Publications by authors named "Dan Xie"

628 Publications

Single-cell exome sequencing reveals multiple subclones in metastatic colorectal carcinoma.

Genome Med 2021 Sep 10;13(1):148. Epub 2021 Sep 10.

National Frontier Center of Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17, Section 3, Renmin South Road, Chengdu, 610041, Sichuan, China.

Background: Colorectal cancer (CRC) is a major cancer type whose mechanism of metastasis remains elusive.

Methods: In this study, we characterised the evolutionary pattern of metastatic CRC (mCRC) by analysing bulk and single-cell exome sequencing data of primary and metastatic tumours from 7 CRC patients with liver metastases. Here, 7 CRC patients were analysed by bulk whole-exome sequencing (WES); 4 of these were also analysed using single-cell sequencing.

Results: Despite low genomic divergence between paired primary and metastatic cancers in the bulk data, single-cell WES (scWES) data revealed rare mutations and defined two separate cell populations, indicative of the diverse evolutionary trajectories between primary and metastatic tumour cells. We further identified 24 metastatic cell-specific-mutated genes and validated their functions in cell migration capacity.

Conclusions: In summary, scWES revealed rare mutations that failed to be detected by bulk WES. These rare mutations better define the distinct genomic profiles of primary and metastatic tumour cell clones.
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http://dx.doi.org/10.1186/s13073-021-00962-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434739PMC
September 2021

Multiplatform discovery and regulatory function analysis of structural variations in non-small cell lung carcinoma.

Cell Rep 2021 Sep;36(10):109660

Frontier Science Center for Disease Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 17 People's South Road, Chengdu, Sichuan 610041, China; Precision Medicine Research Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China; Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China; The Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, No. 37 Guoxue Alley, Chengdu, Sichuan 610041, China. Electronic address:

Non-small cell lung carcinoma (NSCLC), the most common form of lung cancer, is the leading cause of cancer-related death worldwide. We perform whole-genome sequencing (WGS) on samples from 43 primary patients with NSCLC and matched normal samples and analyze their matched open chromatin data and transcriptome data. Our results indicate that next-generation sequencing (NGS) and the Bionano Genomics (BNG) platform should be viewed as complementary technologies in terms of structural variations detection. By creating a framework integrating these two platforms, we detect high-technical-confidence somatic structural variations (SVs) in NSCLC cases, which could aid in the efficient investigation of new candidate oncogenes, such as TRIO and SESTD1. Our findings highlight the impact of somatic SVs on NSCLC oncogenesis and lay a foundation for exploring associations among somatic SVs, gene expression, and regulatory networks in patients with NSCLC.
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http://dx.doi.org/10.1016/j.celrep.2021.109660DOI Listing
September 2021

Long non‑coding RNA HAND2‑AS1/miR‑106a/PTEN axis re‑sensitizes cisplatin‑resistant ovarian cells to cisplatin treatment.

Mol Med Rep 2021 Nov 3;24(5). Epub 2021 Sep 3.

Obstetrics and Gynecology Department, The Fourth Hospital of Changsha, Changsha Hospital of Hunan Normal University, Changsha, Hunan 410006, P.R. China.

Cisplatin (DDP) resistance in patients suffering from ovarian cancer is a considerable hurdle to successful treatment. The present study aimed to identify a possible long non‑coding RNA (lncRNA)‑microRNA (miRNA)‑mRNA axis participating in ovarian cancer DDP‑resistance based on the critical roles of non‑coding RNAs, including lncRNAs and miRNAs, in carcinogenesis. According to online data and experimental results, lncRNA HAND2‑AS1 expression was significantly downregulated within ovarian carcinoma, especially within recurrent and DDP‑resistant ovarian carcinoma. The expression of HAND2‑AS1 was also shown to be markedly inhibited in SKOV3/DDP (DDP) cells with resistance to DDP. In SKOV3/DDP cells, HAND2‑AS1 overexpression inhibited cell viability and promoted cell apoptosis upon DDP treatment through the Bcl‑2/caspase‑3 apoptotic signaling. It was hypothesized that PTEN mRNA expression was also markedly inhibited in SKOV3/DDP ovarian cancer cells, while HAND2‑AS1 overexpression rescued PTEN proteins and blocked PI3K/AKT signaling activation. Moreover, miR‑106a was found to bind directly to PTEN 3' UTR and HAND2‑AS1. Upon DDP treatment, miR‑106a overexpression in SKOV3/DDP cells promoted cell viability. It inhibited cell apoptosis through the Bcl‑2/caspase‑3 apoptotic signaling pathway and downregulated the protein levels of PTEN and upregulated PI3K/AKT signaling activity. Furthermore, miR‑106a overexpression partially reversed the effect of HAND2‑AS1 overexpression upon PTEN proteins and SKOV3/DDP cell proliferation upon DDP treatment. In conclusion, a lncRNA HAND2‑AS1/miR‑106a/PTEN axis that re‑sensitizes DDP‑resistant SKOV3/DDP cells to DDP treatment has been established.
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http://dx.doi.org/10.3892/mmr.2021.12402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436234PMC
November 2021

