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1.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638921

RESUMO

The mass production of graphene oxide (GO) unavoidably elevates the chance of human exposure, as well as the possibility of release into the environment with high stability, raising public concern as to its potential toxicological risks and the implications for humans and ecosystems. Therefore, a thorough assessment of GO toxicity, including its potential reliance on key physicochemical factors, which is lacking in the literature, is of high significance and importance. In this study, GO toxicity, and its dependence on oxidation level, elemental composition, and size, were comprehensively assessed. A newly established quantitative toxicogenomic-based toxicity testing approach, combined with conventional phenotypic bioassays, were employed. The toxicogenomic assay utilized a GFP-fused yeast reporter library covering key cellular toxicity pathways. The results reveal that, indeed, the elemental composition and size do exert impacts on GO toxicity, while the oxidation level exhibits no significant effects. The UV-treated GO, with significantly higher carbon-carbon groups and carboxyl groups, showed a higher toxicity level, especially in the protein and chemical stress categories. With the decrease in size, the toxicity level of the sonicated GOs tended to increase. It is proposed that the covering and subsequent internalization of GO sheets might be the main mode of action in yeast cells.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34647701

RESUMO

BACKGROUND: Isobutyryl-CoA dehydrogenase deficiency is a rare, autosomal recessive hereditary disease caused by a disorder in valine metabolism due to the deficiency of isobutyryl-CoA dehydrogenase.We provided two new mutations for ACAD8 and analyzed new sight to explore the association between the clinical phenotype and genotype of this disease. METHODS: The concentration of butyrylcarnitine was tested by tandem mass spectrometry. Butyryl carnitine and isobutyryl glycine levels were determined based on urine organic acid analysis. gene mutations was analyzed through gene sequencing. RESULTS: Five individuals were diagnosed with isobutyryl-CoA dehydrogenase deficiency via newborn screening, and new mutations of ACAD8 encoding isobutyryl-CoA dehydrogenase were found. The mutations were c.1166G>A in exon 10 and c.986C>T in exon 9, which were analyzed as pathogenic sites. Both manifested as an increase in butyrylcarnitine and slightly elevated isobutyryl glycine levels. No abnormalities in growth and development were observed during follow-up. Additionally, we summarized 32 types of ACAD8 mutations reported worldwide, analyzed the distribution of mutations with clinical symptoms, and found them to be mainly concentrated in the N-terminal domain and C-terminal domain. These findings may provide new clues for the clinical diagnosis and management of isobutyryl-CoA dehydrogenase deficiency. CONCLUSIONS: In this study, we reported new mutations of ACAD8 and performed a retrospective analysis of isobutyryl CoA dehydrogenase deficiency worldwide. Isobutyryl CoA dehydrogenase deficiency may pose a disease risk during the growth process, thereby requiring long-term follow-up.

3.
Nanoscale ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647934

RESUMO

Developing stable and cost-effective catalysts is the key to the next-generation renewable energy conversion technology. Here we unify computational and experimental approaches to use the Zn3V3O8 (001) surface supporting noble metal Ru as a bifunctional catalyst for the OER and HER in alkaline media. In particular, different reaction sites have been studied at four surface terminations along the [001] orientation: the A-layer with V atoms at octahedral sites, the C-layer with V and Zn atoms at octahedral sites, and with additional Zn atoms at tetrahedral sites (B-layer and D-layer, respectively). The first-principles density functional theory (DFT) results indicate that the B-layer termination with V and tetrahedrally coordinated Zn on the top showed the best OER catalytic effect, while the HER favored the D-layer termination with extra Zn atoms at the octahedral sites on the top layer. Our DFT results also suggest that Ru doping by substituting V and Zn atoms at the octahedral site could dramatically enhance the catalytic activities for the OER and HER, respectively. In particular, compared to undoped Zn3V3O8, Ru doping could reduce the calculated OER overpotential from 0.58 V to 0.30 V, which has been confirmed by our experimental results that the OER overpotential decreased from 480 mV to 260 mV at a current density of 10 mA cm-o. Moreover, the experimental results show that Ru doping could reduce the HER overpotential from 152 mV to 70 mV at a current density of 10 mA cm-r. The new insights into the underlying catalytic mechanisms may be further extended to many similar electrocatalytic processes.

