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1.
BMC Cancer ; 24(1): 596, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755542

ABSTRACT

BACKGROUND: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Neoplasm Recurrence, Local , Humans , Male , Female , Middle Aged , Esophageal Neoplasms/pathology , Esophageal Neoplasms/radiotherapy , Esophageal Neoplasms/surgery , Retrospective Studies , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Aged , Lymph Nodes/pathology , Lymph Nodes/surgery , Esophageal Squamous Cell Carcinoma/surgery , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/radiotherapy , Esophagectomy , Adult , Prognosis , China/epidemiology , Neoplasm Staging
2.
JCI Insight ; 9(6)2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38358827

ABSTRACT

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene lead to CF, a life-threating autosomal recessive genetic disease. While recently approved Trikafta dramatically ameliorates CF lung diseases, there is still a lack of effective medicine to treat CF-associated liver disease (CFLD). To address this medical need, we used a recently established CF rabbit model to test whether sotagliflozin, a sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor drug that is approved to treat diabetes, can be repurposed to treat CFLD. Sotagliflozin treatment led to systemic benefits to CF rabbits, evidenced by increased appetite and weight gain as well as prolonged lifespan. For CF liver-related phenotypes, the animals benefited from normalized blood chemistry and bile acid parameters. Furthermore, sotagliflozin alleviated nonalcoholic steatohepatitis-like phenotypes, including liver fibrosis. Intriguingly, sotagliflozin treatment markedly reduced the otherwise elevated endoplasmic reticulum stress responses in the liver and other affected organs of CF rabbits. In summary, our work demonstrates that sotagliflozin attenuates liver disorders in CF rabbits and suggests sotagliflozin as a potential drug to treat CFLD.


Subject(s)
Cystic Fibrosis , Liver Diseases , Animals , Rabbits , Cystic Fibrosis/complications , Cystic Fibrosis/drug therapy , Cystic Fibrosis/genetics , Liver Diseases/complications , Glycosides , Liver Cirrhosis/drug therapy , Liver Cirrhosis/complications
3.
IEEE Trans Vis Comput Graph ; 29(11): 4361-4371, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37788214

ABSTRACT

We present FineStyle, a novel framework for motion style transfer that generates expressive human animations with specific styles for virtual reality and vision fields. It incorporates semantic awareness, which improves motion representation and allows for precise and stylish animation generation. Existing methods for motion style transfer have all failed to consider the semantic meaning behind the motion, resulting in limited controls over the generated human animations. To improve, FineStyle introduces a new cross-modality fusion module called Dual Interactive-Flow Fusion (DIFF). As the first attempt, DIFF integrates motion style features and semantic flows, producing semantic-aware style codes for fine-grained motion style transfer. FineStyle uses an innovative two-stage semantic guidance approach that leverages semantic clues to enhance the discriminative power of both semantic and style features. At an early stage, a semantic-guided encoder introduces distinct semantic clues into the style flow. Then, at a fine stage, both flows are further fused interactively, selecting the matched and critical clues from both flows. Extensive experiments demonstrate that FineStyle outperforms state-of-the-art methods in visual quality and controllability. By considering the semantic meaning behind motion style patterns, FineStyle allows for more precise control over motion styles. Source code and model are available on https://github.com/XingliangJin/Fine-Style.git.

4.
Appl Opt ; 62(29): 7844-7851, 2023 Oct 10.
Article in English | MEDLINE | ID: mdl-37855495

ABSTRACT

In the development of the Cold Atom Physics Research Rack (CAPR) on board the Chinese Space Station, the laser system plays a critical role in preparing the all-optical 87 R b Bose-Einstein condensates (BECs). An all-fiber laser system has been developed for CAPR to provide the required optical fields for atom interaction and to maintain the beam pointing in long-term operation. The laser system integrates a 780 nm fiber laser system and an all-fiber optical control module for sub-Doppler cooling, as well as an all-fiber 1064 nm laser system for evaporative cooling. The high-power, single-frequency 780 nm lasers are achieved through rare-Earth doped fiber amplification, fiber frequency-doubling, and frequency stabilization technology. The all-fiber optical control module divides the output of the 780 nm laser system into 15 channels and regulates them for cooling, trapping, and probing atoms. Moreover, the power consistency of each pair of cooling beams is ensured by three power tracking modules, which is a prerequisite for maintaining stable MOT and molasses. A high-power, compact, controlled-flexible, and highly stable l064 nm all-fiber laser system employing two-stage ytterbium-doped fiber amplifier (YDFA) technology has been designed for evaporative cooling in the optical dipole trap (ODT). Finally, an all-optical 87 R b BEC is realized with this all-fiber laser system, which provides an alternative solution for trapping and manipulating ultra-cold atoms in challenging environmental conditions.

