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1.
Artigo em Inglês | MEDLINE | ID: mdl-32763343

RESUMO

Abnormal perceptual processing in schizophrenia may contribute to the development of positive symptoms such as hallucinations. Experimental findings suggest that such abnormalities result from impaired processing of local signals into complex cortical representations. Because complex processing is needed to generate the perception of illusory motion from local signals, deteriorated perception of illusory motion would be expected in schizophrenia. However, findings are mixed, and the relationship between complex motion processing and symptoms is unclear. Illusions with multiple flow components (e.g. rotation/expansion) are known to strongly engage specialized complex processing mechanisms that may be abnormal in schizophrenia, but have not yet been investigated. We used a recently constructed paradigm based on the Pinna-Brelstaff illusion to manipulate complex-flow illusory perception in a quantitative manner and probe associations with dimensional symptoms. In 102 patients and 90 controls, perceived speed and perceptual variability for the PBF were measured across a range of parameters. Meanwhile, eye movement was recorded and gaze parameters were analysed to examine effects on illusory perception. Our results showed that patients experienced faster illusory rotation than controls, while they made fewer eye fixations. This heightened illusory perception was significantly correlated with positive and general, but not negative, symptom scores. Our results indicate that unusual processing of complex-flow motion in patients may be specifically related to dimensional symptoms, which could provide a promising strategy for parsing heterogeneity in the schizophrenia syndrome. This further highlights the role of motion perception abnormalities in the pathophysiology of schizophrenia, thus encouraging future investigation into visual remediation therapeutics.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33048761

RESUMO

In this article, we come up with a novel Nesterov gradient and heavy-ball double accelerated distributed synchronous optimization algorithm, called NHDA, and adopt a general asynchronous model to further propose an effective asynchronous algorithm, called ASY-NHDA, for distributed optimization problem over directed graphs, where each agent has access to a local objective function and computes the optimal solution via communicating only with its immediate neighbors. Our goal is to minimize a sum of all local objective functions satisfying strong convexity and Lipschitz continuity. Consider a general asynchronous model, where agents communicate with their immediate neighbors and start a new computation independently, that is, agents can communicate with their neighbors at any time without any coordination and use delayed information from their in-neighbors to compute a new update. Delays are arbitrary, unpredictable, and time-varying but bounded. The theoretical analysis of NHDA is based on analyzing the interaction among the consensus, the gradient tracking, and the optimization processes. As for the analysis of ASY-NHDA, we equivalently transform the asynchronous system into an augmented synchronous system without delays and prove its convergence through using the generalized small gain theorem. The results show that NHDA and ASY-NHDA converge to the optimal solution at a linear convergence as long as the largest step size is positive and less than an explicitly estimated upper bound, and the largest momentum parameter is nonnegative and less than an upper bound. Finally, we demonstrate the advantages of ASY-NHDA through simulations.

3.
Int J Legal Med ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067643

RESUMO

Understanding the violence behaviors in schizophrenia patients has always been the focus of forensic psychiatry. Although many studies show gut microbiota could regulate behavior, to our knowledge, no studies have profiled the gut microbiota structure in schizophrenia patients with violence. We profiled the characteristics of gut microbiota structure in 26 schizophrenia patients with violence (V.SCZ) by comparing with that of 16 schizophrenia patients without violence (NV.SCZ) under the control of confounders, and found the differences of gut microbiota structure between the two groups. Violence was assessed by the MacArthur Community Violence Instrument. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale. The 16S rRNA gene sequencing was used to identify and relatively quantify gut microbial composition. Bioinformatics analysis was used to find differential gut microbial composition between the V.SCZ and NV.SCZ groups. Fifty-nine differential microbial taxonomic compositions were found between the two groups. Fifteen gut microbial compositions were the key microbial taxonomic compositions responsible for the differences between the V.SCZ and NV.SCZ groups, including five enriched microbial taxonomic compositions (p_Bacteroidetes, c_Bacteroidia, o_Bacteroidales, f_Prevotellaceae, s_Bacteroides_uniformis), and ten impoverished microbial taxonomic compositions (p_Actinobacteria, c_unidentified_Actinobacteria, o_Bifidobacteriales, f_ Enterococcaceae, f_Veillonellaceae, f_Bifidobacteriaceae, g_Enterococcus, g_Candidatus_Saccharimonas, g_Bifidobacterium, and s_Bifidobacterium_pseudocatenulatum). This study profiled the differences of gut microbiota between schizophrenia patients with violence and without violence. These results could enrich the etiological understanding of violence in schizophrenia and might be helpful to violence management in the future.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1618-1624, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067963

