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1.
Int J Mol Sci ; 21(11)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521790

RESUMO

This study was undertaken to test two therapies for acute kidney injury (AKI) prevention, IGF-1, which is renal protective, and BTP-2, which is a calcium entry (SOCE) inhibitor. We utilized lipopolysaccharide (LPS) IP, as a systemic model of AKI and studied in five groups of animals. Three experiments showed that at 7 days: (1) LPS significantly reduced serum IGF-1 and intramuscular IGF-I in vivo gene therapy rescued this deficiency. (2) Next, at the 7-day time point, our combination therapy,compared to the untreated group,caused a significant increase in survival, which was noteworthy because all of the untreated animals died in 72 hrs. (3) The four pathways associated with inflammation, including (A) increase in cytosolic calcium, (B) elaboration of proinflammatory cytokines, (C) impairment of vascular integrity, and (D) cell injury, were adversely affected in renal tissue by LPS, using a sublethal dose of LPS. The expression of several genes was measured in each of the above pathways. The combined therapy of IGF-1 and BTP-2 caused a favorable gene expression response in all four pathways. Our current study was an AKI study, but these pathways are also involved in other types of severe inflammation, including sepsis, acute respiratory distress syndrome, and probably severe coronavirus infection.

2.
Environ Res ; 188: 109741, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32521306

RESUMO

Ultrathin C3N5 nanosheets with enhanced photocatalytic methylene blue (MB) degradation and H2-evolution performance were prepared from thermal treatment of 3-amino-1,2,4-triazole (3-AT) and NH4Cl followed with a protonate procedure. The characterization results revealed that the protonating process could contribute to the exfoliation of C3N5 with large surface area, the effective charge transfer capability and the modified band structure. The as-prepared C3N5 nanosheets exhibited enhanced properties in photocatalytic reactions such as MB photodegradation and H2-evolution from water splitting. This study offered a feasible route to prepare highly-efficient two-dimensional photocatalyst, which could be applied potentially for implementation in wide range of energy generation and environmental applications.

3.
J Cell Mol Med ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32431079

RESUMO

The expression of tissue inhibitor metalloproteinase-1 (TIMP-1) significantly increased after acute cerebral ischaemia and involved in neurodegeneration. The purpose was to prospectively investigate the relationship between serum TIMP-1 with post-stroke cognitive impairment. Our participants were from an ancillary study of China Antihypertensive Trial in Acute Ischemic Stroke. 598 ischaemic stroke patients from seven participating hospitals were included. Cognitive impairment was evaluated using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at 3 months. 316 (52.84%) or 384 (64.21%) participants had cognitive impairment according to MMSE or MoCA, respectively. Compared with the first quartile of TIMP-1, the multivariate-adjusted odds ratios (95% confidence intervals) for the highest quartile were 1.80 (1.09-2.97) for cognitive impairment defined by MMSE and 2.55 (1.49-4.35) by MoCA. Multiple-adjusted spline regression models showed linear associations between TIMP-1 concentrations and cognitive impairment (P value for linearity < 0.01). The addition of TIMP-1 to models including conventional factors improved reclassification for cognitive impairment, as shown by net reclassification index or integrated discrimination improvement (P < 0.05). Participants with both higher TIMP-1 and matrix metalloproteinase-9 levels simultaneously had highest risk of cognitive impairment. Higher serum TIMP-1 levels were associated with increased risk of cognitive impairment after acute ischaemic stroke, independently of established risk factors.

4.
J Behav Addict ; 9(1): 105-115, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32359234

RESUMO

Objectives: Understanding the neural mechanisms underlying Internet gaming disorder (IGD) is essential for the condition's diagnosis and treatment. Nevertheless, the pathological mechanisms of IGD remain elusive at present. Hence, we employed multi-voxel pattern analysis (MVPA) and spectral dynamic causal modeling (spDCM) to explore this issue. Methods: Resting-state fMRI data were collected from 103 IGD subjects (male = 57) and 99 well-matched recreational game users (RGUs, male = 51). Regional homogeneity was calculated as the feature for MVPA based on the support vector machine (SVM) with leave-one- out cross-validation. Mean time series data extracted from the brain regions in accordance with the MVPA results were used for further spDCM analysis. Results: Results display a high accuracy of 82.67% (sensitivity of 83.50% and specificity of 81.82%) in the classification of the two groups. The most discriminative brain regions that contributed to the classification were the bilateral parahippocampal gyrus (PG), right anterior cingulate cortex (ACC), and middle frontal gyrus (MFG). Significant correlations were found between addiction severity (IAT and DSM scores) and the ReHo values of the brain regions that contributed to the classification. Moreover, the results of spDCM showed that compared with RGU, IGD showed decreased effective connectivity from the left PG to the right MFG and from the right PG to the ACC and decreased self-connection in the right PG. Conclusions: These results show that the weakening of the PG and its connection with the prefrontal cortex, including the ACC and MFG, may be an underlying mechanism of IGD.

