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Abstract Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.

Abstract. Background:. Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson's disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD. Methods:. Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls. Results:. We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions:. Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Abstract Objectives Hereditary spastic paraplegia (HSP) is a genetically heterogeneous disease caused by over 70 genes, with a significant number of patients still genetically unsolved. In this study, we recruited a suspected HSP family characterized by spasticity, developmental delay, ataxia and hypomyelination, and intended to reveal its molecular etiology by whole exome sequencing (WES) and long‐read sequencing (LRS) analyses. Methods WES was performed on 13 individuals of the family to identify the causative mutations, including analyses of SNVs (single‐nucleotide variants) and CNVs (copy number variants). Accurate circular consensus (CCS) long‐read sequencing (LRS) was used to verify the findings of CNV analysis from WES. Results SNVs analysis identified a missense variant c.195G>T (p.E65D) of MORF4L2 at Xq22.2 co‐segregating in this family from WES data. Further CNVs analysis revealed a microdeletion, which was adjacent to the MORF4L2 gene, also co‐segregating in this family. LRS verified this microdeletion and confirmed the deletion range (chrX: 103,690,507–103,715,018, hg38) with high resolution at nucleotide level accuracy. Interpretations In this study, we identified an Xq22.2 microdeletion (about 24.5 kb), which contains distal enhancers of the PLP1 gene, as a likely cause of SPG2 in this family. The lack of distal enhancers may result in transcriptional repression of PLP1 in oligodendrocytes, potentially affecting its role in the maintenance of myelin, and causing SPG2 phenotype. This study has highlighted the importance of noncoding genomic alterations in the genetic etiology of SPG2.

Abstract GBA1 variants are important risk factors for Parkinson’s disease (PD). Most studies assessing GBA1-related PD risk have been performed in European-derived populations. Although the coding region of the GBA1 gene in the Chinese population has been analyzed, the sample sizes were not adequate. In this study, we aimed to investigate GBA1 variants in a large Chinese cohort of patients with PD and healthy control and explore the associated clinical characteristics. GBA1 variants in 4034 patients and 2931 control participants were investigated using whole-exome and whole-genome sequencing. The clinical features of patients were evaluated using several scales. Regression analysis, chi-square, and Fisher exact tests were used to analyze GBA1 variants and the clinical symptoms of different groups. We identified 104 variants, including 8 novel variants, expanding the spectrum of GBA1 variants. The frequency of GBA1 variants in patients with PD was 7.46%, higher than that in the control (1.81%) (P

Non-coding variants in the human genome significantly influence human traits and complex diseases via their regulation and modification effects. Hence, an increasing number of computational methods are developed to predict the effects of variants in human non-coding sequences. However, it is difficult for inexperienced users to select appropriate computational methods from dozens of available methods. To solve this issue, we assessed 12 performance metrics of 24 methods on four independent non-coding variant benchmark datasets: (1) rare germline variants from clinical relevant sequence variants (ClinVar), (2) rare somatic variants from Catalogue Of Somatic Mutations In Cancer (COSMIC), (3) common regulatory variants from curated expression quantitative trait locus (eQTL) data, and (4) disease-associated common variants from curated genome-wide association studies (GWAS). All 24 tested methods performed differently under various conditions, indicating varying strengths and weaknesses under different scenarios. Importantly, the performance of existing methods was acceptable for rare germline variants from ClinVar with the area under the receiver operating characteristic curve (AUROC) of 0.4481–0.8033 and poor for rare somatic variants from COSMIC (AUROC = 0.4984–0.7131), common regulatory variants from curated eQTL data (AUROC = 0.4837–0.6472), and disease-associated common variants from curated GWAS (AUROC = 0.4766–0.5188). We also compared the prediction performance of 24 methods for non-coding de novo mutations in autism spectrum disorder, and found that the combined annotation-dependent depletion (CADD) and context-dependent tolerance score (CDTS) methods showed better performance. Summarily, we assessed the performance of 24 computational methods under diverse scenarios, providing preliminary advice for proper tool selection and guiding the development of new techniques in interpreting non-coding variants.

Green development has become one of the important concepts leading China’s economic developments, and it is extremely meaningful to boost the continuous growth of agricultural green total factor productivity (AGTFP) to achieve the construction of a powerful agricultural country. Using China’s provincial data from 2011 to 2020, this manuscript calculates AGTFP through the SBM–GML model, and the digital green finance (DGF) through a comprehensive indicator system. The double fixed-effect model, quantile model and spatial Durbin model are used for in-depth study of the benchmark influence, the nonlinear effect and spatial spillover effect of DGF on AGTFP. The main research conclusions of the article are as follows: (1) DGF is significantly conducive to the improvement of AGTFP. Along with the continuous growth of AGTFP, the promoting effect of DGF has gradually increased. (2) In terms of impact path, green finance can properly promote the growth of AGTFP, while the role of the degree of digitization is not very significant. Meanwhile, the main channel for DGF to promote AGTFP is through green technology efficiency. (3) The impact of DGF on AGTFP varies spatially, while the role is more effective in regions with a higher degree of economic development and well-developed modernization. (4) There is a spatial spillover effect of DGF’s impact on AGTFP, which means that DGF can simultaneously promote the growth of AGTFP in local regions and neighboring regions.

Abstract Genome-wide association studies (GWASs) have identified numerous susceptibility loci for Parkinson’s disease (PD), but its genetic architecture remains underexplored in populations of non-European ancestry. To identify genetic variants associated with PD in the Chinese population, we performed a GWAS using whole-genome sequencing (WGS) in 1,972 cases and 2,478 controls, and a replication study in a total of 8209 cases and 9454 controls. We identified one new risk variant rs61204179 (P combined = 1.47 × 10−9) with low allele frequency, four previously reported risk variants (NUCKS1/RAB29-rs11557080, SNCA-rs356182, FYN-rs997368, and VPS13C-rs2251086), as well as three risk variants in LRRK2 coding region (A419V, R1628P, and G2385R) with genome-wide significance (P

Phenological changes caused by urbanization may provide evidence of how vegetation responds to global warming. However, the phenological characteristics of vegetation in metropolitan areas have been poorly studied, especially in terms of spatiotemporal variations. In this study, we explored the applicability of Local Climate Zones (LCZs) to investigate the spatiotemporal variations in urban vegetation phenology by linking MODIS-derived phenology metrics with LCZs in the Austin metropolitan area in Texas, USA. We extracted three vegetation phenology metrics from MODIS data between 2008 and 2018, including the start of growing season, end of growing season, and length of the growing season (i.e. SOS, EOS, and LOS, respectively). The results showed that during the study period, the EOS and SOS gradually advanced, while LOS showed no obvious change. Statistical analysis was conducted to examine the spatiotemporal variations of the phenology metrics among different LCZs and along “Urban-Rural Gradients” (URGs). There were 37.5%, 75.0%, and 74.3% pairs of LCZs, indicating statistically significant phenological differences in terms of SOS, EOS, and LOS in 2012, respectively. In contrast, most pairs of URGs showed almost no differences in phenological metrics, especially in EOS. Geographically, SOS showed a fluctuating change with an advancing tendency, whereas the EOS decreased very slowly with distance from the city center (i.e. along the URGs). LCZs can be used to help identify distinctive phenology metrics with statistically significant differences, especially in EOS and LOS. Compared to URGs, LCZs offer a unique analytical framework for studying urban ecosystem patterns, functions, and dynamics. Lastly, LCZs can enable the identification of sensitive areas for ecological protection in support of sustainable urban development and environmental stewardship.

