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1.
Int J Genomics ; 2024: 4596974, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39397896

RESUMO

LncRNA is a major factor in the occurrence and development of many diseases. However, its mechanism in cerebral ischemia/reperfusion injury (CIRI) is yet unknown. In this study, the transcriptional level and methylation modification level of LncRNAs before and after mechanical thrombectomy were compared by high-throughput sequencing. Venn diagram, Spearman correlation analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, TargetScan, and miRanda were used to analyze the experimental data. The results showed that four key LncRNAs changed at both transcription and methylation levels. Specifically, LncRNA FAR2, LINC02431, and AL357060.1 were downregulated and hypomethylated, while LncRNA FOXD2-AS1 was upregulated and hypomethylated. Moreover, positive regulation of angiogenesis, protein domain-specific binding, autophagy pathway, PPAR signaling pathway, and MAPK signaling pathway were co-enriched between LncRNAs with different expression levels and different methylation levels. Finally, a LncRNA-miRNA-mRNA network was constructed. Therefore, this study explored the potential key LncRNAs and regulatory mechanisms of CIRI.

3.
Int J Oncol ; 65(5)2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39301639

RESUMO

Macrophages have crucial roles in immune responses and tumor progression, exhibiting diverse phenotypes based on environmental cues. In the present study, the impact of cinobufagin (CB) on macrophage polarization and the consequences on tumor­associated behaviors were investigated. Morphological transformations of THP­1 cells into M0, M1 and M2 macrophages were observed, including distinct changes in the size, shape and adherence properties of these cells. CB treatment inhibited the viability of A549 and LLC cells in a concentration­dependent manner, with an IC50 of 28.8 and 30.12 ng/ml, respectively. CB at concentrations of <30 ng/ml had no impact on the viability of M0 macrophages and lung epithelial (BEAS­2B) cells. CB influenced the expression of macrophage surface markers, reducing CD206 positivity in M2 macrophages without affecting CD86 expression in M1 macrophages. CB also altered certain expression profiles at the mRNA level, notably downregulating macrophage receptor with collagenous structure (MARCO) expression in M2 macrophages and upregulating tumor necrosis factor­α and interleukin­1ß in both M0 and M1 macrophages. Furthermore, ELISA analyses revealed that CB increased the levels of pro­inflammatory cytokines in M1 macrophages and reduced the levels of anti­inflammatory factors in M2 macrophages. CB treatment also attenuated the migration and invasion capacities of A549 and LLC cells stimulated by M2 macrophage­conditioned medium. Additionally, CB modulated peroxisome proliferator­activated receptor γ (PPARγ) and MARCO expression in M2 macrophages and epithelial­mesenchymal transition in A549 cells, which was partially reversed by rosiglitazone, a PPARγ agonist. Finally, CB and cisplatin treatments hindered tumor growth in vivo, with distinct impacts on animal body weight and macrophage marker expression in tumor tissues. In conclusion, the results of the present study demonstrated that CB exerted complex regulatory effects on macrophage polarization and tumor progression, suggesting its potential as a modulator of the tumor microenvironment and a therapeutic for cancer treatment.


Assuntos
Bufanolídeos , Movimento Celular , Neoplasias Pulmonares , Invasividade Neoplásica , Macrófagos Associados a Tumor , Bufanolídeos/farmacologia , Bufanolídeos/uso terapêutico , Humanos , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/imunologia , Animais , Camundongos , Movimento Celular/efeitos dos fármacos , Células A549 , Ensaios Antitumorais Modelo de Xenoenxerto , Células THP-1 , PPAR gama/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Linhagem Celular Tumoral
4.
Tissue Eng Part C Methods ; 30(8): 353-363, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39113538

RESUMO

This study aims to determine the hemostatic effectivity and biocompatibility of a novel absorbable bone wax in comparison with a commercially available product. Eighteen small fat-tail sheep were used to simulate clinical surface bleeding of sternal injury. Hemostasis effectiveness, the degree of bone healing, micro-computed tomography, and histopathology were evaluated over a period after the application of the material to the surgically created wound. The absorbable bone wax used in the study stopped bleeding immediately and did not affect bone healing. The histopathological results also showed that there were no complications associated with the new material. The results showed that the new absorbable bone wax used in this study was effective and biocompatible.


