Long Non Coding RNA MALAT1 Promotes Tumor Growth and Metastasis by Inducing Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

The prognosis of advanced oral squamous cell carcinoma (OSCC) patients remains dismal, and a better understanding of the underlying mechanisms is critical for identifying effective targets with therapeutic potential to improve the survival of patients with OSCC. This study aims to clarify the clinical and biological significance of metastasis-associated long non-coding RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in OSCC. We found that MALAT1 is overexpressed in OSCC tissues compared to normal oral mucosa by real-time PCR. MALAT1 served as a new prognostic factor in OSCC patients. When knockdown by small interfering RNA (siRNA) in OSCC cell lines TSCCA and Tca8113, MALAT1 was shown to be required for maintaining epithelial-mesenchymal transition (EMT) mediated cell migration and invasion. Western blot and immunofluorescence staining showed that MALAT1 knockdown significantly suppressed N-cadherin and Vimentin expression but induced E-cadherin expression in vitro. Meanwhile, both nucleus and cytoplasm levels of β-catenin and NF-κB were attenuated, while elevated MALAT1 level triggered the expression of β-catenin and NF-κB. More importantly, targeting MALAT1 inhibited TSCCA cell-induced xenograft tumor growth in vivo. Therefore, these findings provide mechanistic insight into the role of MALAT1 in regulating OSCC metastasis, suggesting that MALAT1 is an important prognostic factor and therapeutic target for OSCC

High-Fidelity Clothed Avatar Reconstruction from a Single Image

This paper presents a framework for efficient 3D clothed avatar reconstruction. By combining the advantages of the high accuracy of optimization-based methods and the efficiency of learning-based methods, we propose a coarse-to-fine way to realize a high-fidelity clothed avatar reconstruction (CAR) from a single image. At the first stage, we use an implicit model to learn the general shape in the canonical space of a person in a learning-based way, and at the second stage, we refine the surface detail by estimating the non-rigid deformation in the posed space in an optimization way. A hyper-network is utilized to generate a good initialization so that the convergence o f the optimization process is greatly accelerated. Extensive experiments on various datasets show that the proposed CAR successfully produces high-fidelity avatars for arbitrarily clothed humans in real scenes

Effectiveness and safety of anti-PD-1 monotherapy or combination therapy in Chinese advanced gastric cancer: A real-world study

PurposeGastric cancer (GC) is one of the most frequently diagnosed cancers and one of the leading causes of cancer deaths worldwide, especially in eastern Asia and China. Anti-PD-1 immune checkpoint inhibitors, Pembrolizumab and Nivolumab, have been approved for the treatment of locally advanced or metastatic gastric or gastroesophageal junction cancer (GC/GEJC). Our study evaluated the effectiveness and safety of anti-PD-1-based treatment (monotherapy or combination therapy) in Chinese patients with advanced or metastatic GC/GEJCs in a real-world setting.MethodsA retrospective cohort study was conducted, and 54 patients from May 31, 2015, to May 31, 2021, were included in our analysis, including 19 patients treated with anti-PD-1 monotherapy and 35 patients treated with anti-PD-1 combination therapy. Demographic and clinical information were evaluated. Clinical response, survival outcomes, and safety profile were measured and analyzed.ResultsOverall, the median overall survival (mOS) was 11.10 months (95% CI, 7.05–15.15), and the median progression-free survival (mPFS) was 3.93 months (95% CI, 2.47–5.39). Of the patients, 16.7% achieved a clinical response, and 72.2% achieved disease control. Prolonged overall survival (OS) and progression-free survival (PFS) and increased clinical response were observed in the combination group compared with the monotherapy group, although statistical significance was not reached. In subgroups with live metastases or elevated baseline neutrophil-to-lymphocyte ratio (NLR) levels, combination therapy outperformed anti-PD-1 alone in survival outcomes. Patients treated with anti-PD-1 monotherapy (n = 5, 26.3%) had fewer treatment-related adverse events (TRAEs) than those in the combination group (n = 22, 62.9%). There were also fewer patients with TRAEs of grades 3–5 with monotherapy (n = 2, 10.5%) than with combination therapy (n = 7, 20.0%). Pneumonitis in three patients was the only potential immune-related adverse event reported.ConclusionsAnti-PD-1-based monotherapy and combination therapy showed favorable survival outcomes and manageable safety profiles in advanced or metastatic GC/GEJCs. In clinical treatment, immunotherapy should be an indispensable choice in the treatment strategy for GC/GEJC. Patients with a heavy tumor burden and more metastatic sites might benefit more from combination therapy. Elderly patients and patients with more treatment lines or high Eastern Cooperative Oncology Group (ECOG) performance scores might be more suitable for immune monotherapy, and some clinical benefits have been observed