Emerging Role of E2F Family in Cancer Stem Cells.

Front Oncol 2021 12;11:723137. Epub 2021 Aug 12.

Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China.

The E2F family of transcription factors (E2Fs) consist of eight genes in mammals. These genes encode ten proteins that are usually classified as transcriptional activators or transcriptional repressors. E2Fs are important for many cellular processes, from their canonical role in cell cycle regulation to other roles in angiogenesis, the DNA damage response and apoptosis. A growing body of evidence demonstrates that cancer stem cells (CSCs) are key players in tumor development, metastasis, drug resistance and recurrence. This review focuses on the role of E2Fs in CSCs and notes that many signals can regulate the activities of E2Fs, which in turn can transcriptionally regulate many different targets to contribute to various biological characteristics of CSCs, such as proliferation, self-renewal, metastasis, and drug resistance. Therefore, E2Fs may be promising biomarkers and therapeutic targets associated with CSCs pathologies. Finally, exploring therapeutic strategies for E2Fs may result in disruption of CSCs, which may prevent tumor growth, metastasis, and drug resistance.
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http://dx.doi.org/10.3389/fonc.2021.723137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406691PMC
August 2021

Correction to: Flavagline analog FL3 induces cell cycle arrest in urothelial carcinoma cell of the bladder by inhibiting the Akt/PHB interaction to activate the GADD45α pathway.

J Exp Clin Cancer Res 2021 Mar 30;40(1):115. Epub 2021 Mar 30.

State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

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http://dx.doi.org/10.1186/s13046-021-01923-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377815PMC
March 2021

ITLN1 inhibits tumor neovascularization and myeloid derived suppressor cells accumulation in colorectal carcinoma.

Oncogene 2021 Aug 6. Epub 2021 Aug 6.

State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Low levels of ITLN1 have been correlated with obesity-related colorectal carcinogenesis, however, the specific functions and underlying mechanisms remain unclear. Thus, we sought to explore the inhibitory role of ITLN1 in the tumor-permissive microenvironment that exists during the first occurrence and subsequent development of colorectal carcinoma (CRC). Results indicated that ITLN1 was frequently lost in CRC tissues and ITLN1 to be an independent prognostic predictor of CRC. Orthotopic and subcutaneous tumor xenograft approaches were then used to further confirm the protective role of ITLN1 during tumor progression. Increased ITLN1 expression in CRC cells significantly inhibited local pre-existing vessels sprouting, EPC recruitment and the infiltration of immunosuppressive myeloid-derived suppressor cells (MDSCs) into tumor tissues without affecting the behavior of CRC cells in vitro. Comparatively, ITLN1-derived MDSCs had a lower suppressive effect on T cell proliferation, NOS2 expression, and ROS production. In addition, ITLN1 overexpression markedly suppressed bone marrow (BM)-derived hematopoietic progenitor cells (HPC) differentiation into MDSCs as well as NOS2 activity on MDSCs. Using H-2b+YFP + chimerism through bone marrow transplantation, increased ITLN1 in HCT116 significantly reduced the BM-derived EPCs and MDSCs in vivo mobilization. Mechanistically, results indicated ITLN1 inhibited tumor-derived IL-17D and CXCL2 (MIP2) through the KEAP1/Nrf2/ROS/IL-17D and p65 NF-ĸB/CXCL2 signaling cascades dependent on PI3K/AKT/GSK3ß. This effect was reversed by the PI3K selective inhibitor LY294002. Collectively, ITLN1 synergistically suppressed IL-17D and CXCL2-mediated tumor vascularization, bone marrow derived EPC recruitment, as well as MDSCs generation and trafficking. Thus, ITLN1 potentially serves as a critical prognostic and therapeutic target for CRC.
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http://dx.doi.org/10.1038/s41388-021-01965-5DOI Listing
August 2021

Corrigendum to "The telomere/telomerase binding factor PinX1 regulates paclitaxel sensitivity depending on spindle assembly checkpoint in human cervical squamous cell carcinomas" [Canc. Lett. 353 (2014) 104-114].