4.
J Neurooncol ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599481

RESUMO

INTRODUCTION: Many patients with glioma experience surgery-related language impairment. This study developed a classification system to predict postoperative language prognosis. METHODS: Sixty-eight patients were retrospectively reviewed. Based on their location, tumors were subtyped as follows: (I) inferior frontal lobe or precentral gyrus; (II) posterior central gyrus or supramarginal gyrus (above the lateral fissure level); (III) posterior region of the superior or middle temporal gyri or supramarginal gyrus (below the lateral fissure level); and (IV) insular lobe. The distance from the tumor to the superior longitudinal fasciculus/arcuate fasciculus was calculated. The recovery of language function was assessed using the Western Aphasia Battery before surgery, and a comprehensive language test was conducted on the day of surgery; 3, 7, and 14 days after surgery. Our follow-up information of was the comprehensive language test from telephone interviews in 3 months after surgery. RESULTS: Thirty-three patients experienced transient language impairment within 1 week of surgery. Fourteen patients had permanent language impairment. Type II tumors, shorter distance from the tumor to the posterior superior longitudinal fasciculus/arcuate fasciculus, and isocitrate dehydrogenase mutations were risk factors for surgery-related language impairment. Regarding the presence or absence of permanent surgery-related language impairments, the cut-off distance between the tumor and posterior superior longitudinal fasciculus/arcuate fasciculus was 2.75 mm. CONCLUSIONS: According to our classification, patients with type II tumors had the worst language prognosis and longest recovery time. Our classification, based on tumor location, can reliably predict postoperative language status and may be used to guide tumor resection.

7.
Genome Biol Evol ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34623414

RESUMO

The true bug, Aspongopus chinensis Dallas, 1851 (Hemiptera: Dinidoridae), is a fascinating insect with prolonged diapause and medicinal properties, but also a notorious pest. However, because of the lack of genomic resources, an in-depth understanding of its biological characteristics is lacking. Here, we report the first genome assembly of A. chinensis anchored to 10 pseudochromosomes, which was achieved by combining PacBio long reads and Hi-C sequencing data. This chromosome-level genome assembly was 1.55 Gb in size with a scaffold N50 of 156 Mb. The benchmarking universal single-copy ortholog (BUSCO) analysis of the assembly captured 96.6% of the BUSCO genes. A total of 686,888,052-bp of repeat sequences, 18,511 protein-coding genes, and 1,749 noncoding RNAs were annotated. By comparing the A. chinensis genome with that of 8 homologous insects and 2 model organisms, 213 rapidly evolving gene families were identified, including 83 expanded and 130 contracted gene families. The functional enrichment of Gene Ontology and KEGG pathways showed that the significantly expanded gene families were primarily involved in metabolism, immunity, detoxification, and DNA/RNA replication associated with stress responses. The data reported here shed light on the ecological adaptation of A. chinensis and further expanded our understanding of true bug evolution in general.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34623517

RESUMO

PURPOSE: This study aimed to investigate the efficacy of digital mammography (DM), digital breast tomosynthesis (DBT), diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI separately and combined in the prediction of molecular subtypes of breast cancer. METHODS: A total of 241 patients were enrolled and underwent breast MD, DBT, DW and DCE scans. Radiomics features were calculated from intra- and peritumoral regions, and selected with least absolute shrinkage and selection operator (LASSO) regression to develop radiomics signatures (RSs). Prediction performance of intra- and peritumoral regions in the four modalities were evaluated and compared with area under the receiver-operating characteristic (ROC) curve (AUC), specificity and sensitivity as comparison metrics. RESULTS: The RSs derived from combined intra- and peritumoral regions improved prediction AUCs compared with those from intra- or peritumoral regions alone. DM plus DBT generated better AUCs than the DW plus DCE on predicting Luminal A and Luminal B in the training (Luminal A: 0.859 and 0.805; Luminal B: 0.773 and 0.747) and validation (Luminal A: 0.906 and 0.853; Luminal B: 0.807 and 0.784) cohort. For the prediction of HER2-enriched and TN, the DW plus DCE yielded better AUCs than the DM plus DBT in the training (HER2-enriched: 0.954 and 0.857; TN: 0.877 and 0.802) and validation (HER2-enriched: 0.974 and 0.907; TN: 0.938 and 0.874) cohort. CONCLUSIONS: Peritumoral regions can provide complementary information to intratumoral regions for the prediction of molecular subtypes. Compared with MRI, the mammography showed higher AUCs for the prediction of Luminal A and B, but lower AUCs for the prediction of HER2-enriched and TN.

