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1.
World J Surg Oncol ; 21(1): 281, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37674223

RESUMO

BACKGROUND: The recommended operation for cecum cancer (CC) is right hemicolectomy (RH) in some Western countries while the principle of D3 lymphadenectomy in Japan recommends resecting approximately 10 cm from the tumor edge. Therefore, the optimal surgical approach for cecum cancer (CC) remains controversial. We conducted this retrospective study to explore the pattern of lymph node metastasis and better surgical procedures for CC. METHODS: A total of 224 cecum cancer patients from January 1, 2014, to December 31, 2021, were retrospectively included in the final study. The pattern of lymph node metastasis (LNM) was investigated. RESULTS: A total of 113 (50.4%, 113/224) patients had pathologically confirmed LNM. The most frequent metastatic site was no. 201 lymph node (46%, 103/224), while 20 (8.9%, 20/224) patients had LNM in no. 202 lymph node, and 8 (3.6%, 8/224) patients had LNM in no. 203 lymph node. Only 1 (0.4%, 1/224) patient had LNM in no. 221 lymph node, four (1.8, 4/224%) patients had LNM in no. 223 lymph node, and no patients had LNM in no. 222 lymph node. LNM in no. 223 lymph node was significantly associated with a poor prognosis. Multivariate analysis indicated that LNM in no. 223 lymph node (HR = 4.59, 95% CI 1.18-17.86, P = 0.028) was the only independent risk factor associated with worse disease-free survival (DFS). CONCLUSIONS: The LNM in no. 223 lymph node for cecum cancer was rare. Therefore, standard right hemicolectomy excision is too extensive for most CC cases.


Assuntos
Neoplasias do Ceco , Humanos , Estudos Retrospectivos , Metástase Linfática , Neoplasias do Ceco/cirurgia , Prognóstico , Colectomia
2.
BMC Gastroenterol ; 22(1): 123, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35296259

RESUMO

BACKGROUND: Intraoperative near-infrared fluorescence (NIR) imaging with indocyanine green (ICG) can demonstrate real-time lymphatic drainage and thus improve the accuracy and completeness of lymphadenectomy in colorectal cancer surgery. However, it has not been utilized in the inguinal lymphadenectomy in rectal cancer. This study aimed to describe a case of combined laparoscopic lymphadenectomy of left lateral pelvic and inguinal nodal metastases using NIR imaging with ICG imaging guidance for a rectal cancer patient with left lateral pelvic and inguinal lymph node metastases. CASE PRESENTATION: A 26-year-old man presented rectal cancer located 7 cm from the anal verge and enlarged lymph nodes in the left inguinal area. Pretreatment workup revealed rectal cancer with left lateral pelvic and inguinal lymph node metastases. The patient received preoperative chemoradiotherapy (pCRT), including radiation (total dose of 50.4 Gy in 28 fractions) to the whole pelvis and bilateral inguinal regions together with eight cycles of FOLFOX (oxaliplatin, fluoropyrimidine, and leucovorin) and three cycles of bevacizumab targeted chemotherapy. After pCRT, both colonoscopy and MR scan revealed a significant response of the primary tumor to pCRT, while MR scan revealed enlarged left lateral pelvic and inguinal lymph nodes. After four months from the completion of radiation (2 months after the last course of bevacizumab targeted therapy), the patient underwent laparoscopic-assisted ultra-low anterior resection and lymphadenectomy of left lateral pelvic and inguinal nodal metastases using ICG-NIR fluorescence imaging. The combined procedure was performed successfully without perioperative complication. Total operative time was 480 min and estimated blood loss 50 mL. Totally 34 lymph nodes were retrieved. CONCLUSIONS: This is the first report of the safety and feasibility of ICG-NIR fluorescence imaging-guided laparoscopic lymphadenectomy of left lateral pelvic and inguinal nodal metastases in managing low rectal cancer with lateral pelvic and inguinal LNs metastases.