Cancer Lett 2021 Oct 3;519:345. Epub 2021 Aug 3.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China. Electronic address:

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http://dx.doi.org/10.1016/j.canlet.2021.07.043DOI Listing
October 2021

Erratum to "α4 contributes to bladder urothelial carcinoma cell invasion and/or metastasis via regulation of E-cadherin and is a predictor of outcome in bladder urothelial carcinoma patients" [Eur J Canc 50 (2014) 840-851].

Eur J Cancer 2021 Sep 21;155:317. Epub 2021 Jul 21.

State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangdong, Guangzhou 510060, China; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangdong, Guangzhou 510060, China. Electronic address:

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http://dx.doi.org/10.1016/j.ejca.2021.06.030DOI Listing
September 2021

Inhibition of Perforin-Mediated Neurotoxicity Attenuates Neurological Deficits After Ischemic Stroke.

Front Cell Neurosci 2021 28;15:664312. Epub 2021 Jun 28.

Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Perforin-mediated cytotoxicity plays a crucial role in microbial defense, tumor surveillance, and primary autoimmune disorders. However, the contribution of the cytolytic protein perforin to ischemia-induced secondary tissue damage in the brain has not been fully investigated. Here, we examined the kinetics and subpopulations of perforin-positive cells and then evaluated the direct effects of perforin-mediated cytotoxicity on outcomes after ischemic stroke. Using flow cytometry, we showed that perforinCD45 immune cells could be detected at 12 h and that the percentage of these cells increased largely until on day 3 and then significantly declined on day 7. Surprisingly, the percentage of PerforinCD45 cells also unexpectedly increased from day 7 to day 14 after ischemic stroke in Perforin1-EGFP transgenic mice. Our results suggested that PerforinCD45 cells play vital roles in the ischemic brain at early and late stages and further suggested that PerforinCD45 cells are a heterogeneous population. Surprisingly, in addition to CD8 T cells, NK cells, and NKT cells, central nervous system (CNS)-resident immune microglia, which are first triggered and activated within minutes after ischemic stroke in mice, also secreted perforin during ischemic brain injury. In our study, the percentage of perforin microglia increased from 12 h after ischemic stroke, increased largely until on day 3 after ischemic stroke, and then moderately declined from days 3 to 7. Intriguingly, the percentage of perforin microglia also dramatically increased from days 7 to 14 after ischemic stroke. Furthermore, compared with wild-type littermates, Perforin 1 mice exhibited significant increases in the cerebral infarct volume, neurological deficits, and neurogenesis and inhibition of neurotoxic astrogliosis. Interestingly, the number of CD45CD3 T cells was significantly decreased in Perforin 1 mice compared with their wild-type littermates, especially the number of γδ T cells. In addition, Perforin 1 mice had lower levels of IL-17 than their wild-type littermates. Our results identified a critical function of perforin-mediated neurotoxicity in the ischemic brain, suggesting that targeting perforin-mediated neurotoxicity in brain-resident microglia and invading perforinCD45 immune cells may be a potential strategy for the treatment of ischemic stroke.
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http://dx.doi.org/10.3389/fncel.2021.664312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274971PMC
June 2021

Sevoflurane exerts improved protective effects than propofol on hypoxia-reoxygenation injury by regulating the microRNA-221-5p/ADAM8 axis in cardiomyocytes.

Exp Ther Med 2021 Aug 18;22(2):893. Epub 2021 Jun 18.

Department of Neurosurgery, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.

