Publications by authors named "Lin Su"

428 Publications

P2Y1 purinergic receptor inhibition attenuated remifentanil-induced postoperative hyperalgesia via decreasing NMDA receptor phosphorylation in dorsal root ganglion.

Brain Res Bull 2021 Oct 12. Epub 2021 Oct 12.

Department of Anesthesiology, Tianjin Medical University General Hospital, No. 154 Anshan Road, Heping District, Tianjin 300052, PR China; Tianjin Research Institute of Anesthesiology, No. 154 Anshan Road, Heping District, Tianjin 300052, PR China. Electronic address:

Background: Remifentanil-induced postoperative hyperalgesia is an intractable side effect of the clinical use of remifentanil, the mechanism of which remains obscure, especially in the peripheral nervous system. N-methyl-D-aspartate receptor (NMDAR) phosphorylation in dorsal root ganglion (DRG) plays a pronociceptive role in neuropathic pain. The contribution of the P2Y1 purinergic receptor (P2Y1R) in DRG to pain hypersensitivity derived from various origins and P2Y1R upregulation-induced NMDAR activation in neurons have also been uncovered. This study aimed to investigate whether P2Y1R participates in nociceptive processing in the DRG and spinal cord in remifentanil-induced postoperative hyperalgesia.

Methods: Rats with remifentanil-induced postoperative hyperalgesia were intrathecally injected with NMDAR antagonist MK801 or P2Y1R antagonist MRS2179 at 10min prior to remifentanil infusion. Mechanical allodynia, heat hyperalgesia, and cold hyperalgesia were measured at -24 h, 2h, 6h, 24h, and 48h following remifentanil infusion. The P2Y1R expression and NMDAR expression and phosphorylation in DRG ipsilateral to the incision were detected by Western blot and immunofluorescence.

Results: Incision and remifentanil induced mechanical allodynia, heat hyperalgesia, and cold hyperalgesia accompanied by upregulated P2Y1R expression, increased NMDAR subunit NR1 expression and phosphorylation at Ser896, and NR2B expression and phosphorylation at Tyr1472 in DRG. Inhibition of NMDAR phosphorylation by MK801 effectively attenuated remifentanil-induced postoperative hyperalgesia. Furthermore, P2Y1R blockade by MRS2179 not only lessened remifentanil-evoked postoperative hypersensitivity to mechanical, heat, and cold stimuli, but also suppressed the increases in NR1 and NR2B expression and phosphorylation in DRG induced by incision and remifentanil.

Conclusion: The process by which P2Y1R mediates NMDAR expression and phosphorylation represents a mechanism of remifentanil-induced postoperative hyperalgesia in the DRG and/or spinal cord.
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http://dx.doi.org/10.1016/j.brainresbull.2021.10.006DOI Listing
October 2021

Engineering Wired Life: Synthetic Biology for Electroactive Bacteria.

ACS Synth Biol 2021 Oct 12. Epub 2021 Oct 12.

Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Washington, D.C. 20375, United States.

Electroactive bacteria produce or consume electrical current by moving electrons to and from extracellular acceptors and donors. This specialized process, known as extracellular electron transfer, relies on pathways composed of redox active proteins and biomolecules and has enabled technologies ranging from harvesting energy on the sea floor, to chemical sensing, to carbon capture. Harnessing and controlling extracellular electron transfer pathways using bioengineering and synthetic biology promises to heighten the limits of established technologies and open doors to new possibilities. In this review, we provide an overview of recent advancements in genetic tools for manipulating native electroactive bacteria to control extracellular electron transfer. After reviewing electron transfer pathways in natively electroactive organisms, we examine lessons learned from the introduction of extracellular electron transfer pathways into . We conclude by presenting challenges to future efforts and give examples of opportunities to bioengineer microbes for electrochemical applications.
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http://dx.doi.org/10.1021/acssynbio.1c00335DOI Listing
October 2021

Validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease.

World J Gastroenterol 2021 Sep;27(34):5753-5763

Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China.

Background: Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease (MAFLD).

Aim: To evaluate the diagnostic performance of four non-invasive scores including aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score (BARD), and nonalcoholic fatty liver disease fibrosis score (NFS) in patients with MAFLD.

Methods: Consecutive patients with histologically confirmed MAFLD were included. The discrimination ability of different non-invasive scores was compared.

Results: A total of 417 patients were included; 156 (37.4%) of them had advanced fibrosis (Metavir ≥ F3). The area under receiver operating characteristic curve of FIB-4, NFS, APRI, and BARD for predicting advanced fibrosis was 0.736, 0.724, 0.671, and 0.609, respectively. The area under receiver operating characteristic curve of FIB-4 and NFS was similar ( = 0.523), while the difference between FIB-4 and APRI ( = 0.001) and FIB-4 and BARD ( < 0.001) was statistically significant. The best thresholds of FIB-4, NFS, APRI, and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05, -2.1, 0.42, and 2. A subgroup analysis showed that FIB-4, APRI, and NFS performed worse in the pure MAFLD group than in the hepatitis B virus-MAFLD group.

Conclusion: APRI and BARD scores do not perform well in MAFLD. The FIB-4 and NFS could be more useful, but a new threshold is needed. Novel non-invasive scoring systems for fibrosis are required for MAFLD.
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http://dx.doi.org/10.3748/wjg.v27.i34.5753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473595PMC
September 2021

Loss of Ubiquitin Carboxy-Terminal Hydrolase L1 Impairs Long-Term Differentiation Competence and Metabolic Regulation in Murine Spermatogonial Stem Cells.

Cells 2021 Aug 31;10(9). Epub 2021 Aug 31.

