Publications by authors named "Jun Ye"

653 Publications

Prediction of prokaryotic transposases from protein features with machine learning approaches.

Microb Genom 2021 Jul;7(7)

Wenzhou Key Laboratory of Emergency, Critical Care, and Disaster Medicine, Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China.

Identification of prokaryotic transposases (Tnps) not only gives insight into the spread of antibiotic resistance and virulence but the process of DNA movement. This study aimed to develop a classifier for predicting Tnps in bacteria and archaea using machine learning (ML) approaches. We extracted a total of 2751 protein features from the training dataset including 14852 Tnps and 14852 controls, and selected 75 features as predictive signatures using the combined mutual information and least absolute shrinkage and selection operator algorithms. By aggregating these signatures, an ensemble classifier that integrated a collection of individual ML-based classifiers, was developed to identify Tnps. Further validation revealed that this classifier achieved good performance with an average AUC of 0.955, and met or exceeded other common methods. Based on this ensemble classifier, a stand-alone command-line tool designated TnpDiscovery was established to maximize the convenience for bioinformaticians and experimental researchers toward Tnp prediction. This study demonstrates the effectiveness of ML approaches in identifying Tnps, facilitating the discovery of novel Tnps in the future.
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http://dx.doi.org/10.1099/mgen.0.000611DOI Listing
July 2021

Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China.

Front Genet 2021 7;12:702374. Epub 2021 Jul 7.

Department of Pediatric Endocrinology and Genetic, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: To characterize the phenotypic and genotypic variations associated with Glutaric aciduria type 1 (GA1) in Chinese patients.

Methods: We analyzed the clinical, neuroradiological, biochemical, and genetic information from 101 GA1 patients in mainland China.

Results: 20 patients were diagnosed by newborn screening and the remaining 81 cases were identified following clinical intervention. Macrocephaly was the most common presentation, followed by movement disorders and seizures. A total of 59 patients were evaluated by brain MRI and 58 patients presented with abnormalities, with widening of the sylvian fissures being the most common symptom. The concentration of glutarylcarnitine in the blood, glutarylcarnitine/capryloylcarnitine ratio, and urine levels of glutaric acid were increased in GA1 patients and were shown to decrease following intervention. A total of 88 patient samples were available for genotyping and 74 variants within the gene, including 23 novel variants, were identified. The most common variant was c.1244-2A > C (18.4%) and there were no significant differences in the biochemical or clinical phenotypes described for patients with the four most common variants: c.1244-2A > C, c.1064G > A, c.533G > A, and c.1147C > T. Patients identified by newborn screening had better outcomes than clinical patients.

Conclusion: Our findings expand the spectrum of phenotypes and genotypes for GA1 in Chinese populations and suggest that an expanded newborn screening program using tandem mass spectrometry may facilitate the early diagnosis and treatment of this disease, improving clinical outcomes for patients in China.
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http://dx.doi.org/10.3389/fgene.2021.702374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293753PMC
July 2021

Research on Transfer Rate of Heavy Metals and Harmful Elements in Traditional Chinese Medicine Extraction and Refining Processes and Product Health Risk Assessment.

Biol Trace Elem Res 2021 Jul 18. Epub 2021 Jul 18.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.

Ramulus Mori alkaloids, also known as SangZhi alkaloids (SZ-A), is a natural medicine used for the treatment of type 2 diabetes mellitus in China. SZ-A is extracted from Morus alba L., which grows in the natural environment and may be contaminated by heavy metals and harmful elements. These contaminants can enter SZ-A products during the extraction of M. alba, thereby posing a threat to patient health. Therefore, it is necessary to formulate scientific and reasonable limits to ensure patient safety. For this purpose, in this study, we used the extraction process of SZ-A as the object of investigation and determined the content of five harmful elements: Cd, Pb, As, Hg, and Cu in the herb raw material, SZ-A product, and its intermediates obtained in different extraction steps. Next, the transfer rate of harmful elements in the extraction process was used as an indicator to evaluate the ability of different operations to remove harmful elements. Subsequently, the health risks of heavy metals and harmful elements in SZ-A were assessed. Our results demonstrated that M. alba has little risk of contamination by Hg. The cation and anion resin refining processes are the best effective method to remove Cd, Pb, and Cu from the products. However, As is not easily eliminated during the water extraction. There is as much as 87% of As transferred from the herb raw material to the water-extracted intermediate, while Cd, Pb, and Cu are rarely transferred (6% to 17%) under the same conditions. Overall, the results indicate that the regulatory standard limits for Cd, Pb, As, Hg, and Cu contained in natural medicine Ramulus Mori alkaloids are set to 1, 5, 2, 0.2, and 20 μg/g, respectively, which is the most scientific and it can guarantee the safety of patients.
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http://dx.doi.org/10.1007/s12011-021-02788-xDOI Listing
July 2021

Oral SMEDDS promotes lymphatic transport and mesenteric lymph nodes target of chlorogenic acid for effective T-cell antitumor immunity.

J Immunother Cancer 2021 Jul;9(7)

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China

Background: Mesenteric lymph nodes (MLNs) are critical draining lymph nodes of the immune system that accommodate more than half of the body's lymphocytes, suggesting their potential value as a cancer immunotherapy target. Therefore, efficient delivery of immunomodulators to the MLNs holds great potential for activating immune responses and enhancing the efficacy of antitumor immunotherapy. Self-microemulsifying drug delivery systems (SMEDDS) have attracted increasing attention to improving oral bioavailability by taking advantage of the intestinal lymphatic transport pathway. Relatively little focus has been given to the lymphatic transport advantage of SMEDDS for efficient immunomodulators delivery to the MLNs. In the present study, we aimed to change the intestinal lymphatic transport paradigm from increasing bioavailability to delivering high concentrations of immunomodulators to the MLNs.

