Publications by authors named "Xiaoxia Wang"

433 Publications

Association of thyroid disorders with gestational diabetes mellitus: a meta-analysis.

Endocrine 2021 May 13. Epub 2021 May 13.

Department of Endocrinology, The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China.

Purpose: The current meta-analysis aimed to evaluate the association of thyroid dysfunction and autoimmunity with gestational diabetes mellitus (GDM).

Methods: A comprehensive search from PubMed, Embase, MEDLINE, and Cochrane databases until November 2020 was conducted. Fixed-effect model was used to combine the results when I was <50%. Random-effect model was used to summarize the results when I was >50%.

Results: A total of 44 studies were included in the meta-analysis. Low FT4 levels were closely related with GDM in the first and second trimesters of gestation. Hypothyroxinemia (OR: 1.45; 95% CI: 1.25, 1.68; P < 0.00001), overt (OR: 1.80; 95% CI: 1.73, 1.86; P < 0.00001), and subclinical (OR: 1.54; 95% CI: 1.03, 2.30; P = 0.03) hypothyroidism, overt hyperthyroidism (OR: 1.49; 95% CI: 1.09, 2.04; P = 0.01), and positive thyroid antibodies (OR: 1.49; 95% CI: 1.07, 2.07; P < 0.00001) were observed significantly associated with the risk of GDM. Pregnant women with subclinical hyperthyroidism were less likely to develop GDM (OR: 0.62; 95% CI: 0.39, 0.97; P = 0.04).

Conclusions: Thyroid dysfunction and positive thyroid antibodies were associated with the risk of GDM. Our findings suggest that pregnant women with these thyroid diseases may be offered screening for GDM comprehensively.
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http://dx.doi.org/10.1007/s12020-021-02712-2DOI Listing
May 2021

Morphine may act via DDX49 to inhibit hepatocellular carcinoma cell growth.

Aging (Albany NY) 2021 May 5;13. Epub 2021 May 5.

Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China.

Pain in hepatocellular carcinoma (HCC) is a frequent cause of low quality of life, and morphine is routinely used as a first-line opiate analgesic in HCC. Morphine may exert not only analgesic effects but also anti-cancer effects via unknown mechanisms. Here we show that morphine can inhibit HCC cell proliferation. We further show that DEAD-box helicase 49 (DDX49) is up-regulated in HCC tumors, and that knocking down the DDX49 gene decreases tumor formation and as well as reduces tumor metastasis . Morphine decreases DDX49 expression in HCC cells. Our results suggest that DDX49 contributes to HCC, and that morphine may exert anti-cancer effects by down-regulating it.
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http://dx.doi.org/10.18632/aging.202946DOI Listing
May 2021

Simultaneous multi-slice readout-segmentation of long variable echo-trains for accelerated diffusion-weighted imaging of nasopharyngeal carcinoma: A feasibility and optimization study.

Clin Imaging 2021 Apr 29;79:119-124. Epub 2021 Apr 29.

Department of Radiology, Chongqing University Cancer Hospital, Chongqing, China. Electronic address:

Objectives: We aimed to evaluate the feasibility of simultaneous multi-slice readout segmentation of long variable echo-trains (SMS-RESOLVE) for diffusion-weighted imaging (DWI) of nasopharyngeal carcinoma (NPC) and determine the optimal acceleration factor of SMS-RESOLVE DWI compared with conventional RESOLVE DWI.

Materials And Methods: One hundred and five patients with histologically confirmed NPC were enrolled. DWIs including conventional RESOLVE DWI, SMS-RESOLVE DWI with acceleration factors of 2 and 3 (2 × SMS-RESOLVE and 3 × SMS-RESOLVE) were acquired at b-values of 0 and 800 s/mm. The subjective image quality, including overall image quality, lesion conspicuity, and lesion distortion scores, and objective image quality, including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and contrast in these three protocols, were assessed and compared. The apparent diffusion coefficients (ADCs) of the primary tumor and right masseter muscle and normalized ADCs in the three protocols were measured and compared.

Results: The 2 × SMS-RESOLVE provided comparable image quality and ADCs with a 48.3% reduction in scan time compared with conventional RESOLVE DWI. The 3 × SMS-RESOLVE showed significantly poorer image quality and the highest ADCs with a 56.9% reduction in scan times compared with conventional RESOLVE DWI.

Conclusion: The SMS-RESOLVE DWI with an acceleration factor of 2 yielded the best compromise between image quality and scan time reduction and could be an alternative to conventional RESOLVE DWI for nasopharyngeal carcinoma.
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http://dx.doi.org/10.1016/j.clinimag.2021.04.009DOI Listing
April 2021

Dual-energy CT quantitative parameters for the differentiation of benign from malignant lesions and the prediction of histopathological and molecular subtypes in breast cancer.

Quant Imaging Med Surg 2021 May;11(5):1946-1957

Department of Radiology, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, China.

Background: Dual-energy computed tomography (DECT) is widely used to characterize and differentiate tumors. However, data regarding its diagnostic performance for the characterization of breast tumors are limited. In this study, we assessed the diagnostic performance of quantitative parameters derived from DECT in differentiating benign from malignant lesions and predicting histopathological and molecular subtypes in patients with breast cancer.

Methods: Dual-phase contrast-enhanced DECT of the thorax was performed on participants with breast tumors. Conventional CT attenuation and DECT quantitative parameters, including normalized iodine concentration (NIC), the slope of the spectral Hounsfield unit curve (λ), and normalized effective atomic number (nZ), were obtained and compared between benign and malignant lesions, invasive non-special carcinoma, and ductal carcinoma in situ (DCIS), and among the four molecular subtypes of breast cancer. The diagnostic performance of the quantitative parameters was analyzed using receiver operating characteristic (ROC) curves.

Results: This study included 130 participants with 161 breast lesions (44 benign and 117 malignant). In the arterial and venous phase, NICs, λ, nZ, and attenuation were higher in malignant lesions than benign lesions (all P<0.001). The venous phase λ had the best differential diagnostic capability, with an area under the curve (AUC) of 0.90, a sensitivity of 84.1% (37 of 44), a specificity of 86.3% (101 of 117), and an accuracy of 85.7% (138 of 161). The NICs in the arterial and venous phases were higher in invasive non-special carcinoma than DCIS (both P<0.001). In terms of diagnostic performance, NIC in the venous phase had an AUC of 0.77, a sensitivity of 75.0% (12 of 16), a specificity of 81.2% (82 of 101), and an accuracy of 80.3% (94 of 117). The luminal A subtype produced a lower venous phase NIC, and arterial and venous phase nZ than the non-luminal A subtype (AUC of 0.91 for the combination of these three parameters).

