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1.
J Agric Food Chem ; 72(21): 12003-12013, 2024 May 29.
Article En | MEDLINE | ID: mdl-38748811

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.


Feeding Behavior , Insect Proteins , Larva , Spodoptera , Animals , Spodoptera/metabolism , Spodoptera/physiology , Spodoptera/genetics , Spodoptera/growth & development , Larva/metabolism , Larva/growth & development , Larva/physiology , Insect Proteins/metabolism , Insect Proteins/genetics , Receptors, Cell Surface/metabolism , Receptors, Cell Surface/genetics
2.
Front Med (Lausanne) ; 11: 1353822, 2024.
Article En | MEDLINE | ID: mdl-38741768

Background: Retroperitoneal fibrosis, a condition of uncertain origin, is rarely linked to 8% of malignant cases, including breast, lung, gastrointestinal, genitourinary, thyroid, and carcinoid. The mechanism leading to peritoneal fibrosis induced by tumors is not well understood, possibly encompassing direct infiltration of neoplastic cells or the initiation of inflammatory responses prompted by cytokines released by tumor cells. We report a case of breast cancer with renal metastasis and retroperitoneal fibrosis detected using 18F-FDG PET/CT, providing help for clinical diagnosis and treatment. Case report: A 49-year-old woman was referred to the hospital with elevated creatinine and oliguria for over a month. Abdominal computer tomography (CT) and magnetic resonance imaging (MRI) showed a retroperitoneal fibrosis-induced acute kidney injury (AKI) was suspected. However, a percutaneous biopsy of the kidney lesion confirmed metastasis from breast cancer. The physical examination revealed inverted nipples and an orange peel appearance on the skin of both breasts. Ultrasonography revealed bilateral hyperplasia (BIRADS 4a) of the mammary glands and bilateral neck and axillary lymphadenopathy. Subsequently, 18F-deoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) detected abnormally high uptake (SUVmax) in the bilateral mammary glands and axillary lymph nodes, suggesting bilateral breast cancer. Furthermore, abnormal 18F-FDG uptake was detected in the kidney, suggesting renal metastasis. In addition, abnormal 18F-FDG uptake was observed in the vertebrae, accompanied by an elevation in inhomogeneous bone mineral density, raising suspicion of bone metastases. However, the possibility of myelodysplasia cannot be dismissed, and further investigations will be conducted during close follow-ups. There was significant 18F-FDG uptake in the retroperitoneal position indicating a potential association between retroperitoneal fibrosis and breast cancer. The final pathological diagnosis of the breast tissue confirmed bilateral invasive ductal carcinoma. The patient had been treated with 11 cycles of albumin-bound (nab)-paclitaxel (0.3 mg) and had no significant adverse reaction. Conclusion: In this case, neither the bilateral breast cancer nor the kidney metastatic lesion showed typical nodules or masses, so breast ultrasound, abdominal CT, and MRI did not suggest malignant lesions. PET/CT played an important role in detecting occult metastases and primary lesions, thereby contributing to more accurate staging, monitoring treatment responses, and prediction of prognosis in breast cancer.

3.
Mol Pharm ; 21(5): 2544-2554, 2024 May 06.
Article En | MEDLINE | ID: mdl-38588328

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.


Kidney Neoplasms , Lutetium , Mice, Inbred BALB C , Radioisotopes , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Zirconium , Animals , Receptors, Vascular Endothelial Growth Factor/metabolism , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/pharmacokinetics , Zirconium/chemistry , Mice , Kidney Neoplasms/drug therapy , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/metabolism , Tissue Distribution , Humans , Cell Line, Tumor , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/chemistry , Theranostic Nanomedicine/methods , Female , Positron-Emission Tomography/methods , Xenograft Model Antitumor Assays
4.
Front Immunol ; 15: 1336239, 2024.
Article En | MEDLINE | ID: mdl-38322258