Methods: Chlorogenic acid (CHA)-encapsulated SMEDDS (CHA-SME) were developed for targeted delivery of CHA to the MLNs. The intestinal lymphatic transport, immunoregulatory effects on immune cells, and overall antitumor immune efficacy of CHA-SME were investigated through in vitro and in vivo experiments.

Results: CHA-SME enhanced drug permeation through intestinal epithelial cells and promoted drug accumulation within the MLNs via the lymphatic transport pathway. Furthermore, CHA-SME inhibited tumor growth in subcutaneous and orthotopic glioma models by promoting dendritic cell maturation, priming the naive T cells into effector T cells, and inhibiting the immunosuppressive component. Notably, CHA-SME induced a long-term immune memory effect for immunotherapy.

Conclusions: These findings indicate that CHA-SME have great potential to enhance the immunotherapeutic efficacy of CHA by activating antitumor immune responses.
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http://dx.doi.org/10.1136/jitc-2021-002753DOI Listing
July 2021

Realizing Hopf Insulators in Dipolar Spin Systems.

Phys Rev Lett 2021 Jul;127(1):015301

Department of Physics, University of California, Berkeley, California 94720, USA.

The Hopf insulator is a weak topological insulator characterized by an insulating bulk with conducting edge states protected by an integer-valued linking number invariant. The state exists in three-dimensional two-band models. We demonstrate that the Hopf insulator can be naturally realized in lattices of dipolar-interacting spins, where spin exchange plays the role of particle hopping. The long-ranged, anisotropic nature of the dipole-dipole interactions allows for the precise detail required in the momentum-space structure, while different spin orientations ensure the necessary structure of the complex phases of the hoppings. Our model features robust gapless edge states at both smooth edges, as well as sharp edges obeying a certain crystalline symmetry, despite the breakdown of the two-band picture at the latter. In an accompanying paper [T. Schuster et al., Phys. Rev. A 103, AW11986 (2021)PLRAAN2469-9926] we provide a specific experimental blueprint for implementing our proposal using ultracold polar molecules of ^{40}K^{87}Rb.
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http://dx.doi.org/10.1103/PhysRevLett.127.015301DOI Listing
July 2021

Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations.

J Nanobiotechnology 2021 Jul 5;19(1):199. Epub 2021 Jul 5.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan Street, Beijing, 100050, People's Republic of China.

Background: Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential.

Results: Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation.

Conclusions: The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy.
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http://dx.doi.org/10.1186/s12951-021-00946-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256566PMC
July 2021

Indications for and contraindications of immune checkpoint inhibitors in cancer patients with coronavirus disease 2019 vaccination.

Future Oncol 2021 Jun 30. Epub 2021 Jun 30.

Cancer Institute, Second Affiliated Hospital, Army Medical University, Chongqing, China.

The novel coronavirus disease 2019 (COVID-19) pandemic has lasted over 1 year and will not disappear in a short time. There is no specific remedy against the virus as yet. Vaccination is thus far one of the most important strategies for preventing COVID-19. Cancer patients with COVID-19 have a higher mortality because of immunosuppression. Immune checkpoint inhibitors (ICIs) are a novel anticancer strategy for blocking inhibitory pathways, which are related to the immune response. There is a question regarding whether COVID-19 vaccination and ICI treatment impact each other in cancer patients. This review explores both sides of the relationship between ICI treatment and COVID-19 vaccination and suggests good efficacy and safety of ICI treatment after COVID-19 vaccination as well as little impact on the virus protection and toxicity associated with COVID-19 vaccination during ICI treatment.
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http://dx.doi.org/10.2217/fon-2021-0288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244550PMC
June 2021

Using fluorene to lock electronically active moieties in thermally activated delayed fluorescence emitters for high-performance non-doped organic light-emitting diodes with suppressed roll-off.

Chem Sci 2020 Nov 26;12(4):1495-1502. Epub 2020 Nov 26.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University Suzhou Jiangsu 215123 P.R. China

Thermally activated delayed fluorescence (TADF) emitters with aggregation-induced emission (AIE) features are hot candidates for non-doped organic light-emitting diodes (OLEDs), as they are highly emissive in solid states upon photoexcitation. Nevertheless, not every AIE-TADF emitter in the past had guaranteed decent efficiencies in non-doped devices, indicating that the AIE character alone does not necessarily afford ideal non-doped TADF emitters. As intermolecular electron-exchange interaction that involves long-lived triplet excitons plays a dominant role in the whole quenching process of TADF, we anticipate that it is the main reason for the different electroluminescence performances of AIE-TADF emitters. Therefore, in this work, we designed two TADF emitters SPBP-DPAC and SPBP-SPAC by modifying a reported less successful emitter BP-DPAC with extra fluorenes to increase intermolecular distances and attenuate this electron-exchange interaction. With the fluorene lock as steric hindrance, SPBP-DPAC and SPBP-SPAC exhibit significantly higher exciton utilization in non-doped films due to the suppressed concentration quenching. The non-doped OLEDs based on SPBP-DPAC and SPBP-SPAC show an excellent maximum external quantum efficiency (EQE) of 22.8% and 21.3% respectively, and what's even more promising is that ignorable roll-offs at practical brightness (, 1000 and 5000 cd m) were realized. These results reveal that locking the phenyl rings as steric hindrance can not only enhance the molecular rigidity, but also cause immediate relief of concentration quenching, and result in significant performance improvement under non-doped conditions. Our approach proposes a feasible molecular modification strategy for AIE-TADF emitters, potentially increasing their applicability in OLEDs.
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http://dx.doi.org/10.1039/d0sc05631fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179127PMC
November 2020

Circular RNA 0014715 Facilitates Cell Proliferation and Inhibits Apoptosis in Esophageal Squamous Cell Carcinoma.

Cancer Manag Res 2021 15;13:4735-4749. Epub 2021 Jun 15.

Department of Oncology, Taizhou People's Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, 225300, Jiangsu, People's Republic of China.

