In this study, our objective was to assess the performance of two deep learning-based hippocampal segmentation methods, SynthSeg and TigerBx, which are readily available to the public. We contrasted their performance with that of two established techniques, FreeSurfer-Aseg and FSL-FIRST, using three-dimensional T1-weighted MRI scans (n = 1447) procured from public databases. Our evaluation focused on the accuracy and reproducibility of these tools in estimating hippocampal volume. The findings suggest that both SynthSeg and TigerBx are on a par with Aseg and FIRST in terms of segmentation accuracy and reproducibility, but offer a significant advantage in processing speed, generating results in less than 1 min compared with several minutes to hours for the latter tools. In terms of Alzheimer's disease classification based on the hippocampal atrophy rate, SynthSeg and TigerBx exhibited superior performance. In conclusion, we evaluated the capabilities of two deep learning-based segmentation techniques. The results underscore their potential value in clinical and research environments, particularly when investigating neurological conditions associated with hippocampal structures.
Influenza A virus can infect respiratory tracts and may cause severe illness in humans. Proteins encoded by influenza A virus can interact with cellular factors and dysregulate host biological processes to support viral replication and cause pathogenicity. The influenza viral PA protein is not only a subunit of influenza viral polymerase but also a virulence factor involved in pathogenicity during infection. To explore the role of the influenza virus PA protein in regulating host biological processes, we performed immunoprecipitation and LCâMS/MS to globally identify cellular factors that interact with the PA proteins of the influenza A H1N1, 2009 pandemic H1N1, and H3N2 viruses. The results demonstrated that proteins located in the mitochondrion, proteasome, and nucleus are associated with the PA protein. We further discovered that the PA protein is partly located in mitochondria by immunofluorescence and mitochondrial fractionation and that overexpression of the PA protein reduces mitochondrial respiration. In addition, our results revealed the interaction between PA and the mitochondrial matrix protein PYCR2 and the antiviral role of PYCR2 during influenza A virus replication. Moreover, we found that the PA protein could also trigger autophagy and disrupt mitochondrial homeostasis. Overall, our research revealed the impacts of the influenza A virus PA protein on mitochondrial function and autophagy.
BACKGROUND: The modified Look-Locker inversion recovery (MOLLI) sequence is commonly used for myocardial T1 mapping. However, it acquires images with different inversion times, which causes difficulty in motion correction for respiratory-induced misregistration to a given target image. HYPOTHESIS: Using a generative adversarial network (GAN) to produce virtual MOLLI images with consistent heart positions can reduce respiratory-induced misregistration of MOLLI datasets. STUDY TYPE: Retrospective. POPULATION: 1071 MOLLI datasets from 392 human participants. FIELD STRENGTH/SEQUENCE: Modified Look-Locker inversion recovery sequence at 3 T. ASSESSMENT: A GAN model with a single inversion time image as input was trained to generate virtual MOLLI target (VMT) images at different inversion times which were subsequently used in an image registration algorithm. Four VMT models were investigated and the best performing model compared with the standard vendor-provided motion correction (MOCO) technique. STATISTICAL TESTS: The effectiveness of the motion correction technique was assessed using the fitting quality index (FQI), mutual information (MI), and Dice coefficients of motion-corrected images, plus subjective quality evaluation of T1 maps by three independent readers using Likert score. Wilcoxon signed-rank test with Bonferroni correction for multiple comparison. Significance levels were defined as P < 0.01 for highly significant differences and P < 0.05 for significant differences. RESULTS: The best performing VMT model with iterative registration demonstrated significantly better performance (FQI 0.88 ± 0.03, MI 1.78 ± 0.20, Dice 0.84 ± 0.23, quality score 2.26 ± 0.95) compared to other approaches, including the vendor-provided MOCO method (FQI 0.86 ± 0.04, MI 1.69 ± 0.25, Dice 0.80 ± 0.27, quality score 2.16 ± 1.01). DATA CONCLUSION: Our GAN model generating VMT images improved motion correction, which may assist reliable T1 mapping in the presence of respiratory motion. Its robust performance, even with considerable respiratory-induced heart displacements, may be beneficial for patients with difficulties in breath-holding. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.
