Reducing expression of a nitrate-responsive bZIP transcription factor increases grain yield and N use in wheat.

Nitrogen (N) plays critical role in plant growth; manipulating N assimilation could be a target to increase grain yield and N use. Here, we show that ABRE-binding factor (ABF)-like leucine zipper transcription factor TabZIP60 mediates N use and growth in wheat. The expression of TabZIP60 is repressed when the N-deprived wheat plants is exposed to nitrate. Knock down of TabZIP60 through RNA interference (RNAi) increases NADH-dependent glutamate synthase (NADH-GOGAT) activity, lateral root branching, N uptake and spike number, and improves grain yield more than 25% under field conditions, while overexpression of TabZIP60-6D had the opposite effects. Further investigation shows TabZIP60 binds to ABRE-containing fragment in the promoter of TaNADH-GOGAT-3B and negatively regulates its expression. Genetic analysis reveals that TaNADH-GOGAT-3B overexpression overcomes the spike number and yield reduction caused by overexpressing TabZIP60-6D. As such, TabZIP60-mediated wheat growth and N use is associated with its negative regulation on TaNADH-GOGAT expression. These findings indicate that TabZIP60 and TaNADH-GOGAT interaction plays important roles in mediating N use and wheat growth, and provides valuable information for engineering N use efficiency and yield in wheat.

The Auxin Biosynthetic TRYPTOPHAN AMINOTRANSFERASE RELATED TaTAR2.1-3A Increases Grain Yield of Wheat.

Controlling the major auxin biosynthetic pathway to manipulate auxin content could be a target for genetic engineering of crops with desired traits, but little progress had been made because low or high auxin contents often cause developmental inhibition. Here, we performed a genome-wide analysis of bread wheat (Triticum aestivum) to identify the Tryptophan Aminotransferase of Arabidopsis1/Tryptophan Aminotransferase-Related (TAA1/TAR) genes that function in the tryptophan-dependent pathway of auxin biosynthesis. Sequence mining together with gene cloning identified 15 TaTAR genes, among which 12 and three genes were phylogenetically close to Arabidopsis (Arabidopsis thaliana) AtTAR2 and AtTAR3, respectively. TaTAR2.1 had the most abundant transcripts in the TaTAR2 genes and was expressed mainly in roots and up-regulated by low nitrogen (N) availability. Knockdown of TaTAR2.1 caused vegetative and reproductive deficiencies and impaired lateral root (LR) growth under both high- and low-N conditions. Overexpressing TaTAR2.1-3A in wheat enhanced LR branching, plant height, spike number, grain yield, and aerial N accumulation under different N supply levels. In addition, overexpressing TaTAR2.1-3A in Arabidopsis elevated auxin accumulation in the primary root tip, LR tip, LR primordia, and cotyledon and hypocotyl and increased primary root length, visible LR number, and shoot fresh weight under high- and low-N conditions. Our results indicate that TaTAR2.1 is critical for wheat growth and also shows potential for genetic engineering to reach the aim of improving the grain yield of wheat.

The Nitrate-Inducible NAC Transcription Factor TaNAC2-5A Controls Nitrate Response and Increases Wheat Yield.

Nitrate is a major nitrogen resource for cereal crops; thus, understanding nitrate signaling in cereal crops is valuable for engineering crops with improved nitrogen use efficiency. Although several regulators have been identified in nitrate sensing and signaling in Arabidopsis (Arabidopsis thaliana), the equivalent information in cereals is missing. Here, we isolated a nitrate-inducible and cereal-specific NAM, ATAF, and CUC (NAC) transcription factor, TaNAC2-5A, from wheat (Triticum aestivum). A chromatin immunoprecipitation assay showed that TaNAC2-5A could directly bind to the promoter regions of the genes encoding nitrate transporter and glutamine synthetase. Overexpression of TaNAC2-5A in wheat enhanced root growth and nitrate influx rate and, hence, increased the root's ability to acquire nitrogen. Furthermore, we found that TaNAC2-5A-overexpressing transgenic wheat lines had higher grain yield and higher nitrogen accumulation in aerial parts and allocated more nitrogen in grains in a field experiment. These results suggest that TaNAC2-5A is involved in nitrate signaling and show that it is an exciting gene resource for breeding crops with more efficient use of fertilizer.

