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1.
Sci Data ; 11(1): 463, 2024 May 07.
Article En | MEDLINE | ID: mdl-38714688

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.


Brain , Child Development , Child , Child, Preschool , Humans , Brain/growth & development , Brain/diagnostic imaging , China , Cognition , Databases, Factual , Neuroimaging
2.
Materials (Basel) ; 17(6)2024 Mar 17.
Article En | MEDLINE | ID: mdl-38541530

In order to examine the mechanical properties and rotational bending fatigue performance of 40CrNi2MoE steel subsequent to tempering at varying temperatures, the steel specimen was subjected to tempering within the range of 400~460 °C. SEM, EBSD, and TEM were used to analyze the microstructure as well as precipitates. The strain hardening law was studied using the modified Crussard-Jaoult method. Investigations were undertaken to reveal the rotational bending fatigue life with respect to the tempering temperature. The findings indicate that the strength and fatigue life of the examined steels exhibit a decline as the tempering temperature increases, with the primary factor affecting this trend being the alteration in dislocation density. No notable impact on the fatigue fracture morphology exerted by tempering temperature was found within the range of the experiment. The C-J model analysis reveals that the work-hardening behavior of the trial steels is influenced by dislocations and the second phase.

3.
World J Clin Cases ; 11(32): 7795-7805, 2023 Nov 16.
Article En | MEDLINE | ID: mdl-38073690

BACKGROUND: Laparoscopic gastrectomy (LG) is widely accepted as a minimally invasive approach for the treatment of early gastric cancer. However, its role in locally advanced gastric cancer (LAGC) after neoadjuvant therapy (NAT) remains controversial. This study aimed to compare the efficacy and safety of LG vs open gastrectomy (OG) after NAT for the treatment of LAGC. AIM: To compare the efficacy and safety of LG vs OG after NAT for LAGC. METHODS: We conducted a prospective study of 76 patients with LAGC who underwent NAT followed by LG (n = 38) or OG (n = 38) between 2021 and 2023. The primary endpoint was overall survival (OS), and the secondary endpoints were disease-free survival (DFS), surgical complications, and quality of life (QOL). RESULTS: The two groups had comparable baseline characteristics, with a median follow-up period of 24 mo. The 3-year OS rates in the LG and OG groups were 68.4% and 60.5%, respectively (P = 0.42). The 3-year DFS rates in the LG and OG groups were 57.9% and 50.0%, respectively (P = 0.51). The LG group had significantly less blood loss (P < 0.001), a shorter hospital stay (P < 0.001), and a lower incidence of surgical site infection (P = 0.04) than the OG group. There were no significant differences in other surgical complications between the groups, including anastomotic leakage, intra-abdominal abscess, or wound dehiscence. The LG group had significantly better QOL scores than the OG group regarding physical functioning, role functioning, global health status, fatigue, pain, appetite loss, and body image at 6 months postoperatively (P < 0.05). CONCLUSION: LG after NAT is a viable and safe alternative to OG for the treatment of LAGC, with similar survival outcomes and superior short-term recovery and QOL. LG patients had less blood loss, shorter hospitalizations, and a lower incidence of surgical site infections than OG patients. Moreover, the LG group had better QOL scores in multiple domains 6 mo postoperatively. Therefore, LG should be considered a valid option for patients with LAGC who undergo NAT, particularly for those who prioritize postoperative recovery and QOL.

4.
Environ Sci Pollut Res Int ; 30(48): 105742-105755, 2023 Oct.
Article En | MEDLINE | ID: mdl-37715903

In this work, we have fabricated a novel Fenton-like ferrihydrite/MoS2 (Fh/MoS2) composite and verified that the introduction of a small amount of iron on the surface of MoS2 can directly promote the exposure of Mo4+, finally enhancing the catalytic activity of the catalyst. Even though the content of iron element is only 1.19% in the composite, the reaction rate constant of Fh/MoS2 system for the degradation of environmental pollutants, such as organic dyes, antibiotic, and ionic liquid, is all much better than that of pure MoS2 system, which is attributed to much more generation of reactive oxygen species derived from synergistic effect of Fe3+/Fe2+ and Mo4+/Mo6+ redox cycles. The results of XPS and low-temperature EPR confirm that the exposure amount of Mo4+ active sites of 10% Fh/MoS2 is greatly increased, which is conducive to the conversion of Fe3+ to Fe2+ in the reaction process, thus effectively promoting the activation of H2O2.