Assuntos
Materiais Biocompatíveis , Teste de Materiais , Palmitatos , Ceras , Animais , Ceras/farmacologia , Ceras/química , Ovinos , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Palmitatos/farmacologia , Osso e Ossos/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Microtomografia por Raio-X , Hemostáticos/farmacologia , Implantes Absorvíveis
5.
Sci Rep ; 14(1): 15564, 2024 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971897

RESUMO

Aortic dissection (AD) is a life-threatening condition with a high mortality rate and without effective pharmacological therapies. Our previous study illustrated that leukocyte immunoglobulin-like receptor B4 (LILRB4) knockdown promoted the contractile phenotypic switch and apoptosis of AD cells. This study aimed to further investigate the role of LILRB4 in animal models of AD and elucidate its underlying molecular mechanisms. Animal models of AD were established using 0.1% beta-aminopropionitrile and angiotensin II and an in vitro model was developed using platelet-derived growth factor BB (PDGF-BB). The effects of LILRB4 knockdown on histopathological changes, pyroptosis, phenotype transition, extracellular matrix (ECM), and Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathways were assessed using a series of in vivo and in vitro assays. The effects of the JAK2 inhibitor AG490 on AD cell function, phenotypic transition, and ECM were explored. LILRB4 was highly expressed in AD and its knockdown increased survival rate, reduced AD incidence, and alleviated histopathological changes in the AD mouse model. Furthermore, LILRB4 knockdown promoted contractile phenotype switch, stabilized the ECM, and inhibited pyroptosis. Mechanistically, LILRB4 knockdown inhibited the JAK2/STAT3 signaling pathway. JAK2 inhibitor AG490 inhibited cell viability and migration, enhanced apoptosis, induced G0/G1 cell cycle arrest, and suppressed S-phase progression in PDGF-BB-stimulated human aortic smooth muscle cells. LILRB4 knockdown suppresses AD development by inhibiting pyroptosis and the JAK2/STAT3 signaling pathway.


Assuntos
Dissecção Aórtica , Modelos Animais de Doenças , Janus Quinase 2 , Piroptose , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Dissecção Aórtica/metabolismo , Dissecção Aórtica/patologia , Dissecção Aórtica/genética , Técnicas de Silenciamento de Genes , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Camundongos Endogâmicos C57BL , Piroptose/genética , Fator de Transcrição STAT3/metabolismo , Tirfostinas/farmacologia
6.
J Cardiothorac Surg ; 19(1): 286, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734628

RESUMO

Acute type A aortic dissection is a severe cardiovascular disease characterized by rapid onset and high mortality. Traditionally, urgent open aortic repair is performed after admission to prevent aortic rupture and death. However, when combined with malperfusion syndrome, the low perfusion of the superior mesenteric artery can further lead to intestinal necrosis, significantly impacting the surgery's prognosis and potentially resulting in adverse consequences, bringing. This presents great significant challenges in treatment. Based on recent domestic and international research literature, this paper reviews the mechanism, current treatment approaches, and selection of surgical methods for poor organ perfusion caused by acute type A aortic dissection. The literature review findings suggest that central aortic repair can be employed for the treatment of acute type A aortic dissection with inadequate perfusion of the superior mesenteric artery. The superior mesenteric artery can be windowed and (/or) stented, followed by delayed aortic repair. Priority should be given to revascularization of the superior mesenteric artery, followed by central aortic repair. During central aortic repair, direct blood perfusion should be performed on the distal true lumen of the superior mesenteric artery, leading to resulting in favorable therapeutic outcomes. The research results indicate that even after surgical aortic repair, intestinal ischemic necrosis may still occur. In such cases, prompt laparotomy and necessary necrotic bowel resection are crucial for saving the patient's life.


Assuntos
Dissecção Aórtica , Artéria Mesentérica Superior , Necrose , Humanos , Dissecção Aórtica/cirurgia , Dissecção Aórtica/complicações , Artéria Mesentérica Superior/cirurgia , Intestinos/irrigação sanguínea , Intestinos/cirurgia , Isquemia Mesentérica/cirurgia , Isquemia/cirurgia , Aneurisma Aórtico/cirurgia , Aneurisma Aórtico/complicações , Doença Aguda
7.
J Cardiothorac Surg ; 19(1): 273, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702812

RESUMO

Acute type A aortic dissection is a life-threatening cardiovascular disease characterized by rapid onset and high mortality. Emergency surgery is the preferred and reliable treatment option. However, postoperative complications significantly impact patient prognosis. Hypoxemia, a common complication, poses challenges in clinical treatment, negatively affecting patient outcomes and increasing the risk of mortality. Therefore, it is crucial to study and comprehend the risk factors and treatment strategies for hypoxemia following acute type A aortic dissection to facilitate early intervention.