5.
J Behav Addict ; 9(1): 163-174, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32359238

RESUMO

Background and Aims: Previous studies on smartphone use motivation (SUM) and problematic smartphone use (PSU) have been limited in the utilization of regional samples of emerging adults (e.g., college students) and also in the foci on the direct association between SUM and PSU. To address such gaps, using data from a large, national representative sample of Chinese young adolescents and their parents this study examined the associations between adolescents' various types of SUM and their PSU, and also tested the potential mediating roles of smartphone use time (SUT) that adolescents spent on various activities in such associations. Methods: A nationwide representative sample of 8,261 Chinese adolescents (Mage = 12.86 years old, SD = 1.76; 42.6% females) and their parents (49% mothers) participated in this survey study. Results: Instrumental SUM (i.e., to expand knowledge or acquire information) was associated negatively with PSU via longer SUT spent on learning and shorter SUT spent on entertainment and communication. Self-expression SUM (i.e., to gain acceptance and recognition of others by maintaining or improving self-images) was associated with longer SUT spent on both learning and entertainment, which, in turn, predicted lower and higher levels of PSU, respectively. Last, hedonic SUM (i.e., to gain pleasure) was associated positively with PSU via longer SUT spent on entertainment and communication. Discussion: These findings contribute to the literature by adding greater specificity in our understanding of the implications of SUM and SUT in the etiology of PSU during the critical life stage of adolescence in a Chinese cultural context.

6.
Eur Neuropsychopharmacol ; 36: 29-37, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32446706

RESUMO

Reward-seeking and relief from negative emotions are two central motivational drives underlying addictions. Impaired executive control over craving and negative emotions contributes to compulsive addictive behaviors. Neuroimaging evidence has implicated the prefrontal cortex (PFC) in regulating craving or emotions. This study aims at examining whether anodal transcranial direct current stimulation (tDCS) over a specific region of the PFC would enhance both regulation processes. Thirty-three men with internet gaming disorder received active (1.5 mA for 20 minutes) and sham tDCS over the right dorsolateral PFC (dlPFC) one week apart in a randomized order. During each stimulation session, participants regulated craving for gaming during a regulation of craving (ROC) task and negative emotions during an emotion regulation (ER) task using cognitive reappraisal. Subjective ratings of craving and negative emotions and skin conductance responses (SCRs) were recorded. For both craving and negative emotions, tDCS of the right dlPFC facilitated downregulation and upregulation: active relative to sham tDCS decreased ratings (ROC: 95% CI of difference -1.38 to -0.56, p < 0.001; ER: -1.65 to -0.70, p < 0.001) and/or SCRs (ROC: -1.99 to -0.41 µs, p = 0.004) for downregulation, and increased ratings (ROC: 0.24 to 0.82, p = 0.001; ER: 0.26 to 0.72, p < 0.001) for upregulation. These findings provide the first experimental evidence confirming that tDCS of the right dlPFC enhances both craving- and negative-emotion-regulation. This suggests a promising approach for concurrently enhancing executive control over two central motivational drives underlying addictions.

