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IntroductionSustained hyperglycemia causes glucotoxicity, which has been regarded as a contributor to hepatocyte damage in type 2 diabetes (T2D) and its metabolic comorbidities. Honokiol is a natural biphenolic component derived from the dietary supplement Magnolia officinalis extract. This study aimed to investigate the effects of honokiol on glucose metabolism disorders and oxidative stress in hepatocytes and the underlying mechanisms.MethodsHepG2 cells were treated with glucosamines (18 mM) to induce glucotoxicity as a diabetic complication model in vitro.Results and discussionHonokiol significantly increased glucose consumption, elevated 2-NBDG uptake, and promoted GLUT2 translocation to the plasma membrane in glucosamine-treated HepG2 cells, indicating that honokiol ameliorates glucose metabolism disorders. Furthermore, glucosamine-induced ROS accumulation and loss of mitochondrial membrane potential were markedly reduced by honokiol, suggesting that honokiol alleviated glucotoxicity-induced oxidative stress. These effects were largely abolished by compound C, an AMPK inhibitor, suggesting an AMPK activation-dependent manner of honokiol function in promoting glucose metabolism and mitigating oxidative stress. Molecular docking results revealed that honokiol could interact with the amino acid residues (His151, Arg152, Lys243, Arg70, Lys170, and His298) in the active site of AMPK. These findings provide new insights into the antidiabetic effect of honokiol, which may be a promising agent for the prevention and treatment of T2D and associated metabolic comorbidities.

The mechanism(s) of immune checkpoint inhibitor (ICI)-induced myasthenia gravis (MG), an immune-related adverse event (irAE) that is fatal and limits subsequent ICI use, remain unexplored. Here, through comparative genomic analysis, we identified a pathogenic p.S467C germline variant in SLC22A5 in a thymoma case with ICI-induced MG, which was found to be associated with fatty acid oxidation through its regulation on L-carnitine levels. Remarkably, ICI rechallenge with L-carnitine pretreatment led to durable response without MG-related symptoms. Thus, we provide the first clinical evidence of genetic test-directed irAE management, which integrates individualized ICI treatment into the evolving paradigm of cancer management.

Background: Genetics plays an important role in progressive supranuclear palsy (PSP) and remains poorly understood. A detailed literature search identified 19 PSP-associated genes: MAPT, LRRK2, LRP10, DCTN1, GRN, NPC1, PARK, TARDBP, TBK1, BSN, GBA, STX6, EIF2AK3, MOBP, DUSP10, SLCO1A2, RUNX2, CXCR4, and APOE. To date, genetic studies on PSP have focused on Caucasian population. The gaps in PSP genetic study on East Asian populations need to be filled. Methods: Exon and flanking regions of the PSP-associated genes were sequenced in 104 patients with PSP and 488 healthy controls. Common variant-based association analysis and gene-based association tests of rare variants were performed using PLINK 1.9 and the sequence kernel association test-optimal, respectively. Additionally, the association of APOE and MAPT genotypes with PSP was evaluated. The above association analyses were repeated among probable PSP patients. Finally, PLINK 1.9 was used to test variants associated with the onset age of PSP. Results: A rare non-pathogenic variant of MAPT (c.425C > T,p.A142V) was detected in a PSP patient. No common variants were significantly associated with PSP. In both the rare-variant and the rare-damaging-variant groups, the combined effect for GBA reached statistical significance (p = 1.43 × 10−3, p = 4.98 × 10−4). The result between APOE, MAPT genotypes and PSP risk were inconsistent across all PSP group and probably PSP group. Conclusions: The pathogenic variant in MAPT were uncommon in PSP patients. Moreover, GBA gene was likely to increase the risk of PSP, and GBA-associated diseases were beyond α-synucleinopathies. The association between APOE, MAPT and PSP is still unclear among the non-Caucasian population.

Abstract Background Biallelic HTRA1 pathogenic variants are associated with autosomal recessive cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Recent studies have indicated that heterozygous HTRA1 variants are related to autosomal dominant hereditary cerebral small vessel disease (CSVD). However, few studies have assessed heterozygous HTRA1 carriers or the genotype–phenotype correlation. Methods The clinical data of two unrelated Chinese Han families with CSVD were collected. Panel sequencing was used to search for pathogenic genes, Sanger sequencing was used for verification, three‐dimensional protein models were constructed, and pathogenicity was analyzed. Published HTRA1‐related phenotypes included in PubMed up to September 2021 were extensively reviewed, and the patients' genetic and clinical characteristics were summarized. Results We report a novel heterozygous variant c.920T>C p.L307P in the HTRA1, whose main clinical and neuroimaging phenotypes are stroke and gait disturbance. We report another patient with the previously reported pathogenic variant HTRA1 c.589C>T p.R197X characterized by early cognitive decline. A literature review indicated that compared with CARASIL, HTRA1‐related autosomal dominant hereditary CSVD has a later onset age, milder clinical symptoms, fewer extraneurological symptoms, and slower progression, indicating a milder CARASIL phenotype. In addition, HTRA1 heterozygous variants were related to a higher proportion of vascular risk factors (p

Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with aging, environmental, and genetic factors. Amyloid protein precursor (APP) is a known pathogenic gene for familial Alzheimer’s disease (FAD), and now more than 70 APP mutations have been reported, but the genotype-phenotype correlation remains unclear. In this study, we collected clinical data from patients carrying APP mutations defined as pathogenic/likely pathogenic according to the American college of medical genetics and genomics (ACMG) guidelines. Then, we reanalyzed the clinical characteristics and identified genotype-phenotype correlations in APP mutations. Our results indicated that the clinical phenotypes of APP mutations are generally consistent with typical AD despite the fact that they show more non-demented symptoms and neurological symptoms. We also performed genotype-phenotype analysis according to the difference in APP processing caused by the mutations, and we found that there were indeed differences in onset age, behavioral and psychological disorders of dementia (BPSD) and myoclonus.

BackgroundThe Chinese version of the Mini-Mental State Examination (MMSE-C) and the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) are the most commonly used scales to screen for Alzheimer’s disease (AD) among Chinese patients; however, their consistency varies according to populations and languages. Equivalent conversion of MMSE-C and MoCA-BJ scores is important for meta-analysis.Materials and methodsMMSE-C and MoCA-BJ scoring were performed on the enrolled patients with AD (n = 332). Consistency analysis of MMSE-C and MoCA-BJ scores of patients in the conversion groups was performed. The circle-arc method was used to convert the MMSE-C scores of the conversion groups into MoCA-BJ scores, and the conversion formula was generated. The MMSE-C data of the verification group was converted to MoCA-BJ according to the formula, and the consistency analysis of the original MoCA-BJ of the verification group and the converted MoCA-BJ was performed to verify the conversion model.ResultsThe results of the consistency analysis of MMSE-C and MoCA-BJ in group A showed that the correlation coefficients of the total group, high education years subgroup, medium education years subgroup, and low education years subgroup were 0.905 (P < 0.001), 0.874 (P < 0.001), 0.949 (P < 0.001), and 0.874 (P < 0.001), respectively, with high consistency and statistical significance. After applying the circle-arc method for equivalent conversion, the consistency analysis results of the original and the converted MoCA-BJ of the patients in group B of the total group, high education years subgroup, medium education years subgroup, and low education years subgroup were 0.891 (P < 0.001), 0.894 (P < 0.001), 0.781 (P < 0.001), 0.909 (P < 0.001), respectively, with high consistency and statistical significance.ConclusionWe established and validated a model of MMSE-C and MoCA-BJ score conversion for Chinese patients with AD using the circle-arc method. This model could be useful for multi-centers clinical trials and meta-analysis.