RESUMO

OBJECTIVE: To explore the clinical value of serum bone turnover markers including ß-CrossLaps (ß-CTx), N-MID Osteocalcin (Osteocalcin), and total procollagen type 1 amino-terminal propeptide (TP1NP) in patients with myeloma bone disease (MBD). METHODS: A total of 55 MBD patients(MBD group) and 20 healthy volunteers(control group) were selected, and the serum was collected for detecting ß-CTx, Osteocalcin and TP1NP by Roche analyzer of automated electrochemiluminescence. Meanwhile, the imaging techniques such as MRI and CT were used for evaluation of bone destruction and the damage extent in MBD patients. RESULTS: Measurement data is expressed as median (P25, P75) according to distribution characteristics of data. The detection results showed that concentrations of ß-CTx in MBD patients and control group were 0.72(0.48, 1.28) ng/mL and 0.53(0.34, 0.61) ng/mL respectively, the ß-CTx concentration in MBD patients was significantly higher than that in control group(P=0.002). The ratio ß-CTx to TP1NP (%) in MBD patients and control group was 1.50 (1.05, 3.36) and 1.25 (0.86, 1.35) respectively, the ratio in MBD patients was significantly higher than that in control group (P=0.007). The serum ß-CTx concentrations in MBD patients of localized bone destruction type and extensive bone destruction type were 0.41(0.31, 0.66) ng/mL and 1.14(0.72, 1.81) ng/mL respectively, the ß-CTx concentration in MBD patients of extensive bone destruction type was significantly higher than that in MBD patients of localized bone destruction type (P<0.001). The ratio of ß-CTx to TP1NP(%) in MBD patients of localized and extensive bone destruction type was 1.30 (0.90, 2.49) and 1.98 (1.18, 3.76) respectively, the ratio in the MBD patients of extensive bone destruction type was significantly higher than that in MBD patients of localized bone destruction type (P=0.019). The serum osteocalcin concentrations in MBD patients of localized and extensive bone destruction type were 14.31 (8.82, 19.39) ng/mL and 21.52 (14.42, 47.76) ng/mL respectively, the osteocalcin concentration in MBD patients of extensive bone destruction type was higher than that in MBD patients of localized bone destruction type (P=0.008). The AUC of ß-CTx was 0.88 (95% CI: 0.78-0.98)(P<0.001), and the cut-off value was 0.69 ng/ml in the diagnosis of extensive bone injury for MBD patients, and the sensitivity and specificity were 80.65% and 83.33% respectively. CONCLUSION: The MBD patients show bone resorption hyperthyroidism and high bone turnover. The ß-CTx and osteocalcin in serum bone turnover markers can effectively reflect the extent of bone damage in MBD patients, especially the ß-CTx is more efficient for the diagnosis of MBD patients of extensive bone destruction type. However, ß-CTx, osteocalcin and TP1NP are not relate with the MM disease progression.

