Non-IL-2-blocking anti-CD25 antibody inhibits tumor growth by depleting Tregs and has synergistic effects with anti-CTLA-4 therapy.

CD25, also known as the interleukin-2 receptor α chain (IL-2Rα), is highly expressed on regulatory T cells (Tregs), but relatively lower on effector T cells (Teffs). This makes it a potential target for Treg depletion, which can be used in tumor immunotherapy. However, marketed anti-CD25 antibodies (Basiliximab and Daclizumab) were originally developed as immunosuppressive drugs to prevent graft rejection, because these antibodies can block IL-2 binding to CD25 on Teffs, which in turn destroys the function of Teffs. Recent studies have shown that non-IL-2-blocking anti-CD25 antibodies have displayed exciting antitumor effects. Here, we screened out a non-IL-2-blocking anti-CD25 monoclonal antibody (mAb) 7B7 by hybridoma technology, and confirmed its antitumor activity via depleting Tregs in a CD25 humanized mouse model. Subsequently, we verified that the humanized 7B7, named as h7B7-15S, has comparable activities to 7B7, and that its Treg depletion is further increased when combined with anti-CTLA-4, leading to enhanced remodeling of the tumor immune microenvironment. Moreover, our findings reveal that the Fab form of h7B7-15S has the ability to deplete Tregs, independent of the Fc region. Taken together, our studies expand the application of anti-CD25 in tumor immunotherapy and provide insight into the underlying mechanism.

Preparation of (S)-epichlorohydrin using a novel halohydrin dehalogenase by selective conformation adjustment.

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.

Long-Wavelength Illumination-Induced Photocurrent Enhancement of a ZnPc Photocathodic Material for Bioanalytical Applications.

Herein, a novel photocathodic nanocomposite poly{4,8-bis[5-(2-ethylhexyl)-thiophen-2-yl] benzo[1,2-b:4,5-b']dithiophene-2,6-diyl-alt-3-fluoro-2-[(2-ethylhexyl)-carbonyl]thieno[3,4-b]thiophene-4,6-diyl}/phthalocyanine zinc (PTB7-Th/ZnPc) with high photoelectric conversion efficiency under long-wavelength illumination was prepared to construct an ultrasensitive biosensor for the detection of microRNA-21 (miRNA-21), accompanied by a prominent anti-interference capability toward reductive substances. Impressively, the new heterojunction PTB7-Th/ZnPc nanocomposite could not only generate a strong cathodic photocurrent to improve the detection sensitivity under long-wavelength illumination (660 nm) but also effectively avoid the high damage of biological activity caused by short-wavelength light stimulation. Accordingly, by coupling with rolling circle amplification (RCA)-triggered DNA amplification to form functional biquencher nanospheres, a PEC biosensor was fabricated to realize the ultrasensitive analysis of miRNA-21 in the concentration range of 0.1 fM to 10 nM with a detection limit as low as 32 aM. This strategy provided a novel long-wavelength illumination-induced photocurrent enhancement photoactive material for a sensitive and low-damage anti-interference bioassay and early clinical disease diagnosis.

Randomized controlled trial of intravesical electrical stimulation for underactive bladder.

