Publications by authors named "Yajie Wang"

307 Publications

Scalable High-Pressure Synthesis of sp-sp Carbon Nanoribbon via [4 + 2] Polymerization of 1,3,5-Triethynylbenzene.

J Phys Chem Lett 2021 Jul 23:7140-7145. Epub 2021 Jul 23.

Center for High Pressure Science and Technology Advanced Research, 10 Xibeiwang East Road, Haidian, Beijing 100094, China.

Pressure-induced polymerization of aromatics is an effective method to construct extended carbon materials, including the diamond-like nanothread and graphitic structures, but the reaction pressure of phenyl is typically around 20 GPa and too high to be applied for large-scale preparation. Here by introducing ethynyl to phenyl, we obtained a sp-sp carbon nanoribbon structure by compressing 1,3,5-triethynylbenzene (TEB), and the reaction pressure of phenyl was successfully decreased to 4 GPa, which is the lowest reaction pressure of aromatics at room temperature. Using experimental and theoretical methods, we figured out that the ethynylphenyl of TEB undergoes [4 + 2] dehydro-Diels-Alder (DDA) reaction with phenyl upon compression at an intermolecular C···C distance above 3.3 Å, which is much longer than those of benzene and acetylene. Our research suggested that the DDA reaction between ethynylphenyl and phenyl is a promising route to decrease the reaction pressure of aromatics, which allows the scalable high-pressure synthesis of nanoribbon materials.
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http://dx.doi.org/10.1021/acs.jpclett.1c01945DOI Listing
July 2021

Directed Evolution: Methodologies and Applications.

Chem Rev 2021 Jul 23. Epub 2021 Jul 23.

Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.

Directed evolution aims to expedite the natural evolution process of biological molecules and systems in a test tube through iterative rounds of gene diversifications and library screening/selection. It has become one of the most powerful and widespread tools for engineering improved or novel functions in proteins, metabolic pathways, and even whole genomes. This review describes the commonly used gene diversification strategies, screening/selection methods, and recently developed continuous evolution strategies for directed evolution. Moreover, we highlight some representative applications of directed evolution in engineering nucleic acids, proteins, pathways, genetic circuits, viruses, and whole cells. Finally, we discuss the challenges and future perspectives in directed evolution.
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http://dx.doi.org/10.1021/acs.chemrev.1c00260DOI Listing
July 2021

Prevalence of Among Pregnant Women, Gynecology Clinic Attendees, and Subfertile Women in Guangdong, China: A Cross-sectional Survey.

Open Forum Infect Dis 2021 Jun 24;8(6):ofab206. Epub 2021 Apr 24.

Dermatology Hospital of Southern Medical University, Guangzhou, China.

Background: (CT) is a major cause of infertility and adverse birth outcomes, but its epidemiology among childbearing-age women remains unclear in China. This study investigated the prevalence of CT and associated factors among Chinese women aged 16-44 years who were either (1) pregnant, (2) attending gynecology clinics, or (3) subfertile.

Methods: We conducted a cross-sectional survey and recruited participants from obstetrics, gynecology, and infertility clinics in Guangdong between March and December 2019. We collected information on individuals' sociodemographic characteristics, previous medical conditions, and sexual behaviors. First-pass urine and cervical swabs were tested using nucleic acid amplification testing. We calculated the prevalence in each population and subgroup by age, education, and age at first sex. Multivariable binomial regression models were used to identify factors associated with CT.

Results: We recruited 881 pregnant women, 595 gynecology clinic attendees, and 254 subfertile women. The prevalence of CT was 6.7% (95% CI, 5.2%-8.5%), 8.2% (95% CI, 6.2%-10.7%), and 5.9% (95% CI, 3.5%-9.3%) for the above 3 populations, respectively. The subgroup-specific prevalence was highest among those who first had sex before age 25 years and older pregnant women (>35 years). The proportion of asymptomatic CT was 84.8%, 40.0%, and 60.0% among pregnant women, gynecology clinic attendees, and subfertile women, respectively. Age at first sex (<25 years), multipara, and ever having more than 1 partner increased the risk of CT.

Conclusions: Childbearing-age women in China have a high prevalence of CT. As most women with CT were asymptomatic, more optimal prevention strategies are urgently needed in China.
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http://dx.doi.org/10.1093/ofid/ofab206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253043PMC
June 2021

Breast cancer brain metastasis: insight into molecular mechanisms and therapeutic strategies.

Br J Cancer 2021 Jul 5. Epub 2021 Jul 5.

Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, P.R. China.

Breast cancer is one of the most prevalent malignancies in women worldwide. Early-stage breast cancer is considered a curable disease; however, once distant metastasis occurs, the 5-year overall survival rate of patients becomes significantly reduced. There are four distinct metastatic patterns in breast cancer: bone, lung, liver and brain. Among these, breast cancer brain metastasis (BCBM) is the leading cause of death; it is highly associated with impaired quality of life and poor prognosis due to the limited permeability of the blood-brain barrier and consequent lack of effective treatments. Although the sequence of events in BCBM is universally accepted, the underlying mechanisms have not yet been fully elucidated. In this review, we outline progress surrounding the molecular mechanisms involved in BCBM as well as experimental methods and research models to better understand the process. We further discuss the challenges in the management of brain metastases, as well as providing an overview of current therapies and highlighting innovative research towards developing novel efficacious targeted therapies.
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http://dx.doi.org/10.1038/s41416-021-01424-8DOI Listing
July 2021

Pharmacological inhibition of MELK restricts ferroptosis and the inflammatory response in colitis and colitis-propelled carcinogenesis.

Free Radic Biol Med 2021 Jun 16;172:312-329. Epub 2021 Jun 16.

Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, Lishui, 323000, China; Department of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China. Electronic address:

Introduction: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic recurrent and incurable gastrointestinal diseases with an unknown etiology that leads to a high risk of developing colitis-associated colorectal cancer (CRC).

Objectives: In this study, we measured the expression characteristics of MELK in IBD and CRC tissues and explored the regulatory effect of OTSSP167 (a MELK-selective inhibitor) on the mice models of colitis and colitis-associated carcinogenesis and analyzed the specific molecular mechanisms.

Methods: DSS-induced colitis and colitis-associated carcinogenesis (CAC) model were treated with MELK inhibitor OTSSP167 then the fight against effect of OTSSP167 in the clinical symptoms of colitis and CAC was measured. In addition, underlying mechanism of OTSSP167 treatment in vitro and vivo including anti-ferroptosis and anti-inflammatory response effect was further explored.