5.
J Mol Med (Berl) ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047154

RESUMO

Epidemiological studies have shown an increased prevalence of cancer in some patients with neurodevelopmental disorder (NDD); however, the genetic mechanisms regarding how cancer-related genes (CRGs) contribute to NDD remain unclear. We performed bioinformatic analyses on 219 CRGs from OMIM and de novo mutations (DNMs) from 16,498 patients with different NDDs and 3391 controls. Our results showed that autism spectrum disorder, undiagnosed neurodevelopmental disorder, congenital heart disease and intellectual disability, but not epileptic encephalopathy and schizophrenia, harboured significantly more putative functional DNMs in CRGs, compared with controls, providing genetic evidence supporting previous epidemiological surveys. We further detected 26 CRGs with recurrent putative functional DNMs that showed high expression in the human brain during the prenatal stage and in non-brain organs in adults. The proteins coded by the 26 CRGs and known NDD candidate genes formed a functional network that is involved in brain development and tumorigenesis. Overall, we proposed 39 cancer-targeting drugs that could be investigated for treating patients with NDD, which would be potentially cost-effective. In conclusion, DNMs contribute to specific NDDs and there may be a shared genetic basis between NDDs and cancer, highlighting the importance of considering cancer-targeting drugs with potential curative effects in patients with NDDs. KEY MESSAGES: • The contribution of DNMs in NDD is consistent with epidemiological surveys. • We highlighted 26 CRGs, including nine genes with more than five functional DNMs. • Specific expression patterns underlie the genetic mechanism of CRGs in NDD. • Specific functional networks underlie the genetic mechanism of CRGs in NDD. • The shared genetic aetiology suggests potential mutual treatment strategies.

6.
Kaohsiung J Med Sci ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33022894

RESUMO

Cullin 4B (CUL4B) was reported to be closely related to the progression of some tumors, but its function in clear cell renal cell carcinoma (ccRCC) has not been reported. Our present study found CUL4B was upregulated in ccRCC, and CUL4B knockdown markedly inhibited ccRCC cell growth and induced apoptosis. In addition, CUL4B knockdown markedly inhibited antiapoptotic proteins' expression in ccRCC cells, including Mcl-1 and Bcl-2, and silenced CUL4B also induced the cleavages of PARP, an important index of apoptosis. We also confirmed microRNA-217 (miR-217) was downregulated in ccRCC tumor tissues, and negatively correlated with CUL4B expression. Further investigations revealed miR-217 targeted CUL4B and markedly inhibited its expression in ccRCC cells. In addition, overexpression of miR-217 by mimics significantly suppressed ccRCC cell growth. In contrast, enforced expression of CUL4B significantly abolished miR-217-induced cell survival inhibition in ccRCC cells. In conclusion, our present results suggested targeting miR-217-CUL4B axis would be a promising strategy for ccRCC treatment.

7.
Neurobiol Aging ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-33041088

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disease with inherent sex differences, and sex-determining region Y (SRY) is a gene located in the Y chromosome which encodes a transcription factor involving the regulation of the dopamine system. In this study, we investigated whether SRY variants were associated with PD in Chinese population. A total of 2058 male patients with PD and 1650 male control participants were recruited, and variants in SRY transcript and flanking regions were genotyped by whole-exome sequencing or whole-genome sequencing. Analysis of rare variants by the optimal sequence kernel association test showed no difference in variant burden of coding, 5'-noncoding and 3'-noncoding between the case and control group. In addition, of the 6 common variants identified, none showed a significant effect in altering PD risk in our population using logistic regression. Our results suggested SRY variants were not associated with the risk of PD in Chinese population.

8.
Matter ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33043290

RESUMO

Coronavirus disease 2019 (COVID-19) has become a severe threat to human health worldwide. Early etiological diagnosis plays a critical role in controlling COVID-19 pandemic. However, etiological diagnosis has been largely compromised by high "false negative" rates of viral nucleic acid testing, resulting from limited sampling efficiency using conventional oropharyngeal swabs. Herein, we engineer regular swabs by using a microneedle (MN) patch to significantly improve the quality and quantity of virus collection. The combination of MNs with different crosslinking levels endows the patches with dual capability of mucus penetration and virus extraction. Moreover, the antibody (Ab) against viral spike protein was integrated into the patch, conferring MNs with an active virus capture potential. By taking advantage of the biological and engineered species, it is believed the designed MN/Ab swabs could serve as a promising tool to improve current sampling efficiency with less "false negatives", contributing to the containment of COVID-19 pandemic.

