Comparison of endostatin(endostar)and avastin's inhibition effect on mice choroidal neovascularization

AIM:To observe the inhibition effect of endostatin(endostar)on mice choroidal neovascularization model(CNV)and compare with the Avastin.<p>METHODS: Using 532nm laser photocoagulation to establish a mouse model of CNV. We observed the formation of CNV by histopathological examination after 2wk later. Forty successful models of mice were randomly divided into control group(group 1, 10 rats), normal saline group(group 2, 10 rats), endostatin group(group 3, 10 rats)and avastin group(group 4, 10 rats). The drugs were injected into the mice' vitreous after photocoagulation 2wk later. Then 1wk later, we took the mice eyeballs to perform the HE and immunohistochemical staining to observe. The statistical analysis of ANOVA was done by SPSS 16.0 and the LSD-<i>t</i> test was used for multiple samples, taking <i>P</i><0.05 as the test standards.<p>RESULTS: Two weeks later, HE histopathological examination was done, light microscope showed large amount of new vessels' formation, the positive rate for CNV was 72.8%. The blank control group compared with the normal saline group <i>P</i>>0.05, had no inhibitory effect on CNV; endostatin treated group compared with control group, <i>P</i><0.05, had a certain inhibitory effect; avastin group compared with the control group, <i>P</i><0.05, had an inhibitory effect on CNV; the LSD-<i>t</i> was performed on Avastin group and endostatin group, <i>P</i><0.05, which were statistically significant. We thought that the two drugs have different inhibitory effect on mice' CNV, because <i>(-overx)</i>_Avastin=26.90,<i>(-overx)</i>_endostatin=29.13,<i>(-overx)</i>_Avastin<<i>(-overx)</i>_endostatin, we can infer that endostar had lower inhibitory effect on mice CNV than Avastin.<p>CONCLUSION: Laser-induced CNV animal models of colored mice C57BL/6J is of short time and high rate establishment and it is an ideal model for CNV study. Endostar has certain inhibitory effect on CNV, and it is likely to become one of the important drugs for CNV-related diseases in the future

Intratumoral microbiome impacts immune infiltrates in tumor microenvironment and predicts prognosis in esophageal squamous cell carcinoma patients

BackgroundDifferent intratumoral microbiotaexist in different tumors and play a crucial function in carcinogenesis. However, whether they impact clinical outcomes in esophageal squamous cell carcinoma (ESCC) and their mechanism remain unclear.Methods16S rDNA amplicon sequencing was performed on surgically resected samples from 98 ESCC patients to analyze intratumoral microbiome abundance and composition. Multiplex fluorescent immunohistochemistry staining was used to profile the phenotypes of immune infiltrates in the tumor microenvironment (TME).ResultsPatients with higher intratumoral Shannon index had significantly worse surgical outcomes. When patients were divided into short-term survivors and long-term survivors based on the median survival time, both intratumoral alpha-diversity and beta-diversity were found to be significantly inconsistent, and the relative abundance of Lactobacillus and Leptotrichia emerged as the two microorganisms that probably influenced the survival of ESCC patients. Only Lactobacillus in ESCC was validated to significantly worsen patients’ prognoses and to be positively correlated with the Shannon index. Multivariate analysis revealed that the intratumoral Shannon index, the relative abundance of Lactobacillus, and the pathologic tumor–node–metastasis (pTNM) stage were independently associated with patients’ overall survival. Furthermore, the relative abundance of both Lactobacillus and Shannon index was positively correlated with the proportions of PD-L1+ epithelial cells (ECs) and tumor-associated macrophages (TAMs). The Shannon index was negatively correlated with the proportions of natural killer (NK) cells in the TME.ConclusionsA high abundance of intratumoral Lactobacillus and bacterial alpha-diversity was associated with the formation of the immunosuppressive TME and predicted poor long-term survival in ESCC patients

Multiple Frequency Bands Analysis of Large Scale Intrinsic Brain Networks and Its Application in Schizotypal Personality Disorder