7.
J Med Genet ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376790

RESUMO

BACKGROUND: Infertility affects approximately 15% of couples worldwide with male infertility being responsible for approximately 50% of cases. Although accumulating evidence demonstrates the critical role of the X chromosome in spermatogenesis during the last few decades, the expression patterns and potential impact of the X chromosome, together with X linked genes, on male infertility are less well understood. METHODS: We performed X chromosome exome sequencing followed by a two-stage independent population validation in 1333 non-obstructive azoospermia cases and 1141 healthy controls to identify variant classes with high likelihood of pathogenicity. To explore the functions of these candidate genes in spermatogenesis, we first knocked down these candidate genes individually in mouse spermatogonial stem cells (SSCs) using short interfering RNA oligonucleotides and then generated candidate genes knockout mice by CRISPR-Cas9 system. RESULTS: Four low-frequency variants were identified in four genes (BCORL1, MAP7D3, ARMCX4 and H2BFWT) associated with male infertility. Functional studies of the mouse SSCs revealed that knocking down Bcorl1 or Mtap7d3 could inhibit SSCs self-renewal and knocking down Armcx4 could repress SSCs differentiation in vitro. Using CRISPR-Cas9 system, Bcorl1 and Mtap7d3 knockout mice were generated. Excitingly, Bcorl1 knockout mice were infertile with impaired spermatogenesis. Moreover, Bcorl1 knockout mice exhibited impaired sperm motility and sperm cells displayed abnormal mitochondrial structure. CONCLUSION: Our data indicate that the X-linked genes are associated with male infertility and involved in regulating SSCs, which provides a new insight into the role of X-linked genes in spermatogenesis.

8.
Addict Biol ; : e12917, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32415913

RESUMO

Alterations in brain connectivity have been implicated in internet gaming disorder (IGD). However, little is known about alterations in whole-brain connectivity and their associations with long-term treatment outcomes. Here, we used a relatively new analytic approach, intrinsic connectivity distribution (ICD) analysis, to examine brain connectivity in 74 IGD participants and 41 matched healthy controls (HCs) and conducted post hoc seed-based resting-state functional connectivity (rsFC) analyses based on the ICD findings. We also examined how these findings related to outcomes involving a craving behavioral intervention (CBI) for IGD. IGD participants showed less whole-brain connectivity in the left angular gyrus and ventromedial prefrontal cortex (vmPFC) compared with HC participants. Seed-based rsFC analyses revealed that the left angular gyrus in the IGD group showed less connectivity with areas involved in the default-mode network and greater connectivity with areas in the salience and executive control networks. CBI was associated with improved connectivity within regions in the default-mode network and regions across the default-mode and salience networks. ICD-identified connectivity differences in the left angular gyrus and vmPFC were related to changes in craving and severity of addiction 6 months after the intervention. The findings suggest that IGD is associated with alterations in brain connectivity that may be sensitive to interventions. Thus, the findings have implications for understanding mechanisms underlying CBI effects and for further treatment development.

9.
Chem Asian J ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32167236

RESUMO

To rationally design efficient and cost-effective electrocatalysts, a simple but efficient strategy has been developed to directly anchor prussian blue analogue (PBA) nanocubes on cobalt hydroxide nanoplates (PBA@Co(OH)2 ) via the in-situ interfacial precipitation process. Subsequently, the thermal treatment in the presence of sodium hydrogen phosphite enabled the successful transition into metal phosphides with the hierarchical cube-on-plate structure. When used as electrocatalytsts, the obtained bimetal phosphides exhibited good bifunctional electrocatalytic activities for hydrogen and oxygen evolution reactions with good long-term stability. Thus, an enhanced performance for overall water splitting can be achieved, which could be ascribed to the hierarchical structure and favorable composition of as-prepared bimetal phosphide for rapid electron and mass transfer. The present study demonstrates a favorable approach to modulate the composition and structure of metal phosphide for enhancing the electrocatalytic ability toward water splitting.

10.
Psychiatry Res ; 286: 112892, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32114205

RESUMO

Poor executive function (EF) has been implicated in addictions. Among "hot" EFs (i.e., those involving motivations and emotions), poor regulation of craving has been proposed to underlie addiction development in substance-use disorders (SUDs), making such regulation a potential treatment target. However, regulation of craving remains poorly understood in internet gaming disorder (IGD). Additionally, prior studies of cold EFs (e.g., inhibition and cognitive flexibility under neutral conditions) in IGD have provided mixed results and mostly included only male subjects. We addressed these issues by instructing 54 participants (26 with IGD including males and females, and 28 control subjects) to perform a regulation-of-craving (ROC) task and a Stroop color-word-interference task. Compared to control subjects, individuals with IGD revealed deficits in regulation for both gaming- and food-related craving, but no differences in Stroop performance. The current study provides initial empirical support suggesting regulation impairments for both addiction-related and primary rewards among individuals with IGD. The findings are consistent with studies in SUDs, suggesting that impaired regulation of craving may be a relevant transdiagnostic construct across SUDs and behavioral addictions. The findings suggest targeting regulation of "hot" processes should be considered in IGD treatment development.