This work is developed to improve the current quality of e-commerce logistics services. From the perspective of multiple consumer psychology, based on e-commerce, consumer psychology, and other related theories, vegetable e-commerce B is selected as the research object. The commodity quality, accuracy, and timeliness of commodity distribution and other factors of e-commerce B are discussed through questionnaire survey. Then, according to customers’ opinions about “e-commerce B’s distribution and professional aspects that need to be improved,” the research is conducted. Finally, the direction of follow-up optimization is proposed from four different perspectives of multiple consumption psychology. The research results show that more than 89% of the surveyed customers believe that e-commerce B does a good job in terms of commodity quality, accuracy, and timeliness of commodity distribution, and has a high level of logistics service. However, 26.34% of customers hope that e-commerce B can strengthen the protection of personal privacy, 24.97% hope that the platform can add “delay insurance” for goods, and 39.54% hope that the logistics information of purchased goods can be updated in real time. Therefore, e-commerce B needs to be optimized and improved continuously in the future development. Therefore, research on the optimization of logistics service quality of e-commerce is performed under multiple consumption psychology, which provides certain help for the rapid development of subsequent e-commerce.

BackgroundThe incidence rate of prostate cancer is increasing rapidly. This study aims to explore the gene-associated mechanism of prostate cancer biochemical recurrence (BCR) after radical prostatectomy and to construct a biochemical recurrence of prostate cancer prognostic model.MethodsThe DEseq2 R package was used for the differential expression of mRNA. The ClusterProfiler R package was used to analyze the functional enrichment of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to explore related mechanisms. The Survival, Survminer, and My.stepwise R packages were used to construct the prognostic model to predict the biochemical recurrence-free probability. The RMS R package was used to draw the nomogram. For evaluating the prognostic model, the timeROC R package was used to draw the time-dependent ROC curve (receiver operating characteristic curve).ResultTo investigate the association between mRNA and prostate cancer, we performed differential expression analysis on the TCGA (The Cancer Genome Atlas) database. Seven protein-coding genes (VWA5B2, ARC, SOX11, MGAM, FOXN4, PRAME, and MMP26) were picked as independent prognostic genes by regression analysis. Based on their Cox coefficient, a risk score formula was proposed. According to the risk scores, patients were divided into high- and low-risk groups based on the median score. Kaplan–Meier plot curves showed that the low-risk group had a better biochemical recurrence-free probability compared to the high-risk group. The 1-year, 3-year, and 5-year AUCs (areas under the ROC curve) of the model were 77%, 81%, and 86%, respectively. In addition, we built a nomogram based on the result of multivariate Cox regression analysis. Furthermore, we select the GSE46602 dataset as our external validation. The 1-year, 3-year, and 5-year AUCs of BCR-free probability were 83%, 82%, and 80%, respectively. Finally, the levels of seven genes showed a difference between PRAD tissues and adjacent non-tumorous tissues.ConclusionsThis study shows that establishing a biochemical recurrence prediction prognostic model comprising seven protein-coding genes is an effective and precise method for predicting the progression of prostate cancer.

Abstract Neurodegenerative dementias are a group of diseases with highly heterogeneous pathology and complicated etiology. There exist potential genetic component overlaps between different neurodegenerative dementias. Here, 1795 patients with neurodegenerative dementias from South China were enrolled, including 1592 with Alzheimer’s disease (AD), 110 with frontotemporal dementia (FTD), and 93 with dementia with Lewy bodies (DLB). Genes targeted sequencing analysis were performed. According to the American College of Medical Genetics (ACMG) guidelines, 39 pathogenic/likely pathogenic (P/LP) variants were identified in 47 unrelated patients in 14 different genes, including PSEN1, PSEN2, APP, MAPT, GRN, CHCHD10, TBK1, VCP, HTRA1, OPTN, SQSTM1, SIGMAR1, and abnormal repeat expansions in C9orf72 and HTT. Overall, 33.3% (13/39) of the variants were novel, the identified P/LP variants were seen in 2.2% (35/1592) and 10.9% (12/110) of AD and FTD cases, respectively. The overall molecular diagnostic rate was 2.6%. Among them, PSEN1 was the most frequently mutated gene (46.8%, 22/47), followed by PSEN2 and APP. Additionally, the age at onset of patients with P/LP variants (51.4 years), ranging from 30 to 83 years, was ~10 years earlier than those without P/LP variants (p

Although acoustic and optical tweezers are widely used, it is challenging to create a 3D trap with a simple set-up. Here, acoustic vortex streaming is combined with radiation force to realise 3D trapping of particles in a fluid.

Abstract Background Lewy body dementia (LBD), consisting of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), is the second most common type of neurodegenerative dementia in older people. The current study aimed to investigate the clinical characteristics of LBD in Chinese memory clinics. Methods A total of 8405 dementia medical records were reviewed, revealing 455 patients with LBD. Demographic data, neuropsychological scores, and the scale for Medial Temporal lobe Atrophy (MTA) were then analyzed from nine memory clinics in the China Lewy Body Disease Collaborative Alliance. Results The clinical proportion of LBD among the subjects and among all dementia types was 5.4% (4.9–5.9%) and 7.3% (6.7–8.0%), respectively, with a mean onset age of 68.6 ± 8.4 years. Patients with DLB comprised 5.6% (n = 348, age of onset 69.1 ± 8.3), while PDD comprised 1.7% (n = 107, age of onset 66.7 ± 8.8) of all dementia cases. There were slightly more males than females with DLB (n = 177, 50.9%) and PDD (n = 62, 57.9%). Patients with DLB had a poorer performance compared to those with PDD on the MMSE (16.8 ± 7.1 vs. 19.5 ± 5.7, p = 0.001), the MoCA (11.4 ± 6.6 vs. 14.0 ± 5.8, p

