Publications by authors named "Jie Zhu"

1,307 Publications

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Alteration of serum neuregulin 4 and neuregulin 1 in gestational diabetes mellitus.

Ther Adv Endocrinol Metab 2021 8;12:20420188211049614. Epub 2021 Oct 8.

Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou 256600, Shandong, China.

Context: Neuregulin 4 (Nrg4) and neuregulin 1 (Nrg1) have been shown to play vital roles in several disorders of glucose metabolism. The pathophysiological role of Nrg4 and Nrg1 in gestational diabetes mellitus (GDM), however, remains poorly understood. We assessed the clinical relevance of the two cytokines in patients with GDM.

Methods: The study recruited 36 GDM patients and 38 age-matched, gestational age (24-28 weeks of gestation)-matched, and BMI (during pregnancy)-matched controls in this study. Serum Nrg4 and Nrg1 were measured using ELISA. Inflammatory factors such as IL-6, IL-1β, leptin, TNF-α, and monocyte chemotactic protein 1 (MCP-1) were determined Luminex technique.

Results: Serum Nrg4 in GDM patients was significantly lower than that in the controls, while Nrg1 was significantly higher in the GDM group ( < 0.01). Inflammatory factors such as IL-6, leptin, and TNF-α were significantly increased in GDM patients, while MCP-1 and IL-1β were not significantly different between the two groups. In addition, serum Nrg4 was negatively correlated with fasting glucose (= -0.438,  = 0.008), HOMA-IR (= -0.364,  = 0.029), IL-6 (= -0.384,  = 0.021), leptin (= -0.393,  = 0.018), TNF-α (= -0.346,  = 0.039), and MCP-1 (= -0.342,  = 0.041), and positively correlated with high-density lipoprotein cholesterol (HDL-C) (= -0.357,  = 0.033) in GDM group. Serum Nrg1 was positively correlated with BMI ( = 0.452,  = 0.006), fasting glucose ( = 0.424,  = 0.010), HOMA-IR ( = 0.369,  = 0.027), and triglyceride ( = 0.439,  = 0.007). The decrease of Nrg4 and the increase of Nrg1 were significantly related to the increased prevalence of GDM. Finally, ROC curve results indicated that Nrg1 combined with IL-6 and TNF-α might be an effective means for GDM screening.

Conclusions: Lower circulating Nrg4 and higher circulating Nrg1 serve risk factors of GDM. Nrg1 combined with IL-6 and TNF-α might be a potential tool for GDM screening.
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http://dx.doi.org/10.1177/20420188211049614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504227PMC
October 2021

Identification of a Novel Variant, in an Escherichia coli Isolate from Hospital Wastewater in China.

mSphere 2021 Oct 13:e0077621. Epub 2021 Oct 13.

Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow Universitygrid.452666.5, Suzhou, Jiangsu, China.

Since the discovery of NDM-1 and the worldwide reporting of different variants have raised alarms concerning global health, the problem of carbapenem-resistant (CRE) has become increasingly serious. Therefore, research on the hydrolytic activity and molecular structure of NDM variants is beneficial to the development of antibacterial drugs. NDM has been evolving into variants that possess different hydrolysis activities toward β-lactam antibiotics. Here, we characterized a novel variant, named , identified from a multidrug-resistant Escherichia coli strain from hospital sewage. NDM-33 differed from NDM-5 with a single-amino-acid substitution (A72T). was located in the Tn-related region from an IncX3-type plasmid, pHD6415-NDM, that can be transferred horizontally. The genetic construct of showed higher MICs of carbapenems than a construct. Enzyme kinetics showed that NDM-33 had higher enzymatic activity for meropenem and cefazolin than NDM-5. The emergence of this novel NDM variant could pose a threat to public health because of its transferability and enhanced carbapenem activity. Our study described a novel NDM-33 variant from an E. coli strain isolated from hospital sewage, where it was associated with human disease and antibiotic exposure. Importantly, hospital sewage was increasingly considered to be related to CRE hosts. Pathogens were transmitted from reservoirs through direct and indirect contact, ingestion, and inhalation of contaminated water or aerosols. In addition, under the selective pressure of antibiotics, NDM variants will become the main strain in the hospital water system and evolve into high virulence and high resistance. The monitoring of NDM mutants is of great significance for preventing and controlling the evolution of superbugs.
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http://dx.doi.org/10.1128/mSphere.00776-21DOI Listing
October 2021

Supramolecular Self-Assembly of Nitrogen-Deficient Ag/g-CN Nanofiber Films with Enhanced Charge Transfer Dynamics for Efficient Visible-Light Photocatalytic Activity.

ACS Appl Mater Interfaces 2021 Oct 13. Epub 2021 Oct 13.

Institute for Advanced Study, Chengdu University, Chengdu 610106, China.

Molecular self-assembly of organic molecules through noncovalent interactions is a powerful strategy for designing functional materials. Herein, we fabricated a novel free-standing Ag/g-CN nanofiber (Ag/CNNF) film via a water-based molecular engineering approach followed by pyrolysis using a cyanuric acid-melamine complex as the precursor. Uniform dispersion of plasmonic Ag nanoparticles and incorporation of nitrogen vacancies were synchronously introduced into the 3D highly interconnected porous CNNF framework. The resulting Ag/CNNF film with multilevel interlayer spacing distributions significantly expedited more sufficient charge transfer dynamics not only at Schottky junction sites but also throughout hierarchical CN by exciton dissociation. Benefiting from the synergistic enhancement in visible light harvesting capability and steered charge carrier transfer in a longitudinal direction, the Ag/CNNF film presented remarkably boosted photocatalytic ability both for hydrogen production and tetracycline degradation. The optimal Ag/CNNF-2 film exhibited a prominent photocatalytic hydrogen evolution rate of 1240 μmol g h without the Pt co-catalyst under visible light illumination, which was 10.3 times as high as that of bulk g-CN. Significantly, 1D Ag/g-CN nanofibers self-assembled into an ordered and macroscopic film, which was more favorable in practical applications owing to good reusability and high processability. This work paved the way for the facile preparation of supramolecular self-assembled CN-based film photocatalysts.
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http://dx.doi.org/10.1021/acsami.1c15321DOI Listing
October 2021

Induced neural progenitor cell-derived extracellular vesicles promote neural progenitor cell survival via extracellular signal-regulated kinase pathway.