Conclusions: Dual-energy CT quantitative parameters are a feasible and valuable noninvasive means of differentiating between benign and malignant lesions, and predicting histopathological and molecular subtypes in patients with breast cancer.
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http://dx.doi.org/10.21037/qims-20-825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047348PMC
May 2021

MondoA-TXNIP axis maintains regulatory T cell identity and function in colorectal cancer microenvironment.

Gastroenterology 2021 Apr 23. Epub 2021 Apr 23.

Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai 200025, China. Electronic address:

Background & Aims: The metabolic features and function of intratumoral Tregs are ambiguous in colorectal cancer. Tumor-infiltrating Tregs are reprogrammed to exhibit high glucose-depleting properties and adapt to the glucose-restricted microenvironment. The glucose-responsive transcription factor MondoA is highly expressed in Tregs. However, the role of MondoA in colorectal cancer-infiltrating Tregs in response to glucose limitation remains to be elucidated.

Methods: We performed studies using mice in which MondoA was conditionally deleted in Tregs and human colorectal cancer tissues. Seahorse and other metabolic assays were used to assess Treg metabolism. To study the role of Tregs in anti-tumor immunity, we used a subcutaneous MC38 colorectal cancer model and induced colitis-associated colorectal cancer in mice by azoxymethane (AOM) and dextran sodium sulfate (DSS).

Results: Here we analyzed single-cell RNA-seq data of colorectal cancer patients and revealed that intratumoral Tregs featured low activity of MondoA-TXNIP axis and increased glucose uptake. Although MondoA-deficient Tregs were less immune suppressive and selectively promoted Th1 responses in a subcutaneous MC38 tumor model, Treg-specific MondoA knockout mice were more susceptible to AOM-DSS-induced colorectal cancer. Mechanistically, suppression of MondoA-TXNIP axis promoted glucose uptake and glycolysis, induced hyper-glycolytic Th17-like Tregs, which facilitated Th17 inflammation, promoted IL-17A-induced of CD8 T cell exhaustion and drove colorectal carcinogenesis. Blockade of IL-17A reduced tumor progression and minimized the susceptibility of MondoA-deficient mice to colorectal carcinogenesis.

Conclusions: The MondoA-TXNIP axis is a critical metabolic regulator of Treg identity and function in colorectal cancer microenvironment and a promising target for cancer therapy.
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http://dx.doi.org/10.1053/j.gastro.2021.04.041DOI Listing
April 2021

LncRNA MEG3 involved in NiO NPs-induced pulmonary fibrosis via regulating TGF-β1-mediated PI3K/AKT pathway.

Toxicol Sci 2021 Apr 24. Epub 2021 Apr 24.

Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.

Long noncoding RNA maternally expressed gene 3 (MEG3) involves in fibrotic diseases, but its role in nickel oxide nanoparticles (NiO NPs)-induced pulmonary fibrosis remains unclear. The present study aimed to explore the relationships among MEG3, transforming growth factor-β1 (TGF-β1) and phosphoinositide 3-kinase (PI3K)/AKT pathway in NiO NPs-induced pulmonary fibrosis. Wistar rats were intratracheally instilled with NiO NPs twice a week for 9 weeks, and human lung adenocarcinoma epithelial cells (A549 cells) were exposed to NiO NPs for 24 hours. The pathological alterations and increased hydroxyproline indicated that NiO NPs caused pulmonary fibrosis in rats. The up-regulated type I collagen (Col-I) suggested that NiO NPs induced collagen deposition in A549 cells. Meanwhile, NiO NPs could significantly down-regulate MEG3, up-regulate TGF-β1 and activate PI3K/AKT signaling pathway both in vivo and in vitro. However, we found that the PI3K/AKT pathway activated by NiO NPs could be suppressed by 10 μM TGF-β1 inhibitor (SB431542) in A549 cells. The protein markers (Col-I, Fibronectin and alpha-smooth muscle actin) of collagen deposition up-regulated by NiO NPs were reduced by 10 μM PI3K inhibitor (LY294002). Furthermore, we further found that overexpressed MEG3 inhibited the expression of TGF-β1, resulting in the inactivation of PI3K/AKT pathway and the reduction of collagen formation. In summary, our results validated that MEG3 could arrest NiO NPs-induced pulmonary fibrosis via inhibiting TGF-β1-mediated PI3K/AKT pathway.
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http://dx.doi.org/10.1093/toxsci/kfab047DOI Listing
April 2021

Long non-coding RNA PTCSC3 inhibits human oral cancer cell proliferation by inducing apoptosis and autophagy.

Arch Med Sci 2021 16;17(2):492-499. Epub 2020 Jun 16.

Department of Dermatology, the Second Affiliated Hospital of Air Force Medical University, Xi'an, China.

Introduction: Long non-coding RNAs (lncRNAs) have gained increased attention due to the discovery of their roles in cancer-related processes. LncRNA PTCSC3 has been shown to have tumour-suppressive effects in thyroid cancer and glioblastoma. This study investigated the role of lncRNA PTSC3 in human oral cancer.

Material And Methods: Cell viability was determined by MTT assay. The induction of apoptosis was confirmed by 4',6-diamidino-2-phenylindole (DAPI) and Annexin V/PI assays. Ultrastructural analysis was performed by electron microscopy. Transwell assay was used to monitor the invasion of oral cancer cells.

Results: The results revealed significant ( < 0.05) suppression of PTCSC3 expression in human oral cancer tissues and cell lines. The overexpression of PTCSC3 caused a significant ( < 0.05) decline in the proliferation of the human oral cancer cells via induction of apoptotic cell death which was accompanied by remarkable enhancement of Bax and suppression of Bcl-2. The electron microscopic analysis showed the development of autophagic vesicles in both the SCC-1 and SCC-9 cells indicative of autophagy. The western blotting analysis showed that PTCSC3 overexpression caused a remarkable increase in LC3B-I and Beclin 1 expression. PTCSC3 overexpression caused a significant ( < 0.05) decrease in invasion of the human SCC-1 and SCC-9 oral cancer cells. The invasion of the SCC-1 and SCC-9 cells was inhibited by 62% and 69% respectively.