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease, the clinical manifestations of which are complex and easily misdiagnosed. NIID clinical characteristics are varied, affecting the central and peripheral nervous systems and autonomic nerves. In this study, we present an NIID case with both stroke-like onset and encephalitic attacks, which is a rare case report. Case presentation A 68-year-old Chinese female presented with sudden aphasia and limb hemiplegia as the first symptoms, as well as fever, cognitive impairment and mental irritability from encephalitic attacks. During hospitalization, a brain magnetic resonance imaging (MRI) examination detected high signal intensity from diffusion-weighted imaging (DWI) of the bilateral frontal grey matter-white matter junction. Electrophysiological tests revealed the main site of injury was at the myelin sheath in the motor nerves. A skin biopsy revealed eosinophilic spherical inclusion bodies in the nuclei of small sweat gland cells, fibroblasts and fat cells, whilst immunohistochemistry revealed that p62 and ubiquitin antibodies were positive. From genetic analyses, the patient was not a carrier of the fragile X mental retardation 1 (FMR1) permutation, but repeated GGC sequences in the NOTCH2NLC gene confirmed an NIID diagnosis. Through antipsychotic and nutritional support therapy, the patient’s symptoms were completely relieved within 3 weeks. Conclusions This report of an NIID case with both stroke-like onset and encephalitic attacks provides new information for NIID diagnoses, and a comprehensive classification of clinical characteristics.

Dysregulation of XIAP has been shown to affect the progression of a variety of cancers, including lung adenocarcinoma (LUAD). However, the function and mechanisms of XIAP in lung adenocarcinoma with brain metastasis (LUAD-BM) remains poorly understood. In this study, we analyzed the differential mRNA of 58 lung adenocarcinomas samples and 28 lung adenocarcinomas with brain metastases in GEO database. 191 differentially expressed mRNAs were significantly associated with immune response, the proliferation of the immune cell, cell-cell adhesion. Subsequent analyzed by lasso and SVM found that XIAP was significantly elevated in LUAD-BM and significantly associated with LUAD grade and metastasis. Then we constructed a molecular regulatory network of ncRNA-miRNA-mRNA ceRNA by Cystoscope based on the correlation obtained from Starbase. It was found that SBF2-AS1 or RUNDC3A-AS1, has-miR-338-3p and XIAP may have a regulatory relationship. Furthermore, we also initially found that XIAP was closely correlation with T cells, B cells, Mast cells, macrophages, and dendritic cells. In conclusion, we found that XIAP was significantly higher expressed in LUAD-BM compared with LUAD without brain metastasis, suggesting that XIAP may play an important role in the future prediction and clinical treatment of LUAD-BM.

Summary: Background: COVID-19 vaccination is recommended for patients with multiple sclerosis (pwMS), while disease-modifying therapies (DMTs) may influence the efficacy of SARS-CoV-2 vaccines in this population. Thus, we conducted a meta-analysis to evaluate the impact of DMTs on immune response to COVID-19 vaccines in pwMS. Methods: Literature search from December 1, 2019 to March 31, 2022 was performed in PubMed, MedRxiv, Embase and Cochrane Library. The risk of impaired response to vaccination in pwMS receiving DMTs was estimated in odds ratios (ORs) using random-effects method. Findings: A total of 48 studies comprising 6860 pwMS were included. Overall, pwMS with anti-CD20 (OR=0.02, 95% CI: 0.01-0.03) and sphingosine-1-phosphate receptor modulator (S1PRM) (OR=0.03, 95% CI: 0.01-0.06) treatments had attenuated serologic response after full vaccination compared with those without DMTs. Additionally, pwMS vaccinated within six months since last anti-CD20 therapy were at significantly higher risk of blunted response compared with those receiving anti-CD20 therapy more than six months prior to vaccination (P = 0.001). We found no significant associations between other treatments (including IFN-β, GA, DMF, TERI, NTZ, CLAD, and ALE) and humoral response to SARS-CoV-2 vaccines in pwMS. As for T-cell response, no significant difference was found between pwMS on anti-CD20 and those without DMTs after vaccination, while S1PRM was marginally associated with impaired cellular response (P = 0.03). Interpretation: Our findings suggested that routine serological monitoring may be required for pwMS on anti-CD20 and S1PRMs after SARS-CoV-2 vaccination and highlighted the benefits of a booster dose. The effect of cellular response and optimal interval from last anti-CD20 treatment to vaccination should be further addressed. Funding: This study was supported by Natural Science Foundation of Shanghai (21ZR1433000).

The relationships between multiple visual rating scales based on structural magnetic resonance imaging (sMRI) with disease severity and cerebrospinal fluid (CSF) biomarkers in patients with Alzheimer’s disease (AD) were ambiguous. In this study, a total of 438 patients with clinically diagnosed AD were recruited. All participants underwent brain sMRI scan, and medial temporal lobe atrophy (MTA), posterior atrophy (PA), global cerebral atrophy-frontal sub-scale (GCA-F), and Fazekas rating scores were visually evaluated. Meanwhile, disease severity was assessed by neuropsychological tests such as the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating (CDR). Among them, 95 patients were tested for CSF core biomarkers, including Aβ1–42, Aβ1–40, Aβ1–42/Aβ1–40, p-tau, and t-tau. As a result, the GCA-F and Fazekas scales showed positively significant correlations with onset age (r = 0.181, p < 0.001; r = 0.411, p < 0.001, respectively). Patients with late-onset AD (LOAD) showed higher GCA-F and Fazekas scores (p < 0.001, p < 0.001). With regard to the disease duration, the MTA and GCA-F were positively correlated (r = 0.137, p < 0.05; r = 0.106, p < 0.05, respectively). In terms of disease severity, a positively significant association emerged between disease severity and the MTA, PA GCA-F, and Fazekas scores (p < 0.001, p < 0.001, p < 0.001, p < 0.05, respectively). Moreover, after adjusting for age, gender, and APOE alleles, the MTA scale contributed to moderate to severe AD in statistical significance independently by multivariate logistic regression analysis (p < 0.05). The model combining visual rating scales, age, gender, and APOE alleles showed the best performance for the prediction of moderate to severe AD significantly (AUC = 0.712, sensitivity = 51.5%, specificity = 84.6%). In addition, we observed that the MTA and Fazekas scores were associated with a lower concentration of Aβ1–42 (p < 0.031, p < 0.022, respectively). In summary, we systematically analyzed the benefits of multiple visual rating scales in predicting the clinical status of AD. The visual rating scales combined with age, gender, and APOE alleles showed best performance in predicting the severity of AD. MRI biomarkers in combination with CSF biomarkers can be used in clinical practice.