Assuntos
Dissecção Aórtica , Hipóxia , Complicações Pós-Operatórias , Humanos , Dissecção Aórtica/cirurgia , Dissecção Aórtica/complicações , Fatores de Risco , Hipóxia/etiologia , Doença Aguda , Aneurisma da Aorta Torácica/cirurgia
8.
Nature ; 630(8015): 181-188, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38778098

RESUMO

Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles1-3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision-language pretraining for pathology7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.


Assuntos
Conjuntos de Dados como Assunto , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Patologia Clínica , Humanos , Benchmarking , Processamento de Imagem Assistida por Computador/métodos , Neoplasias/classificação , Neoplasias/diagnóstico , Neoplasias/patologia , Patologia Clínica/métodos , Masculino , Feminino
9.
Nanomaterials (Basel) ; 14(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38786792

RESUMO

After more than five decades, Moore's Law for transistors is approaching the end of the international technology roadmap of semiconductors (ITRS). The fate of complementary metal oxide semiconductor (CMOS) architecture has become increasingly unknown. In this era, 3D transistors in the form of gate-all-around (GAA) transistors are being considered as an excellent solution to scaling down beyond the 5 nm technology node, which solves the difficulties of carrier transport in the channel region which are mainly rooted in short channel effects (SCEs). In parallel to Moore, during the last two decades, transistors with a fully depleted SOI (FDSOI) design have also been processed for low-power electronics. Among all the possible designs, there are also tunneling field-effect transistors (TFETs), which offer very low power consumption and decent electrical characteristics. This review article presents new transistor designs, along with the integration of electronics and photonics, simulation methods, and continuation of CMOS process technology to the 5 nm technology node and beyond. The content highlights the innovative methods, challenges, and difficulties in device processing and design, as well as how to apply suitable metrology techniques as a tool to find out the imperfections and lattice distortions, strain status, and composition in the device structures.

10.
Nat Commun ; 15(1): 3966, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38729935

RESUMO

Rhenium (Re) and uranium (U) are essential proxies in reconstructing past oceanic oxygenation evolution. However, their removal in continental shelf sediments, hotspots of early diagenesis, were previously treated as quantitatively unimportant sinks in the ocean. Here we examine the sedimentary reductive removal of Re and U and their coupling with organic carbon decomposition, utilizing the 224Ra/228Th disequilibria within the East China Sea shelf. We identified positive correlations between their removal fluxes and the rates of sediment oxygen consumption or organic carbon decomposition. These correlations enable an evaluation of global shelf reductive sinks that are comparable to (for Re) or higher than (~4-fold for U) previously established suboxic/anoxic sinks. These findings suggest potential imbalances in the modern budgets of Re and U, or perhaps a substantial underestimation of their sources. Our study thus highlights shelf sedimentary reductive removal as critical yet overlooked sinks for Re and U in the modern ocean.