Assuntos
Laparoscopia , Neoplasias Retais , Adulto , Quimiorradioterapia , Humanos , Verde de Indocianina , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Masculino , Imagem Óptica/métodos , Pelve/patologia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/cirurgia
3.
J Clin Nurs ; 31(5-6): 770-780, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34396613

RESUMO

AIMS AND OBJECTIVES: To describe the current situation and analyse influencing factors of resource utilisation in maintenance haemodialysis patients. BACKGROUND: The self-management level of patients undergoing maintenance haemodialysis in China is low. The applicability of the Chronic Illness Resources Survey in Chinese maintenance haemodialysis patients has been validated, and this survey can be used to assess the utilisation of self-management support resources among haemodialysis patients. Determining the influencing factors of resource utilisation can help improve the self-management behaviour of haemodialysis patients and control the progression of the disease. DESIGN: A descriptive study design was chosen. METHODS: A convenience sample of 314 patients undergoing haemodialysis was recruited from dialysis centres in three hospitals in western Xinjiang from June 2018-April 2019. SPSS19.0 software was used to describe the current situation of resource utilisation. Moreover, t test, analysis of variance and multivariate linear regression were applied to explore the influencing factors of patients' resource utilisation. Standards for observational studies STROBE Statement checklist-v4 were chosen on reporting the study process. RESULTS: The average score of the total resource utilisation was 2.95 ± 0.51. The average item score of seven dimensions from high to low was 3.46 for medical staff, 3.32 for personal, 3.22 for family and friends, 3.16 for work-related, 3.12 for media policy, 2.55 for neighbourhood/community and 2.23 for organisation. Multiple linear regression showed that there have six main factors, which explained 65.4% of the variance of haemodialysis patients' resource utilisation. CONCLUSIONS: The personal, family and friends, work and media and policy subscales were rated the highest, with support from neighbourhood/community and organisation rated the lowest. In general, participants perceived moderate levels of support. Government and healthcare team should pay more attention on haemodialysis patients who had low level of education, poor economic conditions and poor mental condition. RELEVANCE TO CLINICAL PRACTICE: ESRD has caused a burden on healthcare expenditure and has become a critical public health problem worldwide. Self-management is particularly important for dialysis patients which have attracted extensive interest. In the future research, we can use this questionnaire to evaluate the related resources of disease management of dialysis patients, encourage patients to make full use of the resources around them and focus on those patients with low education and monthly income level and bad mental state.


Assuntos
Diálise Renal , China , Doença Crônica , Humanos , Inquéritos e Questionários
4.
Pflugers Arch ; 473(7): 1087-1097, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33686477

RESUMO

Heart diseases are prevalent worldwide and account for the highest mortality than any other illness. Although investment in drug discovery and development has increased, the amount of drug approvals has seen a progressive decline. Moreover, adverse side effects to the heart have become the most common reasons for preclinical project cessation, partly due to the lack of suitable humanized preclinical models. Human pluripotent stem cells (hPSCs) have emerged as a powerful non-animal platform to model heart disease, to screen for novel drugs, and to test drug cardiotoxicity in a high-throughput and cost-effective manner. Here, we review and discuss recent breakthroughs in the development of cardiovascular modeling and their current and future applications of hPSC-based drug discovery and testing.


Assuntos
Doenças Cardiovasculares/patologia , Células-Tronco Pluripotentes/fisiologia , Animais , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Miócitos Cardíacos/fisiologia
5.
J Clin Lab Anal ; 33(6): e22903, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31102307

RESUMO

BACKGROUND: Interleukin-1 promotes tumor angiogenesis through VEGF production. The interleukin-1 receptor antagonist can suppress tumors by blocking this effect. METHODS: Immunohistochemistry, WB, and gene sequencing were used to analyze the expression of IL-1RA in esophageal cancer patients. WB was used to detect the expression of IL-1RA and interleukin-1α in esophageal cancer cells. Stable ESCC cell models overexpressing the IL-1RA were constructed. Their cell functions were tested, and their effects on VEGF were examined. RESULTS: IL-1RA is downregulated in primary EC tumors, and this downregulation of IL-1RA is closely related to TNM staging and survival prognosis. The overexpression of IL-1RA increased the proliferation of KYSE410 EC cells, which have a high level of IL-1α expression. Overexpression of IL-1RA in KYSE410 cells promotes a decrease in the expression of VEGF-A. However, IL-1RA expression did not cause any changes in EC9706 cells with low IL-1α expression. CONCLUSION: IL-1RA acts as a tumor suppressor, and its deletion promotes tumor progression by increasing VEGF-A expression in ESCC.