Myocardial ischemia-reperfusion (I/R) injury is a leading cause of heart disease and death. Decreasing the detrimental effect of I/R remains an urgent issue in clinical practice. The present study examined the interaction of the anesthetics (sevoflurane and propofol), ADAM8, and microRNA (miR)-221-5p in myocardial tissue protection in the hypoxia-reoxygenation (H/R) model. H9C2 cells were cultured and subjected to H/R stimulation for further verifications . Reverse transcription-quantitative PCR or western blotting was performed to evaluate mRNA or protein expression levels. Cell Counting Kit-8, BrdU, and caspase-3 activity assays were performed to investigate cell viability, proliferation and apoptosis. A dual-luciferase reporter assay was performed to verify the association between miR-221-5p and ADAM8. Sevoflurane had greater protective effects on the life of cardiomyocytes with H/R injury compared with propofol by promoting cell viability, proliferation and inhibiting apoptosis. Concurrently, compared with propofol-treated H/R injured cardiomyocytes, the expression level of ADAM8 in sevoflurane-treated H/R injured cardiomyocytes was higher. In addition, overexpression of ADAM8 promoted the cell viability and proliferation of sevoflurane-treated cardiomyocytes with H/R injury but inhibited cell apoptosis, while the downregulation of miR-221-5p showed an opposite trend to that of ADAM8 overexpression. The present data provide evidence that sevoflurane can mediate the miR-221-5p/ADAM8 axis, playing a better protective role compared with propofol in cardiomyocytes with H/R injury.
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http://dx.doi.org/10.3892/etm.2021.10325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243314PMC
August 2021

High-efficiency c-Myc-mediated induction of functional hepatoblasts from the human umbilical cord mesenchymal stem cells.

Stem Cell Res Ther 2021 07 2;12(1):375. Epub 2021 Jul 2.

State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

Background: Direct reprogramming of human fibroblasts to hepatocyte-like cells was proposed to generate large-scale functional hepatocytes demanded by liver tissue engineering. However, the difficulty in obtaining large quantities of human fibroblasts greatly restricted the extensive implementation of this approach. Meanwhile, human umbilical cord mesenchymal stem cells (HUMSCs) are the preferred cell source for HLCs with the advantages of limited ethical concerns, easy accessibility, and propagation in vitro. However, no direct reprogramming protocol for converting HUMSCs to hepatoblast-like cells (HLCs) has been reported.

Methods: HLCs were successfully generated from HUMSCs by forced expression of FOXA3, HNF1A, and HNF4A (collectively as 3TFs) and c-Myc. In vitro and in vivo functional experiments were conducted to demonstrate the hepatic phenotype, characterization, and function of HUMSC-derived HLCs (HUMSC-iHeps). ChIP-seq and RNA-seq were integrated to reveal the potential molecular mechanisms underlying c-Myc-mediated reprogramming.

Results: We showed that c-Myc greatly improved the trans-differentiation efficiency for HLCs from HUMSCs, which remained highly efficient in reprogramming fibroblasts into HLCs, suggesting c-Myc could promote direct reprogramming and its potentially widespread applicability for generating large amounts of HLCs in vitro. Mice transplantation experiments further confirmed the therapeutic potential of HUMSC-iHeps by liver function restoration and survival prolongation. Besides, in vivo safety assessment demonstrated the low risk of the tumorigenic potential of HUMSC-iHeps. We found that c-Myc functioned predominantly at an early phase of reprogramming, and we further unraveled the regulatory network altered by c-Myc.

Conclusions: c-Myc enhanced reprogramming efficiency of HLCs from HUMSCs. A large scale of functional HLCs generated more conveniently from HUMSCs could benefit biomedical studies and applications of liver diseases.
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http://dx.doi.org/10.1186/s13287-021-02419-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254319PMC
July 2021

[Corrigendum] Lentivirus‑mediated RNA interference of clusterin enhances the chemosensitivity of EJ bladder cancer cells to epirubicin .

Mol Med Rep 2021 Sep 2;24(3). Epub 2021 Jul 2.

State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510080, P.R. China.

Subsequently to the publication of the above paper, the authors have realized that Fig. 2A in this paper contained an error. The image selected to represent the experiment showing the invasion ability of EJ cells in the epirubicine/LV‑NC group of Fig. 2A was chosen mistakenly during the figure compilation process. A corrected version of Fig. 2 is shown on the next page. Note that this error did not affect either the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors are grateful to the Editor of for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in 6: 1133‑1139, 2012; DOI: 10.3892/mmr.2012.1017].
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http://dx.doi.org/10.3892/mmr.2021.12267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281266PMC
September 2021

New insight from an old concept for zeolites.