Department of Comparative Biology & Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

Spermatogonia are stem and progenitor cells responsible for maintaining mammalian spermatogenesis. Preserving the balance between self-renewal of spermatogonial stem cells (SSCs) and differentiation is critical for spermatogenesis and fertility. Ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) is highly expressed in spermatogonia of many species; however, its functional role has not been identified. Here, we aimed to understand the role of UCH-L1 in murine spermatogonia using a mouse model. We confirmed that UCH-L1 is expressed in undifferentiated and early-differentiating spermatogonia in the post-natal mammalian testis. The mice showed reduced testis weight and progressive degeneration of seminiferous tubules. Single-cell transcriptome analysis detected a dysregulated metabolic profile in spermatogonia of compared to wild-type mice. Furthermore, cultured SSCs had decreased capacity in regenerating full spermatogenesis after transplantation in vivo and accelerated oxidative phosphorylation (OXPHOS) during maintenance in vitro. Together, these results indicate that the absence of UCH-L1 impacts the maintenance of SSC homeostasis and metabolism and impacts the differentiation competence. Metabolic perturbations associated with loss of UCH-L1 appear to underlie a reduced capacity for supporting spermatogenesis and fertility with age. This work is one step further in understanding the complex regulatory circuits underlying SSC function.
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http://dx.doi.org/10.3390/cells10092265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465610PMC
August 2021

Aminopeptidase N-targeting nanomolecule-assisted delivery of VEGF siRNA to potentiate antitumour therapy by suppressing tumour revascularization and enhancing radiation response.

J Mater Chem B 2021 Sep 22;9(36):7530-7543. Epub 2021 Sep 22.

Department of Radiology, Tianjin Medical University Second Hospital, No. 23, Pingjiang Road, Hexi District, Tianjin 300211, P. R. China.

Tumour revascularization and the consequent radioresistance activated by the up-regulated angiogenic pathway after radiation exposure remain a major bottleneck for improving the tumouricidal effect of radiotherapy (RT) in hepatocellular carcinoma (HCC). Herein, we show that fabricated aminopeptidase N (ANP/CD13)-targeting Gd-hybridized gold nanomolecules (tGd-GNMs) can efficaciously suppress tumour revascularization and the consequent radioresistance, and then synergize in augmenting the RT response. Both and experiments demonstrate that the targeted delivery of vascular endothelial growth factor (VEGF) siRNA into the tumour site and the generation of an abundance of intratumourally cytotoxic reactive oxygen species (ROS) under X-ray radiation by the tGd-GNMs complex has the capability to down-regulate VEGF gene expression and strengthen the radiation response. Furthermore, the tGd-GNMs complex contributes to excellent active tumour targeting ability, remarkably enhancing tumour contrast in the fluorescence, computed tomography (CT) and magnetic resonance (MR) imaging modalities in real-time with a long imaging time window. Overall, the synthesized tGd-GNMs complex with excellent potentiation of the antitumour ability and real-time multimodal imaging ability represents a promising visualized theranostic nanoplatform for the treatment of HCC.
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http://dx.doi.org/10.1039/d1tb00990gDOI Listing
September 2021

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

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

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

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

Effect of Body Mass Index on the Prognosis of Liver Cirrhosis.

Front Nutr 2021 20;8:700132. Epub 2021 Aug 20.

Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, China.

At present, the association of body mass index (BMI) with the prognosis of liver cirrhosis is controversial. Our retrospective study aimed to evaluate the impact of BMI on the outcome of liver cirrhosis. In the first part, long-term death was evaluated in 436 patients with cirrhosis and without malignancy from our prospectively established single-center database. In the second part, in-hospital death was evaluated in 379 patients with cirrhosis and with acute gastrointestinal bleeding (AGIB) from our retrospective multicenter study. BMI was calculated and categorized as underweight (BMI <18.5 kg/m), normal weight (18.5 ≤ BMI < 23.0 kg/m), and overweight/obese (BMI ≥ 23.0 kg/m). In the first part, Kaplan-Meier curve analyses demonstrated a significantly higher cumulative survival rate in the overweight/obese group than the normal weight group ( = 0.047). Cox regression analyses demonstrated that overweight/obesity was significantly associated with decreased long-term mortality compared with the normal weight group [hazard ratio (HR) = 0.635; 95% CI: 0.405-0.998; = 0.049] but not an independent predictor after adjusting for age, gender, and Child-Pugh score (HR = 0.758; 95%CI: 0.479-1.199; = 0.236). In the second part, Kaplan-Meier curve analyses demonstrated no significant difference in the cumulative survival rate between the overweight/obese and the normal weight groups ( = 0.094). Cox regression analyses also demonstrated that overweight/obesity was not significantly associated with in-hospital mortality compared with normal weight group (HR = 0.349; 95%CI: 0.096-1.269; = 0.110). In both of the two parts, the Kaplan-Meier curve analyses demonstrated no significant difference in the cumulative survival rate between underweight and normal weight groups. Overweight/obesity is modestly associated with long-term survival in patients with cirrhosis but not an independent prognostic predictor. There is little effect of overweight/obesity on the short-term survival of patients with cirrhosis and with AGIB.
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http://dx.doi.org/10.3389/fnut.2021.700132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417598PMC
August 2021

Validation of the SURFASA score to define steroid responsiveness in patients with acute autoimmune hepatitis.

J Hepatol 2021 Aug 25. Epub 2021 Aug 25.

Liver failure Group, Institute for Liver and Digestive Health, Division of Medicine, University College London Medical School, Royal Free Hospital, London, UK; European Foundation for the Study of Chronic Liver Failure (EFCLIF), Barcelona, Spain. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2021.08.013DOI Listing
August 2021

Two Putative Cypovirus-Encoded miRNAs Co-regulate the Host Gene of GTP-Binding Nuclear Protein Ran and Facilitate Virus Replication.

Front Physiol 2021 4;12:663482. Epub 2021 Aug 4.

School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, China.