Results: We found that pharmacological inhibition of MELK was indicated to significantly alleviate the inflammatory response in mice with colitis, reduce intestinal damage, and effectively inhibit the occurrence and progression of colitis-propelled carcinogenesis, which was closely related to the regulation of gut microbial composition, and OTSSP167-mediated fecal microbiota transplantation effectively alleviated DSS-induced colitis. In addition, OTSSP167 treatment obviously inhibited ferroptosis in the intestinal tissue and suppressed macrophage infiltration and M1 polarization, which reduced the secretion of pro-inflammatory factors. Further exploration of the molecular mechanism revealed that OTSSP167 inhibited AKT/IKK/P65 and ERK/IKK/P65 signaling cascades both in vivo and in vitro, which may help alleviate intestinal inflammation and control the occurrence of cancer.

Conclusion: Our findings lay a theoretical foundation for the use of OTSSP167 as a treatment for IBD and its inhibition of the occurrence of colitis-associated carcinogenesis; additionally, MELK may be a potentially effective target molecule, thus providing more options for clinical treatment.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.06.012DOI Listing
June 2021

ShenLian Extract Enhances TGF-β Functions in the Macrophage-SMC Unit and Stabilizes Atherosclerotic Plaques.

Front Pharmacol 2021 28;12:669730. Epub 2021 May 28.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Macrophage polarization and phenotypic switching of smooth muscle cells (SMCs) are multi-faceted events dominating atherosclerosis (AS) progression. TGF-β was proved to been one of the bridge on the crosstalk between macrophage and SMC. ShenLian (SL) was extracted from a potent anti-atherosclerotic formula. However, its exact mechanism rebalancing inflammatory microenvironment of AS remain largely unknown. Within the entirety of macrophage and SMC, this study investigated the pharmacological effects of SL on stabilizing atherosclerotic plaques. The main components of SL were examined by high performance liquid chromatography. Co-culture and conditioned medium models of macrophage/SMC interactions were designed to identify the relationship between macrophage polarization and switching of SMC phenotypes. Flow cytometry, immunofluorescent staining, RT-PCR, western blotting, and ELISA were used to determine the expression of molecules relating to AS progression. An atherosclerosis animal model, established by placing a perivascular collar on the right common carotid artery in ApoE mice, was used to investigate whether TGF-β is the key molecular mediator of SL in crosstalk between macrophage and SMC. Plaque size was defined by nuclear magnetic resonance imaging. Key markers related to phenotypic transformation of macrophage and SMC were determined by immunohistochemical staining. Results revealed that, accompanied by rebalanced M2 macrophage polarization, SL supported SMC phenotypic transformation and functionally reconstruct the ECM of plaques specifically in macrophage-SMC co-cultural model. Molecularly, such activity of SL closely related to the activation of STAT3/SOCS3 pathway. Furthermore, in co-culture system, up-regulation of α-SMA induced by SL could neutralized by 1D11, a TGF-β neutralizing antibody, indicating that SL mediated Macrophage-SMC communication by enhancing TGF-β. In the AS model constructed by ApoE mice, effects of SL on phenotypic transformation of macrophage and SMC has been well verified. Specific blocking of TGF-β largely attenuated the aforementioned effects of SL. Our findings highlighted that TGF-β might be the responsive factor of SL within macrophage and SMC communication. This study revealed that crosstalk between macrophage and SMC forms a holistic entirety promoting atherosclerotic plaque stability.
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http://dx.doi.org/10.3389/fphar.2021.669730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193129PMC
May 2021

Dihydroartemisinin inhibits activation of the AIM2 inflammasome pathway and NF-κB/HIF-1α/VEGF pathway by inducing autophagy in A431 human cutaneous squamous cell carcinoma cells.

Int J Med Sci 2021 13;18(12):2705-2715. Epub 2021 May 13.

Department of Dermatology, the Second Affiliated Hospital, Hainan Medical University, Haikou, 570311, Hainan, China.

The therapeutic effect of dihydroartemisinin (DHA) against cutaneous squamous cell carcinoma (cSCC) has been previously demonstrated; however, the underlying mechanism remains unclear. This study sought to verify the therapeutic effect of DHA against cSCC and explore its underlying mechanism in A431 cSCC cells. This study reported that DHA inhibited A431 cells proliferation in a time- and concentration-dependent manner and promoted A431 cells apoptosis. Moreover, DHA inhibited the invasion and migration of A431 cells. Mechanistically, DHA promoted autophagy and inhibited activation of the absent in melanoma 2 (AIM2) inflammasome pathway and NF-κB/HIF-1α/VEGF pathway. Treatment of A431 cells with the mTOR inhibitor, and autophagy promoter, rapamycin also inhibited these two pathways. In conclusion, DHA inhibited activation of the AIM2 inflammasome pathway and NF-κB/HIF-1α/VEGF pathway by promoting autophagy in A431 cells, thus accounting for its therapeutic effect. Induction of autophagy by DHA may be mediated by inhibiting the mTOR pathway and promoting reactive oxygen species production.
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http://dx.doi.org/10.7150/ijms.57167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176175PMC
May 2021

Overexpression of Cassava Enhances the Salt and IAA Tolerance of Transgenic .

Plants (Basel) 2021 May 8;10(5). Epub 2021 May 8.

College of Tropical Crops, Hainan University, Haikou 570228, China.

Annexins are a superfamily of soluble calcium-dependent phospholipid-binding proteins that have considerable regulatory effects in plants, especially in response to adversity and stress. The gene has been reported to play a significant role in various abiotic stress responses. In our study, the cDNA of an annexin gene highly similar to was isolated from the cassava genome and named . It contains domains specific to annexins, including four annexin repeat sequences (I-IV), a Ca-binding sequence, Ca-independent membrane-binding-related tryptophan residues, and a salt bridge-related domain. is localized in the cell membrane and cytoplasm, and it was found to be preferentially expressed in the storage roots of cassava. The overexpression of reduced the sensitivity of transgenic to various Ca, NaCl, and indole-3-acetic acid (IAA) concentrations. The expression of the stress resistance-related gene and auxin signaling pathway-related genes and in transgenic was significantly increased under salt stress, while the Malondialdehyde (MDA) content was significantly lower than that of the control. These results indicate that the gene may increase the salt tolerance of transgenic via the IAA signaling pathway.
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http://dx.doi.org/10.3390/plants10050941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150822PMC
May 2021

Social network distribution of syphilis self-testing among men who have sex with men in China: study protocol for a cluster randomized control trial.