Authors:
Dan Xie

Science 2021 07;373(6550):28

Chevron Technical Center, Richmond, CA 94801, USA.

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http://dx.doi.org/10.1126/science.abj1834DOI Listing
July 2021

The subtype-specific molecular function of SPDEF in breast cancer and insights into prognostic significance.

J Cell Mol Med 2021 Aug 30;25(15):7307-7320. Epub 2021 Jun 30.

Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Sichuan, China.

Breast cancer (BC) is a molecular diverse disease which becomes the most common malignancy among women worldwide. There are four BC subtypes (Luminal A, Luminal B, HER2-enriched and Basal-like) robustly established following gene expression pattern-based characterization, behave significant differences in terms of their incidence, risk factors, prognosis and therapeutic sensitivity. Thus, there is an urgent need to provide mechanism research, treatment strategies and/or prognosis evaluation based on the patient stratification of BC subtypes. The prostate-derived ETS factor SPDEF was first identified as an activator of prostate specific antigen, and then, the involvements in many aspects of BC have been proposed. However, the subtype-specific molecular function of SPDEF in BC and insights into prognostic significance have not been clearly elucidated. This study demonstrated for the first time that SPDEF may play a diversity role in the expression levels, clinicopathologic importance, biological function and prognostic evaluation in BC via bioinformatics and experimental evidence, which mainly depends on different BC subtyping. In summary, our findings would help to better understand the possible mechanisms of various BC subtypes and to find possible candidate genes for prognostic and therapeutic usage.
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http://dx.doi.org/10.1111/jcmm.16760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335683PMC
August 2021

Highly efficient synthesis of 4,4-dimethylsterol oleates using acyl chloride method through esterification.

Food Chem 2021 Dec 18;364:130140. Epub 2021 May 18.

Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, National Engineering Research Center for Functional Food, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China. Electronic address:

In this study, the 4,4-dimethylsterol oleates were efficiently synthesized through esterification of 4,4-dimethylsterols and oleoyl chloride. The impact of reaction parameters on the 4,4-dimethylsterol conversion were investigated. The 4,4-dimethylsterol conversion increased with pyridine dosage, molar ratio of oleoyl chloride to 4,4-dimethylsterols, and temperature. The highest conversion of 99.27% was obtained with molar ratio of 1.1:1 at 313 K for 60 min. A second-order kinetic model describing acyl chloride esterification featuring high correlation coefficients was established. Arrhenius-Van't Hoff plot suggested activation energy and pre-exponential factor were 15.54 kJ mol and 1.78 × 10 L mol min, respectively. The molecular structure of 4,4-dimethylsterol oleates were finally identified by attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR), ultra-performance liquid chromatography system coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS), and nuclear magnetic resonance (NMR).
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http://dx.doi.org/10.1016/j.foodchem.2021.130140DOI Listing
December 2021

Cerebrospinal Fluid Biomarkers in Multiple System Atrophy Relative to Parkinson's Disease: A Meta-Analysis.

Behav Neurol 2021 31;2021:5559383. Epub 2021 May 31.

Department of Neurology, Sichuan University West China Hospital, Chengdu, 610041 Sichuan, China.

Objective: To investigate the differences of candidate cerebrospinal fluid (CSF) biomarkers associated with multiple system atrophy (MSA) and Parkinson's disease (PD).

Method: Here, a systematic review and meta-analysis were conducted on studies related to CSF biomarkers associated with MSA and PD obtained from PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled where appropriate and used to calculate standardized mean differences (SMDs) with 95% confidence intervals (CI). Heterogeneity was assessed using the statistic while Egger's test was used to test for existing publication bias.

Results: MSA patients had higher CSF t-tau (SMD = 0.41, 95% CI: 0.10 to 0.72) and YKL-40 (SMD = 0.63, 95% CI 0.12 to1.15) as well as DJ-1 (SMD = 1.05, 95% CI 0.67 to 1.42) levels than PD patients, while CSF p-tau (SMD = -0.17, 95% CI, -0.31 to -0.02) and A-42 (SMD = -0.33, 95% CI, -0.55 to -0.12) levels in MSA patients were lower than those in PD patients. There were no differences in CSF's GFAP and Flt3 ligand levels in both MSA and PD patients.

