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1.
Exp Cell Res ; : 112178, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32679235

RESUMO

Cdc14a is an evolutionarily conserved dual-specific protein phosphatase, and it plays different roles in different organisms. Cdc14amutations in human have been reported to cause male infertility, while the specific role of Cdc14a in regulation of the male reproductive system remains elusive. In the present study, we established a knockout mouse model to study the function of Cdc14a in male reproductive system.Cdc14a-/- male mice were subfertile and they could only produce very few offspring. The number of sperm was decreased, the sperm motility was impaired, and the proportion of sperm with abnormal morphology was elevated in Cdc14a-/- mice. When we mated Cdc14a-/- male mice with wild-type (WT) female mice, fertilized eggs could be found in female fallopian tubes, however, the majority of these embryos died during development. Some empty spaces were observed in seminiferous tubule of Cdc14a-/- testes. Compared with WT male mice, the proportions of pachytene spermatocytes were increased and germ cells stained with γH2ax were decreased in Cdc14a-/- male mice, indicating that knockout of Cdc14a inhibited meiotic initiation. Subsequently, we analyzed the expression levels of some substrate proteins of Cdc14a, including Cdc25a, Wee1, and PR-Set7, and compared those with WT testes, in which the expression levels of these proteins were significantly increased in Cdc14a-/- testes. Our results revealed that Cdc14a-/-male mice are highly subfertile, and Cdc14a is essential for normal spermatogenesis and sperm function.

2.
Biotechnol Bioeng ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648933

RESUMO

Microbial cell factories are widely used for the production of high-value chemicals. However, maximizing production titers is made difficult by the complicated regulatory mechanisms of these cell platforms. Here, kcat values were incorporated to construct an Escherichia coli enzyme-constrained model. The resulting ec_iML1515 model showed that the protein demand and protein synthesis rate were the key factors affecting lysine production. By optimizing the expression of the 20 top-demanded proteins, lysine titers reached 95.7 ± 0.7 g/L, with a 0.45 g/g glucose yield. Moreover, adjusting NH4 + and dissolved oxygen levels to regulate the synthesis rate of energy metabolism-related proteins caused lysine titers and glucose yields to increase to 193.6 ± 1.8 g/L and 0.74 g/g, respectively. The ec_iML1515 model provides insight into how enzymes required for the biosynthesis of certain products are distributed between and within metabolic pathways. This information can be used to accurately predict and rationally design lysine production.

3.
Nanomedicine ; 29: 102254, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32615335

RESUMO

FGF-2 accumulates in many tumor tissues and is closely related to the development of tumor angiogenesis and the immunosuppressive microenvironment. This study aimed to investigate whether active immunization against FGF-2 could modify antitumor immunity and enhance the efficacy of an HPV16 E7-specific therapeutic vaccine. Combined immunization targeting both FGF-2 and E7 significantly suppressed tumor growth, which was accompanied by significantly increased levels of IFN-γ-expressing splenocytes and effector CD8 T cells and decreased levels of immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells(MDSCs) in both the spleen and tumor; in addition, the levels of FGF-2 and neovascularization in tumors were decreased in the mice receiving the combined immunization, and tumor cell apoptosis was promoted. The combination of an HPV16 E7-specific vaccine and active immunization against FGF-2 significantly enhances antitumor immune responses in mice with TC-1 tumors, indicating a promising strategy for tumor immunotherapy.

