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Background: Developing deep learning models for segmenting medical images in multiple modalities with less data and annotation is an attractive and challenging task, which was previously discussed as being accomplished by complex external frameworks for bridging the gap between different modalities. Exploring the generalization ability of networks in medical images in different modalities could provide more simple and accessible methods, yet comprehensive testing could still be needed., Purpose: To explore the feasibility and robustness of using computed tomography (CT) images to assist the segmentation of magnetic resonance (MR) images via the generalization, in the segmentation of renal parenchyma of renal cell carcinoma (RCC) patients., Methods: Nephrographic CT images and fat-suppressed T2-weighted (fs-T2 W) images were retrospectively collected. The pure CT dataset included 116 CT images. Additionally, 240 MR images were randomly divided into subsets A and B. From subset A, three training datasets were constructed, each containing 40, 80, and 120 images, respectively. Similarly, three datasets were constructed from subset B. Subsequently, datasets with mixed modality were created by combining these pure MR datasets with the 116 CT images. The 3D-UNET models for segmenting the renal parenchyma in two steps were trained using these 13 datasets: segmenting kidneys and then the renal parenchyma. These models were evaluated in internal MR (n = 120), CT (n = 65) validation datasets, and an external validation dataset of CT (n = 79), using the mean of the dice similarity coefficient (DSC). To demonstrate the robustness of generalization ability over different proportions of modalities, we compared the models trained with mixed modality in three different proportions and pure MR, using repeated measures analysis of variance (RM-ANOVA). We developed a renal parenchyma volume quantification tool by the trained models. The mean differences and Pearson correlation coefficients between the model segmentation volume and the ground truth segmentation volume were calculated for its evaluation., Results: The mean DSCs of models trained with 116 data in CT in the validation of MR were 0.826, 0.842, and 0.953, respectively, for the predictions of kidney segmentation model on whole image, renal parenchymal segmentation model on kidneys with RCC and without RCC. For all models trained with mixed modality, the means of DSC were above 0.9, in all validations of CT and MR. According to the results of the comparison between models trained with mixed modality and pure MR, the means of DSC of the former were significantly greater or equal to the latter, at all three different proportions of modalities. The differences of volumes were all significantly lower than one-third of the volumetric quantification error of a previous method, and the Pearson correlation coefficients of volumes were all above 0.96 on kidneys with and without RCC of three validations., Conclusion: CT images could be used to assist the segmentation of MR images via the generalization, with or without the supervision of MR data. This ability showed acceptable robustness. A tool for accurately measuring renal parenchymal volume on CT and MR images was established., (© 2024 American Association of Physicists in Medicine.)

Background: Intermediate phenotypes, such as characteristic neuroimaging patterns, offer unique insights into the genetic and stress-related underpinnings of neuropsychiatric disorders like depression. This study aimed to identify neuroimaging intermediate phenotypes associated with depression, bridging etiological factors to behavioral manifestations and connecting insights from animal models to diverse clinical populations., Methods: We analyzed datasets from both rodents and humans. The rodent studies included a genetic model (P11 knockout) and an environmental stress model (chronic unpredictable mild stress), while the human data comprised 748 participants from three cohorts. Using the amplitude of low-frequency fluctuations, we identified neuroimaging patterns in rodent models. We then applied a machine-learning approach to cluster neuroimaging subtypes of depression. To assess the genetic predispositions and stress-related changes associated with these subtypes, we analyzed genotype and metabolite data. Linear regression was employed to determine which neuroimaging features predicted core depression symptoms across species., Results: The genetic and environmental stress models exhibited distinct neuroimaging patterns in subcortical and sensorimotor regions. Consistent patterns emerged in two neuroimaging subtypes identified across three independent depressed cohorts. The subtype resembling P11 knockout demonstrated higher genetic susceptibility, with enriched expression of risk genes in brain tissues and abnormal metabolites linked to tryptophan metabolism. In contrast, the stress animal-like subtype did not show changes in genetic risk scores but exhibited enriched risk gene expression in somatic and endocrine tissues, along with mitochondrial dysfunction in the antioxidant stress system. Notably, these distinct subcortical-sensorimotor neuroimaging patterns predicted anhedonia, a core symptom of depression, in both rodent models and depressed subtypes., Conclusions: This cross-species validation suggests that these neuroimaging patterns may serve as robust intermediate phenotypes, linking etiology to anhedonia and facilitating the translation of findings from animal models to humans with depression and other psychiatric disorders., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures in these animal experiments were conducted in accordance with the guidelines of the Animal Care and Use Committee at the Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences (APM23010A). The human study was approved by the Ethics Committees of Renmin Hospital of Wuhan University (WDRY2020-K191), Peking University Sixth Hospital (2016–6), and the First Affiliated Hospital of China Medical University (2015–27-2). All human participants provided written informed consent after receiving a detailed description of the study. Consent for publication: Written informed consent was obtained from all participants included in the study for the use of their clinical, demographic, and neuroimaging data in this publication. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: Acute unilateral vestibulopathy (AUVP) is quite common in clinical practice, but lesion localization and etiological diagnosis of AUVP remain the current clinical challenges, and have always been the focus for researchers. The study aimed to explore the lesion site and possible etiology of AUVP., Methods: This study is a retrospective study. Twenty-three AUVP patients who attended the neurology outpatient clinics of our hospital from January 2020 to March 2022 were included. Clinical data of patients including baseline data, cardiovascular risk factors, immunological test results and infection indicators were collected. Vestibular function tests, including video head impulse test (vHIT), caloric testing, vestibular evoked myogenic potentials (VEMPs) and post-contrast delayed 3D-FLAIR MRI, were performed., Results: Among 32 AUVP patients included, there were 10 males and 13 females, with a male-to-female ratio of 1:1.3, and an average age of 42.13 ± 14.57 years (range 19-76 years old). Acute persistent vertigo and relapsing-remitting vertigo accounted for 39.1% (9/23) and 60.9% (14/23) of the patients, respectively. Possible etiologies included cardiovascular risk factors (n = 11), abnormal immunological indicators (n = 8), and evidence of infection (n = 3). About 57.1% (12/21) of the patients showed abnormal vHIT (including reduced gain in horizontal canal (HC) in 14.3%, anterior canal (AC) in 4.8%, both the AC and HC in 19%, both the HC and posterior canal (PC) in 14.3%, and all three canals in 9.5% of cases). Probable entire vestibular nerve damage was found in 38.1% of the patients, only 9.5% of the patients followed the innervation pattern of the entire vestibular nerve, these patients had abnormal vHIT and VEMP results, and were considered to have definite entire vestibular nerve damage. Probable superior vestibular nerve (SVN) damage was found in 47.6% of the patients, but only 4.8% (1/21) of the patients followed the innervation pattern of SVN, with reduced VOR gains for AC and HC and abnormal oVEMP results, and were considered to have definite SVN damage. 3D-FLAIR MRI revealed high signal intensity in the SVN and vestibule in 4.8% (1/21) and 19% (4/21) of the patients, respectively., Conclusion: The majority of AUVP patients had a relapsing-remitting course and had vestibular function test results that did not follow the innervation pattern of the vestibular nerve. Post-contrast delayed 3D-FLAIR MRI revealed damage to the vestibule in some patients, suggesting that damage to the labyrinth itself in AUVP deserves clinical attention. The majority of the AUVP patients had cardiovascular risk factors and abnormal systemic immunological indicators, which might be the possible etiologies of AUVP., Competing Interests: Menglu Zhang and Jianrong Wan are co-first authors for this study. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2025 Zhang et al.)

Conventional administration methods have problems including low bioavailability, complex operation process, and discomfort of patients with fear of needles. Transdermal delivery can avoid these problems, whereas most drugs are difficult to directly penetrate the skin cuticle and reach the diseased site. Microneedling is an emerging method of local drug delivery, enabling the drug penetration through the stratum corneum of the skin in a minimally invasive manner and delivering the drug directly to the diseased site, thereby improving the treatment effect. Stimuli-responsive microneedles have attracted much attention because of the spatiotemporal controllability, high drug delivery efficiency, and mild potential side effects. This review introduced the commonly used materials and various types of stimuli-responsive microneedles and the drug release mechanisms. In addition, this paper expounded the biomedical applications of stimuli-responsive microneedles as drug delivery systems in response to different stimuli and discusses the challenges and potential solutions for stimuli-responsive microneedles.