CpG oligodeoxynucleotides (CpG ODNs) boost the humoral and cellular immune responses to antigens through interaction with Toll-like receptor 9 (TLR9). These CpG ODNs have been extensively utilized in human vaccines. In our study, we evaluated five B-type CpG ODNs that have stimulatory effects on pigs by measuring the proliferation of porcine peripheral blood mononuclear cells (PBMCs) and assessing interferon gamma (IFN-γ) secretion. Furthermore, this study examined the immunoenhancing effects of the MF59 and CpG ODNs compound adjuvant in mouse and piglet models of porcine epidemic diarrhea virus (PEDV) subunit vaccine administration. The in vitro screening revealed that the CpG ODN named CpG5 significantly stimulated the proliferation of porcine PBMCs and elevated IFN-γ secretion levels. In the mouse vaccination model, CpG5 compound adjuvant significantly bolstered the humoral and cellular immune responses to the PEDV subunit vaccines, leading to Th1 immune responses characterized by increased IFN-γ and IgG2a levels. In piglets, the neutralizing antibody titer was significantly enhanced with CpG5 compound adjuvant, alongside a considerable increase in CD8+ T lymphocytes proportion. The combination of MF59 adjuvant and CpG5 exhibits a synergistic effect, resulting in an earlier, more intense, and long-lasting immune response in subunit vaccines for PEDV. This combination holds significant promise as a robust candidate for the development of vaccine adjuvant.


Polysorbates , Porcine epidemic diarrhea virus , Squalene , Animals , Swine , Mice , Humans , Leukocytes, Mononuclear , Adjuvants, Immunologic , Immunity , Vaccines, Subunit , Adjuvants, Pharmaceutic , Oligodeoxyribonucleotides
6.
Eur J Nucl Med Mol Imaging ; 51(5): 1246-1260, 2024 Apr.
Article En | MEDLINE | ID: mdl-38135849

PURPOSE: Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30-60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC. METHODS: Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin-eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software. RESULTS: FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq. CONCLUSION: 89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC.


Carbocyanines , Receptors, Vascular Endothelial Growth Factor , Triple Negative Breast Neoplasms , Vascular Endothelial Growth Factor A , Female , Humans , Animals , Mice , Vascular Endothelial Growth Factor A/metabolism , Triple Negative Breast Neoplasms/diagnostic imaging , Triple Negative Breast Neoplasms/drug therapy , Precision Medicine , Tissue Distribution , Cell Line, Tumor , Placenta Growth Factor/metabolism , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/metabolism
7.
View (Beijing) ; 4(5)2023 Oct.
Article En | MEDLINE | ID: mdl-38076327

The transmembrane glycoprotein adhesion molecule CD146 is overexpressed in a wide variety of cancers. Through molecular imaging, a specific biomarker's expression and distribution can be viewed in vivo non-invasively. Radionuclide-labeled monoclonal antibodies or relevant fragments that target CD146 may find potential applications in cancer imaging, thereby offering tremendous value in cancer diagnosis, staging, prognosis evaluation, and prediction of drug resistance. This review discusses the recent developments of CD146-targeted molecular imaging via nuclear medicine, especially in malignant melanoma, brain tumor, lung cancer, liver cancer, breast cancer, and pancreatic cancer. Many studies have proved that CD146 targeting may present a promising strategy for cancer theranostics.

8.
Bio Protoc ; 13(21): e4870, 2023 Nov 05.
Article En | MEDLINE | ID: mdl-37969757

Brain organoids have been widely used to study diseases and the development of the nervous system. Many reports have investigated the application of brain organoids, but most of these models lack vascular structures, which play essential roles in brain development and neurological diseases. The brain and blood vessels originate from two different germ layers, making it difficult to induce vascularized brain organoids in vitro. We developed this protocol to generate brain-specific blood vessel and cerebral organoids and then fused them at a specific developmental time point. The fused cerebral organoids exhibited robust vascular network-like structures, which allows simulating the in vivo developmental processes of the brain for further applications in various neurological diseases. Key Features • Culturing vascularized brain organoids using human embryonic stem cells (hESCs). • The new approach generates not only neural cells and vessel-like networks but also brain-resident microglia immune cells in a single organoid.

