A novel MICA/B-targeted chimeric antigen receptor augments the cytotoxicity of NK cells against tumor cells.

Chimeric antigen receptor (CAR)-modified immune cells have emerged as a promising approach for cancer treatment, but single-target CAR therapy in solid tumors is limited by immune escape caused by tumor antigen heterogeneity and shedding. Natural killer group 2D (NKG2D) is an activating receptor expressed in human NK cells, and its ligands, such as MICA and MICB (MICA/B), are widely expressed in malignant cells and typically absent from healthy tissue. NKG2D plays an important role in anti-tumor immunity, recognizing tumor cells and initiating an anti-tumor response. Therefore, NKG2D-based CAR is a promising CAR candidate. Nevertheless, the shedding of MICA/B hinders the therapeutic efficacy of NKG2D-CARs. Here, we designed a novel CAR by engineering an anti-MICA/B shedding antibody 1D5 into the CAR construct. The engineered NK cells exhibited significantly enhanced cytotoxicity against various MICA/B-expressing tumor cells and were not inhibited by NKG2D antibody or NKG2D-Fc fusion protein, indicating no interference with NKG2D-MICA/B binding. Therefore, the developed 1D5-CAR could be combined with NKG2D-CAR to further improve the obstacles caused by MICA/B shedding.

Knockdown of protein interacting with C α kinase 1 aggravates sepsis-induced acute liver injury by regulating the TLR4/NF-κB pathway.

Acute liver injury (ALI) may manifest at any phase of sepsis, yet an explicit therapeutic approach remains elusive. In this study, LPS and cecum ligation and puncture (CLP) were utilized to establish an inflammatory cell model and a murine model of sepsis-induced liver injury, respectively, aiming to explore the potential protective effect of protein interacting with C α kinase 1 (PICK1) on sepsis-induced ALI and its underlying mechanisms. In both the cell supernatant and the murine whole blood, the concentrations of inflammatory factors were quantified by ELISA, while the protein and mRNA expressions of PICK1, cleaved-PARP-1, caspase1, TLR4, IκBα, and NF-κB were assessed via western blot and qRT-PCR. The outcomes revealed that the knockdown of PICK1 increased the levels of inflammatory factors and apoptosis, alongside activation of TLR4/NF-κB signaling pathway-related factors in both in vivo and in vitro models. Moreover, the murine liver samples were subjected to Hematoxylin-Eosin (HE) staining for assessment of histopathological morphology. The HE staining and liver injury scoring results manifested a markedly exacerbated hepatic damage in PICK1 knockout mice as compared to WT mice following CLP. Furthermore, the liver macrophages were isolated from murine livers, and the expression and activity of the factors associated with the TLR4/NF-κB signaling pathway were verified through RT-qPCR and western blot, and EMSA assay demonstrated an augmented NF-κB activity subsequent to PICK1 knockout. Finally, the expression and localization of PICK1 in macrophages were further scrutinized via immunofluorescence, and the interaction between PICK1 and TLR4 was identified through co-immunoprecipitation. In conclusion, the knockdown of PICK1 appeared to modulate inflammatory factors by activating the TLR4/NF-κB signaling pathway, thereby exacerbating hepatic damage induced by sepsis.

Direct Electrochemistry of Glucose Dehydrogenase-Functionalized Polymers on a Modified Glassy Carbon Electrode and Its Molecular Recognition of Glucose.

A glucose biosensor was layer-by-layer assembled on a modified glassy carbon electrode (GCE) from a nanocomposite of NAD(P)+-dependent glucose dehydrogenase, aminated polyethylene glycol (mPEG), carboxylic acid-functionalized multi-wall carbon nanotubes (fMWCNTs), and ionic liquid (IL) composite functional polymers. The electrochemical electrode was denoted as NF/IL/GDH/mPEG-fMWCNTs/GCE. The composite polymer membranes were characterized by cyclic voltammetry, ultraviolet-visible spectrophotometry, electrochemical impedance spectroscopy, scanning electron microscopy, and transmission electron microscopy. The cyclic voltammogram of the modified electrode had a pair of well-defined quasi-reversible redox peaks with a formal potential of -61 mV (vs. Ag/AgCl) at a scan rate of 0.05 V s-1. The heterogeneous electron transfer constant (ks) of GDH on the composite functional polymer-modified GCE was 6.5 s-1. The biosensor could sensitively recognize and detect glucose linearly from 0.8 to 100 µM with a detection limit down to 0.46 µM (S/N = 3) and a sensitivity of 29.1 nA µM-1. The apparent Michaelis-Menten constant (Kmapp) of the modified electrode was 0.21 mM. The constructed electrochemical sensor was compared with the high-performance liquid chromatography method for the determination of glucose in commercially available glucose injections. The results demonstrated that the sensor was highly accurate and could be used for the rapid and quantitative determination of glucose concentration.