Tissue engineering scaffolds can mediate the maneuverability of neural stem cell (NSC) niche to influence NSC behavior, such as cell self-renewal, proliferation, and differentiation direction, showing the promising application in spinal cord injury (SCI) repair. Here, dual-network porous collagen fibers (PCFS) are developed as neurogenesis scaffolds by employing biomimetic plasma ammonia oxidase catalysis and conventional amidation cross-linking. Following optimizing the mechanical parameters of PCFS, the well-matched Young's modulus and physiological dynamic adaptability of PCFS (4.0 wt%) have been identified as a neurogenetic exciter after SCI. Remarkably, porous topographies and curving wall-like protrusions are generated on the surface of PCFS by simple and non-toxic CO 2 bubble-water replacement. As expected, PCFS with porous and matched mechanical properties can considerably activate the cadherin receptor of NSCs and induce a series of serine-threonine kinase/yes-associated protein mechanotransduction signal pathways, encouraging cellular orientation, neuron differentiation, and adhesion. In SCI rats, implanted PCFS with matched mechanical properties further integrated into the injured spinal cords, inhibited the inflammatory progression and decreased glial and fibrous scar formation. Wall-like protrusions of PCFS drive multiple neuron subtypes formation and even functional neural circuits, suggesting a viable therapeutic strategy for nerve regeneration and functional recovery after SCI., (© 2024 Wiley‐VCH GmbH.)

Spatial transcriptomics technologies permit the study of the spatial distribution of RNA at near-single-cell resolution genome-wide. However, the feasibility of studying spatial allele-specific expression (ASE) from these data remains uncharacterized. Here, we introduce spASE, a computational framework for detecting and estimating spatial ASE. To tackle the challenges presented by cell type mixtures and a low signal to noise ratio, we implement a hierarchical model involving additive mixtures of spatial smoothing splines. We apply our method to allele-resolved Visium and Slide-seq from the mouse cerebellum and hippocampus and report new insight into the landscape of spatial and cell type-specific ASE therein., (© 2024. The Author(s).)

Background: Early life stress (ELS) significantly increases the risk of mood disorders and affects the neurodevelopment of the primary cortex., Hypothesis: Modulating the primary cortex through neural intervention can ameliorate the impact of ELS on brain development and consequently alleviate its effects on mood disorders., Method: We induced the chronic unpredictable mild stress (CUMS) model in adolescent rats, followed by applying repetitive transcranial magnetic stimulation (rTMS) to their primary cortex in early adulthood. To assess the applicability of primary cortex rTMS in humans, we recruited individuals aged 17-25 with mood disorders who had experienced ELS and performed primary cortex rTMS on them. Functional magnetic resonance imaging (fMRI) and depression-related behavioral and clinical symptoms were conducted in both rats and human subjects before and after the rTMS., Results: In animals, fMRI analysis revealed increased activation in the primary cortex of CUMS rats and decrease subcortical activation. Following the intervention of primary cortex rTMS, the abnormal functional activity was reversed. Similarly, in mood disorders patients with ELS, increased activation in the primary cortex and decreased activation in the frontal cortex were observed. During rTMS intervention, similar neuroimaging improvements were noted, particularly decreased activation in the primary cortex. This suggests that targeted rTMS in the primary cortex can reverse the abnormal neuroimaging., Conclusion: This cross-species translational study has identified the primary cortex as a key region in mood disorders patients with ELS. Targeting the primary cortex with rTMS can correct abnormal functional activity while improving symptoms. Our study provides translational evidence for therapeutics targeting the ELS factor of mood disorders patients., Competing Interests: Declaration of Competing Interest The authors report no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) is a sudden onset, unexplained sensorineural hearing loss. Depression is a common mental disorder and a leading cause of disability. Here, We used a two-sample Mendelian randomization approach using pooled statistics from genome-wide association studies of ISSHL (1491 cases, 196,592 controls) and depression (23,424 cases, 192,220 controls) in European populations. This study investigated the bidirectional relationship between single nucleotide polymorphisms associated with depression and ISSHL using inverse variance weighting.Additional sensitivity analyses, such as Mendelian randomization-Egger (MR-Egger), weighted median estimates, and leave-one-out analysis, were performed to assess the reliability of the findings. Significant causal association between genetic susceptibility to ISSHL and depression in a random-effects IVW approach (OR = 1.037, 95% CI = 1.004-1.072, P = 0.030). In contrast, genetic depression was not risk factors for ISSHL (OR = 1.134, 95% CI = 0.871-1.475, P = 0.350). After validation by different MR methods and the sensitivity analysis, all of the above results are consistent. The evidence we have gathered suggests a causal relationship between ISSHL and depression. The presence of the former induces or further exacerbates the latter, whereas a similar situation does not exist when the latter is an influencing factor., (© 2024. The Author(s).)

Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence. The methylazoxymethanol acetate (MAM) animal model, in which disruption in neurodevelopmental processes is induced, mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective. We conducted longitudinal structural magnetic resonance imaging (MRI) scans during childhood, adolescence, and adulthood in MAM rats to identify specific brain regions and critical windows for intervention. Then, the effect of repetitive transcranial magnetic stimulation (rTMS) intervention on the target brain region during the critical window was investigated. In addition, the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders (diagnosed with major depressive disorder or bipolar disorder) to evaluate its clinical translational potential. The results demonstrated that, compared to the control group, the MAM rats exhibited significantly lower striatal volume from childhood to adulthood (all P <0.001). In contrast, the volume of the hippocampus did not show significant differences during childhood (P >0.05) but was significantly lower than the control group from adolescence to adulthood (both P <0.001). Subsequently, rTMS was applied to the occipital cortex, which is anatomically connected to the hippocampus, in the MAM models during adolescence. The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group (P <0.01), while the volume of the striatum remained unchanged (P >0.05). In the clinical trial, adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline (P <0.01), and these volumetric changes were associated with improvement in depressive symptoms (r = - 0.524, P = 0.018). These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for early-onset mental disorders with neurodevelopmental etiology as well as the promise of rTMS as a therapeutic approach for mitigating aberrant neurodevelopmental processes and alleviating clinical symptoms., (© 2023. The Author(s).)

Aims: Neurodevelopmental impairments are closely linked to the basis of adolescent major psychiatric disorders (MPDs). The visual cortex can regulate neuroplasticity throughout the brain during critical periods of neurodevelopment, which may provide a promising target for neuromodulation therapy. This cross-species translational study examined the effects of visual cortex repetitive transcranial magnetic stimulation (rTMS) on neurodevelopmental impairments in MPDs., Methods: Visual cortex rTMS was performed in both adolescent methylazoxymethanol acetate (MAM) rats and patients with MPDs. Functional magnetic resonance imaging (fMRI) and brain tissue proteomic data in rats and fMRI and clinical symptom data in patients were analyzed., Results: The regional homogeneity (ReHo) analysis of fMRI data revealed an increase in the frontal cortex and a decrease in the posterior cortex in the MAM rats, representing the abnormal neurodevelopmental pattern in MPDs. In regard to the effects of rTMS, similar neuroimaging changes, particularly reduced frontal ReHo, were found both in MAM rats and adolescent patients, suggesting that rTMS may reverse the abnormal neurodevelopmental pattern. Proteomic analysis revealed that rTMS modulated frontal synapse-associated proteins, which may be the underpinnings of rTMS efficacy. Furthermore, a positive relationship was observed between frontal ReHo and clinical symptoms after rTMS in patients., Conclusion: Visual cortex rTMS was proven to be an effective treatment for adolescent MPDs, and the underlying neural and molecular mechanisms were uncovered. Our study provides translational evidence for therapeutics targeting the neurodevelopmental factor in MPDs., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Introduction: The emergence of the Omicron variant has seen changes in the clinical and radiological presentations of COVID-19 in pediatric patients. We sought to compare these features between patients infected in the early phase of the pandemic and those during the Omicron outbreak., Methods: A retrospective study was conducted on 68 pediatric COVID-19 patients, of which 31 were infected with the original SARS-CoV-2 strain (original group) and 37 with the Omicron variant (Omicron group). Clinical symptoms and chest CT scans were examined to assess clinical characteristics, and the extent and severity of lung involvement., Results: Pediatric COVID-19 patients predominantly had normal or mild chest CT findings. The Omicron group demonstrated a significantly reduced CT severity score than the original group. Ground-glass opacities were the prevalent radiological findings in both sets. The Omicron group presented with fewer symptoms, had milder clinical manifestations, and recovered faster than the original group., Discussion: The clinical and radiological characteristics of pediatric COVID-19 patients have evolved with the advent of the Omicron variant. For children displaying severe symptoms warranting CT examinations, it is crucial to weigh the implications of ionizing radiation and employ customized scanning protocols and protective measures. This research offers insights into the shifting disease spectrum, aiding in the effective diagnosis and treatment of pediatric COVID-19 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Lin, Xu, Shen, Huang, Gao, Liu, Xie, Zhao, Xia, Lv, Ren, Zheng, Wang, Hu, Ruan and Zhang.)