Conclusions: Overall, the evidence suggests that lncRNA PTCSC3 acts as a tumour suppressor in human oral cancer and suppresses oral cancer proliferation via induction of apoptosis and autophagy.
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http://dx.doi.org/10.5114/aoms.2020.96409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959011PMC
June 2020

Geranylgeranyl diphosphate synthase deficiency hyperactivates macrophages and aggravates lipopolysaccharide-induced acute lung injury.

Am J Physiol Lung Cell Mol Physiol 2021 Mar 17. Epub 2021 Mar 17.

Department of Respiratory and Critical Care Medicine, Jinling Hospital, Southern Medical University (Guangzhou), China.

Macrophage activation is a key contributing factor for excessive inflammatory responses of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Geranylgeranyl diphosphate synthase (GGPPS) plays a key role in the development of inflammatory diseases. Our group previously showed that GGPPS in alveolar epithelium have deleterious effects on acute lung injury induced by LPS or mechanical ventilation. Herein, we examined the role of GGPPS in modulating macrophage activation in ALI/ARDS. We found significant increased GGPPS expression in alveolar macrophages in ARDS patients compared to healthy volunteers and in ALI mice induced by LPS. GGPPS-floxed control (GGPPS) and myeloid-selective knockout (GGPPSLysMcre) mice were then generated. Interestingly, using a LPS-induced ALI mouse model, we showed that myeloid-specific GGPPS knockout significantly increased mortality, aggravated lung injury, and increased the accumulation of inflammatory cells, total protein, and inflammatory cytokines in BALF. In vitro, GGPPS deficiency up-regulated the production of LPS-induced IL-6, IL-1β, and TNF-α in alveolar macrophages, bone marrow-derived macrophages (BMDMs), and THP-1 cells. Mechanistically, GGPPS knockout increased phosphorylation and nuclear translocation of NF-κB p65 induced by LPS. In addition, GGPPS deficiency increased the level of GTP-Rac1, which was responsible for NF-κB activation. In conclusion, decreased expression of GGPPS in macrophages aggravates lung injury and inflammation in ARDS, at least partly by regulating Rac1-dependent NF-κB signaling. GGPPS in macrophages may represent a novel therapeutic target in ARDS.
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http://dx.doi.org/10.1152/ajplung.00281.2020DOI Listing
March 2021

Iron Deficiency, a Risk Factor of Thyroid Disorders in Reproductive-Age and Pregnant Women: A Systematic Review and Meta-Analysis.

Front Endocrinol (Lausanne) 2021 25;12:629831. Epub 2021 Feb 25.

Department of Endocrinology, Beijing Hospital, The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Background: Iron deficiency (ID) is concerned as the most common nutritional deficiency worldwide. The effects of ID on thyroid function and autoimmunity in pregnant women and reproductive-age women are controversial. The aim of the current study was to summarize the evidences and evaluate the relationship between ID and thyroid disorders.

Methods: In this systematic review and meta-analysis, studies published on the Cochrane, Embase, Medline, and PubMed databases by October 2020 were searched. A total of 636 studies which discussed the correlation between ID and thyroid disorders were eligible in the initial search. Pooled mean differences (MD) and 95% confidence intervals (CI) were calculated for the assessment of thyrotropin (TSH) and free thyroxine (FT4) levels. Combined odd ratios (OR) and 95% CI were calculated for the assessment of the prevalence of overt and subclinical hypothyroidism, positive thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb).

Results: For women of reproductive age, ID could significantly increase the risk of positive TPOAb (OR: 1.89; 95% CI: 1.17, 3.06: = 0.01) and both positive TPOAb and TgAb (OR: 1.48; 95% CI: 1.03, 2.11: = 0.03). The meta-analysis of pregnant women showed that pregnant women with ID had increased serum TSH levels (MD: 0.12; 95% CI: 0.07, 0.17; P < 0.00001) and decreased FT4 levels (MD: -0.73; 95% CI: -1.04, -0.41; P < 0.00001). Meanwhile, the prevalence of overt (OR: 1.60; 95% CI: 1.17, 2.19; P = 0.004) and subclinical (OR: 1.37; 95% CI: 1.13, 1.66; P = 0.001) hypothyroidism in pregnant women with ID was significantly increased.

Conclusions: ID may adversely affect thyroid function and autoimmunity of pregnant and reproductive-age women and it is very necessary for monitoring iron nutritional status and early treatment of ID for them.
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http://dx.doi.org/10.3389/fendo.2021.629831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947868PMC
February 2021

Estimating PM concentrations via random forest method using satellite, auxiliary, and ground-level station dataset at multiple temporal scales across China in 2017.

Sci Total Environ 2021 Mar 6;778:146288. Epub 2021 Mar 6.

College of Geomatics, Xi'an University of Science and Technology, Xi'an, China.

Fine particulate matter with aerodynamic diameters less than 2.5 μm (PM) poses adverse impacts on public health and the environment. It is still a great challenge to estimate high-resolution PM concentrations at moderate scales. The current study calibrated PM concentrations at a 1 km resolution scale using ground-level monitoring data, Aerosol Optical Depth (AOD), meteorological data, and auxiliary data via Random Forest (RF) model across China in 2017. The three ten-folded cross-validations (CV) methods including sample-based, time-based, and spatial-based validation combined with Coefficient Square (R), Root-Mean-Square Error (RMSE), and Mean Predictive Error (MPE) have been used for validation at different temporal scales in terms of daily, monthly, heating seasonal, and non-heating seasonal. Finally, the distribution map of PM concentrations was illustrated based on the RF model. Some findings were achieved. The RF model performed well, with a relatively high sample-based cross-validation R of 0.74, a low RMSE of 16.29 μg × m, and a small MPE of -0.282 μg × m. Meanwhile, the performance of the RF model in inferring the PM concentrations was well at urban scales except for Chengyu (CY). North China, the CY urban agglomeration, and the northwest of China exhibited relatively high PM pollution features, especially in the heating season. The robustness of the RF model in the present study outperformed most statistical regression models for calibrating PM concentrations. The outcomes can supply an up-to-date scientific dataset for epidemiological and air pollutants exposure risk studies across China.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146288DOI Listing
March 2021

Efficacy and safety of a selective URAT1 inhibitor SHR4640 in Chinese subjects with hyperuricemia: a randomized controlled phase II study.

