Publications by authors named "Kai Yan"

293 Publications

Biological Utility of Fluorinated Compounds: from Materials Design to Molecular Imaging, Therapeutics and Environmental Remediation.

Chem Rev 2021 Oct 5. Epub 2021 Oct 5.

Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Queensland 4072, Australia.

The applications of fluorinated molecules in bioengineering and nanotechnology are expanding rapidly with the controlled introduction of fluorine being broadly studied due to the unique properties of C-F bonds. This review will focus on the design and utility of C-F containing materials in imaging, therapeutics, and environmental applications with a central theme being the importance of controlling fluorine-fluorine interactions and understanding how such interactions impact biological behavior. Low natural abundance of fluorine is shown to provide sensitivity and background advantages for imaging and detection of a variety of diseases with F magnetic resonance imaging, F positron emission tomography and ultrasound discussed as illustrative examples. The presence of C-F bonds can also be used to tailor membrane permeability and pharmacokinetic properties of drugs and delivery agents for enhanced cell uptake and therapeutics. A key message of this review is that while the promise of C-F containing materials is significant, a subset of highly fluorinated compounds such as per- and polyfluoroalkyl substances (PFAS), have been identified as posing a potential risk to human health. The unique properties of the C-F bond and the significant potential for fluorine-fluorine interactions in PFAS structures necessitate the development of new strategies for facile and efficient environmental removal and remediation. Recent progress in the development of fluorine-containing compounds as molecular imaging and therapeutic agents will be reviewed and their design features contrasted with environmental and health risks for PFAS systems. Finally, present challenges and future directions in the exploitation of the biological aspects of fluorinated systems will be described.
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http://dx.doi.org/10.1021/acs.chemrev.1c00632DOI Listing
October 2021

Recent advance in the discovery of tyrosinase inhibitors from natural sources via separation methods.

J Enzyme Inhib Med Chem 2021 Dec;36(1):2104-2117

Department of Pharmacy, the Second Hospital of Hebei Medical University, Shijiazhuang, China.

Tyrosinase (TYR) inhibitors are in great demand in the food, cosmetic and medical industrials due to their important roles. Therefore, the discovery of high-quality TYR inhibitors is always pursued. Natural products as one of the most important sources of bioactive compounds discovery have been increasingly used for TYR inhibitors screening. However, due to their complex compositions, it is still a great challenge to rapid screening and identification of biologically active components from them. In recent years, with the help of separation technologies and the affinity and intrinsic activity of target enzymes, two advanced approaches including affinity screening and inhibition profiling showed great promises for a successful screening of bioactive compounds from natural sources. This review summarises the recent progress of separation-based methods for TYR inhibitors screening, with an emphasis on the principle, application, advantage, and drawback of each method along with perspectives in the future development of these screening techniques and screened hit compounds.
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http://dx.doi.org/10.1080/14756366.2021.1983559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480707PMC
December 2021

Biomechanical Evaluation of the Transcortical and Transpedicular Trajectories for Pedicle Screw Insertion in Thoracolumbar Fracture Fixation for Ankylosing Spondylitis.

Front Surg 2021 8;8:706597. Epub 2021 Sep 8.

Department of Education, Beijing Jishuitan Hospital, Beijing, China.

Ankylosing spondylitis (AS) is a chronic disorder characterized by an imbalance between bone formation and resorption. Spinal fractures often occur after minor trauma in patients with AS. For thoracolumbar fractures, transpedicular screw (TPS) fixation through the posterior approach has been suggested. The cortical bone trajectory (CBT) technique has also been used to prevent screw pull-out in patients with poor bone quality. The aim of current study was to assess the biomechanical characteristics of the TPS and CBT technique in thoracolumbar AS fracture fixation by finite element analysis. The three-dimensional finite element models of the AS spine were created. The CBT and TPS methods of screw insertion were used in AS spinal fracture models. An intact AS spine model was considered the control. An axial force and torsion in rotation, flexion/extension and lateral flexion were applied in all models in CBT, TPS, and control groups. The AS spine showed similar construct stiffness after posterior fixation by CBT and TPS techniques under axial, rotational, and flexion/extension loading conditions. The TPS technique showed better intact stability under all loading conditions. Similarly, the TPS technique provided superior fracture regional stability against axial and rotational loads than did the CBT technique. The maximum von Mises stresses were 1714.4 ± 129.8 MPa and 1208.7 ± 107.3 MPa ( < 0.001), which occurred in the CBT and TPS groups under compressive loading. The TPS technique provides better biomechanical strength under axial, rotational, flexion/extension, and lateral flexion loading than does the CBT technique. Compared with CBT, TPS is more effective in maintaining the stability of AS thoracolumbar fractures from a finite element analysis perspective.
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http://dx.doi.org/10.3389/fsurg.2021.706597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456994PMC
September 2021

Ginsenoside Rk1 protects human melanocytes from HO‑induced oxidative injury via regulation of the PI3K/AKT/Nrf2/HO‑1 pathway.

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

Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China.

Vitiligo is a cutaneous depigmentation disorder caused by melanocyte injury or aberrant functioning. Oxidative stress (OS) is considered to be a major cause of the onset and progression of vitiligo. Ginsenoside Rk1 (RK1), a major compound isolated from ginseng, has antioxidant activity. However, whether RK1 can protect melanocytes against oxidative injury remains unknown. The aim of the present study was to investigate the potential protective effect of RK1 against OS in the human PIG1 melanocyte cell line induced with hydrogen peroxide (HO), and to explore its underlying mechanism. PIG1 cells were pretreated with RK1 (0, 0.1, 0.2 and 0.4 mM) for 2 h followed by exposure to 1.0 mM HO for 24 h. Cell viability and apoptosis were determined with Cell Counting Kit‑8 and flow cytometry assays, respectively. The activity levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‑Px) were analyzed using ELISA kits. Protein expression levels, including Bax, caspase‑3, Bcl‑2, phosphorylated‑AKT, AKT, nuclear factor erythroid 2‑related factor 2 (Nrf2), heme oxygenase‑1 (HO‑1), cytosolic Nrf2 and nuclear Nrf2, were analyzed using western blot analysis. In addition, the expression and localization of Nrf2 were detected by immunofluorescence. RK1 treatment significantly improved cell viability, reduced the apoptotic rate and increased the activity levels of SOD, CAT and GSH‑Px in the PIG1 cell line exposed to HO. In addition, RK1 treatment notably induced Nrf2 nuclear translocation, increased the protein expression levels of Nrf2 and HO‑1, and the ratio of phosphorylated‑AKT to AKT in the PIG1 cells exposed to HO. Furthermore, LY294002 could reverse the protective effect of RK1 in melanocytes against oxidative injury. These data demonstrated that RK1 protected melanocytes from HO‑induced OS by regulating Nrf2/HO‑1 protein expression, which may provide evidence for the application of RK1 for the treatment of vitiligo.
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http://dx.doi.org/10.3892/mmr.2021.12462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485120PMC
November 2021

Effect of an arbuscular mycorrhizal fungus on maize growth and cadmium migration in a sand column.