CNS Neurosci Ther 2021 Oct 13. Epub 2021 Oct 13.

Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China.

Proposed model for the anti-apoptotic effects of induced neural stem/progenitor cell (iNPC)-derived extracellular vesicles (EVs). iNPC release EVs that are abundantly loaded with growth factor-related proteins. These growth factor-enriched EVs enhance the phosphorylation of extracellular signal-regulated kinase (ERK), but not AKt. The EV-induced activation of ERK pathway then inhibit the apoptosis of NPCs in various pathological conditions including oxidative stress and starvation.
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http://dx.doi.org/10.1111/cns.13744DOI Listing
October 2021

Miro1 provides neuroprotection via the mitochondrial trafficking pathway in a rat model of traumatic brain injury.

Brain Res 2021 Oct 9:147685. Epub 2021 Oct 9.

Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

The outer mitochondrial membrane protein mitochondrial Rho-GTPase 1 (Miro1) is known to be involved in the regulation of mitochondrial transport required for neuronal protection. Previous reports established that disruption of Miro1-dependent mitochondrial movement could result in nervous system diseases such as Parkinson's disease and Alzheimer's disease. This study was designed to explore the expression and mechanisms of Miro1 in secondary brain injury after traumatic brain injury (TBI). A total of 115 male Sprague Dawley rats were used in the weight-drop TBI rat model, and Miro1 in vivo knockdown was performed 24 h before TBI modeling by treatment with Miro1 short-interfering RNA. Real-time polymerase chain reaction, western blot, immunofluorescence, adenosine triphosphate (ATP) level assay, neuronal apoptosis, brain water content measurement, and neurological score analyses were carried out. Our results showed that the mRNA and protein levels of Miro1 were increased after TBI and co-localized with neurons and astrocytes in the peri-injury cortex. Moreover, Miro1 knockdown further exacerbated neuronal apoptosis, brain edema, and neurological deficits at 48 h after TBI, accompanied by impaired mitochondrial transport, reduction of mitochondria number and energy deficiency. Additionally, the apoptosis-related factors Bax upregulation and Bcl-2 downregulation as Miro1 knockdown after TBI implied that antiapoptotic effects on neuroprotection of Miro1, which were verified by the Fluoro-Jade C (FJC) staining and TUNEL staining. In conclusion, these findings suggest that Miro1 probably plays a neuroprotective role against secondary brain injury through the mitochondria trafficking pathway, suggesting that enhancing Miro1 might be a new strategy for the treatment of TBI.
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http://dx.doi.org/10.1016/j.brainres.2021.147685DOI Listing
October 2021

Pancreatic neuroendocrine tumor with ectopic adrenocorticotropic hormone syndrome: a case report and 5-year follow-up.

Endocr J 2021 Oct 9. Epub 2021 Oct 9.

Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, 230001, China.

Pancreatic neuroendocrine tumors (P-NETs) secreting ectopic adrenocorticotropic hormones (ACTH) are rare and often delayed in diagnosis due to their atypical clinical characteristics. Here, we describe a case of P-NET in the pancreatic tail. The tumor had metastasized to the liver and secreted gastrin and ACTH. A 60-year-old female patient was diagnosed with gastrinoma in the pancreatic tail with liver metastases in 2015. After 3 months, the patient presented refractory hypokalemia and thyroid dysfunction. The final diagnosis was P-NET with ectopic ACTH syndrome (EAS). After cytoreductive surgery and the use of long-acting somatostatin analogs, plasma potassium levels and thyroid function were effectively corrected. Although Sandostatin LAR Depot and proton pump inhibitors (PPIs) were used throughout the follow-up period, the tumor relapsed 4 years later. After aggressive treatment, including right hepatectomy, microwave coagulation of the left liver, and cholecystectomy, the tumor returned 4 months later. Finally, the patient underwent three hepatic artery embolizations and 12 courses of CAPTEM regimen chemotherapy. The markers of disease were almost maintained in the normal ranges until now. We have followed up on this case for more than 5 years. A timely and comprehensive examination of hormones and immunohistochemistry is essential. The prognosis of P-NET is poor. Regular long-term follow-up and the application of combined therapies are helpful to control the disease and improve the prognosis.
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http://dx.doi.org/10.1507/endocrj.EJ21-0297DOI Listing
October 2021

Combined association of early exposure to long-chain n-3 polyunsaturated fatty acids, mercury and selenium with cognitive performance in 1-year-old infants.

Environ Res 2021 Oct 7:112186. Epub 2021 Oct 7.

Department of Obstetrics and Gynecology, Vagelos College of Physicians and Surgeons, Columbia University, New York, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA. Electronic address:

Background: Previous studies on long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) and infant neurodevelopment did not consider effect modifications of mercury (Hg) and selenium (Se).

Objectives: To examine the joint association of prenatal LCn3PUFAs, Hg and Se with infant cognitive performance, and to explore whether DNA methylation may explain this potential association.

Methods: A total of 484 newborns were enrolled from the Shanghai Birth Cohort with available data on cord blood LCn3PUFA, nail Hg and Se during 2015-2016. Cord blood LCn3PUFA concentrations were assessed by gas chromatography, and nail Hg and Se concentrations were measured using clippings collected within 6 months of birth by inductively coupled plasma mass spectrometry. Five aspects of infant neurodevelopment (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Age and Stage Questionnaire (ASQ) at ages 6 and 12 months. Multivariable-adjusted generalized estimating equations models were performed to examine the associations between cord blood LCn3PUFA concentrations and ASQ test scores, and these associations were stratified by nail Hg and Se levels. Epigenome-wide DNA methylation in cord blood was compared in a random subgroup consisting of 19 infants from the highest and 21 from the lowest decile of LCn3PUFA concentrations.

Results: LCn3PUFAs were not significantly associated with any ASQ test scores. However, in the subgroup with lower Hg (
Conclusion: The association of prenatal LCn3PUFA concentrations with infant neurodevelopment, particularly gross motor skills, may be observed among infants with high Se and low Hg levels.
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http://dx.doi.org/10.1016/j.envres.2021.112186DOI Listing
October 2021

WNK3 Promotes Neuronal Survival after Traumatic Brain Injury in Rats.

Neuroscience 2021 Oct 6. Epub 2021 Oct 6.

Jiangsu Key Laboratory of Neuropsychiatric Diseases, Institute of Neuroscience, Soochow University, Suzhou, China.