A wheat CCAAT box-binding transcription factor increases the grain yield of wheat with less fertilizer input.

Increasing fertilizer consumption has led to low fertilizer use efficiency and environmental problems. Identifying nutrient-efficient genes will facilitate the breeding of crops with improved fertilizer use efficiency. This research performed a genome-wide sequence analysis of the A (NFYA), B (NFYB), and C (NFYC) subunits of Nuclear Factor Y (NF-Y) in wheat (Triticum aestivum) and further investigated their responses to nitrogen and phosphorus availability in wheat seedlings. Sequence mining together with gene cloning identified 18 NFYAs, 34 NFYBs, and 28 NFYCs. The expression of most NFYAs positively responded to low nitrogen and phosphorus availability. In contrast, microRNA169 negatively responded to low nitrogen and phosphorus availability and degraded NFYAs. Overexpressing TaNFYA-B1, a low-nitrogen- and low-phosphorus-inducible NFYA transcript factor on chromosome 6B, significantly increased both nitrogen and phosphorus uptake and grain yield under differing nitrogen and phosphorus supply levels in a field experiment. The increased nitrogen and phosphorus uptake may have resulted from the fact that that overexpressing TaNFYA-B1 stimulated root development and up-regulated the expression of both nitrate and phosphate transporters in roots. Our results suggest that TaNFYA-B1 plays essential roles in root development and in nitrogen and phosphorus usage in wheat. Furthermore, our results provide new knowledge and valuable gene resources that should be useful in efforts to breed crops targeting high yield with less fertilizer input.

Auxin biosynthetic gene TAR2 is involved in low nitrogen-mediated reprogramming of root architecture in Arabidopsis.

In plants, the plasticity of root architecture in response to nitrogen availability largely determines nitrogen acquisition efficiency. One poorly understood root growth response to low nitrogen availability is an observed increase in the number and length of lateral roots (LRs). Here, we show that low nitrogen-induced Arabidopsis LR growth depends on the function of the auxin biosynthesis gene TAR2 (tryptophan aminotransferase related 2). TAR2 was expressed in the pericycle and the vasculature of the mature root zone near the root tip, and was induced under low nitrogen conditions. In wild type plants, low nitrogen stimulated auxin accumulation in the non-emerged LR primordia with more than three cell layers and LR emergence. Conversely, these low nitrogen-mediated auxin accumulation and root growth responses were impaired in the tar2-c null mutant. Overexpression of TAR2 increased LR numbers under both high and low nitrogen conditions. Our results suggested that TAR2 is required for reprogramming root architecture in response to low nitrogen conditions. This finding suggests a new strategy for improving nitrogen use efficiency through the engineering of TAR2 expression in roots.

A genotypic difference in primary root length is associated with the inhibitory role of transforming growth factor-beta receptor-interacting protein-1 on root meristem size in wheat.

Previously we identified a major quantitative trait locus (QTL) qTaLRO-B1 for primary root length (PRL) in wheat. Here we compare proteomics in the roots of the qTaLRO-B1 QTL isolines 178A, with short PRL and small meristem size, and 178B, with long PRL and large meristem size. A total of 16 differentially expressed proteins were identified: one, transforming growth factor (TGF)-beta receptor-interacting protein-1 (TaTRIP1), was enriched in 178A, while various peroxidases (PODs) were more abundantly expressed in 178B. The 178A roots showed higher TaTRIP1 expression and lower levels of the unphosphorylated form of the brassinosteroid (BR) signaling component BZR1, lower expression of POD genes and reduced POD activity and accumulation of the superoxide anion O2(-) in the root elongation zone compared with the 178B roots. Low levels of 24-epibrassinolide increased POD gene expression and root meristem size, and rescued the short PRL phenotype of 178A. TaTRIP1 directly interacted with the BR receptor TaBRI1 of wheat. Moreover, overexpressing TaTRIP1 in Arabidopsis reduced the abundance of unphosphorylated BZR1 protein, altered the expression of BR-responsive genes, inhibited POD activity and accumulation of the O2(-) in the root tip and inhibited root meristem size. Our data suggested that TaTRIP1 is involved in BR signaling and inhibited root meristem size, possibly by reducing POD activity and accumulation of O2(-) in the root tip. We further demonstrated a negative correlation between the level of TaTRIP1 mRNA and PRL of landraces and modern wheat varieties, providing a valuable insight for better understanding of the molecular mechanism underlying the genotypic differences in root morphology of wheat in the future.