Ecotoxicol Environ Saf 2021 Dec 15;225:112782. Epub 2021 Sep 15.

College of Resources and Environment, Yunnan Agricultural University, Kunming 650201, Yunnan, China. Electronic address:

The ecological role of arbuscular mycorrhizal fungi (AMF) on altering cadmium (Cd) migration in polluted soil is still unresolved. The present experiment aimed to clarify whether AMF can reduce Cd loss due to leaching at different Cd concentrations (0, 5, 10, and 15 mg L) with maize as a host plant cultured in a sand column. The effects of the arbuscular mycorrhizal fungus Funneliformis mosseae on the root morphology, exudate content, and Cd uptake by maize and Cd loss due to leaching were investigated. The AMF altered the root morphology and exudate content of the maize, resulting in increases in the root length, volume, surface area, tips and branch number and in the contents of soluble sugars, proteins, and amino acids in the root exudates, and the AMF increased maize biomass and Cd uptake by 22.0-31.0%. Moreover, the AMF significantly increased the contents of total and easily extractable glomalin-related soil protein (GRSP), increased Cd adsorption by sand particles and decreased the Cd concentration in the solution at a depth of 20 cm, resulting in a 67.5-97.2% decrease in the Cd loss due to leaching from the sand column. Furthermore, the root exudate content was very significantly positively correlated with Cd adsorption by the sand particles. Root length was significantly positively correlated with Cd uptake by the maize roots, but the average root diameter was very significantly negatively correlated with Cd uptake by maize. Thus, the AMF altered Cd migration by increasing the contents of GRSP and exudates and root morphology, which contributed to reducing the Cd concentration in the solution and Cd loss due to leaching from the sand column. Taken together, these results indicated that AMF serve an ecological function in reducing Cd loss due to leaching from polluted soil.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112782DOI Listing
December 2021

Mapping the evolving landscape of super-enhancers during cell differentiation.

Genome Biol 2021 09 15;22(1):269. Epub 2021 Sep 15.

Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, 02115, USA.

Background: Super-enhancers are clusters of enhancer elements that play critical roles in the maintenance of cell identity. Current investigations on super-enhancers are centered on the established ones in static cell types. How super-enhancers are established during cell differentiation remains obscure.

Results: Here, by developing an unbiased approach to systematically analyze the evolving landscape of super-enhancers during cell differentiation in multiple lineages, we discover a general trend where super-enhancers emerge through three distinct temporal patterns: conserved, temporally hierarchical, and de novo. The three types of super-enhancers differ further in association patterns in target gene expression, functional enrichment, and 3D chromatin organization, suggesting they may represent distinct structural and functional subtypes. Furthermore, we dissect the enhancer repertoire within temporally hierarchical super-enhancers, and find enhancers that emerge at early and late stages are enriched with distinct transcription factors, suggesting that the temporal order of establishment of elements within super-enhancers may be directed by underlying DNA sequence. CRISPR-mediated deletion of individual enhancers in differentiated cells shows that both the early- and late-emerged enhancers are indispensable for target gene expression, while in undifferentiated cells early enhancers are involved in the regulation of target genes.

Conclusions: In summary, our analysis highlights the heterogeneity of the super-enhancer population and provides new insights to enhancer functions within super-enhancers.
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http://dx.doi.org/10.1186/s13059-021-02485-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442463PMC
September 2021

Biologic Pathways Underlying Prognostic Radiomics Phenotypes from Paired MRI and RNA Sequencing in Glioblastoma.

Radiology 2021 Sep 14:203281. Epub 2021 Sep 14.

From the Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, No. 1068, Xueyuan Ave, Shenzhen 518055, China (Q.S., Y. Zhao, K.Y., H.Z., D.L., Z.C.L.); University of Chinese Academy of Sciences, Beijing, China (Q.S., Z.C.L.); Departments of Neurosurgery/Neuro-oncology (Y.C.) and Medical Imaging (X.L.), Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Departments of Neurosurgery (C.L.) and Radiology (Y. Zou), Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Shenzhen Peng Cheng Laboratory, Shenzhen, China (K.Y.); and National Innovation Center for Advanced Medical Devices, Shenzhen, China (H.Z., D.L., Z.C.L.).

Background The biologic meaning of prognostic radiomics phenotypes remains poorly understood, hampered in part by lack of multicenter reproducible evidence. Purpose To uncover the biologic meaning of individual prognostic radiomics phenotypes in glioblastomas using paired MRI and RNA sequencing data and to validate the reproducibility of the identified radiogenomics linkages externally. Materials and Methods This retrospective multicenter study included four data sets gathered between January 2015 and December 2016. From a radiomics analysis set, a 13-feature radiomics signature was built using preoperative MRI for overall survival prediction. Using a radiogenomics training set with both MRI and RNA sequencing, biologic pathways were enriched and correlated with each of the 13 radiomics phenotypes. Radiomics-correlated key genes were identified to derive a prognostic radiomics gene expression (RadGene) score. The reproducibility of identified pathways and genes was validated with an external test set and a public data set (The Cancer Genome Atlas [TCGA]). A log-rank test was performed to assess prognostic significance. Results A total of 435 patients (mean age, 55 years ± 15 [standard deviation]; 263 men) were enrolled. The radiomics signature was associated with overall survival (hazard ratio [HR], 3.68; 95% CI: 2.08, 6.52; < .001) in the radiomics validation subset. Four types of prognostic radiomics phenotypes were correlated with distinct pathways: immune, proliferative, treatment responsive, and cellular functions (false-discovery rate < 0.10). Thirty radiomics-correlated genes were identified. The prognostic significance of the RadGene score was confirmed in an external test set (HR, 2.02; 95% CI: 1.19, 3.41; = .01) and a TCGA test set (HR, 1.43; 95% CI: 1.001, 2.04; = .048). The radiomics-associated pathways and key genes can be replicated in an external test set. Conclusion Individual radiomics phenotypes on MRI scans predictive of overall survival were driven by distinct key pathways involved in immune regulation, tumor proliferation, treatment responses, and cellular functions in glioblastoma, which could be reproduced externally. © RSNA, 2021
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http://dx.doi.org/10.1148/radiol.2021203281DOI Listing
September 2021

α-Lipoic Acid Alleviates Hepatic Lipid Deposition by Inhibiting FASN Expression via miR-3548 in Rats.