4.
J Cell Mol Med ; 24(12): 6928-6942, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32364678

RESUMO

Acidosis, a common feature of cerebral ischaemia and hypoxia, plays a key role in these pathological processes by aggravating the ischaemic and hypoxic injuries. To explore the mechanisms, in this research, we cultured primary neurons in an acidic environment (potential of hydrogen [pH]6.2, 24 hours) to mimic the acidosis. By proteomic analysis, 69 differentially expressed proteins in the acidic neurons were found, mainly related to stress and cell death, synaptic plasticity and gene transcription. And, the acidotic neurons developed obvious alterations including increased neuronal death, reduced dendritic length and complexity, reduced synaptic proteins, tau hyperphosphorylation, endoplasmic reticulum (ER) stress activation, abnormal lysosome-related signals, imbalanced oxidative stress/anti-oxidative stress and decreased Golgi matrix proteins. Then, melatonin (1 × 10-4  mol/L) was used to pre-treat the cultured primary neurons before acidic treatment (pH6.2). The results showed that melatonin partially reversed the acidosis-induced neuronal death, abnormal dendritic complexity, reductions of synaptic proteins, tau hyperphosphorylation and imbalance of kinase/phosphatase. In addition, acidosis related the activations of glycogen synthase kinase-3ß and nuclear factor-κB signals, ER stress and Golgi stress, and the abnormal autophagy-lysosome signals were completely reversed by melatonin. These data indicate that melatonin is beneficial for neurons against acidosis-induced injuries.

5.
Adv Mater ; 32(25): e2001894, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32424910

RESUMO

Research interest and achievements in zinc aqueous batteries, such as alkaline Zn//Mn, Zn//Ni/Co, Zn-air batteries, and near-neutral Zn-ion and hybrid ion batteries, have surged throughout the world due to their features of low-cost and high-safety. However, practical application of Zn-based secondary batteries is plagued by restrictive energy and power densities in which an inadequate output plateau voltage and sluggish kinetics are mutually accountable. Here, a novel paradigm high-rate and high-voltage Zn-Mn hybrid aqueous battery (HAB) is constructed with an expanded electrochemical stability window over 3.4 V that is affordable. As a proof of concept, catalyzed MnO2 /Mn2+ electrolysis kinetics is demonstrated in the HAB via facile introduction of Ni2+ into the electrolyte. Various techniques are employed, including in situ synchrotron X-ray powder diffraction, ex situ X-ray absorption fine structure, and electron energy loss spectroscopy, to reveal the reversible charge-storage mechanism and the origin of the boosted rate-capability. Density functional theory (DFT) calculations reveal enhanced active electron states and charge delocalization after introducing strongly electronegative Ni. Simulations of the reaction pathways confirm the enhanced catalyzed electrolysis kinetics by the facilitated charge transfer at the active O sites around Ni dopants. These findings significantly advance aqueous batteries a step closer toward practical low-cost application.

6.
Nat Commun ; 11(1): 2262, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385264

RESUMO

Cell division can perturb the metabolic performance of industrial microbes. The C period of cell division starts from the initiation to the termination of DNA replication, whereas the D period is the bacterial division process. Here, we first shorten the C and D periods of E. coli by controlling the expression of the ribonucleotide reductase NrdAB and division proteins FtsZA through blue light and near-infrared light activation, respectively. It increases the specific surface area to 3.7 µm-1 and acetoin titer to 67.2 g·L-1. Next, we prolong the C and D periods of E. coli by regulating the expression of the ribonucleotide reductase NrdA and division protein inhibitor SulA through blue light activation-repression and near-infrared (NIR) light activation, respectively. It improves the cell volume to 52.6 µm3 and poly(lactate-co-3-hydroxybutyrate) titer to 14.31 g·L-1. Thus, the optogenetic-based cell division regulation strategy can improve the efficiency of microbial cell factories.

7.
Metab Eng ; 60: 128-137, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32315760

RESUMO

Numerous value-added chemicals can be produced using xylan as a feedstock. However, the product yields are limited by low xylan utilization efficiency, as well as by carbon flux competition between biomass production and biosynthesis. Herein, a dynamic consolidated bioprocessing strategy was developed, which coupled xylan utilization and yield optimization modules. Specifically, we achieved the efficient conversion of xylan to valuable chemicals in a fully consolidated manner by optimizing the expression level of xylanases and xylose transporter in the xylan utilization module. Moreover, a cell density-dependent, and Cre-triggered dynamic system that enabled the dynamic decoupling of biosynthesis and biomass production was constructed in the yield optimization module. The final shake flask-scale titers of xylonate, produced through an exogenous pathway, and shikimate, produced through an endogenous pathway, reached 16.85 and 3.2 g L-1, respectively. This study not only provides an efficient microbial platform for the utilization of xylan, but also opens up the possibility for the large-scale production of high value-added chemicals from renewable feedstocks.