9.
Mol Autism ; 11(1): 75, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023636

RESUMO

BACKGROUND: Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically inherited variants in autosomes or X-linked inherited variants in males and investigate the functional relationships between RIGs and genes with de novo variants (DNGs). METHODS: We used a bioinformatics pipeline to analyze whole-exome sequencing data from 1799 ASD quads (containing one proband, one unaffected sibling, and their parents) from the Simons Simplex Collection and prioritize candidate RIGs with rare biallelically inherited variants in autosomes or X-linked inherited variants in males. The relationships between RIGs and DNGs were characterized based on different genetic perspectives, including genetic variants, functional networks, and brain expression patterns. RESULTS: Among the biallelically or hemizygous constrained genes that were expressed in the brain, ASD probands carried significantly more biallelically inherited protein-truncating variants (PTVs) in autosomes (p = 0.038) and X-linked inherited PTVs in males (p = 0.026) than those in unaffected siblings. We prioritized eight autosomal, and 13 X-linked candidate RIGs, including 11 genes already associated with neurodevelopmental disorders. In total, we detected biallelically inherited variants or X-linked inherited variants of these 21 candidate RIGs in 26 (1.4%) of 1799 probands. We then integrated previously reported known or candidate genes in ASD, ultimately obtaining 70 RIGs and 87 DNGs for analysis. We found that RIGs were less likely to carry multiple recessive inherited variants than DNGs were to carry multiple de novo variants. Additionally, RIGs and DNGs were significantly co-expressed and interacted with each other, forming a network enriched in known functional ASD clusters, although RIGs were less likely to be enriched in these functional clusters compared with DNGs. Furthermore, although RIGs and DNGs presented comparable expression patterns in the human brain, RIGs were less likely to be associated with prenatal brain regions, the middle cortical layers, and excitatory neurons than DNGs. LIMITATIONS: The RIGs analyzed in this study require functional validation, and the results should be replicated in more patients with ASD. CONCLUSIONS: ASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs.

10.
Dis Model Mech ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033107

RESUMO

Improving revascularization is one of the major measures in fracture treatment. Moderate local inflammation triggers angiogenesis, whereas systemic inflammation hampers angiogenesis. Previous studies showed that Akkermansia muciniphila (A. muc), a gut probiotic, ameliorates systemic inflammation by tightening intestinal barrier. In this study, fractured mice intragastrically administrated with A. muc were found to display better fracture healing than mice treated with vehicle. Notably, more preosteclasts positive for platelet-derived growth factor-BB (PDGF-BB) were induced by A. muc at 2 weeks post fracture, coinciding with increased formation of type H vessels, a specific vessel subtype that couples angiogenesis and osteogenesis and can be stimulated by PDGF-BB. Moreover, A. muc treatment significantly reduced gut permeability and inflammation at early stage. Dextran Sulfate Sodium (DSS) was used to disrupt the gut barrier to determine the role of gut barrier in fracture healing and whether A. muc still can stimulate bone fracture healing. As expected, A. muc evidently improved gut barrier, reduced inflammation, and restored the impaired bone healing and angiogenesis in DSS-treated mice. Our results suggest that A. muc reduces intestinal permeability and alleviates inflammation, which probably induces more PDGF-BB positive preosteoclasts and type H vessel formation in callus, thereby promoting fracture healing. This study provides the evidences about the involvement of type H vessels in fracture healing and suggests the potential of A. muc as a promising strategy for bone healing.