BMC Infect Dis 2021 May 27;21(1):491. Epub 2021 May 27.

Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong, China.

Background: Syphilis is a common sexually transmitted infection (STI) among men who have sex with men (MSM). Increasing syphilis testing is important to syphilis control. However, in low- and middle-income countries like China, syphilis testing rates remain low among MSM. We describe a randomized controlled trial protocol to examine the effectiveness of social network distribution approaches of syphilis self-testing among MSM in China.

Methods: We will recruit index and alter MSM. Indexes will be eligible if they: are born biologically male; aged 18 years or above; ever had sex with another man; are willing to distribute syphilis testing packages or referral links to their alters; and willing to provide personal contact information for future follow-up. Three hundred MSM will be recruited and randomly assigned in a 1:1:1 ratio into three arms: standard of care (control arm); standard syphilis self-testing (SST) delivery arm; and referral link SST delivery arm. Indexes will distribute SST packages or referral links to encourage alters to receive syphilis testing. All indexes will complete a baseline survey and a 3-month follow-up survey. Syphilis self-test results will be determined by photo verification via a digital platform. The primary outcome is the mean number of alters who returned verified syphilis testing results per index in each arm.

Discussion: The trial findings will provide practical implications in strengthening syphilis self-testing distribution and increasing syphilis testing uptake among MSM in China. This study also empowers MSM community in expanding syphilis testing by using their own social network.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000036988 . Registered 26 August 2020 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12879-021-06137-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161568PMC
May 2021

Clinical characteristics, genotypes, antifungal susceptibility, and outcomes in human immunodeficiency virus-positive patients in Beijing, China.

J Int Med Res 2021 May;49(5):3000605211016197

Department of Clinical Laboratory Medicine, Beijing Ditan Hospital, 12517Capital Medical University, Beijing, P.R. China.

is an environmental fungal pathogen that causes opportunistic infections and severe disseminated meningoencephalitis, mainly in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS). In this study, the clinical characteristics, treatment protocols, and outcomes of 70 patients with AIDS and infection at Beijing Ditan Hospital were retrospectively analyzed. We performed antimicrobial sensitivity tests and multilocus sequence typing (MLST) on isolates from these patients. The most common symptoms were headache (58.6%), fever (54.3%), and high cerebrospinal fluid pressure (≥200 mm HO) (71.4%). All patients were positive for antigen in blood or cerebrospinal fluid. The CD4 cell counts of 92.8% (65/70) of patients were <100 cells/µL. In total, 74 isolates were obtained from the 70 patients. The 65 isolates that could be typed fell into 12 sequence types (STs) by MLST: ST5, ST31, ST63, ST202, ST237, ST289, ST295, ST296, ST298, ST324, ST337, and ST359. ST5 was the major type, accounting for 78.5% of isolates (51/65). This study comprehensively assessed the clinical and molecular epidemiology of in patients with AIDS and may inform the development of targeted prevention and treatment strategies for immunocompromised patients with infection.
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http://dx.doi.org/10.1177/03000605211016197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161877PMC
May 2021

Spheroidization of ultrasonic degraded corn silk polysaccharide to enhance bioactivity by the anti-solvent precipitation method.

J Sci Food Agric 2021 May 25. Epub 2021 May 25.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, P.R. China.

Background: Corn silk is a very important by-product of corn production with medicinal value. Corn silk polysaccharide (CSP) is the main active ingredient. In the present study, ultrasound and spheroidization by anti-solvent were applied to improve the biological activity of CSP.

Results: The results showed that ultrasonic degradation improved the α-glucosidase inhibitory activity of CSP by changing its physicochemical characteristics. As the anti-solvent ratio increased, the particle size of the nanoparticles (NPs) from the spheroidization of ultrasonic-degraded corn silk polysaccharide (UCSP) gradually increased, and NP-1 exhibited the highest inhibitory effect of α-glucosidase. Isothermal titration calorimetry (ITC) results indicated that the enhanced activity might be due to more α-glucosidase binding sites with NP-1 compared with no spheroidization. Western blotting results showed that NP-1 could improve the 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) uptake in the L6 cells by regulating the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and the translocation of glucose transporter 4 (GLUT4). NP-1 also exhibited excellent stability in different environments.

Conclusion: The study revealed that ultrasonic treatment and spheroidization processing showed potential applications for improving the biological activity of polysaccharides. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11329DOI Listing
May 2021

Distributions of Total Mercury and Methylmercury in Dragonflies from a Large, Abandoned Mercury Mining Region in China.

Arch Environ Contam Toxicol 2021 Jul 23;81(1):25-35. Epub 2021 May 23.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang, 550081, China.

Dragonflies (Order Odonata) often are considered to be biosentinels of environmental contamination, e.g., heavy metals and/or persistent organic pollutants (POPs). Dragonflies (n = 439) belonging to 15 species of 8 genera were collected from an abandoned mercury (Hg) mining region in China to investigate the bioaccumulation of total Hg (THg) and methylmercury (MeHg). THg and MeHg concentrations in dragonflies varied widely within ranges of 0.06-19 mg/kg (average: 1.5 ± 2.2 mg/kg) and 0.02-5.7 mg/kg (average: 0.75 ± 0.65 mg/kg), respectively. THg and MeHg were positively correlated with bodyweight (THg: r = 0.10, P = 0.000; MeHg: r = 0.09, P = 0.000). Significant variations were observed among species, with the highest MeHg value (in Orthetrum triangulare) was fivefold higher than the lowest (in Pantala flavescens). These variations were consistent with those of nitrogen isotope (δN) values, indicating that increased δN, i.e., trophic levels, may reflect increased exposure and uptake of biomagnifying MeHg in dragonflies. A toxicological risk assessment found hazard quotients for specialist dragonfly-consuming birds of up to 7.2, which is 2.4 times greater than the permissible limit of 3, suggesting a potential toxicological risk of exposure.
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http://dx.doi.org/10.1007/s00244-021-00854-yDOI Listing
July 2021

Analysis of cytokine risk factors in the early death of patients with secondary phagocytic lymphocytic histiocytosis.

Am J Transl Res 2021 15;13(4):2388-2398. Epub 2021 Apr 15.

Department of Hematology, The First People's Hospital of Yunnan Province Kunming, China.