With-no-lysine kinase 3 (WNK3) is a key regulator of chloride ion transport and neuronal survival in diverse cell types. WNK3 was previously found to regulate the activity of Na-K-2Cl cotransporter-1 (NKCC1) in ischemia-associated brain damage. However, the role of WNK3 in traumatic brain injury (TBI) has not yet been studied. A weight-drop TBI model was established in Sprague-Dawley rats. Overexpression and specific inhibition were used to investigate the role of WNK3 in TBI via Western blot, immunofluorescence, neuronal apoptosis, brain water content, and neurological score analyses. We found pronounced TBI-induced downregulation of WNK3 expression and upregulation of NKCC1 expression in neurons, especially at 48 h. Overexpression of WNK3 significantly ameliorated neuronal apoptosis, blood-brain barrier (BBB) disruption, brain edema and neurological deficits at 48 h after TBI. These effects were concomitant with reductions in p-NKCC1 and phosphorylated extracellular signal-regulated kinase (p-ERK1/2) expression. Furthermore, bumetanide administration enhanced the neuroprotective effects of WNK3 overexpression against brain injury. Thus, WNK3 plays a neuroprotective role in TBI, and overexpression of WNK3 may increase cell resistance to apoptotic insults and brain edema, thereby alleviating secondary brain injury.
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http://dx.doi.org/10.1016/j.neuroscience.2021.09.021DOI Listing
October 2021

Neonatal encephalopathy plasma metabolites are associated with neurodevelopmental outcomes.

Pediatr Res 2021 Oct 7. Epub 2021 Oct 7.

Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: To investigate mechanisms of injury and recovery in neonatal encephalopathy (NE), we performed targeted metabolomic analysis of plasma using liquid chromatography with tandem mass spectrometry (LC/MS/MS) from healthy term neonates or neonates with NE.

Methods: Plasma samples from the NE (n = 45, day of life 0-1) or healthy neonatal (n = 30, ≥36 weeks gestation) cohorts had LC/MS/MS metabolomic profiling with a 193-plex targeted metabolite assay covering >366 metabolic pathways. Metabolite levels were compared to 2-year neurodevelopmental outcomes measured by the Bayley Scales of Infant and Toddler Development III (Bayley-III).

Results: Out of 193 metabolites, 57 met the pre-defined quality control criteria for analysis. Significant (after false discovery rate correction) KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways included aminoacyl-tRNA biosynthesis, arginine biosynthesis, and metabolism of multiple amino acids. Significant disease pathways included seizures. In regression models, histidine and C6 sugar amine were significantly associated with cognitive, motor, and language and betaine with cognitive and motor Bayley-III composite scores. The addition of histidine, C6 sugar amine, and betaine to a Sarnat score-based clinical regression model significantly improved model performance (Akaike information criterion and adjusted r) for Bayley-III cognitive, motor, and language scores.

Conclusions: Plasma metabolites may help to predict neurological outcomes in neonatal brain injury and enhance current clinical predictors.

Impact: Plasma metabolites may help to predict neurological outcomes in NE and supplement current clinical predictors. Current metabolomics research is limited in terms of clinical application and association with long-term outcomes. Our study presents novel associations of plasma metabolites from the first 24 h of life and 2-year neurodevelopmental outcomes for infants with NE. Our metabolomics discovery provides insight into possible disease mechanisms and methods to rescue and/or supplement metabolic pathways involved in NE. Our metabolomics discovery of metabolic pathway supplementations and/or rescue mechanisms may serve as adjunctive therapies for NE.
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http://dx.doi.org/10.1038/s41390-021-01741-xDOI Listing
October 2021

Neonatal biliary atresia combined with preduodenal portal vein: A case report.

World J Clin Cases 2021 Sep;9(25):7542-7550

Department of Pediatric Surgery, Children's Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China.

Background: Congenital biliary atresia is a type of obstruction of the bile ducts inside and outside the liver, which can lead to cholestatic liver cirrhosis and eventually liver failure. The preduodenal portal vein (PD-PV) is a rare developmental malformation of the PV. The PV courses in front of the duodenum. However, very few cases of neonatal biliary atresia combined with PD-PV have been reported in the scientific literature.

Case Summary: A 1-mo-and-4-d-old child was admitted to the hospital in January because of yellowish skin. After surgical consultation, surgical intervention was recommended. The child underwent Hilar-jejunal anastomosis, duodenal rhomboid anastomosis, and abdominal drainage under general anesthesia. During the operation, the PV was located at the anterior edge of the duodenum.

Conclusion: Diagnoses: (1) Congenital biliary atresia; (2) PD-PV; and (3) Congenital cardiovascular malformations. Outcomes: Recommendation for liver transplantation. Lessons: The choice of treatment options for neonatal biliary atresia combined with PD-PV.
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http://dx.doi.org/10.12998/wjcc.v9.i25.7542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464463PMC
September 2021

Physical properties and antibacterial activity of the composited films based on carboxymethyl cellulose and gelatin functionalized with ε-polylysine.

Int J Biol Macromol 2021 Oct 1. Epub 2021 Oct 1.

Laboratory of Muscle and Meat Biophysics, Institute of Biophysics and College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China; Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, Guangdong 524088, China; Laboratory of Muscle Biology & Meat Science, National Beef Cattle Improvement Center, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address:

Antibacterial composite films were produced from carboxymethyl cellulose-gelatin (CMC-Gel) blend with different concentration of ε-polylysine (ε-PL) and their physical and chemical properties were characterized. Compared with the control CMC-Gel film, the functionalized films had almost indistinguishable crystalline type, thickness, tensile strength, and elongation at break, however, poor water vapor barrier properties. The results showed that the ε-PL was well incorporated into CMC-Gel matrix by electrostatic interaction, as the changes of absorption peaks in the Fourier transform infrared spectrometer and the increase of glass transition temperature in differential scanning calorimeter. The films containing ε-PL showed excellent antibacterial activity against S. aureus, B. subtilis, E. coli and P. aeruginosa. In the composting experiment, the films become degraded on the seventh day, and further degraded with the growth of molds over time. The present results showed that the active films could be a potential material for food packaging.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.09.181DOI Listing
October 2021

The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma.

Cancer Med 2021 Oct 4. Epub 2021 Oct 4.

Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Lenvatinib is a novel multiple receptor tyrosine kinase inhibitor used for hepatocellular carcinoma (HCC) treatment. Although its main function is to suppress VEGFR and FGFR pathway, its immunomodulatory activity in HCC is not elucidated. Thus, this study aimed to investigate the immunomodulatory capability of lenvatinib in HCC.

Material And Methods: Totally 47 patients with HCC were enrolled in this study, and the immune cells and serum cytokine profiles before initiation of treatment and after 1 and 3 months were measured. The immune checkpoint receptors on the immune cells were also evaluated. Kaplan-Meier survival estimate and log rank tests were used to assess the prognostic value.

Result: The frequency of T helper (Th) cells and T regulatory (Treg) cells reduced after lenvatinib treatment, while cytotoxic T lymphocyte (CTL) cells increased significantly. The cytokine profiles showed IL-2, IL-5, IFN-γ increased; other cytokines including IL-6, IL-10, TNF- α and TNF- β decreased with lenvatinib therapy. Furthermore, the PD-1 and TIM-3 expressed on CTL had greatly decreased; the expression of TIM-3 and CTLA-4 was reduced on Treg cells as well. Besides, the new index CTL/Treg ratio was created, and low ratio was associated with the unfavorable outcome of HCC patients.

Conclusion: Our results confirmed that lenvatinib is capable of improving patients' immune status, saving the effector cells from exhaustion status and inhibiting the number and function of immunosuppressive cells. The novel index CTL/Treg ratio qualifies as a predictor for the outcome of patients with lenvatinib therapy.
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http://dx.doi.org/10.1002/cam4.4312DOI Listing
October 2021

Transcriptome Analyses Identify a Metabolic Gene Signature Indicative of Antitumor Immunosuppression of EGFR Wild Type Lung Cancers With Low PD-L1 Expression.

Front Oncol 2021 14;11:643503. Epub 2021 Sep 14.

Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Purpose: With the development and application of targeted therapies like tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), non-small cell lung cancer (NSCLC) patients have achieved remarkable survival benefits in recent years. However, epidermal growth factor receptor (EGFR) wild-type and low expression of programmed death-ligand 1 (PD-L1) NSCLCs remain unmanageable. Few treatments for these patients exist, and more side effects with combination therapies have been observed. We intended to generate a metabolic gene signature that could successfully identify high-risk patients and reveal its underlying molecular immunology characteristics.

Methods: By identifying the bottom 50% PD-L1 expression level as PD-L1 low expression and removing EGFR mutant samples, a total of 640 lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) tumor samples and 93 adjacent non-tumor samples were finally extracted from The Cancer Genome Atlas (TCGA). We identified differentially expressed metabolic genes (DEMGs) by R package limma and the prognostic genes by Univariate Cox proportional hazards regression analyses. The intersect genes between DEMGs and prognostic genes were put into the least absolute shrinkage and selection operator (LASSO) penalty Cox regression analysis. The metabolic gene signature contained 18 metabolic genes generated and successfully stratified LUAD and LUSC patients into the high-risk and low-risk groups, which was also validated by the Gene Expression Omnibus (GEO) database. Its accuracy was proved by the time-dependent Receiver Operating Characteristic (ROC) curve, Principal Components Analysis (PCA), and nomogram. Furthermore, the Single-sample Gene Set Enrichment Analysis (ssGSEA) and diverse acknowledged methods include XCELL, TIMER, QUANTISEQ, MCPcounter, EPIC, CIBERSORT-ABS, and CIBERSORT revealed its underlying antitumor immunosuppressive status. Besides, its relationship with somatic copy number alterations (SCNAs) and tumor mutational burden (TMB) was also discussed.

Results: It is noteworthy that metabolism reprogramming is associated with the survival of the double-negative LUAD and LUSC patients. The SCNAs and TMB of critical metabolic genes can inhibit the antitumor immune process, which might be a promising therapeutic target.
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http://dx.doi.org/10.3389/fonc.2021.643503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476909PMC
September 2021

Pro-protein convertase subtilisin/kexin type 9 promotes intestinal tumor development by activating Janus kinase 2/signal transducer and activator of transcription 3/SOCS3 signaling in Apc mice.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211038345

Department of Pharmacy, Cheeloo College of Medicine, 66555Shandong University, Jinan, China.

Introduction: Pro-protein convertase subtilisin/kexin type 9 (PCSK9) regulates lipoprotein homeostasis in humans. Evolocumab is a selective PCSK9 inhibitor that can reduce low-density lipoprotein cholesterol (LDLC) level and decrease hypercholesterolemia. The current study aimed to explore whether PCSK9 increases the risk of colorectal cancer.

Methods: First, we utilized the classic intestinal tumor Apc mouse model and PCSK9 knock-in (KI) mice to establish ApcPCSK9(KI) mice. Then, we investigated the effect of PCSK9 overexpression in ApcPCSK9(KI) mice and PCSK9 inhibition using evolocumab on the progression of intestinal tumors by hematoxylin and eosin (HE) staining, Western blot, and immunohistochemistry (IHC) assay.

Results: ApcPCSK9(KI) mice had higher numbers and larger sizes of adenomas, with 83.3% of these mice developing adenocarcinoma (vs. 16.7% of Apc mice). However, treatment with evolocumab reduced the number and size of adenomas and prevented the development of adenocarcinomas in Apc mice. PCSK9 overexpression reduced tumor cell apoptosis, the Bax/bcl-2 ratio, and the levels of cytokine signaling 3 protein (SOCS3) suppressors, but activated Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling in intestinal tumors. In contrast, evolocumab treatment had the opposite effect on Apcmice.

Conclusion: PCSK9 might act as an oncogene or have an oncogenic role in the development and progression of colorectal cancer via activation of JAK2/STAT3/SOCS3 signaling.
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http://dx.doi.org/10.1177/20587384211038345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485261PMC
September 2021

Notch-1 signaling promotes reattachment of suspended cancer cells by cdc42-dependent microtentacles formation.

Cancer Sci 2021 Sep 28. Epub 2021 Sep 28.

Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.