11.
Hum Genet ; 143(3): 343-355, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38480539

RESUMO

Colorectal cancer (CRC) is the third most prevalent diagnosed cancer in men and second most prevalent cancer in women. H3K27ac alterations are more commonly than gene mutations in colorectal cancer. Most colorectal cancer genes have significant H3K27ac changes, which leads to an over-expression disorder in gene transcription. Over-expression of STEAP3 is involved in a variety of tumors, participating in the regulation of cancer cell proliferation and migration. The purpose of this work is to investigate the role of STEAP3 in the regulation of histone modification (H3K27ac) expression in colon cancer. Bioinformatic ChIP-seq, ChIP-qPCR and ATAC-seq were used to analyze the histone modification properties and gene accessibility of STEAP3. Western blot and qRT-PCR were used to evaluate relative protein and gene expression, respectively. CRISPR/Cas9 technology was used to knockout STEAP3 on colon cancer cells to analyze the effect of ATF3 on STEAP3. STEAP3 was over-expressed in colon cancer and associated with higher metastases and more invasive and worse stage of colon cancer. ChIP-seq and ChIP-qPCR analyses revealed significant enrichment of H3K27ac in the STEAP3 gene. In addition, knocking down STEAP3 significantly inhibits colon cancer cell proliferation and migration and down-regulates H3K27ac expression. ChIP-seq found that ATF3 is enriched in the STEAP3 gene and CRISPR/Cas9 technology used for the deletion of the ATF3 binding site suppresses the expression of STEAP3. Over-expression of STEAP3 promotes colon cancer cell proliferation and migration. Mechanical studies have indicated that H3K27ac and ATF3 are significantly enriched in the STEAP3 gene and regulate the over-expression of STEAP3.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias do Colo , Regulação Neoplásica da Expressão Gênica , Histonas , Humanos , Proliferação de Células/genética , Movimento Celular/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Histonas/metabolismo , Histonas/genética , Acetilação , Feminino , Linhagem Celular Tumoral , Masculino , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo
12.
Ecotoxicol Environ Saf ; 272: 116076, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38335577

RESUMO

Cr(VI) is known to be seriously toxic and carcinogenic. Hypoxia-inducible factor-1α (HIF-1α) is a crucial regulator to promote tumor development. In this study, we found that Cr(VI) significantly increased the expression of HIF-1α in A549 cells and in lung of BALB/c mice but not in HELF cells. Treatment with Lificiguat (YC-1), HIF-1α inhibitor, or CoCl2, HIF-1α inducer, could alter Cr(VI)-induced autophagy, glycolysis, and cell growth in A549 cells but not in HELF cells, validating the involvement of HIF-1α in these effects of Cr(VI) in A549 cells. Co-treatments of pcATG4B with YC-1, or siATG4B with CoCl2 demonstrated the role of HIF-1α / autophagy axis in inducing glycolysis and cell growth in A549 cells. In HELF cells, however, only autophagy but not HIF-1α played a role in inducing glycolysis. The protein level of p53 was significantly lower in A549 cells than in HELF cells. RITA, a p53 inducer, attenuated Cr(VI)-induced HIF-1α and LC3-II in A549 cells, suggesting that p53 might be the mechanism underlying the different effects of Cr(VI) on HIF-1α in A549 and HELF cells. Thus, p53-dependent HIF-1α / autophagy-mediated glycolysis plays a role in facilitating Cr(VI)-induced carcinogenesis.


Assuntos
Carcinogênese , Cromo , Cobalto , Proteína Supressora de Tumor p53 , Animais , Camundongos , Proteína Supressora de Tumor p53/genética , Autofagia , Movimento Celular , Glicólise , Linhagem Celular Tumoral
13.
Front Oncol ; 14: 1303686, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38347843

RESUMO

Background: Total mesorectal excision (TME), represents a key technique in radical surgery for rectal cancer. This study aimed to construct a preoperative nomogram for predicting the surgical difficulty of laparoscopic total mesorectal excision (L-TME) and to investigate whether there were potential benefits of robotic TME (R-TME) for patients with technically challenging rectal cancer. Methods: Consecutive mid-low rectal cancer patients receiving total mesorectal excision were included. A preoperative nomogram to predict the surgical difficulty of L-TME was established and validated. Patients with technically challenging rectal cancer were screened by calculating the prediction score of the nomogram. Then patients with technically challenging rectal cancer who underwent different types of surgery, R-TME or L-TME, were analyzed for comparison. Results: A total of 533 consecutive patients with mid-low rectal cancer who underwent TME at a single tertiary medical center between January 2018 and January 2021 were retrospectively enrolled. Multivariable analysis demonstrated that mesorectal fat area, intertuberous distance, tumor size, and tumor height were independent risk factors for surgical difficulty. Subsequently, these variables were used to construct the nomogram model to predict the surgical difficulty of L-TME. The area under the receiver operating characteristic curve of the nomogram was 0.827 (95% CI 0.745 - 0.909) and 0.809 (95% CI 0.674- 0.944) in the training and validation cohort, respectively. For patients with technically challenging rectal cancer, R-TME was associated with a lower diverting ileostomy rate (p = 0.003), less estimated blood loss (p < 0.043), shorter procedure time (p = 0.009) and shorter postoperative hospital stay (p = 0.037). Conclusion: In this study, we established a preoperative nomogram to predict the surgical difficulty of L-TME. Furthermore, this study also indicated that R-TME has potential technical advantages for patients with technically challenging rectal cancer.