Secondary hemophagocytic lymphohistiocytosis (sHLH) is an excessive inflammatory response syndrome caused by immune abnormalities. Up to date, the risk factors for cytokines causing early death in sHLH patients have not been elucidated. Our study reviewed the cytokine expression levels in peripheral blood of 50 sHLH patients. Through Cox proportional hazard model analysis, we found that IL-17F ≥2.835 pg/mL (HR = 5.922, 95% CI = 1.793-19.558, P = 0.004) was an independent death risk factor in sHLH patients, and it was also 30 days (Cutoff-value = 2.890 pg/mL, HR = 16.568, 95% CI = 1.917-143.195, P = 0.011), 60 days (Cutoff-value = 2.890 pg/mL, HR = 7.559, 95% CI = 1.449-39.423, P = 0.016), 90 day death risk factor (Cutoff-value = 2.835 pg/mL, HR = 7.649, 95% CI = 1.965-29.778, P = 0.003); IL-10 ≥16.730 pg/mL (HR = 4.821, 95% CI = 1.151-20.116, P = 0.031) is not only a death risk factor within 90 days, but also within 10 days (Cutoff-value = 944.350 pg/mL, HR = 13.321, 95% CI = 1.123-158.03, P = 0.027); and IL-5 ≥2.495 pg/mL (HR = 15.687, 95% CI = 1.377-178.645, P = 0.04) was also a death risk factor within 10 days. Besides, IL-17F, IL-10, IL-5, and the previously reported common risk factors Age, platelets, activated partial thromboplastin time, triglyceride, and lactate dehydrogenase were analyzed together. It was found that the patient age ≥56 years-old is was an important risk factor for death within 30 days, IL-17 ≥2.89 pg/mL and IL-10 ≥16.73 pg/mL are important risk factors for patient death. In summary, our data indicate that age, IL-10 and IL-17F are important risk factors for early death in sHLH patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129357PMC
April 2021

Neural representations of the amount and the delay time of reward in intertemporal decision making.

Hum Brain Mapp 2021 Aug 2;42(11):3450-3469. Epub 2021 May 2.

Key Research Base of Humanities and Social Sciences of the Ministry of Education, Academy of Psychology and Behavior, Tianjin Normal University, Tianjin, China.

Numerous studies have examined the neural substrates of intertemporal decision-making, but few have systematically investigated separate neural representations of the two attributes of future rewards (i.e., the amount of the reward and the delay time). More importantly, no study has used the novel analytical method of representational connectivity analysis (RCA) to map the two dimensions' functional brain networks at the level of multivariate neural representations. This study independently manipulated the amount and delay time of rewards during an intertemporal decision task. Both univariate and multivariate pattern analyses showed that brain activity in the dorsomedial prefrontal cortex (DMPFC) and lateral frontal pole cortex (LFPC) was modulated by the amount of rewards, whereas brain activity in the DMPFC and dorsolateral prefrontal cortex (DLPFC) was modulated by the length of delay. Moreover, representational similarity analysis (RSA) revealed that even for the regions of the DMPFC that overlapped between the two dimensions, they manifested distinct neural activity patterns. In terms of individual differences, those with large delay discounting rates (k) showed greater DMPFC and LFPC activity as the amount of rewards increased but showed lower DMPFC and DLPFC activity as the delay time increased. Lastly, RCA suggested that the topological metrics (i.e., global and local efficiency) of the functional connectome subserving the delay time dimension inversely predicted individual discounting rate. These findings provide novel insights into neural representations of the two attributes in intertemporal decisions, and offer a new approach to construct task-based functional brain networks whose topological properties are related to impulsivity.
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http://dx.doi.org/10.1002/hbm.25445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249888PMC
August 2021

Early and consecutive RT-PCR tests with both oropharyngeal swabs and sputum could improve testing yield for patients with COVID-19: An observation cohort study in China.

Int J Infect Dis 2021 Jun 28;107:242-246. Epub 2021 Apr 28.

Beijing Ditan Hospital, Capital Medical University, Beijing 100102, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100102, China. Electronic address:

Objective: The real-time polymerase chain reaction (RT-PCR) test is recommended for the diagnosis of COVID-19 and provides a powerful tool to identify new infections and facilitate contact tracing. In fact, as the prevalence of COVID-19 decreases, this RT-PCR testing remains as the main preventive measure to avoid rebound. However, inconsistent results can lead to misdiagnoses in the clinic. These inconsistencies are due to the variability in (1) the collection times of biological samples post infection, and (2) sampling procedures.

Methods: We applied the Kaplan-Meier method and multivariate logistic regression on RT-PCR results from 258 confirmed patients with COVID-19 to evaluate the factors associated with negative conversion. We also estimated the proportion (%) of negative conversion among patients who had tested twice or more, and compared the proportions arising from oropharyngeal swabs, sputum, and combined double testing, respectively.

Main Results: The proportion of negative conversion was 6.7% on day 4, 16.4% on day 7, 41.0% at 2 weeks, and 61.0% at 3 weeks post-admission. We also found that 34.1% and 60.3% of subjects had at least one negative RT-PCR result on days 7 and 14 after the onset of symptoms, respectively. The proportion of negative conversions following sputum testing was higher than that from oropharyngeal swabs in the early stages but this declined after the onset of symptoms.

Conclusion: In the absence of effective treatments or vaccines, efficient testing strategies are critical if we are to control the COVID-19 epidemic. According to this study, early, consecutive and combined double testing, will be the key to identify infected patients, particularly for asymptomatic and mild symptomatic cases. These strategies will minimize misdiagnosis and the ineffective isolation of infected patients.
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http://dx.doi.org/10.1016/j.ijid.2021.04.076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079261PMC
June 2021

Photo-oxidation of arsenite in acidic waters containing Suwannee River fulvic acid: roles of SRFA* and hydroxyl radical.

Environ Sci Pollut Res Int 2021 Apr 16. Epub 2021 Apr 16.

School of Eco-Environmental Engineering, Guizhou Minzu University, Guiyang, 550025, People's Republic of China.