9.
Sensors (Basel) ; 22(21)2022 Oct 27.
Article En | MEDLINE | ID: mdl-36365943

In satellite remote sensing applications, waterbody segmentation plays an essential role in mapping and monitoring the dynamics of surface water. Satellite image segmentation-examining a relevant sensor data spectrum and identifying the regions of interests to obtain improved performance-is a fundamental step in satellite data analytics. Satellite image segmentation is challenging for a number of reasons, which include cloud interference, inadequate label data, low lighting and the presence of terrain. In recent years, Convolutional Neural Networks (CNNs), combined with (satellite captured) multispectral image segmentation techniques, have led to promising advances in related research. However, ensuring sufficient image resolution, maintaining class balance to achieve prediction quality and reducing the computational overhead of the deep neural architecture are still open to research due to the sophisticated CNN hierarchical architectures. To address these issues, we propose a number of methods: a multi-channel Data-Fusion Module (DFM), Neural Adaptive Patch (NAP) augmentation algorithm and re-weight class balancing (implemented in our PHR-CB experimental setup). We integrated these techniques into our novel Fusion Adaptive Patch Network (FAPNET). Our dataset is the Sentinel-1 SAR microwave signal, used in the Microsoft Artificial Intelligence for Earth competition, so that we can compare our results with the top scores in the competition. In order to validate our approach, we designed four experimental setups and in each setup, we compared our results with the popular image segmentation models UNET, VNET, DNCNN, UNET++, U2NET, ATTUNET, FPN and LINKNET. The comparisons demonstrate that our PHR-CB setup, with class balance, generates the best performance for all models in general and our FAPNET approach outperforms relative works. FAPNET successfully detected the salient features from the satellite images. FAPNET with a MeanIoU score of 87.06% outperforms the state-of-the-art UNET, which has a score of 79.54%. In addition, FAPNET has a shorter training time than other models, comparable to that of UNET (6.77 min for 5 epochs). Qualitative analysis also reveals that our FAPNET model successfully distinguishes micro waterbodies better than existing models. FAPNET is more robust to low lighting, cloud and weather fluctuations and can also be used in RGB images. Our proposed method is lightweight, computationally inexpensive, robust and simple to deploy in industrial applications. Our research findings show that flood-water mapping is more accurate when using SAR signals than RGB images. Our FAPNET architecture, having less parameters than UNET, can distinguish micro waterbodies accurately with shorter training time.


Artificial Intelligence , Floods , Neural Networks, Computer , Algorithms , Water , Image Processing, Computer-Assisted/methods
10.
Article En | MEDLINE | ID: mdl-35990821

Objective: To investigate the efficacy of donepezil hydrochloride plus olanzapine for senile dementia and its effect on the recovery of cognitive function. Methods: A total of 60 patients with senile dementia admitted to our hospital from April 2020 to July 2021 were recruited and assigned to receive either olanzapine alone (observation group) or donepezil hydrochloride plus olanzapine (experimental group) via the random number table method, with 30 patients in each group. Results: The combined therapy resulted in significantly higher clinical efficacy versus monotherapy of olanzapine (P < 0.05). Before treatment, the difference in the scores of cognitive function between the two groups did not come up to the statistical standard (P > 0.05). Donepezil hydrochloride plus olanzapine was associated with significantly higher scores of cognitive function in patients versus olanzapine alone (P < 0.05). The two groups had a similar incidence of adverse reactions (P > 0.05). Conclusion: Donepezil hydrochloride plus olanzapine substantially enhances the recovery of cognitive function of patients with senile dementia and features a manageable safety. Further trials are, however, required prior to clinical promotion.

12.
Elife ; 112022 05 04.
Article En | MEDLINE | ID: mdl-35506651

Brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis and brain disorders, limits the utility of brain organoids. In this study, we induced vessel and brain organoids, respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood-brain barrier-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids and showed ability of engulfing synapses. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, particularly the vasculature and microglia niche.