Control of root meristem size by DA1-RELATED PROTEIN2 in Arabidopsis.

The control of organ growth by coordinating cell proliferation and differentiation is a fundamental developmental process. In plants, postembryonic root growth is sustained by the root meristem. For maintenance of root meristem size, the rate of cell differentiation must equal the rate of cell division. Cytokinin and auxin interact to affect the cell proliferation and differentiation balance and thus control root meristem size. However, the genetic and molecular mechanisms that determine root meristem size still remain largely unknown. Here, we report that da1-related protein2 (dar2) mutants produce small root meristems due to decreased cell division and early cell differentiation in the root meristem of Arabidopsis (Arabidopsis thaliana). dar2 mutants also exhibit reduced stem cell niche activity in the root meristem. DAR2 encodes a Lin-11, Isl-1, and Mec-3 domain-containing protein and shows an expression peak in the border between the transition zone and the elongation zone. Genetic analyses show that DAR2 functions downstream of cytokinin and SHORT HYPOCOTYL2 to maintain normal auxin distribution by influencing auxin transport. Further results indicate that DAR2 acts through the PLETHORA pathway to influence root stem cell niche activity and therefore control root meristem size. Collectively, our findings identify the role of DAR2 in root meristem size control and provide a novel link between several key regulators influencing root meristem size.

Left ventricular filling pressure assessed by exercise TDI was correlated with early HFNEF in patients with non-obstructive hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) patients are more susceptible to suffer from heart failure with normal ejection fraction (HFNEF). Therefore, it is critical to evaluate the relationship between left ventricular filling pressure (LVFP) and HFNEF, even if a large proportion of HCM patients have normal LVFP at rest. The objective was to assess the correlation between exercise tissue Doppler imaging (TDI) and early HFNEF in HCM patients by treadmill exercise echocardiography combined with cardiopulmonary exercise test (CPET). METHOD: Twenty-seven non-obstructive HCM patients and 31 age- and gender-matched healthy volunteers were enrolled in this study. All subjects underwent treadmill exercise echocardiography combined with CPET. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were analyzed before and after exercise. RESULT: Five HCM patients had normal LVFP at rest and increased after exercise. For this subgroup, the relationship between minute ventilation and carbon dioxide production (VE/VCO2 slope) and NT-proBNP levels were higher compared with controls and the subgroup with normal resting and stress LVFP, but was similar to the subgroup with elevated LVFP both at rest and after exercise. CONCLUSION: Elevated LVFP after exercise suggested the occurrence of early HFNEF in patients with non-obstructive HCM.

A silver nanoparticle-modified evanescent field optical fiber sensor for methylene blue detection.

A silver nanoparticle-modified evanescent field optical fiber sensor based on a MEMS microchannel chip has been successfully fabricated. Experimental results show that the sensor response decreases linearly with increasing concentration of analyte. Over a range of methylene blue concentrations from 0 to 0.4 µmol/mL, the sensor response is linear (R = 0.9496). A concentration variation of 0.1 µmol/mL can cause an absorbance change of 0.402 dB. Moreover, the optical responses of the same sensing fiber without decoration and modified with silver nanoparticles have also been compared. It can be observed that the output intensity of the Ag nanoparticle-modified sensor is enhanced and the sensitivity is higher. Meanwhile, the absorbance spectra are found to be more sensitive to concentration changes compared to the spectra of the peak wavelength.