ObjectiveThe natural history of spinocerebellar ataxia type 3 (SCA3) has been reported in several populations and shows heterogeneity in progression rate and affecting factors. However, it remains unexplored in the population of Mainland China. This study aimed to identify the disease progression rate and its potential affecting factors in patients with SCA3 in Mainland China.Participants and MethodsWe enrolled patients with genetically confirmed SCA3 in Mainland China. Patients were seen at three visits, i.e., baseline, 1 year, and 2 years. The primary outcome was the Scale for the Assessment and Rating of Ataxia (SARA), and the secondary outcomes were the Inventory of Non-Ataxia Signs (INAS) as well as the SCA Functional Index (SCAFI).ResultsBetween 1 October 2015, and 30 September 2016, we enrolled 263 patients with SCA3. We analyzed 247 patients with at least one follow-up visit. The annual progression rate of SARA was 1.49 points per year (SE 0.08, 95% confidence interval [CI] 1.33–1.65, p < 0.0001). The annual progression rates of INAS and SCAFI were 0.56 points per year (SE 0.05, 95% CI 0.47–0.66, p < 0.001) and −0.30 points per year (SE 0.01, 95% CI −0.33∼-0.28, p < 0.001), respectively. Faster progression in SARA was associated with longer length of the expanded allele of ATXN3 (p < 0.0001); faster progression in INAS was associated with lower INAS at baseline (p < 0.0001); faster decline in SCAFI was associated with shorter length of the normal allele of ATXN3 (p = 0.036) and higher SCAFI at baseline (p < 0.0001).ConclusionOur results provide quantitative data on the disease progression of patients with SCA3 in Mainland China and its corresponding affecting factors, which could facilitate the sample size calculation and patient stratification in future clinical trials.Trial RegistrationThis study was registered with Chictr.org on 15 September 2015, number ChiCTR-OOC-15007124.

It has been well documented that the auditory system in the superior temporal cortex is responsible for processing basic auditory sound features, such as sound frequency and intensity, while the prefrontal cortex is involved in higher-order auditory functions, such as language processing and auditory episodic memory. The temporal auditory cortex has vast forward anatomical projections to the prefrontal auditory cortex, connecting with the lateral, medial, and orbital parts of the prefrontal cortex. The connections between the auditory cortex and the prefrontal cortex thus help in localizing, recognizing, and comprehending external auditory inputs. In addition, the medial prefrontal cortex (MPFC) is believed to be a core region of episodic memory retrieval and is one of the most important regions in the default mode network (DMN). However, previous neural evidence with regard to the comparison between basic auditory processing and auditory episodic memory retrieval mainly comes from fMRI studies. The specific neural networks and the corresponding critical frequency bands of neuronal oscillations underlying the two auditory functions remain unclear. In the present study, we reported results of direct cortical stimulations during stereo-electro-encephalography (SEEG) recording in a patient with drug-resistant epilepsy. Electrodes covered the superior temporal gyrus, the operculum and the insula cortex of bilateral hemispheres, the prefrontal cortex, the parietal lobe, the anterior and middle cingulate cortex, and the amygdala of the left hemisphere. Two types of auditory hallucinations were evoked with direct cortical stimulations, which were consistent with the habitual seizures. The noise hallucinations, i.e., “I could hear buzzing noises in my head,” were evoked with the stimulation of the superior temporal gyrus. The episodic memory hallucinations “I could hear a young woman who was dressed in a red skirt saying: What is the matter with you?,” were evoked with the stimulation of MPFC. The patient described how she had met this young woman when she was young and that the woman said the same sentence to her. Furthermore, by analyzing the high gamma power (HGP) induced by direct electrical stimulation, two dissociable neural networks underlying the two types of auditory hallucinations were localized. Taken together, the present results confirm the hierarchical processing of auditory information by showing the different involvements of the primary auditory cortex vs. the prefrontal cortex in the two types of auditory hallucinations.

Objectives To investigate the current and intended future use of dental dams (DDs) and attitudes regarding DD use among final-year dental students at two levels (undergraduate and college) in dental schools in Chongqing, China.Design A cross-sectional study based on a questionnaire was conducted from June to July 2021.Setting Chongqing Medical University (CQMU, undergraduate level) and Chongqing Three Gorges Medical College (CQTGMC, junior college level).Participants A total of 245 final-year dental students.Main outcome measures An anonymous online questionnaire was distributed to dental students less than 1 month before graduation. Students were asked about the DD training they had received, their attitudes towards some aspects of DDs, their current DD use and their intended future DD use in adult or child patients and in various dental procedures.Results A total of 238 valid questionnaires were returned (response rate=97.1%, CQMU=96.2%, n=76; CQTGMC=97.6%, n=162). A total of 47.5% of respondents used DDs on real patients during their internships (CQMU=59.2%, CQTGMC=42.0%, p

Abstract Both Alzheimer's disease (AD) and osteoporosis (OP) are common age‐associated degenerative diseases and are strongly correlated with clinical epidemiology. However, there is a lack of clear pathological relationship between the brain and bone in the current understanding. Here, it is found that young osteocyte, the most abundant cells in bone, secretes extracellular vesicles (OCYYoung‐EVs) to ameliorate cognitive impairment and the pathogenesis of AD in APP/PS1 mice and model cells. These benefits of OCYYoung‐EVs are diminished in aged osteocyte‐derived EVs (OCYAged‐EVs). Based on the self‐constructed OCY‐EVs tracer transgenic mouse models and the in vivo fluorescent imaging system, OCY‐EVs have been observed to be transported to the brain under physiological and pathological conditions. In the hippocampal administration of Aβ40 induced young AD model mice, the intramedullary injection of Rab27a‐shRNA adenovirus inhibits OCYYoung‐EVs secretion from bone and aggravates cognitive impairment. Proteomic quantitative analysis reveals that OCYYoung‐EVs, compared to OCYAged‐EVs, enrich multiple protective factors of AD pathway. The study uncovers the role of OCY‐EV as a regulator of brain health, suggesting a novel mechanism in bone‐brain communication.

Influenza A(H1N1)pdm09 virus has remained in a seasonal circulation since being recognized in 2009. Although it followed a mild course in most patients, in others it caused a series of severe clinical illnesses. Epidemiologic studies have implicated that host factors have a major influence on the disease severity of influenza A(H1N1)pdm09 infection. However, an understanding of relevant genetic variations and the underlying mechanisms is still limited. In this present study, we used a host-based whole genome sequencing (WGS) method to comprehensively explore the genetic risk loci associated with severity of influenza A(H1N1)pdm09 infection. From the common single-nucleotide variants (SNVs) analysis, we identified the abnormal nominally significant (P < 1 × 10−4) common SNVs enriched in PTBP3 gene. The results of rare functional SNVs analysis supported that there were several novel candidate genes might confer risk of severe influenza A(H1N1)pdm09 diseases, such as FTSJ3, CPVL, BST2, NOD2 and MAVS. Moreover, our results of gene set based analysis indicated that the HIF-1 transcription factor and IFN-γ pathway might play an important role in the underlying mechanism of severe influenza A(H1N1)pdm09. These findings will increase our knowledge about biological mechanism underlying the severe influenza A(H1N1)pdm09 and facilitate to design novel personalized treatments.

