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1.
Nat Commun ; 11(1): 5210, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060578

RESUMO

Human insulinomas are rare, benign, slowly proliferating, insulin-producing beta cell tumors that provide a molecular "recipe" or "roadmap" for pathways that control human beta cell regeneration. An earlier study revealed abnormal methylation in the imprinted p15.5-p15.4 region of chromosome 11, known to be abnormally methylated in another disorder of expanded beta cell mass and function: the focal variant of congenital hyperinsulinism. Here, we compare deep DNA methylome sequencing on 19 human insulinomas, and five sets of normal beta cells. We find a remarkably consistent, abnormal methylation pattern in insulinomas. The findings suggest that abnormal insulin (INS) promoter methylation and altered transcription factor expression create alternative drivers of INS expression, replacing canonical PDX1-driven beta cell specification with a pathological, looping, distal enhancer-based form of transcriptional regulation. Finally, NFaT transcription factors, rather than the canonical PDX1 enhancer complex, are predicted to drive INS transactivation.

2.
Liver Int ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064897

RESUMO

BACKGROUND: Endoplasmic reticulum (ER) perturbations are novel subcellular effectors involved in the ischemia-reperfusion injury. As an ER stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to be increased during ischemic brain injury. However, the role of MANF in liver ischemia reperfusion (I/R) injury has not yet been studied. METHODS: To investigate the role of MANF in the process of liver ischemia-reperfusion, Hepatocyte-specific MANF knockout (MANFhep-/- ) mice and their wild-type (WT) littermates were used in our research. Mice partial (70%) warm hepatic I/R model was established by vascular occlusion. We detected the serum levels of MANF in both liver transplant patients and WT mice before and after liver I/R injury. Recombinant human MANF (rhMANF) was injected into the tail vein before 1 h occlusion. AST, ALT and Suzuki score was used to evaluate the extent of I/R injury. OGD/R test was performed on primary hepatocytes to simulate IRI in vitro. RNA sequence and RT-PCR were used to detect the cellular signal pathway activation while MANF knockout. RESULTS: We found MANF expression and secretion is dramatically up-regulated during hepatic I/R. Hepatocyte-specific MANF knockout aggravates the I/R injury through the over-activated ER stress. The systemic administration of rhMANF before ischemia has the potential to ameliorate I/R-triggered UPR and liver injury. Further study showed that MANF deficiency activated ATF4/CHOP and JNK/c-JUN/CHOP pathways, and rhMANF inhibited the activation of the two proapoptotic pathways caused by MANF deletion. CONCLUSION: Collectively, our study unravels a previously unknown relationship among MANF, UPR and hepatic I/R injury.

4.
Nat Commun ; 11(1): 5252, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067438

RESUMO

Simultaneous and efficient ultrafast recording of multiple photon tags contributes to high-dimensional optical imaging and characterization in numerous fields. Existing high-dimensional optical imaging techniques that record space and polarization cannot detect the photon's time of arrival owing to the limited speeds of the state-of-the-art electronic sensors. Here, we overcome this long-standing limitation by implementing stereo-polarimetric compressed ultrafast photography (SP-CUP) to record light-speed high-dimensional events in a single exposure. Synergizing compressed sensing and streak imaging with stereoscopy and polarimetry, SP-CUP enables video-recording of five photon tags (x, y, z: space; t: time of arrival; and ψ: angle of linear polarization) at 100 billion frames per second with a picosecond temporal resolution. We applied SP-CUP to the spatiotemporal characterization of linear polarization dynamics in early-stage plasma emission from laser-induced breakdown. This system also allowed three-dimensional ultrafast imaging of the linear polarization properties of a single ultrashort laser pulse propagating in a scattering medium.