5.
Chemosphere ; 337: 139325, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37356585

ABSTRACT

Adding compost to soil is an effective strategy to promote the degradation of organic pollutants and reduce ecological risks. However, the effect of compost on the degradation of imazethapyr (IMET) in different soil types is not clear. To address this issue, a pot experiment was conducted, and high-throughput sequencing and mass spectrometry technology were used to identify the influence of cow manure compost on the degradation efficiency of IMET in black soil and saline-alkali soil and the role of key microorganisms. The results showed that adding compost to black soil increased the degradation rate of IMET by 12.58% and shortened the half-life by 53.37%, while in saline-alkali soil, the degradation rate of IMET decreased by 6.99% with no significant change in the half-life. High-throughput sequencing results showed that adding cow manure compost (mass ratio of 4%) significantly increased the abundance of bacterial families capable of degrading organic pollutants in black soil, but had an inhibitory effect on this bacterial community in saline-alkali soil. Redundancy analysis (RDA) results showed that total organic carbon (TOC), alkali-hydrolyzable nitrogen (AN), ammonia nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) were the main factors driving microbial community variation. Mass spectrometry analysis indicated that IMET generated three metabolites during the degradation process. Sphingomonadaceae and Vicinamibacteraceae could accelerate the breaking of side-chain alkyl groups, while Chitinophagaceae could cause the rearrangement of the imidazole ring structure, gradually metabolizing IMET into small organic molecules. The application of appropriate cow manure compost can promote the development of IMET-degrading bacteria by adjusting the organic carbon and dissolved nitrogen content in black soil. In the future, the quantitative effects of organic fertilizer application on the IMET degradation process in different soil types should be further analyzed, and microbial isolation and purification should be used to enhance the ability of microorganisms to degrade herbicides.


Subject(s)
Composting , Environmental Pollutants , Animals , Cattle , Soil/chemistry , Manure/microbiology , Carbon/analysis , Alkalies , Environmental Pollutants/analysis , Nitrogen/analysis
6.
PNAS Nexus ; 2(1): pgac306, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36712930

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive genetic disease affecting multiple organs. Approximately 30% CF patients develop CF-related liver disease (CFLD), which is the third most common cause of morbidity and mortality of CF. CFLD is progressive, and many of the severe forms eventually need liver transplantation. The mechanistic studies and therapeutic interventions to CFLD are unfortunately very limited. Utilizing the CRISPR/Cas9 technology, we recently generated CF rabbits by introducing mutations to the rabbit CF transmembrane conductance regulator (CFTR) gene. Here we report the liver phenotypes and mechanistic insights into the liver pathogenesis in these animals. CF rabbits develop spontaneous hepatobiliary lesions and abnormal biliary secretion accompanied with altered bile acid profiles. They exhibit nonalcoholic steatohepatitis (NASH)-like phenotypes, characterized by hepatic inflammation, steatosis, and fibrosis, as well as altered lipid profiles and diminished glycogen storage. Mechanistically, our data reveal that multiple stress-induced metabolic regulators involved in hepatic lipid homeostasis were up-regulated in the livers of CF-rabbits, and that endoplasmic reticulum (ER) stress response mediated through IRE1α-XBP1 axis as well as NF-κB- and JNK-mediated inflammatory responses prevail in CF rabbit livers. These findings show that CF rabbits manifest many CFLD-like phenotypes and suggest targeting hepatic ER stress and inflammatory pathways for potential CFLD treatment.