8.
J Clin Invest ; 130(7): 3654-3670, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32229726

RESUMO

Germinal center (GC) responses require B cells to respond to a dynamic set of intercellular and microenvironmental signals that instruct B cell positioning, differentiation, and metabolic reprogramming. RHO-associated coiled-coil-containing protein kinase 2 (ROCK2), a serine-threonine kinase that can be therapeutically targeted by ROCK inhibitors or statins, is a key downstream effector of RHOA GTPases. Although RHOA-mediated pathways are emerging as critical regulators of GC responses, the role of ROCK2 in B cells is unknown. Here, we found that ROCK2 was activated in response to key T cell signals like CD40 and IL-21 and that it regulated GC formation and maintenance. RNA-Seq analyses revealed that ROCK2 controlled a unique transcriptional program in GC B cells that promoted optimal GC polarization and cholesterol biosynthesis. ROCK2 regulated this program by restraining AKT activation and subsequently enhancing FOXO1 activity. ATAC-Seq (assay for transposase-accessible chromatin with high-throughput sequencing) and biochemical analyses revealed that the effects of ROCK2 on cholesterol biosynthesis were instead mediated via a novel mechanism. ROCK2 directly phosphorylated interferon regulatory factor 8 (IRF8), a crucial mediator of GC responses, and promoted its interaction with sterol regulatory element-binding transcription factor 2 (SREBP2) at key regulatory regions controlling the expression of cholesterol biosynthetic enzymes, resulting in optimal recruitment of SREBP2 at these sites. These findings thus uncover ROCK2 as a multifaceted and therapeutically targetable regulator of GC responses.

10.
Vet Microbiol ; 243: 108646, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32273022

RESUMO

Pasteurella multocida is a gram-negative bacterial pathogen, which causes a large number of diseases in mammals, birds and human. Although the bacterium has been known for decades, the pathogenesis and the mechanisms of P. multocida induced host immunity are poorly understood. Recently, we have reported that nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome plays an important role in caspase-1 activation and IL-1ß secretion in macrophages infected with P. multocida. In this study, the inflammasome activation and IL-1ß secretion were further demonstrated by using high- and low-virulent bovine P. multocida isolates. The results showed that, comparing with macrophages infected with the high-virulent PmCQ2 isolates, the low-virulent PmCQ6 induced higher levels of NLRP3 transcription, caspase-1 activation and mature IL-1ß secretion. Furthermore, the capsule of the high-virulent PmCQ2 was much thicker than that of low-virulent PmCQ6, which indicating that capsular thickness might influence the bacteria colonization and NLRP3 inflammasome activation. The results suggested that differences in maturation of IL-1ß in macrophages upon high- and low- virulent P. multocida infection are critically dependent on the differential activation of NLRP3 inflammasome. This study provided more understanding for the host immune responses induced by P. multocida and further extended the knowledge of P. multocida virulence from the view of host innate immunity.