Clinical value of perivascular fat attenuation index and computed tomography derived fractional flow reserve in identification of culprit lesion of subsequent acute coronary syndrome

PurposeTo explore the potential of perivascular fat attenuation index (FAI) and coronary computed tomography angiography (CCTA) derived fractional flow reserve (CT-FFR) in the identification of culprit lesion leading to subsequent acute coronary syndrome (ACS).MethodsThirty patients with documented ACS event who underwent invasive coronary angiography (ICA) from February 2019 to February 2021 and had received CCTA in the previous 6 months were collected retrospectively. 40 patients with stable angina pectoris (SAP) were matched as control group according to sex, age and risk factors. The study population has a mean age of 59.3 ± 12.3 years, with a male prevalence of 81.4%. The plaque characteristics, perivascular fat attenuation index (FAI), and coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) of 32 culprit lesions and 30 non-culprit lesions in ACS patients and 40 highest-grade stenosis lesions in SAP patients were statistically analyzed.ResultsFAI around culprit lesions was increased significantly (−72.4 ± 3.2 HU vs. −79.0 ± 7.7 HU, vs. −80.4 ± 7.0HU, all p < 0.001) and CT-FFR was decreased for culprit lesions of ACS patients [0.7(0.1) vs. 0.8(0.1), vs.0.8(0.1), p < 0.001] compared to other lesions. According to multivariate analysis, diameter stenosis (DS), FAI, and CT-FFR were significant predictors for identification of the culprit lesion. The integration model of DS, FAI, and CT-FFR showed the significantly highest area under the curve (AUC) of 0.917, compared with other single predictors (all p < 0.05).ConclusionsThis study proposes a novel integrated prediction model of DS, FAI, and CT-FFR that enhances the diagnostic accuracy of traditional CCTA for identifying culprit lesions that trigger ACS. Furthermore, this model also provides improved risk stratification for patients and offers valuable insights for predicting future cardiovascular events

Short-term effects of biochar on soil CO2 efflux in boreal Scots pine forests

Key message During the first summer, wood biochar amendments increased soil temperature, pH, and soil CO(2)effluxes in a xeric boreal Scots pine forest. The increase of soil CO(2)efflux could be largely explained by increases in by soil temperature. Higher biochar application rates (1.0 vs 0.5 kg m(-2)) led to higher soil CO(2)efflux while the pyrolysis temperature of biochar (500 or 650 degrees C) had no effect on soil CO(2)efflux. Context Using biochar as a soil amendment has been proposed to increase the carbon sequestration in soils. However, a more rapid soil organic matter turnover after biochar application might reduce the effectiveness of biochar applications for carbon sequestration. By raising the pyrolysis temperature, biochar with lower contents of labile carbohydrates can be produced. Aims To better understand the effects of biochar on boreal forest soil, we applied two spruce biochar with different pyrolysis temperatures (500 degrees C and 650 degrees C) at amounts of 1.0 and 0.5 kg m(-2)in a young xeric Scots pine forest in southern Finland. Methods Soil CO2, microbial biomass, and physiochemical properties were measured to track changes after biochar application during the first summer. Results Soil CO(2)increased 14.3% in 1.0 kg m(-2)treatments and 4.6% in 0.5 kg m(-2). Soil temperature and pH were obviously higher in the 1.0 kg m(-2)treatments. Differences in soil CO(2)among treatments disappear after correcting by soil temperature and soil moisture. Conclusion Biochar increased soil CO(2)mainly by raising soil temperature in the short term. Higher biochar application rates led to higher soil CO(2)effluxes. The increase in soil CO(2)efflux may be transient. More studies are needed to get the optimum biochar amount for carbon sequestration in boreal forest.Peer reviewe