11.
J Hum Genet ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037392

RESUMO

Dysosteosclerosis (DOS) is a distinct form of sclerosing bone disease characterized by platyspondyly and progressive osteosclerosis. DOS is genetically heterogeneous. Three causal genes, SLC29A3, CSF1R, and TNFRSF11A are reported. TNFRSF11A-associated DOS has been identified in two patients; however, TNFRSF11A is also a causal gene for osteopetrosis, autosomal recessive 7 (OP-AR7). Whole-exome sequencing in a patient with sclerosing bone disease identified novel compound heterozygous variants (c.414_427 + 7del, c.1664del) in TNFRSF11A. We examined the impact of the two variants on five splicing isoforms of TNFRSF11A by RT-PCR. We found that c.1664del resulted in elongated proteins (p.S555Cfs*121, etc.), while c.414_427 + 7del generated two aberrant splicing products (p.A139Wfs*19 and p.E132Dfs*19) that lead to nonsense mediated mRNA decay (NMD). In the previous two cases of TNFRSF11A-associated DOS, their mutations produced truncated TNFRSF11A protein isoforms. The mutations in all three cases thus contrast with TNFRSF11A mutations reported in OP-AR7, which does not generated truncated or elongated TNFRSF11A proteins. Thus, we identified the third case of TNFRSF11A-associated DOS and reinforced the genotype-phenotype correlation that aberrant protein-producing TNFRSF11A mutations cause DOS.

12.
PLoS One ; 15(10): e0237994, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027298

RESUMO

To detect false data injection attacks (FDIAs) in power grid reconstruction and solve the problem of high data dimension and bad abnormal data processing in the power system, thereby achieving safe and stable operation of the power grid system, this study introduces machine learning methods to explore the detection of FDIAs. First, through the utilization of the standard IEEE node system and the simulation of FDIAs under the condition of non-complete topology information, the construction of the attack data set is completed, and the MatPower tool is applied to simulate and analyze the data set. Second, based on the isolated Forest (iForest) abnormal score data processing algorithm combined with the Local Linear Embedding (LLE) data dimensionality reduction method, an algorithm for data feature extraction is constructed. Finally, based on the combination of the Convolutional Neural Network (CNN) and the Gated Recurrent Unit (GRU) network, an algorithm model for FDIAs detection is constructed. The results show that in the IEEE14-bus node and IEEE118-bus node systems, the overall distribution of the state estimated before and after the attack vector injection is consistent with the initial value. In the iFores algorithm, the number of iTree and the number of samples affect the extraction of abnormal score data. When the number of iTree n is determined to be 100, and the corresponding number of samples w is determined to be 10, the algorithm has the best detection effect. The FDIAs detection algorithm model based on CNN-GRU shows good detection effects under high attack intensity, with an accuracy rate of more than 95%, and its performance is better than other traditional detection algorithms. In this study, the bad data detection model based on deep learning has an active role in the realization of the safe and stable operation of the smart grid.

13.
Sci Rep ; 10(1): 16148, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999384

RESUMO

The study design is case-control. To evaluate the impact of preoperative coronal patterns based on the relationship between orientation of L4 coronal tilt and C7 plumb line on immediate postoperative coronal imbalance in degenerative lumbar scoliosis (DLS) patients. Although lumbosacral fractional curve has been long stressed in correction surgery of DLS, there is paucity of literature focusing on preoperative coronal pattern based on the relationship between orientation of L4 coronal tilt and C7 plumb line and its impact on immediate postoperative coronal imbalance in DLS patients. A consecutive series of DLS patients who underwent deformity correction surgery via posterior-only approach were reviewed. According to the relationship between orientation of L4 coronal tilt and C7 plumb line preoperatively, a total of 77 DLS patients who underwent posterior spinal corrective surgery were classified into: 1. Coronal consistency pattern, L4 coronally tilts toward C7 plumb line; 2. Coronal opposition pattern, L4 coronally tilts opposite C7 plumb line. Coronal imbalance was defined as global coronal malalignment (GCM) on either side more than or equal to 20 mm. Whole-spine standing radiographs of both pattern groups were assessed preoperatively and postoperatively. There were 37 patients with coronal consistency pattern and 40 patients with coronal opposition pattern. Compared to patients with coronal opposition pattern, patients with coronal consistency pattern had significantly higher postoperative GCM (P = 0.028), lower amount of GCM correction (P = 0.013) and higher incidence of postoperative coronal imbalance (P = 0.001); further logistic regression analysis revealed coronal consistency pattern was associated with increased odds of postoperative coronal imbalance (odds ratio: 5.981; 95% confidence interval 2.029-17.633; P = 0.001). DLS patients with preoperative coronal consistency pattern carried greater risk for immediate postoperative coronal imbalance following posterior long correction surgery.Level of evidence 3.