Environmental Pollutants , Hydrogen Peroxide , Hydrogen Peroxide/chemistry , Environmental Pollutants/chemistry , Molybdenum/chemistry , Iron/chemistry , Catalysis
5.
Sci Data ; 10(1): 545, 2023 08 21.
Article En | MEDLINE | ID: mdl-37604823

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), the first ten-year stage of the lifespan CCNP (2013-2032), is a two-stages project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community ( https://ccnp.scidb.cn ) at the Science Data Bank.


Asian People , Brain , Humans , Brain/diagnostic imaging , China , Data Warehousing , Databases, Factual , Neurosciences
6.
Int J Stem Cells ; 16(4): 415-424, 2023 Nov 30.
Article En | MEDLINE | ID: mdl-37643762

Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment in vivo. Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals. After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the in vivo fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.

7.
Am J Cancer Res ; 13(6): 2410-2425, 2023.
Article En | MEDLINE | ID: mdl-37424800

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with poor prognosis and limited treatment options. While 5-fluorouracil (5-FU) has not been widely employed in GBM therapy, emerging research indicates its potential for effectiveness when combined with advanced drug delivery systems to improve its transport to brain tumors. This study aims to investigate the role of THOC2 expression in 5-FU resistance in GBM cell lines. We evaluated diverse GBM cell lines and primary glioma cells for 5-FU sensitivity, cell doubling times, and gene expression. We observed a significant correlation between THOC2 expression and 5-FU resistance. To further investigate this correlation, we selected five GBM cell lines and developed 5-FU resistant GBM cells, including T98FR cells, through long-term 5-FU treatment. In 5-FU challenged cells, THOC2 expression was upregulated, with the highest increase in T98FR cells. THOC2 knockdown in T98FR cells reduced 5-FU IC50 values, confirming its role in 5-FU resistance. In a mouse xenograft model, THOC2 knockdown attenuated tumor growth and extended survival duration after 5-FU treatment. RNA sequencing identified differentially expressed genes and alternative splicing variants in T98FR/shTHOC2 cells. THOC2 knockdown altered Bcl-x splicing, increasing pro-apoptotic Bcl-xS expression, and impaired cell adhesion and migration by reducing L1CAM expression. These results suggest that THOC2 plays a crucial role in 5-FU resistance in GBM and that targeting THOC2 expression could be a potential therapeutic strategy for improving the efficacy of 5-FU-based combination therapies in GBM patients.

8.
Am J Cancer Res ; 13(6): 2439-2451, 2023.
Article En | MEDLINE | ID: mdl-37424825

Cancer immunotherapy has emerged as a promising approach for treating various malignancies. In this study, we investigated the combined therapeutic effects of mesenchymal stem cells expressing cytosine deaminase (MSC/CD) and 5-fluorocytosine (5-FC) with α-galactosylceramide (α-GalCer) in a colon cancer model. Our findings demonstrated that the combination of MSC/CD, 5-FC, and α-GalCer resulted in enhanced antitumor activity compared to the individual treatments. This was evidenced by increased infiltration of immune cells, such as natural killer T (NKT) cells, antigen-presenting cells (APCs), T cells, and natural killer (NK) cells, in the tumor microenvironment, as well as elevated expression of proinflammatory cytokines and chemokines. Furthermore, we observed no significant hepatotoxicity following the combined treatment. Our study highlights the potential therapeutic benefits of combining MSC/CD, 5-FC, and α-GalCer for colon cancer treatment and contributes valuable insights to the field of cancer immunotherapy. Future research should focus on elucidating the underlying mechanisms and exploring the applicability of these findings to other cancer types and immunotherapy strategies.