7.
Mol Med Rep ; 27(2)2023 Feb.
Article in English | MEDLINE | ID: mdl-36484396

ABSTRACT

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that several of the panels shown for the cell invasion assays in Figs. 2C and 5D were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 1403­1409, 2019; DOI: 10.3892/mmr.2018.9750].

8.
Mol Nutr Food Res ; 66(16): e2200126, 2022 08.
Article in English | MEDLINE | ID: mdl-35712860

ABSTRACT

SCOPE: Sweet potato (Ipomoea batatas L.) is one of the leading crops worldwide, containing high nutritional components such as fiber and polyphenols. Root tuber of Simon 1 (SIMON), a cultivar of sweet potato, is a folk food in China with a hemostasis function but lacking experimental data support. METHODS AND RESULTS: Now the protective effect of SIMON on chemotherapy-induced thrombocytopenia (CIT), a serious complication of cancer treatment, is investigated for the first time by a CIT mouse model induced by intraperitoneal injection of carboplatin. As a result, SIMON raises the number of peripheral platelets, white blood cells, and bone marrow nucleated cells in CIT mice significantly. Besides, carboplatin-induced atrophy of the thymus, spleen, and disordered metabolism of the inflammatory immune system and glycerophospholipids are also reversed by SIMON. Phytochemical analysis of SIMON indicates 16 compounds including eight phenolic derivatives, which might be associated with its anti-CIT bioactivity. CONCLUSION: Sweet potato (SIMON) may be an efficient function food in the prevention of bleeding disorders.


Subject(s)
Antineoplastic Agents , Ipomoea batatas , Thrombocytopenia , Animals , Carboplatin/metabolism , Functional Food , Ipomoea batatas/chemistry , Ipomoea batatas/metabolism , Mice , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy , Thrombocytopenia/prevention & control
9.
Biochim Biophys Acta Proteins Proteom ; 1870(6): 140792, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35569794

ABSTRACT

As a misfolding protein, almost all of F508del-CFTR is degraded by the ubiquitin-proteasome system before its maturation, which results in no membrane expression of cystic fibrosis transmembrane conductance regulator (CFTR) and therefore, no chloride secretion across epithelial cells of cystic fibrosis (CF) patients. The conjugation of ubiquitin (Ub) chains to protein substrates is necessary for the proteasomal degradation of F508del-CFTR. Ubiquitin contains seven lysine (K) residues, all of which can be conjugated to one another, forming poly-ubiquitin chains on substrates, either by mixing together, or by only one type of lysine providing sorting signals for different pathways. Here, we report that four lysine-linked poly-Ub chains (LLPUCs) were involved in F508del-CFTR biogenesis: LLPUCs linked by K11 or K48 facilitated F508del-CFTR degradation, whereas the other two linked by K63 and K33 protected F508del-CFTR from degradation. LLPUC K11 is more potent for F508del-CFTR degradation than K48. F508del-CFTR utilizes four specific lysine-linked poly-Ub chains during its biogenesis for opposite destiny through different identification by proteasomal shuttle protein or receptors. These findings provide new insights into the CF pathogenesis and are expected to facilitate the development of therapies for this devastating disease.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator , Cystic Fibrosis , Cystic Fibrosis/genetics , Cystic Fibrosis/metabolism , Cystic Fibrosis/pathology , Cystic Fibrosis Transmembrane Conductance Regulator/chemistry , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Humans , Lysine , Proteasome Endopeptidase Complex/metabolism , Ubiquitin
10.
Comput Intell Neurosci ; 2022: 1712258, 2022.
Article in English | MEDLINE | ID: mdl-35281190

ABSTRACT

In this paper, we first propose an accurate edge detector using a distance field-based convolutional neural network (DF-CNN). In recent years, CNNs have been proved to be effective in image processing and computer vision. As edge detection is a fundamental problem among them, we try to improve the accuracy of edge detection based on the deep learning framework. The proposed network combines a feature extraction backbone that can fully exploit the multiscale and multilevel information of the edge with the supervised training of the distance field branch to realize the accurate end-to-end object edge detection. The distance field branch is applied to predict the Euclidean distance from nonedge points to the nearest edge point in the feature maps. And the distance information embedded in the predicted distance field map can effectively improve the accuracy of edge detection. The network is trained to minimize the weighted sum of the distance field branch loss and the cross-entropy loss. Our experimental results show that the proposed edge detector achieves better performance than previous approaches and the effectiveness of the proposed distance field branch.