14.
Sci Rep ; 10(1): 16151, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999411

RESUMO

Including posterior corneal astigmatism (PCA) into consideration may increase the accuracy of astigmatism correction after corneal refractive surgery. In the present study we aim to investigate the distribution pattern of PCA in a large number of myopic patients from multiple ophthalmic centers. There were 7829 eyes retrospectively included in the study. Pentacam data of the eyes were retrieved from the machine and only results with image quality labelled with 'OK' were included. Distribution of PCA was slightly positively skewed (Skewness = 0.419, Kurtosis = 0.435, KS P < 0.0001). Mean PCA was 0.34 ± 0.14 D (range: 0.00 D-0.99 D). PCA was ≥ 0.25 D in 74.91% of the eyes and was ≥ 0.50 D in 11.61% of the eyes. In 97.55% of the eyes the steep meridian of PCA was vertical (SMV). PCA magnitude was significantly higher in eyes with SMV PCA (P < 0.0001) or high manifest astigmatism (MA, P < 0.0001). There was a significant correlation between anterior corneal astigmatism (ACA) magnitude and PCA magnitude in all of the eyes (r = 0.704, P < 0.0001). There was also a trend of decreasing frequency and magnitude of SMV PCA with aging (both P < 0.0001). In conclusion, PCA is present in myopic patients having corneal refractive surgery and PCA magnitude is increased with higher MA or ACA. Consideration of the impact of PCA on laser astigmatism correction may be necessary.

15.
Int J Immunopathol Pharmacol ; 34: 2058738420963818, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33016797

RESUMO

Sepsis, a severe infectious disease in the neonatal period, is considered a risk factor for necrotizing enterocolitis (NEC). To investigate the specific risk factors for NEC in septic infants, septic infants admitted to our center from January 2010 to April 2018 were included. Septic neonates with proven NEC (Bell's stage ⩾II) were enrolled in the NEC group, and those without NEC were enrolled in the control group. Demographics, clinical characteristics, and risk factors were compared between the two groups. Univariate and logistic regression analyses were used to evaluate the potential risk factors for NEC. A total of 610 septic neonates were included, of whom 78 (12.8%) had complicated NEC. The univariate analysis indicated that infants with NEC had a lower birth weight, a lower gestational age, and older age on admission than those without NEC (P < 0.05). Higher rates of anemia, prolonged rupture of membranes (PROM) (⩾18 h), pregnancy-induced hypertension, late-onset sepsis (LOS), red blood cell transfusion and hypoalbuminemia were observed in the NEC group than in the non-NEC group (P<0.05). Logistic regression analysis revealed LOS (P = 0.000), red blood cell transfusion (P = 0.001) and hypoalbuminemia (P = 0.001) were associated with the development of NEC. Among NEC infants, those who needed red blood cell transfusion had a longer hospitalization duration than those who did not need transfusion (P < 0.05). LOS, red blood cell transfusion and hypoalbuminemia were independent risk factors for the development of NEC in infants with sepsis. Taking measures to reduce the occurrence of hypoproteinemia and severe anemia may help to reduce the occurrence of NEC in septic neonates.