microRNA (miRNA) plays important roles in regulating various biological processes, including host-pathogen interaction. Recent studies have demonstrated that virus-encoded miRNAs can manipulate host gene expression to ensure viral effective multiplication. cypovirus (BmCPV), a double-stranded RNA virus with a segmented genome, is one of the important pathogens for the economically important insect silkworm. Our present study indicated that two putative miRNAs encoded by BmCPV could promote viral replication by inhibiting the gene expression of GTP-binding nuclear protein Ran (), an essential component of the exportin-5-mediated nucleocytoplasmic transport of small RNAs. BmCPV-miR-1 and BmCPV-miR-3 are two of the BmCPV-encoded miRNAs identified in our previous studies. is a common target gene of them with binding sites all located in the 3'-untranslated region (3'-UTR) of its mRNA. The expression levels of the two miRNAs in the midgut of larvae infected with BmCPV gradually increased with the advance of infection, while the expression of the target gene decreased gradually. The miRNAs and the recombinant target gene consisting of reporter gene and 3'-UTR of mRNA were expressed in HEK293T cells for validating the interaction between the miRNAs and the target gene. qRT-PCR results revealed that BmCPV-miR-1 and BmCPV-miR-3 negatively regulate target gene expression not only separately but also cooperatively by binding to the 3'-UTR of mRNA. By transfecting miRNA mimics into BmN cells and injecting the mimics into the body of silkworm larvae, it was indicated that both BmCPV-miR-1 and BmCPV-miR-3 could repress the expression of in BmN cells and in the silkworm, and the cooperative action of the two miRNAs could enhance the repression of expression. Furthermore, the repression of could facilitate the replication of BmCPV genomic RNAs. It is speculated that BmCPV-miR-1 and BmCPV-miR-3 might reduce the generation of host miRNAs by inhibiting expression of , thus creating a favorable intracellular environment for virus replication. Our results are helpful to better understand the pathogenic mechanism of BmCPV to the silkworm, and provide insights into one of the evasion strategies used by viruses to counter the host defense for their effective multiplication.
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http://dx.doi.org/10.3389/fphys.2021.663482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373394PMC
August 2021

Prognostic Role of Liver Biopsy in Patients With Severe Indeterminate Acute Hepatitis.

Clin Gastroenterol Hepatol 2021 Aug 11. Epub 2021 Aug 11.

Liver Failure Group, Institute for Liver and Digestive Health, Division of Medicine, Royal Free Hospital, University College London Medical School, London, United Kingdom; European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain. Electronic address:

Background And Aims: Severe indeterminate acute hepatitis (sIAH) is a poorly understood rare disease with no specific therapy. This study aims to define the clinicopathological characteristics of sIAH and the role of liver biopsy in determining prognosis.

Methods: Patients with sIAH admitted to a single center between 2010 and 2019 were included. Histopathological patterns of liver biopsies were reviewed by 2 histopathologists, and key findings further were specified by multiplex immunofluorescence. Patients that died or underwent liver transplantation were analyzed as nonsurvivors.

Results: Of 294 patients with acute hepatitis, 43 with sIAH were included. Seventeen (39.5%) underwent liver transplantation and 7 (16.2%) died within 3 months. Multilobular necrosis was the predominant histopathological feature, being significantly more frequent in nonsurvivors (62.5% vs 21.1%; P = .016). Necrotic areas showed low HNF4α and Ki67 expression but high expression of CK19 and cell death markers identifying areas of severe tissue injury and inadequate regenerative response. Patients with multilobular necrosis had higher international normalized ratio, Model for End-Stage Liver Disease, and Model for End-Stage Liver Disease-Sodium scores compared with those without (P values for all markers <.05). Multivariate Cox analysis revealed that multilobular necrosis (hazard ratio, 3.675; 95% confidence interval, 1.322-10.211) and lower body mass index (hazard ratio, 0.916; 95% confidence interval, 0.848-0.991) independently predicted death or transplantation.

Conclusions: The results of this study provide novel insights into the important role of liver biopsy in sIAH patients, suggesting that the presence of multilobular necrosis is an early indicator of poor prognosis.
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http://dx.doi.org/10.1016/j.cgh.2021.08.008DOI Listing
August 2021

Retrospective Study of the Safety and Efficacy of Anlotinib Combined With Dose-Dense Temozolomide in Patients With Recurrent Glioblastoma.

Front Oncol 2021 20;11:687564. Epub 2021 Jul 20.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.

Purpose: The purpose of this study was to retrospectively analyze the safety and clinical efficacy of anlotinib combined with dose-dense temozolomide (TMZ) as the first-line therapy in the treatment of recurrent glioblastoma (rGBM).

Patients And Methods: We collected the clinical data of 20 patients with rGBM. All patients received anlotinib (12 mg daily, orally for 2 weeks, discontinued for 1 week, repeated every 3 weeks) combined with dose-dense TMZ (100 mg/m, 7 days on with 7 days off) until the disease progressed (PD) or adverse effects (AEs) above grade 4 appeared. Grade 3 AEs need to be restored to grade 2 before continuing treatment, and the daily dose of anlotinib is reduced to 10 mg. The patients were reexamined by head magnetic resonance imaging (MRI) every 1 to 3 months. The therapeutic effect was evaluated according to Response Assessment in Neuro-Oncology (RANO) criteria. The survival rate was analyzed by Kaplan-Meier survival curve analysis. The baseline of all survival index statistics was the start of anlotinib combined with dose-dense of TMZ. National Cancer Institute-Common Terminology Criteria Adverse Events version 4.0 (NCI-CTCAE 4.0) was used to evaluate AEs.

Results: Twenty cases of rGBM were evaluated according to the RANO criteria after treatment with anlotinib and dose-dense TMZ, including five cases of stable disease (SD), thirteen cases of partial response (PR), one case of complete response (CR), and one case of PD. The median follow-up time was 13.4 (95% CI, 10.5-16.3) months. The 1-year overall survival (OS) rate was 47.7%. The 6-month progression-free survival (PFS) rate was 55%. In the IDH wild type group, the median PFS and median OS were 6.1 and 11.9 months, respectively. We observed that AEs associated with treatment were tolerable. One patient stopped taking the drug because of cerebral infarction. There were no treatment-related deaths.

Conclusion: Anlotinib combined with dose-dense TMZ for the first-line therapy showed good efficacy in OS, PFS, ORR, and DCR in the treatment of rGBM, and the AEs were tolerant. Randomized controlled clinical trials investigating the treatment of rGBM with anlotinib are necessary.
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http://dx.doi.org/10.3389/fonc.2021.687564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330423PMC
July 2021

MAFLD Criteria May Overlook a Subtype of Patient with Steatohepatitis and Significant Fibrosis.

Diabetes Metab Syndr Obes 2021 27;14:3417-3425. Epub 2021 Jul 27.

Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350005, People's Republic of China.

Introduction: Metabolic associated fatty liver disease (MAFLD) is a novel concept for fatty liver disease. Different from non-alcoholic fatty liver disease (NAFLD), the diagnosis of MAFLD requires the presence of metabolic risks. This study aimed to characterize patients with liver steatosis but without metabolic risks (non-MR-steatosis) which may not be diagnosed by MAFLD criteria.