Streetlamp light is inevitable in the night landscape of a city and may affect the phenology of newly planted ornamental plants, but it has rarely been fully examined. Newly transplanted ornamental plants probably suffer periodic shocks, which mainly result from the inefficient reuse of internal nutrients for new growth. Exponential nutrient loading (ENL) is well known for its ability to overcome transplant shocks by promoting retranslocation for the reuse of strengthened nutrients from internal reserves in precultured seedlings. Transplantation to urbanized lands is distinct from that of montane areas; this is mainly due to a high frequency of exposure to the artificial illumination of night lighting. It is suspected that this lighting modifies vegetative phenology and generates potential risks by increasing reliance on internal nutrient retranslocation. In this study, Podocarpus macrophyllus seedlings were cultured with ENL at low and high rates of nitrogen (N) deliveries (40 and 120 mg N seedling−1, respectively), and the high-rate treatment was identified as being able to trap seedlings within toxic states. A labeled 15N isotope was pulsed to transplanted seedlings exposed to simulated light qualities in red, green, and blue light spectra. The seedlings harvested at one month showed rare responses to the interactive spectra and preculture treatments, but most of them responded to the low-rate N preculture treatment with stronger abilities in terms of the reuse of internal N and the synthesizing of photosynthetic pigments. In conclusion, it was verified that night light enforces the effect on newly transplanted plants; the red light invoked internal N for reuse, and the blue light promoted the uptake of the current N. The internal N reserve established through preculture ENL rarely made a contribution to the night light effect, except for the enhancement of height growth in the red light. The red light spectrum was recommended for the exposure of newly transplanted seedlings due to its effect on the enhancement of the retranslocation of internal N and the induction of a steady state of uptake from the current N input.

ObjectiveParkinson's disease (PD) and dystonia are two closely related movement disorders with overlaps in clinical phenotype. Variants in several dystonia-related genes were demonstrated to be associated with PD; however, genetic evidence for the involvement of dystonia-related genes in PD has not been fully studied. Here, we comprehensively investigated the association between rare variants in dystonia-related genes and PD in a large Chinese cohort.MethodsWe comprehensively analyzed the rare variants of 47 known dystonia-related genes by mining the whole-exome sequencing (WES) and whole-genome sequencing (WGS) data from 3,959 PD patients and 2,931 healthy controls. We initially identified potentially pathogenic variants of dystonia-related genes in patients with PD based on different inheritance models. Sequence kernel association tests were conducted in the next step to detect the association between the burden of rare variants and the risk for PD.ResultsWe found that five patients with PD carried potentially pathogenic biallelic variants in recessive dystonia-related genes including COL6A3 and TH. Additionally, we identified 180 deleterious variants in dominant dystonia-related genes based on computational pathogenicity predictions and four of which were considered as potentially pathogenic variants (p.W591X and p.G820S in ANO3, p.R678H in ADCY5, and p.R458Q in SLC2A1). A gene-based burden analysis revealed the increased burden of variant subgroups of TH, SQSTM1, THAP1, and ADCY5 in sporadic early-onset PD, whereas COL6A3 was associated with sporadic late-onset PD. However, none of them reached statistical significance after the Bonferroni correction.ConclusionOur findings indicated that rare variants in several dystonia-related genes are suggestively associated with PD, and taken together, the role of COL6A3 and TH genes in PD is highlighted.

In this study, copper slag and low-grade nickel laterite were synergistically utilized via an innovative sintering process with multi-force fields. Their sintering performance and the reduction and softening dripping characteristics of Fe–Ni–Cu product sinter were determined. The strengthening mechanism of the innovative sintering technology was revealed. The obtained Fe–Ni–Cu alloy and smelting slag from the melting dripping process were characterized. Carbon emissions reduction and other valuable elements treatment were also discussed. Due to the formation of the denser sinter microstructure and the reduction of high smelting components, sintering performances in the innovative sintering process are substantially improved. Compared with the base case, tumble index and productivity are improved by 24.87% and 19.59%, respectively. Solid fuel consumption is reduced by 27.14%. The reduction and softening dripping characteristics of Fe–Ni–Cu product sinter are excellent as well. The obtained Fe–Ni–Cu alloy with high purity can be used as the high-quality burden for copper-bearing stainless steel and high-strength alloy steel and its quality can be further improved by optimizing the smelting process parameters in the near future. In addition, the obvious carbon emissions reduction in sintering-blast furnace production can be achieved and other valuable elements such as S, Zn and Pb can be conveniently recycled in form of sulphuric acid and Pb–Zn dust, respectively.

Deubiquitinating enzymes (DUBs) serve to maintain cellular homeostasis via protein ubiquitination and exert diverse regulatory functions in cancers and other diseases. Much progress has been made in characterizing biological roles of DUBs over the decades, yet the specific functions of many subclass members remain largely unexplored. It was not until recent years that the role of ubiquitin‐specific‐processing protease 35 (USP35) in cancers began to be understood. Here, we focus on delineating the roles and underlying mechanisms of USP35 in non‐small cell lung cancer (NSCLC). The isobaric tags for relative and absolute quantitation (iTRAQ) comparative proteomic approach were employed to identify differentially expressed proteins (DEPs) in H1299 cells induced by USP35 overexpression or silencing. Among the potential interactome of USP35, ribosome‐binding protein 1 (RRBP1), a membrane‐bound protein in endoplasmic reticulum (ER), captured our attentions. RRBP1 expression was found to positively correlate with USP35 levels in both genetically modified cells and human NSCLC tissues. Concordantly, both RRBP1 expression and USP35 expression were found to positively correlate with poor prognoses in lung adenocarcinoma patients. At the molecular level, USP35 was verified to directly interact with RRBP1 to prevent it from proteasomal‐dependent degradation. Functionally, USP35 alleviated ER stress‐induced cell apoptosis by stabilizing RRBP1 in NSCLC cells. Collectively, these findings indicate that USP35 plays a critical role in resisting ER stress‐induced cell death through deubiquitinating RRBP1, hence providing a rationale to target the USP35‐RRBP1 axis as an alternative therapeutic option for NSCLC.

Gadolinium-doped ceria (GDC) interlayers are required to prevent the interfacial reaction between La0.6Sr0.4Co0.2Fe0.8O3 (LSCF) cathode and Y2O3-stabilized ZrO2 (YSZ) electrolyte in solid oxide fuel cells (SOFCs). However, it's difficult to prepare a thin and dense GDC interlayer on the sintered half-cell at a low temperature. In this study, the physical vapor deposition (PVD) method was employed to successfully manufacture dense GDC interlayers with the thickness of 1 μm. The influences of GDC sintering temperature (900 °C, 1000 °C and 1100 °C) on cell performance characteristics and degradation behavior were investigated. The cell with GDC interlayer sintered at 1100 °C showed the lowest degradation rate during the 216-h operation. The best stability was attributed to the most effective inhibition of Sr diffusion by the GDC interlayer, which was demonstrated by the almost unchanged Ohmic and polarization resistances during the aging stage and the negligible Sr enrichment at YSZ/GDC interface. Compared to the conventional screen-printed GDC interlayers (sintered above 1250 °C), the GDC interlayer prepared by the PVD method and sintered at 1100 °C was significantly denser and thinner, showing a promising application prospect due to its benefits for cell stability.