11.
Acta Biomater ; 108: 300-312, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32251780

RESUMO

Using monoclonal antibodies to block tumor angiogenesis has yielded effective antitumor effects. However, this treatment method has long cycles and is very expensive; therefore, its long-term and extensive application is limited. In this study, we developed a nanovaccine using bacterial biomembranes as carriers for antitumor therapy. The whole basic fibroblast growth factor (BFGF) molecule (154 amino acids (aa)) was loaded onto bacterial outer membrane vesicles (OMVs) using gene recombination technology. The strong adjuvant effect of OMVs was used to induce the host to produce anti-BFGF autoantibodies. We proved that persistent anti-BFGF autoantibodies can be induced in mice after only 3 immunizations to antagonize BFGF functions. The effects included multiple tumor suppression functions, including inhibition of tumor angiogenesis, induction of tumor cell apoptosis, reversal of tumor immune barriers, and promotion of tumor-specific cytotoxic T lymphocytes (CTLs), eventually causing tumor regression. We confirmed that bacterial biomembranes can be used as a vaccine delivery system to induce the production of antibodies against autoantigens, which may be used for tumor therapy. This study expands the application fields of bacterial biomembrane systems and provides insight for tumor immunotherapy other than monoclonal antibody technology. STATEMENT OF SIGNIFICANCE: In this study, we proved that bacteria-released outer membrane vesicles (OMVs) modified via genetic engineering can be used as a vaccine carrier to break autoimmune tolerance and induce the body to produce autoantibodies to antagonize pathological molecules and block pathological signaling pathways for tumor therapy. OMVs naturally released by bacteria were used to successfully load the full-length BFGF protein (154 aa). We proved that persistent anti-BFGF autoantibodies can be induced in tumor-bearing mice after only 3 immunizations to effectively inhibit tumors. Furthermore, the production of these antibodies successfully inhibited tumor angiogenesis, promoted tumor cell apoptosis, reversed the tumor immunosuppressive microenvironment, increased the cytotoxic T lymphocyte (CTL) reaction, and eventually inhibited tumor growth.

12.
J Med Virol ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134114

RESUMO

The live attenuated hepatitis A virus vaccine (HA-L) is in routine use in the Chinese national immunization program (NIP). The major disadvantages of HA-L include that theoretically, it may be possible for mutation shifts and secondary infections of the live vaccine viral strain. The aim of this study was to explore variation in the viral strain after vaccination with the HA-L. A total of 1297 fecal samples (including 470 for the 18 to 36-month-old age group, 527 for the 3 to 16-year-old group, and 300 for the 16 years and older group) were collected in the study, and the rate of hepatitis A virus (HAV) positivity in fecal samples was 11.36% (31/273), 11.44% (31/271), 9.70% (26/268), 8.47% (21/248), and 9.70% (23/237) on days 0, 7, 14, 21 and 28, respectively. A total of 77 HAV positive samples were randomly selected for VP1/2A (360 bp, 2218-2577) gene analysis. Phylogenetic trees were then constructed by the neighbor-joining method. Phylogenetic analyses showed that all the isolated HAV strains belonged to sub-genotype IB, which was the same as the vaccine strain. Compared with the vaccine strain, HM-175/7MK-5 (M16632.1), there were only two base mutations discovered, at 2291 and 2568. However, the amino acid mutation analysis showed that those base mutations were synonymous mutations. The isolated HAV strains were genetically stable. This study provides a reference for the safety concern regarding the routine and wide-range use in people older than 18 months.

13.
Med Biol Eng Comput ; 58(6): 1251-1264, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32221797

RESUMO

In medicine, white blood cells (WBCs) play an important role in the human immune system. The different types of WBC abnormalities are related to different diseases so that the total number and classification of WBCs are critical for clinical diagnosis and therapy. However, the traditional method of white blood cell classification is to segment the cells, extract features, and then classify them. Such method depends on the good segmentation, and the accuracy is not high. Moreover, the insufficient data or unbalanced samples can cause the low classification accuracy of model by using deep learning in medical diagnosis. To solve these problems, this paper proposes a new blood cell image classification framework which is based on a deep convolutional generative adversarial network (DC-GAN) and a residual neural network (ResNet). In particular, we introduce a new loss function which is improved the discriminative power of the deeply learned features. The experiments show that our model has a good performance on the classification of WBC images, and the accuracy reaches 91.7%. Graphical Abstract Overview of the proposed method, we use the deep convolution generative adversarial networks (DC-GAN) to generate new samples that are used as supplementary input to a ResNet, the transfer learning method is used to initialize the parameters of the network, the output of the DC-GAN and the parameters are applied the final classification network. In particular, we introduced a modified loss function for classification to increase inter-class variations and decrease intra-class differences.