Distinct Role of Surface Hydroxyls in Single-Atom Pt1/CeO2 Catalyst for Room-Temperature Formaldehyde Oxidation: Acid-Base Versus Redox.

The development of highly efficient catalysts for room-temperature formaldehyde (HCHO) oxidation is of great interest for indoor air purification. In this work, it was found that the single-atom Pt1/CeO2 catalyst exhibits a remarkable activity with complete removal of HCHO even at 288 K. Combining density functional theory calculations and in situ DRIFTS experiments, it was revealed that the active OlatticeH site generated on CeO2 in the vicinity of Pt2+ via steam treatment plays a key role in the oxidation of HCHO to formate and its further oxidation to CO2. Such involvement of hydroxyls is fundamentally different from that of cofeeding water which dissociates on metal oxide and catalyzes the acid-base-related chemistry. This study provides an important implication for the design and synthesis of supported Pt catalysts with atom efficiency for a very important practical application-room-temperature HCHO oxidation.

Sugammadex Versus Neostigmine for Neuromuscular Block Reversal and Postoperative Pulmonary Complications in Patients Undergoing Resection of Lung Cancer.

OBJECTIVES: This study aimed to compare the effect of sugammadex and neostigmine on neuromuscular block reversal and the incidence of postoperative pulmonary complications in patients undergoing lung cancer resection. DESIGN: A double-blind, randomized, prospective study. SETTING: A single major urban teaching and university hospital. PARTICIPANTS: One hundred adult patients underwent elective radical resection of lung cancer under general anesthesia. INTERVENTIONS: Patients were assigned into neostigmine (0.05 mg/kg) + atropine 0.02 mg/kg group and sugammadex (2 mg/kg) group. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were the incidence of any postoperative pulmonary complications, and the time to achieve 90% of train-of-four (TOF) after the administration of sugammadex or neostigmine. The secondary endpoints were the number of patients with TOF ratio (TOFr) <0.9 at the time of tracheal extubation, the incidence of readmission 30 days after discharge, and specific postoperative pulmonary complications. Results showed that the average time of recovery to TOFr ≥0.9 with sugammadex was 164.5 ± 27.7 seconds versus 562.9 ± 59.7 seconds with neostigmine + atropine treatment. Fewer sugammadex-treated patients did not achieve TOFr of 0.9 at the time of tracheal extubation than did neostigmine-treated participants. Patients in the sugammadex group had lower incidence of postoperative lung complications, and shorter durations of postanesthesia care unit stay and postoperative hospital stay than those in the neostigmine group. There was no significant difference in the incidence of readmission between the 2 groups. CONCLUSIONS: Administration of sugammadex provided faster recovery of rocuronium-induced neuromuscular block when compared with neostigmine. Moreover, for patients undergoing lung cancer resection, administration of sugammadex could reduce the incidence of postoperative pulmonary complications and duration of postoperative hospital stay.

Construction and Biological Evaluation of Multiple Modification Hollow Mesoporous Silicone Doxorubicin Nanodrug Delivery System.

The combination of functionalized nanoparticles and chemotherapy drugs can effectively target tumor tissue, which can improve efficacy and reduce toxicity. In this article, pPeptide-PDA@HMONs-DOX nanoparticles (phosphopeptide-modified polydopamine encapsulates doxorubicin-loaded hollow mesoporous organosilica nanoparticles) were constructed that based on multiple modification hollow mesoporous organosilica nanoparticles (HMONs). The pPeptide-PDA@HMONs-DOX nanoparticles retain the biological functions of phosphorylated peptide while exhibiting biological safety that are suitable for effective drug delivery and stimulus responsive release. The degradation behaviors showed that pPeptide-PDA@HMONs-DOX has dual-responsive to drug release characteristics of pH and glutathione (GSH). In addition, the prepared pPeptide-PDA@HMONs-DOX nanoparticles have good biological safety, and their anti-tumor efficacy was significantly better than doxorubicin (DOX). This provided new research ideas for the construction of targeted nanodrug delivery systems based on mesoporous silicon. Scheme 1 The preparation of pPeptide-PDA@HMONs-DOX and the process of drug release under multiple responses. (A) Schematic diagram of the synthesis process of pPeptide-PDA@HMONs-DOX. (B) The process in which nanoparticles enter the cell and decompose and release DOX in response to pH and GSH.