With the increasing penetration of renewable energy generation, uncertainty and randomness pose great challenges for optimal dispatching in distribution networks. We propose a cloud-edge cooperative dispatching (CECD) method to exploit the new opportunities offered by Internet of Things (IoT) technology. To alleviate the huge pressure on the modeling and computing of large-scale distribution system, the method deploys edge nodes in small-scale transformer areas in which robust optimization subproblem models are introduced to address the photovoltaic (PV) uncertainty. Considering the limited communication and computing capabilities of the edge nodes, the cloud center in the distribution automation system (DAS) establishes a utility grid master problem model that enforces the consistency between the solution at each edge node with the utility grid based on the alternating direction method of multipliers (AD-MM). Furthermore, the voltage constraint derived from the linear power flow equations is adopted for enhancing the operation security of the distribution network. We perform a cloud-edge system simulation of the proposed CECD method and demonstrate a dispatching application. The case study is carried out on a modified 33-node system to verify the remarkable performance of the proposed model and method.

The traditional financial models used in bond default mainly focus on the analysis and prediction of bonds issued by listed companies, and they lack early warning abilities for a large number of bonds of nonlisted companies. At the same time, there is a great deal of relational data and category data in bond data. It is of great significance for bond default prediction to use these data reasonably, which may bring considerable revenue to companies in the near future. Therefore, this paper uses multisource information from bonds and issuers as well as macroeconomic data to predict bond defaults based on a knowledge graph and deep learning technology. On the basis of constructing a bond knowledge graph, knowledge representation learning technology is used to vectorize the knowledge in the graph, and the extracted vectors are inputted into the deep learning model as features to forecast bond default. The applied model is the deep factorization machine model, and good prediction results are obtained.

Background The relation between neighbourhood built environment and obesity has been described as both nuanced and complex. Aim The objective of this study was to examine the relationship between the built environment, physical activity, and obesity in a rapidly urbanised area of China. Subjects and methods This is a cross-sectional study. Descriptive statistics were used to describe the socio-demographic variables, physical activity levels and BMI status. Multivariable logistic regression models were used to examine the association between neighbourhood environment, the likelihood of engaging in different types of physical activity, and BMI. Results A total of 842 respondents completed the questionnaires and were included (84.1% response rate). Among them, 56.4% reported meeting high physical activity levels, while 40.7% were overweight or obese. Multivariable regression analysis showed that better road conditions (β = 0.122, t = 2.999, p = 0.003) and access to physical activity facilities (β = 0.121, t = 3.193, p = 0.001) were significantly associated with higher levels of physical activity. Physical activity levels were inversely associated with the likelihood of being overweight (OR = 0.565, 95%CI: 0.3 4 9–0.917) or obese (OR = 0.614, 95%CI: 0.3 9 0–0.966). Conclusion The built environment has an important impact on physical activity. However, the direct impact of leisure physical activity on BMI is not significant. This research provides a summary of recent evidence in Pingshan District on built environments that are most favourable for physical activity and obesity.

Viral myocarditis (VMC) caused by coxsackievirus B3 (CVB3) infection is a life-threatening disease. The cardiac damage during VMC is not mainly due to the direct cytotoxic effect of the virus on cardiomyocytes but mostly involves the induction of immune responses. Integrin CD11b plays an important role in immune response, for instance, in the induction of Th17 cells. However, the role of CD11b in the pathogenesis of VMC remains largely unknown. In the present study, a mouse model of VMC was established by CVB3 infection and CD11b was knocked down in the VMC mice by transfection with siRNA-CD11b. The expression of CD11b and IL-17 in heart tissues, frequency of Th17 cells in spleen tissues and serum IL-17 levels were measured using quantitative RT-PCR, Western blot, immunohistochemistry, flow cytometry and ELISA. Results showed that CVB3 infection caused the pathological changes in heart tissues with the increases in the following indexes: expression of CD11b and IL-17 in heart tissues, frequency of Th17 cells in spleen tissues and serum IL-17 levels. The expression of CD11b was positively correlated with IL-17 expression in heart tissues. Depletion of CD11b attenuated the damage caused by CVB3 and decreased the frequency of Th17 cells in spleen tissues as well as in IL-17, IL-23 and STAT3 expression in heart tissues. In summary, our findings reveal that disruption of CD11b function reduced CVB3-induced myocarditis, suggesting that CD11b may be a novel therapeutic target for VMC.

Complicated and large acetabular bone defects present the main challenges and difficulty in the revision of total hip arthroplasty (THA). This study aimed to explore the advantages of three-dimensional (3D) printing technology in the reconstruction of such acetabular bone defects. We retrospectively analyzed the prognosis of four severe bone defects around the acetabulum in three patients who were treated using 3D printing technology. Reconstruction of bone defect by conventional methods was difficult in these patients. In this endeavor, we used radiographic methods, related computer software such as Materialise's interactive medical image control system and Siemens NX software, and actual surgical experience to estimate defect volume, prosthesis stability, and installation accuracy, respectively. Moreover, a Harris hip score was obtained to evaluate limb function. It was found that bone defects could be adequately reconstructed using a 3D printing prosthesis, and its stability was reliable. The Harris hip score indicated a very good functional recovery in all three patients. In conclusion, 3D printing technology had a good therapeutic effect on both complex and large bone defects in the revision of THA. It was able to achieve good curative effects in patients with large bone defects.

Abstract Objective To investigate the impact of rare variants underlying neurodegenerative‐related genes to familial Alzheimer’s disease (AD). Methods We performed targeted sequencing of 277 neurodegenerative‐related genes on probands from 75 Chinese AD families non‐carrying causative mutation of dementia genes. Rare coding variants segregated in families were tested for association in an independent cohort of 506 patients with sporadic AD and 498 cognitively normal controls. East Asians data from the Exome Aggregation Consortium (ExAC) were used as a reference control. Results A novel rare variant, P410S of PLD3 was found in an early‐onset AD family. LRRK2 I2012T, a causative mutation of Parkinson’s disease, was identified in another early‐onset AD family. Missense variants in ABCA7 (P143S and A1507T) and CR1(T239M) were significantly associated with familial AD (P = 0.005437, 0.001383, 0.000549), a missense variant in TREM2(S183C) was significantly associated with AD (P = 0.000396) when compared with the East Asian controls in ExAC database. A non‐frameshift variant in FUS (G223del) was frequent in AD cases and significantly associated with familial AD (P = 0.008). Interpretation Multiple rare coding variants of causal and risk neurodegenerative genes were presented in clinically diagnosed AD families that may confer risk of AD. Our data supported that the clinical, pathological, and genetic architectures of AD, PD, and FTD/ALS may overlapping. We propose that targeted sequencing on neurodegenerative‐related genes is necessary for genetically unclear AD families.