Nutrients 2021 Jul 8;13(7). Epub 2021 Jul 8.

Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.

Excessive liver lipid deposition is a vital risk factor for the development of many diseases. Here, we fed Sprague-Dawley rats with a control or α-lipoic acid-supplemented diet (0.2%) for 5 weeks to elucidate the effects of α-lipoic acid on preventive ability, hepatic lipid metabolism-related gene expression, and the involved regulatory mechanisms. In the current study, α-lipoic acid supplementation lowered plasma triglyceride level and hepatic triglyceride content. Reduced hepatic lipid deposition was closely associated with inhibiting fatty acid-binding protein 1 and fatty acid synthase expression, as well as increasing phosphorylated hormone-sensitive lipase expression at the protein level in α-lipoic acid-exposed rats. Hepatic miRNA sequencing revealed increased expression of miR-3548 targeting the 3'untranslated region of Fasn mRNA, and the direct regulatory link between miRNA-3548 and FASN was verified by dual-luciferase reporter assay. Taken together, α-lipoic acid lowered hepatic lipid accumulation, which involved changes in miRNA-mediated lipogenic genes.
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http://dx.doi.org/10.3390/nu13072331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308747PMC
July 2021

Activating Basal Surface of Palladium by Electronic Modulation via Atomically Dispersed Nitrogen Doping for High-Efficiency Hydrogen Evolution Reaction.

J Phys Chem Lett 2021 Aug 29;12(30):7373-7378. Epub 2021 Jul 29.

School of Physics, Sun Yat-sen University, Guangzhou 510275, China.

Surface doping by atomically dispersed heteroatoms has become one of the most promising strategies for facilitating the catalytic activity of non-noble transition metals to replace platinum-based catalysts in the hydrogen evolution reaction (HER). However, the underlying mechanism for the atomically dispersed heteroatoms to modulate the electronic structure and the HER activity of a metal surface is still ambiguous. Moreover, the active catalytic region is limited by the small fraction of doped atoms, and the remaining basal surface is inactivated. Here, we demonstrate that the nitrogen doping is atomically dispersed on the palladium surface, which can achieve the near-thermoneutral hydrogen adsorption and promote the HER activity of the basal surface. The theoretical modeling reveals that the dispersed nitrogen atoms attract electrons from palladium and downdrift the -band center for accelerating the hydrogen desorption. Our work offers understandings of atomically dispersed nitrogen doping on the surface of transition metals and paves the way for a further optimization of nonprecious-metal HER electrocatalysts.
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http://dx.doi.org/10.1021/acs.jpclett.1c01409DOI Listing
August 2021

Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acetaminophen-induced acute liver failure through activating ERK and IGF-1R/PI3K/AKT signaling pathway.

J Pharmacol Sci 2021 Sep 19;147(1):143-155. Epub 2021 Jun 19.

The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, 330031, PR China. Electronic address:

This study aimed to investigate the therapeutic potential of human umbilical cord mesenchymal stem cells derived exosomes (hUCMSC-Exo) in acute liver failure (ALF) in mice as well as its underlying mechanism. We found that a single tail vein administration of hucMSC-Exo effectively enhanced the survival rate, inhibited apoptosis in hepatocytes, and improved liver function in APAP-induced mouse model of ALF. Furthermore, the deletion of glutathione (GSH) and superoxide dismutase (SOD), generation of malondialdehyde (MDA), and the over production of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP were also inhibited by hucMSC-Exo, indicating that hucMSC-Exo inhibited APAP-induced apoptosis of hepatocytes by reducing oxidative stress. Moreover, hucMSC-Exo significantly down-regulated the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in APAP-treated livers. Western blot showed that hucMSC-Exo significantly promoted the activation of ERK1/2 and IGF-1R/PI3K/AKT signaling pathways in APAP-injured LO2 cells, resulting in the inhibition of apoptosis of LO2 cells. Importantly, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 could reverse the function of hucMSC-Exo on APAP-injured LO2 cells in some extent. Our results suggest that hucMSC-Exo offer antioxidant hepatoprotection against APAP in vitro and in vivo by inhibitiing oxidative stress-induced apoptosis via upregulation of ERK1/2 and PI3K/AKT signaling pathways.
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http://dx.doi.org/10.1016/j.jphs.2021.06.008DOI Listing
September 2021

Intraoral and extraoral approach for surgical treatment of Eagle's syndrome: a retrospective study.

Eur Arch Otorhinolaryngol 2021 Jul 19. Epub 2021 Jul 19.

Department of Otorhinolaryngology, The First Affiliated Hospital of Dalian Medical University, 5 Longbin Road, Development Zone, Dalian, Liaoning, China.

Background And Purpose: Eagle's syndrome is not uncommon in clinical work. Because of its atypical symptoms, it is easy to be misdiagnosed as other diseases, further leading to misdiagnosis and mistreatment. At present, there is no expert consensus or treatment guidelines for the disease. We evaluated the clinical characteristics and postoperative efficacy of 103 patients with Eagle's syndrome based on their clinical symptoms, radiological studies, and physical examination. Through the multicenter clinical study of Tongji Medical College and Dalian Medical University, we found some characteristics of Eagle's syndrome in operation and imaging.

Methods: In total, 103 patients with Eagle's syndrome (treated from January 2010 to January 2020) were retrospectively enrolled. The postoperative curative effect was analyzed by three surgical methods: styloid process resection through the external cervical approach (styloid process could not be touched through the mouth or could be touched under the jaw or when the CT scan showed that the inclination angle was not large), tonsillectomy + styloidectomy, and preservation of the tonsil for styloidectomy (the styloid process bone could be touched directly during intraoral palpation or in whom the distal part of the styloid process could not be directly touched, but the CT scan showed that the bone inclined toward the oropharynx and its distal part was relatively close to the oropharynx cavity; whether tonsillectomy was performed depended on whether the patient's tonsil was too large to affect the surgical incision). According to the Quality of Well-Being Scale (QWB), we calculated the W value of the scale before operation and 30 days, 3 months, 6 months and 12 months after operation, and compared the W value of each group.