IntroductionAlthough the relationship between psychiatric disorders and Parkinson’s disease (PD) has attracted continuous research attention, the causal linkage between them has not reached a definite conclusion.MethodsTo identify the causal relationship between psychiatric disorders and PD, we used public summary-level data from the most recent and largest genome-wide association studies (GWASs) on psychiatric disorders and PD to conduct a bidirectional two-sample Mendelian randomization (MR). We applied stringent control steps in instrumental variable selection using the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method to rule out pleiotropy. The inverse-variance weighted (IVW) method was used to identify the causal relationship between psychiatric disorders and PD. Multiple MR analysis methods, including MR-Egger, weighted-median, and leave-one-out analyses, were used for sensitivity analysis, followed by heterogeneity tests. Further validation and reverse MR analyses were conducted to strengthen the results of the forward MR analysis.ResultsThe lack of sufficient estimation results could suggest a causal relationship between psychiatric disorders and PD in the forward MR analysis. However, the subsequent reverse MR analysis detected a causal relationship between PD and bipolar disorder (IVW: odds ratios [OR] =1.053, 95% confidence interval [CI] =1.02–1.09, p = 0.001). Further analysis demonstrated a causal relationship between genetically predicted PD and the risk of bipolar disorder subtype. No pleiotropy or heterogeneity was detected in the analyses.DiscussionOur study suggested that while psychiatric disorders and traits might play various roles in the risk of developing PD, PD might also be involved in the risk of developing psychiatric disorders.

IntroductionParkinson's disease (PD) is a progressive movement disorder caused by a loss of dopaminergic neurons. Previous studies have highlighted the importance of mitochondria dynamics in the pathogenesis of PD. Dynamin-1-like (DNM1L) is a gene that encodes dynamin-related protein 1 (DRP1), a GTPase essential for proper mitochondria fission. In the present study, we evaluated the relationship between DNM1L variants and PD in the Chinese population.MethodsA total of 3,879 patients with PD and 2,931 healthy controls were recruited and burden genetic analysis combined with high-throughput sequencing was applied.ResultsWe identified 23 rare variants in the coding region of DNM1L, while no difference in variant burden was shown between the cases and controls. We also identified 201 common variants in the coding and flanking regions and found two significant SNPs, namely, rs10844308 and rs143794289 [odds ratio (OR) = 1.220 and 0.718, p = 0.025 and 0.036, respectively]. We also performed a meta-analysis to correlate the two SNPs with PD risk. However, none of the common variants was significant using logistic regression.ConclusionDespite the critical role of DRP1, our study did not support the relationship between DNM1L variants and PD risk in the Chinese population.

ObjectiveCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small vessel disease caused by mutations in the NOTCH3 gene. Previous studies have established a link between NOTCH3 variants and Parkinson’s disease (PD) in terms of neuropathology and clinical characteristics. In this study, we aimed to explore the role of NOTCH3 gene in PD in a large Chinese cohort.MethodsA total of 1,917 patients with early-onset or familial PD and 1,652 matched controls were included. All variants were divided into common or rare types by minor allele frequency (MAF) at a threshold of 0.01 (MAF > 0.01 into common variants and others into rare variants). Common variants were subjected to single-variant tests by PLINK, then gene-based analyses were used for rare variants with the optimized sequence kernel association test (SKAT-O). For genotype–phenotype correlation assessment, regression models were conducted to compare clinical features between the studied groups.ResultsThree common variants (rs1044006, rs1043997, and rs1043994) showed a nominal protective effect against PD. However, none of these SNPs survived Bonferroni correction. The results in the validation cohort revealed a significant but opposite association between these variants and PD. The gene-based analyses of rare variants showed no significant associations of NOTCH3 with PD. Although we did not find significant associations in the following genotype–phenotype analysis, the higher clinical scores of motor symptoms in NOTCH3-variant carriers were of interest.ConclusionOur results indicated that NOTCH3 gene may not play an important role in the early-onset or familial PD of Chinese population.

The seasonal change characteristics of water quality in the Sunxi River watershed, which is a typical watershed in the tail area of the Three Gorges Reservoir Area, must be studied to provide remediation ideas and specific measures for agricultural nonpoint source pollution in the reservoir area. A two-way repeated measures ANOVA was used to analyze the variation characteristics of chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) concentrations in the upstream and downstream of the Sunxi River watershed in spring, summer, and autumn of 2018–2021. With data from autumn 2018 taken as an example, path analysis was applied to study the effect degree of influencing factors on TN concentrations. The two-way repeated measures ANOVA illustrated that the COD, TN, and TP concentrations in the downstream were significantly higher than those in the upstream (P < 0.05). In addition, the COD concentrations were the highest in summer 2019, followed by spring of 2019 and 2021, and TN and TP concentrations were higher in spring and summer. The TN and TP concentrations were comparatively lower in the autumn. The path analysis showed that electrical conductance and dissolved oxygen directly affected the TN concentrations, and water temperature mainly affected the TN concentrations via the indirect effects of electrical conductance and dissolved oxygen. The water quality of upstream Sunxi River watershed was better than that of downstream, and the water quality in autumn was better than spring and summer in 2018–2021. For water quality management and ecological restoration of the Sunxi River watershed, further attention should be paid to the water quality changes in the downstream and in spring and summer and to the impact of water temperature, electrical conductivity, and dissolved oxygen on the water quality.

ObjectivesSpinocerebellar degeneration (SCD) comprises a multitude of disorders with sporadic and hereditary forms, including spinocerebellar ataxia (SCA). Except for progressive cerebellar ataxia and structural atrophy, hemodynamic changes have also been observed in SCD. This study aimed to explore the whole-brain patterns of altered cerebral blood flow (CBF) and its correlations with disease severity and psychological abnormalities in SCD via arterial spin labeling (ASL).MethodsThirty SCD patients and 30 age- and sex-matched healthy controls (HC) were prospectively recruited and underwent ASL examination on a 3.0T MR scanner. The Scale for Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS) scores were used to evaluate the disease severity in SCD patients. Additionally, the status of anxiety, depression and sleep among all patients were, respectively, evaluated by the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Self-Rating Scale of Sleep (SRSS). We compared the whole-brain CBF value between SCD group and HC group at the voxel level. Then, the correlation analyses between CBF and disease severity, and psychological abnormalities were performed on SCD group.ResultsCompared with HC, SCD patients demonstrated decreased CBF value in two clusters (FWE corrected P < 0.05), covering bilateral dentate and fastigial nuclei, bilateral cerebellar lobules I-IV, V and IX, left lobule VI, right lobule VIIIb, lobules IX and X of the vermis in the cerebellar Cluster 1 and the dorsal part of raphe nucleus in the midbrain Cluster 2. The CBF of cerebellar Cluster 1 was negatively correlated with SARA scores (Spearman’s rho = –0.374, P = 0.042) and SDS standard scores (Spearman’s rho = –0.388, P = 0.034), respectively. And, the CBF of midbrain Cluster 2 also had negative correlations with SARA scores (Spearman’s rho = –0.370, P = 0.044) and ICARS scores (Pearson r = –0.464, P = 0.010).ConclusionThe SCD-related whole-brain CBF changes mainly involved in the cerebellum and the midbrain of brainstem, which are partially overlapped with the related function cerebellar areas of hand, foot and tongue movement. Decreased CBF was related to disease severity and depression status in SCD. Therefore, CBF may be a promising neuroimaging biomarker to reflect the severity of SCD and suggest mental changes.