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

Objective To analyze the prognostic value of SUVmax, ΔSUVmax, MTV and BCL-2 and BCL-6 expression on DLBCL patients. Methods We retrospectively analyzed the 18F-FDG PET/CT manifestation of 55 DLBLC patients, and evaluated the middle-stage chemotherapy effect with 5-PS by 18F-FDG PET/CT scan. Chi-square test was used for analysing the correlation of the chemotherapy efficacy with SUVmax, ΔSUVmax, MTV and the expression of BCL-2 and BCL-6. Kaplan-Meier analysis and Cox regression analysis were used for the predictive value of ΔSUVmax, MTV, Deauville score and the expression of BCL-2 and BCL-6 on the 2-years PFS of DLBCL patients. Results There was no correlation between SUVmax and the middle-stage chemotherapy effect (P > 0.05); ΔSUVmax, MTV and the expression of BCL-2 and BCL-6 were positively correlated with chemotherapy effect (P=0.029, 0.005, 0.001, 0.014). By univariate and multivariate analyses, there were statistical differences in 2-years PFS between ΔSUVmax < 10.6, MTV < 30.1 cm3, Deauville score < 4, BCL-6(-) groups and ΔSUVmax≥10.6, MTV≥30.1 cm3, Deauville score≥4, BCL-6(+) groups (P < 0.05). There was statistical difference in 2-years PFS of the patients with BCL-2 by univariate analysis (P=0.039). Conclusion There are negatively correlation between ΔSUVmax, MTV and the middle-stage chemotherapy effect. Patients with BCL2(-) and BCL-6(-) have good efficacy. ΔSUVmax, MTV, Deauville score and BCL-6 are independent prognostic factors for the 2-years PFS of DLBCL patients.

Billions of cells undergo turnover and die via apoptosis throughout our lifetime. A prompt clearance of these apoptotic cells and debris by phagocytic cells, a process known as efferocytosis, is important in maintaining tissue homeostasis. Accordingly, impaired efferocytosis due to the defective clearance and disrupted stages can lead to a growing number of inflammation- and immune-related diseases. Although numerous studies have shown the mechanisms of efferocytosis, its role in disorders, such as non-tumor and tumor diseases, remains poorly understood. This review summarizes the processes and signal molecules in efferocytosis, and efferocytosis-related functions in non-tumor (e.g., atherosclerosis, lung diseases) and tumor diseases (e.g., breast cancer, prostate cancer), as well as describes the role of involved cytokines. Of note, there is a dual role of efferocytosis in the abovementioned disorders, and a paradoxical effect among non-tumor and tumor diseases in terms of inflammation resolution, immune response, and disease progression. Briefly, intact efferocytosis and cytokines promote tissue repair, while they contribute to tumor progression via the tumor microenvironment and macrophage politzerization. Additionally, this review provides potential targets associated with TAM (TYRO3, AXL, MERTK) receptors and cytokines, such as tumor necrosis factor α and CXCL5, suggesting potential novel therapeutic ways in treating diseases.

Abstract Background Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative condition characterized by the loss of neurons and the presence of eosinophilic nuclear inclusions in the central and peripheral nervous system, skin and visceral organs. In this paper, we present a case of NIID with recurrent encephalitic attacks that remained stable and nonprogressive for seven years; no such case has previously been reported. Case presentation A 63-year-old female was hospitalized due to light-headedness, vomiting, unstable gait and cognitive impairment. Seven years prior, she had experienced an episode of light-headedness, central facial paralysis, unstable gait, aphasia, nausea, vomiting and loss of consciousness. She regained consciousness within 12 h, and her other symptoms were completely resolved within one week. During the present hospitalization, a brain magnetic resonance imaging (MRI) examination detected high signal intensity on diffusion-weighted imaging (DWI) of the bilateral frontal grey matter–white matter junction. We reviewed the patient’s previous MRI results and found that she had also had high signal intensity on DWI of the bilateral frontal grey matter–white matter junction seven years prior. In the intervening seven years, the high signal intensity in the frontal lobes had spread along the grey matter–white matter junction, but the deep white matter remained unaffected. Skin biopsy was performed, and intranuclear inclusions were found in adipocytes, fibroblasts and sweat gland cells. GGC repeat expansions in the NOTCH2NLC (Notch 2 N-terminal like C) gene confirmed the diagnosis of NIID. She received supportive treatment such as nutrition support therapy and vitamin B and C supplementation, as well as symptomatic treatment during hospitalization. The patient’s symptoms were completely relieved within one week. Conclusion This is a detailed report of a case of NIID with multiple reversible encephalitic attacks, diagnosed by clinical symptoms, intranuclear inclusions, characteristic DWI signals, and genetic tests.

Abstract Background Among the previous studies about the ADL recovery and its predictors, the researches and resources used to study and protect the baseline-independent older patients from being permanently ADL-dependent was few. We aimed to describe the level of activities of daily living (ADL) at discharge and ADL change within 6 months after discharge in older patients who were ADL-independent before admission but became dependent because of acute illness, and to identify the predictors of early rehabilitation,so as to provide the basis to early intervention. Methods Stratified cluster sampling was used to recruit 520 hospitalised older patients who were ADL-independent from departments of internal medicine at two tertiary hospitals from August 2017 to May 2018. Demographics, clinical data, and ADL status at 1, 3, and 6 months after discharge were collected. Data were analysed using descriptive statistics, Student’s t-test, Pearson’s chi-square test,Spearman’s correlation analysis, binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis. Results There were 403 out of 520 patients completing the 6-month follow-up, and 229 (56.8%) regained independence at 6 months after discharge. There was an overall increasing trend in ADL with time. The recovery rate was the highest within the first month after discharge, gradually declined after 1 month, and changed less obviously from 3 to 6 months after discharge (p

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths globally. Metastasis is associated with a poor prognosis, yet the underlying molecular mechanism(s) remained largely unknown. In this study, a total of 85 CRC patients were included and the primary tumor lesions were evaluated by next-generation sequencing using a targeted panel for genetic aberrations. Patients were sub-divided according to their metastasis pattern into the non-organ metastases (Non-OM) and organ metastases (OM) groups. By comparing the genetic differences between the two groups, we found that mutations in FBXW7 and alterations in its downstream NOTCH signaling pathway were more common in the Non-OM group. Moreover, correlation analysis suggested that FBXW7 mutations were independent of other somatic alterations. The negative associations of alterations in FBXW7 and its downstream NOTCH signaling pathway with CRC organ metastasis were validated in a cohort of 230 patients in the TCGA CRC dataset. Thus, we speculated that the genomic alterations of FBXW7/NOTCH axis might be an independent negative indicator of CRC organ metastases.