Results: The average length of the styloid process was 33 mm (range 25-61 mm). The patients were followed up for 12-36 months (average 15 months). Of the 103 patients, 21 underwent styloid process resection through the external cervical approach, 49 underwent tonsillectomy and styloidectomy, and 33 underwent styloidectomy with preservation of the tonsil. The treatment cured 48 (46%) cases, was effective in 35 (34%) and was ineffective in 20 (20%). The R language 3.6.3 software was used to perform the nonparametric rank sum test, differences in characteristics between groups were analyzed using the Kruskal-Wallis test with Dunn post hoc tests ( R package FSA) for categorical variables, and there was no significant difference between the three types of operations (H = 0.491, P = 0.782). QWB showed that the quality of life after operation was improved compared with that before operation.

Conclusions: Operation is an effective method for treating Eagle's syndrome. There were no significant differences between the effects of the intraoral and external cervical approaches. Imaging examination-especially CT scanning and 3D reconstruction of the styloid process-is very helpful for diagnosis, but not an absolute criterion for the selection of surgery protocol.
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http://dx.doi.org/10.1007/s00405-021-06914-2DOI Listing
July 2021

Selective Production of Phenol-Rich Bio-Oil From Corn Straw Waste by Direct Microwave Pyrolysis Without Extra Catalyst.

Front Chem 2021 1;9:700887. Epub 2021 Jul 1.

Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, School of Environmental Science and Engineering, Sun Yat-sen University, Guangzhou, China.

We report a sustainable strategy to cleanly address biomass waste with high-value utilization. Phenol-rich bio-oil is selectively produced by direct pyrolysis of biomass waste corn straw (CS) without use of any catalyst in a microwave device. The effects of temperature and power on the yield and composition of pyrolysis products are investigated in detail. Under microwave irradiation, a very fast pyrolysis rate and bio-oil yield as high as 46.7 wt.% were obtained, which were competitive with most of the previous results. GC-MS analysis showed that temperature and power (heating rate) had great influences on the yield of bio-oil and the selectivity of phenolic compounds. The optimal selectivity of phenols in bio-oil was 49.4 area% by adjusting the operating parameters. Besides, we have made detailed statistics on the change trend of some components and different phenols in bio-oil and given the law and reason of their change with temperature and power. The formed highly active biochar from CS with high content of potassium (1.34 wt.%) is responsible for the improvement of phenol-rich oils. This study offers a sustainable way to fully utilize biomass waste and promote the achievement of carbon neutrality.
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http://dx.doi.org/10.3389/fchem.2021.700887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280759PMC
July 2021

Major and trace-element geochemistry of Late Cretaceous clastic rocks in the Jitai Basin, southeast China.

Sci Rep 2021 Jul 5;11(1):13846. Epub 2021 Jul 5.

902 Geological Brigade of Jiangxi Bureau of Exploration and Development for Geology and Mineral Resources, Xinyu, 338099, Jiangxi, China.

Major, trace and rare earth element (REE) geochemistry of the late Cretaceous lower Zhoutian Formation from the Jitai Basin of Southeast China were measured by inductively coupled plasma mass spectrometry (ICP-MS) analysis to infer the provenance of the sediments and to reconstruct the palaeoenvironment and palaeoclimate. The wide range of Sr/Cu ratios point to a fluctuating palaeoclimate, and the negative correlation between the FeO/MnO and AlO/MgO ratios and the Sr/Cu ratio indicates that the late Cretaceous climate during the lower Zhoutian Formation in the Jitai Basin can be divided into two parts. The lower part experienced two cooling periods, whilst the upper part was dominated by warm-humid climate. Mostly corresponding trends of the B/Ga, Sr/Ba and Sr/Cu ratios show that the salinity changed consistently with the late Cretaceous climate during the lower Zhoutian Formation in the Jitai Basin. During the lower part, the salinity changed from salt water to fresh/brackish water. In the upper part, water was mainly fresh/brackish, and there were many changes from fresh/brackish water to salt water. The relatively stable Ni/Co, V/Cr, V/(V + Ni) and Ce/Ce* data indicate a long period of oxic conditions. The La-Th-Sc, Th-Sc-Zr/10 and La/Th-Hf data of the silt- and sandstones of the lower Zhoutian Formation show that its provenance was mainly a mixture of felsic upper crust sediments and older sedimentary rocks.
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http://dx.doi.org/10.1038/s41598-021-93125-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257612PMC
July 2021

Combining Metagenomic Sequencing With Whole Exome Sequencing to Optimize Clinical Strategies in Neonates With a Suspected Central Nervous System Infection.

Front Cell Infect Microbiol 2021 18;11:671109. Epub 2021 Jun 18.

Department of Neonatology, Children's Hospital, Fudan University, Shanghai, China.

Objectives: Central nervous system (CNS) infection has a high incidence and mortality in neonates, but conventional tests are time-consuming and have a low sensitivity. Some rare genetic diseases may have some similar clinical manifestations as CNS infection. Therefore, we aimed to evaluate the performance of metagenomic next-generation sequencing (mNGS) in diagnosing neonatal CNS infection and to explore the etiology of neonatal suspected CNS infection by combining mNGS with whole exome sequencing (WES).

Methods: We prospectively enrolled neonates with a suspected CNS infection who were admitted to the neonatal intensive care unit(NICU) from September 1, 2019, to May 31, 2020. Cerebrospinal fluid (CSF) samples collected from all patients were tested by using conventional methods and mNGS. For patients with a confirmed CNS infection and patients with an unclear clinical diagnosis, WES was performed on blood samples.

Results: Eighty-eight neonatal patients were enrolled, and 101 CSF samples were collected. Fourty-three blood samples were collected for WES. mNGS showed a sample diagnostic yield of 19.8% (20/101) compared to 4.95% (5/101) for the conventional methods. In the empirical treatment group, the detection rate of mNGS was significantly higher than that of conventional methods [27% vs. 6.3%, p=0.002]. Among the 88 patients, 15 patients were etiologically diagnosed by mNGS alone, five patients were etiologically identified by WES alone, and one patient was diagnosed by both mNGS and WES. Twelve of 13 diagnoses based solely on mNGS had a likely clinical effect. Six patients diagnosed by WES also experienced clinical effect.

Conclusions: For patients with a suspected CNS infections, mNGS combined with WES might significantly improve the diagnostic rate of the etiology and effectively guide clinical strategies.
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http://dx.doi.org/10.3389/fcimb.2021.671109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253254PMC
July 2021

Antibody heavy chain CDR3 length-dependent usage of human IGHJ4 and IGHJ6 germline genes.