Epithelial ovarian cancer is among the deadliest gynecological tumors worldwide. Clinical treatment usually consists of surgery and adjuvant chemo- and radiotherapies. Due to the high rate of recurrence and rapid development of drug resistance, the current focus of research is on finding effective natural products with minimal toxic side effects for treating epithelial ovarian tumors. Cannabidiol is among the most abundant cannabinoids and has a non-psychoactive effect compared to tetrahydrocannabinol, which is a key advantage for clinical application. Studies have shown that cannabidiol has antiproliferative, pro-apoptotic, cytotoxic, antiangiogenic, anti-inflammatory, and immunomodulatory properties. However, its therapeutic value for epithelial ovarian tumors remains unclear. This study aims to investigate the effects of cannabidiol on epithelial ovarian tumors and to elucidate the underlying mechanisms. The results showed that cannabidiol has a significant inhibitory effect on epithelial ovarian tumors. In vivo experiments demonstrated that cannabidiol could inhibit tumor growth by modulating the intestinal microbiome and increasing the abundance of beneficial bacteria. Western blot assays showed that cannabidiol bound to EGFR/AKT/MMPs proteins and suppressed EGFR/AKT/MMPs expression in a dose-dependent manner. Network pharmacology and molecular docking results suggested that cannabidiol could affect the EGFR/AKT/MMPs signaling pathway.
BACKGROUND: Quantification of metabolites concentrations in institutional unit (IU) is important for inter-subject and long-term comparisons in the applications of magnetic resonance spectroscopy (MRS). Recently, deep learning (DL) algorithms have found a variety of applications on the process of MRS data. A quantification strategy compatible to DL base MRS spectral processing method is, therefore, useful. MATERIALS AND METHODS: This study aims to investigate whether metabolite concentrations quantified using a convolutional neural network (CNN) based method, coupled with a scaling procedure that normalizes spectral signals for CNN input and linear regression, can effectively reflect variations in metabolite concentrations in IU across different brain regions with varying signal-to-noise ratios (SNR) and linewidths (LW). An error index based on standard error (SE) is proposed to indicate the confidence levels associated with metabolite predictions. In vivo MRS spectra were acquired from three brain regions of 43 subjects using a 3T system. RESULTS: The metabolite concentrations in IU of five major metabolites, quantified using CNN and LCModel, exhibit similar ranges with Pearson's correlation coefficients ranging from 0.24 to 0.78. The SE of the metabolites shows a positive correlation with Cramer-Rao lower bound (CRLB) (r=0.46) and absolute CRLB (r=0.81), calculated by multiplying CRLBs with the quantified metabolite content. CONCLUSION: In conclusion, the CNN based method with the proposed scaling procedures can be employed to quantify in vivo MRS spectra and derive metabolites concentrations in IU. The SE can be used as error index, indicating predicted uncertainties for metabolites and sharing information similar to the absolute CRLB.
Immune checkpoint inhibitor (ICI) therapy has dramatically changed cancer treatment, opening novel opportunities to cure malignant diseases. To date, most prevalently targeted immune checkpoints are programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), with many others being under extensive investigations. However, according to available data, only a fraction of patients may respond to ICI therapy. Additionally, this therapy may cause severe adverse immune-related side effects, such as diarrhea, headache, muscle weakness, rash, hepatitis and leucopenia, although most of them are not fatal, they can affect the patient's treatment outcome and quality of life. On the other hand, growing evidence has shown that phytochemicals with anticancer effects may combine ICI therapy to augment the safety and effectiveness of the treatment against cancer while reducing the adverse side effects. In this review, we summarize the state of art in the various experiments and clinical application of ICIs plus phytochemicals, with a focus on their combined use as a novel therapeutic strategy to cure cancer.