Rheumatology (Oxford) 2021 Mar 8. Epub 2021 Mar 8.

Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Objectives: To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor in Chinese subjects with hyperuricemia.

Methods: This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid levels ≥480 µmol/l with gout, or sUA levels ≥480 µmol/l without gout but with comorbidities, or sUA levels ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg/5 mg/10 mg of SHR4640, 50 mg of benzbromarone, and placebo, respectively. The primary end point was the proportion of subjects achieved target sUA level of ≤ 360 µmol/l at week 5.

Results: About 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in 5 mg, 10 mg of SHR4640 and benzbromarone groups, respectively, significantly higher than placebo group (0%; p< 0.05 for 5 mg and 10 mg of SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg of SHR4640 and benzbromarone, respectively, vs placebo (5.9%; p< 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported.

Conclusions: The present study indicated a superior sUA-lowering effect, and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as comparing with placebo in Chinese subjects with hyperuricemia.

Trial Registration: ClinicalTrials.gov number, NCT03185793.
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http://dx.doi.org/10.1093/rheumatology/keab198DOI Listing
March 2021

Do air pollutants as well as meteorological factors impact Corona Virus Disease 2019 (COVID-19)? Evidence from China based on the geographical perspective.

Environ Sci Pollut Res Int 2021 Mar 5. Epub 2021 Mar 5.

School of Public Health, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

The COVID-19 is still a huge challenge that seriously threatens public health globally. Previous studies focused on the influence of air pollutants and probable meteorological parameters on confirmed COVID-19 infections via epidemiological methods, whereas the findings of relations between possible variables and COVID-19 incidences using geographical perspective were scarce. In the present study, data concerning confirmed COVID-19 cases and possible affecting factors were collected for 325 cities across China up to May 27, 2020. The geographically weighted regression (GWR) model was introduced to explore the impact of probable determinants on confirmed COVID-19 incidences. Some results were obtained. AQI, PM, and PM demonstrated significantly positive impacts on COVID-19 during the most study period with the majority lag group (P< 0.05). Nevertheless, the relation of temperature with COVID-19 was significantly negative (P< 0.05). Especially, CO exhibited a negative effect on COVID-19 in most study period with the majority lag group. The impacts of each possible determinant on COVID-19 represented significantly spatial heterogeneity. The obvious influence of the majority of possible factors on COVID-19 was mainly detected during the after lockdown period with the lag 21 group. Although the COVID-19 spreading has been effectively controlled by tough measures taken by the Chinese government, the study findings remind us to address the air pollution issues persistently for protecting human health.
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http://dx.doi.org/10.1007/s11356-021-12934-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935479PMC
March 2021

Rapid, Ultrasensitive, and Highly Specific Diagnosis of COVID-19 by CRISPR-Based Detection.

ACS Sens 2021 03 1;6(3):881-888. Epub 2021 Mar 1.

Experimental Research Center, Capital Institute of Pediatrics, Beijing100020, P. R. China.

Coronavirus Disease 2019 (COVID-19), which is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has rapidly spread leading to a global pandemic. Here, we combined ultiple cross displacement amplification (MCDA) with RISPR-as12a-based etection to develop a novel diagnostic test (MCCD) and applied for the diagnosis of COVID-19, called COVID-19 MCCD. The MCCD protocol conducts reverse transcription MCDA (RT-MCDA) reaction for RNA templates followed by CRISPR-Cas12a/CrRNA complex detection of predefined target sequences after which degradation of a single-strand DNA (ssDNA) molecule confirms detection of the target sequence. Two MCDA primer sets and two CrRNAs were designed targeting the opening reading frame 1a/b (ORF1ab) and nucleoprotein (N) of SARS-CoV-2. The optimal conditions include two RT-MCDA reactions at 63 °C for 35 min and a CRISPR-Cas12a/CrRNA detection reaction at 37 °C for 5 min. The COVID-19 MCCD assay can be visualized on a lateral flow biosensor (LFB) and completed within 1 h including RNA extraction (15 min), RT-MCDA reaction (35 min), CRISPR-Cas12a/CrRNA detection reaction (5 min), and reporting of result (within 2 min). The COVID-19 MCCD assay is very sensitive and detects the target gene with as low as seven copies per test and does not cross-react with non-SARS-CoV-2 templates. SARS-CoV-2 was detected in 37 of 37 COVID-19 patient samples, and nonpositive results were detected from 77 non-COVID-19 patients. Therefore, the COVID-19 MCCD assay is a useful tool for the reliable and quick diagnosis of SARS-CoV-2 infection.
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http://dx.doi.org/10.1021/acssensors.0c01984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945583PMC
March 2021

Core Role of Hydrophobic Core of Polymeric Nanomicelle in Endosomal Escape of siRNA.

Nano Lett 2021 Apr 17;21(8):3680-3689. Epub 2021 Feb 17.

School of Life Science, Advanced Research Institute of Multidisciplinary Science, Institute of Engineering Medicine, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing 100081, China.

Efficient endosomal escape is the most essential but challenging issue for siRNA drug development. Herein, a series of quaternary ammonium-based amphiphilic triblock polymers harnessing an elaborately tailored pH-sensitive hydrophobic core were synthesized and screened. Upon incubating in an endosomal pH environment (pH 6.5-6.8), mPEG-P(DPA--DMAEMA)-PT (PDDT, the optimized polymer) nanomicelles (PDDT-Ms) and PDDT-Ms/siRNA polyplexes rapidly disassembled, leading to promoted cytosolic release of internalized siRNA and enhanced silencing activity evident from comprehensive analysis of the colocalization and gene silencing using a lysosomotropic agent (chloroquine) and an endosomal trafficking inhibitor (bafilomycin A1). In addition, PDDT-Ms/siPLK1 dramatically repressed tumor growth in both HepG2-xenograft and highly malignant patient-derived xenograft models. PDDT-Ms-armed siPD-L1 efficiently blocked the interaction of PD-L1 and PD-1 and restored immunological surveillance in CT-26-xenograft murine model. PDDT-Ms/siRNA exhibited ideal safety profiles in these assays. This study provides guidelines for rational design and optimization of block polymers for efficient endosomal escape of internalized siRNA and cancer therapy.
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http://dx.doi.org/10.1021/acs.nanolett.0c04468DOI Listing
April 2021

Genome-wide CRISPR-Cas9 screen identified KLF11 as a druggable suppressor for sarcoma cancer stem cells.