Antib Ther 2021 Apr 14;4(2):101-108. Epub 2021 Jun 14.

Biotherapeutics, Biocytogen Pharmaceuticals (Beijing) Co. Ltd., #12 Baoshennan St, Daxing District, Beijing 102629, China.

Therapeutic antibody discovery using synthetic diversity has been proved productive, especially for target proteins not suitable for traditional animal immunization-based antibody discovery approaches. Recently, many lines of evidences suggest that the quality of synthetic diversity design limits the development success of synthetic antibody hits. The aim of our study is to understand the quality limitation and to properly address the challenges with a better design. Using VH3-23 as a model framework, we observed and quantitatively mapped CDR-H3 loop length-dependent usage of human IGHJ4 and IGHJ6 germline genes in the natural human immune repertoire. Skewed usage of DH2-JH6 and DH3-JH6 rearrangements was quantitatively determined in a CDR-H3 length-dependent manner in natural human antibodies with long CDR-H3 loops. Structural modeling suggests choices of JH help to stabilize antibody CDR-H3 loop and JH only partially contributes to the paratope. Our observations shed light on the design of next-generation synthetic diversity with improved probability of success.
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http://dx.doi.org/10.1093/abt/tbab010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237691PMC
April 2021

Amplitude of low-frequency fluctuation may be an early predictor of delayed motor development due to neonatal hyperbilirubinemia: a fMRI study.

Transl Pediatr 2021 May;10(5):1271-1284

Department of Neonatology, Children' Hospital of Fudan University, Shanghai, China.

Background: Acute bilirubin encephalopathy or kernicterus is the worst consequence of brain damage caused by the elevation of total unbound serum bilirubin (TSB) in neonates. The present study aimed to visualize the characteristic brain regions of neonates with hyperbilirubinemia (HB) using functional magnetic resonance imaging (fMRI) and to measure the amplitude of low-frequency fluctuation (ALFF) values.

Methods: This was a prospective cohort study, which included newborns with HB who were hospitalized at the Children's Hospital of Fudan University. The control group included neonates admitted with neonatal simple wet lung or pneumonia without neurological disease or brain injury. Newborns were divided into a severe hyperbilirubinemia group (SHB), moderate HB group, and control group based on TSB levels. The newborns completed routine MRI combined with fMRI scans and brainstem auditory evoked potentials (BAEPs) during their hospitalization.

Results: A total of 251 newborns were included in this study. There were 45 patients in the SHB group, 65 in the HB group, and 141 in the control group. The average ALFF value in the basal ganglia region in the SHB group was the highest, which was greater than that in the HB and control groups (P<0.001). The ALFF increased with an increase in TSB concentration. Based on the results of the Bayley Scales of infant development assessment, we further found that the most significant difference in ALFF remained in the basal ganglia region between newborns with motor development scores above 70 (including 70) and below 70. Correlation analysis revealed a strong negative correlation between motor development scores and ALFF (r=-0.691, P<0.001). When ALFF alone was used to predict motor development, the sensitivity was 89%. When ALFF was combined with TSB and BEAP results, the area under the ROC curve was the largest (AUC =0.85). The sensitivity and specificity of the model were 67.86% and 90.77%, respectively.

Conclusions: The ALFF value may be able to serve as an early imaging biomarker and has a greater sensitivity than TSB or BAEP results in predicting long-term motor development (18 m) in HB.
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http://dx.doi.org/10.21037/tp-20-447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192981PMC
May 2021

The association between hypertension and nonalcoholic fatty liver disease (NAFLD): literature evidence and systems biology analysis.

Bioengineered 2021 12;12(1):2187-2202

School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

Nonalcoholic fatty liver disease (NAFLD) has become a major public health issue as its progression increases risks of multisystem morbidity and mortality. Recent evidence indicates a more complex relationship between hypertension and NAFLD than previously thought. In this study, a comprehensive literature search was used to gather information supporting the comorbidity phenomenon of hypertension and NAFLD. Then, systems biology approach was applied to identify the potential genes and mechanisms simultaneously associated with hypertension and NAFLD. With the help of protein-protein interaction network-based algorithm, we found that the distance between hypertension and NAFLD was much less than random ones. Sixty-four shared genes of hypertension and NAFLD modules were identified as core genes. Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis indicated that some inflammatory, metabolic and endocrine signals were related to the potential biological functions of core genes. More importantly, drugs used to treat cardiovascular diseases, hypertension, hyperlipidemia, inflammatory diseases and depression could be potential therapeutics against hypertension-NAFLD co-occurrence. After analyzing public OMICs data, ALDH1A1 was identified as a potential therapeutic target, without being affected by reverse causality. These findings give a clue for the potential mechanisms of comorbidity of hypertension and NAFLD and highlight the multiple target-therapeutic strategy of NAFLD for future clinical research.
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http://dx.doi.org/10.1080/21655979.2021.1933302DOI Listing
December 2021

Overdosage of Gene Associated With Annular Pancreas Detected in Neonate Patients With 17q12 Duplication.

Front Genet 2021 7;12:615072. Epub 2021 May 7.

Center for Molecular Medicine, Children's Hospital of Fudan University, National Children's Medical Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

The annular pancreas (AP) is a congenital anomaly of the pancreas that can cause acute abdominal pain and vomiting after birth. However, the genetic cause of AP is still unknown, and no study has reported AP in patients with 17q12 duplication. This study retrospectively analyzed the next-generation sequencing (NGS) data of individuals from January 2016 to June 2020 for 17q12 duplication. To identify the function of the key gene of in the 17q12 duplication region, human mRNA was microinjected into LiPan zebrafish transgenic embryos. A total of 19 cases of 17q12 duplication were confirmed. AP was diagnosed during exploratory laparotomy in four patients (21.1%). The other common features of 17q12 duplication included intellectual disability (50%), gross motor delay (50%), and seizures/epilepsy (31.58%). The ratio of the abnormal pancreas in zebrafish was significantly higher in the overexpression models. In conclusion, we first reported AP in patients with duplication of the 17q12 region, resulting in the phenotype of 17q12 duplication syndrome. Furthermore, our zebrafish studies verified the role of the gene in pancreatic development.
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http://dx.doi.org/10.3389/fgene.2021.615072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138176PMC
May 2021

Novel deep intronic and frameshift mutations causing a TRIP11-related disorder.

Am J Med Genet A 2021 08 20;185(8):2482-2487. Epub 2021 May 20.

Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.