AIM: To evaluate the efficacy and safety of intravesical electrical stimulation (IVES) performed with a novel device in patients with underactive bladder (UAB). PATIENTS AND METHODS: This was a multicentre, prospective, single-blind, randomized controlled clinical trial of patients with UAB in China. Eligible patients were randomly assigned in a 1:1 ratio to receive conventional IVES (n = 38) or IVES with an open circuit (n = 38). The primary efficacy measure was change from baseline in post-void residual urine volume (PVR) after 4 weeks of treatment. Secondary efficacy measures included changes in maximum urinary flow rate (Qmax ), bladder voiding efficiency (BVE), number of 24-h clean intermittent catheterization (CIC) procedures, and Patient Perception of Bladder Condition-Scale (PPBC-S) and American Urological Association Symptom Index Quality of Life (AUA-SI-QoL) scores from baseline after 4 weeks of treatment. Adverse events (AEs) were monitored throughout the trial. RESULTS: In the full analysis set (FAS), the mean (sd) PVR changes in the trial and control groups at 4 weeks were -97.1 (107.5) mL and -10.5 (86.7) mL, respectively (P < 0.01). Similar results were obtained in the per-protocol set (PPS): -102.9 (100.0) mL vs 0.7 (82.5) mL (P < 0.01). In the FAS and PPS, Qmax improved significantly at 4 weeks (P = 0.04 and P = 0.03). In the FAS and PPS, BVE was significantly improved at 4 weeks in the two groups (P < 0.01 and P < 0.01), whereas no significant differences in the number of 24-h CIC procedures, PPBC-S score or AUA-SI-QoL score were observed between the groups. Six possible therapy-related AEs occurred in six patients (four in the trial group and two in the control group; P = 0.67), all of which were urinary tract infections. No severe AEs were reported. CONCLUSIONS: The results of this clinical study strongly demonstrate that UAB patients benefit from this novel IVES device. More research is needed to validate the clinical utility of this device.

Typical value ranges and signal patterns in patients with neurogenic bladder: Quality control in urodynamics using an air-charged catheter system.

PURPOSE: To establish typical value ranges (TVRs) of the air-charged catheter (ACC) system, and analyze the typical signal patterns (TSPs) of cough under different bladder volumes for quality control of a urodynamic study using the ACC system. MATERIALS AND METHODS: The urodynamic traces of 1977 patients with neurogenic bladder (NB) were analyzed for intravesical pressure (pves ), abdominal pressure (pabd ), and detrusor pressure (pdet ) in the cough test at our center from July 2017 to December 2021. The pdet cough signals were described and classified. The pdet cough signal patterns in different bladder volumes and postures were analyzed. RESULTS: The 50% range of the initial resting pves , pabd , and pdet in the supine and sitting positions were 7-15, 7-14, and 0-0 cmH2 O, and 24-33, 24-33, and 0-0 cmH2 O, respectively. The cough amplitudes for pves and pabd were similar in the 50% range, as follows: 10-27 and 8-25 cmH2 O in the supine position, respectively; and 18-43 and 17-40 cmH2 O in the sitting position, respectively. The cough amplitude of pves and pabd was not related to bladder volume (p > 0.05). The cough spikes of pdet were divided into three types: type I, in which pdet has a minimal change (<5 cmH2 O); type II, a monophasic cough spike, in which could be a positive (IIa, ≥5 cmH2 O) or negative spike (IIb, ≥5 cmH2 O); and type III, a biphasic spike, in which could be a positive-to-negative biphasic (IIIa) or negative-to-positive spike (IIIb). Under different bladder volumes, the cough signals of pdet were all expressed as type I, II, or III, and the cough signals were unrelated to bladder volume (p > 0.05). CONCLUSIONS: TVRs of the initial resting state in patients with NB were established to provide guidance for quantitative quality control of the ACC system. The TSPs of the pdet cough signal under different bladder volume and posture were described, which could be used for qualitative quality control of the ACC system.

mm-TPG: Traffic Policemen Gesture Recognition Based on Millimeter Wave Radar Point Cloud.

Automatic driving technology refers to equipment such as vehicle-mounted sensors and computers that are used to navigate and control vehicles autonomously by acquiring external environmental information. To achieve automatic driving, vehicles must be able to perceive the surrounding environment and recognize and understand traffic signs, traffic signals, pedestrians, and other traffic participants, as well as accurately plan and control their path. Recognition of traffic signs and signals is an essential part of automatic driving technology, and gesture recognition is a crucial aspect of traffic-signal recognition. This article introduces mm-TPG, a traffic-police gesture recognition system based on a millimeter-wave point cloud. The system uses a 60 GHz frequency-modulated continuous-wave (FMCW) millimeter-wave radar as a sensor to achieve high-precision recognition of traffic-police gestures. Initially, a double-threshold filtering algorithm is used to denoise the millimeter-wave raw data, followed by multi-frame synthesis processing of the generated point cloud data and feature extraction using a ResNet18 network. Finally, gated recurrent units are used for classification to enable the recognition of different traffic-police gestures. Experimental results demonstrate that the mm-TPG system has high accuracy and robustness and can effectively recognize traffic-police gestures in complex environments such as varying lighting and weather conditions, providing strong support for traffic safety.