Sci Adv 2021 Jan 27;7(5). Epub 2021 Jan 27.

Department of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China.

Cancer stem cells (CSCs) are involved in tumorigenesis, recurrence, and therapy resistance. To identify critical regulators of sarcoma CSCs, we performed a reporter-based genome-wide CRISPR-Cas9 screen and uncovered Kruppel-like factor 11 (KLF11) as top candidate. In vitro and in vivo functional annotation defined a negative role of KLF11 in CSCs. Mechanistically, KLF11 and YAP/TEAD bound to adjacent DNA sites along with direct interaction. KLF11 recruited SIN3A/HDAC to suppress the transcriptional output of YAP/TEAD, which, in turn, promoted KLF11 transcription, forming a negative feedback loop. However, in CSCs, this negative feedback was lost because of epigenetic silence of KLF11, causing sustained YAP activation. Low KLF11 was associated with poor prognosis and chemotherapy response in patients with sarcoma. Pharmacological activation of KLF11 by thiazolidinedione effectively restored chemotherapy response. Collectively, our study identifies KLF11 as a negative regulator in sarcoma CSCs and potential therapeutic target.
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http://dx.doi.org/10.1126/sciadv.abe3445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840125PMC
January 2021

Subjective and Objective Assessment of Monoenergetic and Polyenergetic Images Acquired by Dual-Energy CT in Breast Cancer.

Korean J Radiol 2021 04 19;22(4):502-512. Epub 2021 Jan 19.

Department of Radiology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China.

Objective: To objectively and subjectively assess and compare the characteristics of monoenergetic images [MEI (+)] and polyenergetic images (PEI) acquired by dual-energy CT (DECT) of patients with breast cancer.

Materials And Methods: This retrospective study evaluated the images and data of 42 patients with breast cancer who had undergone dual-phase contrast-enhanced DECT from June to September 2019. One standard PEI, five MEI (+) in 10-kiloelectron volt (keV) intervals (range, 40-80 keV), iodine density (ID) maps, iodine overlay images, and Z effective (Z) maps were reconstructed. The contrast-to-noise ratio (CNR) and the signal-to-noise ratio (SNR) were calculated. Multiple quantitative parameters of the malignant breast lesions were compared between the arterial and the venous phase images. Two readers independently assessed lesion conspicuity and performed a morphology analysis.

Results: Low keV MEI (+) at 40-50 keV showed increased CNR and SNR compared with PEI, especially in the venous phase ([CNR: 40 keV, 20.10; 50 keV, 14.45; vs. PEI, 7.27; < 0.001], [SNR: 40 keV, 21.01; 50 keV, 16.28; vs. PEI, 10.77; < 0.001]). Multiple quantitative DECT parameters of malignant breast lesions were higher in the venous phase images than in the arterial phase images ( < 0.001). MEI (+) at 40 keV, ID, and Z reconstructions yielded the highest Likert scores for lesion conspicuity. The conspicuity of the mass margin and the visual enhancement were significantly better in 40-keV MEI (+) than in the PEI ( = 0.022, = 0.033, respectively).

Conclusion: Compared with PEI, MEI (+) reconstructions at low keV in the venous phase acquired by DECT improved the objective and subjective assessment of lesion conspicuity in patients with malignant breast lesions. MEI (+) reconstruction acquired by DECT may be helpful for the preoperative evaluation of breast cancer.
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http://dx.doi.org/10.3348/kjr.2020.0310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005343PMC
April 2021

LncRNA MEG3 mediates nickel oxide nanoparticles-induced pulmonary fibrosis via suppressing TGF-β1 expression and epithelial-mesenchymal transition process.

Environ Toxicol 2021 Jun 6;36(6):1099-1110. Epub 2021 Feb 6.

Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China.

Nickel oxide nanoparticles (NiO NPs) causes pulmonary fibrosis via activating transforming growth factor-β1 (TGF-β1) in rats, but its upstream regulatory mechanisms are unknown. This study aimed to explore the role of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) in NiO NPs-induced collagen deposition. Male Wistar rats were intratracheally instilled with NiO NPs (0.015, 0.06, and 0.24 mg/kg b.w.) twice a week for 9 weeks. Human lung adenocarcinoma epithelial cells (A549 cells) were cultured with NiO NPs (25, 50, and 100 μg/ml) to establish collagen deposition model. We discovered that NiO NPs-induced rat pulmonary fibrosis was accompanied by the epithelial-mesenchymal transition (EMT) occurrence and MEG3 down-regulation in rat lung tissues. In cell collagen deposition model, NiO NPs also evoked EMT and decreased MEG3 expression in a dose-dependent manner in A549 cells. By overexpressing MEG3 in A549 cells, we found that MEG3 inhibited the level of TGF-β1, EMT process and collagen formation. Moreover, our data showed that SB431542 (TGF-β1 inhibitor) had an inhibitory effect on NiO NPs-induced EMT and collagen formation. Our results indicated that MEG3 inhibited NiO NPs-induced collagen deposition by regulating TGF-β1-mediated EMT process, which may provide some clues for insighting into the mechanisms of NiO NPs-induced pulmonary fibrosis.
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http://dx.doi.org/10.1002/tox.23109DOI Listing
June 2021

Metabolic Choice Tunes Foxp3+ Regulatory T Cell Function.