Carbon dots derived from Poria cocos polysaccharide as an effective "on-off" fluorescence sensor for chromium (VI) detection.

Chromium is a harmful contaminant showing mutagenicity and carcinogenicity. Therefore, detection of chromium requires the development of low-cost and high-sensitivity sensors. Herein, blue-fluorescent carbon quantum dots were synthesized by one-step hydrothermal method from alkali-soluble Poria cocos polysaccharide, which is green source, cheap and easy to obtain, and has no pharmacological activity due to low water solubility. These carbon quantum dots exhibit good fluorescence stability, water solubility, anti-interference and low cytotoxicity, and can be specifically combined with the detection of Cr(VI) to form a non-fluorescent complex that causes fluorescence quenching, so they can be used as a label-free nanosensor. High-sensitivity detection of Cr(VI) was achieved through internal filtering and static quenching effects. The fluorescence quenching degree of carbon dots fluorescent probe showed a good linear relationship with Cr(VI) concentration in the range of 1-100 µM. The linear equation was F 0/F = 0.9942 + 0.01472 [Cr(VI)] (R 2 = 0.9922), and the detection limit can be as low as 0.25 µM (S/N = 3), which has been successfully applied to Cr(VI) detection in actual water samples herein.

Characteristics of Computed Tomography Images for Patients with Acute Liver Injury Caused by Sepsis under Deep Learning Algorithm.

This study was aimed at exploring the application of image segmentation based on full convolutional neural network (FCN) in liver computed tomography (CT) image segmentation and analyzing the clinical features of acute liver injury caused by sepsis. The Sigmoid function, encoder-decoder, and weighted cross entropy loss function were introduced and optimized based on FCN. The Dice value, precision, recall rate, volume overlap error (VOE), relative volume difference (RVD), and root mean square error (RMSE) values of the optimized algorithms were compared and analyzed. 92 patients with sepsis were selected as the research objects, and they were divided into a nonacute liver injury group (50 cases) and acute liver injury group (42 cases) based on whether they had acute liver injury. The differences in the proportion of patients with different disease histories, the proportion of patients with different infection sites, the number of organ failure, and the time of admission to intensive care unit (ICU) were compared between the two groups. It was found that the optimized window CT image Dice value after preprocessing (0.704 ± 0.06) was significantly higher than the other two methods (P < 0.05). The Dice value, precision, and recall rate of the optimized-FCN algorithm were (0.826 ± 0.06), (0.91 ± 0.08), and (0.88 ± 0.09), respectively, which were significantly higher than other algorithms (P < 0.05). The VOE, RVD, and RMSE values were (21.19 ± 1.97), (10.45 ± 1.02), and (0.25 ± 0.02), respectively, which were significantly lower than other algorithms (P < 0.05). The proportion of patients with a history of drinking in the nonacute liver injury group was lower than that in the acute liver injury group (P < 0.05), and the proportion of patients with a history of hypotension was greatly higher than that in the nonacute liver injury group (P < 0.01). CT images of sepsis patients with acute liver injury showed that large areas of liver parenchyma mixed with high-density hematoma, the number of organ failures, and the length of stay in ICU were significantly higher than those in the nonacute liver injury group (P < 0.05). It showed that the optimization algorithm based on FCN greatly improved the performance of CT image segmentation. Long-term drinking, low blood pressure, number of organ failures, and length of stay in ICU were all related to sepsis and acute liver injury. Conclusion in this study could provide a reference basis for the diagnosis and prognosis of acute liver injury caused by sepsis.

Potential Roles of Extracellular Vesicles as Diagnosis Biomarkers and Therapeutic Approaches for Cognitive Impairment in Alzheimer's Disease.

Cognitive dysfunction, the major clinical manifestation of Alzheimer's disease (AD), is caused by irreversible progressive neurological dysfunction. With the aging of the population, the incidence of AD is increasing year by year. However, there is neither a simple and accurate early diagnosis method, nor an effective method to alleviate or prevent the occurrence and progression of AD. Extracellular vesicles (EVs) are a number of heterogeneous membrane structures that arise from the endosome system or shed from the plasma membrane. In the brain, almost every kind of cell may have EVs, which are related to cell-cell communication and regulate cellular function. At present, an increasing body of evidence suggests that EVs play a crucial role in the pathogenesis of AD, and it is of great significance to use them as specific biomarkers and novel therapeutic targets for cognitive impairment in AD. This article reviews the potential role of EVs as diagnostic biomarkers and treatments for cognitive dysfunction in AD.

Molecular Dynamics Calculation on the Adhesive Interaction Between the Polytetrafluoroethylene Transfer Film and Iron Surface.

