Repetitive Transcranial Magnetic Stimulation Reversing Abnormal Brain Function in Mood Disorders with Early Life Stress: from preclinical models to clinical applications.

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.

Bidirectional causality between idiopathic sudden sensorineural hearing loss and depression: a Mendelian randomization study.

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.

Biomimetic Dual-Network Collagen Fibers with Porous and Mechanical Cues Reconstruct Neural Stem Cell Niche via AKT/YAP Mechanotransduction after Spinal Cord Injury.

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 CO2 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.

Visual cortex repetitive transcranial magnetic stimulation (rTMS) reversing neurodevelopmental impairments in adolescents with major psychiatric disorders (MPDs): A cross-species translational study.

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.

Aberrant Hippocampal Development in Early-onset Mental Disorders and Promising Interventions: Evidence from a Translational Study.

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.

Clinical and radiological characteristics of pediatric COVID-19 before and after the Omicron outbreak: a multi-center study.

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.

The value of postcontrast delayed 3D fluid-attenuated inversion recovery MRI in the diagnosis of unilateral peripheral vestibular dysfunction.

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.

Automatic renal mass segmentation and classification on CT images based on 3D U-Net and ResNet algorithms.

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.

The value of vestibular graviceptive pathway evaluation in the diagnosis of unilateral peripheral vestibular dysfunction.

BACKGROUND: Evaluation of vestibular graviceptive pathway (VGP) in patients with unilateral peripheral vestibular dysfunction (UPVD) has received increasing attention from researchers. The study aimed to investigate the value of VGP evaluation in the diagnosis of UPVD. METHODS: Ninety-five UPVD patients were divided into attack and remission phase groups. VGP evaluation-related indicators, including subjective visual vertical (SVV), subjective visual horizontal (SVH), head tilt, ocular torsion (OT), and skew deviation (SD), were measured, and their correlations with cochleovestibular function test results were analyzed. The possible etiologies of contralesional VGP (c-VGP) were analyzed. RESULTS: Positive rates of SVV, SVH, OT, and SD were significantly higher, and the degrees of SVV, SVH, and OT were significantly greater in the attack phase group than the remission phase group. The sides with abnormal VGP evaluation results were correlated with the sides with hearing loss, abnormal caloric, and video head impulse test (vHIT) results. A total of 14 patients showed c-VGP, and possible etiologies included contralateral benign paroxysmal positional vertigo (n = 4), bilateral hearing loss (n = 8), bilateral vHIT gain reduction (n = 1), autoimmune diseases (n = 6), vascular risk factors (n = 6), lacunar infarction (n = 3), and endolymphatic hydrops (n = 3). CONCLUSIONS: Alterations in SVV, SVH, OT, and SD were noted in UPVD patients in different phases, which are presumed to be related to dynamic vestibular compensation; correlations between VGP evaluation results and cochleovestibular function test results indicate that VGP evaluation may be helpful for the diagnosis of the side affected in UPVD; the presence of c-VGP may be related to bilateral labyrinth lesions or endolymphatic hydrops on the affected side; and the involvement of autoimmune mechanisms also deserves attention.

Spontaneous nystagmus with an upbeat component: Central or peripheral vestibular disorders?

Objective: To determine the topical diagnosis and etiologies of spontaneous nystagmus (SN) with an upbeat component. Methods: We retrospectively recruited 43 patients with SN with an upbeat component at a university hospital in China from 2020 to 2022. SN with an upbeat component was divided into pure upbeat nystagmus (UBN), SN with a predominant upbeat component, and SN with a non-predominant upbeat component. We analyzed their clinical and neurotologic findings and the final diagnosis. Results: Fourteen (32.6%) of them showed pure UBN, while 29 (67.4%) exhibited SN mixed with an upbeat component, mixed upbeat-horizontal in 15, mixed upbeat-horizontal-torsional in 13, and upbeat-torsional in the remaining one. Pure UBN and SN with a predominant upbeat component were more common in central than in peripheral vestibular disorders [16 (80.0%) vs. 0 (0%), Chi-Square test, p < 0.001]. Central vestibular disorders were diagnosed in 20 (46.5%) patients, peripheral in 14 (32.6%), and undetermined in nine (20.9%) patients. The underlying causes mainly included acute unilateral peripheral vestibulopathy (n = 11), posterior circulation infarction (n = 9), benign recurrent vertigo (n = 4), vestibular migraine (VM, n = 3), and VM of childhood (n = 2). Conclusion: SN with an upbeat component can be seen in both central and peripheral vestibular disorders. Pure UBN was a characteristic sign of central vestibular dysfunction. Central vestibular disorders should be highly suspected when patients show pure UBN or SN with a predominant upbeat component.