Neuroimaging alterations in dementia with Lewy bodies and neuroimaging differences between dementia with Lewy bodies and Alzheimer's disease: An activation likelihood estimation meta-analysis.

AIMS: The aim of this study was to identify brain regions with local, structural, and functional abnormalities in dementia with Lewy bodies (DLB) and uncover the differences between DLB and Alzheimer's disease (AD). The neural networks involved in the identified abnormal brain regions were further described. METHODS: PubMed, Web of Science, OVID, Science Direct, and Cochrane Library databases were used to identify neuroimaging studies that included DLB versus healthy controls (HCs) or DLB versus AD. The coordinate-based meta-analysis and functional meta-analytic connectivity modeling were performed using the activation likelihood estimation algorithm. RESULTS: Eleven structural studies and fourteen functional studies were included in this quantitative meta-analysis. DLB patients showed a dysfunction in the bilateral inferior parietal lobule and right lingual gyrus compared with HC patients. DLB patients showed a relative preservation of the medial temporal lobe and a tendency of lower metabolism in the right lingual gyrus compared with AD. The frontal-parietal, salience, and visual networks were all abnormally co-activated in DLB, but the default mode network remained normally co-activated compared with AD. CONCLUSIONS: The convergence of local brain regions and co-activation neural networks might be potential specific imaging markers in the diagnosis of DLB. This might provide a pathway for the neural regulation in DLB patients, and it might contribute to the development of specific interventions for DLB and AD.

Reorganization of rich clubs in functional brain networks of dementia with Lewy bodies and Alzheimer's disease.

The purpose of this study was to reveal the patterns of reorganization of rich club organization in brain functional networks in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). The study found that the rich club node shifts from sensory/somatomotor network to fronto-parietal network in DLB. For AD, the rich club nodes switch between the temporal lobe with obvious structural atrophy and the frontal lobe, parietal lobe and cerebellum with relatively preserved structure and function. In addition, compared with healthy controls, rich club connectivity was enhanced in the DLB and AD groups. The connection strength of DLB patients was related to cognitive assessment. In conclusion, we revealed the different functional reorganization patterns of DLB and AD. The conversion and redistribution of rich club members may play a causal role in disease-specific outcomes. It may be used as a potential biomarker to provide more accurate prevention and treatment strategies.

Ethanol vapor sensing properties of triangular silver nanostructures based on localized surface plasmon resonance.

A sensitive volatile organic vapor sensor based on the LSPR properties of silver triangular nanoprisms is proposed in this paper. The triangular nanoprisms were fabricated by a nanosphere lithography (NSL) method. They have sharp vertices and edges, and are arranged in an ideal hexangular array. These characteristics ensure that they exhibit an excellent LSPR spectrum and a high sensitivity to the exterior environment changes. The LSPR spectra responding to ethanol vapor and four other volatile organic vapors-acetone, benzene, hexane and propanol-were measured with a UV-vis spectrometer in real time. Compared with the other four vapors, ethanol exhibits the highest sensitivity (∼0.1 nm/mg L(-1)) and the lowest detection limit (∼10 mg/L) in the spectral tests. The ethanol vapor test process is also fast (∼4 s) and reversible. These insights demonstrate that the triangular nanoprism based nano-sensor can be used in ethanol vapor detection applications.

Differences Changes in Cerebellar Functional Connectivity Between Mild Cognitive Impairment and Alzheimer's Disease: A Seed-Based Approach.