Background: Circular RNAs (circRNAs) have recently been verified to have multiple biological functions and participate in diverse biological processes in different malignant tumors, including esophageal squamous cell carcinoma (ESCC). Nonetheless, the function of circular RNA 0014715 (hsa_circ_0014715, circ_0014715) in ESCC has not been described.

Materials And Methods: We investigated clinical data from sixty-seven patients undergoing surgery for esophageal cancer. The clinical data were collected. And we analyzed the correlation between the clinical characteristics of these patients and the expression of circ_0014715. Besides, we explored the expression of circ_0014715 in ESCC cell lines. We used cell counting kit-8, colony formation, transwell assay, and flow cytometry to detect changes in cell proliferation, migration, apoptosis, and cell cycle progression.

Results: We found that circ_0014715 was highly expressed in esophageal squamous cell carcinoma tissues and cell lines. The correlation analysis of clinicopathological features and gene expression revealed that high expression of circ_0014715 was related to nerve invasion, vascular invasion, more advanced tumor-node-metastasis (TNM) stage and poor differentiation grade. Receiver operating characteristic (ROC) curves revealed that circ_0014715 might have diagnostic value for ESCC. Experiments with cultured cells showed that knockdown of circ_0014715 significantly restrained cell proliferation, migration, invasion, wound healing and accelerated cell apoptosis. And cell cycle arrest at G2 phase was observed via flow cytometry. Overexpression of circ_0014715 caused the opposite effects. Collectively, these studies show that circ_0014715 is closely connected with the pathogenesis and development of ESCC. The excess expression of circ_0014715 may have promoting effects on the progression of esophageal cell carcinoma.

Conclusion: Our finding revealed that circ_0014715 promoted tumor growth and cell proliferation. All of these suggest that targeting circ_0014715 has potential therapeutic value in the treatment of ESCC.
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http://dx.doi.org/10.2147/CMAR.S314882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214545PMC
June 2021

Hundred-watt-level phosphosilicate Raman fiber laser with less than 1% quantum defect.

Opt Lett 2021 Jun;46(11):2662-2665

Quantum defect (QD)-induced high thermal load in high-power fiber lasers can largely affect the conversion efficiency, pose a threat to the system security, and even prohibit the further power scaling. In this Letter, we investigate evolutions and influences of the reflectivity of the output coupler, the length of phosphosilicate fiber, and the pump bandwidth, and demonstrate a hundred-watt-level low-QD Raman fiber laser (RFL). The RFL enabled by the boson peak of phosphosilicate fiber achieves a maximum power of 100.9 W with a reduced QD down to 0.97%; the corresponding conversion efficiency reaches 69.8%. This Letter may offer not only an alternative scheme for a high-power, high-efficiency fiber laser, but also great potential on the suppression of thermal-induced effects such as thermal mode instability and the thermal lens effect.
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http://dx.doi.org/10.1364/OL.426752DOI Listing
June 2021

Exploration of simulation-based medical education for undergraduate students.

Medicine (Baltimore) 2021 May;100(20):e25982

The State Key Lab of Reproductive, Department of Urology, the First Affiliated Hospital of Nanjing Medical University.

Abstract: Over the past decades, extensive studies have underscored the growing importance of simulation-based medical education (SBME) for medical students. However, the underlying influence of SBME on undergraduate students is yet to be investigated. This work is a single-center cohort study involving 1178 undergraduate students who were divided into a control group and an SBME group. All participants gave their written informed consent. We compared the theoretical and practical achievements of these 2 groups and distributed a feedback questionnaire. Results show that SBME significantly improves the practical or theoretical achievements of students (P < .001). The humanistic care (improvement rate: 69.2%) and doctor-patient communication (improvement rate: 56.3%) performances of these studies were vastly improved. The students in the SBME group tend to allocate more time to communicating with others. SBME is an effective teaching method that can improve the reflective capacity and communication skills of undergraduate medical students, thereby resulting in their relatively improved performance.
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http://dx.doi.org/10.1097/MD.0000000000025982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137105PMC
May 2021

Experimental Constraint on Axionlike Particles over Seven Orders of Magnitude in Mass.

Phys Rev Lett 2021 Apr;126(17):171301

JILA, NIST and University of Colorado, Boulder, Colorado 80309, USA.

We use our recent electric dipole moment (EDM) measurement data to constrain the possibility that the HfF^{+} EDM oscillates in time due to interactions with candidate dark matter axionlike particles (ALPs). We employ a Bayesian analysis method which accounts for both the look-elsewhere effect and the uncertainties associated with stochastic density fluctuations in the ALP field. We find no evidence of an oscillating EDM over a range spanning from 27 nHz to 400 mHz, and we use this result to constrain the ALP-gluon coupling over the mass range 10^{-22}-10^{-15}  eV. This is the first laboratory constraint on the ALP-gluon coupling in the 10^{-17}-10^{-15}  eV range, and the first laboratory constraint to properly account for the stochastic nature of the ALP field.
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http://dx.doi.org/10.1103/PhysRevLett.126.171301DOI Listing
April 2021

Digestion liquid based alkaline pretreatment of waste activated sludge promotes methane production from anaerobic digestion.

Water Res 2021 Jul 29;199:117198. Epub 2021 Apr 29.

Hunan Qing Zhi Yuan Environmental Protection Technology Co., Ltd, Changsha 410004, PR China.