Adv Exp Med Biol 2021 ;1278:81-94

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Metabolic programs and dynamic nutrient signaling can direct cell biological function. Cellular metabolism and biological function are coordinated to cell activity. Regulatory T cells (Foxp3+ Tregs) expressing the key transcription factor FOXP3 play critical roles in the maintenance of immune tolerance and in the control of immune homeostasis. A bundle of data demonstrated that Foxp3+ Tregs were influenced and regulated by Toll-cell receptor (TCR) and costimulatory signals, cytokine conditions and metabolic changes, including metabolites, etc. In this context, Foxp3+ Tregs are impacted by different environmental conditions and metabolic differences associated with diverse transcriptional patterns, which, in turn, display a high degree of plasticity and tissue specificity. During the past decades, significant progresses have been made in understanding the correlation between metabolic changes and manipulation of Foxp3+ Treg function. Taken together, this chapter aims to summarize the important advances in the fields, decipher what metabolic ways are involved in Foxp3+ Tregs, and how metabolism modulates Foxp3 expression, stability, and suppressive functions, which may provide a potential pace on lightening up Foxp3+ Treg-mediated immune functions.
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http://dx.doi.org/10.1007/978-981-15-6407-9_5DOI Listing
February 2021

Identification and screening of host proteins interacting with ORFV-ORF047 protein.

Virol J 2021 01 26;18(1):27. Epub 2021 Jan 26.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Public Health of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.

Background: Orf virus (ORFV) is a member of the genus Parapoxvirus and family Poxviridae. The virus has a worldwide distribution and infects sheep, goats, humans, and wild animals. However, due to the complex structure of the poxvirus, the underlying mechanism of the entry and infection by ORFV remains largely unknown. ORFV ORF047 encodes a protein named L1R. Poxviral L1R serves as the receptor-binding protein and blocks virus binding and entry independently of glycosaminoglycans (GAGs). The study aimed to identify the host interaction partners of ORFV ORF047.

Methods: Yeast two-hybrid cDNA library of sheep testicular cells was applied to screen the host targets with ORF047 as the bait. ORF047 was cloned into a pBT3-N vector and expressed in the NMY51 yeast strain. Then, the expression of bait proteins was validated by Western blot analysis.

Results: Sheep SERP1and PABPC4 were identified as host target proteins of ORFV ORF047, and a Co-IP assay further verified their interaction.

Conclusions: New host cell proteins SERP1and PABPC4 were found to interact with ORFV ORF047 and might involve viral mRNA translation and replication.
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http://dx.doi.org/10.1186/s12985-021-01499-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836158PMC
January 2021

Achieving simultaneous nitritation, anammox and denitrification (SNAD) in an integrated fixed-biofilm activated sludge (IFAS) reactor: Quickly culturing self-generated anammox bacteria.

Sci Total Environ 2021 May 6;768:144446. Epub 2021 Jan 6.

School of Environmental Science and Engineering, Qingdao University, Qingdao 266071, PR China. Electronic address:

In this study, by inoculating nitritation suspended sludge, simultaneous nitritation, anammox and denitrification (SNAD) was established quickly in an integrated fixed-biofilm activated sludge (IFAS) reactor to treat high-ammonia municipal wastewater. Results showed that, deep-level total nitrogen and chemical oxygen demand removal efficiencies (92.8% and 78.8%, respectively) were achieved, and their effluent concentrations were 13.2 and 39.3 mg/L, respectively. Excess generation of nitrate was once occurred under continuous aerobic condition, but it could be solved by suppressing nitrite oxidizing bacteria activity stably via switching to intermittent aeration mode (alternate 7 min of aerobic and 21 min of anoxic) and rising influent ammonium concentration temporarily (lasted 31 days). High-throughput sequencing analysis revealed that, Candidatus_Brocadia, as dominant anammox bacteria, was self-generated in flocs (2.93%) but mainly biofilm (7.67%), whereas uncultured_f_Nitrosomonadaceae as ammonia oxidizing bacteria was mainly found in flocs (2.4%). This work not only demonstrated that anammox bacteria could be self-generated and retained in the SNAD-IFAS system, but also suggested a promising application of the SNAD-IFAS in wastewater treatment plants.
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http://dx.doi.org/10.1016/j.scitotenv.2020.144446DOI Listing
May 2021

FoxM1 promotes Wnt/β-catenin pathway activation and renal fibrosis via transcriptionally regulating multi-Wnts expressions.

J Cell Mol Med 2021 Feb 12;25(4):1958-1971. Epub 2021 Jan 12.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.

The activation of Wnt/β-catenin pathway plays a pivotal role in promoting renal fibrosis. The activation of Wnt/β-catenin pathway relies on the binding of Wnts to Frizzled receptors on cell membrane. However, the factor regulating Wnts production remains unclear. Here, we demonstrated that transcriptional factor FoxM1 was significantly increased in obstructed kidneys and patients' kidneys with fibrosis. The up-regulation of FoxM1 mainly distributed in tubular epithelial cells. Pharmacological inhibition of FoxM1 down-regulated multi-Wnts elevation in UUO mice and attenuated renal fibrosis. In cultured renal tubular epithelial cells, overexpression of FoxM1 promoted 8 Wnts expression, while knock-down on FoxM1-suppressed multi-Wnts including Wnt1, Wnt2b and Wnt3 expression induced by Ang II. Chromatin immunoprecipitation PCR confirmed that FoxM1 bound to Wnt1, Wnt2b, Wnt3 promoters and luciferase assay further identified that the transcriptions of Wnt1, Wnt2b and Wnt3 were regulated by FoxM1. Thus, our findings show that multi-Wnt family members were regulated by transcriptional factor FoxM1. FoxM1 might be a key switch for activating β-catenin pathway and renal fibrosis. Therefore, FoxM1 might be a potential therapeutic target in manipulating renal fibrosis.
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http://dx.doi.org/10.1111/jcmm.15948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882937PMC
February 2021

Dual-energy CT quantitative parameters for evaluating Immunohistochemical biomarkers of invasive breast cancer.

Cancer Imaging 2021 Jan 7;21(1). Epub 2021 Jan 7.

Department of Radiology, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, 400030, People's Republic of China.

Background: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67 are the most useful immunohistochemical biomarkers of invasive breast cancer. The purpose of this study is to investigate the possibility of quantitative parameters derived from dual-energy CT (DECT) to discriminate immunohistochemical biomarkers of invasive breast cancer.