ObjectivesParkinson’s disease (PD) is a neurodegenerative disorder with the manifestation of motor symptoms and non-motor symptoms. Previous studies have indicated the role of several transmembrane (TMEM) protein family genes in PD pathogenesis.Materials and MethodsIn order to better investigate the genetic role of PD-related TMEM protein family genes in PD, including TMEM230, TMEM59, TMEM108, TMEM163, TMEM175, and TMEM229B, 1,917 sporadic early onset PD (sEOPD) or familial PD (FPD) patients and 1,652 healthy controls were analyzed by whole-exome sequencing (WES) while 1,962 sporadic late-onset PD (sLOPD) and 1,279 healthy controls were analyzed by whole-genome sequencing (WGS). Rare and common variants for each gene were included in the analysis.ResultsOne hundred rare damaging or loss of function variants of six genes were found at the threshold of MAF < 0.1%. Three rare Dmis variants of TMEM230 were specifically identified in PD. Rare missense variants of TMEM59 were statistically significantly associated with PD in the WES cohort, indicating the role of TMEM59 in FPD and sEOPD. Rare missense variants of TMEM108 were suggestively associated with PD in the WGS cohort, indicating the potential role of TMEM108 in sLOPD. The rare variant of the other three genes and common variants of six genes were not significantly associated with PD.ConclusionWe performed a large case-control study to systematically investigate the role of several PD-related TMEM protein family genes in PD. We identified three PD-specific variants in TMEM230, the significant association of TMEM59 with FPD, and sEOPD and the suggestive association of TMEM108 with sLOPD.

Glass material has been widely used in modern architecture. Scratch-induced surface damage of aged monolithic glass panel leads to the strength degradation of material and thus threatens the glass safety. Therefore, in order to accurately evaluate the strength of aged glass elements, it is crucial to extract key damage features including the damage location and depth in a precise way. This study aims to develop a non-contact stage-wise scanning method to extract 3D damage characteristics on glass surface, which can further facilitate the investigation into the associated influences on the flexural strength of glass. Coaxial double ring tests on annealed glass specimens under various magnitudes of applied loads were performed, which aimed to explore the influence of the surface damage on the flexural strength. Monocular microscope equipped with an industrial camera was used to detect damage area throughout the glass panel in the first stage rapidly. It was then followed by a chromatic confocal scanner to precisely measure the damage depth within local damage area. The results via confocal microscope scanning were considered as the reference values. It shows that the proposed method can be a potentially alternative solution instead of confocal microscope for damage quantification.

The bridging behavior between fragments is one vital factor in the post-fracture stage of glass laminates. A particle-based discrete element model was developed in this work to simulate the bridging behavior of fractured glass laminates. The model was based on the calibration of hyperelastic PVB material properties using soft-bond model and further validated with the experimental data as well as the observations from through-crack-tensile tests. In order to investigate the bridging performance of fractured glass laminates with multiple fragments under uniaxial tension, three factors encompassing the crack aligning, fragment number and adhesion conditions were considered to perform a parametric study. The results give an exploratory application of the developed discrete element models in the estimation of the post-fracture behaviors. It is found that the smaller fragment size can diminish the tension-stiffening effect in the non-aligned case which might generate an enhancing ratio of initial modulus up to nearly 3.6. The non-aligned cracks can also lead to a very high strength if the adhesion ability can be guaranteed. However, the delamination of fragments is expected to control the post-fracture strength of fractured glass laminates with PVB interlayer.

Background: Short tandem repeats (STRs) are highly variable elements that play a pivotal role in multiple genetic diseases and the regulation of gene expression. Long-read sequencing (LRS) offers a potential solution to genome-wide STR analysis. However, characterizing STRs in human genomes using LRS on a large population scale has not been reported.Methods: We conducted the large LRS-based STR analysis in 193 unrelated samples of the Chinese population and performed genome-wide profiling of STR variation in the human genome. The repeat dynamic index (RDI) was introduced to evaluate the variability of STR. We sourced the expression data from the Genotype-Tissue Expression to explore the tissue specificity of highly variable STRs related genes across tissues. Enrichment analyses were also conducted to identify potential functional roles of the high variable STRs.Results: This study reports the large-scale analysis of human STR variation by LRS and offers a reference STR database based on the LRS dataset. We found that the disease-associated STRs (dSTRs) and STRs associated with the expression of nearby genes (eSTRs) were highly variable in the general population. Moreover, tissue-specific expression analysis showed that those highly variable STRs related genes presented the highest expression level in brain tissues, and enrichment pathways analysis found those STRs are involved in synaptic function-related pathways.Conclusion: Our study profiled the genome-wide landscape of STR using LRS and highlighted the highly variable STRs in the human genome, which provide a valuable resource for studying the role of STRs in human disease and complex traits.

Genotype–phenotype correlations are the basis of precision medicine of human genetic diseases. However, it remains a challenge for clinicians and researchers to conveniently access detailed individual-level clinical phenotypic features of patients with various genetic variants. To address this urgent need, we manually searched for genetic studies in PubMed and catalogued 8,309 genetic variants in 1,288 genes from 17,738 patients with detailed clinical phenotypic features from 1,855 publications. Based on genotype–phenotype correlations in this dataset, we developed an user-friendly online database called GPCards (http://genemed.tech/gpcards/), which not only provided the association between genetic diseases and disease genes, but also the prevalence of various clinical phenotypes related to disease genes and the patient-level mapping between these clinical phenotypes and genetic variants. To accelerate the interpretation of genetic variants, we integrated 62 well-known variant-level and gene-level genomic data sources, including functional predictions, allele frequencies in different populations, and disease-related information. Furthermore, GPCards enables automatic analyses of users’ own genetic data, comprehensive annotation, prioritization of candidate functional variants, and identification of genotype–phenotype correlations using custom parameters. In conclusion, GPCards is expected to accelerate the interpretation of genotype–phenotype correlations, subtype classification, and candidate gene prioritisation in human genetic diseases.

Folate deficiency is an environmental risk factor for several developmental disorders. De novo mutations (DNMs) also play important etiological roles in various developmental disorders. However, it remains unclear whether DNMs in folate-related genes (FRGs) contribute to developmental disorders. We obtained a list of 1,821 FRGs from folate metabolism pathways and the Comparative Toxicogenomics Database, along with data concerning DNMs in 15,404 cases and 3,391 controls from the Gene4Denovo database. We used a TADA-Denovo model to prioritize candidate disease-associated FRGs, and characterized these genes in terms of genic intolerance, functional networks, and expression patterns. Compared with the controls, FRGs were significantly enriched in likely damaging DNMs (ldDNMs) in patients with developmental disorders (1.54 ≤ odds ratio ≤ 3.39, Padj ≤ 0.0075). Furthermore, FRGs with ldDNMs rather than with likely non-damaging DNMs (lndDNMs) overlapped significantly among the five developmental disorders included in the datasets. The TADA-Denovo model prioritized 96 candidate disease-associated FRGs, which were intolerant to genetic variants. Their functional networks mainly involved pathways associated with chromatin modification, organ development, and signal transduction pathways. DNMT3A, KMT2B, KMT2C, and YY1 emerged as hub FRGs from the protein–protein interaction network. These candidate disease-associated FRGs are preferentially expressed in the excitatory neurones during embryonic development, and in the cortex, cerebellum, striatum, and amygdala during foetal development. Overall, these findings show that DNMs in FRGs are associated with the risk of developmental disorders. Further research on these DNMs may facilitate the discovery of developmental disorder biomarkers and therapeutic targets, enabling detailed, personalized, and precise folate treatment plan.