Subject(s)
Image Processing, Computer-Assisted , Neural Networks, Computer
11.
Radiat Oncol ; 17(1): 47, 2022 Mar 05.
Article in English | MEDLINE | ID: mdl-35248100

ABSTRACT

BACKGROUND: To study lymphatic recurrence distribution after radical surgery in the real world and guide clinical tumor volume delineation for regional lymph nodes during postoperative radiotherapy for lower thoracic squamous cell esophageal carcinomas. METHODS: We enrolled patients who underwent radical esophagectomy, without radiation before or after surgery, at 3 cancer hospitals. Patients were classified into groups according to tumor locations. We included patients with tumors in the lower thoracic segment and analyzed the postoperative lymph node recurrence mode. A cutoff value of 10% was used to differentiate high-risk lymph node drainage areas from others. RESULTS: We enrolled 1905 patients in the whole study series, including 652 thoracic esophageal carcinomas that met our inclusion criteria; there were 241 cases of lower thoracic esophageal carcinomas. 1st, 2nd, 4th, 7th, 8th groups of lymph nodes, according to the 8th edition of the AJCC classification, displayed as high-risk recurrence areas, representing 17.8%, 23.9%, 11.7%, 10.9% and 12.2% of lymph node recurrence. Stage III-IV tumors located in the lower segment of the thoracic esophagus showed a tendency to recur in the left gastric nodes (7.9%) and celiac nodes (10.6%). CONCLUSIONS: According to our results, we recommended including the 4th, 7th and 8th groups of lymph nodes in the radiation field, and for patients with stage III-IV disease, the 17th and 20th groups of nodes should be irradiated during postoperative treatment. Whether including 1st/2nd groups in preventive irradiation needed more proofs.


Subject(s)
Esophageal Neoplasms/radiotherapy , Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma/radiotherapy , Esophageal Squamous Cell Carcinoma/surgery , Esophagectomy , Lymphatic Metastasis/radiotherapy , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/secondary , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Postoperative Period
12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-940430

ABSTRACT

ObjectiveTo investigate the quality variation of Lonicera japonica flower from different harvesting periods by ultraviolet visible(UV-Vis) fingerprint combined with chemometrics. MethodTwenty-five L. japonica flower samples from five harvesting periods, including young bud stage,green bud stage,white bud stage,silver and golden flower stages, were collected, with five samples for each stage. UV-Vis fingerprints of L. japonica flower from different harvesting periods were established in the context of the optimum extraction method based on the single factor experiment. The results showed that the absorption values at 209,216,226,250,280,303,318, and 350 nm were significantly different. Moreover,after data pretreatment and normalization,multivariate statistical analyses, such as principal component analysis (PCA),partial least squares discriminant analysis (PLS-DA),and orthogonal PLS-DA (OPLS-DA)were performed by SIMCA-P+ to establish the quality variation model of L. japonicas flower from harvesting periods. ResultAs revealed by PCA and PLS-DA, L. japonicas flower samples from five harvesting periods were clustered separately and closely in a harvesting time-dependent manner, suggesting that the content of components contained in samples from different harvesting periods was highly distinct and correlated with harvesting periods. The pairwise comparison of OPLS-DA indicated that triterpenoids or volatile oils were the main components causing the changes from the young bud stage to the green bud stage,and the content of them decreased. The main components from the green bud stage to the white bud stage were triterpenoids (or iridoids),volatile oils,phenolic acids, or flavonoids,and the content of them decreased, which was consistent with the HPLC result of chlorogenic acid. From the white bud stage to the silver flower stage, the main components were iridoids (increasing in content) and triterpenoids (or volatile oils) (decreasing in content). The main altered components from the silver flower stage to the golden flower stage were triterpenoids (or volatile oils) whose content increased. ConclusionThis method is simple and feasible, which can provide references for the quality control of Chinese medicine.