Methods: Consecutive patients who underwent biopsy were included in this study. The clinic-pathological characteristics of non-MR-steatosis, NAFLD and MAFLD were compared.

Results: A total of 1217 cases were included. There were 426 (35.00%) cases with MAFLD, 585 (48.07%) with NAFLD and 168 (13.80%) with non-MR-steatosis. The majority of the cases were infected with HBV (93.26%). The age and metabolic profiles were highest in MAFLD and lowest in non-MR-steatosis. The body mass index (BMI) level was also lowest in non-MR-steatosis (20.78 ± 1.54 kg/m). The ALT and AST levels of the non-MR-steatosis group were not statistically different from those of MAFLD or NAFLD groups (p > 0.05). Histologically, there was no significant difference in the degrees of inflammation and fibrosis among the three groups. The severity of steatosis in non-MR-steatosis group was lower than MAFLD or NAFLD groups (p < 0.05). These results were consistent in both HBV and non-HBV subgroups.

Conclusion: MAFLD criteria may overlook some steatotic patients without metabolic risks, who may also have steatohepatitis and significant fibrosis.
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http://dx.doi.org/10.2147/DMSO.S316096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326380PMC
July 2021

A Novel Indel in the Alpha Globin 2 (HBA2) Gene Resulting in False Positive -α3.7 on Multiplex gap-PCR Assay.

Clin Chem 2021 Sep;67(9):1284-1287

Department of Laboratory Medicine, National University Hospital, Singapore.

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http://dx.doi.org/10.1093/clinchem/hvab113DOI Listing
September 2021

Maternal height, gestational diabetes mellitus and pregnancy complications.

Diabetes Res Clin Pract 2021 Aug 23;178:108978. Epub 2021 Jul 23.

Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Aims: To explore the glucose-overload hypothesis of artefactual gestational diabetes (GDM) diagnosis in shorter women during oral glucose tolerance testing (OGTT), by investigating associations between height and maternal glycemia; and GDM and pregnancy complications in height-groups.

Methods: Women from GUSTO (n = 1100, 2009-2010) and NUH (n = 4068, 2017-2018) cohorts underwent a mid-gestation two and three time-point 75 g 2-hour OGTT, respectively. GDM-related complications (hypertensive disorders of pregnancy, preterm delivery, emergency cesarean section, neonatal intensive care unit admission, macrosomia, birthweight) were compared within shorter and taller groups, dichotomized by ethnic-specific median height.

Results: Using WHO-1999 criteria, 18.8% (GUSTO) to 22.9% (NUH) of women were diagnosed with GDM-1999; and by WHO-2013 criteria, 21.9% (NUH) had GDM-2013. Each 5-cm height increment was inversely associated with GDM-1999 (adjusted odds ratio [aOR, 95% CI] = 0.81 [0.76-0.87], 2-h glycemia (adjusted β [aβ, 95% CI] = -0.171 mmol/L [-0.208, -0.135]) and 1-h glycemia (aβ = -0.160 mmol/L [-0.207, -0.112]). The inverse association between height and 2-h glycemia was most marked in "Other" ethnicities (Eurasians/Caucasians/mixed/other Asians) and Indians, followed by Chinese, then Malays. Compared with non-GDM, GDM-1999 was associated with preterm delivery (aOR = 1.76 [1.19-2.61]) and higher birthweight (aβ = 57.16 g [20.95, 93.38]) only among taller but not shorter women.

Conclusions: Only taller women had an increased odds of GDM-related pregnancy complications. An artefactual GDM diagnosis due to glucose-overload among shorter women is plausible.
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http://dx.doi.org/10.1016/j.diabres.2021.108978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611603PMC
August 2021

Bombyx mori Apolipophorin-III inhibits Beauveria bassiana directly and through regulating expression of genes relevant to immune signaling pathways.

J Invertebr Pathol 2021 Sep 23;184:107647. Epub 2021 Jul 23.

School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China; Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China. Electronic address:

Insect Apolipophorin-III is a multifunctional protein and also plays an important role in insect innate immunity. Early transcriptome and proteome studies indicated that the gene expression level of Bombyx mori Apolipophorin-III (BmApoLp-III) in silkworm larvae infected with Beauveria bassiana was significantly up-regulated. In this study, BmApoLp-III gene was cloned, its expression patterns in different larval tissues investigated, the BmApoLp-III protein was successfully expressed with prokaryotic expression system and its antifungal effect was verified. The results showed that the BmApoLp-III gene was expressed in all the tested tissues of the 5th instar larvae infected by B. bassiana, with the highest expression in fat body. The fungistatic zone test showed that the recombinant BmApoLp-III has a significant antifungal effect on B. bassiana. Injecting purified BmApoLp-III to the larvae delayed the onset and death of the infected larvae. Conversely, silencing BmApoLp-III gene by RNAi resulted in early morbidity and death of the infected larvae. At the same time, injecting BmApoLp-III up-regulated the expression of genes including BmβGRP4 and BmMyd88 in the Toll signaling pathway, BmCTL5 and BmHOP in the Jak/STAT signaling pathway, serine proteinase inhibitor BmSerpin5, and antimicrobial peptide BmCecA, but down-regulated the expression of BmTak1 of Imd signaling pathway; while silencing BmApoLp-III gene down-regulated the expression of BmβGRP1 and BmSpaetzle, BmCTL5 and BmHOP, BmSerpin2 and BmSerpin5, BmBAEE and BmPPO2 of relevant pathways and BmCecA, but up-regulated the expression of BmPGRP-Lc and BmTak1 of Imd pathway. These results indicate that the BmApoLp-III could not only directly inhibit B. bassiana, but also participate in regulation of the expression of immune signaling pathway related genes, promote the expression of immune effectors, and indirectly inhibit the reproduction of B. bassiana in the silkworm.
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http://dx.doi.org/10.1016/j.jip.2021.107647DOI Listing
September 2021

Perioperative stress dose steroid management of children with classical congenital adrenal hyperplasia: Too much or too little?

J Pediatr Urol 2021 Jul 2. Epub 2021 Jul 2.