Background: Recent studies have discovered that functional connections are impaired among patients with Alzheimer's disease (AD), even at the preclinical stage. The cerebellum has been implicated as playing a role in cognitive processes. However, functional connectivity (FC) among cognitive sub-regions of the cerebellum in patients with AD and mild cognitive impairment (MCI) remains to be further elucidated. Objective: Our study aims to investigate the FC changes of the cerebellum among patients with AD and MCI, compared to healthy controls (HC). Additionally, we explored the role of cerebellum FC changes in the cognitive performance of all subjects. Materials: Resting-state functional magnetic resonance imaging (rs-fMRI) data from three different groups (28 AD patients, 26 MCI patients, and 30 HC) was collected. We defined cerebellar crus II and lobule IX as seed regions to assess the intragroup differences of cortico-cerebellar connectivity. Bias correlational analysis was performed to investigate the relationship between changes in FC and neuropsychological performance. Results: Compared to HC, AD patients had decreased FC within the caudate, limbic lobe, medial frontal gyrus (MFG), middle temporal gyrus, superior frontal gyrus, parietal lobe/precuneus, inferior temporal gyrus, and posterior cingulate gyrus. Interestingly, MCI patients demonstrated increased FC within inferior parietal lobe, and MFG, while they had decreased FC in the thalamus, inferior frontal gyrus, and superior frontal gyrus. Further analysis indicated that FC changes between the left crus II and the right thalamus, as well as between left lobule IX and the right parietal lobe, were both associated with cognitive decline in AD. Disrupted FC between left crus II and right thalamus, as well as between left lobule IX and right parietal lobe, was associated with attention deficit among subjects with MCI. Conclusion: These findings indicate that cortico-cerebellar FC in MCI and AD patients was significantly disrupted with different distributions, particularly in the default mode networks (DMN) and fronto-parietal networks (FPN) region. Increased activity within the fronto-parietal areas of MCI patients indicated a possible compensatory role for the cerebellum in cognitive impairment. Therefore, alterations in the cortico-cerebellar FC represent a novel approach for early diagnosis and a potential therapeutic target for early intervention.

Regional Homogeneity Brain Alterations in Schizophrenia: An Activation Likelihood Estimation Meta-Analysis.

OBJECTIVE: Resting state functional magnetic resonance imaging (rsfMRI) provides a lot of evidence for local abnormal brain activity in schizophrenia, but the results are not consistent. Our aim is to find out the consistent abnormal brain regions of the patients with schizophrenia by using regional homogeneity (ReHo), and indirectly understand the degree of brain damage of the patients with drug-naive first episode schizophrenia (Dn-FES) and chronic schizophrenia. METHODS: We performed the experiment by activation likelihood estimation (ALE) software to analysis the differences between people with schizophrenia group (all schizophrenia group and chronic schizophrenia group) and healthy controls. RESULTS: Thirteen functional imaging studies were included in quantitative meta-analysis. All schizophrenia group showed decreased ReHo in bilateral precentral gyrus (PreCG) and left middle occipital gyrus (MOG), and increased ReHo in bilateral superior frontal gyrus (SFG) and right insula. Chronic schizophrenia group showed decreased ReHo in bilateral MOG, right fusiform gyrus, left PreCG, left cerebellum, right precuneus, left medial frontal gyrus and left anterior cingulate cortex (ACC). No significant increased brain areas were found in patients with chronic schizophrenia. CONCLUSION: Our findings suggest that patients with chronic schizophrenia have more extensive brain damage than FES, which may contribute to our understanding of the progressive pathophysiology of schizophrenia.

An ALE Meta-Analysis of Specific Functional MRI Studies on Subcortical Vascular Cognitive Impairment.

Background: Subcortical vascular cognitive impairment (sVCI), caused by cerebral small vessel disease, accounts for the majority of vascular cognitive impairment, and is characterized by an insidious onset and impaired memory and executive function. If not recognized early, it inevitably develops into vascular dementia. Several quantitative studies have reported the consistent results of brain regions in sVCI patients that can be used to predict dementia conversion. The purpose of the study was to explore the exact abnormalities within the brain in sVCI patients by combining the coordinates reported in previous studies. Methods: The PubMed, Embase, and Web of Science databases were thoroughly searched to obtain neuroimaging articles on the amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity in sVCI patients. According to the activation likelihood estimation (ALE) algorithm, a meta-analysis based on coordinate and functional connectivity modeling was conducted. Results: The quantitative meta-analysis included 20 functional imaging studies on sVCI patients. Alterations in specific brain regions were mainly concentrated in the frontal lobes including the middle frontal gyrus, superior frontal gyrus, medial frontal gyrus, and precentral gyrus; parietal lobes including the precuneus, angular gyrus, postcentral gyrus, and inferior parietal lobule; occipital lobes including the lingual gyrus and cuneus; temporal lobes including the fusiform gyrus and middle temporal gyrus; and the limbic system including the cingulate gyrus. These specific brain regions belonged to important networks known as the default mode network, the executive control network, and the visual network. Conclusion: The present study determined specific abnormal brain regions in sVCI patients, and these brain regions with specific changes were found to belong to important brain functional networks. The findings objectively present the exact abnormalities within the brain, which help further understand the pathogenesis of sVCI and identify them as potential imaging biomarkers. The results may also provide a basis for new approaches to treatment.