Human Movement Recognition Based on 3D Point Cloud Spatiotemporal Information from Millimeter-Wave Radar.

Human movement recognition is the use of perceptual technology to collect some of the limb or body movements presented. This practice involves the use of wireless signals, processing, and classification to identify some of the regular movements of the human body. It has a wide range of application prospects, including in intelligent pensions, remote health monitoring, and child supervision. Among the traditional human movement recognition methods, the widely used ones are video image-based recognition technology and Wi-Fi-based recognition technology. However, in some dim and imperfect weather environments, it is not easy to maintain a high performance and recognition rate for human movement recognition using video images. There is the problem of a low recognition degree for Wi-Fi recognition of human movement in the case of a complex environment. Most of the previous research on human movement recognition is based on LiDAR perception technology. LiDAR scanning using a three-dimensional static point cloud can only present the point cloud characteristics of static objects; it struggles to reflect all the characteristics of moving objects. In addition, due to its consideration of privacy and security issues, the dynamic millimeter-wave radar point cloud used in the previous study on the existing problems of human body movement recognition performance is better, with the recognition of human movement characteristics in non-line-of-sight situations as well as better protection of people's privacy. In this paper, we propose a human motion feature recognition system (PNHM) based on spatiotemporal information of the 3D point cloud of millimeter-wave radar, design a neural network based on the network PointNet++ in order to effectively recognize human motion features, and study four human motions based on the threshold method. The data set of the four movements of the human body at two angles in two experimental environments was constructed. This paper compares four standard mainstream 3D point cloud human action recognition models for the system. The experimental results show that the recognition accuracy of the human body's when walking upright can reach 94%, the recognition accuracy when moving from squatting to standing can reach 84%, that when moving from standing to sitting can reach 87%, and the recognition accuracy of falling can reach 93%.

KCa3.1-dependent uptake of the cytotoxic DNA-binding dye Hoechst 33258 into cancerous but not healthy cervical cells.

The poor and nonselective penetration of current chemotherapeutics across the plasma membranes of cancer cells, which is necessary for the targeted disruption of the intracellular machinery, remains a major pharmaceutical challenge. In several cell types, including mast cells and macrophages, exposure to extracellular ATP is known to stimulate passive entry of large and otherwise membrane impermeable cationic dyes, which is usually attributed to conduction through ionotropic P2X receptors. Here, we report that elevations in cytosolic Ca2+ stimulate the rapid uptake and nuclear accumulation of a DNA-binding fluorescent cation, Hoechst 33258 (H33258), in cervical cancer cells. The H33258 uptake was dependent on activation of intermediate conductance Ca2+-activated K+ channels (KCa3.1), and direct stimulation of the channel with the activators SKA 31 and DCEBIO was sufficient to induce cellular uptake of H33258 directly. In contrast to the results from cancerous cervical cells, KCa3.1-dependent H33258 uptake was rarely observed in epithelial cells derived from the ectocervix and transformation zone of healthy cervical tissue. Furthermore, whole-cell patch clamp experiments and assessment of membrane potential using the slow voltage-sensitive dye bis-(1,3-diethylthiobarbituric acid)trimethine oxonol revealed a significant difference in functional KCa3.1 activity between cancerous and healthy cervical epithelial cells, which correlated strongly with the incidence of KCa3.1-dependent H33258 uptake. Finally, we show that activation of KCa3.1 channels caused a modest but significant sensitization of cancer cells to the growth suppressant effects of H33258, lending plausibility to the idea of using KCa3.1 channel activators to enhance cell penetration of small cationic toxins into cancer cells expressing these channels.

Discovery of Charge Order and Corresponding Edge State in Kagome Magnet FeGe.