9.
Int J Stem Cells ; 16(4): 438-447, 2023 11 30.
Article En | MEDLINE | ID: mdl-37385638

Recently, ex-vivo gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes in vitro. Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene (PuroR) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate in vivo horizontal transfer of the PuroR gene in vivo, we generated a puromycin-resistant E. coli (E. coli/PuroR) by introducing the PuroR gene and assessed its responsiveness to various antibiotics. We found that the anti-cancer effect of MSCs/CD was directly proportional to their purity, suggesting the crucial role of the PuroR gene in eliminating impure unmodified MSCs and enhancing the purity of MSCs/CD during the manufacturing process. Additionally, we found that clinically available antibiotics were effective in inhibiting the growth of hypothetical microorganism, E. coli/PuroR. In summary, our study highlights the potential benefits of using the PuroR gene as a selection marker to enhance the purity and efficacy of therapeutic cells in MSC-based gene therapy. Furthermore, our study suggests that the potential risk of horizontal transfer of antibiotics resistance genes in vivo can be effectively managed by clinically available antibiotics.

10.
Huan Jing Ke Xue ; 44(3): 1583-1592, 2023 Mar 08.
Article Zh | MEDLINE | ID: mdl-36922219

In order to study the vertical pollution characteristics of polycyclic aromatic hydrocarbons (PAHs) in soils of different land use types in suburban areas of Nanjing, 15 types of controlled PAHs were studied in each section (0-100 cm) of soils from six different land use types, including a vegetable field, forestland, residential area, urban land, paddy field, and industrial area. The vertical distribution and composition characteristics, influencing factors, and sources of PAHs were analyzed. The results showed that:the total concentrations of Σ15PAHs in the six sampling site profiles were as follows:vegetable field (69.3-299.2 µg·kg-1), forestland (20.8-128.3 µg·kg-1), residential area (30.7-142.1 µg·kg-1), urban land (185.6-1728.7 µg·kg-1), paddy field (208.3-693.0 µg·kg-1), and industrial area (165.6-739.2 µg·kg-1). There was no pollution in the residential area or forestland and a light pollution level in the vegetable field, medium pollution level in the paddy field and industrial area, and more serious pollution in the urban land. Soil PAHs were mainly distributed in the surface or subsurface layer, except in the residential area and urban land; however, they were still detected in the deep layers, and high-molecular-weight PAHs were dominant in most depths and sampling sites. The vertical distribution and migration of PAHs in soils were affected by molecular characteristics and component concentrations of PAHs, soil physical and chemical properties, and land use types. PMF source analysis indicated that coke sources, traffic sources, and coal combustion sources from human activities were the main sources of PAHs in this study region.

11.
Huan Jing Ke Xue ; 44(2): 944-953, 2023 Feb 08.
Article Zh | MEDLINE | ID: mdl-36775617

In order to clarify the pollution characteristics of PAHs in suburban agricultural soils, the content of 16 types of PAHs was measured in agricultural soils with different land use types (paddy fields, vegetable fields, and forest land) in the suburbs of Nanjing. The results showed that acenaphthene (Acy) was not detected in any soil samples. The concentration of 15 PAHs in agricultural soil in suburban Nanjing ranged from 24.49 to 925.54 µg·kg-1, with an average concentration of 259.88 µg·kg-1. In different land use types, the order of PAHs concentration in soil from high to low was:forest land>paddy fields>vegetable fields, and the high-ring PAHs content was dominant in general. The effects of different soil physicochemical properties on PAHs showed that there was a certain correlation between soil organic carbon (TOC) and clay (clay) content and PAHs, whereas pH and total nitrogen (TN) had no significant correlation with PAHs. The toxic equivalence method and CSI index method were used for ecological risk assessment, which showed that the ecological risk of PAHs in agricultural soils in suburban Nanjing was relatively small; however, the ecological risk of PAHs in forest land should be given some attention, and supervision should be strengthened. Health risk assessment using incremental lifetime cancer risk (ILCR) showed that the threat to the health of children was slightly greater than that of adults, and the CR of forest land was significantly higher than that of vegetable and paddy fields, though still within an acceptable range. Uncertain health assessments were performed in adults, showing that risk analyses of deterministic health risks underestimated the health risks of PAHs. The results of sensitivity analysis showed that the input parameter that had the greatest impact on the total variance of the total carcinogenic risk CR was the exposure frequency EF (50.7%), followed by the pollutant concentration CS (43.3%).