Understanding how the organs form and how their cells behave is essential to finding the causes and treatment for developmental disorders, as well as understanding certain diseases. However, studying most organs in live animals or humans is technically difficult, expensive and invasive. To address this issue, scientists have developed models called 'organoids' that recapitulate the development of organs using stem cells in the lab. These models are easier to study and manipulate than the live organs. Brain organoids have been used to recapitulate brain formation as well as developmental, degenerative and psychiatric brain conditions such as microcephaly, autism and Alzheimer's disease. However, these brain organoids lack the vasculature (the network of blood vessels) that supplies a live brain with nutrients and regulates its development, and which has important roles in brain disorders. Partly due to this lack of blood vessels, brain organoids also do not develop a blood brain barrier, the structure that prevents certain contents of the blood, including pathogens, toxins and even certain drugs from entering the brain. These characteristics limit the utility of existing brain organoids. To overcome these limitations, Sun, Ju et al. developed brain organoids and blood vessel organoids independently, and then fused them together to obtain vascularized brain organoids. These fusion organoids developed a robust network of blood vessels that was well integrated with the brain cells, and produced more neural cell precursors than brain organoids that had not been fused. This result is consistent with the idea that blood vessels can regulate brain development. Analyzing the fusion organoids revealed that they contain structures similar to the blood-brain barrier, as well as microglial cells (immune cells specific to the brain). When exposed to lipopolysaccharide ­ a component of the cell wall of certain bacteria ­ these cells responded by initiating an immune response in the fusion organoids. Notably, the microglial cells were also able to engulf connections between brain cells, a process necessary for the brain to develop the correct structures and work normally. Sun, Ju et al. have developed a new organoid system that will be of broad interest to researchers studying interactions between the brain and the circulatory system. The development of brain-blood-barrier-like structures in the fusion organoids could also facilitate the development of drugs that can cross this barrier, making it easier to treat certain conditions that affect the brain. Refining this model to allow the fusion organoids to grow for longer times in the lab, and adding blood flow to the system will be the next steps to establish this system.


Brain , Organoids , Blood-Brain Barrier , Neurogenesis , Neurons
13.
Am J Nucl Med Mol Imaging ; 12(6): 188-194, 2022.
Article En | MEDLINE | ID: mdl-36636232

Malignant melanoma (MM) is an aggressive malignant tumor, which mostly occurs on the skin, uvea, etc. The mucosal MM accounts for a small proportion of all MM and can occur in the digestive tract. Primary MM of the digestive tract is rare and can be found in the middle and lower third of the esophagus and the rectum containing melanocytes. Primary rectal MM often occurs in middle-aged and elderly women, with rapid progress and strong invasion. We report a case of a 61-year-old man diagnosed with primary malignant melanoma of the rectum with liver metastases mimicking rectum cancer. 18F-FDG PET/CT showed the rectal wall was markedly thickened with a high metabolic level (SUVmax 10.6) and the boundary between the lesions and the prostate was unclear. In addition, increased FDG uptake were found in multiple lymph nodes, lung, liver, and bones, suggesting metastasis. In this case, 18F-FDG PET/CT shows the advantage of evaluating the whole-body situation and provides valuable information for the diagnosis, tumor stage, evaluation of treatment efficacy, and prognosis of MM.