Kagome materials often host exotic quantum phases, including spin liquids, Chern gap, charge density wave, and superconductivity. Existing scanning microscopy studies of the kagome charge order have been limited to nonkagome surface layers. Here, we tunnel into the kagome lattice of FeGe to uncover features of the charge order. Our spectroscopic imaging identifies a 2×2 charge order in the magnetic kagome lattice, resembling that discovered in kagome superconductors. Spin mapping across steps of unit cell height demonstrates the existence of spin-polarized electrons with an antiferromagnetic stacking order. We further uncover the correlation between antiferromagnetism and charge order anisotropy, highlighting the unusual magnetic coupling of the charge order. Finally, we detect a pronounced edge state within the charge order energy gap, which is robust against the irregular shape fluctuations of the kagome lattice edges. We discuss our results with the theoretically considered topological features of the kagome charge order including unconventional magnetism and bulk-boundary correspondence.

A clinical study of a CD44v6-targeted fluorescent agent for the detection of non-muscle invasive bladder cancer.

BACKGROUND: Bladder cancer is the fifth most common malignancy in humans. Cystoscopy under white light imaging is the gold standard for bladder cancer diagnosis, but some tumors are difficult to visualize and can be overlooked, resulting in high recurrence rates. We previously developed a phage display-derived peptide-based near-infrared imaging probe, PLSWT7-DMI, which binds specifically to bladder cancer cells and is nontoxic to animals. Here, we report a clinical research of this probe for near-infrared fluorescence endoscopic detection of bladder cancer. RESULTS: The purity, efficacy, safety, and nontoxicity of PLSWT7-DMI were confirmed prior to its clinical application. Twenty-two patients diagnosed with suspected non-muscle invasive bladder cancer were enrolled in the present study. Following intravesical administration of the probe, the entire mucosa was imaged under white and near-infrared imaging using an in-house developed endoscope that could switch between these two modes. The illuminated lesions under near-infrared light were biopsied and sent for histopathological examination. We observed a 5.1-fold increase in the fluorescence intensity in the tumor samples compared to normal tissue, and the probe demonstrated a sensitivity and specificity of 91.2% and 90%, respectively. Common diagnostic challenges, such as small satellite tumors, carcinoma in situ, and benign suspicious mucosa, were visualized and could be distinguished from cancer. Furthermore, no adverse effects were observed in humans. These first-in-human results indicate that PLSWT7-DMI-based near-infrared fluorescence endoscopy is a safe and effective approach for the improved detection of bladder cancer, and may enable thorough resection to prevent recurrence.

Targeted-detection and sequential-treatment of small hepatocellular carcinoma in the complex liver environment by GPC-3-targeted nanoparticles.

Despite advancements in diagnostic methods and therapeutic strategies, the mortality rate of hepatocellular carcinoma (HCC) remains as high as its incidence rate. Most liver cancers are detected in the advanced stages, when treatment options are limited. Small HCC is difficult to diagnose and is often overlooked by current imaging methods because of the complexity of the liver environment, especially in cirrhotic livers. In the present study, we developed a tumor "cruise missile", mesoporous Fe3O4-containing glucose oxidase-conjugated GPC3 peptide nanoparticles (FGP NPs). It was designed to enhance the accuracy of small HCC visualization to 85.7% using combined ultrasound/photoacoustic imaging in complex liver environment, which facilitated sequential catalytic targeted therapy for small HCC. In a carcinogen-induced mouse HCC model, FGP NPs could be used to accurately diagnose HCC in a liver cirrhosis background as well as distinguish HCC nodules from other abnormal liver nodules, such as cirrhosis nodules and necrotic nodules, by dynamic contrast-enhanced photoacoustic imaging. In a mouse xenograft HCC model, highly reactive oxygen species were formed by sequential catalytic reactions, which promoted HCC cell apoptosis, significantly increasing the survival of the model mice. The present study provides a basis for the precise detection and elimination of small HCCs in the complex liver environment.

Reliability assessment of the upper urinary tract dilation grading system based on magnetic resonance urography in patients with neurogenic bladder.