Conclusion: The study revealed the differences in CSF biomarker levels between MSA and PD cohorts that can be further explored to clinically distinguish MSA from PD.
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http://dx.doi.org/10.1155/2021/5559383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188602PMC
August 2021

Fatigue prevalence and associated factors in patients with multiple system atrophy.

Acta Neurol Scand 2021 Jun 16. Epub 2021 Jun 16.

Department of Neurology, West China Hospital, Sichuan University, Chengdu, China.

Objective: Fatigue was reported a determinant of poor quality of life in multiple system atrophy (MSA) patients. This study aimed to determine fatigue prevalence and associated demographic, motor, and non-motor symptoms in MSA patients.

Materials And Methods: A total of 174 MSA patients met "Probable" diagnostic criteria were included in this cross-sectional study. Fatigue Severity Scale (FSS) was used to measure fatigue prevalence. Unified MSA Rating Scale (UMSARS), Non-Motor Symptoms Scale (NMSS), Hamilton Depression Rating Scale-17 (HDRS-17), Hamilton Anxiety Scale (HAMA), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), and Mini-Mental State Exam (MMSE) were used for comprehensive clinical assessments. Nonparametric Mann-Whitney or Pearson's chi-square test was used to compare the patient score with or without fatigue (defined as a mean FSS score≥4). Binary logistic regression analysis was performed to determine features independently associated with the presence of fatigue.

Results: Fifty (28.7%) patients enrolled reported fatigue. Results of multivariate analysis revealed that anxiety (OR = 3.01, 95% CI = 1.43-6.31), excessive daytime sleepiness (OR = 2.70, 95% CI = 1.23-5.90), and use of sleep medicine (OR = 3.58, 95% CI = 1.39-9.24) were significantly associated with fatigue in MSA patients.

Conclusions: Fatigue is common in our MSA patients. Anxiety, excessive daytime sleepiness, and current sleep medicine use may be associated with an increased risk of fatigue. However, the severity of motor symptoms may not be associated with fatigue. Our findings highlight the need to identify, investigate, and treat fatigue in MSA.
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http://dx.doi.org/10.1111/ane.13488DOI Listing
June 2021

Out-of-plane and in-plane ferroelectricity of atom-thick two-dimensional InSe.

Nanotechnology 2021 Jun 29;32(38). Epub 2021 Jun 29.

State Key Lab of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, People's Republic of China.

Two-dimensional (2D) ferroelectric materials are promising substitutes of three-dimensional perovskite based ferroelectric ceramic materials. Yet most studies have been focused on the construction of non-centrosymmetric 2D van der Waals materials and only a few are constructed experimentally. Herein, we experimentally demonstrate the co-existence of voltage-tunable out-of-plane (OOP) and in-plane (IP) ferroelectricity in few-layer InSe prepared by a solution-processable method and fabricate ferroelectric semiconductor channel transistors. The reversible polarization can initiate instant switch of resistance with high ON/OFF ratios and a comparable subthreshold swing of 160 mV/dec under gate modulation. The origins of such unique OOP and IP ferroelectricity of the centrosymmetric structure are theoretically analyzed.
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http://dx.doi.org/10.1088/1361-6528/ac0ac5DOI Listing
June 2021

Prognostic Model for the Risk Stratification of Early and Late Recurrence in Hepatitis B Virus-Related Small Hepatocellular Carcinoma Patients with Global Histone Modifications.

J Hepatocell Carcinoma 2021 28;8:493-505. Epub 2021 May 28.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.

Background And Aim: To assess the profile of global histone modifications in small hepatocellular carcinoma (small HCC) and identify its prognostic value in predicting recurrence.

Methods: The expression profiles of global histone modifications, including H2AK5AC, H2BK20AC, H3K4me2, H3K9AC, H3K18AC, H4K12AC, and H4R3me2, were evaluated with immunohistochemistry in 335 HBV related small HCC patients. Two histone signature classifiers were then developed using least absolute shrinkage and selection operator Cox regression. A nomogram was built using the classifier and independent risk factors. The performances of the classifier and nomogram were assessed by receiver operating characteristic curves.