5.
Int J Biol Macromol ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33049237

RESUMO

In this work, the biological polysaccharide-based antioxidant polyglucose-sorbitol-carboxymethyl ether (PSC) was used as the precursor to synthesize Fe2O3@PSC nanoparticles, which are expected to scavenge excess reactive oxygen species (ROS) to inhibit osteogenesis and promote osteoclast differentiation in iron accumulation (IA)-related osteoporosis. The Fe2O3@PSC nanoparticles obtained were of a uniform particle size of 7.3 nm with elemental O/Fe/Cl/C at a ratio of 190:7:2:88. In addition, the Fe2O3@PSC nanoparticles showed the ability to supply equivalent amounts of iron as the typical iron agent ferric ammonium citrate (FAC) in vitro and in vivo. Importantly, the Fe2O3@PSC nanoparticles not only induced antioxidative MC3T3-E1 and Raw 264.7 cells to scavenge ROS but also promoted osteogenic differentiation by activating Akt-GSK-3ß-ß-catenin and inhibiting osteoclast differentiation by inhibiting the MAPK and NF-κB pathways in vitro. In vivo, no IA-related osteoporosis was induced in a mouse model when enough iron was supplied by the Fe2O3@PSC nanoparticles. Overall, the biological polysaccharide-based antioxidant PSC can supply iron and prevent IA-related osteoporosis, indicating that it is a promising novel iron agent for applications to treat iron deficiency diseases.

6.
Biosci Rep ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030522

RESUMO

CD44 has been considered as a cancer stem cell marker in various tumors. With great enthusiasm, we read an article written by Wu et al. entitled "Expression of CD44 and the survival in glioma: a meta-analysis" published in Bioscience Reports. The authors performed meta-analyses to study the prognostic significance of CD44 in gliomas, and drown the conclusion that high expression of CD44 may predict poor survival in glioma, particularly in WHO grade II-III gliomas. However, two major defects exist in this study, which made the meta-analysis on the prognostic significance of CD44 in all gliomas unreliable. In this commentary, we listed several defects of this study.

7.
PLoS One ; 15(10): e0239960, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33017421

RESUMO

The outbreak of Corona Virus Disease 2019 (COVID-19) in Wuhan has significantly impacted the economy and society globally. Countries are in a strict state of prevention and control of this pandemic. In this study, the development trend analysis of the cumulative confirmed cases, cumulative deaths, and cumulative cured cases was conducted based on data from Wuhan, Hubei Province, China from January 23, 2020 to April 6, 2020 using an Elman neural network, long short-term memory (LSTM), and support vector machine (SVM). A SVM with fuzzy granulation was used to predict the growth range of confirmed new cases, new deaths, and new cured cases. The experimental results showed that the Elman neural network and SVM used in this study can predict the development trend of cumulative confirmed cases, deaths, and cured cases, whereas LSTM is more suitable for the prediction of the cumulative confirmed cases. The SVM with fuzzy granulation can successfully predict the growth range of confirmed new cases and new cured cases, although the average predicted values are slightly large. Currently, the United States is the epicenter of the COVID-19 pandemic. We also used data modeling from the United States to further verify the validity of the proposed models.

8.
Nanoscale ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043911

RESUMO

Silver nanocubes have found use in an array of applications but their performance has been plagued by the shape instability arising from the oxidation and dissolution of Ag atoms from the edges and corners. Here we demonstrate that the shape of Ag nanocubes can be well preserved by covering their edges and corners with a corrosion-resistant metal such as Ir. In a typical process, we titrate a Na3IrCl6 solution in ethylene glycol (EG) into a suspension of Ag nanocubes in an EG solution in the presence of poly(vinylpyrrolidone) (PVP) held at 110 °C. The Ir atoms derived from the reduction of Na3IrCl6 by EG and Ag are deposited onto the edges and then corners for the generation of Ag-Ir core-frame nanocubes. Remarkably, our results indicate that a small amount of Ir atoms on the edges and corners is adequate to prevent the Ag nanocubes from transforming into nanospheres when heated in a PVP/EG solution up to 110 °C. We further demonstrate that these Ag-Ir nanocubes embrace plasmonic properties comparable to those of the original Ag nanocubes, making them immediately useful in a variety of applications. This strategy for stabilizing the shape of Ag nanocubes should be extendible to Ag nanocrystals with other shapes or nanocrystals comprised of other metals.