Abstract Background Common and rare variants of guanosine triphosphate cyclohydrolase 1 (GCH1) gene may play important roles in Parkinson’s disease (PD). However, there is a lack of comprehensive analysis of GCH1 genotypes, especially in non-coding regions. The aim of this study was to explore the genetic characteristics of GCH1, including rare and common variants in coding and non-coding regions, in a large population of PD patients in Chinese mainland, as well as the phenotypic characteristics of GCH1 variant carriers. Methods In the first cohort of this case-control study, we performed whole-exome sequencing in 1555 patients with early-onset or familial PD and 2234 healthy controls; then in the second cohort, whole-genome sequencing was performed in sporadic late-onset PD samples (1962 patients), as well as 1279 controls. Variants at target GCH1 regions were extracted, and then genetic and detailed phenotypic data were analyzed using regression models and the sequence kernel association test. We also performed a meta-analysis to correlate deleterious GCH1 variants with age at onset (AAO) in PD patients. Results For coding variants, we identified a significant burden of GCH1 deleterious variants in early-onset or familial PD cases compared to controls (1.2% vs 0.1%, P

Direct reduction-magnetic separation process (DRMSP) is a highly effective and clean method to upgrade the complex resources, which has been widely used to recovery the value metals in copper slag (CS) and nickel laterite (NL) in recent years. Adequate growth of the alloy particles is a key parameter influencing the complete extraction of alloys from CS and NL in this process. Therefore, the liquid phase formation mechanism, growth kinetics of the alloy particles, and the correlation between the alloy particle growth and liquid phase formation were studied to reveal the synergistic effect of the co-reduction of CS and NL. The results indicated that fayalite in the copper slag reacted with forsterite in nickel laterite to form augite group minerals with low melting points, resulting in more liquid phase formation in the reductive roasting process. A comparison with the reduction kinetic parameters of the single nickel laterite showed that the growth index and activation energy decreased significantly from 2.85 and 272.98 KJ/mol to 2.08 and 171.99 KJ/mol, respectively, after the addition of 40% copper slag, which confirmed that copper slag promoted the particle growth. Moreover, the liquid phase increased the total cohesive force between the alloy particles, revealing the correlation between alloy particle growth and liquid phase.

Increasing evidence reveals sex as an important factor in the development of Parkinson’s disease (PD), but associations between genes on the sex chromosomes and PD remain unknown. TAF1 is a gene located on the X chromosome which is known to cause X-linked syndromic mental retardation-33 (MRXS33) and X-linked Dystonia-Parkinsonism (XDP). In this study, we conducted whole-exome sequencing (WES) among 1,917 patients with early-onset or familial PD and 1,652 controls in a Chinese population. We detected a hemizygous frameshift variant c.29_53dupGGA(CAG)2CTACCATCA(CTG)2C (p.A19Dfs*50) in two unrelated male patients. Further segregation analysis showed an unaffected family member carried this variant, which suggested the penetrance of the variant may be age-related and incomplete. To verify the effects of TAF1 on PD, genetic analyses were carried separately by gender. Analysis of rare variants by optimal sequence kernel association (SKAT-O) test showed a nominally significant difference in variant burden between the male PD patients and controls (2.01 vs. 1.38%, p = 0.027). In the female group, none of the variant types showed significant association with PD in this study. In conclusion, we found rare variants in TAF1 may be implicated in PD, but further genetic and functional analyses were needed.

ObjectiveThis study analyzed the differences in the cerebral blood flow (CBF) between unilateral Sudden Sensorineural Hearing Loss (SSNHL) patients and healthy controls (HCs). We also investigated CBF differences in auditory-related areas in patients with left- and right-sided SSNHL (lSSNHL and rSSNHL) and HCs. We further explore the correlation between unilateral SSNHL characteristics and changes in the CBF.Methods36 patients with unilateral SSNHL (15 males and 21 females, 40.39 ± 13.42 years) and 36 HCs (15 males and 21 females, 40.39 ± 14.11 years) were recruited. CBF images were collected and analyzed using arterial spin labeling (ASL). CereFlow software was used for the post-processing of the ASL data to obtain the CBF value of 246 subregions within brainnetome atlas (BNA). The Two-sample t-test was used to compare CBF differences between SSNHL patients and HCs. One-way ANOVA or Kruskal-Wallis test was used to compare the CBF difference of auditory-related areas among the three groups (lSSNHL, rSSNHL, and HCs). Then, the correlation between CBF changes and specific clinical characteristics were calculated.ResultsThe SSNHL patients exhibited decreased CBF in the bilateral middle frontal gyrus (MFG, MFG_7_1 and MFG_7_3), the contralateral precentral gyrus (PrG, PrG_6_3) and the bilateral superior parietal lobule (SPL, bilateral SPL_5_1, SPL_5_2, and ipsilateral SPL_5_4), p < 0.0002. Compared with HCs, unilateral SSNHL patients exhibited increased rCBF in the bilateral orbital gyrus (OrG, OrG_6_5), the bilateral inferior temporal gyrus (ITG, contralateral ITG_7_1 and bilateral ITG_7_7), p < 0.0002. lSSNHL showed abnormal CBF in left BA21 caudal (p = 0.02) and left BA37 dorsolateral (p = 0.047). We found that the CBF in ipsilateral MFG_7_1 of SSNHL patients was positively correlated with tinnitus Visual Analog Scale (VAS) score (r = 0.485, p = 0.008).ConclusionOur preliminary study explored CBF pattern changes in unilateral SSNHL patients in auditory-related areas and non-auditory areas, suggesting that there may exist reduced attention and some sensory compensation in patients with SSNHL. These findings could advance our understanding of the potential pathophysiology of unilateral SSNHL.

Playing a significant role in electrochemical energy conversion and storage systems, heteroatom-doped transition metal oxides are key materials for oxygen-involving reactions. Herein, mesoporous surface-sulfurized Fe–Co3O4 nanosheets integrated with N/S co-doped graphene (Fe–Co3O4–S/NSG) were designed as composite bifunctional electrocatalysts for the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR). Compared with the Co3O4–S/NSG catalyst, it exhibited superior activity in the alkaline electrolytes by delivering an OER overpotential of 289 mV at 10 mA cm−2 and an ORR half-wave potential of 0.77 V vs. RHE. Additionally, Fe–Co3O4–S/NSG kept stable at 4.2 mA cm−2 for 12 h without significant attenuation to render robust durability. This work not only demonstrates the satisfactory effect of the transition-metal cationic modification represented by iron doping on the electrocatalytic performance of Co3O4, but it also provides a new insight on the design of OER/ORR bifunctional electrocatalysts for efficient energy conversion.