Sensitivity enhancement of a Cu (II) metal organic framework-acetylene black-based electrochemical sensor for ultrasensitive detection of imatinib in clinical samples

Imatinib (IMB), an anticancer drug, is extensively used for chemotherapy to improve the quality of life of cancer patients. The aim of therapeutic drug monitoring (TDM) is to guide and evaluate the medicinal therapy, and then optimize the clinical effect of individual dosing regimens. In this work, a highly sensitive and selective electrochemical sensor based on glassy carbon electrode (GCE) modified with acetylene black (AB) and a Cu (II) metal organic framework (CuMOF) was developed to measure the concentration of IMB. CuMOF with preferable adsorbability and AB with excellent electrical conductivity functioned cooperatively to enhance the analytical determination of IMB. The modified electrodes were characterized using X-rays diffraction (XRD), X-ray photoelectron spectroscopy (XPS), fourier transform infrared (FT-IR), ultraviolet and visible spectrophotometry (UV-vis), electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), energy dispersive X‐ray spectroscopy (EDS), brunauer‒emmett‒teller (BET) and barrett‒joyner‒halenda (BJH) techniques. Analytical parameters such as the ratio of CuMOF to AB, dropping volumes, pH, scanning rate and accumulation time were investigated through cyclic voltammetry (CV). Under optimal conditions, the sensor exhibited an excellent electrocatalytic response for IMB detection, and two linear detection ranges were obatined of 2.5 nM-1.0 μM and 1.0–6.0 μM with a detection limit (DL) of 1.7 nM (S/N = 3). Finally, the good electroanalytical ability of CuMOF-AB/GCE sensor facilitated the successful determination of IMB in human serum samples. Due to its acceptable selectivity, repeatability and long-term stability, this sensor shows promising application prospects in the detection of IMB in clinical samples

High-efficiency 100-W Kerr-lens mode-locked Yb:YAG thin-disk oscillator

We demonstrate a Kerr-lens mode-locked femtosecond Yb:YAG thin-disk oscillator and investigate the approach to increase the optical-to-optical efficiency based on the scheme of direct multiple passes of the laser beam through the thin-disk medium. With twelve passes through the thin disk, 266-fs pulses were delivered from the oscillator with an average power of 105.6 W at a repetition rate of 20 MHz. The corresponding optical-to-optical efficiency is 31.1%, which is, to the best of our knowledge, the highest efficiency of any mode-locked thin-disk oscillator with pulse duration below 300 fs. This demonstration paves the way to even more efficient mode-locked femtosecond thin-disk oscillators, and provides an excellent laser source for the applications such as non-linear frequency conversion and high-precision industrial processing

Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer's disease model

阿尔茨海默病（Alzheimer’s Disease, AD）是一种以渐进性认知功能丧失为主要特征的神经退行性疾病，是最为常见的老年痴呆类型。随着全球人口老龄化的加剧，AD正在成为二十一世纪最大的疾病之一。该研究首次揭示sTREM2在AD中具有重要的保护功能，提出sTREM2或可用于AD治疗的新观点，同时也进一步佐证了小胶质细胞在AD治疗中的核心作用，研究为AD等神经退行性疾病的防治开辟了新思路、提供了新靶点。 厦门大学医学院博士后钟力和硕士研究生徐颖为论文共同第一作者，陈小芬教授和卜国军教授为该论文的共同通讯作者。厦门大学的文磊、孙灏、卓仁恭等教授和美国Sanford-Burnham-Prebys医学研究所的许华曦教授共同参与了该项目的研究。【Abstract】Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor genetically linked to the risk for Alzheimer’s disease (AD). A proteolytic product, soluble TREM2 (sTREM2), is abundant in the cerebrospinal fluid and its levels positively correlate with neuronal injury markers. To gain insights into the pathological roles of sTREM2, we studied sTREM2 in the brain of 5xFAD mice, a model of AD, by direct stereotaxic injection of recombinant sTREM2 protein or by adeno-associated virus (AAV)-mediated expression. We found that sTREM2 reduces amyloid plaque load and rescues functional deficits of spatial memory and long-term potentiation. Importantly, sTREM2 enhances microglial proliferation, migration, clustering in the vicinity of amyloid plaques and the uptake and degradation of Aβ. Depletion of microglia abolishes the neuroprotective effects of sTREM2. Our study demonstrates a protective role of sTREM2 against amyloid pathology and related toxicity and suggests that increasing sTREM2 can be explored for AD therapy.Research by the authors was supported by grants from the National Natural Science Foundation of China 81370459, 31400914 (to X.C.), 81701079 (to L.Z.), 81373999, 81774377 (to L.W.), and 81601227 (to R.Z.), grants from the Natural Science Foundation of Guangdong Province 2016A030306005 (to X.C.), 2016A030310371 (to R.Z.), grants from the Fundamental Research Funds for the Central Universities 20720180055 (to X.C.), grants from the Alzheimer's Association AARG-18-56635 (to X.C.), and C4C-15-369446 (to H.X.). NIH grants RF1AG056130 (to G.B. and H.X.), R01AG035355 (to G.B.), R37AG027924 (to G.B.), and RF1AG056114 (to H.X.), grants from the Postdoctoral Science Foundation of China 2016M600503 and 2017T100469 (to L.Z.), a grant from the Tanz Family Funds (to H.X.), and a grant from the Natural Science Foundation of Fujian Province 2016J05203 (to R.Z.).该工作得到国家自然科学基金、厦门大学校长基金、广东省自然科学杰出青年基金、美国阿尔茨海默氏症协会基金和中国博士后科学基金等的资助

Associations between plasma metal mixture exposure and risk of hypertension: A cross-sectional study among adults in Shenzhen, China

BackgroundMetal exposure affects human health. Current studies mainly focus on the individual health effect of metal exposure on hypertension (HTN), and the results remain controversial. Moreover, the studies assessing overall effect of metal mixtures on hypertension risk are limited.MethodsA cross-sectional study was conducted by recruiting 1,546 Chinese adults who attended routine medical check-ups at the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen. The plasma levels of 13 metals were measured using inductively coupled plasma mass spectrometry. Multivariate logistic regression model, restricted cubic spline (RCS) model and the Bayesian Kernel Machine Regression (BKMR) model were applied to explore the single and combined effect of metals on the risk of HTN.ResultsA total of 642 (41.5%) participants were diagnosed with HTN. In the logistic regression model, the adjusted odds ratios (ORs) were 0.71 (0.52, 0.97) for cobalt, 1.40 (1.04, 1.89) for calcium, 0.66 (0.48, 0.90), and 0.60 (0.43, 0.83) for aluminum in the second and third quartile, respectively. The RCS analysis showed a V-shaped or an inverse V-shaped dose-response relationship between metals (aluminum or calcium, respectively) and the risk of HTN (P for non-linearity was 0.017 or 0.009, respectively). However, no combined effect was found between metal mixture and the risk of hypertension.ConclusionsPlasma levels of cobalt, aluminum and calcium were found to be associated with the risk of HTN. Further studies are needed to confirm our findings and their potential mechanisms with prospective studies and experimental study designs

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data