14.
Sci Adv ; 7(3)2021 01.
Article En | MEDLINE | ID: mdl-33523893

Genomic changes during human linage evolution contribute to the expansion of the cerebral cortex to allow more advanced thought processes. The hominoid-specific gene TBC1D3 displays robust capacity of promoting the generation and proliferation of neural progenitors (NPs), which are thought to contribute to cortical expansion. However, the underlying mechanisms remain unclear. Here, we found that TBC1D3 interacts with G9a, a euchromatic histone lysine N-methyltransferase, which mediates dimethylation of histone 3 in lysine 9 (H3K9me2), a suppressive mark for gene expression. TBC1D3 displayed an inhibitory role in G9a's histone methyltransferase activity. Treatment with G9a inhibitor markedly increased NP proliferation and promoted human cerebral organoid expansion, mimicking the effects caused by TBC1D3 up-regulation. By contrast, blockade of TBC1D3/G9a interaction to disinhibit G9a caused up-regulation of H3K9me2, suppressed NP proliferation, and impaired organoid development. Together, this study has demonstrated a mechanism underlying the role of a hominoid-specific gene in promoting cortical expansion.


Histones , Lysine , Cell Proliferation , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/metabolism , Histone Methyltransferases/metabolism , Histone-Lysine N-Methyltransferase/metabolism , Histones/metabolism , Humans , Proto-Oncogene Proteins/metabolism
15.
Brief Bioinform ; 22(4)2021 07 20.
Article En | MEDLINE | ID: mdl-33313674

Although long noncoding RNAs (lncRNAs) have significant tissue specificity, their expression and variability in single cells remain unclear. Here, we developed ColorCells (http://rna.sysu.edu.cn/colorcells/), a resource for comparative analysis of lncRNAs expression, classification and functions in single-cell RNA-Seq data. ColorCells was applied to 167 913 publicly available scRNA-Seq datasets from six species, and identified a batch of cell-specific lncRNAs. These lncRNAs show surprising levels of expression variability between different cell clusters, and has the comparable cell classification ability as known marker genes. Cell-specific lncRNAs have been identified and further validated by in vitro experiments. We found that lncRNAs are typically co-expressed with the mRNAs in the same cell cluster, which can be used to uncover lncRNAs' functions. Our study emphasizes the need to uncover lncRNAs in all cell types and shows the power of lncRNAs as novel marker genes at single cell resolution.


Databases, Nucleic Acid , Gene Expression Regulation , RNA, Long Noncoding , Single-Cell Analysis , Software , Animals , Humans , Molecular Sequence Annotation , RNA, Long Noncoding/biosynthesis , RNA, Long Noncoding/genetics
16.
Development ; 147(10)2020 05 15.
Article En | MEDLINE | ID: mdl-32321712

Cortex development is controlled by temporal patterning of neural progenitor (NP) competence with sequential generation of deep and superficial layer neurons, but underlying mechanisms remain elusive. Here, we report a role for heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) in regulating the division of early cortical NPs that mainly give rise to deep-layer neurons via direct neurogenesis. HNRNPA3 is expressed at high levels in NPs of mouse and human cortex at early stages, with a unique peri-chromosome pattern. Intriguingly, downregulation of HNRNPA3 caused chromosome disarrangement, which hindered normal separation of chromosomes during NP division, leading to mitotic delay. Furthermore, HNRNPA3 is associated with the cohesin-core subunit SMC1A and controls its association with chromosomes, implicating a mechanism for the role of HNRNPA3 in regulating chromosome segregation in dividing NPs. Hnrnpa3-deficient mice exhibited reduced cortical thickness, especially of deep layers. Moreover, downregulation of HNRNPA3 in cultured human cerebral organoids led to marked reduction in NPs and deep-layer neurons. Thus, this study has identified a crucial role for HNRNPA3 in NP division and highlighted the relationship between mitosis progression and early neurogenesis.


Cell Cycle Proteins/metabolism , Chromosomal Proteins, Non-Histone/metabolism , Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism , Mitosis/genetics , Neural Stem Cells/metabolism , Neurogenesis/genetics , Animals , Cell Line , Cell Proliferation/genetics , Cerebral Cortex/embryology , Chromosome Segregation/genetics , Female , Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Neurons/metabolism , Transfection , Cohesins
17.
Mitochondrial DNA B Resour ; 4(2): 2633-2634, 2019 Jul 18.
Article En | MEDLINE | ID: mdl-33365658

Polypodiodes amoena is an important medical fern of Polypodiaceae. Its complete chloroplast genome is obtained through Illumina sequencing, which is 152,067 bp in length with a large single copy (LSC) region (81,187 bp), a small single copy (SSC) region (21,590 bp), and two inverted repeats (IRa and IRb) regions (24,645 bp). The genome encodes 130 genes, including 88 protein-coding genes, 33 tRNA genes, eight rRNA genes, and one pseudogene. ML phylogenetic analysis reveals that P. amoena is clustered with polypodiaceous ferns.