This work proved an efficient method to significantly increase methane production from anaerobic digestion of WAS. This method is to reflux proper of digestion liquid into waste activated sludge pretreatment unit (pH 9.5 for 24 h). The yield of maximum methane improved between 174.2 ± 7.3 and 282.5 ± 14.1 mL/g VSS with the reflux ratio of digestion liquid increasing from 0% to 20%. It was observed that the biodegradable organics in the digestion liquid did not affect the biological processes related to anaerobic digestion but increased methane production through reutilization. The ammonium in the digestion liquid was the main contributor to the increase in methane production via promoting sludge solubilization, but refractory organics were the major inhibitors to anaerobic digestion. It should be emphasized that the metal ions present in the digestion liquid were beneficial rather than harmful to the biological processes in the anaerobic digestion, which may be connected with the fact that certain metal ions were involved in the expression and activation of key enzymes. In addition, it was found that anaerobes in digestion liquid were another potential contributor to the enhanced anaerobic digestion.
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http://dx.doi.org/10.1016/j.watres.2021.117198DOI Listing
July 2021

Rapid detection of twenty-nine common Chinese glucose-6-phosphate dehydrogenase variants using a matrix-assisted laser desorption/ionization-time of flight mass spectrometry assay on dried blood spots.

Clin Biochem 2021 Aug 18;94:27-34. Epub 2021 Apr 18.

Department of Pediatric Endocrinology and Genetics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China. Electronic address:

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common inherited disease. Current neonatal screening methods for G6PD deficiency primarily rely on the use of biochemical tests. However, only 15%-20% of female carriers were estimated to have been detected using these tests. As a better alternative, DNA-based tests could be used for G6PD deficiency screening. We aimed to develop a matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) assay for G6PD variant detection.

Methods: A MALDI-TOF MS assay with multiprimer extension (multi-PEX) was developed to rapidly and accurately detect the 29 common G6PD variants in the Chinese population using a dried blood spot as a template. A parallel study screening 571 unrelated neonatal samples using the MALDI-TOF MS and fluorescence quantitative enzymatic assays was performed. All results were confirmed by Sanger sequencing in a blind study.

Results: In 571 unrelated neonatal samples, 34 positive samples, including 26 samples from hemizygous males and eight samples from heterozygous females, were correctly identified, yielding a clinical sensitivity of 100%. The results were validated using Sanger sequencing with 100% concordance. In contrast, the fluorescence quantitative enzymatic assay had a 75% false negative and 88.8% false positive rate for the detection of heterozygous G6PD deficient females.

Conclusions: We established a reliable MALDI-TOF MS assay for G6PD deficiency screening in the Chinese population maximizing the chance of detection of heterozygous G6PD deficient females and reducing the false negative and false positive rates associated with routinely used newborn screening procedures.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.04.012DOI Listing
August 2021

Clinical, Biochemical, and Molecular Analyses of Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients.

Front Genet 2021 23;12:577046. Epub 2021 Mar 23.

Department of Pediatric Endocrinology/Genetics, Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Objective: Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare inherited metabolic disorder of fatty acid β-oxidation. The present study aimed to evaluate clinical and biochemical manifestations, and the mutation spectrum of this disorder in a large cohort of Chinese patients.

Methods: A total of 24 patients were enrolled, and blood acylcarnitine and urinary organic acid levels were measured by tandem mass spectrometry and gas chromatography-mass spectrometry (GC-MS), respectively. Mutations in the gene were detected by Sanger or next-generation sequencing. Clinical progression, acylcarnitine spectra, and mutations were analyzed and described in detail.

Results: Among the 24 patients, six cases were diagnosed because of disease onset with symptoms such as vomiting, diarrhea, convulsion, and hypoglycemia; 18 patients without symptoms were diagnosed by newborn screening (NBS). All patients who accepted treatment after diagnosis developed normal intelligence and physique. The concentrations of octanoylcarnitine, the octanoylcarnitine/decanoylcarnitine ratio, and the octanoylcarnitine/acetylcarnitine ratio in the blood and urinary dicarboxylic acid concentrations were consistently elevated. Blood biomarkers failed to decrease after treatment. DNA sequencing revealed seven known and 17 novel mutations in the gene of patients. Mutation p.T150Rfs4 was most frequent, followed by p.R31C, p.F103Y, p.I223T, p.G362E, and c.387+1delG.

Conclusion: Despite biochemical abnormalities, medium-chain acyl-CoA dehydrogenase deficiency showed relatively mild clinical phenotypes with low mortality and optimistic prognoses in China. NBS is crucial for early diagnosis, treatment, and prognosis.
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http://dx.doi.org/10.3389/fgene.2021.577046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025081PMC
March 2021

Dynamical Generation of Spin Squeezing in Ultracold Dipolar Molecules.

Phys Rev Lett 2021 Mar;126(11):113401

JILA, National Institute of Standards and Technology and Department of Physics, University of Colorado, Boulder, Colorado, 80309, USA.

We study a bulk fermionic dipolar molecular gas in the quantum degenerate regime confined in a two-dimensional geometry. Using two rotational states of the molecules, we encode a spin 1/2 degree of freedom. To describe the many-body spin dynamics of the molecules, we derive a long-range interacting XXZ model valid in the regime where motional degrees of freedom are frozen. Because of the spatially extended nature of the harmonic oscillator modes, the interactions in the spin model are very long ranged, and the system behaves close to the collective limit, resulting in robust dynamics and generation of entanglement in the form of spin squeezing even at finite temperature and in the presence of dephasing and chemical reactions. We discuss how the internal state structure can be exploited to realize time reversal and enhanced metrological sensing protocols.
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http://dx.doi.org/10.1103/PhysRevLett.126.113401DOI Listing
March 2021

Longitudinal association between home and community-based services provision and cognitive function in Chinese older adults: Evidence from the Chinese Longitudinal Healthy Longevity Survey.

Health Soc Care Community 2021 Mar 24. Epub 2021 Mar 24.

School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.