The photo-oxidation of arsenite (As(III)) in solution containing Suwannee River fulvic acid (SRFA) under the ultraviolet A (UVA) irradiation (λ = 365 nm) was studied. In a solution containing 100.0 μg·L As(III) and 10.0 mg·L SRFA at pH 3.0, SRFA induced As(III) photo-oxidation by producing the triplet excited state of SRFA (SRFA*) and hydroxyl radical(HO˙). Approximately 82% of As(III) oxidation was attributed to HO˙ which depended strongly on HO˙/O˙. The remaining 18% of As(III) oxidation was attributed to the direct reaction between As(III) and SRFA*. The photo-oxidation of As(III) was significantly affected by solution pH. Excess SRFA inhibited As(III) photo-oxidation. The addition of a low concentration of ferric ions retarded the photo-oxidation of As(III) due to the poor photo-activity of Fe(III)-SRFA complexes. In contrast, the addition of ferric ions at high concentration greatly accelerated As(III) photo-oxidation because of the high photo-activity of Fe(III)-OH complexes. The fractions of SRFA with different molecular weight showed different oxidizing capacities under UV irradiation which was possibly related to the different contents of phenolic OH groups. The findings have important environmental implications for the photo-transformation behavior of As(III) in natural surface waters containing dissolved organic matter, especially acidic waters.
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http://dx.doi.org/10.1007/s11356-021-13900-yDOI Listing
April 2021

Reactivation of SARS-CoV-2 infection following recovery from COVID-19.

J Infect Public Health 2021 May 8;14(5):620-627. Epub 2021 Feb 8.

Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun East Street, Chaoyang District, Beijing 100015, PR China. Electronic address:

Introduction: Many individuals test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA after recovering from the coronavirus disease (COVID-19), but the incidence of reactivation is unknown. We, therefore, estimated the incidence of reactivation among individuals who had recovered from COVID-19 and determined its predictors.

Methods: In this retrospective cohort study, patients with COVID-19 were followed up for at least 14 days after two consecutive negative SARS-CoV-2 polymerase chain reaction test results obtained ≥24 h apart, and the frequency of SARS-CoV-2 reactivation was assessed.

Results: Of the 109 patients, 29 (27%) experienced reactivation, and seven (24%) of these were symptomatic. The mean period for the real-time PCR tests for SARS-CoV-2 from negative to positive results was 17 days. Compared with patients without reactivation, those with reactivation were significantly younger and more likely to have a lymphocyte count of <1500/μL (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.12-0.94) and two or fewer symptoms (OR: 0.20, 95% CI: 0.07-0.55) during the initial episode.

Conclusion: Risk-stratified surveillance should be conducted among patients who have recovered from COVID-19.
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http://dx.doi.org/10.1016/j.jiph.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869688PMC
May 2021

The structural characteristic of acidic-hydrolyzed corn silk polysaccharides and its protection on the HO-injured intestinal epithelial cells.

Food Chem 2021 Sep 26;356:129691. Epub 2021 Mar 26.

Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, PR China. Electronic address:

This work aims to describe the purification and characterization of acidic-hydrolyzed corn silk polysaccharides (AH-CSP) and evaluate their protection on the HO-injured intestinalepithelial cells (IEC-6). Two fractions named AHP-1 and AHP-2 were obtained from AH-CSP, and physicochemical properties of them were investigated by gel permeation chromatography (GPC), gas chromatography (GC), nuclear magnetic resonance (NMR), fourier transform infrared (FT-IR) spectroscopy, scanning electronic microscopy (SEM), and Congo red test. Results showed that AHP-1 (2.80 × 10 Da) and AHP-2 (1.25 × 10 Da) were consisted of xylose, mannose, galactose, rhamnose, arabinose, and glucose. AHP-1 and AHP-2 had strong scavenging activities on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-Azobis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), and OH· free radicals. Furthermore, pretreatment with AHP-2 could protect the HO-injured IEC-6 cells by effectively scavenging the overproduced reactive oxygen species (ROS) and regulating of Kelch-like ECH-associated protein 1(Keap1)/ nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway.
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http://dx.doi.org/10.1016/j.foodchem.2021.129691DOI Listing
September 2021

The Effect and Mechanism of LINC00663 on the Biological Behavior of Glioma.

Neurochem Res 2021 Jul 8;46(7):1737-1746. Epub 2021 Apr 8.

Department of Clinical Laboratory, Capital Medical University Affiliated Beijing Ditan Hospital, No. 8 Jingshun Dongjie, Chaoyang District, Beijing, 100015, People's Republic of China.

Glioma is the most frequent primary malignant brain tumor, which is characterized by high incidence and mortality, with a poor prognosis. Numerous studies have revealed the abnormal expression of long non-coding RNAs in gliomas. This study explored the effects and potential mechanism of LINC00663 in glioma. The LINC00663 levels and their prognostic values were analyzed from the GEO databases using bioinformatics. Also, LINC00663 expression in tissue samples and cell lines was measured using qRT-PCR. The roles of LINC00663 in glioma were confirmed using CCK8, EdU assay as well as Transwell tests. Moreover, the influences of LINC00663 on the AKT/mTOR signal cascades were detected using western blotting assay. LINC00663 expression was higher in both glioma tissues and cell lines than that in the normal brain tissues and human astrocytes. High expression of LINC00663 led to the low overall survival rate of patients with glioma. LINC00663 knockdown notably restrained cell proliferation, migration, and invasion abilities by decreasing the activation of AKT and mTOR. This study indicated that LINC00663 might have a cancer-promoting role in accelerating glioma development and progression through regulating AKT/mTOR pathway.
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http://dx.doi.org/10.1007/s11064-021-03311-3DOI Listing
July 2021

Deep learning-enhanced T mapping with spatial-temporal and physical constraint.

Magn Reson Med 2021 09 6;86(3):1647-1661. Epub 2021 Apr 6.

Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.

Purpose: To propose a reconstruction framework to generate accurate T maps for a fast MR T mapping sequence.

Methods: A deep learning-enhanced T mapping method with spatial-temporal and physical constraint (DAINTY) was proposed. This method explicitly imposed low-rank and sparsity constraints on the multiframe T -weighted images to exploit the spatial-temporal correlation. A deep neural network was used to efficiently perform T mapping as well as denoise and reduce undersampling artifacts. Additionally, the physical constraint was used to build a bridge between low-rank and sparsity constraint and deep learning prior, so the benefits of constrained reconstruction and deep learning can be both available. The DAINTY method was trained on simulated brain data sets, but tested on real acquired phantom, 6 healthy volunteers, and 7 atherosclerosis patients, compared with the narrow-band k-space-weighted image contrast filter conjugate-gradient SENSE (NK-CS) method, kt-sparse-SENSE (kt-SS) method, and low-rank plus sparsity (L+S) method with least-squares T fitting and direct deep learning mapping.