Background: Clinically, unilateral peripheral vestibular dysfunction (UPVD) with dizziness or vertigo as the chief complaint is quite common. This study aimed to investigate the correlations between 3-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI) findings and cochleovestibular function test results in patients with UPVD and to explore the possible etiologies of UPVD., Methods: This retrospective study enrolled 76 patients with UPVD. Endolymphatic hydrops (EH) and perilymphatic enhancement (PE) in the vestibule and cochlea on 3D-FLAIR images, their correlations with the parameters of the cochleovestibular function test and vascular risk factors, and the immunological findings of patients with EH and PE were assessed., Results: Of the included patients, 48.7% showed positive MRI findings (the presence of EH and PE on 1 side). The pure-tone average (PTA) was higher in patients with cochlear PE than in those with vestibular (P=0.014) and cochlear EH (P=0.02). The canal paresis (CP) value was also higher in patients with vestibular PE than in those with vestibular (P=0.002) and cochlear EH (P=0.003). Video head impulse test (vHIT) gains were lower in patients with vestibular and cochlear PE than in those with vestibular and cochlear EH (P<0.001). A positive correlation was observed between the degree of vestibular and cochlear EH and PTA (both P values <0.001). PTA and CP with a cutoff value of 32 dB and 46.5%, respectively, yielded high sensitivity and specificity in determining positive MRI findings (P<0.001 and P=0.029, respectively). The prevalence of vascular risk factors was significantly higher in patients with PE than in those with EH (P=0.033)., Conclusions: (I) Nearly half of the patients UPVD exhibited abnormal MRI findings. Cutoff values for PTA and CP of 32 dB and 46.5%, respectively, indicated that patients were more likely to have abnormal imaging findings. (II) The severity of EH was positively correlated with hearing impairment. (III) Patients with PE showed severe hearing impairment and vestibular dysfunction, which was presumed to be associated with vascular damage., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1268/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Purpose: To automatically evaluate renal masses in CT images by using a cascade 3D U-Net- and ResNet-based method to accurately segment and classify focal renal lesions., Material and Methods: We used an institutional dataset comprising 610 CT image series from 490 patients from August 2009 to August 2021 to train and evaluate the proposed method. We first determined the boundaries of the kidneys on the CT images utilizing a 3D U-Net-based method to be used as a region of interest to search for renal mass. An ensemble learning model based on 3D U-Net was then used to detect and segment the masses, followed by a ResNet algorithm for classification. Our algorithm was evaluated with an external validation dataset and kidney tumor segmentation (KiTS21) challenge dataset., Results: The algorithm achieved a Dice similarity coefficient (DSC) of 0.99 for bilateral kidney boundary segmentation in the test set. The average DSC for renal mass delineation using the 3D U-Net was 0.75 and 0.83. Our method detected renal masses with recalls of 84.54% and 75.90%. The classification accuracy in the test set was 86.05% for masses (<5 mm) and 91.97% for masses (≥5 mm)., Conclusion: We developed a deep learning-based method for fully automated segmentation and classification of renal masses in CT images. Testing of this algorithm showed that it has the capability of accurately localizing and classifying renal masses., Competing Interests: Authors YS and YZ were employed by the company Beijing Smart Tree Medical Technology Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Sun, Guo, Sun, Zhang and Wang.)

High levels of reactive oxygen species (ROS) and inflammation create a complicated extrinsic neural environment that dominates the initial post-injury period after spinal cord injury (SCI). The compensatory pathways between ROS and inflammation limited the efficacy of modulating the above single treatment regimen after SCI. Here, novel "nanoflower" Mn 3 O 4 integrated with "pollen" IRF-5 SiRNA was designed as a combination antioxidant and anti-inflammatory treatment after SCI. The "nanoflower" and "pollen" structure was encapsulated with a neutrophil membrane for protective and targeted delivery. Furthermore, valence-engineered nanozyme Mn 3 O 4 imitated the cascade response of antioxidant enzymes with a higher substrate affinity compared to natural antioxidant enzymes. Nanozymes effectively catalyzed ROS to generate O 2 , which is advantageous for reducing oxidative stress and promoting angiogenesis. The screened "pollen" IRF-5 SiRNA could reverse the inflammatory phenotype by reducing interferon regulatory factors-5 (IRF-5) expression (protein level: 73.08% and mRNA level: 63.10%). The decreased expression of pro-inflammatory factors reduced the infiltration of inflammatory cells, resulting in less neural scarring. In SCI rats, multifunctional nanozymes enhanced the proliferation of various neuronal subtypes (motor neurons, interneurons, and sensory neurons) and the recovery of locomotor function, demonstrating that the remodeling of the extrinsic neural environment is a promising strategy to facilitate nerve regeneration., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

How to eliminate haze pollution is a major concern for all countries around the world. Based on panel data from 286 cities in China from 2011 to 2019, the article examines the impact of the digital economy development (DIGS) on haze pollution and the impact of transmission mechanisms in different dimensions using various methods such as the fixed effects model, mediated effects model, and threshold effects model. The study found that firstly, DIGS helps reduce pollution, and further research found that DIGS contributes to the reduction of haze pollution in the western region by improving the market allocation of factors. Secondly, the study concludes that the DIGS shows heterogeneity by dividing the full sample according to region, level of factor marketization, and city size. Finally, the threshold test model finds that the relationship between the DIGS and haze pollution is non-linear depending on the economic development level. The research in this paper provides new research literature on the development of the digital economy and the reduction of haze pollution, contributing to the development of a green economy in China., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To investigate the localization diagnostic value of the ocular tilt reaction (OTR) plus head tilt subjective visual vertical (SVV) in patients with acute central vascular vertigo (ACVV)., Methods: We enrolled 40 patients with acute infarction, 20 with unilateral brainstem infarction (BI) and 20 with unilateral cerebellar infarction (CI). We also included 20 patients with unilateral peripheral vestibular disorders (UPVD) as the control group. The participants completed the OTR and SVV during head tilt (±45°) within 1 week of symptom onset., Results: In patients with ACVV, including that caused by lateral medullary infarction (100%, 2/2), partial pontine infarction (21%, 3/14), and cerebellum infarction (35%, 7/20), we observed ipsiversive OTR, similar to that seen in UPVD patients (80.0%, 16/20). Some of the patients with medial medullary infarction (50%, 1/2), partial pons infarction (42%, 6/14), midbrain infarction (100%, 2/2), and partial cerebellum infarction (30.0%, 6/20) showed contraversive OTR. The skew deviation (SD) of the BI group with ACVV was significantly greater than that of the UPVD group (6.60 ± 2.70° vs. 1.80 ± 1.30°, Z = -2.50, P = 0.012), such that the mean SD of the patients with a pons infarction was 9.50° and that of patients with medulla infarction was 5.00°. In ACVV patients with no cerebellar damage, the area under the curve of the receiver operating characteristic curve corresponding to the use of SD to predict brainstem damage was 0.92 (95%CI: 0.73-1.00), with a sensitivity of 100% and a specificity of 80% when SD ≥ 3°. We found no statistical difference in SD between the UPVD and CI groups (1.33 ± 0.58° vs. 1.80 ± 1.30°, Z = -0.344, P = 0.73). Compared with the UPVD patients, the ACVV patients with a partial pons infarction (43%, 6/14, χ 2 = 13.68, P = 0.002) or medulla infarction (25%, 1/4, χ 2 = 4.94, P = 0.103) exhibited signs of the ipsiversive E-effect with the contraversive A-effect, while those with a partial medulla infarction (50%, 2/4), pons infarction (43%, 6/14), or cerebellar infarction (60%, 12/20) exhibited a pathological symmetrical increase in the E-effect., Conclusions: The evaluation of OTR plus head tilt SVV (±45°) in vertigo patients is helpful for identifying and diagnosing ACVV, especially when SD is ≥ 3° or the E-effect is symmetrically increased., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Feng, Zhao, Wu, Ling, Zhang, Song, Kim and Yang.)