16.
Oncol Rep ; 44(5): 2080-2092, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000261

RESUMO

Emerging studies have demonstrated that long non­coding RNAs (lncRNAs) play essential roles in tumorigenesis. However, the role and function of lncRNAs in hypopharyngeal squamous cell carcinoma (HSCC) have not been completely elucidated. The present study explored the function of a novel lncRNA, RP11­156L14.1, in HSCC. RP11­156L14.1 was revealed to be highly expressed in HSCC tissues and cell lines. Knockdown of RP11­156L14.1 inhibited proliferation, migration, and invasion in HSCC cells. Furthermore, RP11­156L14.1 regulated epithelial­mesenchymal transition (EMT) by controlling EMT­related protein expression. Mechanistically, RP11­156L14.1 exerted its function as a competing endogenous RNA (ceRNA) and directly interacted with miR­548ao­3p. The present study also demonstrated that miR­548ao­3p regulated signal sequence receptor subunit 1 (SSR1) expression by targeting SSR1 3'­UTR. Moreover, the xenograft HSCC tumor model revealed that knockdown of RP11­156L14.1 markedly suppressed HSCC tumor growth in vivo. In summary, these findings indicated that the lncRNA RP11­156L14.1 functions as an oncogene in HSCC by competing with miR­548ao­3p in regulating SSR1 expression. The RP11­156L14.1/miR­548ao­3p/SSR1 axis could be utilized as a potential novel biomarker and therapeutic target for HSCC.

17.
J Affect Disord ; 277: 495-502, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32882506

RESUMO

BACKGROUND: COVID-19 has gained intense attention globally. However, little is known about the COVID-19-ralated mental health status among workers. METHODS: The cross-sectional online survey with 123,768 workers was conducted from February 2, 2020 to February 7, 2020 on a mega-size labor-intensive factory in Shenzhen, China. Oral consent was obtained prior to the questionnaire survey. The information collected in the survey included demographic characteristics, psychological symptoms, COVID-19-related information, and demands for psychological education and interventions. Symptoms of anxiety and depression were measured by the Zung's Self-Rating Anxiety Scale and Self-Rating Depression Scale. Logistic regression models were performed to determine the association between related factors and mental health status. RESULTS: The prevalence of anxiety and depression symptoms was 3.4% and 22.8%, respectively. The dominant epidemic-related factors were having confirmed cases in the community (odds ratio [OR], 2.75, 95% CI, 2.37-3.19) and having confirmed friends (OR, 2.44; 95% CI, 1.69-3.52) for the increased risk of anxiety and depression symptoms, respectively. Nevertheless, major traditional risk factors such as general or poor health status and always drinking alcohol were still the dominant factors associated with the increased risk of anxiety and depression symptoms. Overall, 67.3% and 26.8% workers reported desire for psychological education and interventions, respectively. LIMITATIONS: All assessments were self-reported, resulting in a risk of method bias. CONCLUSIONS: Our findings show a relatively low prevalence of anxiety symptoms, a relatively high prevalence of depression symptoms, and urgent demand for psychological education and interventions among workers during the COVID-19 outbreak.