During the friction process, the polytetrafluoroethylene (PTFE) adhered on the counterpart surface was known as the PTFE transfer film, which was fundamental to the lubricating performance of the PTFE. However, the adhesive interaction between the iron surface and the adhered PTFE transfer film is still unclear. In present study, molecular dynamics simulations were used to reveal the adhesive interaction between the iron surface and PTFE transfer film. Based on the atomic trajectories obtained through the molecular dynamics, the interaction energy, concentration profile, radial distribution function, and mean square displacement were calculated to analyze the structure of the interface. The negative values of the interaction energy demonstrated the adhesive interaction between the PTFE transfer film and Fe surfaces, resulting in the accumulation of the PTFE transfer film on the Fe surface. Among the (100) (110), and (111) surfaces of α-Fe (110) surface owns the strongest adhesive interaction with the PTFE transfer film. Compared with the original PTFE molecule, the chain broken PTFE, hydroxyl substituted PTFE, and carbonyl substituted PTFE exhibited stronger adhesive interaction with Fe surface. The adhesive interaction between the PTFE transfer film and Fe surfaces was mainly originated from the Fe atoms and the F atoms of the adsorbate PTFE transfer film, which was governed by the van der Waals force. The bonding distance between the Fe atom and the F atom of the adsorbate PTFE transfer film is around 2.8 Å. Moreover, the chain broken of PTFE molecule and the rise of temperature can remarkably increase the mobility of polymer chains in the interface system.

Theoretical characterization of zeolite encapsulated platinum clusters in the presence of water molecules.

Zeolite encapsulated metal clusters have shown high catalytic activity and superior stability due to confinement effects, the synergy between acidic and metal active sites, and strong metal-zeolite interactions. In the present work, density functional theory calculations were employed to study the stability of encapsulated Ptn (n = 1-6) clusters in the zeolitic frameworks including Silicalite-1 and H-MFI. It has been found that the metal-zeolite interaction becomes stronger with the increasing Ptn cluster size for both zeolitic frameworks. The encapsulated Ptn clusters in the vicinity of the Brønsted acid site (BAS) of H-MFI form more stable PtnHx (x = 1, 2) clusters. The presence of water molecules around the encapsulated Pt6 cluster further enhances its stability, while the oxidation states of the encapsulated Ptn cluster are largely affected by the BAS site and the surrounding water molecules. As the water concentration increases, water dissociation becomes more facile on the Pt6@Silicalite-1 cluster while an opposite trend is found over the Pt6H2@H-MFI cluster. The proton of the BAS site can be transferred to the encapsulated Pt6 cluster via a hydronium cluster H+(H2O)n, leading to the formation of the Pt6H2@H-MFI cluster.

Tumor-Derived Extracellular Vesicles Regulate Cancer Progression in the Tumor Microenvironment.

Extracellular vesicles (EVs) are nanosized particles released by numerous kinds of cells, which are now increasingly considered as essential vehicles of cell-to-cell communication and biomarkers in disease diagnosis and treatment. They contain a variety of biomolecular components, including lipids, proteins and nucleic acids. These functional molecules can be transmitted between tumor cells and other stromal cells such as endothelial cells, fibroblasts and immune cells utilizing EVs. As a result, tumor-derived EVs can deliver molecules to remodel the tumor microenvironment, thereby influencing cancer progression. On the one hand, tumor-derived EVs reprogram functions of endothelial cells, promote cancer-associated fibroblasts transformation, induce resistance to therapy and inhibit the immune response to form a pro-tumorigenic environment. On the other hand, tumor-derived EVs stimulate the immune response to create an anti-tumoral environment. This article focuses on presenting a comprehensive and critical overview of the potential role of tumor-derived EVs-mediated communication in the tumor microenvironment.

Super-resolution imaging by anticorrelation of optical intensities.

Photon bunching, a feature of classical thermal fields, has been widely exploited to implement ghost imaging. Here we show that spatial photon antibunching can be experimentally observed via low-pass filtering of the intensities of the two thermal light beams from a beamsplitter correlation system. Through suitable choice of the filter thresholds, the minimum of the measured normalized anti-correlation function, i.e., antibunching dip, can be lower than 0.2, while its full-width-at-half-maximum can be much narrower than that of the corresponding positive correlation peak. Based on this anti-correlation effect, a super-resolution negative ghost image is achieved in a lensless scheme, in which the spatial resolution can exceed the Rayleigh diffraction limit by more than a factor of two. The setup is quite simple and easy to implement, which is an advantage for practical applications.