13.
Appl Opt ; 60(28): 8930-8938, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34613122

ABSTRACT

With the development of laser communication networking, laser-ranging technology is becoming more and more applicable. In this paper, high-accuracy ranging is implemented based on intradyne coherent detection at a communication rate of 1048.576 Mbps. The ranging accuracy is affected by clock phase calculation error and code loop track error. Parallel clock phase difference calculation, frame head correlation, and ranging ambiguity region handle are combined with the ranging calibration method, realizing millimeter-level corrected distance measurement. Dynamic range measurement above 1 m is proven to be continuous through the ranging ambiguity region handle. In addition, high-precision clock frequency deviation between two asynchronous terminals can be obtained through derivation of one-way distance at static ranging or by derivative of distance difference at bidirectional ranging. The methods proposed in this paper are verified by inter-satellite laser-ranging on orbit, and the results are analyzed.

14.
Onco Targets Ther ; 14: 3051-3062, 2021.
Article in English | MEDLINE | ID: mdl-33994797

ABSTRACT

INTRODUCTION: Programmed cell death 1 ligand 1 (PD-L1) can be upregulated in cancer cells via interferon gamma (IFNγ) in the tumor microenvironment. IFNγ/PD-L1 signaling is associated with the response to immune checkpoint blockade in melanoma patients. Our previous investigation indicated that the microsatellite instability-high (MSI-H) cell line might exhibit selective hyperresponsiveness to IFNγ treatment, which contributes to increased PD-L1 expression and may be a mechanism of response to anti-PD-1 therapy in colorectal cancer. METHODS: The present study evaluated the expression of PD-L1 in a set of MSI and microsatellite stability (MSS) cell lines with IFNγ treatment. The differential signaling molecules associated with signal transducer and activator of transcription (STAT) contributing to hyperresponsiveness to IFNγ exposure were also investigated. Furthermore, we established a coculture assay containing CT26 cells with higher expression of PD-L1 and peripheral blood mononuclear cells (PBMCs) in vitro. Changes in cancer cell viability as well as apoptosis status in response to anti-PD-1 therapy were demonstrated. We further observed changes in the percentage of CD4+ and CD8+ lymphocytes after PD-1 immunotherapy in the coculture assay. Finally, the average extent of inflammation and adaptive immunity factors in the assay was also investigated. RESULTS: This in vitro study revealed that the MSI cell line might exhibit hyperresponsiveness to IFNγ exposure, and IFNγ induced upregulation of PD-L1 mainly through increased STAT1 and decreased STAT3 signaling. IFNγ/PD-L1 signaling participated in the response to anti-PD-1 therapy mainly through the CTL profile. DISCUSSION: Our findings reinforce previous knowledge of the fact that the response to immune checkpoint blockade occurs mainly in patients with a preexisting intratumoral IFNγ/PD-L1 signal, thus suggesting potential therapeutic strategies to enhance responsiveness to PD-1 blockade immunotherapy in most patients with colorectal cancer.

15.
J Pers Med ; 11(2)2021 Feb 16.
Article in English | MEDLINE | ID: mdl-33669429

ABSTRACT

Individuals with cystic fibrosis (CF) often experience gastrointestinal (GI) abnormalities. In recent years, the intestinal microbiome has been postulated as a contributor to the development of CF-associated GI complications, hence representing a potential therapeutic target for treatment. We recently developed a rabbit model of CF, which is shown to manifest many human patient-like pathological changes, including intestinal obstruction. Here, we investigated the feces microbiome in young CF rabbits in the absence of antibiotics treatment. Stool samples were collected from seven- to nine-week-old CF rabbits (n = 7) and age-matched wild-type (WT) rabbits (n = 6). Microbiomes were investigated by iTag sequencing of 16S rRNA genes, and functional profiles were predicted using PICRUSt. Consistent with reports of those in pediatric CF patients, the fecal microbiomes of CF rabbits are of lower richness and diversity than that of WT rabbits, with a marked taxonomic and inferred functional dysbiosis. Our work identified a new CF animal model with the manifestation of intestinal dysbiosis phenotype. This model system may facilitate the research and development of novel treatments for CF-associated gastrointestinal diseases.