In this paper, a microfluidic chip for the manipulation and capture of cancer cells was introduced, in which the combination of dielectrophoresis (DEP) and a binding method based on chemical interactions by using cell-specific aptamers was performed to enhance the capture strength and specificity. The device has been simply constructed from a straight-channel PDMS placed on a glass substrate that has patterned electrode structures and a self-assembled monolayer of gold nanoparticles (AuNPs). The target cells were transported to the manipulation area by flow and attracted down to the region between the electrodes under the influence of positive DEP force. This approach facilitated subsequent selective capture by the modified aptamers on the AuNPs. The distribution of the electric field in the channel has also been simulated to clarify the DEP operation. As a result, the device has been shown to effectively capture target lung cancer cells with a concentration as low as 2 × 10 4 $2\ \ensuremath{\times{}}\ {10}^{4}\ $ cells/mL. The capture specificity in a sample of mixed cells is up to 80.4%. This technique has the potential to be applied to detection methods for many types of cancer.
Metal Nanoparticles , Microfluidic Analytical Techniques , Neoplasms , Humans , Microfluidics/methods , Gold/chemistry , Electrodes , Oligonucleotides , Electrophoresis/methods
OBJECTIVE: To observe the effect of electroacupuncture (EA) at different frequencies on learning and memory functions, as well as the relevant proteins of brain insulin signal transduction pathway in Alzheimer's disease (AD) mice and explore the effect mechanism of EA in treatment of AD. METHODS: Seventy-two SPF Kunming male mice were randomized into a blank group, a sham-operation group, a model group, a 2 Hz EA group, a 15 Hz EA group and a 30 Hz EA group, 12 mice in each one. In the model group and each EA group, AD model were established by the injection with streptozotocin (ST2) solution (8 mg/kg) into the left lateral ventricles. In the sham-operation group, 0.9% sodium chloride solution of the same volume was injected into the left lateral ventricles. After successful modeling, in each EA group, EA was applied at "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenshu" (BL 23) with corresponding frequencies, once daily. One course of EA intervention consisted of 7 treatments and 2 courses were given totally at interval of 1 day. After modeling and intervention, Morris water maze test was conducted for the mice of each group. Using immunohistochemistry and Western blot method, the protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) was detected in the hippocampal of the mice after intervention. RESULTS: Compared with the blank group, in the model group, the 2 Hz, 15 Hz and 30 Hz EA groups, the escape latency and the first time of crossing the platform were all extended (P<0.01), and the number of crossing the platform was reduced (P<0.01) after modeling. When compared with the blank group, the escape latency and the first time of crossing the platform were all extended (P<0.01), and the number of crossing the platform was reduced (P<0.01) in the model group after intervention. In the 2 Hz, 15 Hz and 30 Hz EA groups, the escape latency and the first time of crossing the platform were all shortened (P<0.01), and the number of crossing the platform was increased (P<0.05, P<0.01) after intervention when compared with the model group. The escape latency and the first time of crossing the platform were all shortened (P<0.01, P<0.05), and the number of crossing the platform was increased (P<0.05) in the 15 Hz and 30 Hz EA groups in comparison with the 2 Hz EA group. The protein expression levels of IR, IRS-1 and PI3K were reduced in the model group when compared with those of the blank group (P<0.01, P<0.05); and these protein expression levels were increased in the 15 Hz and 30 Hz EA groups compared with the model group (P<0.05, P<0.01). Compared with the 2 Hz EA group, the protein expression levels of IR, IRS-1 and PI3K were all elevated in the 15 Hz and 30 Hz EA groups (P<0.05). CONCLUSION: The learning and memory function of AD mice may be improved through regulating brain insulin signaling transconduction pathway with electroacupuncture, and electroacupuncture at 15 Hz and 30 Hz obtains the overall better effect compared with the intervention at 2 Hz.