Mutations of the thyroid hormone receptor interactor 11 gene (TRIP11, OMIM: 604505) at 14q32.12 have been associated with the autosomal recessive achondrogenesis type IA (ACG1A, OMIM: 200600) or osteochondrodysplasia (ODCD, OMIM: 184260). In this clinical report of a Chinese family, the mother had two consecutive pregnancies with similar aberrant phenotypes in the fetuses showing severe limb shortening. Whole exome sequencing (WES) of DNA from the second fetus identified a heterozygous frameshift mutation (NM_004239: c.3852delT) of TRIP11. Although this was consistent with the fetal clinical phenotypes, initial review of the WES results implied another novel mutation. To test this, we used high-precision clinical exome sequencing (HPCES) and found a mutation in Intron 18 of TRIP11 (c.5457+77T>G). Moreover, the sequencing depth of this mutation was only 3× that of WES compared with 161× that by HPCES. To ascertain the pathogenesis of the mutation (c.5457+77T>G), RT-PCR conducted using the parents' blood samples showed a 77-bp intronic sequence in the transcripts, which might have encoded for a shortened protein because of early termination due to code shifting. Our study furthers current understanding of deep intron function and provides a novel diagnostic method of deep intragenic mutations in families having two or more consecutive pregnancies with similar aberrant fetal phenotypes.
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http://dx.doi.org/10.1002/ajmg.a.62260DOI Listing
August 2021

Biomass waste-derived porous carbon efficient for simultaneous removal of chlortetracycline and hexavalent chromium.

iScience 2021 May 12;24(5):102421. Epub 2021 Apr 12.

Instrumentation Lab, Lakehead University, Thunder Bay, ON P7B5E1, Canada.

The simultaneous removal of mixed containments of antibiotics and heavy metals is still a big challenge in wastewater treatment. Herein, we report the successful synthesis of N-doped porous carbon (abbreviated as NC) from straw waste through the Maillard reaction to activate sp-sp conversion efficient for the simultaneous removal of chlortetracycline (CTC) and hexavalent chromium (Cr(VI)). In 200 min, 96.9% of Cr(VI) was reduced into Cr(III) and 93.1% of CTC was oxidatively degraded. Reactive substances (e.g., h, e, ⋅OH, and ⋅O ) were verified for the photocatalytic reactions. Besides, the possible degradation intermediates of CTC were analyzed with ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS), and the mechanism of photocatalytic degradation of CTC was then proposed. The synthesized bifunctional NC materials could also be applied for the similar system; this will open the door for promising practical applications.
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http://dx.doi.org/10.1016/j.isci.2021.102421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105648PMC
May 2021

Application of Full-Spectrum Rapid Clinical Genome Sequencing Improves Diagnostic Rate and Clinical Outcomes in Critically Ill Infants in the China Neonatal Genomes Project.

Crit Care Med 2021 10;49(10):1674-1683

Center for Molecular Medicine, Children's Hospital of Fudan University, Shanghai, China.

Objectives: To determine the diagnostic and clinical utility of trio-rapid genome sequencing in critically ill infants.

Design: In this prospective study, samples from critically ill infants were analyzed using both proband-only clinical exome sequencing and trio-rapid genome sequencing (proband and biological parents). The study occurred between April 2019 and December 2019.

Setting: Thirteen member hospitals of the China Neonatal Genomes Project spanning 10 provinces were involved.

Participants: Critically ill infants (n = 202), from birth up until 13 months of life were enrolled based on eligibility criteria (e.g., CNS anomaly, complex congenital heart disease, evidence of metabolic disease, recurrent severe infection, suspected immune deficiency, and multiple malformations).

Interventions: None.

Measurements And Main Results: Of the 202 participants, neuromuscular (45%), respiratory (22%), and immunologic/infectious (18%) were the most commonly observed phenotypes. The diagnostic yield of trio-rapid genome sequencing was higher than that of proband-only clinical exome sequencing (36.6% [95% CI, 30.1-43.7%] vs 20.3% [95% CI, 15.1-26.6%], respectively; p = 0.0004), and the average turnaround time for trio-rapid genome sequencing (median: 7 d) was faster than that of proband-only clinical exome sequencing (median: 20 d) (p < 2.2 × 10-16). The metagenomic analysis identified pathogenic or likely pathogenic microbes in six infants with symptoms of sepsis, and these results guided the antibiotic treatment strategy. Sixteen infants (21.6%) experienced a change in clinical management following trio-rapid genome sequencing diagnosis, and 24 infants (32.4%) were referred to a new subspecialist.

Conclusions: Trio-rapid genome sequencing provided higher diagnostic yield in a shorter period of time in this cohort of critically ill infants compared with proband-only clinical exome sequencing. Precise and fast molecular diagnosis can alter medical management and positively impact patient outcomes.
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http://dx.doi.org/10.1097/CCM.0000000000005052DOI Listing
October 2021

Time Distributions of Common Respiratory Pathogens Under the Spread of SARS-CoV-2 Among Children in Xiamen, China.

Front Pediatr 2021 12;9:584874. Epub 2021 Apr 12.

Xiamen Key Laboratory of Neonatal Diseases, Xiamen Children's Hospital (Children's Hospital of Fudan University Xiamen Branch), Xiamen, China.

The aim of this study was to observe the effect of COVID-19 prevention and control measures on the transmission of common respiratory viruses in a pediatric population. This was a retrospective observational study. The study population was selected from children with respiratory diseases who attended Xiamen Children's Hospital from January 1, 2018 to January 31, 2021. All children were screened for influenza virus, parainfluenza virus, respiratory syncytial virus (RSV), adenovirus, and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The changes in respiratory virus detection rates before and after the SARS-CoV-2 intervention were analyzed using an interrupted time-series model. Polynomial curve fitting was also used to predict future short-term trends in respiratory virus detection. A total of 56,859 children were seen at Xiamen Children's Hospital from January 1, 2018 to Jan 31, 2021, of which 32,120 were tested for respiratory viruses via pharyngeal swabs. The overall positive detection rates of the four respiratory viral infections decreased significantly ( = 0.0017) after the implementation of the quarantine and school suspension measures in January 2020. Among them, the detection rate of RSV decreased most significantly ( = 0.008), and although there was no statistically significant difference in the detection rates of the influenza virus, parainfluenza virus, and adenovirus, a downward trend in the graph was observed. The positive detection rates of RSV in the 0-1-, 1-3-, and 3-7-year-old groups all decreased significantly ( = 0.035, 0.016, and 0.038, respectively). The change in the positive detection rate of RSV was relatively stable in the 7-18-year-old group. A total of 10,496 samples were tested for SARS-CoV-2, and no positive cases were reported. The combination of preventive and control measures for COVID-19 reduced the detection rate of four common respiratory viruses, with the greatest impact on RSV. If prevention and control measures continue to be maintained, the overall detection rate or absolute number of detections for the four respiratory viruses will remain low in the short term. However, this trend is likely to vary with the changes in measures.
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http://dx.doi.org/10.3389/fped.2021.584874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075055PMC
April 2021

Synergistic impact of resection margin and microscopic vascular invasion for patients with HBV-related intrahepatic cholangiocarcinoma.