16.
Front Psychol ; 12: 755039, 2021.
Article in English | MEDLINE | ID: mdl-35222140

ABSTRACT

The advent of the intelligence age has injected new elements into the development of literature. The synergic modification of Anglo-American (AAL) traumatic narrative (TN) literature by artificial intelligence (AI) technology and interactive design (ID) psychology will produce new possibilities in literary creation. First, by studying natural language processing (NLP) technology, this study proposes a modification language model (LM) based on the double-layered recurrent neural network (RNN) algorithm and constructs an intelligent language modification system based on the improved LM model. The results show that the performance of the proposed model is excellent; only about 30% of the respondents like AAL literature; the lack of common cultural background, appreciation difficulties, and language barriers have become the main reasons for the decline of reading willingness of AAL literature. Finally, AI technology and ID psychology are used to modify a famous TN work respectively and synergically, and the modified work is appreciated by respondents to collect their comments. The results corroborate that 62% of the respondents like original articles, but their likability scores have decreased for individually modified work by AI or ID psychology. In comparison, under the synergic modification efforts of AI and ID psychology, the popularity of the modified work has increased slightly, with 65% of the respondents showing a likability to read. Therefore, it is concluded that literary modification by single ID psychology or AI technology will reduce the reading threshold by trading off the literary value of the original work. The core of literary creation depends on human intelligence, and AI might still not be able to generate high-standard literary works independently because human minds and thoughts cannot be controlled and predicted by machines. The research results provide new ideas and improvement directions for the field of AI-assisted writing.

17.
JCI Insight ; 6(1)2021 01 11.
Article in English | MEDLINE | ID: mdl-33232302

ABSTRACT

Existing animal models of cystic fibrosis (CF) have provided key insights into CF pathogenesis but have been limited by short lifespans, absence of key phenotypes, and/or high maintenance costs. Here, we report the CRISPR/Cas9-mediated generation of CF rabbits, a model with a relatively long lifespan and affordable maintenance and care costs. CF rabbits supplemented solely with oral osmotic laxative had a median survival of approximately 40 days and died of gastrointestinal disease, but therapeutic regimens directed toward restoring gastrointestinal transit extended median survival to approximately 80 days. Surrogate markers of exocrine pancreas disorders were found in CF rabbits with declining health. CFTR expression patterns in WT rabbit airways mimicked humans, with widespread distribution in nasal respiratory and olfactory epithelia, as well as proximal and distal lower airways. CF rabbits exhibited human CF-like abnormalities in the bioelectric properties of the nasal and tracheal epithelia. No spontaneous respiratory disease was detected in young CF rabbits. However, abnormal phenotypes were observed in surviving 1-year-old CF rabbits as compared with WT littermates, and these were especially evident in the nasal respiratory and olfactory epithelium. The CF rabbit model may serve as a useful tool for understanding gut and lung CF pathogenesis and for the practical development of CF therapeutics.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/antagonists & inhibitors , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/genetics , Animals , CRISPR-Cas Systems , Cystic Fibrosis/pathology , Cystic Fibrosis/physiopathology , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Disease Models, Animal , Female , Gastrointestinal Tract/pathology , Gastrointestinal Tract/physiopathology , Gene Knockout Techniques , Humans , Male , Phenotype , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rabbits , Respiratory System/pathology , Respiratory System/physiopathology , Tissue Distribution , Transcriptome
18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-879096

ABSTRACT

Prunella vulgaris(PV) is an edible and traditional medicinal herb which has a wide range application in fighting inflammation and oxidative stress, and protecting liver. Now it has been used to treat various types of liver diseases and has significant clinical efficacy. This study aims to investigate the effects of PV on ethanol-induced oxidative stress injury in rats and its metabolic mechanism. The rats were divided into control group, model group, PV group, and VC group. The liver protection of PV was identified by measuring pharmacological indexes such as antioxidant and anti-inflammatory activity. The metabolic mechanism of long-term ethanol exposure and the metabolic regulation mechanism of PV treatment were studied by LS-MS metabonomics. The pharmacological investigation indicated that ethanol could significantly decrease the contents of SOD, GSH-Px, CAT and other antioxidant enzymes in liver and increase the content of MDA. At the same time, PV could significantly reduce the contents of inflammatory factors(TNF-α, IL-6 and IL-1β) and liver function markers(ALT, AST, ALP) in serum. What's more, long-term ethanol exposure could significantly cause liver injury, while PV could protect liver. Metabolomics based on multiple statistical analyses showed that long-term ethanol exposure could cause significant metabolic disorder, and fatty acids, phospholipids, carnitines and sterols were the main biomarkers. Meanwhile, pathway analysis and enrichment analysis showed that the β oxidation of branched fatty acids was the main influencing pathway. Also, PV could improve metabolic disorder of liver injury induced by ethanol, and amino acids, fatty acids, and phospholi-pids were the main biomarkers in PV treatment. Metabolic pathway analysis showed that PV mainly regulated metabolic disorder of ethanol-induced liver injury through phenylalanine, tyrosine and tryptophan biosynthetic pathways. This study could provide a new perspective on the hepatoprotective effect of natural medicines, such as PV.