Alzheimer Disease , Electroacupuncture , Hippocampus , Insulin , Animals , Male , Mice , Alzheimer Disease/therapy , Hippocampus/metabolism , Insulin/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction
Achieving large-area organic photovoltaic (OPV) modules with reasonable cost and performance is an important step toward commercialization. In this work, solution-processed conventional and inverted OPV modules with an area of 216 cm2 were fabricated by the blade coating method. Film uniformity was controlled by adjusting the fabrication parameters of the blade coating procedure. The influence of the concentration of the solutions of the interfacial materials on OPV module performance was investigated. For OPV modules based on the PM6:Y6 photoactive layer, a certificated power conversion efficiency (PCE) of 9.10% was achieved for the conventional OPV modules based on the TASiW-12 interfacial layer while a certificated PCE of 11.27% was achieved for the inverted OPV modules based on the polyethylenimine (PEI) interfacial layer. As for OPV modules based on a commercially available photoactive layer, PV-X Plus, a PCE of 8.52% was achieved in the inverted OPV modules. A halogen-free solvent, o-xylene, was used as the solvent for PV-X Plus, which makes the industrial production much more environmentally friendly.
BACKGROUND: Ovarian cancer has the highest mortality among all gynecological malignancies; currently, no effective therapeutics are available for its treatment. Naringenin has been shown to inhibit the progression of various cancers, but its inhibitory effect on ovarian cancer remains unknown. PURPOSE: This study aimed to evaluate the inhibitory effects of naringenin on ovarian cancer and elucidate the underlying mechanisms. METHODS: Cancer cell proliferation was detected by cell counting kit-8 and crystal violet assays, and the migration capability was determined by wound healing and transwell assays. Western blotting and immunohistochemistry assays were employed to determine the expression levels of the epidermal growth factor receptor, phosphatidylinositol 3-kinase (PI3K) and cyclin D1 in vitro and in vivo, respectively. An ES-2 xenograft nude mouse model was established for the in vivo experiments, and fecal samples were collected for intestinal microbiota analysis by 16S rDNA sequencing. RESULTS: Naringenin suppressed the proliferation and migration of A2780 and ES-2 cancer cell lines and downregulated PI3K in vitro. In animal experiments, naringenin treatment significantly decreased the tumor weight and volume, and oral administration exhibited greater effects than intraperitoneal injection. Additionally, naringenin treatment ameliorated the population composition of the microbiota in animals with ovarian cancer and significantly increased the abundances of Alistipes and Lactobacillus. CONCLUSION: Naringenin suppresses epithelial ovarian cancer by inhibiting PI3K pathway expression and ameliorating the gut microbiota, and the oral route is more effective than parenteral administration.
Gastrointestinal Microbiome , Ovarian Neoplasms , Animals , Carcinoma, Ovarian Epithelial/drug therapy , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cyclin D1 , DNA, Ribosomal/pharmacology , ErbB Receptors/metabolism , Female , Flavanones , Gentian Violet/pharmacology , Gentian Violet/therapeutic use , Humans , Mice , Mice, Nude , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinases/metabolism
Trabectedin, a tetrahydroisoquinoline alkaloid, is the first marine antineoplastic agent approved with special anticancer mechanisms involving DNA binding, DNA repair pathways, transcription regulation and regulation of the tumor microenvironment. It has favorable clinical applications, especially for the treatment of patients with advanced soft tissue sarcoma, who failed in anthracyclines and ifosfamide therapy or could not receive these agents. Currently, trabectedin monotherapy regimen and regimens of combined therapy with other agents are both widely used for the treatment of malignancies, including soft tissue sarcomas, ovarian cancer, breast cancer, and non-small-cell lung cancer. In this review, we have summarized the basic information and some updated knowledge on trabectedin, including its molecular structure, metabolism in various cancers, pharmaceutical mechanisms, clinical applications, drug combination, and adverse reactions, along with prospects of its possibly more optimal use in cancer treatment.