Circulating tumor cells (CTCs) are associated with a higher risk of metastasis in tumor patients. The adhesion and arrest of CTCs at a secondary site is an essential prerequisite for the occurrence of tumor metastasis. CTC reattachment has shown to be dependent on microtentacle (McTN) formation in vivo. However, the specific molecular mechanism of McTN formation in suspended cancer cells remains largely unclear. Here, we demonstrated that the activation of Notch-1 signaling triggers McTN formation to facilitate cell reattachment in suspended cell culture conditions. Moreover, molecular mechanistic studies revealed that McTN formation is governed by the balance between microtubule-driven outgrowth and actomyosin-driven cell contractility. The activation of Notch-1 downregulates the acetylation level of microtubules via the Cdc42/HDAC6 pathway, which contributes to microtubule polymerization. Simultaneously, Notch-1 signaling-induced Cdc42 activation also reduced phosphorylation of myosin regulatory light chain, leading to cell contractility attenuation. Altogether, these results defined a novel mechanism by which Notch-1 signaling disturbs the balance between the expansion of microtubules and contraction of the cortical actin, which promotes McTN formation and cell reattachment. Our findings provide a new perspective on the effective therapeutic target to prevent CTC reattachment.
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http://dx.doi.org/10.1111/cas.15146DOI Listing
September 2021

Controlling plasticizer migration based on crystal structure and micromorphology in propionylated starch-based food packaging nanocomposites.

Carbohydr Polym 2021 Dec 1;273:118621. Epub 2021 Sep 1.

Key Laboratory of Healthy Food Development and Nutrition Regulation of China National Light Industry, School of Chemical Engineering and Energy Technology, Dongguan University of Technology, Dongguan 523808, China. Electronic address:

Migration of additives is an important issue for proper application in food packaging. In this work, propionylated waxy and normal starch-based nanocomposites (PW-N and PN-N) with two different amylopectin content were immersed in distilled water, and structural changes and migration mechanism of plasticizer (triacetin) were discussed in detail. Results showed that when immersion time was prolonged to 150 h, small crystals of PN-N disappeared, and amorphous structures formed gradually in PW-N and PN-N. Exfoliated structures still remained in PW-N with prolonged immersion time, while exfoliated structures gradually formed from intercalated ones in PN-N, and the peak representing d001 (d-spacing) at q = 1.70 nm faded. The migration mechanism of triacetin obeyed the first-order kinetic model and Fick's law; furthermore, in comparison with PW-N, PN-N showed a larger diffusion coefficient (D = 12.13 μm·h). These results contributed to expanding the application of starch-based nanocomposites in future environmentally friendly food packaging.
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http://dx.doi.org/10.1016/j.carbpol.2021.118621DOI Listing
December 2021

Relationship between age, refractive errors and motor fusion in a normal Chinese adult population: a cross-sectional study.

BMC Ophthalmol 2021 Sep 23;21(1):345. Epub 2021 Sep 23.

Department of Ophthalmology, Jinshan Hospital of Fudan University, 201508, Shanghai, China.

Background: To investigate the relationships between motor fusion and sex, age and spherical equivalent (SE).

Methods: This observational study enrolled 243 healthy, nonstrabismic adults, including 94 men and 149 women aged 20 to 59 years. The subjects were divided into three groups according to SE: myopic, emmetropic and hyperopic groups. The subjects were also divided into four groups according to age: 20-29, 30-39, 40-49 and 50-59 years groups. Motor fusion was measured with a synoptophore, including subjective angle (SA), divergence, convergence and fusional vergence range (FVR).

Results: The mean values of divergence, convergence and FVR for the whole sample group were 9.72 ± 0.26°, 19.34 ± 0.54°, and 29.06 ± 0.62°, respectively. A higher value of divergence was found in the myopic group than in the emmetropic group (p < 0.05). SE and divergence were significantly different among age groups (all p < 0.05). In addition, linear regression analysis showed that SE was correlated with divergence (p = 0.003). Age was correlated with SE, divergence and FVR (p < 0.001, p = 0.005, p = 0.002, respectively). In addition, the proportion of SA being in the comfort zone (defined as the value of SA satisfying Percival's criterion) in the age groups was significantly different (χ = 8.283, p = 0.041).

Conclusions: Motor fusion is associated with age and SE in the normal Chinese adult population.
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http://dx.doi.org/10.1186/s12886-021-02105-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461894PMC
September 2021

IPR-mediated activation of BK channels contributes to mGluR5-induced protection against spinal cord ischemia-reperfusion injury.

Neurochem Int 2021 Nov 20;150:105191. Epub 2021 Sep 20.

Department of Neurosurgery, The 904th Hospital of PLA, Medical School of Anhui Medical University, Wuxi, Jiangsu, 214044, China; Department of Neurosurgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210000, China. Electronic address:

Spinal cord ischemia-reperfusion injury (SCIRI) can cause dramatic neuron loss and lead to paraplegia in patients. In this research, the role of mGluR5, a member of the metabotropic glutamate receptors (mGluRs) family, was investigated both in vitro and in vivo to explore a possible method to treat this complication. In vitro experiment, after activating mGluR5 via pretreating cells with (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG) and 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB), excitotoxicity induced by glutamate (Glu) was attenuated in primary spinal cord neurons, evidenced by higher neuron viability, decreased lactate dehydrogenase (LDH) release and less detected TUNEL-positive cells. According to Western Blot (WB) results, Glu treatment resulted in a high level of large-conductance Ca2+- and voltage-activated K+ (BK) channels, with activation relying on the mGluR5-IP3R (inositol triphosphate) pathway. In vivo part, a rat model of SCIRI was built to further investigate the role of mGluR5. After pretreating them with CHPG and CDPPB, the rats showed markedly lower spinal water content, attenuated motor neuron injury in the spinal cord of L4 segments, and better neurological function. This effect could be partially reversed by paxilline, a blocker of BK channels. In addition, activating BK channels alone using specific openers: NS1619 or NS11021 can protect spinal cord neurons from injury induced by either SCIRI or Glu. In conclusion, in this research, we proved that mGluR5 exerts a protective role in SCIRI, and this effect partially works via IPR-mediated activation of BK channels.
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http://dx.doi.org/10.1016/j.neuint.2021.105191DOI Listing
November 2021

Berberine Acts on C/EBPβ/lncRNA Gas5/miR-18a-5p Loop to Decrease the Mitochondrial ROS Generation in HK-2 Cells.

Front Endocrinol (Lausanne) 2021 30;12:675834. Epub 2021 Aug 30.

Department of Endocrinology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Background: Berberine (BBR) has therapeutic effect on diabetic nephropathy (DN), but its molecular mechanism is not completely clear.