Low Impact Development (LID) is an effective measure in controlling the urban runoff and mitigating the non-point source pollution. The determination of LID facilities and layouts for a sub-catchment is important for designing stormwater management system. However, there are remain large uncertainty and challenge exist in determination of LID facilities when consider budget, land use, soil surface and groundwater as well as local climate etc. To address this issue, this study employed Genetic Algorithm (GA) for optimization of the selection and layout of LID. The urban runoff was simulated using Environmental Protection Agency (EPA) Storm Water Management Model (SWMM). The LID planning was encoded as 0 and 1 in GA algorithm. The multiple objectives which include runoff reduction, area of LID and life cycle cost were selected as optimization targets. To test the model performance, the Airport Economic Zone in Tianjin, China was chosen as the study area. The results demonstrate that the combination of LID approaches are most effective measures on runoff reduction through long-term simulation (10 years' rainfall events). The impact of different weights of land area and cost on LID selection were evaluated when considering life cycle cost. Bio-Retention is preferred when considering the area of LID and Green Roof is recommended when the cost is prioritized. The present research proved GA is feasible for LID planning in urban area. The proposed method can help the decision-makers to determine the LID plan more scientific based on SWMM model and GA., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study uses the bioecological model of human development to understand the academic career development of Chinese returnees with overseas Ph.D. degrees (CROPs). Focuses are placed on how CROPs engaged in this process through interactions with contexts, which lead to their differentiated and similar career development in Chinese higher education. Using a qualitative approach of semi-structured interviews with 31 CROPs, our findings reveal that CROPs' academic career development is co-shaped by personal characteristics and multi-layered environmental contexts. The study highlights the dysfunctionality of Chinese higher education system in the context of China's ambition to build First-class Universities and First-class Subjects (Double First-class), which constrains CROPs' academic career development. The paper offers important implications for potential CROPs, policy, and future research studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Xu, Zhao and Che.)

Background: Mild cognitive impairment (MCI) is a kind of non-functional cognitive decline between normal aging and dementia. With the increase of individual age, the quality of cognitive function has become a more and more important topic. The study of gene loci in patients with MCI is essential for the prevention of dementia. In this study, we evaluate the gene polymorphism in Chinese Han patients with MCI by propensity score matching (PSM) and comparing them to healthy control (HC) subjects., Methods: Four hundred seventeen patients with mild cognitive impairment and 508 healthy people were included. The two groups were matched by applying one-to-one PSM, and the matching tolerance was set to 0.002. The matching covariates included gender,age,occupation,marital status,living mode. Then, a case-control associated analysis was conducted to analyze the genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in the MCI group and the control group., Results: Three hundred eleven cases were successfully matched in each group, and there was no statistical difference on all the matching variables, gender, age, occupation, marital status, living mode between two groups after the match (P > 0.05). The allele frequency of bridging integrator 1(BIN1) rs7561528 showed minimal association with MCI in the Han Chinese population (P = 0.01). Compared with the healthy control (HC) group, A allele frequency of MCI group patients was significantly decreased. The genotype frequency of BIN1 rs6733839 showed minimal association with MCI in the recessive model (P = 0.03). The genotype frequency of rs7561528 showed minimal association with MCI in the codominant, dominant, overdominant, and log-additive model (P < 0.05). The genotype frequencies of StAR-related lipid transfer domain 6 (STARD6) rs10164112 showed nominal association with MCI in the codominant, dominant, and log-additive model (P < 0.05). Unfortunately, the significant differences did not survive Benjamini-Hochberg false discovery rate correction (adjusted P > 0.05). The patients with SPI1 rs1057233 may be the protective factor of MCI (OR = 0.733, 95%CI 0.625-0.859, P < 0.001), and patients with APOE rs10164112 may be a risk factor for MCI (OR = 1.323, 95%CI 1.023-1.711, P = 0.033)., Conclusions: The polymorphisms of rs7561528, rs6733839 loci in the BIN1 gene, and rs1057233 loci in the SPI1 gene may be associated with the MCI in Chinese Han population. APOE gene was the risk factor of MCI, but further verification in a large sample population is still needed., (© 2022. The Author(s).)

The state and behaviour of a cell can be influenced by both genetic and environmental factors. In particular, tumour progression is determined by underlying genetic aberrations 1-4 as well as the makeup of the tumour microenvironment 5,6 . Quantifying the contributions of these factors requires new technologies that can accurately measure the spatial location of genomic sequence together with phenotypic readouts. Here we developed slide-DNA-seq, a method for capturing spatially resolved DNA sequences from intact tissue sections. We demonstrate that this method accurately preserves local tumour architecture and enables the de novo discovery of distinct tumour clones and their copy number alterations. We then apply slide-DNA-seq to a mouse model of metastasis and a primary human cancer, revealing that clonal populations are confined to distinct spatial regions. Moreover, through integration with spatial transcriptomics, we uncover distinct sets of genes that are associated with clone-specific genetic aberrations, the local tumour microenvironment, or both. Together, this multi-modal spatial genomics approach provides a versatile platform for quantifying how cell-intrinsic and cell-extrinsic factors contribute to gene expression, protein abundance and other cellular phenotypes., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Rationale: Enhanced proliferation and distal migration of human pulmonary arterial smooth muscle cells (hPASMCs) both contribute to the progressive increases in pulmonary vascular remodeling and resistance in pulmonary arterial hypertension (PAH). Our previous studies revealed that Rictor deletion, to disrupt mTOR Complex 2 (mTORC2), over longer periods result in a paradoxical rise in platelet-derived growth factor receptor (PDGFR) expression in PASMCs. Thus, the purpose of this study was to evaluate the role of combination therapy targeting both mTOR signaling with PDGFR inhibition to attenuate the development and progression of PAH. Methods and Results: Immunoblotting analyses revealed that short-term exposure to rapamycin (6h) significantly reduced phosphorylation of p70S6K (mTORC1-specific) in hPASMCs but had no effect on the phosphorylation of AKT (p-AKT S473, considered mTORC2-specific). In contrast, longer rapamycin exposure (>24 h), resulted in differential AKT (T308) and AKT (S473) phosphorylation with increases in phosphorylation of AKT at T308 and decreased phosphorylation at S473. Phosphorylation of both PDGFRα and PDGFRβ was increased in hPASMCs after treatment with rapamycin for 48 and 72 h. Based on co-immunoprecipitation studies, longer exposure to rapamycin (24-72 h) significantly inhibited the binding of mTOR to Rictor, mechanistically suggesting mTORC2 inhibition by rapamycin. Combined exposure of rapamycin with the PDGFR inhibitor, imatinib significantly reduced the proliferation and migration of hPASMCs compared to either agent alone. Pre-clinical studies validated increased therapeutic efficacy of rapamycin combined with imatinib in attenuating PAH over either drug alone. Specifically, combination therapy further attenuated the development of monocrotaline (MCT)- or Hypoxia/Sugen-induced pulmonary hypertension (PH) in rats as demonstrated by further reductions in the Fulton index, right ventricular systolic pressure (RVSP), pulmonary vascular wall thickness and vessel muscularization, and decreased proliferating cell nuclear antigen (PCNA) staining in PASMCs. Conclusion: Prolonged rapamycin treatment activates PDGFR signaling, in part, via mTORC2 inhibition. Combination therapy with rapamycin and imatinib may be a more effective strategy for the treatment of PAH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shi, Gu, Zhao, Jia, Bao, Luo, Guo, Han, Wang, Black, Desai and Tang.)