9.
Aging Clin Exp Res ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044736

RESUMO

Malnutrition is a risk factor for postoperative infectious complications of elderly patients undergoing posterior lumbar arthrodesis. At present, there is no gold standard for nutrition screening tools. We analyzed the value of predicting infectious complications among elderly patients over 70 years undergoing posterior lumbar arthrodesis by comparing the MNA-SF and GNRI. Demographic data, anthropometric measurements, serum albumin, surgical data and the occurrence of infectious complications and LOS were collected. Mini Nutritional Assessment short form (MNA-SF), Geriatric Nutritional Risk Index (GNRI) were performed within 24 h before surgery. Multivariable logistic regression analyses were used to identify predictors of infectious complications. The discriminatory performances of GNRI and MNA-SF scores for the occurrence of infectious complications were determined by receiver operating characteristic curves (ROC) analyses and the area under the curve (AUC). The study included 252 patients with a median age of 76.82 ± 6.41 years (range 70-84 years), and 142 patients (56.3%) were female. There were no significant differences in infectious complications (p = 0.236) and LOS (p = 0.580) among different GNRI categories. 27.3% malnourished patients evaluated by the MNA-SF suffered from infectious complications and 10.1% patients at risk of malnourished had infectious complications. Those patients had statistically significant higher prevalence of infectious complications (p = 0.002) and longer LOS (p = 0.023) than well-nourished patients. Multivariable analysis revealed that preoperative malnutrition and at risk of malnourished by the MNA-SF was significantly associated with infections. The area under the curve (AUC) of MNA-SF was 0.754, which was significantly high than AUC of GNRI (0.623) (Delong's test, p = 0.033). This study demonstrated that MNA-SF is a simple and effective tool for predicting the risk of infectious complications in elderly patients undergoing posterior lumbar arthrodesis.

10.
Org Lett ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045166

RESUMO

We report herein an efficient chemical synthesis of homogeneous human E-cadherin N-linked glycopeptides consisting of a heptapeptide sequence adjacent to the Asn-633 N-glycosylation site with representative N-glycan structures, including a conserved trisaccharide, a core-fucosylated tetrasaccharide, and a complex-type biantennary octasaccharide. The key steps are a chemoselective on-resin aspartylation using a pseudoproline-containing peptide and stereoselective glycosylation using glycosyl fluororide as a donor. This synthetic strategy demonstrates potential utility in accessing a wide range of homogeneous N-linked glycopeptides for the examination of their biological function.

11.
Nature ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33029011

RESUMO

An important tenet of learning and memory is the notion of a molecular switch that promotes the formation of long-term memory1-4. The regulation of proteostasis is a critical and rate-limiting step in the consolidation of new memories5-10. One of the most effective and prevalent ways to enhance memory is by regulating the synthesis of proteins controlled by the translation initiation factor eIF211. Phosphorylation of the α-subunit of eIF2 (p-eIF2α), the central component of the integrated stress response (ISR), impairs long-term memory formation in rodents and birds11-13. By contrast, inhibiting the ISR by mutating the eIF2α phosphorylation site, genetically11 and pharmacologically inhibiting the ISR kinases14-17, or mimicking reduced p-eIF2α with the ISR inhibitor ISRIB11, enhances long-term memory in health and disease18. Here we used molecular genetics to dissect the neuronal circuits by which the ISR gates cognitive processing. We found that learning reduces eIF2α phosphorylation in hippocampal excitatory neurons and a subset of hippocampal inhibitory neurons (those that express somatostatin, but not parvalbumin). Moreover, ablation of p-eIF2α in either excitatory or somatostatin-expressing (but not parvalbumin-expressing) inhibitory neurons increased general mRNA translation, bolstered synaptic plasticity and enhanced long-term memory. Thus, eIF2α-dependent mRNA translation controls memory consolidation via autonomous mechanisms in excitatory and somatostatin-expressing inhibitory neurons.