14.
Adv Mater ; : e1907557, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32058658

RESUMO

Confinement of polysulfides in sulfur cathodes is pivotal for eliminating the "shuttle effect" in metal-sulfur batteries, which represent promising solutions for large-scale and sustainable energy storage. However, mechanistic exploration and in-depth understanding for the confinement of polysulfides remain limited. Consequently, it is a critical challenge to achieve highly stable metal-sulfur batteries. Here, based on a 2D metal-organic framework (2D MOF), a new mechanism to realize effective confinement of polysulfides is proposed. A combination of in situ synchrotron X-ray diffraction, electrochemical measurements, and theoretical computations reveal that the dynamic electron states of the Ni centers in the 2D MOF enable the interaction between polysulfides and the MOF in the discharge/charge process to be tuned, resulting in both strong adsorption and fast conversion kinetics of polysulfides. The resultant room-temperature sodium-sulfur batteries are amongst the most stable reported so far, thus demonstrating that the new mechanism opens a promising avenue for the development of high-performance metal-sulfur batteries.

15.
Nat Prod Res ; : 1-10, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32037886

RESUMO

Sanguisorba officinalis L. is a traditional herbal plant that belongs to the genus Sanguisorba and the family Rosaceae. Two new phenolic glycosides (1-2), ten known phenolics (3-12), and six known monoterpenoid glycosides (13-18) were isolated from the roots of S. officinalis using silica gel column and preparative middle pressure liquid chromatography (MPLC). The chemical structures were elucidated based on extensive spectroscopic experiments, including 1D and 2D NMR as well as HR-ESI-MS, and comparison with those reported in the literature. Compounds 3-5, and 13 were isolated from the Rosaceae family and compound 7 was obtained from the genus Sanguisorba for the first time. Additionally, all compounds were evaluated for their anti-complementary activities against the classical pathway. Furthermore, compounds 1, 5, 9, and 14 showed significant anti-complementary activities with the 50% haemolytic inhibition concentrations (CH50) values of 0.40 ± 0.03, 0.57 ± 0.01, 0.51 ± 0.07, and 0.53 ± 0.05 mM, respectively.

16.
Biotechnol Bioeng ; 117(5): 1562-1574, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32022245

RESUMO

Biological network construction for Saccharomyces cerevisiae is a widely used approach for simulating phenotypes and designing cell factories. However, due to a complicated regulatory mechanism governing the translation of genotype to phenotype, precise prediction of phenotypes remains challenging. Here, we present WM_S288C, a computational whole-cell model that includes 15 cellular states and 26 cellular processes and which enables integrated analyses of physiological functions of Saccharomyces cerevisiae. Using WM_S288C to predict phenotypes of S. cerevisiae, the functions of 1140 essential genes were characterized and linked to phenotypes at five levels. During the cell cycle, the dynamic allocation of intracellular molecules could be tracked in real-time to simulate cell activities. Additionally, one-third of non-essential genes were identified to affect cell growth via regulating nucleotide concentrations. These results demonstrated the value of WM_S288C as a tool for understanding and investigating the phenotypes of S. cerevisiae.

17.
Nanoscale ; 12(5): 3076-3089, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31965136

RESUMO

Human papillomavirus (HPV) is the identified causative agent of cervical cancer. Current therapeutic HPV vaccine candidates lack significant clinical efficacy, which can be attributed to insufficient activation of effector cells, lack of effective modification of the immunosuppressive tumor microenvironment, and the limitations of applied tumor models for preclinical vaccine evaluation. Here, a mouse model of orthotopic genital tumors was used to assess the effect of self-assembled nanofibers on eliciting a robust antitumor response via local mucosal immunization. A candidate vaccine was obtained by fusing HPV16 E744-62 to the self-assembling peptide Q11, which was assembled into nanofibers in a salt solution. Mice bearing an established genital TC-1 tumor were immunized with nanofibers through the intravaginal, intranasal, or subcutaneous route. Mucosal vaccination, especially via the intravaginal route, was more effective for suppressing tumor growth than subcutaneous immunization. The potential underlying mechanisms include promoting the systemic generation and tumor accumulation of antigen-specific cytotoxic T lymphocytes expressing high levels of interferon (IFN)-γ or granzyme-B, and reducing the tumor infiltration of immunosuppressive regulatory T cells and myeloid-derived suppressor cells. The levels of IFN-γ, the chemokines CXCL9 and CXCL10, and CXCR3+CD8+ T cells were significantly increased in tumor tissues, which may account for the improved recruitment of effector T cells into the tumor. Local mucosal immunization of nanofibers via the intravaginal route represents a new and promising vaccination strategy for the treatment of genital tumor lesions such as cervical cancer.