Results: Histone modifications were more pronounced in tumor tissues than in adjacent liver tissues. In tumor tissues, the risk score built based on the seven-histone signature exhibited satisfactory prediction efficiency, with an AUC = 0.71 (0.63-0.79) for 2-year survival in the training cohort. Patients with a high risk score had shorter recurrence-free survival than those with a low risk score (HR: 1.96, 95% CI: 1.24-3.08, = 0.004; HR: 1.95, 95% CI: 1.12-3.42, = 0.019; and HR: 1.97, 95% CI: 1.39-2.80, < 0.001 for the training, validation and total cohorts, respectively). Furthermore, the statistical nomogram built using the histone classifier for early recurrence had a C-index = 0.68. In non-neoplastic liver tissues, the hepatic signature based on H3K4me2 and H4R3me2 was related to late recurrence (HR: 2.00, 95% CI: 1.15-3.48, = 0.01).

Conclusion: Global histone modifications in tumor and adjacent liver tissues are novel predictors of early and late recurrence, respectively, in HBV-related small HCC patients.
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http://dx.doi.org/10.2147/JHC.S309451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170593PMC
May 2021

Corrigendum to ‟The telomere/telomerase binding factor PinX1 regulates paclitaxel sensitivity depending on spindle assembly checkpoint in human cervical squamous cell carcinomas" [Canc. Lett. 353 (2014) 104-114].

Cancer Lett 2021 Sep 3;516:61-63. Epub 2021 Jun 3.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China. Electronic address:

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http://dx.doi.org/10.1016/j.canlet.2021.05.023DOI Listing
September 2021

Probing low-copy-number proteins in single living cells using single-cell plasmonic immunosandwich assays.

Nat Protoc 2021 07 4;16(7):3522-3546. Epub 2021 Jun 4.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.

Cellular heterogeneity is pervasive and of paramount importance in biology. Single-cell analysis techniques are indispensable for understanding the heterogeneity and functions of cells. Low-copy-number proteins (fewer than 1,000 molecules per cell) perform multiple crucial functions such as gene expression, cellular metabolism and cell signaling. The expression level of low-copy-number proteins of individual cells provides key information for the in-depth understanding of biological processes and diseases. However, the quantitative analysis of low-copy-number proteins in a single cell still remains challenging. To overcome this, we developed an approach called single-cell plasmonic immunosandwich assay (scPISA) for the quantitative measurement of low-copy-number proteins in single living cells. scPISA combines in vivo microextraction for specific enrichment of target proteins from cells and a state-of-the-art technique called plasmon-enhanced Raman scattering for ultrasensitive detection of low-copy-number proteins. Plasmon-enhanced Raman scattering detection relies on the plasmonic coupling effect (hot-spot) between silver-based plasmonic nanotags and a gold-based extraction microprobe, which dramatically enhances the signal intensity of the surface-enhanced Raman scattering of the nanotags and thereby enables sensitivity at the single-molecule level. scPISA is a straightforward and minimally invasive technique, taking only ~6-15 min (from in vivo extraction to Raman spectrum readout). It is generally applicable to all freely floating intracellular proteins provided that appropriate antibodies or alternatives (for example, molecularly imprinted polymers or aptamers) are available. The entire protocol takes ~4-7 d to complete, including material fabrication, single-cell manipulation, protein labeling, signal acquisition and data analysis.
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http://dx.doi.org/10.1038/s41596-021-00547-9DOI Listing
July 2021

Design, Synthesis, and Antifungal Activity of 2,6-Dimethyl-4-aminopyrimidine Hydrazones as PDHc-E1 Inhibitors with a Novel Binding Mode.

J Agric Food Chem 2021 Jun 19;69(21):5804-5817. Epub 2021 May 19.

Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, 152 Luoyu Road, Wuhan 430079, P. R. China.

A series of novel 2,6-dimethyl-4-aminopyrimidine hydrazones were rationally designed and synthesized as pyruvate dehydrogenase complex E1 (PDHc-E1) inhibitors. Compounds strongly inhibited () PDHc-E1 (IC values 0.94-15.80 μM). As revealed by molecular docking, site-directed mutagenesis, enzymatic, and inhibition kinetic analyses, compounds competitively inhibited PDHc-E1 and bound in a "straight" pattern at the PDHc-E1 active site, which is a new binding mode. In antifungal assays, most compounds at 50 μg/mL showed more than 80% inhibition against the mycelial growth of six tested phytopathogenic fungi, including , , , and. Notably, and were 1.8-380 fold more potent against than the commercial fungicides captan and chlorothalonil. , and controlled the growth of comparably to the commercial fungicide tebuconazole. Thus, and have potential commercial value for the control of peach brown rot caused by .
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http://dx.doi.org/10.1021/acs.jafc.0c07701DOI Listing
June 2021

Erratum: Acidic Microenvironment Up-Regulates Exosomal miR-21 and miR-10b in Early-Stage Hepatocellular Carcinoma to Promote Cancer Cell Proliferation and Metastasis: Erratum.