12.
Clin Chim Acta ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035501

RESUMO

BACKGROUND: Our study aimed to formulate a nomogram based on the albumin-to-fibrinogen ratio (AFR) and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) to predict the prognosis of hepatocellular carcinoma (HCC) patients after curative hepatic resection. METHODS: A total of 825 HCC patients who underwent curative resection from 2008 to 2015 in West China Hospital of Sichuan University were divided into a training (n=616) and a validation (n=209) cohort. The AFR-GPR risk stratification was generated and confirmed by multivariate analysis. Nomograms for recurrence-free survival (RFS) and overall survival (OS) were constructed. The concordance indexes (C-index) , calibration, and decision curve analysis (DCA) were used to assess the predictive performance and clinical benefits of the nomograms. RESULTS: The AFR-GPR risk stratification was the independent prognostic factor for RFS (p=0.044) and OS (p=0.002) in the training cohort and integrated into the construction of nomograms. The C-indexes of RFS and OS in the training and validation cohorts were 0.654 (95%CI: 0.626-0.681)/0.699 (95%CI: 0.654-0.743) and 0.699 (95%CI: 0.668-0.729)/0.736 (95%CI: 0.684-0.787), respectively. Furthermore, the C-indexes of the nomograms were greater than those of other conventional staging systems. CONCLUSION: Our nomograms based on the AFR-GPR risk stratification presents the more reliable, convenient and accurate prognostic predictions for HCC patients.

13.
Microb Pathog ; : 104550, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035634

RESUMO

BACKGROUND: Mycobacterium tuberculosis (Mtb) is an intractable pathogen for humans to overcome. While as an important part of innate immunity, macrophages play an important role in resisting foreign pathogenic microorganisms, and it has been proved that there is a close relationship between macrophages and Mtb. In recent years, with the in-depth study of LncRNA, there have been crucial breakthroughs in the diagnosis and treatment of a number of diseases, and understanding the impact of LncRNA on Mtb may also be conducive to providing new therapeutic targets for tuberculosis prevention and treatment in the future. Therefore, this study explore the role of MEG3 in the proliferation and apoptosis of Mtb-infected macrophages. METHODS: Between September 2017 and September 2019, 84 consecutive pulmonary Mtd patients admitted to our hospital were selected as the observation group (OG), and concurrently, 88 healthy controls were selected as the control group (CG). MEG3 and miR-145-5p in peripheral blood of the two groups were detected, and their diagnostic value in pulmonary tuberculosis (PTB) was analyzed by receiver operating characteristic (ROC) curves. In addition, Bacillus Calmette-Guérin (BCG) and mouse Raw264.7 macrophage strains were purchased to establish the Mtb-infected macrophage model. Colony forming unit (CFU) and flow cytometry were employed to determine the effects of MEG3 and miR-145-5p on macrophages, and the correlation between the two was performed by dual-luciferase reporter (DLR) assay. RESULTS: MEG3 was highly expressed in PTB, while miR-145-5p was lowly expressed (P < 0.050). ROC analysis demonstrated that both MEG3 and miR-145-5p enjoyed favorable predictive value for the occurrence of PTB (P < 0.001). In the Mtb-infected macrophage model, MEG3 decreased (P < 0.050) while miR-145-5p increased with the time of infection (P < 0.050). Inhibited MEG3 and overexpressed miR-145-5p resulted in increased CFU and decreased apoptosis ability of macrophages (P < 0.050). The DLR assay identified a targeting relationship between miR-145-5p and MEG3 (P < 0.050). The increase of MEG3 could inhibit the expression of in miR-145-5p (P < 0.050). CONCLUSION: MEG3 affects the biological activity of Mtb-infected macrophages by targeting miR-145-5p, which may be the key to the diagnosis and treatment of PTB and even all kinds of tuberculosis in the future.