Results: The DAINTY method can generate more accurate T maps and higher-quality T -weighted images compared with other methods. For atherosclerosis patients, the intraplaque hemorrhage can be successfully detected. The computation speed of DAINTY was 10 times faster than traditional methods. Meanwhile, DAINTY can reconstruct images with comparable quality using only 50% of k-space data.

Conclusion: The proposed method can provide accurate T maps and good-quality T -weighted images with high efficiency.
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http://dx.doi.org/10.1002/mrm.28793DOI Listing
September 2021

Carbon emission of energy consumption of the electric vehicle development scenario.

Environ Sci Pollut Res Int 2021 Apr 4. Epub 2021 Apr 4.

College of Management Science, Chengdu University of Technology, Chengdu, 610059, China.

To explore the impact of promotion of electric vehicles on carbon emissions in China, this paper used the principal component analysis (PCA)-logistic regression model to predict the demand for traditional vehicles, and used the scenario analysis method to analyze the proportion of electric vehicles in traditional vehicles qualitatively. Then this paper calculated the carbon emissions during the power generation process based on the existing power structure. In addition, the IPCC carbon emission calculation method is used to compare the CO emissions produced by electric vehicles and fuel vehicles with similar vehicle quality while driving the same distance and consuming different energy sources. The results showed that the CO emissions of electric vehicles accounted for only 37.05% of fuel vehicles. By 2050, the annual electricity demand of electric vehicles will be 828.7, 776.9, and 752.1 billion kWh under the radical scenario, the reference scenario, and the negative scenario, respectively. According to the current power structure, the carbon emissions will be 1.2, 1.1, and 1 billion tons, respectively. The rapid growth of electric vehicles has a substantial impact on the grid load. Studying the changes in CO emissions from energy substitution is significant to formulate the development strategy of the automobile industry and adjust energy structure policies.
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http://dx.doi.org/10.1007/s11356-021-13632-zDOI Listing
April 2021

Radiomic nomogram based on MRI to predict grade of branching type intraductal papillary mucinous neoplasms of the pancreas: a multicenter study.

Cancer Imaging 2021 Mar 9;21(1):26. Epub 2021 Mar 9.

Department of Radiology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, 158 Shangtang Road, Hangzhou, 310000, China.

Background: Accurate diagnosis of high-grade branching type intraductal papillary mucinous neoplasms (BD-IPMNs) is challenging in clinical setting. We aimed to construct and validate a nomogram combining clinical characteristics and radiomic features for the preoperative prediction of low and high-grade in BD-IPMNs.

Methods: Two hundred and two patients from three medical centers were enrolled. The high-grade BD-IPMN group comprised patients with high-grade dysplasia and invasive carcinoma in BD-IPMN (n = 50). The training cohort comprised patients from the first medical center (n = 103), and the external independent validation cohorts comprised patients from the second and third medical centers (n = 48 and 51). Within 3 months prior to surgery, all patients were subjected to magnetic resonance examination. The volume of interest was delineated on T1-weighted (T1-w) imaging, T2-weighted (T2-w) imaging, and contrast-enhanced T1-weighted (CET1-w) imaging, respectively, on each tumor slice. Quantitative image features were extracted using MITK software (G.E.). The Mann-Whitney U test or independent-sample t-test, and LASSO regression, were applied for data dimension reduction, after which a radiomic signature was constructed for grade assessment. Based on the training cohort, we developed a combined nomogram model incorporating clinical variables and the radiomic signature. Decision curve analysis (DCA), a receiver operating characteristic curve (ROC), a calibration curve, and the area under the ROC curve (AUC) were used to evaluate the utility of the constructed model based on the external independent validation cohorts.

Results: To predict tumor grade, we developed a nine-feature-combined radiomic signature. For the radiomic signature, the AUC values of high-grade disease were 0.836 in the training cohort, 0.811 in external validation cohort 1, and 0.822 in external validation cohort 2. The CA19-9 level and main pancreatic duct size were identified as independent parameters of high-grade of BD-IPMNs using multivariate logistic regression analysis. The CA19-9 level and main pancreatic duct size were then used to construct the radiomic nomogram. Using the radiomic nomogram, the high-grade disease-associated AUC values were 0.903 (training cohort), 0.884 (external validation cohort 1), and 0.876 (external validation cohort 2). The clinical utility of the developed nomogram was verified using the calibration curve and DCA.

Conclusions: The developed radiomic nomogram model could effectively distinguish high-grade patients with BD-IPMNs preoperatively. This preoperative identification might improve treatment methods and promote personalized therapy in patients with BD-IPMNs.
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http://dx.doi.org/10.1186/s40644-021-00395-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942000PMC
March 2021

Microscopic Invasion of Nerve Is Associated With Aggressive Behaviors in Pancreatic Neuroendocrine Tumors.

Front Oncol 2021 25;11:630316. Epub 2021 Feb 25.

Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Objectives: The role of neural invasion has been reported in cancers. Few studies also showed that neural invasion was related to survival rate in patients with pancreatic neuroendocrine tumor (PNET). The aim of this study is to explore the association between neural invasion and aggressive behaviors in PNET.

Methods: After excluding those patients with biopsy and with missing histological data, a total 197 patients with PNET who underwent surgery were retrospectively analyzed. The demographic data and histological data were obtained. Aggressive behavior was defined based on extra-pancreatic extension including vascular invasion, organ invasion and lymph node metastases. Logistic regression analyses were used to identify risk factor for aggressive behavior. Receiver operating characteristic (ROC) curves were performed to show the performance of nomograms in evaluating aggressive behavior of PNET.

Results: The prevalence of neural invasion in the cohort was 10.1% (n = 20). The prevalence of lymph node metastasis, organ invasion, and vascular invasion in PNET patients with neural invasion was higher than those in patients without neural invasion (p < 0.05). Neural invasion was more common in grade 3 (G3) tumors than G1/G2 (p < 0.01). Tumor size, tumor grade, and neural invasion were independent associated factors of aggressive behavior (p < 0.05) after adjusting for possible cofounders in total tumors and G1/G2 tumors. Two nomograms were developed to predict the aggressive behavior. The area under the ROC curve was 0.84 (95% confidence interval (CI): 0.77-0.90) for total population and was 0.84 (95% CI: 0.78-0.89) for patients with G1/G2 PNET respectively.