Expert Rev Gastroenterol Hepatol 2021 May 25;15(5):575-582. Epub 2021 Apr 25.

Department of Hepatic Surgery V, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China.

Objectives: The resection margin (RM) status and microscopic vascular invasion (MVI) are known prognostic factors for intrahepatic cholangiocarcinoma (ICC). An enhanced understanding of their impact on long-term prognosis is required to improve oncological outcomes.

Methods: A total of 711 consecutive patients who underwent curative liver resection for hepatitis B virus-related ICC were retrospectively analyzed. The different impact of the RM status (narrow, <1 cm, or wide, ≥1 cm) and MVI (positive, +, or negative, -) on overall survival (OS) and recurrence-free survival (RFS) were analyzed.

Results: The 1-, 3-, and 5-year OS rates were 67.6%, 42.5%, and 33.2% in wide RM & MVI (-), 58.0%, 36.1%, and 26.5% in narrow RM & MVI (-), 51.0%, 27.0%, and 24.3% in wide RM & MVI (+), and 39.0%, 20.4% and 14.3% in narrow RM & MVI (+) ( < 0.001). Multivariate analysis showed that RM & MVI were independent risk factors for the OS and RFS.

Conclusion: Combined analysis of RM and MVI can better stratify the risks of postoperative death and recurrence in patients with HBV-related ICC, which may help subsequent adjuvant therapy and closer follow-up.
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http://dx.doi.org/10.1080/17474124.2021.1913053DOI Listing
May 2021

LncRNA XIST upregulates TRIM25 via negatively regulating miR-192 in hepatitis B virus-related hepatocellular carcinoma.

Mol Med 2021 04 15;27(1):41. Epub 2021 Apr 15.

Department of Interventional Radiology, Huaian Hospital of Huai'an City, No. 161 Zhenhuailou East Road, Huai'an City, 223200, Jiangsu Province, People's Republic of China.

Background: Long non-coding RNA (lncRNA) XIST has been implicated in the progression of a variety of tumor diseases. The purpose of this study was to explore the molecular role of lncRNA XIST in human hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Methods: The expression levels of lncRNA XIST, miR-192 and TRIM25 in HBV-related HCC tissues and HepG2.2.15 cells were detected by qRT-PCR. Biological information and luciferin gene reporter assay were performed to detect the interaction among lncRNA XIST, miR-192 and TRIM25. CCk-8 assay, wound healing assay and colony formation assay were conducted to detect the proliferation and migration ability of HepG2.2.15 cells.

Results: qRT-PCR results showed that the expression levels of lncRNA XIST were remarkably increased in HBV-related HCC tissues and HepG2.2.15 cells. In addition, miR-192 was a direct target gene of lncRNA XIST, and the expression of miR-192 and lncRNA XIST were negatively correlated. Moreover, overexpression of miR-192 observably inhibited the proliferation and migration of HCC cells, while overexpression of lncRNA XIST showed an opposite effect. Furthermore, TRIM25 was a direct target of miR-192, and lncRNA XIST could up-regulate the expression of TRIM25 by targeting miR-192.

Conclusion: LncRNA XIST could up-regulate the expression of TRIM25 by targeting and binding to miR-192, thus accelerating the occurrence and development of HCC.
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http://dx.doi.org/10.1186/s10020-021-00278-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050905PMC
April 2021

Short-term developmental outcomes in neonates born to mothers with COVID-19 from Wuhan, China.

World J Pediatr 2021 06 12;17(3):253-262. Epub 2021 Apr 12.

National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China.

Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging disease. The consequences of SARS-CoV-2 exposure in infants remain unknown. Therefore, this study aims to investigate whether neonates born to mothers with COVID-19 have adverse brain development.

Methods: This multicenter observational study was conducted at two designated maternal and children's hospitals in Hubei Province, mainland China from February 1, 2020 to May 15, 2020. Neonates born to mothers with COVID-19 were enrolled. Brain magnetic resonance imaging (MRI) findings, and volumes of grey and white matters, and physical growth parameters were observed at 44 weeks corrected gestational age.

Results: Of 72 neonates born to mothers with COVID-19, 8 (11%) were diagnosed with COVID-19, 8 (11%) were critically ill, and no deaths were reported. Among the eight neonates that underwent brain MRI at corrected gestational age of 44 weeks, five neonates were diagnosed with COVID-19. Among these five neonates, three presented abnormal MRI findings including abnormal signal in white matter and delayed myelination in newborn 2, delayed myelination and brain dysplasia in newborn 3, and abnormal signal in the bilateral periventricular in newborn 5. The other three neonates without COVID-19 presented no significantly changes of brain MRI findings and the volumes of grey matter and white matter compared to those of healthy newborns at the equivalent age (P > 0.05). Physical growth parameters for weight, length, and head circumference at gestational age of 44 weeks were all above the 3rd percentile for all neonates.

Conclusions: Some of the neonates born to mothers with COVID-19 had abnormal brain MRI findings but these neonates did not appear to have poor physical growth. These findings may provide the information on the follow-up schedule on the neonates exposed to SARS-CoV-2, but further study is required to evaluate the association between the abnormal MRI findings and the exposure to SARS-CoV-2.
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http://dx.doi.org/10.1007/s12519-021-00426-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039812PMC
June 2021

Association between programmed cell death ligand 1 expression and thyroid cancer: A meta-analysis.

Medicine (Baltimore) 2021 Apr;100(14):e25315

Department of Nuclear Medicine.

Background: Programmed cell death ligand 1 (PD-L1), which is highly expressed in a variety of malignant tumors, is closely related to clinicopathological features and prognosis. However, there are few studies on the potential effects of PD-L1 on thyroid carcinoma, the incidence of which has shown an upward trend worldwide. This study aimed to explore the association between PD-L1 expression and clinicopathological features and prognosis of thyroid cancer.