Altered Frequency-Dependent Brain Activation and White Matter Integrity Associated With Cognition in Characterizing Preclinical Alzheimer's Disease Stages.

BACKGROUND: Subjective cognitive decline (SCD), non-amnestic mild cognitive impairment (naMCI), and amnestic mild cognitive impairment (aMCI) are regarded to be at high risk of converting to Alzheimer's disease (AD). Amplitude of low-frequency fluctuations (ALFF) can reflect functional deterioration while diffusion tensor imaging (DTI) is capable of detecting white matter integrity. Our study aimed to investigate the structural and functional alterations to further reveal convergence and divergence among SCD, naMCI, and aMCI and how these contribute to cognitive deterioration. METHODS: We analyzed ALFF under slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) bands and white matter fiber integrity among normal controls (CN), SCD, naMCI, and aMCI groups. Correlation analyses were further utilized among paired DTI alteration, ALFF deterioration, and cognitive decline. RESULTS: For ALFF calculation, ascended ALFF values were detected in the lingual gyrus (LING) and superior frontal gyrus (SFG) within SCD and naMCI patients, respectively. Descended ALFF values were presented mainly in the LING, SFG, middle frontal gyrus, and precuneus in aMCI patients compared to CN, SCD, and naMCI groups. For DTI analyses, white matter alterations were detected within the uncinate fasciculus (UF) in aMCI patients and within the superior longitudinal fasciculus (SLF) in naMCI patients. SCD patients presented alterations in both fasciculi. Correlation analyses revealed that the majority of these structural and functional alterations were associated with complicated cognitive decline. Besides, UF alterations were correlated with ALFF deterioration in the SFG within aMCI patients. CONCLUSIONS: SCD shares structurally and functionally deteriorative characteristics with aMCI and naMCI, and tends to convert to either of them. Furthermore, abnormalities in white matter fibers may be the structural basis of abnormal brain activation in preclinical AD stages. Combined together, it suggests that structural and functional integration may characterize the preclinical AD progression.

A practical nanofabrication method: surface plasmon polaritons interference lithography based on backside-exposure technique.

For the experiments of surface plasmon polaritons (SPPs) interference lithography based on attenuated total reflection-coupling mode to be done conveniently, we introduce a backside-exposure technique in this paper. The physical mechanisms of SPPs interference with the backside -exposure method are studied and the interference fringes with feature size below 65 nm are experimentally obtained. The technique can be used to fabricate nanostructures conveniently with large area, and avoids the difficulties for seeking high refractive prism and matching fluid.

Functional MRI-Specific Alterations in Executive Control Network in Mild Cognitive Impairment: An ALE Meta-Analysis.

Background: Mild cognitive impairment (MCI) is regarded as a transitional stage between normal aging and Alzheimer's disease (AD) dementia. MCI individuals with deficits in executive function are at higher risk for progressing to AD dementia. Currently, there is no consistent result for alterations in the executive control network (ECN) in MCI, which makes early prediction of AD conversion difficult. The aim of the study was to find functional MRI-specific alterations in ECN in MCI patients by expounding on the convergence of brain regions with functional abnormalities in ECN. Methods: We searched PubMed, Embase, and Web of Science to identify neuroimaging studies using methods including the amplitude of low frequency fluctuation/fractional amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity in MCI patients. Based on the Activation Likelihood Estimation algorithm, the coordinate-based meta-analysis and functional meta-analytic connectivity modeling were conducted. Results: A total of 25 functional imaging studies with MCI patients were included in a quantitative meta-analysis. By summarizing the included articles, we obtained specific brain region changes, mainly including precuneus, cuneus, lingual gyrus, middle frontal gyrus, posterior cingulate cortex, and cerebellum posterior lobe, in the ECN based on these three methods. The specific abnormal brain regions indicated that there were interactions between the ECN and other networks. Conclusions: This study confirms functional imaging specific abnormal markers in ECN and its interaction with other networks in MCI. It provides novel targets and pathways for individualized and precise interventions to delay the progression of MCI to AD.