Theranostics 2021 20;11(13):6522-6523. Epub 2021 Apr 20.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

[This corrects the article DOI: 10.7150/thno.30958.].
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http://dx.doi.org/10.7150/thno.60140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120223PMC
April 2021

Comparative analysis of type 2 diabetes-associated gut microbiota between Han and Mongolian people.

J Microbiol 2021 Jul 15;59(7):693-701. Epub 2021 May 15.

School of Pharmacy, Minzu University of China, Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, 100081, China.

Due to the different rates of diabetes in different ethnic groups and the structural differences in intestinal microbiota, this study evaluated the changes in diabetes-related intestinal microbiota in two ethnic groups. Fifty-six stool samples were collected from subjects from the Han and Mongolian ethnic groups in China, including participants without diabetes (non-diabetic, ND) and with type 2 diabetes (T2D). The 16S rDNA gene V3 + V4 area was extracted from microbiota, amplified by PCR, and used to perform high-throughput sequencing and screen differential microbiota associated with ethnicity. The results showed that there were 44 T2D-related bacterial markers in the Han subjects, of which Flavonifractor, Alistipes, Prevotella, Oscillibacter, Clostridium XlVa, and Lachnospiracea_incertae_sedis were most closely related to diabetes. There were 20 T2D-related bacterial markers in the Mongolian subjects, of which Fastidiosipila and Barnesiella were most closely related to diabetes. The common markers of T2D bacteria in the two ethnic groups were Papillibacter and Bifidobacterium. There were 17 metabolic pathways with significant differences between the ND and T2D groups in the Han group, and 29 metabolic pathways in the Mongolian group. The glutamatergic metabolic pathway was the only common metabolic pathway in two ethnic groups. The composition and function of diabetes-related bacteria were significantly different among the different ethnic groups, which suggested that the influence of ethnic differences should be fully considered when studying the association between diabetes and bacteria. In addition, the common bacterial markers found in diabetic patients of different ethnic groups in this study can be used as potential targets to study the pathogenesis and treatment of diabetes.
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http://dx.doi.org/10.1007/s12275-021-0454-8DOI Listing
July 2021

Corrigendum: Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway.

Front Oncol 2021 6;11:670798. Epub 2021 Apr 6.

Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

[This corrects the article DOI: 10.3389/fonc.2020.01756/full.].
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http://dx.doi.org/10.3389/fonc.2021.670798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057108PMC
April 2021

Bilayer of polyelectrolyte films for spontaneous power generation in air up to an integrated 1,000 V output.

Nat Nanotechnol 2021 Jul 26;16(7):811-819. Epub 2021 Apr 26.

Key Laboratory of Organic Optoelectronics & Molecular Engineering, Ministry of Education, Department of Chemistry and State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, P. R. China.

Environmentally adaptive power generation is attractive for the development of next-generation energy sources. Here we develop a heterogeneous moisture-enabled electric generator (HMEG) based on a bilayer of polyelectrolyte films. Through the spontaneous adsorption of water molecules in air and induced diffusion of oppositely charged ions, one single HMEG unit can produce a high voltage of ~0.95 V at low (25%) relative humidity (RH), and even jump to 1.38 V at 85% RH. A sequentially aligned stacking strategy is created for large-scale integration of HMEG units, to offer a voltage of more than 1,000 V under ambient conditions (25% RH, 25 °C). Using origami assembly, a small section of folded HMEGs renders an output of up to 43 V cm. Such integration devices supply sufficient power to illuminate a lamp bulb of 10 W, to drive a dynamic electronic ink screen and to control the gate voltage for a self-powered field effect transistor.
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http://dx.doi.org/10.1038/s41565-021-00903-6DOI Listing
July 2021
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