9.
Cancer Biol Med ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34623790

RESUMO

OBJECTIVE: Lower grade gliomas (LGGs), classified as World Health Organization (WHO) grade II and grade III gliomas, comprise a heterogeneous group with a median survival time ranging from 4-13 years. Accurate prediction of the survival times of LGGs remains a major challenge in clinical practice. METHODS: We reviewed the expression data of 865 LGG patients from 5 transcriptomics cohorts. The comparative profile of immune genes was analyzed for signature identification and validation. In-house RNAseq and microarray data from the Chinese Glioma Genome Atlas (CGGA) dataset were used as training and internal validation cohorts, respectively. The samples from The Cancer Genome Atlas (TCGA) and GSE16011 cohorts were used as external validation cohorts, and the real-time PCR of frozen LGG tissue samples (n = 36) were used for clinical validation. RESULTS: A total of 2,214 immune genes were subjected to pairwise comparison to generate 2,449,791 immune-related gene pairs (IGPs). A total of 402 IGPs were identified with prognostic values for LGGs. The HOXA9-related and CRH-related scores facilitated identification of patients with different prognoses. An immune signature based on 10 IGPs was constructed to stratify patients into low and high risk groups, exhibiting different clinical outcomes. A nomogram, combining immune signature, 1p/19q status, and tumor grade, was able to predict the overall survival (OS) with c-indices of 0.85, 0.80, 0.80, 0.79, and 0.75 in the training, internal validation, external validation, and tissue sample cohorts, respectively. CONCLUSIONS: This study was the first to report a comparative profiling of immune genes in large LGG cohorts. A promising individualized immune signature was developed to estimate the survival time for LGG patients.

10.
Respir Res ; 22(1): 258, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34602075

RESUMO

BACKGROUND: Diabetes mellitus (DM) is a key contributing factor to poor survival in lung transplantation recipients. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of diabetic lung ischemia-reperfusion (IR) injury. The protective effects of adiponectin have been demonstrated in our previous study, but the underlying mechanism remains unclear. Here we demonstrated an important role of mitophagy in the protective effect of adiponectin during diabetic lung IR injury. METHODS: High-fat diet-fed streptozotocin-induced type 2 diabetic rats were exposed to adiponectin with or without administration of the SIRT1 inhibitor EX527 following lung transplantation. To determine the mechanisms underlying the action of adiponectin, rat pulmonary microvascular endothelial cells were transfected with SIRT1 small-interfering RNA or PINK1 small-interfering RNA and then subjected to in vitro diabetic lung IR injury. RESULTS: Mitophagy was impaired in diabetic lungs subjected to IR injury, which was accompanied by increased oxidative stress, inflammation, apoptosis, and mitochondrial dysfunction. Adiponectin induced mitophagy and attenuated subsequent diabetic lung IR injury by improving lung functional recovery, suppressing oxidative damage, diminishing inflammation, decreasing cell apoptosis, and preserving mitochondrial function. However, either administration of 3-methyladenine (3-MA), an autophagy antagonist or knockdown of PINK1 reduced the protective action of adiponectin. Furthermore, we demonstrated that APN affected PINK1 stabilization via the SIRT1 signaling pathway, and knockdown of SIRT1 suppressed PINK1 expression and compromised the protective effect of adiponectin. CONCLUSION: These data demonstrated that adiponectin attenuated reperfusion-induced oxidative stress, inflammation, apoptosis and mitochondrial dysfunction via activation of SIRT1- PINK1 signaling-mediated mitophagy in diabetic lung IR injury.

11.
Waste Manag ; 135: 389-396, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34610538

RESUMO

In this study, a novel method for producing direct reduced iron (DRI) powders based on microwave-assisted self-reduction of core-shell composite pellets composed of blast furnace (BF) dust and hazardous electric arc furnace (EAF) dust followed by magnetic separation was reported. The proper core-shell structure of the composite pellets was designed according to the rule of impedance matching and properties of BF dust and EAF dust by adjusting the thickness of shell (i.e., thickness of impedance matching layer) via controlling the C/O molar ratio of the raw materials from 0.55 to 0.70. The results showed that the EAF dust with high content of CaO was beneficial to the mechanical strength of green, dried, and metallized pellets (collected after reduction), while the BF dust with high content of carbon enabled sufficient microwave-assisted reduction of the pellets, facilitating subsequent magnetic separation and also the removal of zinc from EAF dust. By reduction of the core-shell BF dust-EAF dust composite pellets with the C/O molar ratio of 0.65 at 1050 °C for 15 min, the resulting metallized pellets showed superior reduction and magnetic separation indexes with higher removal percentages of zinc and lead, in comparison with conventional metallized pellets. The DRI powders obtained after magnetic separation had total iron content of 91.2 wt%, iron metallization degree of 95.8%, yield of 68.1%, and iron recovery of 88.0%. This study provided a good example for efficient and environmentally friendly comprehensive utilization of typical and hazardous wastes in the iron and steel industry.