Methods: The DN model was established to observe the therapeutic effect of BBR. The expression levels of lncRNA Gas5 were detected by PCR. The transcriptional regulation of CCAAT enhancer binding protein beta (C/EBPβ) on Gas5 was analyzed by chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) and luciferase reporter gene assay. The targeted regulation between Gas5 and miR-18a-5p and between miR-18a-5p and C/EBPβ 3'-untranslated region (3'-UTR) was also analyzed.

Results: In HG environment, BBR decreased the mitochondrial reactive oxygen species (ROS) generation and activated the C/EBPβ expression in HK-2 cells; C/EBPβ could combine with the reaction element on the promoter of Gas5 to promote its expression. Gas5 also inhibited the miR-18a-5p expression as competing endogenous RNA (ceRNA) and reduce the negative regulatory effect of miR-18a-5p on C/EBPβ. BBR could activate C/EBPβ/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signal pathway, regulate mitochondrial energy metabolism, and inhibit ROS production and apoptosis by activating C/EBPβ/Gas5/miR-18a-5p positive feedback loop in HG environment. It also showed that BBR alleviated streptozotocin (STZ) induced renal injury in DN rats .

Conclusions: This study suggested that BBR could regulate the mitochondrial ROS generation by activating the positive feedback loop of C/EBPβ/Gas5/miR-18a-5p.
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http://dx.doi.org/10.3389/fendo.2021.675834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435884PMC
August 2021

Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma.

J Exp Med 2021 Oct 8;218(10). Epub 2021 Sep 8.

Institut National de la Santé et de la Recherche Médicale U1015, Université Paris-Saclay, Gustave Roussy Cancer Campus, Villejuif, France.

Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract.
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http://dx.doi.org/10.1084/jem.20200853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429038PMC
October 2021

Over 50,000 Metagenomically Assembled Draft Genomes for the Human Oral Microbiome Reveal New Taxa.

Genomics Proteomics Bioinformatics 2021 Sep 4. Epub 2021 Sep 4.

BGI-Shenzhen, Shenzhen 518083, China; Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen 518083, China; Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen DK-2100, Denmark. Electronic address:

The oral cavity of each person is home to hundreds of bacterial species. While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing, metagenomic and genomic information remains scarce compared to the fecal microbiome. Here, using metagenomic shotgun data for 3346 oral metagenomics samples together with 808 published samples, we obtain 56,213 metagenome-assembled genomes (MAGs), more than 64% of the 3589 species-level genome bins (SGBs) contained no publicly available genomes. The resulting genome collection is representative of samples around the world and containing many genomes from candidate phyla radiation (CPR) which lack monoculture. Also, it enables the discovery of new taxa such as a family Candidatus Bgiplasma within order Acholeplasmataceae. Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Porphyromonas and Neisseria. The oral microbes encode genes that could potentially metabolize drugs. Apart from these findings, a strongly male-enriched Campylobacter species was identified. Oral samples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis. Thus, these data lay down a genomic framework for future inquiries of the human oral microbiome.
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http://dx.doi.org/10.1016/j.gpb.2021.05.001DOI Listing
September 2021

Integrated Analysis of mRNA and Non-coding RNA Transcriptome in Pepper () Hybrid at Seedling and Flowering Stages.

Front Genet 2021 20;12:685788. Epub 2021 Aug 20.

Key Laboratory for Quality Regulation of Tropical Horticultural Crops of Hainan Province, College of Horticulture, Hainan University, Haikou, China.

Pepper is an important vegetable in the world. In this work, mRNA and ncRNA transcriptome profiles were applied to understand the heterosis effect on the alteration in the gene expression at the seedling and flowering stages between the hybrid and its parents in . Our phenotypic data indicated that the hybrid has dominance in leaf area, plant scope, plant height, and fruit-related traits. Kyoto Encyclopedia of Genes and Genomes analysis showed that nine members of the plant hormone signal transduction pathway were upregulated in the seedling and flowering stages of the hybrid, which was supported by weighted gene coexpression network analysis and that (auxin response factor 8), (auxin-responsive protein IAA20), (ethylene-responsive transcription factor), and (ethylene-responsive transcription factor WIN1) were candidate hub genes, suggesting the important potential role of the plant hormone signal transduction in pepper heterosis. Furthermore, some transcription factor families, including bHLH, MYB, and HSF were greatly over-dominant. We also identified 2,525 long ncRNAs (lncRNAs), 47 micro RNAs (miRNAs), and 71 circle RNAs (circRNAs) in the hybrid. In particular, downregulation of miR156, miR169, and miR369 in the hybrid suggested their relationship with pepper growth vigor. Moreover, we constructed some lncRNA-miRNA-mRNA regulatory networks that showed a multi-dimension to understand the ncRNA relationship with heterosis. These results will provide guidance for a better understanding of the molecular mechanism involved in pepper heterosis.
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http://dx.doi.org/10.3389/fgene.2021.685788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417703PMC
August 2021

Association Between Physical Exercise and Mental Health During the COVID-19 Outbreak in China: A Nationwide Cross-Sectional Study.

Front Psychiatry 2021 16;12:722448. Epub 2021 Aug 16.

College of Health Sciences, Wuhan Sports University, Wuhan, China.

The COVID-19 has undergone several mutations, and caused deleterious effects on physical and mental health of people worldwide. Whilst physical exercise is known for its positive effect on enhancing immunity and reducing the negative consequences of unhealthy emotional states caused by the pandemic; there is a severe lack of psychological exercise intervention measures and mitigation strategies to advance the knowledge and role of physical exercise to improve mental health in most countries. This study surveyed the association between physical exercise and mental health burden during the COVID-19 outbreak in China to better understand the influence of different physical exercise types on reducing mental health burden during the pandemic. ANOVA, binary logistic regression, the chi-square test, and Spearman's correlation analysis were used for statistical analysis. 14,715 participants were included. The results showed that Chinese residents had several poor mental health conditions during the COVID-19 outbreak. And there was a significant positive correlation between the extent of adverse effects on mental health and provincial proportions of confirmed COVID-19 cases (r = 0.365, < 0.05). Some main factors caused an unhealthy psychological status, including epidemic severity (62.77%, 95% CI 58.62-65.64%), prolonged home quarantine (60.84%, 95% CI 58.15-63.25%), spread of large amounts of negative information about COVID-19 in the media (50.78%, 95% CI 47.46-53.15%), limitations in daily life and social interaction (45.93%, 95%CI 42.46-47.55%), concerns about students' learning (43.13%, 95% CI 40.26-45.48%), and worries about being infected (41.13%, 95% CI 39.16-45.23%). There was a significant association between physical exercise and mental health. The largest associations were seen for home-based group entertainment exercise (i.e., family games, rope skipping, and badminton), Chinese traditional sports (i.e., Chinese martial arts, Taijiquan and Qigong), and popular sports (i.e., yoga, video dancing, sensory-motor games, and whole-body vibration), as well as durations of 30-60 min per session, frequencies of three to five times per week and a total of 120-270 min of moderate-intensity exercise weekly during the COVID-19 outbreak ( < 0.05).
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http://dx.doi.org/10.3389/fpsyt.2021.722448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418057PMC
August 2021