Polycyclic Aromatic Hydrocarbons , Soil Pollutants , Adult , Child , Humans , Soil/chemistry , Environmental Monitoring/methods , Polycyclic Aromatic Hydrocarbons/analysis , Clay , Carbon/analysis , Soil Pollutants/analysis , Risk Assessment , Vegetables , China
12.
Plant Cell Rep ; 42(2): 433-448, 2023 Feb.
Article En | MEDLINE | ID: mdl-36693991

KEY MESSAGE: Ectopic expression of MmCYP1A1 gene from Mus musculus in apple calli and Arabidopsis increased the levels of melatonin and 6-hydroxymelatonin, and improved their stress resistance. Melatonin occurs widely in organisms, playing a key regulatory role. CYP1A1 is a cytochrome P450 monooxygenase, involved in the melatonin metabolism, and is responsible for the synthesis of 6-hydroxymelatonin from melatonin. Melatonin and 6-hydroxymelatonin have strong antioxidant activities in animals. Here, we cloned MmCYP1A1 from Mus musculus and found that ectopic expression of MmCYP1A1 improved the levels of melatonin and 6-hydroxymelatonin in transgenic apple calli and Arabidopsis. Subsequently, we observed that MmCYP1A1 increased the tolerance of transgenic apple calli and Arabidopsis to osmotic stress simulated by polyethylene glycol 6000 (PEG 6000), as well as resistance of transgenic Arabidopsis to drought stress. Further, the number of lateral roots of MmCYP1A1 transgenic Arabidopsis were enhanced significantly after PEG 6000 treatment. The expression of MmCYP1A1 remarkably reduced malondialdehyde (MDA) content, electrolyte leakage, accumulation of H2O2 and O2- during stress treatment. Moreover, MmCYP1A1 enhanced stress tolerance in apple calli and Arabidopsis by increasing the expression levels of resistance genes. MmCYP1A1 also promoted stomatal closure in transgenic Arabidopsis to reduce leaf water loss during drought. Our results indicate that MmCYP1A1 plays a key role in plant stress tolerance, which may provide a reference for future plant stress tolerance studies.


Arabidopsis , Malus , Melatonin , Animals , Mice , Arabidopsis/genetics , Arabidopsis/metabolism , Malus/genetics , Malus/metabolism , Melatonin/metabolism , Ectopic Gene Expression , Hydrogen Peroxide/metabolism , Plants, Genetically Modified/metabolism , Stress, Physiological/genetics , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Gene Expression Regulation, Plant , Droughts , Plant Proteins/genetics , Plant Proteins/metabolism
13.
J Neurosurg ; 138(3): 629-638, 2023 03 01.
Article En | MEDLINE | ID: mdl-35986732