14.
Asian J Surg ; 47(2): 982-989, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38030495

RESUMO

BACKGROUND: Surgery is the preferred treatment for acute Stanford type A aortic dissection (STAAD); however, due to the complexity of the procedure, cardiac ischaemia and cardiopulmonary bypass (CPB) time are longer than general heart surgery, leading to complications. In this present study, we used an integrated tetra-furcate graft for both modified aortic root and distal arch anastomoses (frozen elephant trunk technique, [FET]), and investigated postoperative outcomes associated with this technique in patients with STAAD. METHODS: We included a total of 140 patients who underwent total arch replacement and FET between January 2019 and June 2022 in the present study, 41 patients who underwent the modified technique, and 99 who underwent the graft eversion technique. We subsequently analyzed the perioperative outcomes to compare the differences between the two techniques. RESULTS: There were no statistically significant differences between the two groups in regards to the preoperative characteristics; however, the intraoperative CPB, cardiac ischaemia, and operation times of the modified technique group were significantly shorter than those of the eversion technique group (P = 0.02, P = 0.01, and P = 0.04, respectively), as were postoperative hypoxaemia, intensive care unit (ICU) stay, and ventilation times (P = 0.04, P = 0.03, and P = 0.04, respectively). Additionally, the degree of postoperative bilirubin elevation was milder in the modified technique group (P = 0.002 for direct bilirubin and P = 0.01 for indirect bilirubin). CONCLUSIONS: The modified anastomosis technique can significantly shorten CPB, cardiac ischemia, and operation times, and reduce the intraoperative FFP transfusion and postoperative hypoxemia times. This modified technique, therefore, is worth utilizing for patients with STAAD.


Assuntos
Dissecção Aórtica , Implante de Prótese Vascular , Humanos , Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Anastomose Cirúrgica , Bilirrubina , Isquemia/cirurgia , Estudos Retrospectivos , Stents , Resultado do Tratamento
15.
World J Surg Oncol ; 21(1): 380, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38082330

RESUMO

BACKGROUND: Prolonged postoperative ileus (PPOI) is a common complication after colorectal surgery that increases patient discomfort, hospital stay, and financial burden. However, predictive tools to assess the risk of PPOI in patients undergoing laparoscopic low anterior resection have not been developed. Thus, the purpose of this study was to develop a nomogram to predict PPOI after laparoscopic low anterior resection for rectal cancer. METHODS: A total of 548 consecutive patients who underwent laparoscopic low anterior resection for mid-low rectal cancer at a single tertiary medical center were retrospectively enrolled between January 2019 and January 2023. Univariate and multivariate logistic regression analysis was performed to analyze potential predictors of PPOI. The nomogram was constructed using the filtered variables and internally verified by bootstrap resampling. Model performance was evaluated by receiver operating characteristic curve and calibration curve, and the clinical usefulness was evaluated by the decision curve. RESULTS: Among 548 consecutive patients, 72 patients (13.1%) presented with PPOI. Multivariate logistic analysis showed that advantage age, hypoalbuminemia, high surgical difficulty, and postoperative use of opioid analgesic were independent prognostic factors for PPOI. These variables were used to construct the nomogram model to predict PPOI. Internal validation, conducted through bootstrap resampling, confirmed the great discrimination of the nomogram with an area under the curve of 0.738 (95%CI 0.736-0.741). CONCLUSIONS: We created a novel nomogram for predicting PPOI after laparoscopic low anterior resection. This nomogram can assist surgeons in identifying patients at a heightened risk of PPOI.