Pediatric Endocrinology, Weill Cornell Medicine/Komansky Children's Hospital/New York Presbyterian Hospital, 525 E. 68th Street, New York, NY, 10021, USA. Electronic address:

Background: Children with congenital adrenal hyperplasia (CAH) are at risk for adrenal crises in the perioperative period and require higher doses of glucocorticoids. However, there are no specific protocols detailing the appropriate stress dosing required for children with CAH undergoing surgery with anesthesia.

Objective: To evaluate CAH patients using our current hydrocortisone stress dose surgical protocol. We hypothesized that current clinical protocols may overestimate the endogenous response to perioperative stress.

Study Design: 14 children with CAH scheduled to have genital surgery and a control group of 10 unaffected children scheduled to have cardiac or urologic surgery (of a similar duration) were evaluated in a prospective observational study. Urinary free cortisol (UFC) and urinary 17-hydroxycorticosteroids (17-OHCS) per body surface area were measured in the postoperative period.

Results: UFC levels were significantly higher in CAH patients (115.8 ± 24.6 nmol/m) than in controls (26.5 ± 12.2 nmol/m), P < 0.05.17-OHCS levels were also higher in CAH patients than in controls (6.5 ± 0.5 nmol/m vs. 3.4 ± 0.5 nmol/m), P < 0.05).

Conclusion: In the immediate postoperative period, urinary cortisol and its metabolites are significantly higher in pediatric CAH patients receiving stress dose corticosteroids compared to controls. Results suggest that the amount of hydrocortisone given during our stress dose protocol may be higher than physiologic needs. Future dynamic studies are needed to determine appropriate perioperative and postoperative cortisol requirements in pediatric CAH patients in order to develop optimal stress dose regimens.
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http://dx.doi.org/10.1016/j.jpurol.2021.06.027DOI Listing
July 2021

A mobile magnetic pad with fast light-switchable adhesion capabilities.

Bioinspir Biomim 2021 08 3;16(5). Epub 2021 Aug 3.

Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Shatin NT, Hong Kong SAR, People's Republic of China.

Octopus suckers that possess the ability to actively control adhesion through muscle actuation have inspired artificial adhesives for safe manipulation of thin and delicate objects. However, the design of adhesives with fast adhesion switching speed to transport cargoes in confined spaces remains an open challenge. Here, we present an untethered magnetic adhesive pad combining the functionality of fast adhesion switching and remotely controlled locomotion. The adhesive pad can be activated from low-adhesion state to high-adhesion state by near infrared laser within 30 s, allowing to fulfill a high-throughput task of retrieving and releasing objects. Moreover, under the guidance of external magnetic field, the proposed pad is demonstrated to transport thin and fragile electronic components across a tortuous path, thus indicating its potential for dexterous delivery in complex working environments.
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http://dx.doi.org/10.1088/1748-3190/ac114aDOI Listing
August 2021

A reasoned approach towards administering COVID-19 vaccines to pregnant women.

Prenat Diagn 2021 07 30;41(8):1018-1035. Epub 2021 Jun 30.

Department of Obstetrics and Gynaecology, National University Hospital Singapore, Singapore.

There are over 50 SARS-CoV-2 candidate vaccines undergoing Phase II and III clinical trials. Several vaccines have been approved by regulatory authorities and rolled out for use in different countries. Due to concerns of potential teratogenicity or adverse effect on maternal physiology, pregnancy has been a specific exclusion criterion for most vaccine trials with only two trials not excluding pregnant women. Thus, other than limited animal studies, gradually emerging development and reproductive toxicity data, and observational data from vaccine registries, there is a paucity of reliable information to guide recommendations for the safe vaccination of pregnant women. Pregnancy is a risk factor for severe COVID-19, especially in women with comorbidities, resulting in increased rates of preterm birth and maternal morbidity. We discuss the major SARS-CoV-2 vaccines, their mechanisms of action, efficacy, safety profile and possible benefits to the maternal-fetal dyad to create a rational approach towards maternal vaccination while anticipating and mitigating vaccine-related complications. Pregnant women with high exposure risks or co-morbidities predisposing to severe COVID-19 infection should be prioritised for vaccination. Those with risk factors for adverse effects should be counselled accordingly. It is essential to support patient autonomy by shared decision-making involving a risk-benefit discussion with the pregnant woman.
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http://dx.doi.org/10.1002/pd.5985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362094PMC
July 2021

Combination immunotherapy with two attenuated Listeria strains carrying shuffled HPV-16 E6E7 protein causes tumor regression in a mouse tumor model.

Sci Rep 2021 06 28;11(1):13404. Epub 2021 Jun 28.

West China School of Public Health and West China Fourth Hospital, Sichuan University, 17#, Section 3, Renmin Nan Road, Chengdu, 610041, Sichuan, People's Republic of China.

Cervical cancer continues to impose a heavy burden worldwide, and human papilloma virus (HPV) infection, especially persistent infection with type 16 (HPV-16), is known to be the primary etiological factor. Therapeutic vaccines are urgently needed because prophylactic vaccines are ineffective at clearing pre-existing HPV infection. Here, two recombinant Listeria strains (LMΔ-E6E7 & LIΔ-E6E7) with deletions of the actA and plcB genes, expressing the shuffled HPV-16 E6E7 protein were constructed. The strains were delivered into the spleen and liver by intravenous inoculation, induced antigen-specific cellular immunity and were eliminated completely from the internal organs several days later. Intravenously treating with single strain for three times, or with both strains alternately for three times significantly reduced the tumor size and prolonged the survival time of model mice. Combination immunotherapy with two strains seemed more effective than immunotherapy with single strain in that it enhanced the survival of the mice, and the LMΔ-E6E7-prime-LIΔ-E6E7-boost strategy showed significant stronger efficacy than single treatment with the LIΔ-E6E7 strain. The antitumor effect of this treatment might due to its ability to increase the proportion of CD8 T cells and reduce the proportion of T regulatory cells (Tregs) in the intratumoral milieu. This is the first report regarding Listeria ivanovii-based therapeutic vaccine candidate against cervical cancer. Most importantly we are the first to confirm that combination therapy with two different recombinant Listeria strains has a more satisfactory antitumor effect than administration of a single strain. Thus, we propose a novel prime-boost treatment strategy.
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http://dx.doi.org/10.1038/s41598-021-92875-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238941PMC
June 2021

P2Y1 Purinergic Receptor Contributes to Remifentanil-Induced Cold Hyperalgesia via Transient Receptor Potential Melastatin 8-Dependent Regulation of N-methyl-d-aspartate Receptor Phosphorylation in Dorsal Root Ganglion.

