Engineering zinc oxide hybrid selenium nanoparticles for synergetic anti-tuberculosis treatment by combining Mycobacterium tuberculosis killings and host cell immunological inhibition

IntroductionAs a deadly disease induced by Mycobacterium tuberculosis (Mtb), tuberculosis remains one of the top killers among infectious diseases. The low intracellular Mtb killing efficiency of current antibiotics introduced the long duration anti-TB therapy in clinic with strong side effects and increased drug-resistant mutants. Therefore, the exploration of novel anti-TB agents with potent anti-TB efficiency becomes one of the most urgent issues for TB therapies. MethodsHere, we firstly introduced a novel method for the preparation of zinc oxide-selenium nanoparticles (ZnO-Se NPs) by the hybridization of zinc oxide and selenium to combine the anti-TB activities of zinc oxide nanoparticles and selenium nanoparticles. We characterized the ZnO-Se NPs by dynamic laser light scattering and transmission electron microscopy, and then tested the inhibition effects of ZnO-Se NPs on extracellular Mtb by colony-forming units (CFU) counting, bacterial ATP analysis, bacterial membrane potential analysis and scanning electron microscopy imaging. We also analyzed the effects of ZnO-Se NPs on the ROS production, mitochondrial membrane potential, apoptosis, autophagy, polarization and PI3K/Akt/mTOR signaling pathway of Mtb infected THP-1 macrophages. At last, we also tested the effects of ZnO-Se NPs on intracellular Mtb in THP-1 cells by colony-forming units (CFU) counting. ResultsThe obtained spherical core-shell ZnO-Se NPs with average diameters of 90 nm showed strong killing effects against extracellular Mtb, including BCG and the virulent H37Rv, by disrupting the ATP production, increasing the intracellular ROS level and destroying the membrane structures. More importantly, ZnO-Se NPs could also inhibit intracellular Mtb growth by promoting M1 polarization to increase the production of antiseptic nitric oxide and also promote apoptosis and autophagy of Mtb infected macrophages by increasing the intracellular ROS, disrupting mitochondria membrane potential and inhibiting PI3K/Akt/mTOR signaling pathway. DiscussionThese ZnO-Se NPs with synergetic anti-TB efficiency by combining the Mtb killing effects and host cell immunological inhibition effects were expected to serve as novel anti-TB agents for the development of more effective anti-TB strategy

An Ultra-Wideband MIMO Bowl-Shaped Monopole Antenna with Sturdy and Simple Construction

Anultra-wideband (UWB) bowl-shaped monopole antenna with a sturdy, simple, and lightweight structure is proposed, and then is used to compose the 3 × 3 multiple input multiple output (MIMO) antenna. The wide bandwidth is determined by the outline of the monopole, which has a quarter wavelength and high-order modes. The inner part of the bowl-shaped monopole is removed for a light weight. The simulated and measured results show that an ultra-wide band of 2.3–8.1 GHz (5.8 GHz, 111.5%) and a high isolation of greater than 20 dB between the antenna elements of the MIMO antenna can be achieved

A systematic review of unilateral versus bilateral percutaneous vertebroplasty/percutaneous kyphoplasty for osteoporotic vertebral compression fractures

Objective: The aim of this study was to compare the unilateral and bilateral approaches in treating osteoporotic vertebral compression fractures. Methods: Based on the principles and methods of the Cochrane systematic reviews, the records of the Cochrane Library, PubMed, Web of Science, Chinese Bio-medicine database, China Journal Full-text Database, VIP database, and Wanfang database were reviewed until October 2014. The randomized controlled trials on unilateral and bilateral approaches to percutaneous vertebroplasty (PVP)/percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures were included. The risk of bias of included trials was assessed based on the Cochrane Handbook for Systematic Reviews of Interventions Version. The RevMan Software 5.0 was used for meta-analysis. Results: Fifteen randomized controlled trials with a total of 850 patients were included. Risk of bias in the included studies was inevitable. There was no statistically significant difference in visual analog scale, vertebral height, kyphotic angular, and quality of life. The main operative complications were bone cement leakage and adjacent vertebral fracture, without difference between the two groups. Conclusions: In view of the current evidence, there is insufficient evidence to show any difference between the unilateral and bilateral approaches in both the PVP and PKP treatment in osteoporotic vertebral compression fractures. Level of Evidence: Level I, Therapeutic study. Keywords: Minimally invasive surgery, Osteoporotic vertebral compression fracture, Percutaneous kyphoplasty, Percutaneous vertebroplasty, Systematic revie

Ultrathin Cellulose Nanofiber Assisted Ambient-Pressure-Dried, Ultralight, Mechanically Robust, Multifunctional MXene Aerogels

Ambient-pressure-dried (APD) preparation of transition metal carbide/nitrides (MXene) aerogels is highly desirable yet remains highly challenging. Here, ultrathin, high-strength-to-weight-ratio, renewable cellulose nanofibers (CNFs) are efficiently utilized to assist in the APD preparation of ultralight yet robust, highly conductive, large-area MXene-based aerogels via a facile, energy-efficient, eco-friendly, and scalable freezing-exchanging-drying approach. The strong interactions of large-aspect-ratio CNF and MXene as well as the biomimetic nacre-like microstructure induce high mechanical strength and stability to avoid the structure collapse of aerogels in the APD process. Abundant functional groups of CNFs facilitate the chemical crosslinking of MXene-based aerogels, significantly improving the hydrophobicity, water resistance, and even oxidation stability. The ultrathin, one-dimensional nature of the CNF renders the minimal MXenes' interlayered gaps and numerous heterogeneous interfaces, yielding the excellent conductivity and electromagnetic interference (EMI) shielding performance of aerogels. The synergies of the MXene, CNF, and abundant pores efficiently improve the EMI shielding performance, photothermal conversion, and absorption of viscous crude oil. Our work shows great promises of the APD, multifunctional MXene-based aerogels in electromagnetic protection or compatibility, thermal therapy, and oil-water separation applications. This article is protected by copyright. All rights reserved