Assuntos
Íleus , Laparoscopia , Neoplasias Retais , Humanos , Nomogramas , Estudos Retrospectivos , Fatores de Risco , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Laparoscopia/efeitos adversos , Neoplasias Retais/cirurgia , Neoplasias Retais/complicações , Íleus/diagnóstico , Íleus/epidemiologia , Íleus/etiologia
16.
Nat Commun ; 14(1): 7913, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036543

RESUMO

Recent large language models (LLMs), such as ChatGPT, have demonstrated remarkable prediction performance for a growing array of tasks. However, their proliferation into high-stakes domains and compute-limited settings has created a burgeoning need for interpretability and efficiency. We address this need by proposing Aug-imodels, a framework for leveraging the knowledge learned by LLMs to build extremely efficient and interpretable prediction models. Aug-imodels use LLMs during fitting but not during inference, allowing complete transparency and often a speed/memory improvement of greater than 1000x for inference compared to LLMs. We explore two instantiations of Aug-imodels in natural-language processing: Aug-Linear, which augments a linear model with decoupled embeddings from an LLM and Aug-Tree, which augments a decision tree with LLM feature expansions. Across a variety of text-classification datasets, both outperform their non-augmented, interpretable counterparts. Aug-Linear can even outperform much larger models, e.g. a 6-billion parameter GPT-J model, despite having 10,000x fewer parameters and being fully transparent. We further explore Aug-imodels in a natural-language fMRI study, where they generate interesting interpretations from scientific data.


Assuntos
Conhecimento , Aprendizagem , Idioma , Modelos Lineares , Processamento de Linguagem Natural
17.
Ecotoxicol Environ Saf ; 266: 115608, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37856981

RESUMO

The saline, alkaline environment of arid soils is conducive to the diffusion of the metalloid arsenic (As). Desert plants in this area are of great ecological importance and practical value. However, there are few studies on the mechanism of arsenic action in desert plants. Therefore, in this study, Eremostachys moluccelloides Bunge was treated with different concentrations of As2O5 [As(V)] to analyze the physiological, biochemical, and transcriptomic changes of its roots and leaves and to explore the molecular mechanism of its response to As(Ⅴ) stress. The activities of catalase, superoxidase, peroxidase, and the contents of malondialdehyde and proline in roots and leaves first increased and then decreased under the As(Ⅴ) stress of different concentrations. The content of As was higher in roots than in leaves, and the As content was positively correlated with As(Ⅴ) stress concentration. In the differentially expressed gene analysis, the key enzymes of the oxidative stress response in roots and leaves were significantly enriched in the GO classification. In the KEGG pathway, genes related to the abscisic acid signal transduction pathway were co-enriched and up-regulated in roots and leaves. The related genes in the phenylpropanoid biosynthesis pathway were significantly enriched and down-regulated only in roots. In addition, the transcription factors NAC, HB-HD-ZIP, and NF-Y were up-regulated in roots and leaves. These results suggest that the higher the As(V) stress concentration, the more As is taken up by roots and leaves of E. molucelloides Bunge. In addition to causing greater oxidative damage, this may interfere with the production of secondary metabolites. Moreover, it may improve As(V) tolerance by regulating abscisic acid and transcription factors. The results will deepen our understanding of the molecular mechanism of As(Ⅴ) response in E. moluccelloides Bunge, lay the foundation for developing and applying desert plants, and provide new ideas for the phytoremediation of As pollution in arid areas.


Assuntos
Arsênio , Transcriptoma , Arsênio/análise , Ácido Abscísico/metabolismo , Perfilação da Expressão Gênica , Folhas de Planta/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
18.
Zhen Ci Yan Jiu ; 48(9): 890-7, 2023 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-37730259

