that sponging of microRNA-24-3p by MT1JP released Bcl-2 like 2 (BCL2L2), an anti-apoptotic protein, thereby forming a positive-feedback loop. The role of this feedback loop was validated using rescue assays. Additionally, we found that upregulation of MT1JP and BCL2L2 impaired the sensitivity of HCC cells to Lenvatinib both vitro and vivo. CONCLUSIONS: Our results suggest a novel molecular feedback loop between MT1JP and apoptosis signaling in Lenvatinib sensitive HCC cells.

Prediction of Pretreatment 18F-FDG-PET/CT Parameters on the Outcome of First-Line Therapy in Patients with Metastatic Breast Cancer.

OBJECTIVE: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) can provide prognostic information, especially 18F-FDG uptake has been proven to be a predictor for the prognosis of various tumors. Nevertheless, the prognosis of other PET parameters in the metastatic setting remains unclear. This study was aimed at investigating pretreatment parameters based on 18F-FDG-PET/CT so as to estimate the progression-free survival (PFS) of metastatic breast cancer (MBC) patients receiving first-line treatment. METHODS: MBC patients who underwent a whole-body 18F-FDG-PET/CT prior to first-line therapy were enrolled. The heterogeneity parameter of PET/CT was analyzed, including heterogeneity index (HI) and general parameters (metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax) and mean SUV (SUVmean). PFS was used to evaluate the treatment outcome. Kaplan-Meier method was adopted to carry out survival analysis and Log rank test was conducted to make a comparison. RESULTS: A total of 177 MBC patients were selected, in which 68 were in De novo stage IV. Thirty patients were human epidermal growth factor receptor 2 (HER2)-positive, 60 patients were triple-negative, and 87 patients were hormone receptor (HR)-positive and HER2-negative. In the whole population, patients with high baseline SUVmax, SUVmean, MTV, TLG or HI were associated with lower PFS (P=0.028, 0.005, 0.017, 0.026 and 0.035, respectively). Among the patients in De novo stage IV, those with high HI at baseline had significantly shorter PFS (P=0.001). In HR+/HER2- and HER2+ subgroups, only baseline HI showed the predictive value of PFS (P=0.023 and 0.049, respectively). In the triple-negative subgroup, high baseline SUVmax, MTV or TLG showed the predictive value of worse PFS (P=0.030, 0.011 and 0.023, respectively). CONCLUSION: Pretreatment 18F-FDG-PET/CT parameters show the predictive value of PFS in MBC patients receiving first-line treatment. However, predictive PET/CT parameters might be different in patients with different molecular subtypes and De novo stage IV.

Self-healable castor oil-based waterborne polyurethane/MXene film with outstanding electromagnetic interference shielding effectiveness and excellent shape memory performance.

Recently, the increasing demands of the portable devices and flexible electronics have caused lots of electromagnetic wave pollution. MXene, a novel two-dimensional material, was considered as a promising two-dimensional material for preparing flexible electromagnetic interference (EMI) shielding films. Herein, we firstly synthesized a series of flexible and self-healable EMI shielding waterborne polyurethane (ADWPU) films by mechanically blending with Ti3C2Tx (ADWPU-T). Interestingly, the self-assembling between ADWPU and Ti3C2Tx constructed a tunable analogical structure providing reflection-absorption-multiple reflection shielding mechanism. Furthermore, the ADWPU-T emulsions were prepared from castor oil which is a low-cost and eco-friendly biomass polyol. The chain extender 2-aminophenyl disulfide endow a reversible dynamic polymer network which leading to shape memory performance (45°C heat treatment) and self-healing ability (60°C, 5 min healed). Above all, these multifunctional flexible films also exhibited outstanding EMI shielding performance (51.37 dB) and performed less decrement after 200 times bending and 80°C aging test for five days. Therefore, this work would provide a novel promising method for preparing responsive electromagnetic interference shielding products and smart electronic devices.

Nacre-Inspired Tunable Electromagnetic Interference Shielding Sandwich Films with Superior Mechanical and Fire-Resistant Protective Performance.