OBJECTIVE: Several limitations are associated with the early diagnosis and treatment of incidental lower-grade glioma (iLGG), and due to its unknown molecular features, its management is categorized as either the "wait-and-see" strategy or immediate treatment. Therefore, in this study the authors explored iLGG's clinical and molecular landscape to improve its management. METHODS: The authors retrospectively assessed the differences between the molecular and clinical characteristics of iLGG and symptomatic lower-grade glioma (sLGG) samples filtered based on symptom data corresponding to The Cancer Genome Atlas cohort with mutations. Thereafter, genomic and transcriptomic analysis was performed. RESULTS: There was no significant difference between iLGG and sLGG with respect to mutation status; however, there was an increase in the interaction between major mutations in sLGG, depending on the histological subtype and the IDH1 mutation status. Furthermore, the IDH1 mutation characteristics corresponding to wild-type glioma were much more obvious in sLGG than in iLGG. Additionally, in sLGG, genes associated with malignancy, including cell proliferation-related, cell migration-related, epithelial-to-mesenchymal transition-related, and negative regulation of cell death-related genes, were significantly upregulated, and groups showing higher expression levels of these genes were associated with worse prognosis. Also, 8 of the 75 identified upregulated genes showed positive correlation with resistance to the drugs that are normally used for glioma treatment, including procarbazine, carmustine, vincristine, and temozolomide. CONCLUSIONS: The new insights regarding the different molecular features of iLGG and sLGG indicated that the immediate management of iLGG could result in better prognosis than the wait-and-see strategy.


Brain Neoplasms , Glioma , Humans , Brain Neoplasms/pathology , Retrospective Studies , Glioma/pathology , Prognosis , Carmustine , Mutation , Isocitrate Dehydrogenase/genetics
14.
JAMA ; 328(7): 627-636, 2022 08 16.
Article En | MEDLINE | ID: mdl-35972485

Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy of RIC for acute moderate ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). Main Outcomes and Measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. Conclusions and Relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03740971.


Ischemic Postconditioning , Ischemic Stroke , Aged , China , Female , Humans , Ischemic Postconditioning/methods , Ischemic Stroke/complications , Ischemic Stroke/therapy , Male , Middle Aged , Nervous System Diseases/etiology , Nervous System Diseases/prevention & control , Nervous System Diseases/therapy , Recovery of Function , Treatment Outcome , Upper Extremity/blood supply
15.
Sci Total Environ ; 830: 154818, 2022 Jul 15.
Article En | MEDLINE | ID: mdl-35341871

Under the background of indoor air formaldehyde decontamination, a freestanding ultra-light assembly was fabricated via ice-templating approach starting from MnO2 nanoparticles and environmentally benign agar powder. The 3D composite of agar and MnO2 (AM-3D) was comparatively studied with powdered counterparts (including pure MnO2 and mixture of agar and MnO2) and the 3D-structured agar for formaldehyde oxidation, and their physicochemical properties were examined with XRD, ATR, SEM, XPS, isothermal N2 adsorption, ESR, Raman, CO-TPR and O2-TPD. For the single test of formaldehyde oxidation, the AM-3D catalyst exhibited 62.0%-67.0% removal percentage for ~400 mg/m3 formaldehyde, which did not demonstrate significant advantage over the control samples. However, thanks to the porous 3D agar scaffold with large spatial volume that could promote a rapid gas-phase formaldehyde concentration reduction, and the strong interaction between the dispersed MnO2 particles and agar substrate that could afford a large amount of reactive oxygen species to further oxidize the adsorbed formaldehyde, the AM-3D composite was a much better HCHO-to-CO2 converter and possessed much more advantageous stability for repeated cycles of formaldehyde oxidation: even after ten cycles, there was still 41.7% of formaldehyde removed. Furthermore, the viable sunlight irradiation could easily restore the activity of the used AM-3D catalyst back to the level approaching that of the fresh one. Finally, reaction pathways were put forward via the infrared spectroscopic and ion chromatographic investigations on the surface intermediates of the spent materials.