11.
Adv Mater ; : e1906432, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134141

RESUMO

Delicate design of nanostructures for oxygen-evolution electrocatalysts is an important strategy for accelerating the reaction kinetics of water splitting. In this work, Ni-Fe layered-double-hydroxide (LDH) nanocages with tunable shells are synthesized via a facile one-pot self-templating method. The number of shells can be precisely controlled by regulating the template etching at the interface. Benefiting from the double-shelled structure with large electroactive surface area and optimized chemical composition, the hierarchical Ni-Fe LDH nanocages exhibit appealing electrocatalytic activity for the oxygen evolution reaction in alkaline electrolyte. Particularly, double-shelled Ni-Fe LDH nanocages can achieve a current density of 20 mA cm-2 at a low overpotential of 246 mV with excellent stability.

12.
Dev Psychol ; 56(5): 1009-1021, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32105117

RESUMO

Based on 4 annual waves of data from a large sample of Chinese college students (N = 2,329, Mage = 18.40 years old, SD = .85; 63.10% females), this study examines the within-person and between-person effects in the association between problematic Internet use (PIU) and mental health issues. Results of analyses using the developmental equilibrium model (i.e., an autoregressive, cross-lagged panel model) demonstrate a reciprocal positive association between PIU and mental health issues consistently across waves. In contrast, results of analyses utilizing the random intercept, cross-lagged panel model (i.e., a model that can disaggregate within-person and between-person effects) indicate a unidirectional positive within-person effect from PIU to mental health issues (rather than the reverse) consistently over time, while controlling for the between-person effects that exist when comparing different individuals. Such findings highlight the importance of disaggregating within-person and between-person effects in understanding the nature of the temporal dynamics of the association between PIU and mental health. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

13.
J Diabetes Investig ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32100945

RESUMO

AIMS/INTRODUCTION: Type 2 diabetes mellitus is a specific risk factor for intracranial atherosclerosis. The purpose of this study was to investigate the relationship between type 2 diabetes mellitus, especially uncontrolled glycemia, and intracranial plaque characteristics using high-resolution magnetic resonance imaging. MATERIALS AND METHODS: A total of 263 patients (182 men; mean age 62.6 ± 11.5 years) with intracranial atherosclerotic plaques detected on high-resolution magnetic resonance imaging from December 2017 to March 2019 were included in this study. Patients were divided into different groups: (i) patients with and without type 2 diabetes mellitus; (ii) diabetes patients with uncontrolled glycemia (glycated hemoglobin level ≥7.0%) and controlled glycemia; and (iii), diabetes patients with diabetes duration of <5, 5-10 and >10 years. Comparisons of plaque features between groups were made, respectively. RESULTS: Type 2 diabetes mellitus was diagnosed in 118 patients (44.9%). Diabetes patients had a significantly greater prevalence of enhanced plaque, greater maximum plaque length, maximum wall thickness and more severe luminal stenosis than non-diabetes patients. Compared with diabetes patients with controlled glycemia, those with uncontrolled glycemia had a significantly greater prevalence of enhanced plaque and greater maximum plaque length (all P < 0.05). There were no significant differences in plaque features among patients with different durations of type 2 diabetes mellitus. Uncontrolled glycemia was an independent factor for plaque enhancement after adjustment for potential confounding factors (odds ratio 5.690; 95% confidence interval 1.748-18.526; P = 0.004). CONCLUSIONS: Type 2 diabetes mellitus is closely related to intracranial plaque enhancement and burden. Recently uncontrolled glycemia might play an important role in the development of enhanced plaque.