Anesth Analg 2021 09;133(3):794-810

From the Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

Background: Remifentanil can induce postinfusion cold hyperalgesia. N-methyl-d-aspartate receptor (NMDAR) activation and upregulation of transient receptor potential melastatin 8 (TRPM8) membrane trafficking in dorsal root ganglion (DRG) are critical to cold hyperalgesia derived from neuropathic pain, and TRPM8 activation causes NMDAR-dependent cold response. Contribution of P2Y1 purinergic receptor (P2Y1R) activation in DRG to cold pain hypersensitivity and NMDAR activation induced by P2Y1R upregulation in neurons are also unraveled. This study explores whether P2Y1R contributes to remifentanil-induced cold hyperalgesia via TRPM8-dependent regulation of NMDAR phosphorylation in DRG.

Methods: Rats with remifentanil-induced cold hyperalgesia were injected with TRPM8 antagonist or P2Y1R antagonist at 10 minutes before remifentanil infusion. Cold hyperalgesia (paw lift number and withdrawal duration on cold plate) was measured at -24, 2, 6, 24, and 48 hours following remifentanil infusion. After the last behavioral test, P2Y1R expression, TRPM8 expression and membrane trafficking, and NMDAR subunit (NR1 and NR2B) expression and phosphorylation in DRG were detected by western blot, and colocalization of P2Y1R with TRPM8 was determined by double-labeling immunofluorescence. Two-way repeated measures analysis of variance (ANOVA) or 2 × 2 factorial design ANOVA with repeated measures was used to analyze behavioral data of cold hyperalgesia. One-way ANOVA followed by Bonferroni post hoc comparisons was used to analyze the data in western blot and immunofluorescence.

Results: Remifentanil infusion (1 μg·kg-1·min-1 for 60 minutes) induced cold hyperalgesia (hyperalgesia versus control, paw lift number and withdrawal duration on cold plate at 2-48 hours, P < .0001) with upregulated NR1 (hyperalgesia versus naive, 48 hours, mean ± standard deviation [SD], 114.00% ± 12.48% vs 41.75% ± 5.20%, P < .005) and NR2B subunits expression (104.13% ± 8.37% vs 24.63% ± 4.87%, P < .005), NR1 phosphorylation at Ser896 (91.88% ± 7.08% vs 52.00% ± 7.31%, P < .005) and NR2B phosphorylation at Tyr1472 (115.75% ± 8.68% vs 59.75% ± 7.78%, P < .005), TRPM8 expression (115.38% ± 9.27% vs 40.50% ± 4.07%, P < .005) and membrane trafficking (112.88% ± 5.62% vs 48.88% ± 6.49%, P < .005), and P2Y1R expression (128.25% ± 14.86% vs 45.13% ± 7.97%, P < .005) in DRG. Both TRPM8 and P2Y1R antagonists attenuated remifentanil-induced cold hyperalgesia and downregulated increased NR1 and NR2B expression and phosphorylation induced by remifentanil (remifentanil + RQ-00203078 versus remifentanil + saline, NR1 phosphorylation, 69.38% ± 3.66% vs 92.13% ± 4.85%; NR2B phosphorylation, 72.25% ± 6.43% vs 111.75% ± 11.00%, P < .0001). NMDAR activation abolished inhibition of TRPM8 and P2Y1R antagonists on remifentanil-induced cold hyperalgesia. P2Y1R antagonist inhibited remifentanil-evoked elevations in TRPM8 expression and membrane trafficking and P2Y1R-TRPM8 coexpression (remifentanil + 2'-deoxy-N6-methyl adenosine 3',5'-diphosphate [MRS2179] versus remifentanil + saline, coexpression, 8.33% ± 1.33% vs 22.19% ± 2.15%, P < .0001).

Conclusions: Attenuation of remifentanil-induced cold hyperalgesia by P2Y1R inhibition is attributed to downregulations in NMDAR expression and phosphorylation via diminishing TRPM8 expression and membrane trafficking in DRG.
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http://dx.doi.org/10.1213/ANE.0000000000005617DOI Listing
September 2021

Defining the prognosis of critically ill patients with alcohol-related liver disease.

J Hepatol 2021 Oct 18;75(4):986-987. Epub 2021 May 18.

Institute for Liver and Digestive Health, Royal Free Campus, UCL, London, UK; Institute of Hepatology, Foundation for Liver Research, London, UK. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2021.04.054DOI Listing
October 2021

Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990-2019.

J Hepatol 2021 Sep 4;75(3):547-556. Epub 2021 May 4.

Department of Hepatology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China; Hepatology Research Institute, Fujian Medical University, Fuzhou, Fujian, China. Electronic address:

Background & Aims: Acute viral hepatitis (AVH) represents an important global health problem; however, the progress in understanding AVH is limited because of the priority of combating persistent HBV and HCV infections. Therefore, an improved understanding of the burden of AVH is required to help design strategies for global intervention.

Methods: Data on 4 major AVH types, including acute hepatitis A, B, C, and E, excluding D, were collected by the Global Burden of Disease (GBD) 2019 database. Age-standardized incidence rates and disability-adjusted life year (DALY) rates for AVH were extracted from GBD 2019 and stratified by sex, level of socio-demographic index (SDI), country, and territory. The association between the burden of AVH and socioeconomic development status, as represented by the SDI, was described.

Results: In 2019, there was an age-standardized incidence rate of 3,615.9 (95% CI 3,360.5-3,888.3) and an age-standardized DALY rate of 58.0 (47.3-70.0) per 100,000 person-years for the 4 major types of AVH. Among the major AVH types, acute hepatitis A caused the heaviest burden. There was a significant downward trend in age-standardized DALY rates caused by major incidences of AVH between 1990 and 2019. In 2019, regions or countries located in West and East Africa exhibited the highest age-standardized incidence rates of the 4 major AVH types. These rates were stratified by SDI: high SDI and high-middle SDI locations recorded the lowest incidence and DALY rates of AVH, whereas the low-middle SDI and low SDI locations showed the highest burden of AVH.