Manganese Compounds , Oxides , Agar , Catalysis , Formaldehyde , Manganese Compounds/chemistry , Oxidation-Reduction , Oxides/chemistry , Oxygen/chemistry
16.
Mol Cells ; 45(7): 479-494, 2022 Jul 31.
Article En | MEDLINE | ID: mdl-35356894

Human mesenchymal stem cells (MSCs) are multipotent stem cells that have been intensively studied as therapeutic tools for a variety of disorders. To enhance the efficacy of MSCs, therapeutic genes are introduced using retroviral and lentiviral vectors. However, serious adverse events (SAEs) such as tumorigenesis can be induced by insertional mutagenesis. We generated lentiviral vectors encoding the wild-type herpes simplex virus thymidine kinase (HSV-TK) gene and a gene containing a point mutation that results in an alanine to histidine substitution at residue 168 (TK(A168H)) and transduced expression in MSCs (MSC-TK and MSC-TK(A168H)). Transduction of lentiviral vectors encoding the TK(A168H) mutant did not alter the proliferation capacity, mesodermal differentiation potential, or surface antigenicity of MSCs. The MSC-TK(A168H) cells were genetically stable, as shown by karyotyping. MSC-TK(A168H) responded to ganciclovir (GCV) with an half maximal inhibitory concentration (IC50) value 10-fold less than that of MSC-TK. Because MSC-TK(A168H) cells were found to be non-tumorigenic, a U87-TK(A168H) subcutaneous tumor was used as a SAE-like condition and we evaluated the effect of valganciclovir (vGCV), an oral prodrug for GCV. U87-TK(A168H) tumors were more efficiently ablated by 200 mg/kg vGCV than U87-TK tumors. These results indicate that MSC-TK(A168H) cells appear to be pre-clinically safe for therapeutic use. We propose that genetic modification with HSV-TK(A168H) makes allogeneic MSC-based ex vivo therapy safer by eliminating transplanted cells during SAEs such as uncontrolled cell proliferation.


Mesenchymal Stem Cells , Neoplasms , Thymidine Kinase , Animals , Antiviral Agents/pharmacology , Ganciclovir/therapeutic use , Genetic Therapy/methods , Genetic Vectors/genetics , Humans , Mesenchymal Stem Cells/metabolism , Mice , Neoplasms/therapy , Simplexvirus/enzymology , Thymidine Kinase/therapeutic use
17.
Ying Yong Sheng Tai Xue Bao ; 33(2): 467-476, 2022 Feb.
Article Zh | MEDLINE | ID: mdl-35229521

To assess the high-resolution digital soil mapping method for small watersheds in hilly areas, we explored the role of landscape classification and multiscale micro-landform features in predicting soil pH, soil clay content (SCC), and cation exchange capacity (CEC). Geomorphons (GM) terrain classification method was used to create landform units. The traditional digital elevation model (DEM) derivatives and remote sensing variables were employed for different combinations with landscape and micro-landform classification variables, with further compa-rison and analysis being conducted. In addition, three machine learning techniques, including support vector machine (SVM), partial least squares regression (PLSR), and random forest (RF), were used to build prediction models. The best method was then selected, and then combined with regression kriging by modeling spatial structure of the model residuals. The results showed that the application of landscape and multiscale micro-landform classification variables effectively improved the prediction accuracy of pH, SCC, and CEC by 18.8%, 8.2% and 8.7%, respectively. The map of landscape classification that contained vegetation coverage information had greater model contribution than land use data. The GM classification map with 5 m resolution was more suitable for high-precision DSM than those with lower resolution. The composite model of RF performed the best in predicting SCC, while the pH and CEC were not suitable for adding the residual regression kriging on the basis of RF model. Finally, the combination of landscape and multiscale micro-landform classification variables, DEM derivatives and remote sensing variables had the highest prediction accuracy for all the three soil properties. This result indicated that multivariable contained more effective soil information than single data source for rolling areas. The landscape variables composed of GM and surface classified data explained about 40% of the spatial variation of tested soil attributes in hilly area. Therefore, multi-resolution GM and landscape classified variables could be included into the construction of prediction model in research of soil mapping.