Methods: An elaborate retrieval was performed using Medline, PubMed, Cochrane Library, EMBASE, Web of Science, WanFang databases, and China National Knowledge Infrastructure to determine the association between PD-L1 expression and disease-free survival (DFS), overall survival (OS), and clinicopathological features in patients with thyroid cancer. Study selection, data extraction, risk assessment, and data synthesis were performed independently by 2 reviewers. In this meta-analysis, RevMan 5.3 and Stata 15.1 were used for bias risk assessment and data synthesis.

Results: After a detailed search, 2546 cases reported in 13 articles were included in this meta-analysis. The outcomes revealed that high expression of PD-L1 in patients with thyroid cancer was associated with poor DFS (hazard ratio [HR] = 3.37, 95% confidence interval [CI] 2.54-4.48, P < .00001) and OS (HR = 2.52, 95% CI: 1.20-5.32, P = .01). High PD-L1 expression was associated with tumor size ≥2 cm, tumor recurrence, extrathyroidal extension, concurrent thyroiditis, unifocal tumor, and absence of psammoma body (P < .05). Subgroup analysis showed that positive expression of PD-L1 was related to poor prognosis for DFS of non-medullary thyroid carcinoma, and the overexpression of PD-L1 in differentiated thyroid carcinoma (DTC) was related to tumor recurrence, concurrent thyroiditis, extrathyroidal extension, unifocal DTC, late stage DTC, and BRAFV600E mutation in DTC.

Conclusion: PD-L1 is a significant predictor of prognosis and malignancy of thyroid cancer (especially DTC), and PD-L1 inhibitors may be a promising therapeutic option for refractory thyroid cancer in the future.
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http://dx.doi.org/10.1097/MD.0000000000025315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036129PMC
April 2021

Simultaneous Determination of Typical Chlorinated, Oxygenated, and European Union Priority Polycyclic Aromatic Hydrocarbons in Milk Samples and Milk Powders.

J Agric Food Chem 2021 Apr 29;69(13):3923-3931. Epub 2021 Mar 29.

Department of Food Science and Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

An increasing number of studies have suggested that PAH contamination in dairy products demands high concern. This study established an efficient determination method for the European Union 15 + 1 PAHs and four PAH derivatives in dairy samples using a QuEChERS method coupled with GC-QqQ-MS. The optimized method obtained a recovery of 63.38-109.17% with a precision of 3.82-15.62%, and the limit of detection and limit of quantification were 0.08-0.78 and 0.27-2.59 μg/kg, respectively. The validated method was then successfully applied to identify the 20 PAHs in 82 dairy samples, including 43 commercial milk samples and 39 milk powders. The total PAH concentrations ranged from 2.37 to 11.83 μg/kg, and benzo[]pyrene was only quantified in one milk and one milk powder sample at 0.35 and 0.42 μg/kg, respectively. The concentrations of PAH4 in milk samples and milk powders were not quantified (nq)-3.99 and nq-4.51 μg/kg, respectively. The results confirmed the appreciable occurrence of PAHs in dairy products, especially in infant formula. The data in this study provide a scientific basis for assessment on origin tracing, dietary exposure, and health risk of PAHs and their derivatives.
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http://dx.doi.org/10.1021/acs.jafc.1c00283DOI Listing
April 2021

Effects of SARS-CoV-2 infection on neuroimaging and neurobehavior in neonates.

World J Pediatr 2021 04 19;17(2):171-179. Epub 2021 Mar 19.

Department of Neonatology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: We collected neonatal neurological, clinical, and imaging data to study the neurological manifestations and imaging characteristics of neonates with coronavirus disease 2019 (COVID-19).

Methods: This case-control study included newborns diagnosed with COVID-19 in Wuhan, China from January 2020 to July 2020. All included newborns had complete neurological evaluations and head magnetic resonance imaging. We normalized the extracted T2-weighted imaging data to a standard neonate template space, and segmented them into gray matter, white matter, and cerebrospinal fluid. The comparison of gray matter volume was conducted between the two groups.

Results: A total of five neonates with COVID-19 were included in this study. The median reflex scores were 2 points lower in the infected group than in the control group (P = 0.0094), and the median orientation and behavior scores were 2.5 points lower in the infected group than in the control group (P = 0.0008). There were also significant differences between the two groups in the total scale score (P = 0.0426). The caudate nucleus, parahippocampal gyrus, and thalamus had the strongest correlations with the Hammersmith neonatal neurologic examination (HNNE) score, and the absolute correlation coefficients between the gray matter volumes and each part of the HNNE score were all almost greater than 0.5.

Conclusions: We first compared the neurological performance of neonates with and without COVID-19 by quantitative neuroimaging and neurological examination methods. Considering the limited numbers of patients, more studies focusing on the structural or functional aspects of the virus in the central nervous system in different age groups will be carried out in the future.
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http://dx.doi.org/10.1007/s12519-021-00423-2DOI Listing
April 2021

Insights into the stabilization of landfill by assessing the diversity and dynamic succession of bacterial community and its associated bio-metabolic process.

Sci Total Environ 2021 May 30;768:145466. Epub 2021 Jan 30.

Qingdao MSW Management & Treatment Co. Ltd., Qingdao, China.

The distribution of bacterial community in an actual landfill was analyzed and the bioprocess involved in refuse degradation was clarified. The results showed that the degradation degree of refuse showed great differences with the landfill age, in which the contents of organic matter (OM) and total Kjeldahl nitrogen (TKN) in refuse as well as the chemical oxygen demand (COD) in leachate presented decreasing trends with increasing landfill age. The diversity of bacterial community increased first and then decreased with increasing landfill age. The main bacterial phyla involved in refuse degradation were Proteobacteria, Firmicutes and Bacteroidetes, among which, Proteobacteria had an absolute advantage with a relative abundance ranging of 66-78%. With increasing landfill age, the abundance of Firmicutes decreased gradually, while that of Bacteroidetes increased. Pseudomonas, Thiopseudomonas, Psychrobacter and Desemzia were the main genera. The distribution of bacterial community in samples with landfill ages of 0-1 and 1-3 years were greatly influenced by TKN and pH, respectively. Amino acid and carbohydrate metabolism were the main biological pathways according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the biodegradation of xenobiotics as well as terpenoids and polyketides also accounted relatively high frequencies in the landfill. These results provide a better understanding of landfill microbiology and bioprocesses for landfill stabilization.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145466DOI Listing
May 2021

Author Correction: Transcription factor competition at the γ-globin promoters controls hemoglobin switching.

Nat Genet 2021 Apr;53(4):586

Cancer and Blood Disorders Center, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1038/s41588-021-00834-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189157PMC
April 2021
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