Conclusions: The socioeconomic development status and burden of AVH are associated. Therefore, the GBD 2019 data should be used by policymakers to guide cost-effective interventions for AVH.

Lay Summary: We identified a negative association between socioeconomic development status and the burden of acute viral hepatitis. The lowest burden of acute viral hepatitis was noted for rich countries, whereas the highest burden of acute viral hepatitis was noted for poor countries.
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http://dx.doi.org/10.1016/j.jhep.2021.04.035DOI Listing
September 2021

Localization of Immersed Sources by Modified Convolutional Neural Network: Application to a Deep-Sea Experiment.

Sensors (Basel) 2021 Apr 29;21(9). Epub 2021 Apr 29.

Institute of Acoustics, Chinese Academy of Sciences, Beijing 100190, China.

A modified convolutional neural network (CNN) is proposed to enhance the reliability of source ranging based on acoustic field data received by a vertical array. Compared to the traditional method, the output layer is modified by outputting Gauss regression sequences, expressed using a Gaussian probability distribution form centered on the actual distance. The processed results of deep-sea experimental data confirmed that the ranging performance of the CNN with a Gauss regression output was better than that using single regression and classification outputs. The mean relative error between the predicted distance and the actual value was ~2.77%, and the positioning accuracy with 10% and 5% error was 99.56% and 90.14%, respectively.
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http://dx.doi.org/10.3390/s21093109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124261PMC
April 2021

Dietary Structure and Nutritional Status of Chinese Beekeepers: Demographic Health Survey.

JMIR Public Health Surveill 2021 May 3;7(5):e28726. Epub 2021 May 3.

Department of Clinical Nutrition, Peking University People's Hospital, Beijing, China.

Background: Beekeeping and honey gathering are traditional forms of agricultural farming in China. However, only few studies have focused on the nutritional status and health level of this special occupational group.

Objective: By comparing the health status of apiculturists (beekeepers) and vegetable farmers in plain areas of Hubei Province, and analyzing the influence of dietary structure and intake on their nutritional level, this paper provides a scientific theoretical basis for the further development of health education and disease prevention for beekeepers.

Methods: From February to April 2016, 191/236 beekeepers (80.9% of the total beekeepers) with large-scale breeding (300-500 colonies) and 182 vegetable farmers in the same area were sampled by the cluster sampling method. Their nutrient composition was analyzed using a human body composition analyzer, dietary structure information was collected using the dietary frequency query method, and cognitive function was investigated. In addition, blood samples of both groups were collected.

Results: A total of 362 valid questionnaires (beekeepers/vegetable farmers: 185/177) were collected, with an effective response rate of 97.1% (362/373). Both beekeepers and vegetable farmers were overweight, and the beekeepers' grip strength was much stronger than that of the vegetable farmers' regardless of gender. The dietary structure of beekeepers is very unique: 29.7% (55/185) of beekeepers indicated consuming royal jelly regularly for more than 10 years. Their main foods are grain, cereals, and fresh vegetables; 68.1% (126/185) of the beekeepers never drank milk and other dairy products, and their overall nutrient intake is unbalanced. The average intake of cellulose in this group was also significantly higher than that in the epidemiological survey in the same sex and age group. The intake of vitamin A and selenium in the beekeepers group was significantly higher than that in the vegetable-farmers group (all P<.001). The blood indices of creatinine (P=.03) and blood copper (P<.001) in the beekeepers group were significantly higher than those in the vegetable-farmers group, and the total protein, albumin, calcium, sodium, potassium, phosphorus, folic acid, and vitamin B12 in the beekeepers group were significantly lower than those in the vegetable-farmers group (P<.03 for potassium and P<.001 for others). The total Mini-Mental State Examination (MMSE) score of the beekeepers group was 28.1, significantly higher (P=.006) than that of the vegetable-farmers group (23.3).

Conclusions: The beekeepers in this area have their special dietary structure, body nutrient level, and disease characteristics. The cognitive level of the beekeepers who regularly consume royal jelly is significantly higher than that of their peers. The chronic diseases of this special occupational group are closely related to their lifestyle and nutritional status, so more attention and in-depth studies are needed to improve the quality of life of this population.
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http://dx.doi.org/10.2196/28726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129875PMC
May 2021

Identification and Characterization of Long Non-coding RNAs in the Intestine of Olive Flounder () During Infection.

Front Immunol 2021 31;12:623764. Epub 2021 Mar 31.

School of Marine Science and Engineering, Qingdao Agricultural University, Qingdao, China.

Long non-coding RNAs (lncRNAs) play widespread roles in fundamental biological processes, including immune responses. The olive flounder (), an important economical flatfish widely cultured in Japan, Korea, and China, is threatened by infectious pathogens, including bacteria, viruses, and parasites. However, the role of lncRNAs in the immune responses of this species against pathogen infections is not well-understood. Therefore, in this study, we aimed to identify lncRNAs in the intestine of olive flounder and evaluate their differential expression profiles during infection, which is an important zoonotic and intestinal pathogen. A total of 4,445 putative lncRNAs were identified, including 3,975 novel lncRNAs and 470 annotated lncRNAs. These lncRNAs had shorter lengths and fewer exons compared with mRNAs. In total, 115 differentially expressed lncRNAs (DE-lncRNAs) were identified during infection. To validate the expression pattern of lncRNAs, six DE-lncRNAs were randomly selected for quantitative real-time PCR. The co-located and co-expressed mRNAs of DE-lncRNAs were predicted, which were used to conduct the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The target genes of DE-lncRNAs enriched numerous immune-related processes and exhibited a strong correlation with immune-related signaling pathways. To better understand the extensive regulatory functions of lncRNAs, the lncRNA-miRNA-mRNA regulatory networks were constructed, and two potential competing endogenous RNA (ceRNA) networks, LNC_001979-novel_171-Potusc2 and LNC_001979-novel_171-Podad1, were preliminarily identified from the intestine of olive flounders for the first time. In conclusion, this study provides an invaluable annotation and expression profile of lncRNAs in the intestine of olive flounder infected with ; this forms a basis for further studies on the regulatory function of lncRNAs in the intestinal mucosal immune responses of olive flounder.
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http://dx.doi.org/10.3389/fimmu.2021.623764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044400PMC
September 2021

Ze-Qi-Tang Formula Induces Granulocytic Myeloid-Derived Suppressor Cell Apoptosis via STAT3/S100A9/Bcl-2/Caspase-3 Signaling to Prolong the Survival of Mice with Orthotopic Lung Cancer.