12.
Oxid Med Cell Longev ; 2021: 2216314, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616502

RESUMO

Objectives: Observational studies indicate that insomnia may increase risk of peptic ulcer disease (PUD). Our purpose is to clarify the possible causal relationship between insomnia and PUD by Mendelian randomization analyses. Methods: We carried out analyses using summary statistics data for genetic variants reported from a GWAS of insomnia (N = up to 1,331,010 individuals) and from a GWAS of PUD (N = up to 456,327 individuals). Three Mendelian randomization approaches were used to explore whether insomnia might play a causal role in PUD, and pathway and functional enrichment analyses were conducted to anticipate the underlying mechanisms. Results: Conventional Mendelian randomization analysis showed clear causality between insomnia and PUD; 1 SD increased insomnia incident was related to a 19% higher risk of PUD (P = 6.69 × 10-16; OR, 1.19 (95% CI, 1.14-1.24)). The associations between insomnia and PUD were consistent in the other two analyses performed using the weighted median method (P = 7.75 × 10-7; OR, 1.16 (95% CI, 1.09-1.23)) and MR-Egger regression (P = 5.00 × 10-3; OR, 1.27 (95% CI, 1.07-1.50)). Moreover, no evidence indicated a reverse causality between PUD events and insomnia symptoms. Pathway and functional enrichment analyses indicated that the mechanisms of insomnia effect on PUD may be through various ways, such as the immune system and oxidative stress. Conclusions: This Mendelian randomization study suggests insomnia as a causal risk factor for PUD. The potential mechanisms included may be immune and oxidative stress. These findings indicate that improving sleep quality could have substantial health benefits.

13.
Macromol Biosci ; : e2100317, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34626523

RESUMO

The mechanical properties of artificial skins are complicated to maintain under ensuring air permeability and antimicrobial. Thus, a series of hydrophilic antimicrobial polymer networks are prepared by crosslinking chitosan and polyvinyl alcohol with the lauramidopropyl betaine and Hydrogen bond organic framework (CS/PVA/LPB/2D-HOF). The mechanical performance of the control groups and the complex are systematically evaluated to attain an artificial strength skin. The CS/PVA/LPB/2D-HOF complex exhibits strong mechanical abilities than other control groups. By analyzing the IR spectra and the morphology, The synergistic effect of hydrogen bonds between molecules and cracks significantly improves the mechanical properties of the complex. Its maximum tensile strength can reach 29 MPa, and its maximum load capacity can reach 3700 g. Notably, the composite membrane also performs an excellent antimicrobial activity. In vivo and in vitro experiments show that the hybrid membrane can promote tissue regeneration and wound healing (95༅). These results may open up the opportunity for future composite material investigations in the artificial skin and tissue engineering field. This article is protected by copyright. All rights reserved.

14.
Environ Res ; : 112161, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34626591

RESUMO

BACKGROUND: Congenital anomalies (CAs) are the leading causes for children's disabilities and mortalities worldwide. The associations between air pollution and CAs are not fully characterized in fetuses born by in vitro fertilization (IVF) who are at high risk of congenital anomalies. METHODS: We conducted a cross-sectional study including 16,971 IVF cycles from three hospitals in Hebei Province, China, 2014-2019. Air quality data was obtained from 149 air monitoring stations. Individual average daily concentrations of PM2.5, PM10, NO2, SO2, CO, and O3 were estimated by spatiotemporal kriging method. Exposure windows were divided into 5: preantral follicle period, antral follicle period, germinal period, embryonic period and early fetal period. Logistic generalized estimating equations were used to estimate the associations between air pollutants and overall or organ-system specific congenital anomalies. Negative control exposure method was used to detect and reduce bias of estimation. RESULTS: We found increasing levels of PM2.5 and PM10 were associated with higher risk of overall congenital anomalies during early fetal period, equating gestation 10-12 weeks (OR: 1.05, 95% CI: 1.02-1.09, p = 0.013 for a 10 µg/m3 increase of PM2.5; OR: 1.03, 95% CI: 1.01-1.06, p = 0.021 for a 10 µg/m3 increase of PM10). Cleft lip and cleft palate were associated with PM10 in germinal period and early fetal period. The CAs of eye, ear, face and neck were related to CO in preantral follicle stage. We did not find the association between chromosome abnormalities and air pollution exposure. CONCLUSIONS: We concluded that ambient air pollution was a risk factor for congenital anomalies of fetus conceived by IVF, especially exposure in early fetal period.