18.
Mitochondrial DNA B Resour ; 3(2): 772-773, 2018 Jul 11.
Article En | MEDLINE | ID: mdl-33474317

Histiopteris incisa is a core member to address the issue of relationship between Histiopteris and Pteris. Its complete chloroplast genome was generated by de novo assembly using Illumina sequencing. The complete chloroplast genome is a quadripartite structure of 16,0567 bp in length, with two inverted repeat regions (IRs) of 27,119 bp each, a large single-copy (LSC) region of 84,897 bp and a small single-copy (SSC) region of 21,432 bp. A total of 132 genes were predicted, involving in 88 protein-coding genes, eight rRNA genes, 35 tRNA genes, and one pseudogene. ML phylogenetic analysis showed that H. incisa was closely related to Pteridium aquilinum subsp. aquilinum.

19.
EBioMedicine ; 20: 19-26, 2017 Jun.
Article En | MEDLINE | ID: mdl-28527830

Precisely targeted genome editing is highly desired for clinical applications. However, the widely used homology-directed repair (HDR)-based genome editing strategies remain inefficient for certain in vivo applications. We here demonstrate a microhomology-mediated end-joining (MMEJ)-based strategy for precisely targeted gene integration in transfected neurons and hepatocytes in vivo with efficiencies up to 20%, much higher (up to 10 fold) than HDR-based strategy in adult mouse tissues. As a proof of concept of its therapeutic potential, we demonstrate the efficacy of MMEJ-based strategy in correction of Fah mutation and rescue of Fah-/- liver failure mice, offering an efficient approach for precisely targeted gene therapies.


CRISPR-Cas Systems , Gene Targeting , Recombinational DNA Repair , Animals , Biomarkers , Cell Line , Female , Gene Transfer Techniques , Genetic Engineering , Genetic Therapy , Genetic Vectors/genetics , Genotype , Hepatocytes/metabolism , Humans , Hydrolases/genetics , Male , Mice , Mice, Knockout , Neurons/metabolism , Phenotype
20.
J Med Syst ; 41(2): 24, 2017 Feb.
Article En | MEDLINE | ID: mdl-28000118

We introduce a smart sensor-based motion detection technique for objective measurement and assessment of surgical dexterity among users at different experience levels. The goal is to allow trainees to evaluate their performance based on a reference model shared through communication technology, e.g., the Internet, without the physical presence of an evaluating surgeon. While in the current implementation we used a Leap Motion Controller to obtain motion data for analysis, our technique can be applied to motion data captured by other smart sensors, e.g., OptiTrack. To differentiate motions captured from different participants, measurement and assessment in our approach are achieved using two strategies: (1) low level descriptive statistical analysis, and (2) Hidden Markov Model (HMM) classification. Based on our surgical knot tying task experiment, we can conclude that finger motions generated from users with different surgical dexterity, e.g., expert and novice performers, display differences in path length, number of movements and task completion time. In order to validate the discriminatory ability of HMM for classifying different movement patterns, a non-surgical task was included in our analysis. Experimental results demonstrate that our approach had 100 % accuracy in discriminating between expert and novice performances. Our proposed motion analysis technique applied to open surgical procedures is a promising step towards the development of objective computer-assisted assessment and training systems.


Clinical Competence , Computer-Assisted Instruction/methods , Fingers , Movement , Surgical Procedures, Operative/education , Computer-Assisted Instruction/instrumentation , Formative Feedback , Humans , Markov Chains
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