BACKGROUND: To assess the inter-observer and intra-observer reliability of the magnetic resonance urography (MRU)-upper urinary tract dilation (UUTD) grading system. METHODS: A total of 40 patients with a diagnosis of NB were enrolled in this study. The images were assembled in an electronic presentation randomly. The presentations were reviewed and graded by 4 junior and 4 senior urologists. One week later, the images were randomized again and reassessed. The inter-observer reliability was estimated by Kendall's coefficient of concordance and intra-class correlation coefficient (ICC), and the intra-observer reliability was estimated by weighted Cohen's kappa. RESULTS: The inter-observer reliability strength was excellent for all urologists, with the ICC value of 0.939 (0.908-0.963) and Kendall's W value of 0.967. The highest agreement was shown in Grade 4 at 92.50%, and the lowest in Grade 2 at 82.14%. All disagreements were within one grade of difference. Moreover, the Intra-observer reliability was excellent, with the weighted kappa value ranging from 0.904 to 0.954. CONCLUSIONS: The inter-observer and intra-observer reliability of this novel MRU-UUTD grading system is confirmed, providing adequate evidence for broader clinical application.

Colourful fluorescence-based carbon dots for tumour imaging-guided nanosurgery.

Fluorescent-intraoperative navigation is a visual technique that allows surgeons to accurately distinguish malignant and normal tissues during surgery. It has the advantages of immediacy, high resolution, and high specificity. However, a single fluorescent source cannot provide sufficient surgical information. Multicolour carbon dots (CDs) are more suitable since they provide outstanding water solubility, photostability, and multicolour-fluorescence imaging. Here, we prepared an optical probe with CD-based multicolour-fluorescence imaging via a hydrothermal method. CDs can be endocytosed by tumour cells, and after intravenous injection, they can effectively accumulate at the tumour site. In a pancreatic cancer mouse model, we demonstrated the multicolour-fluorescence imaging capabilities of CDs, which aided the accurate resection of tumours under fluorescent-intraoperative navigation. Stereoscopic fluorescence microscopy imaging and H&E staining proved that the removed tissue belonged to the pancreatic tumour. This study emphasizes the potential of CDs for fluorescence-guided intraoperative resection and expands the application of CDs in biological fields.

14N NMR as a General Tool to Characterize the Nitrogen-Containing Species and Monitor the Nitration Process.

The usefulness of 14N NMR spectroscopy was highly underestimated compared with 15N NMR, which usually required tedious and expensive 15N-labeling manipulations. It is of great significance to make the 14N NMR spectroscopy convenient and useful considering 14N nuclei's high natural abundance of 99.6%. Herein, lots of efforts have been made to generalize routine 14N NMR to characterize nitrogen-containing species by tuning the balance between the solubility and viscosity of the samples. Satisfactory 14N NMR spectra of more than 60 nitrogen-containing compounds have been recorded, and the chemical shifts and the peaks' full width at half-maxima of more than 10 nitrogen-based functionalities have been summarized. Successful monitoring of the ortho-selective nitration of aniline has been demonstrated using the 14N NMR protocol developed in this paper, which will help realize the visualization of nitration processes in the industry.

Glutathione Reductase Promotes Fungal Clearance and Suppresses Inflammation during Systemic Candida albicans Infection in Mice.

Glutathione reductase (Gsr) catalyzes the reduction of glutathione disulfide to glutathione, which plays an important role in redox regulation. We have previously shown that Gsr facilitates neutrophil bactericidal activities and is pivotal for host defense against bacterial pathogens. However, it is unclear whether Gsr is required for immune defense against fungal pathogens. It is also unclear whether Gsr plays a role in immunological functions outside of neutrophils during immune defense. In this study, we report that Gsr-/- mice exhibited markedly increased susceptibility to Candida albicans challenge. Upon C. albicans infection, Gsr-/- mice exhibited dramatically increased fungal burden in the kidneys, cytokine and chemokine storm, striking neutrophil infiltration, histological abnormalities in both the kidneys and heart, and substantially elevated mortality. Large fungal foci surrounded by massive numbers of neutrophils were detected outside of the glomeruli in the kidneys of Gsr -/- mice but were not found in wild-type mice. Examination of the neutrophils and macrophages of Gsr-/- mice revealed several defects. Gsr -/- neutrophils exhibited compromised phagocytosis, attenuated respiratory burst, and impaired fungicidal activity in vitro. Moreover, upon C. albicans stimulation, Gsr -/- macrophages produced increased levels of inflammatory cytokines and exhibited elevated p38 and JNK activities, at least in part, because of lower MAPK phosphatase (Mkp)-1 activity and greater Syk activity. Thus, Gsr-mediated redox regulation is crucial for fungal clearance by neutrophils and the proper control of the inflammatory response by macrophages during host defense against fungal challenge.