Few studies have assessed the impact of home and community-based services (HCBSs) provision on cognitive function among older adults over time. This study examined the longitudinal association between HCBSs provision and cognitive function in Chinese older adults. The study included 5,134 participants aged 65 years and older in the Chinese Longitudinal Healthy Longevity Survey from 2008 to 2014. The Mini-Mental State Examination (MMSE) was used to evaluate cognitive function over the same time period. Participants were asked what kind of HCBSs were provided in his or her community. However, they were not asked whether services were utilised. The study used the number of HCBSs provided each wave to represent the strength of HCBSs, and used the MMSE score of each wave to represent the older adults' cognitive function status. A latent growth model was used to explore the relationship between HCBSs provision and cognitive function of older adults. The number of HCBSs provided was positively associated with older adults' cognitive function (2008: β = 0.03, p = 0.031; 2011: β = 0.06, p < 0.001; 2014: β = 0.06, p < 0.001) after controlling for gender, age, residence, education, income, medical insurance, activities of daily living disability, instrumental activities of daily living disability, serious illness, living arrangement and marital status. Results provided longitudinal evidence that an increase in HCBSs provision at a national level can result in better cognitive function in Chinese older adults.
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http://dx.doi.org/10.1111/hsc.13353DOI Listing
March 2021

Prognostic Value of Peroxiredoxin-1 Expression in Patients with Solid Tumors: a Meta-Analysis of Cohort Study.

Dis Markers 2021 3;2021:9508702. Epub 2021 Mar 3.

The Center for Translational Medicine, Taizhou People's Hospital, Taizhou, 225300 Jiangsu Province, China.

Methods: We comprehensively searched electronic databases, namely, PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases up to December 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the association between PRDX1 protein expression and the survival of patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to estimate the correlation between PRDX1 protein expression and clinicopathologic characteristics in the patients.

Results: Seventeen cohort studies that involved 2,858 patients were included in this meta-analysis. The pooled results indicated that positive PRDX1 expression was related to poor overall survival (HR = 1.68, 95% CI: 1.24-2.27, = 0.001) and disease-free survival (HR = 1.88, 95% CI: 1.31-2.70, = 0.001). In addition, high PRDX1 expression was associated with large tumor size (OR = 1.69, 95% CI: 1.07-2.68, = 0.025), advanced TNM stage (OR = 2.26, 95% CI: 1.24-4.13, = 0.008), and poor tumor differentiation (OR = 0.59, 95% CI: 0.44-0.81, = 0.001).

Conclusions: PRDX1 overexpression is associated with poor outcomes of cancers and may serve as a prognostic biomarker for malignant patients. Hence, PRDX1 could be a new target for antitumor therapy.
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http://dx.doi.org/10.1155/2021/9508702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952178PMC
March 2021

High power tunable multiwavelength random fiber laser at 1.3 μm waveband.

Opt Express 2021 Feb;29(4):5516-5524

Multiwavelength fiber lasers, especially those operating at optical communication wavebands such as 1.3 μm and 1.5 μm wavebands, have huge demands in wavelength division multiplexing communications. In the past decade, multiwavelength fiber lasers operating at 1.5 μm waveband have been widely reported. Nevertheless, 1.3 μm waveband multiwavelength fiber laser is rarely studied due to the lack of proper gain mechanism. Random fiber laser (RFL), owing to its good temporal stability and flexible wavelength tunability, is a great candidate for multiwavelength generation. Here, we reported high power multiwavelength generation at 1.3 μm waveband in RFL for the first time. At first, we employed a section of 10 km G655C fiber to provide Raman gains, as a result of which, 1.07 W multiwavelength generation at 1.3 μm waveband with an optical to signal noise ratio of ∼33 dB is demonstrated. By tuning the pump wavelength from 1055 nm to 1070 nm, tunable multiwavelength output covering the range of 1300-1330 nm can be achieved. Furtherly, we realized 4.67 W multiwavelength generation at 1.3 μm waveband by shortening the fiber length to 4 km. To the best of our knowledge, this is the highest output power ever reported for multiwavelength fiber lasers.
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http://dx.doi.org/10.1364/OE.412224DOI Listing
February 2021

Clinical study on cystogastrostomy and Roux-en-Y-type cystojejunostomy in the treatment of pancreatic pseudocyst: A single-center experience.

Medicine (Baltimore) 2021 Mar;100(10):e25029

Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Abstract: The main purpose is to compare the efficacy of cystogastrostomy (CG) and Roux-en-Y-type cystojejunostomy (RCJ) in the treatment of pancreatic pseudocyst (PPC), and to explore the risk factors of recurrence and complications after internal drainage.Two hundred eight patients undergoing either CG or RCJ for PPC Between January 1, 2013and February 1, 2019, at West China Hospital of Sichuan University were retrospectively analyzed. The cure rate, complication rate and related factors were compared between the 2 groups.Two hundred eight patients with PPC underwent either a CG (n = 119) or RCJ (n = 89). The median follow-up time was 42.7 months. Between the 2 cohorts, there were no significant differences in cure rate, reoperation rate, and mortality (all P > .05). The operative time, estimated intraoperative blood loss, install the number of drainage tubes and total expenses in CG group were lower than those in RCJ group (all P < .05). The Logistic regression analysis showed that over twice of pancreatitis' occurrence was were independent risk factor for recurrence after internal drainage of PPC (OR 2.760, 95% CI 1.006∼7.571, P = .049). Short course of pancreatitis (OR 0.922, 95% CI 0.855∼0.994, P = .035), and RCJ (OR 2.319, 95% CI 1.033∼5.204, P = .041) were independent risk factors for complications after internal drainage of PPC.Both CG and RCJ are safe and effective surgical methods for treating PPC. There were no significant differences in cure rate, reoperation rate, and mortality between the 2 groups, while the CG group had a short operation time, less intraoperative bleeding and less cost.
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http://dx.doi.org/10.1097/MD.0000000000025029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969232PMC
March 2021

Prognostic significance of chemokines CCL11 and CCL5 modulated by low-density lipoprotein cholesterol in colon cancer patients with normal body mass index.

Ann Transl Med 2021 Feb;9(3):202

Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Many studies have shown an elevated level of cholesterol in colon tumors as compared to normal tissue. Obesity and high low-density lipoprotein cholesterol (LDL-C) are known risk factors for colon cancer. However, the role of LDL-C in colon cancer patients with normal body mass index (BMI) remains elusive.