Machine Learning , Soil , Least-Squares Analysis , Soil/chemistry , Spatial Analysis
18.
Neuroimage ; 249: 118875, 2022 04 01.
Article En | MEDLINE | ID: mdl-34998971

Brain entropy (BEN) calculated from resting state fMRI has been the subject of increasing research interest in recent years. Previous studies have shown the correlations between rest BEN and neurocognition and task performance, but how this relates to task-evoked brain activations and deactivations remains unknown. The purpose of this study is to address this open question using large data (n = 862). Voxel wise correlations were calculated between rest BEN and task activations/deactivations of five different tasks. For most of the assessed tasks, lower rest BEN was found to be associated with stronger activations (negative correlations) and stronger deactivations (positive correlations) only in brain regions activated or deactivated by the tasks. Higher workload evoked spatially more extended negative correlations between rest BEN and task activations. These results not only confirm that resting brain activity can predict brain activity during task performance but also for the first time show that resting brain activity may facilitate both task activations and deactivations. In addition, the results provide a clue to understanding the individual differences of task performance and brain activations.


Biological Variation, Population/physiology , Brain Mapping , Brain/physiology , Psychomotor Performance/physiology , Rest/physiology , Adult , Entropy , Humans , Magnetic Resonance Imaging
19.
Huan Jing Ke Xue ; 42(11): 5510-5518, 2021 Nov 08.
Article Zh | MEDLINE | ID: mdl-34708990

In order to assess the pollution of polycyclic aromatic hydrocarbons(PAHs) in a suburban farmland soil, 29 sampling sites were collected around Nanjing according to the grid method, and the contents of 15 different PAHs were determined. Acenaphthene(Ace) was not detected in any of the samples. The total content of PAHs in farmland soil ranged from 24.49 to 750.04 µg·kg-1, with an average of 226.64 µg·kg-1. The spatial distribution of high-ring PAHs, the main PAHs in the farmland soil, was similar to that of total PAHs. There was no significant correlation between PAHs and soil organic matter(SOM), pH, cation exchange capacity(CEC), and total nitrogen(TN), whereas bulk density and low ring PAHs were significantly correlated. The results of source apportionment show that the main source of PAHs in the farmland soil is a mixture of combustion and petroleum. The contamination severity index(CSI) index shows that the PAHs does not pose an ecological risk. The results of the health risk assessment show that there is no potential carcinogenic risk to children or adults, and the main sequence of exposure is skin contact>ingestion>inhalation.


Polycyclic Aromatic Hydrocarbons , Soil Pollutants , Adult , Child , China , Environmental Monitoring , Farms , Humans , Polycyclic Aromatic Hydrocarbons/analysis , Risk Assessment , Soil , Soil Pollutants/analysis
20.
Int J Mol Sci ; 22(13)2021 Jun 28.
Article En | MEDLINE | ID: mdl-34203489

The most common type of spinal cord injury is the contusion of the spinal cord, which causes progressive secondary tissue degeneration. In this study, we applied genetically modified human neural stem cells overexpressing BDNF (brain-derived neurotrophic factor) (F3.BDNF) to determine whether they can promote functional recovery in the spinal cord injury (SCI) model in rats. We transplanted F3.BDNF cells via intrathecal catheter delivery after a contusion of the thoracic spinal cord and found that they were migrated toward the injured spinal cord area by MR imaging. Transplanted F3.BDNF cells expressed neural lineage markers, such as NeuN, MBP, and GFAP and were functionally connected to the host neurons. The F3.BDNF-transplanted rats exhibited significantly improved locomotor functions compared with the sham group. This functional recovery was accompanied by an increased volume of spared myelination and decreased area of cystic cavity in the F3.BDNF group. We also observed that the F3.BDNF-transplanted rats showed reduced numbers of Iba1- and iNOS-positive inflammatory cells as well as GFAP-positive astrocytes. These results strongly suggest the transplantation of F3.BDNF cells can modulate inflammatory cells and glia activation and also improve the hyperalgesia following SCI.


Brain-Derived Neurotrophic Factor/metabolism , Neural Stem Cells/metabolism , Animals , Electrophysiology , Humans , Immunohistochemistry , Rats, Sprague-Dawley , Recovery of Function/physiology , Spinal Cord Injuries/metabolism
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