15.
Artif Intell Rev ; : 1-70, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34602697

RESUMO

Microorganisms such as bacteria and fungi play essential roles in many application fields, like biotechnique, medical technique and industrial domain. Microorganism counting techniques are crucial in microorganism analysis, helping biologists and related researchers quantitatively analyze the microorganisms and calculate their characteristics, such as biomass concentration and biological activity. However, traditional microorganism manual counting methods, such as plate counting method, hemocytometry and turbidimetry, are time-consuming, subjective and need complex operations, which are difficult to be applied in large-scale applications. In order to improve this situation, image analysis is applied for microorganism counting since the 1980s, which consists of digital image processing, image segmentation, image classification and suchlike. Image analysis-based microorganism counting methods are efficient comparing with traditional plate counting methods. In this article, we have studied the development of microorganism counting methods using digital image analysis. Firstly, the microorganisms are grouped as bacteria and other microorganisms. Then, the related articles are summarized based on image segmentation methods. Each part of the article is reviewed by methodologies. Moreover, commonly used image processing methods for microorganism counting are summarized and analyzed to find common technological points. More than 144 papers are outlined in this article. In conclusion, this paper provides new ideas for the future development trend of microorganism counting, and provides systematic suggestions for implementing integrated microorganism counting systems in the future. Researchers in other fields can refer to the techniques analyzed in this paper.

16.
Nature ; 598(7879): 188-194, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34616074

RESUMO

The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1-4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.

17.
Nat Genet ; 53(10): 1425-1433, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34611362

RESUMO

Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.

18.
Signal Transduct Target Ther ; 6(1): 355, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34650034

RESUMO

This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).

19.
Orthop Surg ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34651434

RESUMO

OBJECTIVE: To explore the main causes of hypertrophied ligamentum flavum (HLF) and the possibility of using bipedal standing mouse model to simulate the pathological changes in human HLF. METHODS: Thirty-two 8-week-old C57BL/6 male mice were randomly assigned to the experimental group (n = 16) and control group (n = 16). In the experimental group, mice were induced to adopt a bipedal standing posture by their hydrophobia. The experimental mice were maintained bipedal standing for 8 h a day with an interval of 2 h to consume food and water. The control mice were placed in a similar environment without bipedal standing. Eight 18-month-old C57BL/6 male mice were compared to evaluate the LF degeneration due to aging factor. Three-dimensional (3D) reconstruction and finite element models were carried out to analyze the stress and strain distribution of the mouse LF in sprawling and bipedal standing postures. Hematoxylin and Eosin (HE), Verhoeff-Van Gieson (VVG), and immunohistochemistry (IHC) staining were used to evaluate the LF degeneration of mice and humans. RT-qPCR and immunofluorescence analysis were used to evaluate the expressions of fibrosis-related factors and inflammatory cytokines of COL1A1, COL3A1, α-SMA, MMP2, IL-1ß, and COX-2. RESULTS: The von Mises stress (8.85 × 10-2 MPa) and maximum principal strain (6.64 × 10-1 ) in LF were increased 4944 and 7703 times, respectively, in bipedal standing mice. HE staining showed that the mouse LF area was greater in the bipedal standing 10-week-old group ([10.01 ± 2.93] × 104 µm2 ) than that in the control group ([3.76 ± 1.87] × 104 µm2 ) and 18-month-old aged group ([6.09 ± 2.70] × 104 µm2 ). VVG staining showed that the HLF of mice (3.23 ± 0.58) and humans (2.23 ± 0.31) had a similar loss of elastic fibers and an increase in collagen fibers. The cell density was higher during the process of HLF in mice (39.63 ± 4.81) and humans (23.25 ± 2.05). IHC staining showed that the number of α-SMA positive cells were significantly increased in HLF of mice (1.63 ± 0.74) and humans (3.50 ± 1.85). The expressions of inflammatory cytokines and fibrosis-related factors of COL1A1, COL3A1, α-SMA, MMP2, IL-1ß, and COX-2 were consistently higher in bipedal standing group than the control group. CONCLUSION: Our study suggests that 3D finite element models can help analyze the abnormal stress and strain distributions of LF in modeling mice. Mechanical stress is the main cause of hypertrophied ligamentum flavum compared to aging. The bipedal standing mice model can reflect the pathological characteristics of human HLF. The bipedal standing mice model can provide a standardized condition to elucidate the molecular mechanisms of mechanical stress-induced HLF in vivo.

20.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4208-4213, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467734

RESUMO

In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Angústia Psicológica , Animais , Cápsulas , Camundongos , Camundongos Endogâmicos BALB C
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