Methods: Levels of serum cholesterol and oxysterols were quantified by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) from 129 individuals with normal BMI, including 32 with solitary polyp, 36 with multiple polyps, and 31 with adenocarcinoma as well as 32 healthy controls. In vitro, colon cancer cells were treated with LDL-C and assayed for chemokines via RNA-Seq and mitochondrial morphology via transmission electron microscopy and immunofluorescence. Additionally, correlation analysis was performed between LDL-C-induced chemokines and the overall survival of colon cancer patients from the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), and the Human Protein Atlas (HPA) database.

Results: The serum cholesterol level was significantly higher in colon adenocarcinoma patients with normal BMI than that in healthy controls (P<0.001). LDL-C potentiated colon cancer cell invasion and resistance to glucose-deprivation in vitro via chemokine-mediated signaling, mainly upregulation of CC chemokine ligand (CCL) 5 and downregulation of CCL 11. By analyzing the RNA expression data of colorectal cancer from TCGA, GTEx, and HPA, we demonstrated that the CCL5 level in colorectal adenocarcinoma tissues was significantly increased relative to adjacent normal tissues (P=0.01) while the CCL11 level was decreased (P=0.01). Both increased CCL5 and decreased CCL11 showed a negative correlation with the 5-year overall survival in tumor node metastasis (TNM) stage II colon cancer patients (P=0.0032, 0.026 for CCL5 and CCL11, respectively).

Conclusions: Our study supports the idea that LDL-C regulates the expression of CCL5 and CCL11 chemokines, which may have predictive values for survival in colon cancer patients with normal BMI, especially for patients in TNM stage II.
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http://dx.doi.org/10.21037/atm-20-1604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940920PMC
February 2021

Value of amniotic fluid homocysteine assay in prenatal diagnosis of combined methylmalonic acidemia and homocystinuria, cobalamin C type.

Orphanet J Rare Dis 2021 03 10;16(1):125. Epub 2021 Mar 10.

Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China.

Background: Combined methylmalonic acidemia and homocystinuria, cobalamin C type (cblC defect) is the most common inborn error of cobalamin metabolism, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability of biochemical method for the prenatal diagnosis of cblC defect, we conducted a retrospective study of our 10-year experience at a single center.

Methods: 248 pregnancies whose probands were diagnosed as cblC defect were referred to our center for prenatal diagnosis from January 2010 to December 2019. Prenatal data of Hcy levels determined by enzymatic cycling assay, acylcarnitine analysis using liquid chromatography tandem mass spectrometry, organic acid analysis using gas chromatography mass spectrometry, and genetic analysis by direct sequencing of 248 at-risk fetuses were retrospectively reviewed.

Results: For 2.0 and 16.0 μmol/L levels of Hcy AF samples, the relative errors were - 2.5% and 2.8%, respectively. The respective measurement uncertainties were 13.07% and 14.20%. For the 248 at-risk fetuses, 63 fetuses were affected and 185 fetuses were unaffected. Hcy level of 13.20 (6.62-43.30) μmol/L in 63 affected fetuses was significantly higher than that in 185 unaffected fetuses of 2.70 (0.00-5.80) μmol/L, and there was no overlap between the affected and unaffected groups. The diagnostic sensitivity and specificity of Hcy were 100% and 92.05%, respectively. The positive and negative predictive values of the combination of Hcy, propionylcarnitine (C3), ratio of C3 to acetylcarnitine (C2; C3/C2), methylmalonic acid (MMA), and methylcitric acid (MCA) were both 100%. Sixteen fetuses displayed inconclusive genetic results of MMACHC variants, in which seven fetuses were determined to be affected with elevated levels of Hcy, C3, C3/C2 and MMA, and their levels were 18.50 (6.70-43.30) μmol/L, 8.53(5.02-11.91) μmol/L, 0.77 (0.52-0.97), 8.96 (6.55-40.32) mmol/mol Cr, respectively. The remaining nine fetuses were considered unaffected based on a normal amniotic fluid metabolite profile.

Conclusions: Hcy appears to be another characteristic biomarker for the prenatal diagnosis of cblC defect. The combination of Hcy assay with acylcarnitine and organic acid analysis is a fast, sensitive, and reliable prenatal diagnostic biochemical approach. This approach could overcome the challenge of the lack of genetic analysis for families with at-risk cblC defect fetuses.
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http://dx.doi.org/10.1186/s13023-021-01762-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945211PMC
March 2021

Exploring for Municipality-Level Socioeconomic Variables Related to Zika Virus Incidence in Colombia.

Int J Environ Res Public Health 2021 02 13;18(4). Epub 2021 Feb 13.

Department of Global Health, Indiana University, Indianapolis, IN 46202, USA.

Colombia experienced an outbreak of Zika virus infection during September 2015 until July 2016. This study aimed to identify the socioeconomic factors that at the municipality level correlate with this outbreak and therefore could have influenced its incidence. An analysis of publicly available, municipality-aggregated data related to eight potential explanatory socioeconomic variables was conducted. These variables are school dropout, low energy strata, social security system, savings capacity, tax, resources, investment, and debt. The response variable of interest in this study is the number of reported cases of Zika virus infection per people (projected) per square kilometer. Binomial regression models were performed. Results show that the best predictor variables of Zika virus occurrence, assuming an expected inverse relationship with socioeconomic status, are "school", "energy", and "savings". Contrary to expectations, proxies of socioeconomic status such as "investment", "tax", and "resources" were associated with an increase in the occurrence of Zika virus infection, while no association was detected for "social security" and "debt". Energy stratification, school dropout rate, and the percentage of the municipality's income that is saved conformed to the hypothesized inverse relationship between socioeconomic standing and Zika occurrence. As such, this study suggests these factors should be considered in Zika risk modeling.
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http://dx.doi.org/10.3390/ijerph18041831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918893PMC
February 2021

(iso)flavone 7- and 3'-O-Glycosyltransferases Can Be Induced by CuCl.