14.
J Magn Reson Imaging ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027071

RESUMO

BACKGROUND: The interpretation system for prostate MRI is largely based on qualitative image contrast of different tissue types. Therefore, a fast, standardized, and robust quantitative technique is necessary. Synthetic MRI is capable of quantifying multiple relaxation parameters, which might have potential applications in prostate cancer (PCa). PURPOSE: To investigate the use of quantitative relaxation maps derived from synthetic MRI for the diagnosis and grading of PCa. STUDY TYPE: Prospective. SUBJECTS: In all, 94 men with pathologically confirmed PCa or benign pathological changes. FIELD STRENGTH/SEQUENCE: T1 -weighted imaging, T2 -weighted imaging, diffusion-weighted imaging, and synthetic MRI at 3.0T. ASSESSMENT: Four kinds of tissue types were identified on pathology, including PCa, stromal hyperplasia (SH), glandular hyperplasia (GH), and noncancerous peripheral zone (PZ). PCa foci were grouped as low-grade (LG, Gleason score ≤6) and intermediate/high-grade (HG, Gleason score ≥7). Regions of interest were manually drawn by two radiologists in consensus on parametric maps according to the pathological results. STATISTICAL TESTS: Independent sample t-test, Mann-Whitney U-test, and receiver operating characteristic curve analysis. RESULTS: T1 and T2 values of PCa were significantly lower than SH (P = 0.015 and 0.002). The differences of T1 and T2 values between PCa and noncancerous PZ were also significant (P ≤ 0.006). The area under the curve (AUC) of the apparent diffusion coefficient (ADC) value was significantly higher than T1 , T2 , and proton density (PD) values in discriminating PCa from SH and noncancerous PZ (P ≤ 0.025). T2 , PD, and ADC values demonstrated similar diagnostic performance in discriminating LG from HG PCa (AUC = 0.806 [0.640-0.918], 0.717 [0.542-0.854], and 0.817 [0.652-0.925], respectively; P ≥ 0.535). DATA CONCLUSION: Relaxation maps derived from synthetic MRI were helpful for discriminating PCa from other benign pathologies. But the overall diagnostic performance was inferior to the ADC values. T2 , PD, and ADC values performed similarly in discriminating LG from HG PCa lesions. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2.

15.
Pain ; 161(6): 1381-1398, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32028334

RESUMO

Headache disorders are highly prevalent and debilitating, with limited treatment options. Previous studies indicate that many proinflammatory immune cells contribute to headache pathophysiology. Given the well-recognized role of regulatory T (Treg) cells in maintaining immune homeostasis, we hypothesized that enhancing Treg function may be effective to treat multiple headache disorders. In a mouse model of chronic migraine, we observed that repeated nitroglycerin (NTG, a reliable trigger of migraine in patients) administration doubled the number of CD3 T cells in the trigeminal ganglia without altering the number of Treg cells, suggesting a deficiency in Treg-mediated immune homeostasis. We treated mice with low-dose interleukin-2 (ld-IL2) to preferentially expand and activate endogenous Treg cells. This not only prevented the development of NTG-induced persistent sensitization but also completely reversed the established facial skin hypersensitivity resulting from repeated NTG administration. The effect of ld-IL2 was independent of mouse sex and/or strain. Importantly, ld-IL2 treatment did not alter basal nociceptive responses, and repeated usage did not induce tolerance. The therapeutic effect of ld-IL2 was abolished by Treg depletion and was recapitulated by Treg adoptive transfer. Furthermore, treating mice with ld-IL2 1 to 7 days after mild traumatic brain injury effectively prevented as well as reversed the development of behaviors related to acute and chronic post-traumatic headache. In a model of medication overuse headache, Ld-IL2 completely reversed the cutaneous hypersensitivity induced by repeated administration of sumatriptan. Collectively, this study identifies ld-IL2 as a promising prophylactic for multiple headache disorders with a mechanism distinct from the existing treatment options.

16.
Neuroimage Clin ; 26: 102202, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045732

RESUMO

Current models of addiction biology highlight altered neural responses to non-drug rewards as a central feature of addiction. However, given that drugs of abuse can directly impact reward-related dopamine circuitry, it is difficult to determine the extent to which reward processing alterations are a trait feature of individuals with addictions, or primarily a consequence of exogenous drug exposure. Examining individuals with behavioral addictions is one promising approach for disentangling neural features of addiction from the direct effects of substance exposure. The current fMRI study compared neural responses during monetary reward processing between drug naïve young adults with a behavioral addiction, internet gaming disorder (IGD; n = 22), and healthy controls (n = 27) using a monetary incentive delay task. Relative to controls, individuals with IGD exhibited blunted caudate activity associated with loss magnitude at the outcome stage, but did not differ from controls in neural activity at other stages. These findings suggest that decreased loss sensitivity might be a critical feature of IGD, whereas alterations in gain processing may be less characteristic of individuals with IGD, relative to those with substance use disorders. Therefore, classic theories of altered reward processing in substance use disorders should be translated to behavioral addictions with caution.