Assuntos
Neoplasias Esofágicas/patologia , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1alfa/metabolismo , Idoso , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidade , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1alfa/genética , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Antimicrob Agents Chemother ; 60(6): 3813-6, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26976874

RESUMO

In vitro interactions of INK128, a target of rapamycin (TOR) kinase inhibitor, and antifungals, including itraconazole, voriconazole, posaconazole, amphotericin B, and caspofungin, against Aspergillus spp. were assessed with the broth microdilution checkerboard technique. Our results suggested synergistic effects between INK128 and all azoles tested, against multiple Aspergillus fumigatus and Aspergillus flavus isolates. However, no synergistic effects were observed when INK128 was combined with amphotericin B or caspofungin. No antagonism was observed for any combination.


Assuntos
Antifúngicos/farmacologia , Aspergillus flavus/efeitos dos fármacos , Aspergillus fumigatus/efeitos dos fármacos , Benzoxazóis/farmacologia , Itraconazol/farmacologia , Pirimidinas/farmacologia , Triazóis/farmacologia , Voriconazol/farmacologia , Anfotericina B/farmacologia , Aspergillus flavus/genética , Aspergillus flavus/crescimento & desenvolvimento , Aspergillus flavus/metabolismo , Aspergillus fumigatus/genética , Aspergillus fumigatus/crescimento & desenvolvimento , Aspergillus fumigatus/metabolismo , Caspofungina , Combinação de Medicamentos , Sinergismo Farmacológico , Equinocandinas/farmacologia , Proteínas Fúngicas/antagonistas & inibidores , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Expressão Gênica , Lipopeptídeos/farmacologia , Testes de Sensibilidade Microbiana , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
7.
Phys Chem Chem Phys ; 18(2): 974-81, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26661743

RESUMO

Hybridized two-dimensional materials incorporating domains from the hexagonal boron nitride (h-BN) and graphene is an interesting branch of materials science due to their highly tunable electronic properties. In the present study, we investigate the hydrogenated two-dimensional (2D) h-BN/C superlattices (SLs) with zigzag edges using first-principles calculations. We found that the domain width, the phase ratio, and the vertical dipole orientation all have significant influence on the stability of SLs. The electronic reconstruction is associated with the lateral polar discontinuities at the zigzag edges and the vertically polarized (B2N2H4)(m) domains, which modifies the electronic structures and the spatial potential of the SLs significantly. Furthermore, we demonstrate that the hydrogenated 2D h-BN/C SLs can be applied in engineering the electronic structure of graphene: laterally-varying doping can be achieved by taking advantage of the spatial variation of the surface potential of the SLs. By applying an external vertical electric field on these novel bidirectional heterostructures, graphene doping levels and band offsets can be tuned to a wide range, such that the graphene doping profile can be switched from the bipolar (p-n junction) to unipolar (n(+)-n junction) mode. It is expected that such bidirectional heterostructures provide an effective approach for developing novel nanoscale electronic devices and improving our understanding of the fundamentals of low-dimensional materials.

8.
Phys Chem Chem Phys ; 18(42): 29239-29248, 2016 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-27731436

RESUMO

Elucidation of homoepitaxial growth mechanisms on vicinal non-polar surfaces of GaN is highly important for gaining an understanding of and control thin film surface morphology and properties. Using first-principles calculations, we study the step-flow growth in m-plane GaN based on atomic row nucleation and kink propagation kinetics. Ga-N dimer adsorption onto the m-plane is energetically more favorable than that of Ga and N isolated adatoms. Therefore, we have treated the dimers as the dominant growth species attached to the step edges. By calculating the free energies of sequentially attached Ga-N dimers, we have elucidated that the a-step edge kink growth proceeds by parallel attachment rather than by across the step edge approach. We found a series of favorable configurations of kink propagation and calculated the free energy and nucleation barriers for kink evolution on five types of step edges (a, +c, -c, +a + c, and -a - c). By changing the chemical potential µGa and the excess chemical potential Δµ, the growth velocities at the five types of edges are controlled by the corresponding kink pair nucleation barrier E* in their free energy profiles. To explore the kink-flow growth instability observed at different Ga/N flux ratios, calculations of kink pairs on the incompact -c and +c-step edges are further performed to study their formation energies. Variations of these step edge morphologies with a tuned chemical environment are consistent with previous experimental observations, including stable diagonal ±a ± c-direction steps. Our work provides a first-principles approach to explore step growth and surface morphology of the vicinal m-plane GaN, which is applicable to analyze and control the step-flow growth of other binary thin films.