18.
Int J Hyg Environ Health ; 229: 113580, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32917367

RESUMO

Perinatal exposure to dioxins affects steroid hormone synthesis. The purpose of the present study was to evaluate the associations between perinatal exposure to dioxins and serum steroid hormone levels in preschool-aged children from an e-waste recycling region in China. In the present study, we enrolled 50 pairs of mothers and infants from the Taizhou, Luqiao region in 2015. Of the 50 pairs of mothers and infants, 42 pairs participated in this study when the children were 4 years old. We measured breast milk dioxin concentrations using high-resolution gas chromatography/mass spectrometry. Additionally, we used liquid chromatography-tandem mass spectrometry to measure the concentrations of progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA) in serum samples from the 4-year-old children. We used multivariate linear regressions to assess the associations between dioxin congeners and steroid hormones. Results were reported as beta estimates and 95% confidence intervals by bootstrapping. We observed sex-related differences between breast milk dioxins and serum steroid hormone levels in 4-year-old children. An increase in breast milk dioxins was associated with a decrease in testosterone in serum samples from boys. Similarly, an increase in breast milk dioxins was associated with a decrease in progesterone levels in serum samples from girls. However, dioxins were not associated with changes in the levels of testosterone, DHEA, or A-dione in girls. Based on these results, we conclude that perinatal exposure to dioxins modifies steroidogenesis in preschool-aged children. However, the long-term impact of dioxins requires further large-scale studies to assess these effects in school-going children and adolescents.

19.
Biol Reprod ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32902620

RESUMO

Oxidative stress and apoptosis of trophoblasts are involved in preeclampsia (PE). Numerous studies have shown that acetylcholine (ACh), the principal vagal neurotransmitter, plays a crucial role in attenuating oxidative stress, inflammation, and apoptosis in a variety of human diseases. However, the role of ACh in PE management remains unclear. Here, we aimed to determine the effects of ACh on TNF-α-treated human primary trophoblast cells. Western blotting, CCK-8, DHE, TUNEL immunofluorescence staining, transwell assays, and wound-healing assays were performed to evaluate the role of ACh in vitro. We found that both TNF-α expression and the apoptotic index were higher in placentas from preeclamptic women than in normal placentas. TNF-α enhanced oxidative stress and increased the number of TUNEL-positive nuclei, Bax/Bcl-2 ratio, and the cleaved caspase-3/caspase-3 ratio while decreasing cell viability in primary human trophoblast cells. TNF-α promoted cell migration and invasion. PDTC, a selective NF-κB inhibitor, significantly blunted TNF-α-induced effects. ACh treatment attenuated oxidative stress and apoptosis while further promoting migration and invasion of TNF-α-treated primary trophoblast cells. The effects of ACh could be reversed by the muscarinic receptor antagonist atropine. Overall, our findings indicate that ACh significantly ameliorates TNF-α-induced oxidative stress and apoptosis of human primary trophoblast cells via muscarinic receptors. This is the first time that the improvement of vagal activity served as a therapeutic strategy for PE-like trophoblasts, suggesting its potential value in clinical practice.

20.
Eur J Med Chem ; 207: 112755, 2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32882611

RESUMO

The receptor tyrosine kinase rearranged during transfection (RET) plays pivotal roles in several cancers, including thyroid carcinoma and non-small cell lung cancer (NSCLC). Currently, there are several FDA-approved RET inhibitors, but their indication is limited to thyroid cancer, and none can overcome their gatekeeper mutants (V804L and V804M). Here, we report the discovery of 9x representing a new chemotype of potent and selective RET inhibitors, using a rational design strategy of type II kinase inhibitors. 9x exhibited both superior antiproliferative activities against NSCLC-related carcinogenic fusions KIF5B-RET and CCDC6-RET and gatekeeper mutant-transformed Ba/F3 cells, with the lowest GI50 of 9 nM, and substantial inhibitory activities against wild-type RET and RET mutant proteins, with the best IC50 of 4 nM. More importantly, 9x also showed nanomole potency against RET-positive NSCLC cells LC-2/ad, but not against a panel of RET-negative cancer cells, such as A549, H3122, A375 or parental Ba/F3 cells, demonstrating its selective 'on-target' effect. In mouse xenograft models, 9x repressed tumor growth driven by both wild type KIF5B-RET-Ba/F3 and gatekeeper mutant KIF5B-RET(V804M)-Ba/F3 cells in a dose-dependent manner. Together, these data establish that 9x provides a good starting point for the development of targeted therapeutics against RET-positive cancers, especially NSCLC.

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