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Sarcoma , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Alkylating/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Dioxoles/pharmacology , Dioxoles/therapeutic use , Humans , Lung Neoplasms/drug therapy , Sarcoma/chemically induced , Sarcoma/drug therapy , Sarcoma/pathology , Trabectedin/therapeutic use , Tumor Microenvironment
BACKGROUND: HIV-1 pol, which encodes enzymes required for virus replication, is initially translated as a Gag-Pol fusion protein. Gag-Pol is incorporated into virions via interactions with Gag precursor Pr55gag. Protease (PR) embedded in Gag-Pol mediates the proteolytic processing of both Pr55gag and Gag-Pol during or soon after virus particle release from cells. Since efficient Gag-Pol viral incorporation depends on interaction with Pr55gag via its N-terminal Gag domain, the prevention of premature Gag cleavage may alleviate Gag-Pol packaging deficiencies associated with cleavage enhancement from PR. RESULTS: We engineered PR cleavage-blocking Gag mutations with the potential to significantly reduce Gag processing efficiency. Such mutations may mitigate the negative effects of enhanced PR activation on virus assembly and Gag-Pol packaging due to an RT dimerization enhancer or leucine zipper dimerization motif. When co-expressed with Pr55gag, we noted that enhanced PR activation resulted in reduced Gag-Pol cis or trans incorporation into Pr55gag particles, regardless of whether or not Gag cleavage sites within Gag-Pol were blocked. CONCLUSIONS: Our data suggest that the amount of HIV-1 Gag-Pol or Pol viral incorporation is largely dependent on virus particle production, and that cleavage blocking in the Gag-Pol N-terminal Gag domain does not exert significant impacts on Pol packaging.
HIV-1 , Fusion Proteins, gag-pol/genetics , Fusion Proteins, gag-pol/metabolism , HIV-1/genetics , Leucine Zippers/genetics , Virion , Virus Assembly
OBJECTIVE: To compare the therapeutic results and the occurrence of adverse reactions of medicine between the combined therapy of warm acupuncture at back-shu points of five zang organs and the western medicine and the simple wes-tern medication, and observe the therapeutic effect and attenuating effect of this combined therapy in treatment on depression of yang deficiency pattern. METHODS: A total of 80 patients with depression of yang deficiency pattern were randomly divided into an observation group and a control group ï¼39 cases/groupï¼. In the control group, escitalopram oxalate tablets were administered orally every day. In the observation group, on the base of the medication as the control group, warm acupuncture therapy was exerted at back-shu points of five zang organs, for 30 min each time, 5 times a week. The duration of treatment was 6 weeks in two groups. Before and after treatment, the scores of Hamilton depression scale (HAMD) and the antidepressant side effect scale (SERS) were evaluated and electroencephalogram (EEG) was detected; and the curative effect was assessed according to HAMD reduction rate in patients of the two groups. RESULTS: After treatment, the HAMD and SERS scores were lower than those before treatment in both groups. Compared with the control group, the HAMD and SERS scores were lower (P<0.05, P<0.01), and the EEG result was improved (P<0.01) in the observation group. The clinical total effective rate of the observation group was 97.43% (38/39), higher than 92.30% (36/39) of the control group (P<0.05). CONCLUSION: The combined therapy of warm acupuncture at back-shu points of five zang organs and western medicine effectively relieves depression of yang deficiency pattern in the patients and its overall therapeutic effect is better than simple western medication, besides, the combined therapy alleviates the adverse reactions induced by simple western medication.