Video-Assisted Thoracoscopic Sleeve Lobectomy for Centrally Located Non-small Cell Lung Cancer: A Meta-analysis.

BACKGROUND: Whether video-assisted thoracoscopic surgery (VATS) sleeve lobectomy could be an alternative to traditional thoracotomy sleeve lobectomy in treating centrally located non-small cell lung cancer (NSCLC) remains unclear. Therefore, we conducted the first meta-analysis to compare the effects of VATS sleeve lobectomy with thoracotomy sleeve lobectomy. METHODS: We systematically searched relevant studies from Pubmed, Embase, and Web of Science on May 12, 2020. Data for analysis included short-term outcomes (blood loss, lymph node dissected, operation time, hospital stay, complications) and long-term outcomes (3-year overall survival (OS) and progression-free survival (PFS) rates). We calculated the weighted mean differences (WMDs) for continuous data and risk ratio (RR) for pooling categorical data. RESULTS: We finally included 5 retrospective cohort study consisting of 436 patients. VATS sleeve lobectomy yielded significantly less blood loss (WMD = -37.83; 95% confidence intervals (CIs) = [-58.56, -17.11]; P < 0.001) than thoracotomy sleeve lobectomy and comparable total number of dissected lymph node to thoracotomy sleeve lobectomy (WMD = - 0.07; 95%CI = [-1.14, 0.99]; P = 0.89). However, VATS sleeve lobectomy consumed significantly more operation time than thoracotomy sleeve lobectomy (WMD = 49.00; 95%CI = [14.67, 83.34]; P = 0.005). VATS sleeve lobectomy yielded significantly less postoperative hospital stay time than thoracotomy sleeve lobectomy (WMD = -1.68; 95%CI = [-2.98, -0.39]; P = 0.011) and comparable postoperative complication rate to thoracotomy sleeve lobectomy (RR = 0.84; 95%CI = [0.49, 1.44]; P = 0.52). Moreover, VATS sleeve lobectomy yielded comparable 3-year OS (RR = 1.08; 95%CI = [0.95, 1.22]; P = 0.23) and PFS (RR = 1.15; 95%CI = [0.96, 1.37]; P = 0.13) rates to thoracotomy sleeve lobectomy. No significant heterogeneities were observed. CONCLUSIONS: VATS sleeve lobectomy yielded less surgical trauma than thoracotomy sleeve lobectomy and improved postoperative recovery without compromising oncological prognosis. Even though VATS sleeve lobectomy may consume more operation time, it could be recommended as an alternative to thoracotomy sleeve lobectomy for treating centrally located NSCLC in carefully selected cases.

Assessing Differences in Lymph Node Metastasis Based Upon Sex in Early Non-Small Cell Lung Cancer.