An ultrawide bandwidth and single-mode polarization beam splitter (PBS) based on an air-gap type of dual-hollow-core antiresonant fiber (DHC-ARF) is proposed. Nested tubes are introduced into two cladding tubes between two cores to weaken the wavelength dependence of coupling length in DHC-ARF for obtaining ultrawide bandwidth. By tuning the cladding tube sizes, higher-order core modes with the lowest loss can be coupled with cladding tube modes, and thus, effectively, single-mode operation is achieved. Numerical results demonstrate that an 8.15 cm long DHC-ARF can be used to develop a PBS with an operating bandwidth of 370 nm ranging from 1.28 to 1.65 µm, where a polarization extinction ratio is below -20 d B and a high-order mode extinction ratio exceeds 100.

Cartilage damage is one of the main causes of disability, and 3D bioprinting technology can produce complex structures that are particularly suitable for constructing a customized and irregular tissue engineering scaffold for cartilage repair. Alginate is an attractive biomaterial for bioinks because of its good biological safety profile and fast ionic gelation. However, ionically crosslinked alginate hydrogels are recognized as lacking enough mechanical property and long-term stability due to ion exchange. Here, we developed a double crosslinked alginate (DC-Alg) hydrogel for 3D bioprinting, and human umbilical cord mesenchymal stem cells (huMSCs) could differentiate into chondrocytes on its printed 3D scaffold after 4 weeks' culture. We performed sequential modification of alginate with L-cysteine and 5-norbornene-2-methylamine, and the DC-Alg hydrogels were obtained in the presence of CaCl 2 and ultraviolet light with stronger mechanical properties than those of the single ionic crosslinked alginate hydrogels, which was similar to natural cartilage. They also had better stability and could be maintained in DMEM medium for over 1 month, as well good viability for huMSCs. Moreover, the DC-Alg as 3D printing inks demonstrated a better printing accuracy (∼200 µm). After 4 weeks culture of huMSCs in the 3D printed DC-Alg scaffolds, the expressions of chondrogenic genes such as aggrecan (agg), collagen II (col II), and SRY-box transcription factor 9 (sox- 9) were obviously observed, indicating the differentiation of huMSCs into cartilage. Immumohistochemical staining analysis further exhibited cartilage tissue developed well in the 3D printed scaffolds. Our study is the first demonstration of DC-Alg in 3D printing for MSC differentiation into cartilage, which shows a potential application in cartilage defect repair., (© 2021 IOP Publishing Ltd.)

Objectives: Leptin is a crucial regulator of energy balance and is associated with obesity. In recent years, it has also been recognized as involved in the psychopathological mechanism. Our study aimed to elucidate the relationships between serum leptin levels, body mass index (BMI), and psychopathology symptoms in patients with schizophrenia. Methods: A cross-sectional assessment of 324 inpatients with schizophrenia was conducted. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS). Serum leptin levels were assessed by the Enzyme-Linked Immunosorbent Assay (ELISA). Results: Significant differences in sex, BMI, and negative symptom subscale (PANSS-N) scores were found between the groups with high and low leptin levels in the study. Leptin levels were positively correlated with BMI (B = 2.322, t = 9.557, P < 0.001) and negatively correlated with PANSS-N scores (B = -0.303, t = -2.784, P = 0.006). Conclusions: Our results suggest that the increase in leptin levels is responsible for antipsychotic-induced weight gain and improved psychopathological symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Li, Yao, Yang, Ning, Zhao, Xia, Zhang, Zhang and Liu.)

Protein micropatterning on microfabricated surfaces is a promising technology in applications for biochip microarrays, cell attachment, and biosensors. In the present work, a novel photoresponsive polymer based on light-triggered charge shifting bridged polysilsesquioxane (CBPS) is designed and prepared. The organic bridged units containing a photocleavable group of diethylaminocoumarin-4-yl in CBPS could be cleaved rapidly upon irradiation at 410 nm, resulting in the polymer surface switching from a positive charge to a negative charge property. The photoresponsive behavior of CBPS is studied using FTIR, UV-vis, SEM, fluorescence microscopy, and zeta potential analysis. Proteins are easily immobilized on the polymer surface via electrostatic interactions and released after irradiation as required. Combined with photopatterning techniques, accurate protein micropatterns are fabricated by covering a photomask upon irradiation. A gradient protein pattern is also spatially and temporally controlled by regulating irradiation parameters. This smart photoresponsive polymer surface provides a gentle and straightforward strategy to micropattern charged proteins. Moreover, the photoresponsive polymer holds permitting potential in biomedical applications such as conjugating biomolecules, guiding cell arrays, and resisting bacteria.

Precise control of target molecule release time, site, and dosage remains a challenge in controlled release systems. We employed a photoresponsive molecule release system via light-triggered charge reversal nanoparticles to achieve a triggered, stepwise, and precise controlled release platform. This release system was based on photocleavage-bridged polysilsesquioxane nanoparticles which acted as nanocarriers of doxorubicin loaded on the surface via electrostatic interaction. The nanoparticles could reverse into positive charges triggered by 254 nm light irradiation due to the photocleavage of the o -nitrobenzyl bridged segment. The charge reversal property of the nanoparticles could release loaded molecules. Doxorubicin was selected as a positively charged model molecule. The as-prepared nanoparticles with an average size of 124 nm had an acceptable doxorubicin loading content up to 12.8%. The surface charge of the nanoparticles could rapidly reverse from negative (-28.20 mV) to positive (+18.9 mV) upon light irradiation for only 10 min. In vitro release experiments showed a cumulative release up to 96% with continuously enhancing irradiation intensity. By regulating irradiation parameters, precisely controlled drug release was carried out. The typical "stepped" profile could be accurately controlled in an on/off irradiation mode. This approach provides an ideal light-triggered molecule release system for location, timing, and dosage. This updated controlled release system, triggered by near-infrared or infrared light, will have greater potential applications in biomedical technology.

Rationale and Objective: Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders., Methods: We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue., Results: Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients' BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α., Conclusion: Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.

Background: Convenient and precise assessment of the severity in coronavirus disease 2019 (COVID-19) contributes to the timely patient treatment and prognosis improvement. We aimed to evaluate the ability of CT-based radiomics nomogram in discriminating the severity of patients with COVID-19 Pneumonia., Methods: A total of 150 patients (training cohort n = 105; test cohort n = 45) with COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR) test were enrolled. Two feature selection methods, Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO), were used to extract features from CT images and construct model. A total of 30 radiomic features were finally retained. Rad-score was calculated by summing the selected features weighted by their coefficients. The radiomics nomogram incorporating clinical-radiological features was eventually constructed by multivariate regression analysis. Nomogram, calibration, and decision-curve analysis were all assessed., Results: In both cohorts, 40 patients with COVID-19 pneumonia were severe and 110 patients were non-severe. By combining the 30 radiomic features extracted from CT images, the radiomics signature showed high discrimination between severe and non-severe patients in the training set [Area Under the Curve (AUC), 0.857; 95% confidence interval (CI), 0.775-0.918] and the test set (AUC, 0.867; 95% CI, 0.732-949). The final combined model that integrated age, comorbidity, CT scores, number of lesions, ground glass opacity (GGO) with consolidation, and radiomics signature, improved the AUC to 0.952 in the training cohort and 0.98 in the test cohort. The nomogram based on the combined model similarly exhibited excellent discrimination performance in both training and test cohorts., Conclusions: The developed model based on a radiomics signature derived from CT images can be a reliable marker for discriminating the severity of COVID-19 pneumonia.

Background: Previous research has indicated that there are significant sex differences in serum BDNF levels and metabolic indicators in patients with schizophrenia. Studies have found that BDNF is involved in blood sugar regulation. Homeostasis model assessment of insulin resistance (HOMA-IR) is currently a sensitive indicator for measuring insulin resistance. Our study aims to explore the sex differences in the relationship between serum BDNF levels and HOMA-IR in patients with chronic schizophrenia (CS). Methods: A total of 332 patients with CS were enrolled in this study. General information of all participants was collected. Haematological indicators were collected, and the Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychiatric symptoms. Sex differences in serum BDNF levels, HOMA-IR index and other metabolic indexes were investigated. Then, linear regression analysis was used to analyse the relationship between the HOMA-IR index and BDNF levels in male and female patients. Results: The HOMA-IR index of female patients was significantly higher than that of males, but there was no significant difference in serum BDNF levels between male patients and female patients. There was a positive correlation between BDNF level and HOMA-IR index, and this relationship only existed in female patients. Conclusion: The results show that there are significant sex differences in HOMA-IR in patients with CS. In addition, only in female patients was there a positive correlation between the HOMA-IR index and BDNF level, which suggests that sex factors should be taken into account in evaluating the relationship between BDNF and blood glucose in patients with CS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Zhang, Wang, Ning, Zhang, Zhao, Zhong, Liu, Xia, Li, Yao, Zhang and Liu.)