Acupuncture Therapy , Acupuncture , Acupuncture Points , Escitalopram , Humans , Yang Deficiency/drug therapy
BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Choroidal neovascularization (CNV) is the major pathologic feature of neovascular AMD. Oxidative damages and the ensuing chronic inflammation are representative of trigger events. Hydrogen gas (H2) has been demonstrated as an antioxidant and plays a role in the regulation of oxidative stress and inflammation. This experiment aimed to investigate the influence of H2 inhalation on a mouse model of CNV. METHODS: Laser was used to induce CNV formation. C57BL/6J mice were divided into five groups: the control group; the laser-only group; and the 2 h, 5 h, and 2.5 h/2.5 h groups that received laser and H2 inhalation (21% oxygen, 42% hydrogen, and 37% nitrogen mixture) for 2 h, 5 h, and 2.5 h twice every day, respectively. RESULTS: The severity of CNV leakage on fluorescence angiography showed a significant decrease in the H2 inhalation groups. The mRNA expression of hypoxia-inducible factor 1 alpha and its immediate downstream target vascular endothelial growth factor (VEGF) showed significant elevation after laser, and this elevation was suppressed in the H2 inhalation groups in an inhalation period length-related manner. The mRNA expression of cytokines, including tumor necrosis factor alpha and interlukin-6, also represented similar results. CONCLUSION: H2 inhalation could alleviate CNV leakage in a laser-induced mouse CNV model, and the potential mechanism might be related to the suppression of the inflammatory process and VEGF-driven CNV formation.
Anti-Inflammatory Agents/administration & dosage , Choroidal Neovascularization/therapy , Hydrogen/administration & dosage , Wet Macular Degeneration/therapy , Administration, Inhalation , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Choroidal Neovascularization/etiology , Choroidal Neovascularization/pathology , Disease Models, Animal , Fluorescein Angiography , Fundus Oculi , Gases , Hydrogen/pharmacology , Lasers , Macular Degeneration/etiology , Macular Degeneration/pathology , Macular Degeneration/therapy , Mice , Mice, Inbred C57BL , Wet Macular Degeneration/etiology , Wet Macular Degeneration/pathology
Introduction: To establish a pilot study on applying two low dose (40 h) constraint-induced movement therapy (CIMT) interventions in children with hemiplegic cerebral palsy (CP) after botulinum toxin (BoNT-A) injection during preschool education. Methods: Five children with spastic CP (mean age: 5.31 years; Gross Motor Function Classification System level I and II) undergoing regular BoNT-A injections and rehabilitation programs were included. Participants were randomly allocated to one of two CIMT programs (40 h): a 2-week 4-hours/day CIMT program and a 4-week 2-hours/day CIMT program. One CIMT program was performed 1 month after a BoNT-A injection, and then the second program was implemented with the next injection. The outcomes were measured by changes in Goal Attainment Scaling (GAS), the grasp and Visual-Motor Integration (VMI) test in Peabody-Developmental Motor Scales (PDMS), the self-care scale on the Functional Skill Scale, and the Caregiver Assistance in Chinese Version of Pediatric Evaluation of Disability Inventory (PEDI-C), Anxiety and Oppositional Defiance Problems of Achenbach System of Empirically-Based Assessment before and after the CIMT interventions, and at every 2 months' follow-up thereafter. Results: The mean age of the participants was 5.31 years, BMI was 16.7 (kg/m2), VIQ was 86.4 ± 8.5, and dose of BoNT-A injection in the upper limb was 42 ± 26.6 units. Grasp, VMI, and self-care on the Functional Skill Scale were significantly better in the 4-week 2-hours/day CIMT program (p < 0.001, p = 0.001, p < 0.001). GAS, grasp, VMI, two 2 self-care scales of PEDI were significantly improved after the CIMT programs, and improvement continued for up to 4 months after the programs. There was no clinical evidence showing changes in the scores for anxiety and oppositional defiance problems during the study period. Conclusions: The preliminary findings, although limited, suggest a potential therapeutic role for the school-based CIMT program after BoNT-A injection. The 4-week 2-hours/day CIMT program might be better than a 2-week 4-hours/day program in terms of self-care and hand function when performed in kindergarten in this pilot study. Furthermore, this pilot study provides valuable information; therefore, it is crucial to include more CP children and blinded assessors for hand function and ADL in the future study.