Conclusions: Neural invasion is associated with aggressive behavior in PNET. Nomograms based on tumor size, grade and neural invasion show acceptable performances in predicting aggressive behavior in PNET.
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http://dx.doi.org/10.3389/fonc.2021.630316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947608PMC
February 2021

Case Report: Identification of SARS-CoV-2 in Cerebrospinal Fluid by Ultrahigh-Depth Sequencing in a Patient With Coronavirus Disease 2019 and Neurological Dysfunction.

Front Med (Lausanne) 2021 22;8:629828. Epub 2021 Feb 22.

Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

We reported that the complete genome sequence of SARS-Coronavirus-2 (SARS-CoV-2) was obtained from a cerebrospinal fluid (CSF) sample by ultrahigh-depth sequencing. Fourteen days after onset, seizures, maxillofacial convulsions, intractable hiccups and a significant increase in intracranial pressure developed in an adult coronavirus disease 2019 patient. The complete genome sequence of SARS-CoV-2 obtained from the cerebrospinal fluid indicates that SARS-CoV-2 can invade the central nervous system. In future, along with nervous system assessment, the pathogen genome detection and other indicators are needed for studying possible nervous system infection of SARS-CoV-2.
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http://dx.doi.org/10.3389/fmed.2021.629828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937706PMC
February 2021

Neuroanatomical and functional substrates of the greed personality trait.

Brain Struct Funct 2021 May 8;226(4):1269-1280. Epub 2021 Mar 8.

Key Research Base of Humanities and Social Sciences of the Ministry of Education, Academy of Psychology and Behavior, Tianjin Normal University, Tianjin, 300387, China.

Greedy individuals often exhibit more impulsive decision-making and short-sighted behaviors. It has been assumed that altered reward circuitry and prospection network is associated with greed personality trait (GPT). In this study, we first explored the morphological characteristics (i.e., gray matter volume; GMV) of GPT combined with univariate and multivariate pattern analysis (MVPA) approaches. Second, we adopted a revised version of inter-temporal choice task and independently manipulated the amount and delay time of future rewards. Using brain-imaging design, reward- and prospection-related brain activations were assessed and their associations with GPT were further examined. The MVPA results showed that GPT was associated with the GMVs in the right lateral frontal pole cortex, left ventromedial prefrontal cortex, right lateral occipital cortex, and right occipital pole. Additionally, we observed that the amount-relevant brain activations (responding to reward circuitry) in the lateral orbitofrontal cortex were negatively associated with individual's variability in GPT scores, whereas the delay time-relevant brain activations (responding to prospection network system) in the dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, superior parietal lobule, and anterior cingulate cortex were positively associated with individual's variability in GPT scores. These findings not only provide novel insights into the neuroanatomical substrates underlying the human dispositional greed, but also suggest the critical roles of reward and prospection processing on the greed.
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http://dx.doi.org/10.1007/s00429-021-02240-9DOI Listing
May 2021

Establishment of an immunological detection method of fleroxacin by fluorescence-linked immunosorbent assay.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2021 Apr 5;38(4):594-601. Epub 2021 Mar 5.

School of Life Sciences, Zhengzhou University, Zhengzhou, China.

The direct and indirect competitive fluorescence-linked immunosorbent assay (FLISA and icFLISA) incorporating quantum dots (QDs) for the detection of fleroxacin (FLE) was established for the first time in this study. The monoclonal antibody specific for FLE was successfully conjugated with QDs after purification by the caprylic acid-ammonium sulphate method. The limits of detection of FLISA and icFLISA were 0.012 ng/mL and 0.006 ng/mL, respectively; IC were 0.32 ng/mL and 0.19 ng/mL; and the detection ranges were 0.012-24.490 ng/mL and 0.006-16.210 ng/mL. The recovery was 93.8%-112.4% and the coefficient of variation was below 11.75%. The fabricated FLISA and icFLISA are cost-effective, high sensitive and can be an alternative method in the detection of FLE residues.
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http://dx.doi.org/10.1080/19440049.2021.1876251DOI Listing
April 2021

Serum Exosomal miRNA-1226 as Potential Biomarker of Pancreatic Ductal Adenocarcinoma.

Onco Targets Ther 2021 26;14:1441-1451. Epub 2021 Feb 26.

Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People's Republic of China.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality and it is urgent to find biomarkers for early detection of PDAC. Exosomal miRNAs are useful biomarkers for cancer detection. The aims of this study were to investigate the potential role of serum exosomal miRNA in detection of PDAC and to analyze the correlation between the levels of exosome miRNA and the tumor biological behaviors.

Materials And Methods: Thirteen serum samples were collected from five patients with PDACs, three healthy individuals (HIs) and five benign pancreatic lesions (BP) for a high throughput profiling analysis to identify an altered miRNA expression patterns in PDAC. Candidate exosomal miRNAs were filtered based on a second independent cohort that included 17 PDACs and 12 benign pancreatic lesions by quantitative real-time polymerase chain reaction (qRT-PCR). Four miRNAs were selected for miRNA validation as PDAC biomarkers in a subsequent set of samples. The association between candidate exosomal miRNA and tumor behavior (tumor invasion or metastases) was evaluated in 17 PDACs. In vitro studies were performed to evaluate the role of candidate exosomal miRNA on cell viability, apoptosis and cell migration in two PDAC cell lines.

Results: The expression of 11 miRNAs showed same trend between PDAC and BP, and between PDAC and HIs. Six of them were upregulated (miR-203b-5p, miR-342-5p, miR-337-5p, miR-149-5p, miR-877-5p, miR-203a-3p), and five were downregulated (miR-1226-3p, miR-3182, miR-625-3p, miR-624-5p, miR-664a-5p). miR-1226-3p was selected as the candidate exosomal biomarker for the PDAC detection. The expression of serum exosomal miRNA-1226-3p was downregulated in PDACs compared to the BPs (p = 0.025). miR-1226-3p had acceptable performance in predicting [area under the curve (AUC) = 0.74] PDAC. Exosomal miRNA-1226-3p level in PDAC with invasion or metastases was lower than that without invasion or metastases (p = 0.028). Transfection of miRNA-1226-3p significantly inhibited the proliferation of PANC-1 and BXP-3 cells, stimulated cell apoptosis and inhibited cell migration.