Graphene oxide-assisted multiple cross-linking of MXene for large-area, high-strength, oxidation-resistant, and multifunctional films

Transition metal carbides/nitrides (MXenes) with metallic electrical conductivity and excellent processability attract increasing attention for assembling multifunctional macrostructures. However, the challenges, involving poor mechanical strength, inferior oxidation stability, and limited scalable manufacturing, impede their wide applications. Herein, the large-area, high-strength, ultra-flexible hybrid films are developed through the multiple physical and chemical cross-linking of MXene/cellulose films facilitated by graphene oxide. The MXene-based films manifest significantly improved hydrophobicity, water/solvent resistance, and oxidation stability, and meanwhile, maintain excellent conductivity and electromagnetic interference shielding performance. The X-band surface-specific shielding effectiveness (SE) of 18,837.5 dB cm2 g−1 and an SE over 60 dB in an ultra-broadband frequency range are achieved, comparable to the best shields ever reported. Furthermore, the wearable films demonstrate excellent photothermal antibacterial and electrothermal deicing applications. Thus, such high-performance MXene-based films developed through a facile and scalable manufacturing method have substantial application prospects in flexible electronics, thermotherapy, electromagnetic compatibility, and aerospace.This work was financially supported by the National Key R&D Program of China (No. 2021YFB3502500), National Natural Science Foundation of China (NO. 22205131, 61905232), Natural Science Foundation of Shandong Province (No. 2022HYYQ-014, ZR2016BM16), and Provincial Key Research and Development Program of Shandong (No. 2021ZLGX01), Distinguished Young Scholars Foundation of Hubei Province (ZRJQ2022000503), "20 Clauses about Colleges and Universities (new)" (Independent Training of Innovation Team) Program of Jinan (2021GXRC036), the Joint Laboratory project of Electromagnetic Structure Technology (637-2022-70-F-037), Shenzhen municipal special fund for guiding local scientific and Technological Development (China 2021Szvup071), and Qilu Young Scholar Program of Shandong University (No. 31370082163127)

4‑Amino-1-(3-mercapto-propyl)-pyridine Hexafluorophosphate Ionic Liquid Functionalized Gold Nanoparticles for IgG Immunosensing Enhancement

A novel ionic liquid, 4-amino-1-(3-mercapto-propyl)-pyridine hexafluorophosphate (AMPPH), was successfully synthesized and characterized. Subsequently, AMPPH was used as a functional monomer to fabricate AMPPH-modified gold nanoparticles (AMPPH–AuNPs) via a one-pot synthesis method. The as-prepared AMPPH–AuNPs were confirmed with transmission electron microscopy and X-ray photoelectron spectroscopy. AMPPH–AuNPs were used to construct a biocompatible interface to immobilize rabbit anti-human IgG (anti-HIgG) onto a glassy carbon electrode (GCE) surface, followed by a cross-linking step with glutaraldehyde to fabricate an anti-HIgG–AMPPH–AuNPs/GCE. The nonspecific binding sites were enclosed with bovine serum albumin (BSA) to develop an immunosensor for human IgG. Electrochemical impedance spectroscopy, cyclic voltammetry and differential pulse voltammetry were used to investigate the electrochemical properties of the developed immunosensor. The results indicate that AMPPH–AuNPs can improve the immunosensing performance. The current response of the immunosensor was found linearly related to human IgG concentration in the range of 0.1–5.0 ng mL^–1 and 5.0–100.0 ng mL^–1. The detection limit is estimated to be 0.08 ng mL^–1 (<i>S</i>/<i>N</i> = 3). The obtained immunosensor was successfully applied to the analysis human IgG immunoglobulin in human serum, and the results were well consistent with ELISA method

Printable Aligned Single-Walled Carbon Nanotube Film with Outstanding Thermal Conductivity and Electromagnetic Interference Shielding Performance

Ultrathin, lightweight, and flexible aligned single-walled carbon nanotube (SWCNT) films are fabricated by a facile, environmentally friendly, and scalable printing methodology. The aligned pattern and outstanding intrinsic properties render “metal-like” thermal conductivity of the SWCNT films, as well as excellent mechanical strength, flexibility, and hydrophobicity. Further, the aligned cellular microstructure promotes the electromagnetic interference (EMI) shielding ability of the SWCNTs, leading to excellent shielding effectiveness (SE) of ~ 39 to 90 dB despite a density of only ~ 0.6 g cm−3 at thicknesses of merely 1.5–24 µm, respectively. An ultrahigh thickness-specific SE of 25 693 dB mm−1 and an unprecedented normalized specific SE of 428 222 dB cm2 g−1 are accomplished by the freestanding SWCNT films, significantly surpassing previously reported shielding materials. In addition to an EMI SE greater than 54 dB in an ultra-broadband frequency range of around 400 GHz, the films demonstrate excellent EMI shielding stability and reliability when subjected to mechanical deformation, chemical (acid/alkali/organic solvent) corrosion, and high-/low-temperature environments. The novel printed SWCNT films offer significant potential for practical applications in the aerospace, defense, precision components, and smart wearable electronics industries

Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial

Background Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response.Methods In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m2) and oxaliplatin (85 mg/m2). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment.Results 54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS &lt;1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p&gt;0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28).Conclusion Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX.Trial registration number NCT03486678