18.
Neurosci Bull ; 36(5): 463-474, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31989424

RESUMO

Chemical stimulation of the kidney increases sympathetic activity and blood pressure in rats. The hypothalamic paraventricular nucleus (PVN) is important in mediating the excitatory renal reflex (ERR). In this study, we examined the role of molecular signaling in the PVN in mediating the capsaicin-induced ERR and sympathetic activation. Bilateral PVN microinjections were performed in rats under anesthesia. The ERR was elicited by infusion of capsaicin into the cortico-medullary border of the right kidney. The reflex was evaluated as the capsaicin-induced changes in left renal sympathetic nerve activity and mean arterial pressure. Blockade of angiotensin type 1 receptors with losartan or inhibition of angiotensin-converting enzyme with captopril in the PVN abolished the capsaicin-induced ERR. Renal infusion of capsaicin significantly increased NAD(P)H oxidase activity and superoxide anion production in the PVN, which were prevented by ipsilateral renal denervation or microinjection of losartan into the PVN. Furthermore, either scavenging of superoxide anions or inhibition of NAD(P)H oxidase in the PVN abolished the capsaicin-induced ERR. We conclude that the ERR induced by renal infusion of capsaicin is mediated by angiotensin type 1 receptor-related NAD(P)H oxidase activation and superoxide anion production within the PVN.

19.
Nat Prod Res ; 34(2): 225-232, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30580619

RESUMO

One new aryldihydronaphthalene-type lignan (1) together with eight known lignans (2-4, 7-11) as well as two caffeic-acid dimers (5, 6) were isolated from an ethanol extract of the whole plant of Corispermum mongolicum Iljin (Chenopodiaceae). The chemical structures of these compounds were determined from 1D and 2D NMR and HR-ESI-MS spectra, and results were compared with data from the literature. This study is the first demonstration of nine compounds (2 and 4-11) isolated from the Chenopodiaceae family, with one of these (3) from the genus Corispermum. Anti-inflammatory effects of the isolated compounds were evaluated in terms of inhibition of production of nitric oxide, tumour necrosis factor-α, and interleukin-6 in lipopolysaccharide-induced RAW 264.7 cells.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Chenopodiaceae/química , Lignanas/isolamento & purificação , Extratos Vegetais/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Chenopodiaceae/metabolismo , Interleucina-6/biossíntese , Lignanas/química , Lignanas/farmacologia , Lipopolissacarídeos , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/efeitos dos fármacos
20.
Turk Neurosurg ; 30(1): 48-59, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31452175

RESUMO

AIM: To predict the overall survival (OS) and the cancer-specific survival (CSS) of patients with high-grade glioma (HGG) using nomograms and the surveillance, epidemiology, and end results (SEER) database (2000-2013). MATERIAL AND METHODS: A total of 3706 patients with high-grade glioma were identified by the SEER database (2000-2013). Based on the relevant information of these patients, we divided the primary cohort into a training cohort (n=3336) and a validation cohort (n=370). The nomograms were constructed by the training cohort and corroborated by the validation cohort. RESULTS: According to the multivariate analysis of the training cohort, the nomograms of OS and CSS indicated that patient age at diagnosis, laterality, radiation, and the extent of resection are significantly correlated with the survival rate. The c-indexes of the nomograms of OS and CSS of the training cohort are 0.682 [95% confidence interval (CI): 0.671-0.693] and 0.678 (95%CI: 0.666- 0.690), respectively. The calibration curve plots of 1- and 3-year OS and CSS showed that the nomogram predictions are consistent with the observed outcomes for both the training and validation cohorts. CONCLUSION: Based on the data obtained, we established a scoring model to predict the OS and the CSS of patients with HGG. All calibration curves showed high consistency between the predicted and actual survival.

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