Background: Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson’s disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal storage disorder (LSD) genes and Chinese mainland PD.Methods: We explored the association between rare variants of 69 LSD genes and PD in 3,879 patients and 2,931 controls from Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) using next-generation sequencing, which were analyzed by using the optimized sequence kernel association test.Results: We identified the significant burden of rare putative LSD gene variants in Chinese mainland patients with PD. This association was robust in familial or sporadic early-onset patients after excluding the GBA variants but not in sporadic late-onset patients. The burden analysis of variant sets in genes of LSD subgroups revealed a suggestive significant association between variant sets in genes of sphingolipidosis deficiency disorders and familial or sporadic early-onset patients. In contrast, variant sets in genes of sphingolipidoses, mucopolysaccharidoses, and post-translational modification defect disorders were suggestively associated with sporadic late-onset patients. Then, SMPD1 and other four novel genes (i.e., GUSB, CLN6, PPT1, and SCARB2) were suggestively associated with sporadic early-onset or familial patients, whereas GALNS and NAGA were suggestively associated with late-onset patients.Conclusion: Our findings supported the association between LSD genes and PD and revealed several novel risk genes in Chinese mainland patients with PD, which confirmed the importance of lysosomal mechanisms in PD pathogenesis. Moreover, we identified the genetic heterogeneity in early-onset and late-onset of patients with PD, which may provide valuable suggestions for the treatment.

Autonomic dysfunction (AutD) is one of the non-motor symptoms (NMSs) in Parkinson’s disease (PD). To investigate the prevalence and clinical features of AutD in Chinese patients with PD, a large multicenter cohort of 2,556 individuals with PD were consecutively involved in the Parkinson’s Disease and Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) between January 1, 2017, and December 31, 2019. The assessment of AutD was performed using the Scale for Outcomes in Parkinson’s Disease for Autonomic Symptoms (SCOPA-AUT). The evaluation of motor symptoms and other NMSs were performed using well-established scales recommended by the Movement Disorder Society. We found that out of 2,556 patients with PD, 2,333 patients with PD (91.28%) had AutD. Compared with the group of patients with PD without AutD, the group of patients with PD with AutD had older age, older age of onset, longer disease duration, more severe motor symptoms, motor complications, and more frequent NMSs. As for partial correlation analysis, the total SCOPA-AUT score was significantly and positively associated with motor severity scales [Unified Parkinson’s Disease Rating Scale (UPDRS) total score] and some of the NMSs [Rapid Eye Movement Sleep Behavior Disorder Questionnaire (RBD), Epworth Sleepiness Scale, Hamilton Depression Scale], Fatigue Severity Scale, and Parkinson’s disease questionnaire. PD Sleep Scale was significantly and negatively correlated with AutD. With logistic regression analysis for potentially related factors, age, UPDRS total score, RBD, hyposmia, depression, and fatigue may be associated with PD with AutD. In conclusion, our multicenter cohort study reported the high prevalence of AutD in Chinese PD and revealed the associated factors of PD with AutD.

Objective: Hemifacial spasm (HFS) is a kind of motor disorder, and the striatum plays a significant role in motor function. The purpose of this study was to explore the alterations of the cortical-striatal network in HFS using resting-state functional magnetic resonance imaging (fMRI).Methods: The fMRI data of 30 adult patients with primary unilateral HFS (15 left-side and 15 right-side) and 30 healthy controls were collected. Six subregions of the striatum in each hemisphere were selected for functional connectivity (FC) analysis. One-sample t-test was used to analyze the intragroup FC of the HFS group and the control group. Two-sample t-test was used to compare the difference of FC between the two groups. The correlation between the abnormal FC and severity of HFS was evaluated by using the Spearman correlation analysis.Results: Compared with the controls, the striatal subregions had altered FC with motor and orbitofrontal cortex in patients with HFS. The altered FC between striatal subregions and motor cortex was correlated with the spasm severity in patients with HFS.Conclusion: The FC of the cortical-striatal network was altered in primary HFS, and these alterations were correlated with the severity of HFS. This study indicated that the cortical-striatal network may play different roles in the underlying pathological mechanism of HFS.

Background: Computed tomography plays an important role in the identification and characterization of thymomas. It has been mainly used during preoperative evaluation for clinical staging. However, the reliable prediction of histological risk types of thymomas based on CT imaging features requires further study. In this study, we developed and validated a nomogram based on CT imaging and included new indices for individualized preoperative prediction of the risk classification of thymomas.Methods: We conducted a retrospective, multicenter study that included 229 patients from two Chinese medical centers. All the patients underwent cross-sectional CT imaging within 2 weeks before surgery. The results of pathological assessments were retrieved from existing reports of the excised lesions. The tumor perimeter that contacted the lung (TPCL) was evaluated and a new quantitative indicator, the acute angle (AA) formed by adjacent lobulations, was measured. Two predictive models of risk classification were created using the least absolute shrinkage and selection operator (LASSO) method in a training cohort for features selection. The model with a smaller Akaike information criterion was then used to create an individualized imaging nomogram, which we evaluated regarding its prediction ability and clinical utility.Results: A new CT imaging-based model incorporating AA was developed and validated, which had improved predictive performance during risk classification of thymomas when compared with a model using traditional imaging predictors. The new imaging nomogram with AA demonstrated its clinical utility by decision curve analysis.Conclusions: Acute angle can improve the performance of a CT-based predictive model during the preoperative risk classification of thymomas and should be considered a new imaging marker for the evaluation and treatment of patients with thymomas. On the contrary, TPCL is not useful as a predictor for the risk classification of thymomas in this study.

Automatic segmentation of gastric tumor not only provides image-guided clinical diagnosis but also assists radiologists to read images and improve the diagnostic accuracy. However, due to the inhomogeneous intensity distribution of gastric tumors in CT scans, the ambiguous/missing boundaries, and the highly variable shapes of gastric tumors, it is quite challenging to develop an automatic solution. This study designs a novel 3D improved feature pyramidal network (3D IFPN) to automatically segment gastric tumors in computed tomography (CT) images. To meet the challenges of this extremely difficult task, the proposed 3D IFPN makes full use of the complementary information within the low and high layers of deep convolutional neural networks, which is equipped with three types of feature enhancement modules: 3D adaptive spatial feature fusion (ASFF) module, single-level feature refinement (SLFR) module, and multi-level feature refinement (MLFR) module. The 3D ASFF module adaptively suppresses the feature inconsistency in different levels and hence obtains the multi-level features with high feature invariance. Then, the SLFR module combines the adaptive features and previous multi-level features at each level to generate the multi-level refined features by skip connection and attention mechanism. The MLFR module adaptively recalibrates the channel-wise and spatial-wise responses by adding the attention operation, which improves the prediction capability of the network. Furthermore, a stage-wise deep supervision (SDS) mechanism and a hybrid loss function are also embedded to enhance the feature learning ability of the network. CT volumes dataset collected in three Chinese medical centers was used to evaluate the segmentation performance of the proposed 3D IFPN model. Experimental results indicate that our method outperforms state-of-the-art segmentation networks in gastric tumor segmentation. Moreover, to explore the generalization for other segmentation tasks, we also extend the proposed network to liver tumor segmentation in CT images of the MICCAI 2017 Liver Tumor Segmentation Challenge.