BACKGROUNDS: Whether sex has any impact on the risk of lymph node (LN) metastasis (LNM) in patients with early-stage non-small cell lung cancer (NSCLC) remains controversial. Therefore, we aimed to objectively compared the risk of LNM between female and male patients with early-stage NSCLC so as to figure out whether sex-different extent of surgery may be justified for treating these patients. METHODS: We retrospectively collected clinical data of patients undergoing lobectomy or segmentectomy with systematic hilar and mediastinal LN dissection for clinical stage IA peripheral NSCLC from June 2014 to April 2019. Both multivariate logistic regression analysis and propensity score-matched(PSM) analysis were applied to compare the risk of LNM between female and male patients. RESULTS: We finally included a total of 660 patients for analysis. In the analysis of unmatched cohorts, there was no significant different rate of LNM (12.4% Vs 13.9%, P=0.556), hilar/intrapulmonary LNM (8.4% Vs 10.7%, P=0.318) and mediastinal LNM(7.9% Vs 7.5%, P=0.851) between female and male patients. In the multivariate analysis, sex was not found to be an independent predictor of LN in these patients. Moreover, in the analysis of well-matched cohorts generated by PSM analysis, there was still no significant different rate of LNM (13.8% Vs 13.4%, P=0.892), hilar/intrapulmonary LNM (9.1% Vs 11.2%, P=0.442) and mediastinal LNM (9.1% Vs 6.5%, P=0.289) between female and male patients. CONCLUSIONS: Sex was not an independent predictor of LNM in early-stage NSCLC and there is no sufficient evidence justifying for sex-different extent of surgical resection for these patients.

Thymoquinone loaded calcium alginate and polyvinyl alcohol carrier inhibits the 7,12-dimethylbenz[a]anthracene-induced hamster oral cancer via the down-regulation of PI3K/AKT/mTOR signaling pathways.

Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12-Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF-κBp50, NF-κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT-PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca-alg-PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF-κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca-alg-PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti-invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca-alg-PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

[Feasibility Study of Ultra-High-Resolution Low-Dose Temporal Bone CT with 1 024×1 024 Reconstruction Matrix Size].

OBJECTIVE: To investigate the feasibility of low-dose CT scan of the temporal bone combined with reconstruction matrix size of 1 024×1 024 and the effect of the reconstruction matrix size on image quality. METHODS: Normal-dose and low-dose bilateral temporal bone CT scans were performed on twelve adult male cadaveric skull specimens using the 160-slice multi-detector CT scanning of United Imaging Healthcare. Normal-dose CT images were reconstructed with matrix sizes of 512×512 and 1 024×1 024, while low-dose CT images were reconstructed with the matrix size of 1 024×1 024. CT value, noise, signal-to-noise ratio, contrast-to-noise ratio, the visualization scoring of 15 anatomical structures of the temporal bone, and the result of three-dimensional reconstruction of the ossicular chain were compared among the three groups. RESULTS: The radiation dose of low-dose CT scanning was reduced by about 50% compared with that of normal-dose CT. There was no significant difference in CT values of air, soft tissues and bones among the three groups. Low-dose temporal bone CT with the matrix size of 1 024×1 024 had higher noise, but much better visualization of temporal bone structure than the normal-dose temporal bone CT with matrix size of 512×512. Both the three-dimensional reconstructions of normal-dose and low-dose 1 024×1 024 matrix images were satisfactory and showed no significant difference. The morphology, size and relative position of malleus, incus, stapes, cochlea, and labyrinth, as well as the location of the ossicular chain in the cranium were all clearly displayed. CONCLUSION: Low-dose temporal bone CT with the matrix size of 1 024×1 024 can be used to effectively reduce the radiation dose and significantly improve the spatial resolution and the visualization of the temporal bone anatomical structures compared with the normal-dose temporal bone CT with a matrix size of 512×512.

Dimeric Cycloparaphenylenes with a Rigid Aromatic Linker.

Dimeric cycloparaphenylene (CPP) architectures with well-defined flipping motion are constructed taking advantage of an efficient cyclocondensation reaction. Variable-temperature nuclear magnetic resonance (VT-NMR) analyses and theoretical calculations indicate rapid interconversion of cis and trans conformers at room temperature, while energetically favorable trans conformer exists at low temperature with the metastable cis conformer hidden. The trihexylsilylethynyl-substituted dimer exhibits bright emission in solution at 616 nm with quantum yield up to 80 %, representing the brightest CPP-based emitter beyond 600 nm. A 1:2 host-guest complex of the dimer and C60 is established with negative cooperativity, demonstrating the first example of 1:2 complex from CPP derivatives.