17.
Eur J Pharmacol ; 872: 172941, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31972179

RESUMO

Cardiac hypertrophy is a heart reaction to the increase of cardiac load, with the characteristics of increased expression of cardiac hypertrophy markers, enhanced protein synthesis, and enlarged cell area. However, molecular mechanisms in cardiac hypertrophy are still poorly substantiated. It has been reported that miRNAs can modulate human diseases, among which miR-326 has been reported as a biological regulator in human cancers, but its role in cardiac hypertrophy is rarely explored. This study focused on the exploration of the potential of miR-326 in cardiac hypertrophy. Our data revealed the downregulation of miR-326 in the TAC-induced hypertrophic mice and the Ang II-induced hypertrophic H9c2 cells. Functionally, miR-326 attenuated the effect of Ang II on cardiac hypertrophy in vitro. In addition, miR-326 negatively regulated JAK/STAT and MAPK signaling pathways. Mechanistically, miR-326 targeted and inhibited MDK to induce JAK/STAT and MAPK pathways. Rescue assays certified that miR-326 attenuated cardiac hypertrophy through targeting MDK and inhibiting JAK/STAT and MAPK signaling pathways. In brief, our study unveiled that miR-326 targets MDK to regulate the progression of cardiac hypertrophy through blocking JAK/STAT and MAPK signaling pathways, indicating that targeting miR-326 as a potential approach for cardiac hypertrophy treatment.

18.
J Med Genet ; 57(2): 89-95, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31501240

RESUMO

BACKGROUND: Male infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of the sperm flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent and irregular-calibre flagella resulting in severely decreased motility. Previous studies reported several MMAF-associated genes accounting for approximately half of MMAF cases. METHODS AND RESULT: We conducted genetic analysis using whole-exome sequencing in 88 Han Chinese MMAF probands. CFAP65 homozygous mutations were identified in four unrelated consanguineous families, and CFAP65 compound heterozygous mutations were found in two unrelated cases with MMAF. All these CFAP65 mutations were null, including four frameshift mutations (c.1775delC [p.Pro592Leufs*8], c.3072_3079dup [p.Arg1027Profs*41], c.1946delC [p.Pro649Argfs*5] and c.1580delT [p.Leu527Argfs*31]) and three stop-gain mutations (c.4855C>T [p.Arg1619*], c.5270T>A [p.Leu1757*] and c.5341G>T [p.Glu1781*]). Additionally, two homozygous CFAP65 variants likely affecting splicing were identified in two MMAF-affected men of Tunisian and Iranian ancestries, respectively. These biallelic variants of CFAP65 were verified by Sanger sequencing and were absent or very rare in large data sets aggregating sequence information from various human populations. CFAP65, encoding the cilia and flagella associated protein 65, is highly and preferentially expressed in the testis. Here we also generated a frameshift mutation in mouse orthologue Cfap65 using CRISPR-Cas9 technology. Remarkably, the phenotypes of Cfap65-mutated male mice were consistent with human MMAF. CONCLUSIONS: Our experimental observations performed on both human subjects and on Cfap65-mutated mice demonstrate that the presence of biallelic mutations in CFAP65 causes the MMAF phenotype and impairs sperm motility.

20.
Neurosci Bull ; 36(3): 307-320, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31792911

RESUMO

The cognitive disease consensus was prepared by panels of health and public representatives based on actual clinical practice in Geriatric Departments in Chinese hospitals and a systematic literature review. This consensus reflects the medical knowledge accumulated by those experts and provides information about professional medical care and advice. A multidisciplinary panel of specialists (neurologists, psychiatrists, and nursing specialists) reports an expert consensus on the medical knowledge accumulated from those experts and provides information about professional medical care and advice. The recommendations focus on the care and management of older adults with mild cognitive impairment, the objectives and methods of maintaining cognition and training, the assessments and measures of daily care for patients at different stages of dementia, the assessments and coping strategies for the behavioral and psychological symptoms of dementia, principles and suggestions for an appropriate living environment, arrangements for recreational activities, the care and management of patients with end-stage dementia, and suggestions for addressing stress in caregivers.

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