The human brain is a complex system composed by several large scale intrinsic networks with distinct functions. The low frequency oscillation (LFO) signal of blood oxygen level dependent (BOLD), measured through resting-state fMRI, reflects the spontaneous neural activity of these networks. We propose to characterize these networks by applying the multiple frequency bands analysis (MFBA) to the LFO time courses (TCs) resulted from the group independent component analysis (ICA). Specifically, seven networks, including the default model network (DMN), dorsal attention network (DAN), control executive network (CEN), salience network, sensorimotor network, visual network and limbic network, are identified. After the power spectral density (PSD) analysis, the amplitude of low frequency fluctuation (ALFF) and the fractional amplitude of low frequency fluctuation (fALFF) is determined in three bands: &lt;0.1 Hz; slow-5; and slow-4. Moreover, the MFBA method is applied to reveal the frequency-dependent alternations of fALFF for seven networks in schizotypal personality disorder (SPD). It is found that seven networks can be divided into three categories: the advanced cognitive networks, primary sensorimotor networks and limbic networks, and their fALFF successively decreases in both slow-4 and slow-5 bands. Comparing to normal control group, the fALFF of DMN, DAN and CEN in SPD tends to be higher in slow-5 band, but lower in slow-4. Higher fALFF of sensorimotor and visual networks in slow-5, higher fALFF of limbic network in both bands have been observed for SPD group. The results of ALFF are consistent with those of fALFF. The proposed MFBA method may help distinguish networks or oscillators in the human brain, reveal subtle alternations of networks through locating their dominant frequency band, and present potential to interpret the neuropathology disruptions

Label-Free Biomedical Imaging with High Sensitivity by Stimulated Raman Scattering Microscopy

Label-free chemical contrast is highly desirable in biomedical imaging. Spontaneous Raman microscopy provides specific vibrational signatures of chemical bonds, but is often hindered by low sensitivity. Here we report a three-dimensional multiphoton vibrational imaging technique based on stimulated Raman scattering (SRS). The sensitivity of SRS imaging is significantly greater than that of spontaneous Raman microscopy, which is achieved by implementing high-frequency (megahertz) phase-sensitive detection. SRS microscopy has a major advantage over previous coherent Raman techniques in that it offers background-free and readily interpretable chemical contrast. We show a variety of biomedical applications, such as differentiating distributions of omega-3 fatty acids and saturated lipids in living cells, imaging of brain and skin tissues based on intrinsic lipid contrast, and monitoring drug delivery through the epidermis.Chemistry and Chemical Biolog

Learning to infer inner-body under clothing from monocular video

Accurately estimating the human inner-body under clothing is very important for body measurement, virtual try-on and VR/AR applications. In this paper, we propose the first method to allow everyone to easily reconstruct their own 3D inner-body under daily clothing from a self-captured video with the mean reconstruction error of 0.73 cm within 15 s. This avoids privacy concerns arising from nudity or minimal clothing. Specifically, we propose a novel two-stage framework with a Semantic-guided Undressing Network (SUNet) and an Intra-Inter Transformer Network (IITNet). SUNet learns semantically related body features to alleviate the complexity and uncertainty of directly estimating 3D inner-bodies under clothing. IITNet reconstructs the 3D inner-body model by making full use of intra-frame and inter-frame information, which addresses the misalignment of inconsistent poses in different frames. Experimental results on both public datasets and our collected dataset demonstrate the effectiveness of the proposed method. The code and dataset is available for research purposes at http://cic.tju.edu.cn/faculty/likun/projects/Inner-Body

Rice plants respond to ammonium‐stress by adopting a helical root growth pattern

High levels of ammonium nutrition reduce plant growth and different plant species have developed distinct strategies to maximize ammonium acquisition while alleviate ammonium toxicity through modulating root growth. Up to now, the mechanism underlying plant tolerance or sensitivity towards ammonium remain unclear. Rice uses ammonium as its main N source. Here we show that ammonium supply restricts rice root elongation and induces a helical growth pattern, which is attributed to root acidification resulting from ammonium uptake. Ammonium-induced low pH triggers asymmetric auxin distribution in rice root tips through changes in auxin signaling, thereby inducing a helical growth response. Blocking auxin signaling completely inhibited this root response. In contrast, this root response is not activated in ammonium-treated Arabidopsis. Acidification of Arabidopsis roots leads to the protonation of IAA, and dampening the intracellular auxin signaling levels that are required for maintaining root growth. Our study suggests a different mode of action by ammonium on the root pattern and auxin response machinery in rice versus Arabidopsis, and the rice-specific helical root response towards ammonium is an expression of the ability of rice in moderating auxin signaling and root growth to utilize ammonium while confronting acidic stress

UBR4 deficiency causes male sterility and testis abnormal in Drosophila

IntroductionIt has been established that UBR4 encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of UBR4 on fertility with a Drosophila model.MethodsDifferent Ubr4 knockdown flies were established using the UAS/GAL4 activating sequence system. Fertility, hatchability, and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that UBR4 deficiency could induce male sterility and influent egg hatchability in Drosophila.ResultsWe found that Ubr4 deficiency affected the testis during morphological analysis. Proteomics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of Ubr4 knockdown flies. Gene Ontology analysis revealed significant upregulation of CG11598 and Sfp65A, and downregulation of Pelota in Ubr4 knockdown flies. These proteins were involved in the biometabolic or reproductive process in Drosophila. These regulated proteins are important in testis generation and sperm storage promotion. Bioinformatics analysis verified that UBR4 was low expressed in cryptorchidism patients, which further supported the important role of UBR4 in male fertility.DiscussionOverall, our findings suggest that UBR4 deficiency could promote male infertility and may be involved in the protein modification of UBR4 by upregulating Sfp65A and CG11598, whereas downregulating Pelota protein expression