9.
Phys Chem Chem Phys ; 17(17): 11692-9, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25866036

RESUMO

Using first-principles calculations, we examined the bipolar doping of double-layer graphene vertical heterostructures, which are constructed by hydrogenated boron nitride (BN) sheets sandwiched into two parallel graphene monolayers. The built-in potential difference in hydrogenated BN breaks the interlayer symmetry, resulting in the p- and n-type doping of two graphene layers at 0.83 and -0.8 eV, respectively. By tuning the interlayer spacing between the graphene and hydrogenated BN, the interfacial dipole and screening charge distribution can be significantly affected, which produces large modulations in band alignments, doping levels and tunnel barriers. Furthermore, we present an analytical model to predicate the doping level as a function of the average interlayer spacing. With large interlayer spacings, the "pillow effect" (Pauli repulsion at the highly charge overlapped interface) is diminished and the calculated Dirac point shifts are in good accordance with our prediction models. Our investigations suggest that this double-layer graphene heterostructures constructed using two-dimensional Janus anisotropic materials offer exciting opportunities for developing novel nanoscale optoelectronic and electronic devices.


Assuntos
Compostos de Boro/química , Grafite/química , Hidrogenação , Estrutura Molecular , Teoria Quântica
10.
Vet Anim Sci ; 25: 100332, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38975272

RESUMO

Currently, there are plenty of histochemical methods to classify pig muscle fibers, which confused the naming and classification of muscle fibers. This study aims to analyze the difference and correlation of 6 different histochemical methods and select the most suitable method for muscle fiber classification at the molecular and histomological levels by in-situ RT-PCR and enzyme histochemical methods. Muscle fiber samples, including psoas (PM), semitendinosus (SM) and trapezius muscle (TM), were collected from Large Spotted (LS), Lantang (LT) and Landrace (LR) pigs at their market-ages (LS at 150 d, LT at 210 d, and LR at 150 d). 6 kinds of histochemical methods combining actomyosin adenosine triphosphatase (AM-ATPase) with succinate dehydrogenase (SDH) enzyme were conducted to differentiate fiber types. 2 types of fibers (I and II) were differentiated by acid 2-fibre (2-AC) or alkaline 2-fibre classification(2-AL), 3 types of fibers (ßR, αR and αW) by 3-AC or 3-AL, and 4 types of fibers (I, IIa, IIx and IIb) by 4-AC, or 4-AL. Results showed that AC and AL muscle-fiber classification were consistent in reflecting the characteristics of muscle fibers(P > 0.05), but the color of each muscle fiber type was just opposite. AC methods may be superior to AL methods because of their clear staining background, the sensitivity to staining condition. But there were breed differences and tissue specificity in the optimal preincubation condition. The optimal acid preincubation condition for classifying muscle fibers was pH4.30 for LT, while pH 4.35 for the LS and LR pigs. Meanwhile the optimal acid preincubation condition was pH4.35 for PM, while pH4.40 for TM or SM. For further selection from 2, 3, 4-AC, in-situ RT-PCR was applied to detect the mRNA distribution of myosin heavy chain I (MyHC-I). By combining in-situ PCR with enzyme histochemistry methods, MyHC-I gene and its product - Type I fibrocytes were directly located in cells at both molecular level and morphological level. Compared with the cross-sectional area (CSA) of different muscle fibers (i.e. I, II, ßR, αR, αW, IIa, IIx and IIb) identified by enzyme histochemistry, it was found that the CSAs with stronger mRNA expression signal of MyHC-Ⅰ were closer to those of the Type I muscle fiber measured by 4-AC enzyme histochemistry (P > 0.05). Therefore, 4-AC may be considered as the most proper muscle typing method to study muscle fiber typing as well as meat quality. And the combination of in-situ RT-PCR and histochemistry may help better understand porcine muscle fiber characteristics and meat quality in pigs.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38736427

RESUMO

BACKGROUND: The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. METHODS: Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. RESULTS: Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P<0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P<0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P<0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. CONCLUSIONS: Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.