Tannins are important polyphenol compounds with different component proportions in different plant species. The plants in the Juglandaceae are rich in tannins, including condensed tannins and hydrolyzable tannins. In this study, we identified seven tannase genes (TAs) responsible for the tannin metabolism from walnut, pecan, and Chinese hickory, and three nut tree species in the Juglandaceae, which were divided into two groups. The phylogenetic and sequence analysis showed that TA genes and neighboring clade genes (TA-like genes) had similar sequences compared with other carboxylesterase genes, which may be the origin of TA genes produced by tandem repeat. TA genes also indicated higher expressions in leaf than other tissues and were quickly up-regulated at 3 h after leaf injury. During the development of the seed coat, the expression of the synthesis-related gene GGTs and the hydrolase gene TAs was continuously decreased, resulting in the decrease of tannin content in the dry sample of the seed coat of Chinese hickory. However, due to the reduction in water content during the ripening process, the tannin content in fresh sample increased, so the astringent taste was obvious at the mature stage. In addition, the CcGGTs’ expression was higher than CiGGTs in the initiation of development, but CcTAs continued to be down-regulated while CiTA2a and CiTA2b were up-regulated, which may bring about the significant differences in tannin content and astringent taste between Chinese hickory and pecan. These results suggested the crucial role of TAs in wound stress of leaves and astringent ingredient accumulation in seed coats of two nut tree species in the Juglandaceae.

ObjectivesThis study aimed to investigate whether radiomics classifiers from mammography can help predict tumor-infiltrating lymphocyte (TIL) levels in breast cancer.MethodsData from 121 consecutive patients with pathologically-proven breast cancer who underwent preoperative mammography from February 2018 to May 2019 were retrospectively analyzed. Patients were randomly divided into a training dataset (n = 85) and a validation dataset (n = 36). A total of 612 quantitative radiomics features were extracted from mammograms using the Pyradiomics software. Radiomics feature selection and radiomics classifier were generated through recursive feature elimination and logistic regression analysis model. The relationship between radiomics features and TIL levels in breast cancer patients was explored. The predictive capacity of the radiomics classifiers for the TIL levels was investigated through receiver operating characteristic curves in the training and validation groups. A radiomics score (Rad score) was generated using a logistic regression analysis method to compute the training and validation datasets, and combining the Mann–Whitney U test to evaluate the level of TILs in the low and high groups.ResultsAmong the 121 patients, 32 (26.44%) exhibited high TIL levels, and 89 (73.56%) showed low TIL levels. The ER negativity (p = 0.01) and the Ki-67 negative threshold level (p = 0.03) in the low TIL group was higher than that in the high TIL group. Through the radiomics feature selection, six top-class features [Wavelet GLDM low gray-level emphasis (mediolateral oblique, MLO), GLRLM short-run low gray-level emphasis (craniocaudal, CC), LBP2D GLRLM short-run high gray-level emphasis (CC), LBP2D GLDM dependence entropy (MLO), wavelet interquartile range (MLO), and LBP2D median (MLO)] were selected to constitute the radiomics classifiers. The radiomics classifier had an excellent predictive performance for TIL levels both in the training and validation sets [area under the curve (AUC): 0.83, 95% confidence interval (CI), 0.738–0.917, with positive predictive value (PPV) of 0.913; AUC: 0.79, 95% CI, 0.615–0.964, with PPV of 0.889, respectively]. Moreover, the Rad score in the training dataset was higher than that in the validation dataset (p = 0.007 and p = 0.001, respectively).ConclusionRadiomics from digital mammograms not only predicts the TIL levels in breast cancer patients, but can also serve as non-invasive biomarkers in precision medicine, allowing for the development of treatment plans.

This study adopted diffusion tensor imaging to detect alterations in the diffusion parameters of the white matter fiber in Alzheimer’s disease (AD) and used quantitative susceptibility mapping to detect changes in magnetic susceptibility. However, whether the changes of susceptibility values due to excessive iron in the basal ganglia have correlations with the alterations of the diffusion properties of the white matter in patients with AD are still unknown. We aim to investigate the correlations among magnetic susceptibility values of the basal ganglia, diffusion indexes of the white matter, and cognitive function in patients with AD. Thirty patients with AD and nineteen healthy controls (HCs) were recruited. Diffusion indexes of the whole brain were detected using tract-based spatial statistics. The caudate nucleus, putamen, and globus pallidus were selected as regions of interest, and their magnetic susceptibility values were measured. Compared with HCs, patients with AD showed that there were significantly increased axial diffusivity (AxD) in the internal capsule, superior corona radiata (SCR), and right anterior corona radiata (ACR); increased radial diffusivity (RD) in the right anterior limb of the internal capsule, ACR, and genu of the corpus callosum (GCC); and decreased fractional anisotropy (FA) in the right ACR and GCC. The alterations of RD values, FA values, and susceptibility values of the right caudate nucleus in patients with AD were correlated with cognitive scores. Besides, AxD values in the right internal capsule, ACR, and SCR were positively correlated with the magnetic susceptibility values of the right caudate nucleus in patients with AD. Our findings revealed that the magnetic susceptibility of the caudate nucleus may be an MRI-based biomarker of the cognitive dysfunction of AD and abnormal excessive iron distribution in the basal ganglia had adverse effects on the diffusion properties of the white matter.

ObjectivesAnterior mediastinal disease is a common disease in the chest. Computed tomography (CT), as an important imaging technology, is widely used in the diagnosis of mediastinal diseases. Doctors find it difficult to distinguish lesions in CT images because of image artifact, intensity inhomogeneity, and their similarity with other tissues. Direct segmentation of lesions can provide doctors a method to better subtract the features of the lesions, thereby improving the accuracy of diagnosis.MethodAs the trend of image processing technology, deep learning is more accurate in image segmentation than traditional methods. We employ a two-stage 3D ResUNet network combined with lung segmentation to segment CT images. Given that the mediastinum is between the two lungs, the original image is clipped through the lung mask to remove some noises that may affect the segmentation of the lesion. To capture the feature of the lesions, we design a two-stage network structure. In the first stage, the features of the lesion are learned from the low-resolution downsampled image, and the segmentation results under a rough scale are obtained. The results are concatenated with the original image and encoded into the second stage to capture more accurate segmentation information from the image. In addition, attention gates are introduced in the upsampling of the network, and these gates can focus on the lesion and play a role in filtering the features. The proposed method has achieved good results in the segmentation of the anterior mediastinal.ResultsThe proposed method was verified on 230 patients, and the anterior mediastinal lesions were well segmented. The average Dice coefficient reached 87.73%. Compared with the model without lung segmentation, the model with lung segmentation greatly improved the accuracy of lesion segmentation by approximately 9%. The addition of attention gates slightly improved the segmentation accuracy.ConclusionThe proposed automatic segmentation method has achieved good results in clinical data. In clinical application, automatic segmentation of lesions can assist doctors in the diagnosis of diseases and may facilitate the automated diagnosis of illnesses in the future.

Background and Purpose: The purpose of this study was to explore the changes of iron level using quantitative susceptibility mapping (QSM) in the bilateral basal ganglia region in middle cerebral artery occlusion (MCAO) patients with long-term ischemia.Methods: Twenty-seven healthy controls and nine patients with MCAO were recruited, and their QSM images were obtained. The bilateral caudate nucleus (Cd), putamen (Pt), and globus pallidus (Gp) were selected as the regions of interest (ROIs). Susceptibility values of bilateral ROIs were calculated and compared between the affected side and unaffected side in patients with MCAO and between patients with MCAO and healthy controls. In addition, receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic capability of susceptibility values in differentiating healthy controls and patients with MCAO by the area under the curve (AUC).Results: The susceptibility values of bilateral Cd were asymmetric in healthy controls; however, this asymmetry disappeared in patients with MCAO. In addition, compared with healthy controls, the average susceptibility values of the bilateral Pt in patients with MCAO were increased (P < 0.05), and the average susceptibility value of the bilateral Gp was decreased (P < 0.05). ROC curves showed that the susceptibility values of the Pt and Gp had a larger AUC (AUC = 0.700 and 0.889, respectively).Conclusion: As measured by QSM, the iron levels of the bilateral basal ganglia region were significantly changed in patients with MCAO. Iron dyshomeostasis in the basal ganglia region might be involved in the pathophysiological process of middle cerebral artery stenosis and occlusion. These findings may provide a novel insight to profoundly address the pathophysiological mechanisms of MCAO.