Previous studies have shown that high homocysteine worsens the occurrence, symptoms, and prognosis of patients with schizophrenia. The purpose of this study was to evaluate the prevalence, clinical correlation, and demographic characteristics of hyperhomocysteinemia in Han Chinese schizophrenia patients. In this study, we enrolled 330 schizophrenia patients and 190 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to evaluate the psychiatric symptoms of patients with schizophrenia. The plasma homocysteine level was measured by the enzyme cycle method and the concentration of homocysteine > 15 μmol/L was defined as hyperhomocysteinemia. The prevalence of hyperhomocysteinemia in Han Chinese schizophrenia patients and healthy controls was 55.05% and 26.98%, respectively. Schizophrenia patients with hyperhomocysteinemia had more male proportion, older age, higher smoking rate, lower HDL level, higher PANSS total score, and higher negative factor than those patients without hyperhomocysteinemia. Binary logical regression result showed that gender and age were the independent risk factors of hyperhomocysteinemia. Han Chinese patients with schizophrenia had high prevalence hyperhomocysteinemia than healthy controls, and elderly male patients have a higher risk of hyperhomocysteinemia. This study was registered in the China Clinical Trial Registration Center (chiCTR 1800017044).

Purpose: By analyzing the CT manifestations and evolution of COVID in non-epidemic areas of southeast China, analyzing the developmental abnormalities and accompanying signs in the early and late stages of the disease, providing imaging evidence for clinical diagnosis and identification, and assisting in judging disease progression and monitoring prognosis. Methods: This retrospective and multicenter study included 1,648 chest CT examinations from 693 patients with laboratory-confirmed COVID-19 infection from 16 hospitals of southeast China between January 19 and March 27, 2020. Six trained radiologists analyzed and recorded the distribution and location of the lesions in the CT images of these patients. The accompanying signs include crazy-paving sign, bronchial wall thickening, microvascular thickening, bronchogram sign, fibrous lesions, halo and reverse-halo signs, nodules, atelectasis, and pleural effusion, and at the same time, they analyze the evolution of the abovementioned manifestations over time. Result: There were 1,500 positive findings in 1,648 CT examinations of 693 patients; the average age of the patients was 46 years, including 13 children; the proportion of women was 49%. Early CT manifestations are single or multiple nodular, patchy, or flaky ground-glass-like density shadows. The frequency of occurrence of ground-glass shadows (47.27%), fibrous lesions (42.60%), and microvascular thickening (40.60%) was significantly higher than that of other signs. Ground-glass shadows increase and expand 3-7 days after the onset of symptoms. The distribution and location of lesions were not significantly related to the appearance time. Ground-glass shadow is the most common lesion, with an average absorption time of 6.2 days, followed by consolidation, with an absorption time of about 6.3 days. It takes about 8 days for pure ground-glass lesions to absorb. Consolidation change into ground glass or pure ground glass takes 10-14 days. For ground-glass opacity to evolve into pure ground-glass lesions, it takes an average of 17 days. For ground-glass lesions to evolve into consolidation, it takes 7 days, pure ground-glass lesions need 8 days to evolve into ground-glass lesions. The average time for CT signs to improve is 10-15 days, and the first to improve is the crazy-paving sign and nodules; while the progression of the disease is 6-12 days, the earliest signs of progression are air bronchogram signs, bronchial wall thickening, and bronchiectasis. There is no severe patient in this study. Conclusion: This study depicts the CT manifestation and evolution of COVID in non-epidemic origin areas, and provides valuable first-hand information for clinical diagnosis and judgment of patient's disease evolution and prediction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Jiaerken, Li, Huang, Shen, Zhao, Zheng, Ji, Gao, Xia, Cheng, Ma, Liu, Liu, Su, Ruan, Shu, Ren, Zhao, Yao, Yang and Zhang.)

Natural mitochondrial DNA (mtDNA) mutations enable the inference of clonal relationships among cells. mtDNA can be profiled along with measures of cell state, but has not yet been combined with the massively parallel approaches needed to tackle the complexity of human tissue. Here, we introduce a high-throughput, droplet-based mitochondrial single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq), a method that combines high-confidence mtDNA mutation calling in thousands of single cells with their concomitant high-quality accessible chromatin profile. This enables the inference of mtDNA heteroplasmy, clonal relationships, cell state and accessible chromatin variation in individual cells. We reveal single-cell variation in heteroplasmy of a pathologic mtDNA variant, which we associate with intra-individual chromatin variability and clonal evolution. We clonally trace thousands of cells from cancers, linking epigenomic variability to subclonal evolution, and infer cellular dynamics of differentiating hematopoietic cells in vitro and in vivo. Taken together, our approach enables the study of cellular population dynamics and clonal properties in vivo.

OBJECTIVE. The purpose of this study is to characterize the CT findings of 30 children from mainland China who had laboratory-confirmed coronavirus disease (COVID-19). Although recent American College of Radiology recommendations assert that CT should not be used as a screening or diagnostic tool for patients with suspected COVID-19, radiologists should be familiar with the imaging appearance of this disease to identify its presence in patients undergoing CT for other reasons. MATERIALS AND METHODS. We retrospectively reviewed the CT findings and clinical symptoms of 30 pediatric patients with laboratory-confirmed COVID-19 who were seen at six centers in China from January 23, 2020, to February 8, 2020. Patient age ranged from 10 months to 18 years. Patients older than 18 years of age or those without chest CT examinations were excluded. Two cardiothoracic radiologists and a cardiothoracic imaging fellow characterized and scored the extent of lung involvement. Cohen kappa coefficient was used to calculate interobserver agreement between the readers. RESULTS. Among children, CT findings were often negative (77%). Positive CT findings seen in children included ground-glass opacities with a peripheral lung distribution, a crazy paving pattern, and the halo and reverse halo signs. There was a correlation between increasing age and increasing severity of findings, consistent with reported symptomatology in children. Eleven of 30 patients (37%) underwent follow-up chest CT, with 10 of 11 examinations (91%) showing no change, raising questions about the utility of CT in the diagnosis and management of COVID-19 in children. CONCLUSION. The present study describes the chest CT findings encountered in children with COVID-19 and questions the utility of CT in the diagnosis and management of pediatric patients.

A novel vortex ring personalized ventilation system (VRPV) is proposed for efficiently supplying fresh air to room occupants. A vortex ring generator with a piston-cylinder is developed for an experimental study of the formation, transportation, and ventilation characteristics of the VRPV. The translational velocity, volume, and fresh air ratio of the vortex rings are studied using high-speed cameras and tracer gas experiments. According to the results, the categories of the vortex ring volume in the formation stage are studied. It is observed that the velocity of the piston determines the initial translational velocity of the vortex ring, and a fitting equation is proposed to predict the evolution of the translational velocity. The deviation range of the VRPV over different distances is studied, and it is shown to be affected by interference from both the generator and the environment. Finally, the total volumes, fresh air volumes, and fresh air ratios of the VRPV are studied at different distances. The results indicate that, as a personalized ventilation system, the fresh air ratio of the VRPV is up to 159.3% higher than that of a symmetrical round jet within a 0-4 m range. This shows the excellent application potential of the VRPV for providing high-efficiency personalized ventilation with lower fresh airflow rates., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Orexin-A is involved in numerous physiological functions, such as feeding behavior and energy balance. Yet, the associations among the orexin system, weight changes and the clinical symptoms of schizophrenia patients remain uncertain, especially in inpatients with chronic schizophrenia (CS). The purpose of this study was to investigate the relationship between the orexin-A levels, body mass index (BMI) and clinical symptoms of CS inpatients. Methods: Altogether, 324 inpatients were enrolled in our study. The clinical symptoms of all inpatients were measured using a 30-item Positive and Negative Syndrome Scale (PANSS), and then we calculated the BMI of each subject and tested the orexin-A levels by ELISA methods. Results: The orexin-A levels of the CS inpatients in the obesity group (1.24   ±   1.45   ng/ml, n   =   52) were significantly higher than those in the non-overweight group (0.85   ±   1.18   ng/ml, n   =   176) and the overweight group (0.97   ±   1.15   ng/ml, n   =   96). Spearman's correlation analysis showed that higher BMIs were associated with higher plasma orexin-A levels and fewer negative symptoms. Furthermore, the multiple regression analysis indicated that the orexin-A level could be a contributor to BMI ( F   =   30.21, p   <   0.001). However, there was no correlation between plasma orexin-A concentrations and clinical symptoms in our research. Conclusion: A higher plasma orexin-A level may be a factor influencing the BMI of inpatients with CS, and fewer negative symptoms seem to be correlated with higher BMI, but the causality among BMI, orexin-A and clinical symptoms of schizophrenia requires further clinical research.