Subject(s)
Animals , Rats , Antioxidants/metabolism , Ethanol/toxicity , Liver/metabolism , Metabolomics , Oxidative Stress , Prunella
19.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4652-4657, 2020 Oct.
Article in Chinese | MEDLINE | ID: mdl-33164429

ABSTRACT

High performance liquid chromatography-ultraviolet(HPLC-UV) fingerprint is one of the most important methods for the quality control of Chinese medicines in Chinese Pharmacopoeia. However, certain subjectivity is present in selection of specific band of UV, and the inherent quality differences of Chinese medicine can't be well characterized by this method. Therefore, with different grades of Scrophulariae Radix were taken as the research object in this study, a new quality control model of HPLC-UV was established in this study based on the ultraviolet full-wavelength scanning spectrum. Firstly, different grades of Scrophulariae Radix samples were collected, and the full-wavelength ultraviolet absorption spectra of all the samples were established at the bands of 200-400 nm. In order to analyze the differences among samples, the analysis model was built following multivariate statistical analysis methods such as principal component analysis(PCA) and partial least squares discrimination analysis(PLS-DA) after the pretreatment of spectral data. The result showed that the ultraviolet band at 251 nm may contribute most to distinguish the quality differences among different grades of samples. Then, the HPLC fingerprints of samples were established with the band at 251 nm. The multivariate statistical analysis showed that there was a more significant classification trend in HPLC fingerprints than that in the original UV fingerprints, which could be used to distinguish different grades of samples, and could better reflect the differences among different grades. The method reported in this study can be of a great guidance and reference for the establishment of specific fingerprints of Chinese medicines as well as for the quality control of Chinese medicine.


Subject(s)
Drugs, Chinese Herbal , Chromatography, High Pressure Liquid , Plant Roots , Principal Component Analysis , Quality Control
20.
Cancer Manag Res ; 12: 10389-10396, 2020.
Article in English | MEDLINE | ID: mdl-33116893

ABSTRACT

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy, and cases have been rising steadily worldwide in the past few decades. Despite great progress having been made in surgery and chemotherapy for PTC, the survival rate of PTC patients has not increased significantly. Therefore, there is an urgent need to explore novel treatment strategies. MATERIALS AND METHODS: The levels of circRNA_103598, miR-23a-3p and IL-6 mRNA in PTC tissues and cells were examined by qRT-PCR assay. Cell proliferation and IC50 values of oncolytic vaccinia virus (OVV) were detected by CCK-8 assay. A dual-luciferase reporter assay was performed to detect the relationships among circRNA_103598, miR-23a-3p and IL-6. ELISA was carried out to detect the expression of IL-6. RESULTS: We found that circRNA_103598 was increased in PTC tissues and cell lines and acted as a sponge for miR-23a-3p. Moreover, knockdown of miR-23a-3p suppressed the OVV-mediated antitumor effect and cell proliferation in PTC. In addition, we revealed that circRNA_103598 bound to miR-23a-3p as a sponge to promote IL-6 expression. CONCLUSION: Our study first revealed the high expression and oncogenic function of circRNA_103598 in PTC cells. Then, circRNA_103598 sponged miR-23a-3p to upregulate IL-6 expression, with the resulted that cell proliferation was promoted and the OVV-mediated antitumor effect was enhanced by strengthening the viral replication, providing new insights into future therapy for PTC.

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