Serological surveillance of GI norovirus reveals persistence of blockade antibody in a Jidong community-based prospective cohort, 2014–2018

IntroductionHerd immunity against norovirus (NoV) is poorly understood in terms of its serological properties and vaccine designs. The precise neutralizing serological features of genotype I (GI) NoV have not been studied.MethodsTo expand insights on vaccine design and herd immunity of NoVs, seroprevalence and seroincidence of NoV genotypes GI.2, GI.3, and GI.9 were determined using blockade antibodies based on a 5-year longitudinal serosurveillance among 449 residents in Jidong community.ResultsCorrelation between human histo-blood group antigens (HBGAs) and GI NoV, and dynamic and persistency of antibodies were also analyzed. Seroprevalence of GI.2, GI.3, and GI.9 NoV were 15.1%–18.0%, 35.0%–38.8%, and 17.6%–22.0%; seroincidences were 10.0, 21.0, and 11.0 per 100.0 person-year from 2014 to 2018, respectively. Blockade antibodies positive to GI.2 and GI.3 NoV were significantly associated with HBGA phenotypes, including blood types A, B (excluding GI.3), and O+; Lewis phenotypes Leb+/Ley+ and Lea+b+/Lex+y+; and secretors. The overall decay rate of anti-GI.2 antibody was -5.9%/year (95% CI: -7.1% to -4.8%/year), which was significantly faster than that of GI.3 [-3.6%/year (95% CI: -4.6% to -2.6%/year)] and GI.9 strains [-4.0%/year (95% CI: -4.7% to -3.3%/year)]. The duration of anti-GI.2, GI.3, and GI.9 NoV antibodies estimated by generalized linear model (GLM) was approximately 2.3, 4.2, and 4.8 years, respectively.DiscussionIn conclusion, enhanced community surveillance of GI NoV is needed, and even one-shot vaccine may provide coast-efficient health benefits against GI NoV infection

Moringa oleifera Leaf Petroleum Ether Extract Inhibits Lipogenesis by Activating the AMPK Signaling Pathway

In recent years, obesity has become a key factor affecting human health. Moringa oleifera Lam. is a perennial tropical deciduous tree, which is widely used in human medicine due to its nutritional and unique medicinal value. It has a cholesterol-lowering effect, but its mechanism of action is unclear. In this study, we elucidated the inhibitory effect of M. oleifera leaf petroleum ether extract (MOPEE) on lipid accumulation by in vitro and in vivo experiments, and we described its mechanism of action. MOPEE suppressed adipogenesis in 3T3-L1 adipocytes in a dose-dependent manner and had no effect on cell viability at doses up to 400 μg/ml. Furthermore, MOPEE (400 μg/ml) significantly downregulated the expression of adipogenesis-associated proteins [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding proteins α and β (C/EBPα and C/EBPβ), and fatty acid synthase (FAS)] and upregulated the expression of a lipolysis-associated protein [hormone-sensitive lipase (HSL)] in 3T3-L1 adipocytes. Additionally, MOPEE (400 μg/ml) significantly increased the degree of phosphorylation of AMP-activated protein kinase α (AMPKα) and acetyl-CoA carboxylase (ACC). An AMPK inhibitor reversed the MOPEE-induced activation of AMPKα and ACC in 3T3-L1 adipocytes. Animal experiments showed that, in high-fat diet (HFD) mice, MOPEE [0.5 g/kg body weight (BW)] effectively decreased BW; relative epididymal, perirenal, and mesenteric fat weight and fat tissue size; and hepatic fat accumulation. Furthermore, MOPEE markedly reduced the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and aspartate aminotransferase (AST). Moreover, MOPEE significantly downregulated the expression of adipogenesis-associated proteins (PPARγ and FAS) and upregulated the expression of a lipolysis-associated protein [adipose triglyceride lipase (ATGL)] in HFD mice hepatic and epididymal fat tissue. Additionally, MOPEE markedly increased the degree of phosphorylation of AMPKα and ACC in HFD mice hepatic and epididymal fat tissue. Following ultrahigh-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) analysis, three phytocompounds (isoquercitrin, chrysin-7-glucoside, and quercitrin) were identified as compounds with relatively high levels in MOPEE. Among them, quercitrin showed excellent fat accumulation inhibitory activity, and the three compounds had synergistic effects in inhibiting adipogenesis. Taken together, MOPEE inhibits fat accumulation by inhibiting the adipogenesis and promoting the lipolysis, and this process is related to AMPK activation