Front Plant Sci 2021 9;12:632557. Epub 2021 Feb 9.

Department of Resources Science of Traditional Chinese Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.

In many plants, isoflavones are the main secondary metabolites that have various pharmacological activities, but the low water solubility of aglycones limits their usage. The O-glycosylation of (iso)flavones is a promising way to overcome this barrier. O-glycosyltransferases (UGTs) are key enzymes in the biosynthesis of (iso)flavonoid O-glycosides in plants. However, limited investigations on isoflavonoid O-UGTs have been reported, and they mainly focused on legumes. Goldblatt et Mabberley is a non-legume plant rich in various isoflavonoid glycosides. However, there are no reports regarding its glycosylation mechanism, despite the transcriptome previously being annotated as having non-active isoflavone 7-O-UGTs. Our previous experiments indicated that isoflavonoid glycosides were induced by CuCl in calli; therefore, we hypothesized that isoflavone O-UGTs may be induced by Cu. Thus, a comparative transcriptome analysis was performed using seedlings treated with CuCl, and eight new active BcUGTs were obtained. Biochemical analyses showed that most of the active BcUGTs had broad substrate spectra; however, substrates lacking 5-OH were rarely catalyzed. Real-time quantitative PCR results further indicated that the transcriptional levels of BcUGTs were remarkably induced by Cu. Our study increases the understanding of UGTs and isoflavone biosynthesis in non-legume plants.
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http://dx.doi.org/10.3389/fpls.2021.632557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900552PMC
February 2021

Cancer-Associated Fibroblasts Suppress Cancer Development: The Other Side of the Coin.

Front Cell Dev Biol 2021 4;9:613534. Epub 2021 Feb 4.

Department of Radiation Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Cancer-associated fibroblasts (CAFs) are the main stromal components of cancer, representing a group of heterogeneous cells. Many studies indicate that CAFs promote tumor development. Besides, evidence of the tumor suppression effects of CAFs keeps on merging. In the tumor microenvironment, multiple stimuli can activate fibroblasts. Notably, this does not necessarily mean the activated CAFs become strong tumor promoters immediately. The varying degree of CAFs activation makes quiescent CAFs, tumor-restraining CAFs, and tumor-promoting CAFs. Quiescent CAFs and tumor-restraining CAFs are more present in early-stage cancer, while comparatively, more tumor-promoting CAFs present in advanced-stage cancer. The underlying mechanism that balances tumor promotion or tumor inhibition effects of CAFs is mostly unknown. This review focus on the inhibitory effects of CAFs on cancer development. We describe the heterogeneous origin, markers, and metabolism in the CAFs population. Transgenetic mouse models that deplete CAFs or deplete CAFs activation signaling in the tumor stroma present direct evidence of CAFs protective effects against cancer. Moreover, we outline CAFs subpopulation and CAFs derived soluble factors that act as a tumor suppressor. Single-cell RNA-sequencing on CAFs population provides us new insight to classify CAFs subsets. Understanding the full picture of CAFs will help translate CAFs biology from bench to bedside and develop new strategies to improve precision cancer therapy.
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http://dx.doi.org/10.3389/fcell.2021.613534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890026PMC
February 2021

TLR4 knockout ameliorates streptozotocin-induced osteoporosis in a mouse model of diabetes.

Biochem Biophys Res Commun 2021 03 16;546:185-191. Epub 2021 Feb 16.

Department of Endocrinology, The Second People's Hospital of Hefei, Guangde Road, Hefei, 230011, Anhui, China. Electronic address:

Type 1 diabetes mellitus (T1DM) is characterized by hyperglycemia manifesting as insufficient insulin. Toll-like receptor-4 (TLR4) has been implicated in diabetic osteoporosis. We established streptozotocin (STZ)-induced diabetic mouse model and examined the relevant osteoporosis factors in different experimental groups, the WT-CON group, WT-STZ group, KO-CON group and KO-STZ group, respectively. No obvious protection of TLR4 deletion was shown in mice with diabetes. There was no obvious difference in the body weight or blood glucose concentration between WT-STZ group and KO-STZ group. However, TLR4 deletion reduced the receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation. Furthermore, TLR4 knockout attenuated STZ-induced diabetic osteoporosis via inhibiting osteoblasts and pre-inflammation factors mediated by the NF-κB pathway. TLR4 deletion ameliorated STZ-induced diabetic osteoporosis in mice, and TLR4 may be used as a potential therapeutic target for the treatment of diabetic osteoporosis.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.102DOI Listing
March 2021

Thermal noise and mechanical loss of SiO/TaO optical coatings at cryogenic temperatures.

Opt Lett 2021 Feb;46(3):592-595

Mechanical loss of dielectric mirror coatings sets fundamental limits for both gravitational wave detectors and cavity-stabilized optical local oscillators for atomic clocks. Two approaches are used to determine the mechanical loss: ringdown measurements of the coating quality factor and direct measurement of the coating thermal noise. Here we report a systematic study of the mirror thermal noise at 4, 16, 124, and 300 K by operating reference cavities at these temperatures. The directly measured thermal noise is used to extract the mechanical loss for / coatings, which are compared with previously reported values.
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http://dx.doi.org/10.1364/OL.413758DOI Listing
February 2021

Comparison of Different Ultrasound Classification Systems of Thyroid Nodules for Identifying Malignant Potential: A Cross-sectional Study.

Clinics (Sao Paulo) 2021 20;76:e2126. Epub 2021 Jan 20.

Department of Ultrasonic, The second affiliated hospital of nanchang university, Nanchang, Jiangxi, China.