Methods: This prospective study enrolled 120 patients with invasive breast cancer who underwent preoperative contrast-enhanced DECT for staging purposes from June 2019 to January 2020. DECT quantitative parameters, including normalized iodine concentration (NIC), the slope of the spectral Hounsfield unit curve (λ), and the normalized effective atomic number (nZ), were obtained from reconstructed images. DECT quantitative parameters were compared with the expression status, and the correlations with the value of immunohistochemical biomarkers were evaluated. Inter-observer reproducibility analysis was performed to assess the measurement reproducibility of quantitative parameters. The diagnostic performance of the quantitative parameters was analyzed by receiver operating characteristic curve.

Results: The ER-negative group tended to display higher venous phase NIC and nZ compared with the ER-positive group (individually, p = 0.003, 0.011; area under the curve [AUC] of 0.65, 0.60). The PR-negative group demonstrated higher arterial and venous phase NIC compared with the PR-positive group (individually, p = 0.022, 0.005; AUC of 0.63, 0.65). NIC was correlated negatively with the value of ER and PR expression (r = - 0.175 ~ - 0.265, p = 0.002 ~ 0.042). The HER2-positive group tended to display higher venous phase nZ than the HER2-negative group (p = 0.022; AUC of 0.59). The Ki67 high-proliferation group demonstrated higher arterial phase, venous phase NIC and nZ than the Ki67 low-proliferation group (p < 0.001 ~ 0.005; AUC of 0.67 ~ 0.75). Both the NIC and nZ were correlated positively with the value of Ki67 (r = 0.240 ~ 0.490, p < 0.001 ~ 0.014).

Conclusions: NIC and nZ derived from DECT could be used to discriminate expression status and may associate with the value of immunohistochemical biomarkers of invasive breast cancer.
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http://dx.doi.org/10.1186/s40644-020-00370-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791709PMC
January 2021

Setosphlides A-D, New Isocoumarin Derivatives from the Entomogenous Fungus Setosphaeria rostrate LGWB-10.

Nat Prod Bioprospect 2021 Feb 7;11(1):137-142. Epub 2021 Jan 7.

College of Life Science, Institute of Life Science and Green Development, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding, 071002, China.

Investigation of the entomogenous fungus Setosphaeria rostrate LGWB-10 from Harmonia axyridis led to the isolation of four new isocoumarin derivatives, setosphlides A-D (1-4), and four known analogues (5-8). Their planar structures and the relative configurations were elucidated by comprehensive spectroscopic methods. The absolute configurations of isocoumarin nucleus for 1-4 were elucidated by their ECD spectra. The C-10 relative configurations for the pair of C-10 epimers (1 and 2) were established by comparing the magnitude of the computed C NMR chemical shifts (Δδ) with the experimental C NMR values (Δδ) for the epimers. All of the isolated compounds (1-8) were evaluated for their cytotoxicities against four human tumor cell lines MCF-7, MGC-803, HeLa, and Huh-7.
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http://dx.doi.org/10.1007/s13659-020-00292-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933304PMC
February 2021

Harnessing pH-Sensitive Polycation Vehicles for the Efficient siRNA Delivery.

ACS Appl Mater Interfaces 2021 Jan 6;13(2):2218-2229. Epub 2021 Jan 6.

College of Pharmacy, Xinxiang Medical University, 453003 Xinxiang, P.R. China.

pH-sensitive hydrophobic segments have been certificated to facilitate siRNA delivery efficiency of amphiphilic polycation vehicles. However, optimal design concepts for these vehicles remain unclear. Herein, by studying the library of amphiphilic polycations mPEG-PAMA-P(DEA--D5A) (EAE5), we concluded a multifactor matching concept (p values, "proton buffering capacities" (BCs), and critical micelle concentrations (CMCs)) for polycation vehicles to improve siRNA delivery efficiency and . We identified that the stronger BCs in a pH 5.5-7.4 subset induced by EAE5 (p = 6.79) and EAE5 (p = 6.20) are effective for siRNA delivery . Further, the stronger BCs occurred in a narrow subset of pH 5.5-6.5 and the lower CMC attributed to higher siRNA delivery capacity of EAE5 than EAE5 after intravenous administration and subcutaneous injection. More importantly, 87.2% gene knockdown efficacy was achieved by EAE5 subcutaneous injection, which might be useful for an mRNA vaccine adjuvant. Furthermore, EAE5 also successfully delivered siRRM2 to tumor intravenous administration and received highly efficient antitumor activity. Taken together, the suitable p values, strong BCs occurred in pH 5.5-6.5, and low CMCs were probably the potential solution for designing efficient polycationic vehicles for siRNA delivery.
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http://dx.doi.org/10.1021/acsami.0c17866DOI Listing
January 2021

miR-30b-5p modulate renal epithelial-mesenchymal transition in diabetic nephropathy by directly targeting SNAI1.

Biochem Biophys Res Commun 2021 01 29;535:12-18. Epub 2020 Dec 29.

Department of Nephrology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Object: Renal tubulointerstitial fibrosis plays a significant role in the development of diabetic nephropathy (DN). SNAI1 is a main activator of epithelial-to-mesenchymal transition (EMT) in the process of fibrosis. This study aimed to investigate the effect of miR-30b-5p targeting SNAI1 on the EMT in DN.

Methods: Bioinformatics and miRNAs microarray analyses were used to predict the candidate miRNA targeting SNAI1, that is miR-30b-5p. The db/db mice was as DN animal model and renal tissues of mice were stained with PAS. The miR-30b-5p expression in mouse and human renal tissue were examined by quantitative RT-PCR (qRT-PCR) and fluorescence in situ hybridization (FISH), while SNAI1 expression was determined by qRT-PCR and immunohistochemistry. Luciferase reporter gene assay was used to confirm miR-30b-5p directly target 3'-UTR of the SNAI1 mRNA. In vitro, HK-2 cells were treated with high glucose to establish hyperglycemia cell model and transfected with miR-30b-5p mimics to overexpress miR-30b-5p. Expression of miR-30b-5p, SNAI1 and EMT related indicators (E-cadherin, a-SMA and Vimentin) in HK-2 cells under different treatments were determined by qRT-PCR and/or western-blot. In addition, immunofluorescence was performed to evaluate a-SMA expression in HK-2 cells under different treatments.