With the rapidly increasing development of portable device hardware and flexible electronics, ultrathin electromagnetic interference (EMI) shielding films with a combination of high flexibility and excellent mechanical properties are noticeably required. In addition to minimizing the electromagnetic wave pollution problem, the fire hazards caused by accidental electrical leakage or aging are also a cause of extensive concern. Inspired by nacre and sandwich structure, herein, we fabricated for the first time an electrical insulating sandwich-structured film based on Ca ion cross-linked sodium alginate (SA)-montmorillonite (MMT) and Ti3C2Tx MXene through a step-by-step vacuum-assisted filtration process. This novel design strategy not only maintains the inner EMI shielding network but also can act as an excellent fire-resistant barrier to protect the electronic device in case of accidental fire. Compared with the pure Ti3C2Tx layer, such kind of sandwich film can effectively maintain the EMI shielding performance (50.01 dB), dramatically enhance the mechanical properties (84.4 MPa), and exhibit excellent fire-resistant performance. Especially, compared with the film composed of mixture, the EMI shielding effectiveness value is only 55% that of sandwich films. Besides, it functions well under long-term heat aging test at 80 °C. Therefore, this unique design provides a novel EMI material strategy to facilitate its future applications in flexible electronics.

High Serum Levels of Cholesterol Increase Antitumor Functions of Nature Killer Cells and Reduce Growth of Liver Tumors in Mice.

BACKGROUND AND AIMS: The relationship between serum cholesterol level and development of hepatocellular carcinoma (HCC) remains unclear. We investigated the effects of serum cholesterol level on development of liver tumors in mice. METHODS: We performed studies with C57BL/6J mice, mice with disruption of the low-density lipoprotein receptor gene (Ldlr-/-mice), and mice with conditional deletion of nature killer (NK) cells (NKdele mice). Some C57BL/6J and NKdele mice were given injections of diethylinitrosamine to induce liver tumor formation. Mice were placed on a normal diet (ND) or high-cholesterol diet (HCD) to induce high serum levels of cholesterol. We also studied mice with homozygous disruption of ApoE (ApoE-/- mice), which spontaneously develop high serum cholesterol. C57BL/6J and NKdele mice on the ND or HCD were implanted with Hep1-6 (mouse hepatoma) cells and growth of xenograft tumors and lung metastases were monitored. Blood samples were collected from mice and analyzed by biochemistry and flow cytometry; liver and tumor tissues were collected and analyzed by histology, immunohistochemistry, and RNA-sequencing analysis. NK cells were isolated from mice and analyzed for cholesterol content, lipid raft formation, immune signaling, and changes in functions. We obtained matched tumor tissues and blood samples from 30 patients with HCC and blood samples from 40 healthy volunteers; levels of cholesterol and cytotoxicity of NK cells were measured. RESULTS: C57BL/6J mice on HCD and ApoE-/- mice with high serum levels of cholesterol developed fewer and smaller liver tumors and lung metastases after diethylinitrosamine injection or implantation of Hep1-6 cells than mice on ND. Liver tumors from HCD-fed mice and ApoE-/- mice had increased numbers of NK cells compared to tumors from ND-fed mice. NKdele mice or mice with antibody-based depletion for NK cells showed similar tumor number and size in ND and HCD groups after diethylinitrosamine injection or implantation of Hep1-6 cells. NK cells isolated from C57BL/6J mice fed with HCD had increased expression of NK cell-activating receptors (natural cytotoxicity triggering receptor 1 and natural killer group 2, member D), markers of effector function (granzyme B and perforin), and cytokines and chemokines compared with NK cells from mice on ND; these NK cells also had enhanced cytotoxic activity against mouse hepatoma cells, accumulated cholesterol, increased lipid raft formation, and immune signaling activation. NK cells isolated from HCD-fed Ldlr-/- mice did not have increased cholesterol content or cytotoxic activity against mouse hepatoma cells compared with ND-fed Ldlr-/- mice. Serum levels of cholesterol correlated with number and activity of NK cells isolated from human HCCs. CONCLUSIONS: Mice with increased serum levels of cholesterol due to an HCD or genetic disruption of ApoE develop fewer and smaller tumors after injection of hepatoma cells or a chemical carcinogen. We found cholesterol to accumulate in NK cells and activate their effector functions against hepatoma cells. Strategies to increase cholesterol uptake by NK cells can be developed for treatment of HCC.