Background and Purpose: Recent evidence shows that the fractional motion (FM) model may be a more appropriate model for describing the complex diffusion process of water in brain tissue and has shown to be beneficial in clinical applications of Alzheimer's disease (AD). However, the FM model averaged the anomalous diffusion parameter values, which omitted the impacts of anisotropy. This study aimed to investigate the potential feasibility of anisotropy of anomalous diffusion using the FM model for distinguishing and grading AD patients.Methods: Twenty-four patients with AD and 11 matched healthy controls were recruited, diffusion MRI was obtained from all participants and analyzed using the FM model. Generalized fractional anisotropy (gFA), an anisotropy metric, was introduced and the gFA values of FM-related parameters, Noah exponent (α) and the Hurst exponent (H), were calculated and compared between the healthy group and AD group and between the mild AD group and moderate AD group. The receiver-operating characteristic (ROC) analysis and the multivariate logistic regression analysis were used to assess the diagnostic performances of the anisotropy values and the directionally averaged values.Results: The gFA(α) and gFA(H) values of the moderate AD group were higher than those of the mild AD group in left hippocampus. The gFA(α) value of the moderate AD group was significantly higher than that of the healthy control group in both the left and right hippocampus. The gFA(ADC) values of the moderate AD group were significantly lower than those of the mild AD group and healthy control group in the right hippocampus. Compared with the gFA(α), gFA(H), α, and H, the ROC analysis showed larger areas under the curves for combination of α + gFA(α) and the combination of H + gFA(H) in differentiating the mild AD and moderate AD groups, and larger area under the curves for combination of α + gFA(α) in differentiating the healthy controls and AD groups.Conclusion: The anisotropy of anomalous diffusion could significantly differentiate and grade patients with AD, and the diagnostic performance was improved when the anisotropy metric was combined with commonly used directionally averaged values. The utility of anisotropic anomalous diffusion may provide novel insights to profoundly understand the neuropathology of AD.

Most diffusion magnetic resonance imaging (dMRI) techniques use the mono-exponential model to describe the diffusion process of water in the brain. However, the observed dMRI signal decay curve deviates from the mono-exponential form. To solve this problem, the fractional motion (FM) model has been developed, which is regarded as a more appropriate model for describing the complex diffusion process in brain tissue. It is still unclear in the identification and classification of Alzheimer’s disease (AD) patients using the FM model. The purpose of this study was to investigate the potential feasibility of FM model for differentiating AD patients from healthy controls and grading patients with AD. Twenty-four patients with AD and 11 healthy controls were included. The left and right hippocampus were selected as regions of interest (ROIs). The apparent diffusion coefficient (ADC) values and FM-related parameters, including the Noah exponent (α), the Hurst exponent (H), and the memory parameter (μ=H−1/α), were calculated and compared between AD patients and healthy controls and between mild AD and moderate AD patients using a two-sample t-test. The correlations between FM-related parameters α, H, μ, and ADC values and the cognitive functions assessed by mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) scales were investigated using Pearson partial correlation analysis in patients with AD. The receiver-operating characteristic analysis was used to assess the differential performance. We found that the FM-related parameter α could be used to distinguish AD patients from healthy controls (P < 0.05) with greater sensitivity and specificity (left ROI, 0.917 and 0.636; right ROI, 0.917 and 0.727) and grade AD patients (P < 0.05) showed higher sensitivity and specificity (right ROI, 0.917, 0.75). The α was found to be positively correlated with MMSE (P < 0.05) and MoCA (P < 0.05) scores in patients with AD, indicating that the α values in the bilateral hippocampus were a potential MRI-based biomarker of disease severity in AD patients. This novel diffusion model may be useful for further understanding neuropathologic changes in patients with AD.

Objectives: Tumor-infiltrating lymphocytes (TILs) have been identified as a significant prognostic indicator of response to neoadjuvant therapy and immunotherapy for triple-negative breast cancer (TNBC) patients. Herein, we aim to assess the association between TIL levels and mammographic features in TNBC patients.Methods: Forty-three patients with surgically proven TNBC who underwent preoperative mammography from January 2018 to December 2018 were recruited. Pyradiomics software was used to extract 204 quantitative radiomics features, including morphologic, grayscale, and textural features, from the segmented lesion areas. The correlation between radiological characteristics and TIL levels was evaluated by screening the most statistically significant radiological features using Mann–Whitney U-test and Pearson correlation coefficient. The patients were divided into two groups based on tumor TIL levels: patients with TIL levels

The self-face processing advantage (SPA) refers to the research finding that individuals generally recognize their own face faster than another’s face; self-face also elicits an enhanced P3 amplitude compared to another’s face. It has been suggested that social evaluation threats could weaken the SPA and that self-esteem could be regarded as a threat buffer. However, little research has directly investigated the neural evidence of how self-esteem modulates the social evaluation threat to the SPA. In the current event-related potential study, 27 healthy Chinese undergraduate students were primed with emotional faces (angry, happy, or neutral) and were asked to judge whether the target face (self, friend, and stranger) was familiar or unfamiliar. Electrophysiological results showed that after priming with emotional faces (angry and happy), self-face elicited similar P3 amplitudes to friend-face in individuals with low self-esteem, but not in individuals with high self-esteem. The results suggest that as low self-esteem raises fears of social rejection and exclusion, priming with emotional faces (angry and happy) can weaken the SPA in low self-esteem individuals but not in high self-esteem individuals.

Assembling Ln3+(HPBAn) (Ln = Eu or Tb, HPBA = N-(2-pyridinyl)benzoylacetamide) in the cavities of zeolite Y (ZY) via the “ship-in-a-bottle„ strategy leads to the formation of novel luminescent composite, Ln(HPBAn)@ZY, whose luminescence can be easily modulated by ammonia on the basis of the energy level variation of HPBA after deprotonation process. Additionally the bimetallic complex doping sample, Eu0.5Tb0.5(HPBAn)@ZY, show great potential as self-referencing luminescent sensor for detecting low ammonia concentration of 10−12⁻0.25 wt%.

In this study, a directly irradiated, milli-scale chemical reactor with a simple nickel catalyst was designed for dry reforming of methane for syngas. A milli-scale reactor was used to facilitate rapid heating, which is conducive to combating thermal transience caused by intermittent solar energy, as well as reducing startup times. Milli-scale reactors also allow for a distributed and modular process to produce chemicals on a more local scale. In this setup, the catalyst involved in the reaction is located directly in the focal area of the solar simulator, resulting in rapid heating. The effects of mean residence time and temperature on conversion and energy efficiency were tested. The process, which is intended to store thermal energy as chemical enthalpy, achieved 10% thermal-to-chemical energy conversion efficiency at a mean residence time of 0.028 s, temperature of 1000 °C, and molar feed ratio of 1:1 CO2:CH4. A significant portion of the thermal energy input into the reactor was directed toward sensible heating of the feed gas. Thus, this technology has potential to achieve solar-to-chemical efficiency with the integration of recuperative heat exchange.