BackgroundRepeat expansions, including those in C9orf72 and ATXN2, have been implicated in amyotrophic lateral sclerosis (ALS). However, there have been few studies on the association of AR and NOP56 repeat expansion with ALS, especially in China. Accordingly, we aimed to evaluate the frequency of C9orf72 and ATXN2 repeat mutations and investigate whether NOP56 and AR repeat expansion are risk factors for ALS.MethodsIn this study, 736 ALS patients and several hundred healthy controls were recruited. Polymerase chain reaction (PCR) and repeat-primed PCR (RP-PCR) were performed to determine the repeat lengths in C9orf72, ATXN2, AR, and NOP56.ResultsGGGGCC repeats in C9orf72 were observed in six ALS patients (0.8%, 6/736) but not in any of the controls (0/365). The patients with pathogenic GGGGCC repeats showed shorter median survival times than those with a normal genotype (p = 0.006). Regarding ATXN2 CAG repeats, we identified that intermediate repeat lengths (29–34 copies) were associated with ALS (p = 0.033), and there was no difference in clinical characteristics between the groups with and without intermediate repeats (p > 0.05). Meanwhile, we observed that there was no association between the repeat size in AR and NOP56 and ALS (p > 0.05).ConclusionsOur results demonstrated that pathogenetic repeats in C9orf72 are rare in China, while intermediate CAG repeats in ATXN2 are more frequent but have no effect on disease phenotypes; the repeat size in AR and NOP56 may not be a risk factor for ALS.

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.

Motivated by the potential of objective neurophysiological markers to index thalamocortical function in patients with severe psychiatric illnesses, we comprehensively characterized key non-rapid eye movement (NREM) sleep parameters across multiple domains, their interdependencies, and their relationship to waking event-related potentials and symptom severity. In 72 schizophrenia (SCZ) patients and 58 controls, we confirmed a marked reduction in sleep spindle density in SCZ and extended these findings to show that fast and slow spindle properties were largely uncorrelated. We also describe a novel measure of slow oscillation and spindle interaction that was attenuated in SCZ. The main sleep findings were replicated in a demographically distinct sample, and a joint model, based on multiple NREM components, statistically predicted disease status in the replication cohort. Although also altered in patients, auditory event-related potentials elicited during wake were unrelated to NREM metrics. Consistent with a growing literature implicating thalamocortical dysfunction in SCZ, our characterization identifies independent NREM and wake EEG biomarkers that may index distinct aspects of SCZ pathophysiology and point to multiple neural mechanisms underlying disease heterogeneity. This study lays the groundwork for evaluating these neurophysiological markers, individually or in combination, to guide efforts at treatment and prevention as well as identifying individuals most likely to benefit from specific interventions.

With the development of the sequencing technique, more than 40 repeat expansion diseases (REDs) have been identified during the past two decades. Moreover, the clinical features of these diseases show some commonality, and the nervous system, especially the cognitive function was affected in part by these diseases. However, the specific cognitive domains impaired in different diseases were inconsistent. Here, we survey literature on the cognitive consequences of the following disorders presenting cognitive dysfunction and summarizing the pathogenic genes, epidemiology, and different domains affected by these diseases. We found that the cognitive domains affected in neuronal intranuclear inclusion disease (NIID) were widespread including the executive function, memory, information processing speed, attention, visuospatial function, and language. Patients with C9ORF72-frontotemporal dementia (FTD) showed impairment in executive function, memory, language, and visuospatial function. While in Huntington's disease (HD), the executive function, memory, and information processing speed were affected, in the fragile X-associated tremor/ataxia syndrome (FXTAS), executive function, memory, information processing speed, and attention were impaired. Moreover, the spinocerebellar ataxias showed broad damage in almost all the cognitive domains except for the relatively intact language ability. Some other diseases with relatively rare clinical data also indicated cognitive dysfunction, such as myotonic dystrophy type 1 (DM1), progressive myoclonus epilepsy (PME), Friedreich ataxia (FRDA), Huntington disease like-2 (HDL2), and cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). We drew a cognitive function landscape of the related REDs that might provide an aspect for differential diagnosis through cognitive domains and effective non-specific interventions for these diseases.

Abstract Objective Tourette syndrome (TS) is a childhood neurodevelopmental disorder caused by various genetic and environmental factors and presents with apparent genetic heterogeneity. As ASH1L potentially contributes to neurodevelopmental diseases, especially in TS, we aim to investigate the susceptibility of ASH1L on TS in the Chinese Han population. Methods Three tag single nucleotide polymorphisms (SNPs) (rs5005770, rs12734374, and rs35615695) in ASH1L were screened in 271 TS nuclear family trios and 337 healthy subjects by the TaqMan assays real time. A case–control study combined with family‐based analysis was applied to study the genetic susceptibility of common variants of ASH1L. Results The results revealed a significant over‐transmission of rs35615695 and rs5005770 (for rs35615695, transmission disequilibrium test, χ2 = 57.375, p = .000, HHRR, χ2 = 4.807, p = .028; for rs5005770, HRR, χ2 = 4.116, p = .042, HHRR, χ2 = 8.223, p = .004) in family‐based study. Furthermore, rs5005770 and rs35615695 still remained significant after Bonferroni correction (p

The performance of traditional model-based constant false-alarm ratio (CFAR) detection algorithms can suffer in complex environments, particularly in scenarios involving multiple targets (MT) and clutter edges (CE) due to an imprecise estimation of background noise power level. Furthermore, the fixed threshold mechanism that is commonly used in the single-input single-output neural network can result in performance degradation due to changes in the scene. To overcome these challenges and limitations, this paper proposes a novel approach, a single-input dual-output network detector (SIDOND) using data-driven deep neural networks (DNN). One output is used for signal property information (SPI)-based estimation of the detection sufficient statistic, while the other is utilized to establish a dynamic-intelligent threshold mechanism based on the threshold impact factor (TIF), where the TIF is a simplified description of the target and background environment information. Experimental results demonstrate that SIDOND is more robust and performs better than model-based and single-output network detectors. Moreover, the visual explanation technique is employed to explain the working of SIDOND.

Offline handwritten Chinese recognition is an important research area of pattern recognition, including offline handwritten Chinese character recognition (offline HCCR) and offline handwritten Chinese text recognition (offline HCTR), which are closely related to daily life. With new deep learning techniques and the combination with other domain knowledge, offline handwritten Chinese recognition has gained breakthroughs in methods and performance in recent years. However, there have yet to be articles that provide a technical review of this field since 2016. In light of this, this paper reviews the research progress and challenges of offline handwritten Chinese recognition based on traditional techniques, deep learning methods, methods combining deep learning with traditional techniques, and knowledge from other areas from 2016 to 2022. Firstly, it introduces the research background and status of handwritten Chinese recognition, standard datasets, and evaluation metrics. Secondly, a comprehensive summary and analysis of offline HCCR and offline HCTR approaches during the last seven years is provided, along with an explanation of their concepts, specifics, and performances. Finally, the main research problems in this field over the past few years are presented. The challenges still exist in offline handwritten Chinese recognition are discussed, aiming to inspire future research work.