All-optical transistor based on Rydberg atom-assisted optomechanical system.

We study the optical response of a double optomechanical cavity system assisted by two Rydberg atoms. The target atom is only coupled with one side cavity by a single cavity mode, and gate one is outside the cavities. It has been realized that a long-range manipulation of optical properties of a hybrid system, by controlling the Rydberg atom decoupled with the optomechanical cavity. Switching on the coupling between atoms and cavity mode, the original spatial inversion symmetry of the double cavity structure has been broken. Combining the controllable optical non-reciprocity with the coherent perfect absorption/transmission/synthesis effect (CPA/CPT/CPS reported by [ X.-B.Yan Opt. Express 22, 4886 (2014)], we put forward the theoretical schemes of an all-optical transistor which contains functions such as a controllable diode, rectifier, and amplifier by controlling a single gate photon.

Critical role of oxygen for rapid degradation of organic contaminants in permanganate/bisulfite process.

Organic contaminants can be oxidized rapidly in permanganate/bisulfite (PM/BS) process due to generation of Mn(III)aq. However, the influence of O2 and its role in contaminants degradation in PM/BS process are poorly understood. Thus, the influence of O2 concentration on phenol removal was quantified and isotopic oxygen tracers (18O-labeled water and 18O2) were employed to further unravel the mechanisms of PM/BS process. The introduction of O2 to PM/BS process appreciably improved phenol oxidation. Under oxic conditions the oxidation products of bisulfite included SO42- and HSO5- while SO42- was the single stable oxidation product under anaerobic conditions. The oxygen isotope labeling experiments confirmed that HSO5- originated from the oxidation of SO3- by O2 to SO5- and the following reduction of SO5- by HSO3-. Incorporation of oxygen isotope from H218O to MnO2 due to the disproportionation of Mn(III)aq was observed, which verified the generation of Mn(III)aq in PM/BS process. The critical influence of O2 on PM/BS process was mainly associated with rapid oxidation of SO3- by O2 to SO5-, which otherwise competed with target contaminants for Mn(III)aq. Oxygen from H2O and/or O2 can also be incorporated in the degradation products of organics in PM/BS process.

Resonant gain suppression and superluminal group velocity in a multilevel system.

We investigate the interaction of an open (N + 1)-level extended V-type atomic system (i.e. a closed (N + 2)-level atomic system) with N coherent laser fields and one incoherent pumping field through both analytical and numerical calculations. Our results show that the system can exhibit multiple resonant gain suppressions via perfect quantum destructive interference, which is usually believed to be absent in closed three-level V system and its extended versions involving more atomic levels, with at most N - 1 transparency windows associated with very steep anomalous dispersions occurring in the system. The superluminal group velocity of the probe-laser pulse with at most N - 1 negative values can also be generated and controlled with little gain or absorption.

Dynamic generation of robust and controlled beating signals in an asymmetric procedure of light storage and retrieval.

We propose an efficient scheme for the robust and controlled generation of beating signals in a sample of stationary atoms driven into the tripod configuration. This scheme relies on an asymmetric procedure of light storage and retrieval where the two classical coupling fields have equal detunings in the storage stage but opposite detunings in the retrieval stage. A quantum probe field, incident upon such an atomic sample, is first transformed into two spin coherence wave-packets and then retrieved with two optical components characterized by different time-dependent phases. Therefore the retrieved quantum probe field exhibits a series of maxima and minima (beating signals) in intensity due to the alternative constructive and destructive interference. This interesting phenomenon involves in fact the coherent manipulation of two dark-state polaritons and may be explored to achieve the fast quantum limited measurement.

(Dimethyl-formamide-κO)[2-meth-oxy-6-(2-pyridylmethyl-imino-meth-yl)phenolato-κN,N',O](thio-cyanato-κN)copper(II).

In the title compound, [Cu(C(14)H(13)N(2)O(2))(NCS)(C(3)H(7)NO)], the Cu(2+) ion is coordinated by an N,N',O-tridentate 2-meth-oxy-6-(2-pyridylmethyl-imino-meth-yl)phenolate ligand, an N-bonded thio-cyanate ion and an O-bonded dimethyl-formamide (DMF) mol-ecule, resulting in a distorted CuN(3)O(2) square-based pyramidal geometry for the metal ion, with the DMF O atom in the apical site. The dihedral angle between the aromatic rings in the ligand is 8.70 (16)°. The S atom is disordered over two positions in a 0.901 (6):0.099 (6) ratio. In the crystal, mol-ecules inter-act by way of π-π stacking inter-actions [centroid-centroid separation = 3.720 (2) Å].