Pressure dependent thermoreflectance spectroscopy induced by interband transitions in metallic nano-film.

iScience 2021 Sep 17;24(9):102990. Epub 2021 Aug 17.

School of Energy and Power Engineering, Key Laboratory of Ocean Energy Utilization and Energy Conservation of Ministry of Education, Dalian University of Technology, Dalian 116024, Liaoning, P. R. China.

Utilizing high-pressure to modulate optical properties, such as thermoreflectance (), over a wide range has received much attention. Nevertheless, how the pressure exerts on the complex dielectric constant and finally on remains elusive. Here, we perform a thoroughly experimental and theoretical investigation on of Al nano-film from 0 to 25 GPa. The values exhibit a sine-like pressure-dependence, with the zero-crossing appearing at around 6 GPa. These special phenomena are well explained from electron transition viewpoints. The calculations show that the energy difference of parallel bands is enlarged from 1.45 to 2 eV, thereby increasing the threshold for electron transitions. The lifted threshold changes the optical absorption rates of Al and the density of states of the electrons involving interband transitions; finally, the resulting exhibits such a pressure-dependent behavior. Our findings provide a deep insight on pressure-induced electronic transitions and photon-electron interactions in metals.
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http://dx.doi.org/10.1016/j.isci.2021.102990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405916PMC
September 2021

Role of the PD-1/PD-L1 Signaling in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Recent Insights and Future Directions.

Mol Neurobiol 2021 Sep 3. Epub 2021 Sep 3.

Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Xinmin Street 71#, Changchun, 130021, China.

Multiple sclerosis (MS) is an autoimmunity-related chronic demyelination disease of the central nervous system (CNS), causing young disability. Currently, highly specific immunotherapies for MS are still lacking. Programmed cell death 1 (PD-1) is an immunosuppressive co-stimulatory molecule, which is expressed on activated T lymphocytes, B lymphocytes, natural killer cells, and other immune cells. PD-L1, the ligand of PD-1, is expressed on T lymphocytes, B lymphocytes, dendritic cells, and macrophages. PD-1/PD-L1 delivers negative regulatory signals to immune cells, maintaining immune tolerance and inhibiting autoimmunity. This review comprehensively summarizes current insights into the role of PD-1/PD-L1 signaling in MS and its animal model experimental autoimmune encephalomyelitis (EAE). The potentiality of PD-1/PD-L1 as biomarkers or therapeutic targets for MS will also be discussed.
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http://dx.doi.org/10.1007/s12035-021-02495-7DOI Listing
September 2021

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells.

Int J Oncol 2021 10 3;59(4). Epub 2021 Sep 3.

Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.

Pyroptosis is mediated by gasdermins and serves a critical role in ionizing radiation (IR)‑induced damage in normal tissues, but its role in cancer radiotherapy and underlying mechanisms remains unclear. Long non‑coding (lnc) RNAs serve important roles in regulating the radiosensitivity of cancer cells. The present study aimed to investigate the mechanistic involvement of lncRNAs in IR‑induced pyroptosis in human colorectal cancer HCT116 cells. LncRNA, microRNA (miR)‑448 and gasdermin E (GSDME) levels were evaluated using reverse transcription‑quantitative polymerase chain reaction. Protein expression and activation of gasdermins were measured using western blotting. The binding association between miR‑448 and GSDME was assessed using the dual‑luciferase reporter assay. Pyroptosis was examined using phase‑contrast microscopy, flow cytometry, Cell Counting Kit‑8 assay and lactate dehydrogenase release assay. IR dose‑dependently induced GSDME‑mediated pyroptosis in HCT116 cells. GSDME was identified as a downstream target of miR‑448. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was upregulated in response to IR and enhanced GSDME expression by negatively regulating miR‑448 expression. Notably, NEAT1 knockdown suppressed IR‑induced pyroptosis, full‑length GSDME expression and GSDME cleavage compared with that in irradiated cells. In addition, NEAT1 knockdown rescued the IR‑induced decrease in cell viability in HCT116 cells. The findings of the present study indicated that lncRNA NEAT1 modulates IR‑induced pyroptosis and viability in HCT116 cells via miR‑448 by regulating the expression, but not activation of GSDME. The present study provides crucial mechanistic insight into the potential role of lncRNA NEAT1 in IR‑induced pyroptosis.
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http://dx.doi.org/10.3892/ijo.2021.5259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448542PMC
October 2021

Metabolic flexibility maintains proliferation and migration of FGFR signaling-deficient lymphatic endothelial cells.

J Biol Chem 2021 Aug 30;297(4):101149. Epub 2021 Aug 30.

Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. Electronic address:

Metabolic flexibility is the capacity of cells to alter fuel metabolism in response to changes in metabolic demand or nutrient availability. It is critical for maintaining cellular bioenergetics and is involved in the pathogenesis of cardiovascular disease and metabolic disorders. However, the regulation and function of metabolic flexibility in lymphatic endothelial cells (LECs) remain unclear. We have previously shown that glycolysis is the predominant metabolic pathway to generate ATP in LECs and that fibroblast growth factor receptor (FGFR) signaling controls lymphatic vessel formation by promoting glycolysis. Here, we found that chemical inhibition of FGFR activity or knockdown of FGFR1 induces substantial upregulation of fatty acid β-oxidation (FAO) while reducing glycolysis and cellular ATP generation in LECs. Interestingly, such compensatory elevation was not observed in glucose oxidation and glutamine oxidation. Mechanistic studies show that FGFR blockade promotes the expression of carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme of FAO; this is achieved by dampened extracellular signal-regulated protein kinase activation, which in turn upregulates the expression of the peroxisome proliferator-activated receptor alpha. Metabolic analysis further demonstrates that CPT1A depletion decreases total cellular ATP levels in FGFR1-deficient rather than wildtype LECs. This result suggests that FAO, which makes a negligible contribution to cellular energy under normal conditions, can partially compensate for energy deficiency caused by FGFR inhibition. Consequently, CPT1A silencing potentiates the effect of FGFR1 knockdown on impeding LEC proliferation and migration. Collectively, our study identified a key role of metabolic flexibility in modulating the effect of FGFR signaling on LEC growth.
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http://dx.doi.org/10.1016/j.jbc.2021.101149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498002PMC
August 2021

Recommender system of scholarly papers using public datasets.