Complex terrain conditions of wind farms, the large weight and the long size of wind turbine equipment, the high economic requirements of transportation on roads, and a shortage of relevant standards and codes lead to difficulty in road design and route selection of wind farms. In addition, frequent excavations and landfills in wind farm construction have seriously destroyed vegetation cover and soil structure on the primary surface, resulting in a large amount of water and soil loss and ecological damage to the wind farm. In view of the above problems, this paper reviews the relevant research status of the wind farm road route selection method, circular curve, longitudinal section design index, and water and soil loss problems, and summarizes them. Several calculation models for circular curve widening, the recommendation of a minimum radius under different restrictions, calculation models for longitudinal slope and vertical curve, and recommended values are listed. The causes of water and soil losses in wind farms are discussed and the characteristics of the diversity of erosion and the uneven distribution of time and space are put forward. Prediction models of wind farm water and soil loss and comprehensive prevention measures are given. The existing problems in the road design field of wind farms are put forward and the future development direction in this field is forecasted.

BackgroundRetinal microvascular density has been studied in neurodegenerative diseases, whereas patients with Parkinson’s disease (PD) at different clinical stages have been rarely investigated. The present study aimed to evaluate the microvascular variations in superficial retinal capillary plexus (SCP) in patients with PD on different Hoehn-Yahr (H-Y) stages by optical coherence tomography angiography (OCTA), as well as determine their relationships with clinical parameters.MethodsIn total, 115 patients with PD and 67 healthy controls (HCs) were recruited. The PD group was divided into three groups based on the H-Y stage. The OCTA examination was performed in all participants, and the macular vessel density (m-VD), peripapillary vessel density (p-VD), and foveal avascular zone (FAZ) area were measured.ResultsThe m-VD in all regions, p-VD in center [6.1 (4.8, 6.95) mm–1 in healthy eyes vs. 5.1 (3.7, 6.4) mm–1 in patients], nasal inner (NI) [18.5 (17.8, 19.3) mm–1 in healthy eyes vs. 17.9 (17.1, 18.7) mm–1 in patients], temporal outer (TO) [19.6 (18.9, 20.2) mm–1 in healthy eyes vs. 19.3 (18.5, 19.7) mm–1 in patients] regions and FAZ area [0.36 (0.32, 0.39) mm2 in healthy eyes vs. 0.29 (0.26, 0.33) mm2 in patients] noticeably decreased in PD groups compared with HC (p < 0.05). Moreover, the FAZ area was suggested to decline significantly in patients with PD with H-Y I stage (p < 0.05), while it was more serious in the H-Y III stage in patients. Furthermore, we found that m-VD exhibited a significant negative correlation with age, disease duration, UPDRS scores, NMSS scores, and H-Y stage.ConclusionOCTA has the potential to non-invasively detect the microvascular changes in patients with PD with different clinical stages in vivo, and it may be a valuable tool to monitor the PD progression.

Background and AimsCharcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of inherited peripheral neuropathies. The wide phenotypic variability may not be completely explained by a single mutation.Aims and MethodsTo explore the existence of concomitant variants in CMT, we enrolled 189 patients and performed molecular diagnosis by application of next-generation sequencing combined with multiplex ligation-dependent probe amplification. We conducted a retrospective analysis of patients harboring coinherited variants in different genes.ResultsFour families were confirmed to possess variants in two genes, accounting for 2.1% (4/189) of the total in our cohort. One CMT1 patient with PMP22 duplication and MPZ variant (c.286A>C, p.K96Q) exhibited moderate neuropathy with infantile onset, while her father possessing MPZ variant was mildly affected with adolescence onset. A CMT2 patient with heterozygous variants in MFN2 (c.613_622delGTCACCACAG, p.V205Sfs*26) and GDAP1 (c.713G>T, p.W238L) exhibited childhood onset mild phenotype, while his mother with MFN2 variant developed bilateral pes cavus only. A CMT2 patient with heterozygous variants in MFN2 (c.839G>A, p.R280H) and GDAP1 (c.3G>T, p.M1?) presented infantile onset and rapid progression, while her father with MFN2 variant presented with absence of deep tendon reflexes. One sporadic CMT2 patient with early onset was confirmed harboring de novo MFN2 variant (c.1835C>T, p.S612F) and heterozygous GDAP1 variant (c.767A>G, p.H256R).ConclusionOur results suggest that the possibility of concomitant variants was not uncommon and should be considered when significant intrafamilial clinical heterogeneity is observed.

We report the discovery of a candidate galaxy with a photo- z of z ∼ 12 in the first epoch of the James Webb Space Telescope (JWST) Cosmic Evolution Early Release Science Survey. Following conservative selection criteria, we identify a source with a robust z _phot = ${11.8}_{-0.2}^{+0.3}$ (1 σ uncertainty) with m _F200W = 27.3 and ≳7 σ detections in five filters. The source is not detected at λ < 1.4 μ m in deep imaging from both Hubble Space Telescope (HST) and JWST and has faint ∼3 σ detections in JWST F150W and HST F160W, which signal a Ly α break near the red edge of both filters, implying z ∼ 12. This object (Maisie’s Galaxy) exhibits F115W − F200W > 1.9 mag (2 σ lower limit) with a blue continuum slope, resulting in 99.6% of the photo- z probability distribution function favoring z > 11. All data-quality images show no artifacts at the candidate’s position, and independent analyses consistently find a strong preference for z > 11. Its colors are inconsistent with Galactic stars, and it is resolved ( r _h = 340 ± 14 pc). Maisie’s Galaxy has log M _* / M _⊙ ∼ 8.5 and is highly star-forming (log sSFR ∼ −8.2 yr ^−1 ), with a blue rest-UV color ( β ∼ −2.5) indicating little dust, though not extremely low metallicity. While the presence of this source is in tension with most predictions, it agrees with empirical extrapolations assuming UV luminosity functions that smoothly decline with increasing redshift. Should follow-up spectroscopy validate this redshift, our universe was already aglow with galaxies less than 400 Myr after the Big Bang.

This paper investigates the relationship between technological finance, high-quality economic growth, and financial stability. Based on data of 30 provinces (including autonomous regions and municipalities) collected between 2004 and 2017, this paper adopts the method of factor analysis to construct comprehensive indexes of technological finance and financial stability before calculating green total factor productivity as the index of high-quality development, using the CRS Multiplicative Model. Then it constructs the spatial SAC model and PVAR model for analyses of the just-mentioned relationship based on the total sample of the nation and regional samples in eastern, middle, and western China, respectively. The results reveal that (1) All samples, whether the total national samples or regional samples of eastern, middle, and western China demonstrate the positive influence of technological finance on high-quality economic development, with an obvious spatial spillover effect. The impact factor is the highest in the eastern region, while the western region holds the lowest factor among the three. (2) Judging by the general national sample, technological finance has an obvious negative shock effect on financial stability within a short period, but the effect gradually dwindles as time goes by. This rule applies to the sample of the eastern region, as its technological finance poses a short-time negative shock effect on financial stability, before gradually diminishing to 0. Neither western nor middle regions have displayed an obvious shock impact on financial stability.