Voxelwise Meta-Analysis of Gray Matter Abnormalities in Mild Cognitive Impairment and Subjective Cognitive Decline Using Activation Likelihood Estimation.

BACKGROUND: Voxel-based morphometry studies have not yielded consistent results among patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). OBJECTIVE: Therefore, we aimed to conduct a meta-analysis of gray matter (GM) abnormalities acquired from these studies to determine their respective neuroanatomical changes. METHODS: We systematically searched for voxel-based whole-brain morphometry studies that compared MCI or SCD subjects with healthy controls in PubMed, Web of Science, and EMBASE databases. We used the coordinate-based method of activation likelihood estimation to determine GM changes in SCD, MCI, and MCI sub-groups (amnestic MCI and non-amnestic MCI). RESULTS: A total of 45 studies were included in our meta-analysis. In the MCI group, we found structural atrophy of the bilateral hippocampus, parahippocampal gyrus (PHG), amygdala, right lateral globus pallidus, right insula, and left middle temporal gyrus. The aMCI group exhibited GM atrophy in the bilateral hippocampus, PHG, and amygdala. The naMCI group presented with structural atrophy in the right putamen, right insula, right precentral gyrus, left medial/superior frontal gyrus, and left anterior cingulate. The right lingual gyrus, right cuneus, and left medial frontal gyrus were atrophic GM regions in the SCD group. CONCLUSION: Our meta-analysis identified unique patterns of neuroanatomical alternations in both the MCI and SCD group. Structural changes in SCD patients provide new evidence for the notion that subtle impairment of visual function, perception, and cognition may be related to early signs of cognitive impairment. In addition, our findings provide a foundation for future targeted interventions at different stages of preclinical Alzheimer's disease.

Long-term performance of right ventricular pacing leads: risk factors associated with permanent right ventricular pacing threshold increase.

PURPOSE: Right ventricular pacing threshold (RVPT) may rise over time accompanied by the increased use of implantable cardiac pacemakers. However, risk factors for permanent RVPT increase are not fully clarified in patients without definite lead fracture and dislodgment. We aimed to evaluate the long-term performance of RV pacing leads and identify risk factors associated with the occurrence of permanent RVPT increase in this population. METHODS: Patients with first implantation of cardiac pacemakers from January 2008 to June 2016 were consecutively enrolled. Follow-up for RVPT increase was until December 2017. The clinical data, specific data on the pacemaker implantation, and routine follow-up were retrieved. RESULTS: During a follow-up duration of 5.4 ± 2.1 years, permanent RVPT increase (except lead fracture and dislodgment) was found in 8.4% (87/1033) patients. Patients with permanent RVPT increase had higher prevalence of myocardial infarction (MI), diabetes, and the use of amiodarone. The risk factors independently associated with permanent RVPT increase were MI (HR = 1.094, 95% CI 1.014-1.180, p = 0.031), diabetes (HR = 2.804, 95% CI 1.064-3.775, p = 0.003). MI patients with RVPT increase had higher prevalence of multivessel disease and atrioventricular block. Diabetic patients with RVPT increase exhibited higher serum fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels, which were correlated with the maximum RVPT (p < 0.001). CONCLUSIONS: Our data showed that permanent RVPT increases (except lead fracture and dislodgement) during long-term follow-up after pacemaker implantation. The likely risk factors predisposing to chronic permanent RVPT increase are MI and diabetes with higher FBG and HbA1c levels.