14.
Med Sci Monit ; 26: e926539, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33027245

RESUMO

BACKGROUND The aims of this study were to summarize the clinical characteristics and risk factors for bezoars and to analyze the effectiveness and safety of the endoscopic treatment of bezoars. MATERIAL AND METHODS From January 2015 to February 2020, 75 of the 23 950 patients who underwent gastroscopic examination in our medical center were diagnosed with bezoars. Clinical and treatment information for these patients was collected retrospectively and analyzed. RESULTS The detection rate of bezoars was 0.31%. Risk factors included the time of year (autumn and winter seasons), alcohol consumption, hypertension, diabetes, and residing in the Mentougou district, which is rich in hawthorn and persimmon. Abdominal pain (90.7%) and bloating (80.0%) were common clinical symptoms of bezoars, while gastric mucosa erosion (90.7%) and gastric ulcers (60%) were common manifestations on endoscopic examination. Six patients with bezoars were successfully discharged after drug treatment. The success rate for bezoars treated by gastroscopic lithotripsy was 94.2% (65/69 patients). The factors affecting the therapeutic effect of bezoars include patient age (P=0.025) and bezoar size (P=0.042). Patients with bezoars larger than 9 cm were significantly more likely to have intestinal obstructions than were patients with bezoars smaller than 9 cm (P<0.001). CONCLUSIONS Bezoars mainly occur in elderly patients with diseases such as gastrointestinal dyspraxia and diabetes, and are most common in hawthorn and persimmon producing areas. Endoscopic treatment is safe and effective for bezoars in general, but intestinal obstruction should be considered for bezoars larger than 9 cm.

15.
Urology ; 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33010291

RESUMO

OBJECTIVE: To investigate the feasibility of erectile function restoration by the genitofemoral nerve to pelvic nerve transfer in rats. METHODS;: Thirty-six male rats were included in this study. Rats in the nerve transfer group (n=12) were subjected to pelvic nerve, sacral roots and L6 roots transection and then bilateral genitofemoral nerve to pelvic nerve transfer, rats in the nerve resection group (n=12) were subjected to pelvic nerve, sacral roots and L6 roots transection without nerve transfer, and rats in the control group (n=12) served as controls. After reinnervation, awake intracavernous pressure (ICP) assessment was performed. Fluoro-Gold was injected into the corpus cavernosum. Immediately before euthanasia, transferred nerves were stimulated to test penile intracavernous pressure. The L6, S1and L1-2 spinal cord segments were used for retrogradely labeled neurons. Regenerative nerve morphological examination assessment was performed. RESULTS: Genitofemoral nerve stimulation induced an increase in ICP in the nerve transfer group. The mean ICP in this group was (33.8±9.4 mmHg), which is higher than the mean value in the nerve resection group (3.9±1.0 mmHg) but lower than that in the control group (69.8±12.2 mmHg) (p < 0.05). The formation of new neural pathways was confirmed by the appearance of Fluoro-Gold labeled neurons in the L-1 and L-2 spinal cord segments in the nerve transfer group. Regenerative nerve morphological examination showed good axonal regeneration after genitofemoral nerve transfer. CONCLUSIONS;: Nerve regeneration can be obtained by genitofemoral nerve to pelvic nerve transfer, and erectile function can be restored.