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture(EA) stimulation on proliferation and diffe-rentiation of endogenous neural stem cells as well as Jagged1/Notch1 pathway in AD model mice, so as to explore its mechanism underlying amelioration of AD. METHODS: A total of 40 6-week-old male APP/PS1 transgenic AD mice were randomly divided into EA group (n=20) and AD model group ( n=20), and other 20 normal C57BL/6J mice of the same age were used as the normal control group. The mice in the EA group received EA (10 Hz, 2 mA) at "Baihui"(GV20), "Fengfu"(GV16) and bilateral "Shenshu" (BL23) for 20 min, once daily, 6 days a week for 16 weeks. The mice's learning-memory ability was detected by Morris water maze tests. The Aß senile plaques in the hippocampal CA1 region were detected by Congo red staining, the immunofluorescence double label of BrdU, neuronal nuclear antigen (NeuN) and astrocyte specific protein GFAP in dentate gyrus of hippocampus was performed for detecting the proliferation and differentiation of the endogenous neural stem cells. The expression levels of Nestin (neuron specific protein) and GFAP were detected by Western blot, and those of Jagged1 and Notch1 mRNAs and proteins in the hippocampus were detected by real-time fluorescence quantifative PCR and Western blot. RESULTS: Compared with the normal control group, the escape latencies at 2nd, 3rd and 4th day, and Aß senile plaques were significantly increased (P<0.05, P<0.01), whereas the platform crossing times and time spent in the target quadrant, the expression levels of Jagged1 mRNA and Nestin protein were remarkably down-regulated (P<0.05) in the model group. Following EA intervention, the escape latencies at the 3rd and 4th day, Aß senile plaques, immunofluorescence density of BrdU/GFAP, and GFAP protein expression were pronouncedly decreased (P<0.05, P<0.01), while the platform crossing times, platform quadrant residence time, immunofluorescence density of BrdU/NeuN, expression levels of Jagged1 and Notch1 mRNAs and proteins and Nestin protein evidently increased (P<0.05, P<0.01), suggesting an enhancement of proliferation and diffe-rentiation of endogenous neural stem cells into neurons and a suppression of the proliferation and differentiation towards astrocytes in the hippocampus. CONCLUSION: EA at GV20, GV16 and BL23 can improve the learning-memory ability, promote the proliferation and differentiation of endogenous neural stem cells towards neurons and inhibit the proliferation and differentiation of endogenous neural stem cells towards astrocytes in the hippocampus, which may be achieved by regulating Jagged1/Notch1 pathway.


Assuntos
Eletroacupuntura , Células-Tronco Neurais , Masculino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Nestina , Bromodesoxiuridina , Placa Amiloide , Hipocampo , Diferenciação Celular/genética , Camundongos Transgênicos , Proliferação de Células
19.
Int Wound J ; 2023 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-37740672

RESUMO

We examined whether small incision aortic root replacement could reduce the amount of blood transfusion during operation and the risk of postoperative complications. An extensive e-review of the 4 main databases (PubMed, Cochrane, Web of Science and EMBASE) was carried out to determine all the published trials by July 2023. The search terms used were associated with partial versus full sternotomy and aortic root. This analysis only included the study articles that compared partial and full sternotomy. After excluding articles based on titles or abstracts, selected full-text articles had reference lists searched for any potential further articles. We analysed a total of 2167 subjects from 10 comparable trials. The minimally invasive aortic root graft in breastbone decreased the duration of hospitalization (MD, -2.58; 95% CI, -3.15, -2.01, p < 0.0001) and intraoperative red blood cell transfusion (MD, -1.27; 95% CI, -2.34, -0.19, p = 0.02). However, there were no significant differences in wound infection (OR, 0.88; 95% CI, 0.16, 4.93, p = 0.88), re-exploration for bleeding (OR, 0.96; 95% CI, 0.60, 1.53, p = 0.86), intraoperative blood loss (MD, -259.19; 95% CI, -615.11, 96.73, p = 0.15) and operative time (MD, -7.39; 95% CI, -19.10, 4.32, p = 0.22); the results showed that the microsternotomy did not differ significantly from that of the routine approach. Small sternotomy may be an effective and safe substitute for the treatment of the aorta root. Nevertheless, the wide variety of data indicates that larger, well-designed studies are required to back up the current limited literature evidence showing a benefit in terms of complications like postoperative wound infections or the volume of intraoperative red blood cell transfusion.

20.
Polymers (Basel) ; 15(18)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37765636

RESUMO

The rapid and effective fabrication of polyvinyl alcohol (PVA) hydrogels with good mechanical properties is of great significance yet remains a huge challenge. The preparation of PVA hydrogels via the conventional cyclic freeze-thaw method is intricate and time-intensive. In this study, a pioneering approach involving the utilization of low-temperature continuous freezing is introduced to produce a novel PVA-ethylene glycol (EG) gel. Fourier transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD) and scanning electron microscopy (SEM) confirm that with the assistance of EG, PVA molecular chains can self-assemble to generate an abundance of microcrystalline domains at low temperatures, thus improving the mechanical properties of PVA-EG gel. Remarkably, when the mass ratio of H2O/EG is 4:6, the gel's maximum tensile strength can reach 2.5 MPa, which is much higher than that of PVA gels prepared via the freeze-thaw method. The preparation process of PVA-EG gel is simple, and its properties are excellent, which will promote the wide application of PVA tough gel in many fields.

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