Multifunctional Integrated Nanozymes Facilitate Spinal Cord Regeneration by Remodeling the Extrinsic Neural Environment.

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" Mn3 O4 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 Mn3 O4 imitated the cascade response of antioxidant enzymes with a higher substrate affinity compared to natural antioxidant enzymes. Nanozymes effectively catalyzed ROS to generate O2 , 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.

Design, synthesis, and fungicidal activities of novel piperazine thiazole derivatives containing oxime ether or oxime ester moieties.

BACKGROUND: To study the effect of changing the piperidine ring of oxathiapiprolin on the fungicidal activity, we designed and synthesized novel piperazine thiazole derivatives containing oxime ether or oxime ester moieties, and studied their fungicidal activities against Phytophthora capsici in vitro. RESULTS: These derivatives showed moderate to good fungicidal activities against Phytophthora capsici, two oxime ether derivatives showed higher fungicidal activity in vitro than dimethomorph (EC50  = 0.1331 µg mL-1 ) and comparable to oxathiapiprolin (EC50  = 0.0042 µg mL-1 ). Oxime ester derivatives showed significantly reduced activities compared with oxime ether derivatives. Most of these derivatives showed broad-spectrum fungicidal activity against the other eight kinds of fungi. Moreover, four derivatives exhibited good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. The hyphae morphology study showed that compound 10d might cause mycelial abnormalities of Phytophthora capsici. CONCLUSION: The activity of 10b against Phytophthora infestans was better than that of mandipropamid, and compound 10d exhibited higher fungicidal activities against Pseudoperonospora cubensis and Phytophthora infestans than mandipropamid. These two derivatives emerged as promising candidates for antifungal drugs. © 2023 Society of Chemical Industry.

The impact of the digital economy development on haze pollution: evidence from the perspective of factor marketization.

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.

The diagnostic value of the ocular tilt reaction plus head tilt subjective visual vertical (±45°) in patients with acute central vascular vertigo.

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, χ2 = 13.68, P = 0.002) or medulla infarction (25%, 1/4, χ2 = 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.

Flow characteristics and formation optimization of vortex ring air supply.

The vortex rings ventilation (VRV) is a new type of air supply system comprising vortex rings. Compared with an air supply jet, a vortex ring reduces the loss of fresh air during transportation because of its stable structure. However, during the formation of the vortex ring, it entrains the ambient air and reduces the fresh air in the vortex ring. In this study, a vortex ring generator with a fresh air cavity is proposed to form confined vortex rings. This improved the fresh air ratio of the VRV. Based on previous experiments, a piston-orifice axisymmetric model with a dynamic grid was developed to form an air vortex ring. The flow characteristics of free and confined vortex rings during the generation stage were studied. First, the evolution of free vortex rings with different stroke lengths was studied, and the optimal piston stroke length and radial constraint size were determined. Subsequently, the mixing ratios of the free and confined vortex rings were compared and analyzed. The results showed that the mixing ratio of the confined vortex ring formed by the fresh air cavity in the formation stage was zero. Moving to the location of 4.9 times the orifice diameter ( D 0 $$ {D}_0 $$ ), reduced the mixing ratio of the confined vortex ring by 77.78% compared with that of the free vortex ring. In addition, the influence of three inner diameters and four outlet diameters of fresh air cavities on the vortex rings was studied to optimize the size of the vortex ring generator. The results showed that the inner diameter of the fresh air cavity was greater than 3 D 0 $$ 3{D}_0 $$ and that an outlet diameter greater than 2.5 D 0 $$ 2.5{D}_0 $$ had little influence on the vortex rings.

Academic Career Development of Chinese Returnees With Overseas Ph.D. Degrees: A Bioecological Development Perspective.

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.

Evaluation of mild cognitive impairment genetic susceptibility risks in a Chinese population.

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.

The optimization of Low Impact Development placement considering life cycle cost using Genetic Algorithm.

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.

Spatial genomics enables multi-modal study of clonal heterogeneity in tissues.

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 aberrations1-4 as well as the makeup of the tumour microenvironment5,6. 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.