AMIA Annu Symp Proc 2021 17;2021:672-679. Epub 2021 May 17.

University of Texas Health Science Center at Houston Houston, TX, USA.

The exponential growth of public datasets in the era of Big Data demands new solutions for making these resources findable and reusable. Therefore, a scholarly recommender system for public datasets is an important tool in the field of information filtering. It will aid scholars in identifying prior and related literature to datasets, saving their time, as well as enhance the datasets reusability. In this work, we developed a scholarly recommendation system that recommends research-papers, from PubMed, relevant to public datasets, from Gene Expression Omnibus (GEO). Different techniques for representing textual data are employed and compared in this work. Our results show that term-frequency based methods (BM25 and TF-IDF) outperformed all others including popular Natural Language Processing embedding models such as doc2vec, ELMo and BERT.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378599PMC
September 2021

Tumor stiffness measured by 3D magnetic resonance elastography can help predict the aggressiveness of endometrial carcinoma: preliminary findings.

Cancer Imaging 2021 Aug 28;21(1):50. Epub 2021 Aug 28.

Department of Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China.

Background: Preoperative evaluation of aggressiveness, including tumor histological subtype, grade of differentiation, Federation International of Gynecology and Obstetrics (FIGO) stage, and depth of myometrial invasion, is significant for treatment planning and prognosis in endometrial carcinoma (EC). The purpose of this study was to evaluate whether three-dimensional (3D) magnetic resonance elastography (MRE) can help predict the aggressiveness of EC.

Methods: From August 2015 to January 2019, 82 consecutive patients with suspected uterine tumors underwent pelvic MRI and MRE scans, and 15 patients with confirmed EC after surgical resection were enrolled. According to pathological results (tumor grade, histological subtype, FIGO stage, and myometrial invasiveness), the patients were divided into two subgroups. The independent-samples t-test or Mann-Whitney U test was used to compare the stiffness between different groups. The diagnostic performance was determined with receiver operating characteristic (ROC) curve analysis.

Results: The stiffness of EC with ≥ 50 % (n = 6) myometrial invasion was significantly higher than that with < 50 % (n = 9) myometrial invasion (3.68 ± 0.59 kPa vs. 2.61 ± 0.72 kPa, p = 0.009). Using a stiffness of 3.04 kPa as a cutoff value resulted in 100 % sensitivity and 77.8 % specificity for differentiating ≥ 50 % myometrial invasion from < 50 % myometrial invasion of EC. The stiffness of poorly differentiated EC (n = 8) was significantly higher than that of well/moderately differentiated EC (n = 7) (3.47 ± 0.64 kPa vs. 2.55 ± 0.82 kPa, p = 0.028). Using a stiffness of 3.04 kPa as a cutoff value resulted in 75 % sensitivity and 71.4 % specificity for differentiating poorly differentiated from well/moderately differentiated EC. The stiffness of FIGO stage II/III EC was significantly higher than that of FIGO stage I EC (3.69 ± 0.65 kPa vs. 2.72 ± 0.76 kPa, p = 0.030). Using a stiffness of 3.04 kPa as a cutoff value resulted in 100 % sensitivity and 70 % specificity for differentiating FIGO stage I EC from FIGO stage II/III EC. The tumor stiffness value in type II (n = 3) EC was higher than that in type I (n = 12) EC (3.67 ± 0.59 kPa vs. 2.88 ± 0.85 kPa), but the difference was not significant (p = 0.136).

Conclusions: Tumor stiffness measured by 3D MRE may be potentially useful for predicting tumor grade, FIGO stage and myometrial invasion of EC and can aid in the preoperative risk stratification of EC.
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http://dx.doi.org/10.1186/s40644-021-00420-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399726PMC
August 2021

The brain mechanism of awakening dysfunction in children with primary nocturnal enuresis based on PVT-NAc neural pathway: a resting-state fMRI study.

Sci Rep 2021 08 24;11(1):17079. Epub 2021 Aug 24.

Department of Pediatrics, Changzhou Children's Hospital of Nantong University, No. 468 Yanling Road, Changzhou, 213003, Jiangsu, People's Republic of China.

Primary nocturnal enuresis (PNE) affects children's physical and mental health with a high rate. However, its neural mechanism is still unclear. Studies have found that the paraventricular thalamus (PVT) is among the key brain regions implicated with awakening regulation and its control of the transition between sleep and wakening is dependent on signaling through the PVT-nucleus accumbens (NAc) pathway. So this study analyzed the function of brain regions and their connectivity of PVT and NAc. A total of twenty-six PNE and typically developing (TD) children were involved in the study and the methods of amplitude of low frequency fluctuation (ALFF), degree centrality (DC) and functional connectivity (FC) based on resting-state functional magnetic resonance imaging (rs-fMRI) were used to analyze the brain functions. Results showed that there was no statistical significant difference in ALFF and DC between PNE and TD children in bilateral PVT and NAc. And there was statistical significant difference of the comparison of the FC of left PVT (lPVT) and left NAc (lNAc) between PNE and TD children. Meanwhile, there was negative correlation between awakening score and the FC of rPVT and lNAc, and no obvious correlation between awakening score and the FC of lPVT and lNAc in PNE children. Meanwhile, there was both negative correlation between awakening score and the FC of lPVT, rPTV and lNAc in TD children. Therefore, the FC between rPVT and lNAc was more reliable in assessing the degree of awakening ability in PNE children. This finding could help establish the evaluation index of PNE.
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http://dx.doi.org/10.1038/s41598-021-96519-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385036PMC
August 2021
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