Objective: In our organization, it has been necessary in our organization to calculate the risk categories according to the American Thyroid Association (ATA), the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME), and the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TIRADS) classification systems for each patient, from the year 2019; these are also required to be registered in the database. This creates a barrier to medical collaboration in everyday radiological practice because using multiple rating systems can be confusing for both readers and patients. For the change in routine practice, this study aimed to compare diagnostic parameters of the ATA, AACE/ACE/AME, and ACR TIRADS classification systems for the detection of suspicious thyroid nodule(s) considering the results of fine-needle aspiration cytopathology as the reference standard.

Methods: Data on ultrasound characteristics (2,000 nodules) and fine-needle aspiration cytopathology (39 nodules) were included in the analysis. The decision making of fine-needle aspiration biopsies was evaluated from the ultrasound characteristics as per the ATA, AACE/ACE/AME, and ACR TIRADS classification systems.

Results: The ATA, AACE/ACE/AME, and ACR TIRADS recommended 26, 32, and 37 nodules for fine-needle aspiration biopsies, respectively. Considering the results of fine-needle aspiration cytopathology as the reference standard, the ATA, AACE/ACE/AME, and ACR TIRADS classification systems had 0.993, 0.996, and 0.998 sensitivity, respectively. The accuracies were 0.641, 0.795, and 0.923, respectively.

Conclusion: The ACR TIRADS classification system is less invasive and can identify suspicious nodules more accurately than that of ATA and AACE/ACE/AME.
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http://dx.doi.org/10.6061/clinics/2021/e2126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798132PMC
April 2021

Improved Safety and Anti-Glioblastoma Efficacy of CAT3-Encapsulated SMEDDS through Metabolism Modification.

Molecules 2021 Jan 18;26(2). Epub 2021 Jan 18.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

13-()-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13()-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood-brain barrier to cause an anti-glioma effect. However, PF403, which is produced in the gastrointestinal tract and plasma, causes significant gastrointestinal side effects, limiting the clinical application of CAT3. The objective of this paper was to propose a metabolism modification for CAT3 using a self-microemulsifying drug delivery system (SMEDDS), in order to reduce the generation of PF403 in the gastrointestinal tract and plasma, as well as increase the bioavailability of CAT3 in vivo and the amount of anti-tumor substances in the brain. Thus, a CAT3-loaded self-microemulsifying drug delivery system (CAT3-SMEDDS) was prepared, and its physicochemical characterization was systematically carried out. Next, the pharmacokinetic parameters of CAT3 and its metabolite in the rats' plasma and brain were measured. Furthermore, the in vivo anti-glioma effects and safety of CAT3-SMEDDS were evaluated. Finally, Caco-2 cell uptake, MDCK monolayer cellular transfer, and the intestinal lymphatic transport mechanisms of SMEDDS were investigated in vitro and in vivo. Results show that CAT3-SMEDDS was able to form nanoemulsion droplets in artificial gastrointestinal fluid within 1 min, displaying an ideal particle size (15-30 nm), positive charge (5-9 mV), and controlled release behavior. CAT3-SMEDDS increased the membrane permeability of CAT3 by 3.9-fold and promoted intestinal lymphatic transport. Hence, the bioavailability of CAT3 was increased 79% and the level of its metabolite, PF403, was decreased to 49%. Moreover, the concentrations of CAT3 and PF403 were increased 2-6-fold and 1.3-7.2-fold, respectively, in the brain. Therefore, the anti-glioma effect in the orthotopic models was improved with CAT3-SMEDDS compared with CAT3 in 21 days. Additionally, CAT3-SMEDDS reduced the gastrointestinal side effects of CAT3, such as severe diarrhea, necrosis, and edema, and observed less inflammatory cell infiltration in the gastrointestinal tract, compared with the bare CAT3. Our work reveals that, through the metabolism modification effect, SMEDDS can improve the bioavailability of CAT3 and reduce the generation of PF403 in the gastrointestinal tract and plasma. Therefore, it has the potential to increase the anti-glioma effect and reduce the gastrointestinal side effects of CAT3 simultaneously.
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http://dx.doi.org/10.3390/molecules26020484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831126PMC
January 2021

Nerve growth factor-chondroitin sulfate/hydroxyapatite-coating composite implant induces early osseointegration and nerve regeneration of peri-implant tissues in Beagle dogs.

J Orthop Surg Res 2021 Jan 13;16(1):51. Epub 2021 Jan 13.

State Key Laboratory of Oral Diseases, Department of Oral Implant, West China School of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.

Background: Osseointegration is the premise of the chewing function of dental implant. Nerve growth factor (NGF), as a neurotrophic factor, can induce bone healing. However, the influence of NGF-chondroitin sulfate (CS)/hydroxyapatite (HA)-coating composite implant on the osseointegration and innervations is still not entirely clear.

Materials And Methods: NGF-CS/HA-coating composite implants were prepared using the modified biomimetic method. The characteristics of NGF-CS/HA-coating implants were determined using a scanning electron microscope. After NGF-CS/HA-coating implants were placed in the mandible of Beagle dogs, the early osseointegration and innervation in peri-implant tissues were assessed through X-ray, Micro-CT, maximal pull-out force, double fluorescence staining, toluidine blue staining, DiI neural tracer, immunohistochemistry, and RT-qPCR assays.

Results: NGF-CS/HA-coating composite implants were made successfully, which presented porous mesh structures with the main components (Ti and HA). Besides, we revealed that implantation of NGF-CS/HA-coating implants significantly changed the morphology of bone tissues and elevated maximum output, MAR, BIC, and nerve fiber in the mandible of Beagle dogs. Moreover, we proved that the implantation of NGF-CS/HA-coating implants also markedly upregulated the levels of NGF, osteogenesis differentiation, and neurogenic differentiation-related genes in the mandible of Beagle dogs.

Conclusion: Implantation of NGF-CS/HA-coating composite implants has significant induction effects on the early osseointegration and nerve regeneration of peri-implant tissues in the mandible of Beagle dogs.
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http://dx.doi.org/10.1186/s13018-020-02177-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805124PMC
January 2021
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