Results: Bioinformatics analyses revealed miR-30b-5p had complementary sequences with SNAI1 mRNA and the seed region of miR-30b-5p was conserved in human and a variety of animals, including mice. Microarray analysis showed miR-30b expression decreased in DN mice, which was further verified in db/db mice by qRT-PCR and in human DN by FISH. Contrary to miR-30b-5p, SNAI1 expression level was upregulated in db/db mice. Correlation analysis suggested SNAI1 mRNA level was negatively with miR-30b-5p level in renal tissue of db/db mice. Luciferase reporter gene assay confirmed miR-30b-5p directly targeted SNAI1 mRNA. In high glucose induced HK-2 cells, expression levels of miR-30b-5p and E-cadherin were decreased, while SNAI1, a-SMA and Vimentin were increased. Overexpression miR-30b-5p in high glucose induced HK-2 cells could reverse that phenomenon to some extent.

Conclusion: These findings suggest that miR-30b-5p play a protective role by targeting SNAI1 in renal EMT in DN.
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http://dx.doi.org/10.1016/j.bbrc.2020.10.096DOI Listing
January 2021

Strain-activated light-induced halide segregation in mixed-halide perovskite solids.

Nat Commun 2020 Dec 10;11(1):6328. Epub 2020 Dec 10.

Institute of Materials for Electronics and Energy Technology (i-MEET), Department of Materials Science and Engineering, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Martensstraße 7, 91058, Erlangen, Germany.

Light-induced halide segregation limits the bandgap tunability of mixed-halide perovskites for tandem photovoltaics. Here we report that light-induced halide segregation is strain-activated in MAPb(IBr) with Br concentration below approximately 50%, while it is intrinsic for Br concentration over approximately 50%. Free-standing single crystals of CHNHPb(IBr) (35%Br) do not show halide segregation until uniaxial pressure is applied. Besides, 35%Br single crystals grown on lattice-mismatched substrates (e.g. single-crystal CaF) show inhomogeneous segregation due to heterogenous strain distribution. Through scanning probe microscopy, the above findings are successfully translated to polycrystalline thin films. For 35%Br thin films, halide segregation selectively occurs at grain boundaries due to localized strain at the boundaries; yet for 65%Br films, halide segregation occurs in the whole layer. We close by demonstrating that only the strain-activated halide segregation (35%Br/45%Br thin films) could be suppressed if the strain is properly released via additives (e.g. KI) or ideal substrates (e.g. SiO).
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http://dx.doi.org/10.1038/s41467-020-20066-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730187PMC
December 2020

Overexpression of protein regulator of cytokinesis 1 facilitates tumor growth and indicates unfavorable prognosis of patients with colon cancer.

Cancer Cell Int 2020 Oct 31;20(1):528. Epub 2020 Oct 31.

Department of General Surgery, Jinling Hospital, Southern Medical University , Nanjing, 210002, Jiangsu, China.

Background: Protein regulator of cytokinesis 1 (PRC1) has been reported to play important role in the pathogenesis of various cancers. However, its role in colon cancer has not been studied. Here, we aimed to investigate the biological functions and potential mechanism of PRC1 in colon cancer.

Methods: The expression level of PRC1 in colon cancer tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemical (IHC) staining of a tissue microarray (TMA). Furthermore, colon cancer cell lines HCT116 and SW480 were treated with short hairpin RNAs against PRC1. The biological function of PRC1 was determined by MTT proliferation, colony formation assay, cell cycle, and apoptosis assays. Then, an in vivo tumor formation assay was conducted to explore the effects of PRC1 on tumor growth.

Results: The mRNA and protein expression levels of PRC1 were highly expressed in colon cancer tissues and cell lines. PRC1 expression was associated with clinicopathological characteristics and overall survival of patients with colon cancer. Knockdown of PRC1 could decrease proliferation and colony forming ability of colon cancer cells, as well as arrested more cells at G2/M phase and promoted cell apoptosis. In cancer cells, the expression pattern of protein regulators included in cell cycle and apoptosis progress were reverted by PRC1 down-regulation. Additionally, PRC1 down-regulation could suppress colon tumor growth and differentiation.

Conclusions: We confirmed that PRC1 was overexpressed in colon cancer and was associated with poor prognosis of colon cancer patients. PRC1 down-regulation could arrest cell cycle at G2/M stage, inhibit proliferation, and elicit apoptosis. These findings showed the potential of PRC1 to be used for therapeutic approaches in colon cancer.
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http://dx.doi.org/10.1186/s12935-020-01618-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603724PMC
October 2020

Feasibility of MRI-based radiomics features for predicting lymph node metastases and VEGF expression in cervical cancer.

Eur J Radiol 2021 Jan 21;134:109429. Epub 2020 Nov 21.

Department of Radiology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, People's Republic of China; Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400044, People's Republic of China. Electronic address:

Purpose: To investigate the predictive value of MRI-based radiomics features for lymph node metastasis (LNM) and vascular endothelial growth factor (VEGF) expression in patients with cervical cancer.

Method: A total of 163 patients with cervical cancer were enrolled in this study. A total of 134 patients were included for LNM differentiation, and 118 were included for VEGF expression discrimination. The patients were randomly assigned to the training group or test group at a ratio of 2:1. Radiomics features were extracted from T1WI enhanced and T2WI MRI scans of each patient, and tumor stage was also documented according to the International Federation of Gynecology and Obstetrics (FIGO) guidelines. The least absolute shrinkage and selection operator algorithm was used for feature selection. The results of 5-fold cross validation were applied to select the best classification models. The performances of the constructed models were further evaluated with the test group.

Results: Sixteen radiomics features and the FIGO stage were selected to construct the LNM discrimination model. The LNM prediction model achieved the best diagnostic performance, with areas under the receiver operating curve (AUCs) of 0.95 and 0.88 in the training group and test group, respectively. Nine radiomics characteristics were screened to build the VEGF prediction model, with AUCs of 0.82 and 0.70 in the training group and test group, respectively. Decision curve analysis confirmed their clinical usefulness.

Conclusions: The presented radiomics prediction models demonstrated potential to noninvasively differentiate LNM and VEGF expression in cervical cancer.
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http://dx.doi.org/10.1016/j.ejrad.2020.109429DOI Listing
January 2021