16.
Front Immunol ; 11: 1717, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013823

RESUMO

Vascular endothelial injury caused by post-hemorrhagic shock mesenteric lymph (PHSML) return is an important manifestation during refractory hemorrhagic shock. Using human umbilical vein endothelial cells (HUVECs) and transcriptome analysis, this study sought to investigate the molecular mechanism underlying the adverse effect of PHSML on vascular endothelium. Post-hemorrhagic shock mesenteric lymph was collected from male rats after they underwent hemorrhagic shock and following resuscitation, while normal mesenteric lymph (NML) was harvested from sham rats. Human umbilical vein endothelial cells were incubated with the culture medium containing either 10% phosphate buffered saline (Control), NML, or PHSML for 3 h, and then were harvested for RNA sequencing. In comparison with NML treated cells, 37 genes were differentially expressed in PHSML-treated HUVECs, including 32 upregulated genes and five downregulated genes. These differentially expressed genes were mainly enriched in inflammatory pathways, including signaling pathways for activation of the NOD-like receptors, NF-κB, and TNF. Furthermore, we found that C-C motif chemokine ligand 2 (CCL2) was increased significantly after PHSML treatment, and Bindarit, a CCL2 production inhibitor, attenuated the damage of HUVECs induced by PHSML. The results provide molecular evidence on vascular endothelium damage caused by PHSML. C-C motif chemokine ligand 2 might represent a new target for reducing vascular injury after severe hemorrhagic shock.

17.
Inflammation ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026555

RESUMO

After publication of our article [1], we found that the second images in the first row in Figure 2a were inadvertently replaced with the first image in Figure 2a.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33001292

RESUMO

OBJECTIVE: To investigate the occurrence rate of the prelacrimal recess (PLR) and its medial bony wall dimensions based on the radiological analysis to help surgeons enhance the understanding of anatomic structures for the endoscopic prelacrimal recess approach. METHODS: Cone-beam computed tomography images of 255 patients were evaluated retrospectively. The prevalence of the PLR in maxillary sinus was investigated and the thickness of its medial bony wall was measured and statistically assessed. Meanwhile, the width of the PLR was measured. The correlation between the width of the PLR and its medial bony wall thickness was assessed. The data were compared between the left side and right side, male and female. RESULTS: The PLR was present in 82.5% of the maxillary sinus, with no significant differences between the left and right sides, as well as different gender groups. The mean thickness of the medial bony wall of the PLR was 2.84 ± 1.41 mm, without statistical difference between the left and right sides but significantly larger in males than in females. The mean width of the PLR was 4.62 ± 1.74 mm and it had a significant negative correlation with the thickness of the medial bony wall of the PLR. CONCLUSION: A large individual variation exists in the anatomy of PLR, including its prevalence and dimensions of its medial bony wall. When considering the intranasal endoscopic prelacrimal recess approach, the surgeons should carefully evaluate the anatomical structure of the PLR preoperatively so as to minimize the risks of surgical complications.

19.
Mar Drugs ; 18(10)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003577

RESUMO

Inflammatory bowel disease (IBD) has been gradually considered a public health challenge worldwide. Sulfated polysaccharides, extracted from seaweed, have been shown to have an anti-inflammatory effect on the disease[...].

20.
Elife ; 92020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33006314

RESUMO

Osteoporosis is a common systemic skeletal disorder resulting in bone fragility and increased fracture risk. It is still necessary to explore its detailed mechanisms and identify novel targets for the treatment of osteoporosis. Previously, we found that a lncRNA named GAS5 in human could negatively regulate the lipoblast/adipocyte differentiation. However, it is still unclear whether GAS5 affects osteoblast differentiation and whether GAS5 is associated with osteoporosis. Our current research found that GAS5 was decreased in the bones and BMSCs, a major origin of osteoblast, of osteoporosis patients. Mechanistically, GAS5 promotes the osteoblast differentiation by interacting with UPF1 to degrade SMAD7 mRNA. Moreover, a decreased bone mass and impaired bone repair ability were observed in Gas5 heterozygous mice, manifesting in osteoporosis. The systemic supplement of Gas5-overexpressing adenoviruses significantly ameliorated bone loss in an osteoporosis mouse model. In conclusion, GAS5 promotes osteoblast differentiation by targeting the UPF1/SMAD7 axis and protects against osteoporosis.

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