Mediators Inflamm 2021 1;2021:8856326. Epub 2021 Apr 1.

School of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.
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http://dx.doi.org/10.1155/2021/8856326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035014PMC
April 2021

MicroRNA-431-5p encapsulated in serum extracellular vesicles as a biomarker for proliferative diabetic retinopathy.

Int J Biochem Cell Biol 2021 06 7;135:105975. Epub 2021 Apr 7.

Tianjin International Joint Research and Development Center of Ophthalmology and Vision Science, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, No. 251, Fukang Road, Nankai District, Tianjin, 300384, China. Electronic address:

Early diagnosis and precise monitoring of the development of proliferative diabetic retinopathy (PDR) can significantly improve therapeutic strategies and help decrease blindness caused by it. Extracellular vesicles (EVs) were recently found to be involved in intercellular communications and are a potential source for the discovery of novel biomarkers. The current study aims to investigate the effectiveness of microRNAs (miRNAs) encapsulated in small EVs (sEVs) as minimally invasive biomarkers for PDR. SEVs were extracted from plasma of healthy subjects, diabetic patients, nonPDR patients and PDR patients. Then, we performed microarray analysis to determine the miRNA expression profile. MiR-431-5p expression doubled in the PDR patients compared with the healthy controls and the diabetic patients. We further found that miR-431-5p expression was 2.3 times higher in 4-hydroxynonenal treated human retinal capillary endothelial cells (HRCECs) than the control. After transfection with miR-431-5p mimics, proliferation of HRCECs was promoted, while transfection with miR-431-5p inhibitor demonstrated the opposite effect. The present findings indicate that circulating sEVs showed a differential miRNA profile in PDR patients. MiR-431-5p was involved in the pathogenesis of PDR development and may function as a novel biomarker for PDR.
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http://dx.doi.org/10.1016/j.biocel.2021.105975DOI Listing
June 2021

Deep transfer learning for underwater direction of arrival using one vector sensor.

J Acoust Soc Am 2021 Mar;149(3):1699

Key Laboratory of Underwater Acoustic Environment, Institute of Acoustics, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

A deep transfer learning (DTL) method is proposed for the direction of arrival (DOA) estimation using a single-vector sensor. The method involves training of a convolutional neural network (CNN) with synthetic data in source domain and then adapting the source domain to target domain with available at-sea data. The CNN is fed with the cross-spectrum of acoustical pressure and particle velocity during the training process to learn DOAs of a moving surface ship. For domain adaptation, first convolutional layers of the pre-trained CNN are copied to a target CNN, and the remaining layers of the target CNN are randomly initialized and trained on at-sea data. Numerical tests and real data results suggest that the DTL yields more reliable DOA estimates than a conventional CNN, especially with interfering sources.
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http://dx.doi.org/10.1121/10.0003645DOI Listing
March 2021

The Current Role of Adjuvant Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma.

Front Oncol 2020 24;10:585046. Epub 2021 Feb 24.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck, and it originates from the mucous epithelium of the nasopharynx. Because it is "hidden", the symptoms of NPC can easily be missed, and more than 70% of patients present with locally advanced disease at diagnosis. Concurrent radiation therapy with chemotherapy can significantly improve regional control of NPC. At present, distant metastasis is the main cause of treatment failure. At the end of the 20th century, clinical trial No. IG0099 in the United States confirmed the effectiveness of adjuvant chemotherapy (AC) for the first time. However, in the past 20 years, various clinical trials and meta-analyses conducted globally have yielded contradictory results regarding the effect of AC on locally advanced NPC. AC has changed from category 1 to the current category 2A in the National Comprehensive Cancer Network (NCCN) guidelines, and it remains controversial whether AC can significantly improve the survival of NPC patients. Here, we comprehensively analyzed the role of AC in locally advanced NPC by comparing some treatment methods. We conclude the role of AC in treating locally advanced NPC, based on the studies presented, remains undefined but is associated with increased toxicity.
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http://dx.doi.org/10.3389/fonc.2020.585046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970762PMC
February 2021

Outcome of very preterm infants delivered outside tertiary perinatal centers in China: a multi-center cohort study.

Transl Pediatr 2021 Feb;10(2):306-314

Department of Neonatology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.

Background: To describe the incidence of outborns among very preterm infants (VPIs, <32 weeks of gestation) in Chinese perinatal centers and to examine the association of outborn status with adverse outcomes.

Methods: A cohort study enrolling all VPIs admitted to 18 perinatal centers in China from May 1st, 2015 to April 30th, 2018. Neonatal outcomes including rates of discharge against medical advice (DAMA), in-hospital mortality, overall mortality, severe intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL), sepsis, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and severe retinopathy of prematurity (ROP) were compared between outborn and inborn infants. A multivariate logistic regression model was used to estimate the independent association of outborn status with neonatal outcomes.

Results: Among 12,014 VPIs, 1,991 (16.6%) infants were outborn. Outborn infants had lower Apgar scores and higher illness severity score on admission. Mothers of outborn infants were less likely to receive antenatal steroids, prenatal care and caesarean section. The incidence of DAMA (18.0% 12.5%, P<0.001), overall mortality (19.9% 15.8%, P<0.001) and severe brain injury (10.8% 9.1%, P=0.024) of outborn infants were significantly higher than inborn infants. Outborn status was independently associated with increased risks of DAMA (aOR, 1.6; 95% CI: 1.4-1.8), overall-hospital mortality (aOR, 1.3; 95% CI: 1.1-1.5) and severe IVH/PVL (aOR, 1.2; 95% CI: 1.0-1.5).

Conclusions: The incidence of outborn VPIs was high in China. Outborn infants were more likely to be delivered in an uncontrolled situation and were at significantly higher risk of neonatal mortality and severe brain injury compared with inborn infants. Quality improvement efforts are needed to facilitate in-utero transfer of high-risk pregnancies to tertiary centers.
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http://dx.doi.org/10.21037/tp-20-232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944173PMC
February 2021
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