Background: Schizophrenia patients with a metabolically abnormal obese (MAO) phenotype have been shown poor cardiovascular outcomes, but the characteristics of their current psychiatric symptoms have not been characterized. This study mainly explored the psychiatric symptoms of schizophrenia patients with the MAO phenotype., Methods: A total of 329 patients with schizophrenia and 175 sex- and age-matched people without schizophrenia from Anhui Province in China were enrolled. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms of the schizophrenia patients. The MAO phenotype was defined as meeting 1-4 metabolic syndrome criteria (excluding waist circumference) and having a body mass index (BMI) ≥ 28 kg/m 2 . And, metabolically healthy normal-weight (MHNW) phenotype was defined as meeting 0 criteria for metabolic syndrome and 18.5 ≤ BMI < 24 kg/m 2 ., Results: Overall, 15.8% of the schizophrenia patients and 9.1% of the control group were consistent with the MAO phenotype, and the prevalence of MAO in the schizophrenia group was higher than that in the control group. Among the patients with schizophrenia, the MAO group had lower negative factor, cognitive factor and total PANSS scores than the MHNW group. However, when confounding factors were controlled, only the negative factor remained lower significantly., Conclusion: We found that schizophrenia patients with the MAO phenotype had reduced negative symptoms, which may indicate an internal mechanism linking metabolic disorders and negative symptoms., Trial Registration: This study was registered in the China Clinical Trial Registration Center (No. chiCTR 1,800,017,044 ).

Background: Chest CT is used for the assessment of the severity of patients infected with novel coronavirus 2019 (COVID-19). We collected chest CT scans of 202 patients diagnosed with the COVID-19, and try to develop a rapid, accurate and automatic tool for severity screening follow-up therapeutic treatment., Methods: A total of 729 2D axial plan slices with 246 severe cases and 483 non-severe cases were employed in this study. By taking the advantages of the pre-trained deep neural network, four pre-trained off-the-shelf deep models (Inception-V3, ResNet-50, ResNet-101, DenseNet-201) were exploited to extract the features from these CT scans. These features are then fed to multiple classifiers (linear discriminant, linear SVM, cubic SVM, KNN and Adaboost decision tree) to identify the severe and non-severe COVID-19 cases. Three validation strategies (holdout validation, tenfold cross-validation and leave-one-out) are employed to validate the feasibility of proposed pipelines., Results and Conclusion: The experimental results demonstrate that classification of the features from pre-trained deep models shows the promising application in COVID-19 severity screening, whereas the DenseNet-201 with cubic SVM model achieved the best performance. Specifically, it achieved the highest severity classification accuracy of 95.20% and 95.34% for tenfold cross-validation and leave-one-out, respectively. The established pipeline was able to achieve a rapid and accurate identification of the severity of COVID-19. This may assist the physicians to make more efficient and reliable decisions.

Purpose: In the clinical management of hypopharyngeal squamous cell carcinoma (HSCC), preoperative identification of early recurrence (≤2 years) after curative resection is essential. Thus, we aimed to develop a CT-based radiomic signature to predict early recurrence in HSCC patients preoperatively., Methods: In total, 167 HSCC patients who underwent partial surgery were enrolled in this retrospective study and divided into two groups, i.e., the training cohort ( n = 133) and the validation cohort ( n = 34). Each individual was followed up for at least for 2 years. Radiomic features were extracted from CT images, and the radiomic signature was built with the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) model. The associations of preoperative clinical factors with early recurrence were evaluated. A radiomic signature-combined model was built, and the area under the curve (AUC) was used to explore their performance in discriminating early recurrence., Results: Among the 1415 features, 335 of them were selected using the variance threshold method. Then, the SelectKBest method was further used for the selection of 31 candidate features. Finally, 11 out of 31 optimal features were identified with the LASSO algorithm. In the LR classifier, the AUCs of the training and validation sets in discriminating early recurrence were 0.83 (95% CI: 0.76-0.90) (sensitivity 0.8 and specificity 0.83) and 0.83 (95% CI: 0.67-0.99) (sensitivity 0.69 and specificity 0.71), respectively., Conclusions: Using the radiomic signature, we developed a radiomic signature to preoperatively predict early recurrence in patients with HSCC, which may serve as a potential noninvasive tool to guide personalized treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Wenming Li et al.)

For diagnosis of coronavirus disease 2019 (COVID-19), a SARS-CoV-2 virus-specific reverse transcriptase polymerase chain reaction (RT-PCR) test is routinely used. However, this test can take up to 2 d to complete, serial testing may be required to rule out the possibility of false negative results and there is currently a shortage of RT-PCR test kits, underscoring the urgent need for alternative methods for rapid and accurate diagnosis of patients with COVID-19. Chest computed tomography (CT) is a valuable component in the evaluation of patients with suspected SARS-CoV-2 infection. Nevertheless, CT alone may have limited negative predictive value for ruling out SARS-CoV-2 infection, as some patients may have normal radiological findings at early stages of the disease. In this study, we used artificial intelligence (AI) algorithms to integrate chest CT findings with clinical symptoms, exposure history and laboratory testing to rapidly diagnose patients who are positive for COVID-19. Among a total of 905 patients tested by real-time RT-PCR assay and next-generation sequencing RT-PCR, 419 (46.3%) tested positive for SARS-CoV-2. In a test set of 279 patients, the AI system achieved an area under the curve of 0.92 and had equal sensitivity as compared to a senior thoracic radiologist. The AI system also improved the detection of patients who were positive for COVID-19 via RT-PCR who presented with normal CT scans, correctly identifying 17 of 25 (68%) patients, whereas radiologists classified all of these patients as COVID-19 negative. When CT scans and associated clinical history are available, the proposed AI system can help to rapidly diagnose COVID-19 patients.

Background: Coronavirus disease 2019 (COVID-19) has widely spread worldwide and caused a pandemic. Chest CT has been found to play an important role in the diagnosis and management of COVID-19. However, quantitatively assessing temporal changes of COVID-19 pneumonia over time using CT has still not been fully elucidated. The purpose of this study was to perform a longitudinal study to quantitatively assess temporal changes of COVID-19 pneumonia., Methods: This retrospective and multi-center study included patients with laboratory-confirmed COVID-19 infection from 16 hospitals between January 19 and March 27, 2020. Mass was used as an approach to quantitatively measure dynamic changes of pulmonary involvement in patients with COVID-19. Artificial intelligence (AI) was employed as image segmentation and analysis tool for calculating the mass of pulmonary involvement., Results: A total of 581 confirmed patients with 1,309 chest CT examinations were included in this study. The median age was 46 years (IQR, 35-55; range, 4-87 years), and 311 (53.5%) patients were male. The mass of pulmonary involvement peaked on day 10 after the onset of initial symptoms. Furthermore, the mass of pulmonary involvement of older patients (>45 years) was significantly severer (P<0.001) and peaked later (day 11 vs. day 8) than that of younger patients (≤45 years). In addition, there were no significant differences in the peak time (day 10 vs. day 10) and median mass (P=0.679) of pulmonary involvement between male and female., Conclusions: Pulmonary involvement peaked on day 10 after the onset of initial symptoms in patients with COVID-19. Further, pulmonary involvement of older patients was severer and peaked later than that of younger patients. These findings suggest that AI-based quantitative mass evaluation of COVID-19 pneumonia hold great potential for monitoring the disease progression., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-4004). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

In this work, the gene of conjugated linoleic acid hydrase (CLA-HY) was cloned from L. plantarum p-8, and the protein of CLA-HY was expressed in Escherichia coli BL21. Gas chromatography-mass spectrometry was employed to verify that the purified CLA-HY can convert linoleic acid (LA) into 10-hydroxy-cis-12-octadecenoic acid (10-HOE) in the presence of flavin adenine dinucleotide (FAD). The optimal pH and temperature for maximizing CLA-HY catalytic activity were found to be 6.0 and 35°C, respectively. In addition, the catalytic ability of CLA-HY can be inhibited by a number of cations such as Mg2+, Mn2+, Zn2+, Cu2+, Fe2+, Fe3+, Ni2+ and Ca2+. Finally, the Km,Vmax, Kcat and Kcat/Km of CLA-HY were determined as 7.62 mM, 2.59 mM h-1, 8.33 × 103 h-1 and 1.09 × 103 mM-1 h-1, respectively. Moreover, it was demonstrated that both M76 and G74 residues played significant roles in catalysing the conversion of LA into 10-HOE using site-directed mutation technology and molecular simulations., (© FEMS 2020.)