Conclusion: Serum exosomal miRNA-1226-3p is a potential biomarker in diagnosing and predicting the tumor invasion or metastases of PDAC.
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http://dx.doi.org/10.2147/OTT.S296816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924134PMC
February 2021

Voxel-based morphometric MRI post-processing and PET/MRI co-registration reveal subtle abnormalities in cingulate epilepsy.

Epilepsy Res 2021 Mar 8;171:106568. Epub 2021 Feb 8.

Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China. Electronic address:

Objective: Diagnostic challenges exist in the presurgical evaluation of patients with magnetic resonance imaging (MRI) negative cingulate epilepsy (CE) because of the heterogeneity in clinical semiology and lack of localizing findings on scalp electroencephalographic (EEG) recordings. We aimed to examine the neuroimaging characteristics in a consecutive cohort of patients with MRI-negative CE with a focus on two image post-processing methods, including the MRI post-processing morphometric analysis program (MAP) and F-fluorodeoxyglucose-positron emission tomography-MRI (PET/MRI) co-registration.

Methods: Included in this retrospective study were patients with MRI-negative CE who met the following criteria: negative on preoperative MRI, invasive EEG (iEEG) confirmed cingulate gyrus-onset seizures, surgical resection of the cingulate gyrus with/without adjacent cortex, and seizure-free for more than 12 months. MAP and PET/MRI co-registration were performed and investigated by comparison to ictal intracranial EEG findings. Other characteristics obtained from scalp EEG, magnetoencephalography (MEG), iEEG, and pathological study were also reported.

Results: Ten patients were included, of which eight were diagnosed with anterior CE, one with middle CE, and one with posterior CE. The semiology included fear, embarrassment, vocalization, ictal pouting, asymmetric tonic posture, hypermotor, and automatism. Scalp EEG revealed unilateral or bilateral frontal-temporal onset. MEG localized the dipoles correctly in one patient (1/10). MAP detected subtle abnormalities in regions concordant with iEEG onset in seven patients (7/10) while PET/MRI co-registration revealed focal concordant hypometabolism in five patients (5/10). Combining MAP with PET/MRI co-registration improved the detection rate to 90 % in this cohort. The pathology was focal cortical dysplasia (FCD), including FCD type IIA in three, type IIB in three, and type I in four.

Conclusion: MAP and PET/MRI co-registration show promising results in identifying subtle FCD abnormalities in CE with negative results on conventional MRI, which can be otherwise challenging. More importantly, a combination of MRI post-processing and PET/MRI co-registration can greatly improve the identification of epileptic abnormalities, which can be used as surgical target. MAP and PET/MRI co-registration should be incorporated into the routine presurgical evaluation.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106568DOI Listing
March 2021

Hematopoietic Stem Cell Niche During Homeostasis, Malignancy, and Bone Marrow Transplantation.

Front Cell Dev Biol 2021 22;9:621214. Epub 2021 Jan 22.

Department of Hematology, National Key Clinical Specialty of Hematology, Yunnan Blood Disease Clinical Medical Center, Yunnan Blood Disease Hospital, The First People's Hospital of Yunnan Province, Kunming, China.

Self-renewal and multidirectional differentiation of hematopoietic stem cells (HSCs) are strictly regulated by numerous cellular components and cytokines in the bone marrow (BM) microenvironment. Several cell types that regulate HSC niche have been identified, including both non-hematopoietic cells and HSC-derived cells. Specific changes in the niche composition can result in hematological malignancies. Furthermore, processes such as homing, proliferation, and differentiation of HSCs are strongly controlled by the BM niche and have been reported to be related to the success of hematopoietic stem cell transplantation (HSCT). Single-cell sequencing and imaging are powerful techniques to study BM microenvironment in hematological malignancies and after HSCT. In this review, we discuss how different components of the BM niche, particularly non-hematopoietic and hematopoietic cells, regulate normal hematopoiesis, and changes in the BM niche in leukemia and after HSCT. We believe that this comprehensive review will provide clues for further research on improving HSCT efficiency and exploring potential therapeutic targets for leukemia.
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http://dx.doi.org/10.3389/fcell.2021.621214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862549PMC
January 2021

The mechanism of 5-aminolevulinic acid photodynamic therapy in promoting endoplasmic reticulum stress in the treatment of HR-HPV-infected HeLa cells.

Photodermatol Photoimmunol Photomed 2021 Jul 8;37(4):348-359. Epub 2021 Feb 8.

Department of Dermatology and Venereology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: 5-aminoketovaleric acid, as a precursor of the strong photosensitizer protoporphyrin IX (PpIX), mainly enters the mitochondria after entering the cell, and the formed PpIX is also mainly localized in the mitochondria. So at present the research on the mechanism of 5-aminoketovalerate photodynamic therapy (ALA-PDT) mainly focuses on its impact on mitochondria. There are few reports on whether ALA-PAT can affect the endoplasmic reticulum and trigger endoplasmic reticulum stress (ERS).

Aims/objectives: Here we investigated the effects of ALA-PDT on endoplasmic reticulum and its underlying mechanisms in high-risk human papillomavirus (HR-HPV) infection.

Materials And Methods: The human cervical cancer cell line HeLa (containing whole genome of HR-HPV18) was treated with ALAPDT, and cell viability, ROS production, the level of Ca2+ in the cytoplasm and apoptosis were evaluated by CCK8, immunofluorescence and flow cytometry, respectively. The protein expression of the markers of ERS and autophagy and CamKKβ-AMPK pathway was examined by western blot.

Results: The results showed that ALA-PDT inhibited cell viability of HeLa cells in vitro; ALA-PDT induced autophagy in HeLa cells ; ALA-PDT induced autophagy via the Ca2+-CamKKβ-AMPK pathway, which could be suppressed by the inhibition of ERS;ALA-PDT induced ERS-specific apoptosis via the activation of caspase 12.

Conclusions: Our study demonstrated that ALA-PDT could exert a killing effect by inducing HeLa cell apoptosis, including endoplasmic reticulum-specific apoptosis. Meanwhile, ERS via the Ca2+ -CamKKβ-AMPK pathway promoted the occurrence of autophagy in HeLa cells. Inhibition of autophagy could increase the apoptosis rate of HeLa cells after ALA-PDT, suggesting that autophagy may be one of the mechanisms of PDT resistance; The Ca2+-CamKKβ-AMPK pathway and autophagy may be targets to improve the killing effect of ALA-PDT in treating HR-HPV infection.
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http://dx.doi.org/10.1111/phpp.12663DOI Listing
July 2021
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