For diagnosis of COVID-19, a SARS-CoV-2 virus-specific reverse transcriptase polymerase chain reaction (RT-PCR) test is routinely used. However, this test can take up to two days to complete, serial testing may be required to rule out the possibility of false negative results, and there is currently a shortage of RT-PCR test kits, underscoring the urgent need for alternative methods for rapid and accurate diagnosis of COVID-19 patients. Chest computed tomography (CT) is a valuable component in the evaluation of patients with suspected SARS-CoV-2 infection. Nevertheless, CT alone may have limited negative predictive value for ruling out SARS-CoV-2 infection, as some patients may have normal radiologic findings at early stages of the disease. In this study, we used artificial intelligence (AI) algorithms to integrate chest CT findings with clinical symptoms, exposure history, and laboratory testing to rapidly diagnose COVID-19 positive patients. Among a total of 905 patients tested by real-time RT-PCR assay and next-generation sequencing RT-PCR, 419 (46.3%) tested positive for SARS-CoV-2. In a test set of 279 patients, the AI system achieved an AUC of 0.92 and had equal sensitivity as compared to a senior thoracic radiologist. The AI system also improved the detection of RT-PCR positive COVID-19 patients who presented with normal CT scans, correctly identifying 17 of 25 (68%) patients, whereas radiologists classified all of these patients as COVID-19 negative. When CT scans and associated clinical history are available, the proposed AI system can help to rapidly diagnose COVID-19 patients.

Here we describe TRACE (T7 polymerase-driven continuous editing), a method that enables continuous, targeted mutagenesis in human cells using a cytidine deaminase fused to T7 RNA polymerase. TRACE induces high rates of mutagenesis over multiple cell generations in genes under the control of a T7 promoter integrated in the genome. We used TRACE in a MEK1 inhibitor-resistance screen, and identified functionally correlated mutations.

OBJECTIVE. The objective of our study was to preoperatively predict fat-poor angiomyolipoma (fp-AML) and renal cell carcinoma (RCC) by conducting quantitative analysis of contrast-enhanced CT images. MATERIALS AND METHODS. One hundred fifteen patients with a pathologic diagnosis of fp-AML or RCC from a single institution were randomly allocated into a train set (tumor size: mean ± SD, 4.50 ± 2.62 cm) and test set (tumor size: 4.32 ± 2.73 cm) after data augmentation. High-dimensional histogram-based features, texture-based features, and Laws features were first extracted from CT images and were then combined as different combinations sets to construct a logistic prediction model based on the least absolute shrinkage and selection operator procedure for the prediction of fp-AML and RCC. Prediction performances were assessed by classification accuracy, area under the ROC curve (AUC), positive predictive value, negative predictive value, true-positive rate, and false-positive rate (FPR). In addition, we also investigated the effects of different gray-scales of quantitative features on prediction performances. RESULTS. The following combination sets of features achieved satisfying performances in the test set: histogram-based features (mean AUC = 0.8492, mean classification accuracy = 91.01%); histogram-based features and texture-based features (mean AUC = 0.9244, mean classification accuracy = 91.81%); histogram-based features and Laws features (mean AUC = 0.8546, mean classification accuracy = 88.76%); and histogram-based features, texture-based features, and Laws features (mean AUC = 0.8925, mean classification accuracy = 90.36%). The different quantitative gray-scales did not have an obvious effect on prediction performances. CONCLUSION. The integration of histogram-based features with texture-based features and Laws features provided a potential biomarker for the preoperative diagnosis of fp-AML and RCC. The accurate diagnosis of benign or malignant renal masses would help to make the clinical decision for radical surgery or close follow-up.

Neurons are highly dependent on mitochondrial function, and mitochondrial damage has been implicated in many neurological and neurodegenerative diseases. Here we show that axonal mitochondria are necessary for neuropeptide secretion in Caenorhabditis elegans and that oxidative phosphorylation, but not mitochondrial calcium uptake, is required for secretion. Oxidative phosphorylation produces cellular ATP, reactive oxygen species, and consumes oxygen. Disrupting any of these functions could inhibit neuropeptide secretion. We show that blocking mitochondria transport into axons or decreasing mitochondrial function inhibits neuropeptide secretion through activation of the hypoxia inducible factor HIF-1 Our results suggest that axonal mitochondria modulate neuropeptide secretion by regulating transcriptional responses induced by metabolic stress., (Copyright © 2018 by the Genetics Society of America.)

Background: In mammalian females, progressive activation of dormant primordial follicles in adulthood is crucial for the maintenance of the reproductive lifespan. Misregulated activation of primordial follicles leads to various ovarian diseases, such as premature ovarian insufficiency (POI). Although recent studies have revealed that several functional genes and pathways, such as phosphoinositide 3-kinase (PI3K) signaling, play roles in controlling the activation of primordial follicles, our understanding of the molecular networks regulating the activation progress is still incomplete., Results: Here, we identify a new role for cell division cycle 42 (CDC42) in regulating the activation of primordial follicles in mice. Our results show that CDC42 expression increases in oocytes during the activation of primordial follicles in the ovary. Disruption of CDC42 activity with specific inhibitors or knockdown of Cdc42 expression significantly suppresses primordial follicle activation in cultured mouse ovaries. Conversely, the follicle activation ratio is remarkably increased by overexpression of CDC42 in ovaries. We further demonstrate that CDC42 governs the process of primordial follicle activation by binding to phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (p110β) and regulating the expression levels of PTEN in oocytes. Finally, we extend our study to potential clinical applications and show that a short-term in vitro treatment with CDC42 activators could significantly increase the activation rates of primordial follicles in both neonatal and adult mouse ovaries., Conclusion: Our results reveal that CDC42 controls the activation of primordial follicles in the mammalian ovary and that increasing the activity of CDC42 with specific activators might improve the efficiency of in vitro activation approaches, opening avenues for infertility treatments.

A novel twin-core photonic crystal fiber-based sensor for simultaneous measurement of curvature, strain and temperature is proposed. The fiber sensor is constructed by splicing the homemade twin-core photonic crystal fiber between two segments of single mode fiber. Affected by the coupling between two cores, the transmission spectrum of the fiber sensor has different wavelength responses to curvature, strain, and temperature. The maximal sensitivities to curvature, strain and temperature are 10.89 nm/m -1 , 1.24 pm/με and 73.9 pm/°C, respectively. Simultaneous measurement of curvature, strain and temperature can be achieved by monitoring the wavelength shifts of selected valleys in the transmission spectrum. Contrast experiment based on traditional twin-core fiber is carried out. Experimental results demonstrate that twin-core photonic crystal fiber-based sensor has higher sensitivity and better linearity than traditional twin-core fiber-based sensor., Competing Interests: The authors declare no conflict of interest.

We design an ultrabroadband polarization splitter based on three-core photonic crystal fiber (PCF). A modulation core and two fluorine-doped cores are introduced to achieve an ultrawide bandwidth. The properties of three-core PCF are modeled by using the full-vector finite element method along with the full-vector beam propagation method. Numerical results demonstrate that an ultrabroadband splitter with 320 nm bandwidth with an extinction ratio as low as -20  dB can be achieved by using 52.8 mm long three-core PCF. This splitter also has high compatibility with standard single-mode fibers as the input and output ports due to low splicing loss of 0.02 dB. All the air holes in the proposed structure are circular holes and arranged in a triangular lattice that makes it easy to fabricate.