12.
Gastroenterol Rep (Oxf) ; 12: goae012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510669

RESUMO

Background: Radiation-induced colorectal fibrosis (RICF) is a common pathological alteration among patients with rectal cancer undergoing neoadjuvant chemoradiotherapy (nCRT). Anastomotic stenosis (AS) causes symptoms and negatively impacts patients' quality of life and long-term survival. In this study, we aimed to evaluate the fibrosis signature of RICF and develop a nomogram to predict the risk of AS in patients with rectal cancer undergoing nCRT. Methods: Overall, 335 pairs of proximal and distal margins were collected and randomly assigned at a 7:3 ratio to the training and testing cohorts. The RICF score was established to evaluate the fibrosis signature in the anastomotic margins. A nomogram based on the RICF score for AS was developed and evaluated by using the area under the curve, decision curve analysis, and the DeLong test. Results: The training cohort included 235 patients (161 males [68.51%]; mean age, 59.61 years) with an occurrence rate of AS of 17.4%, whereas the testing cohort included 100 patients (72 males [72.00%]; mean age, 57.17 years) with an occurrence rate of AS of 11%. The RICF total score of proximal and distal margins was significantly associated with AS (odds ratio, 3.064; 95% confidence interval [CI], 2.200-4.268; P < 0.001). Multivariable analysis revealed that the RICF total score, neoadjuvant radiotherapy, and surgical approach were independent predictors for AS. The nomogram demonstrated good discrimination in the training cohort (area under the receiver-operating characteristic curve, 0.876; 95% CI, 0.816-0.937), with a sensitivity of 68.3% (95% CI, 51.9%-81.9%) and a specificity of 85.5% (95% CI, 78.7%-89.3%). Similar results were observed in the testing cohort. Conclusions: This study results suggest that the RICF total score of anastomotic margins is an independent predictor for AS. The prediction model developed based on the RICF total score may be useful for individualized AS risk prediction in patients with rectal cancer undergoing nCRT and sphincter-preserving surgery.

13.
Cell Death Dis ; 15(1): 75, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38242872

RESUMO

The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy.


Assuntos
Rejeição de Enxerto , Fatores de Transcrição NFATC , Neutrófilos , Ratos , Animais , Trogocitose , Macrófagos
14.
IEEE Trans Cybern ; 53(2): 718-731, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34936566

RESUMO

In pattern classification, there may not exist labeled patterns in the target domain to train a classifier. Domain adaptation (DA) techniques can transfer the knowledge from the source domain with massive labeled patterns to the target domain for learning a classification model. In practice, some objects in the target domain are easily classified by this classification model, and these objects usually can provide more or less useful information for classifying the other objects in the target domain. So a new method called distribution adaptation based on evidence theory (DAET) is proposed to improve the classification accuracy by combining the complementary information derived from both the source and target domains. In DAET, the objects that are easy to classify are first selected as easy-target objects, and the other objects are regarded as hard-target objects. For each hard-target object, we can obtain one classification result with the assistance of massive labeled patterns in the source domain, and another classification result can be acquired based on the easy-target objects with confidently predicted (pseudo) labels. However, the weights of these classification results may vary because the reliabilities of the used information sources are different. The weights are estimated by mean difference reflecting the information source quality. Then, we discount the classification results with the corresponding weights under the framework of the evidence theory, which is expert at dealing with uncertain information. These discounted classification results are combined by an evidential combination rule for making the final class decision. The effectiveness of DAET for cross-domain pattern classification is evaluated with respect to some advanced DA methods, and the experiment results show DAET can significantly improve the classification accuracy.

15.
IEEE Trans Pattern Anal Mach Intell ; 45(7): 8757-8772, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37015492

RESUMO

Open set recognition (OSR) aims to correctly recognize the known classes and reject the unknown classes for increasing the reliability of the recognition system. The distance-based loss is often employed in deep neural networks-based OSR methods to constrain the latent representation of known classes. However, the optimization is usually conducted using the nondirectional euclidean distance in a single feature space without considering the potential impact of spatial distribution. To address this problem, we propose orientational distribution learning (ODL) with hierarchical spatial attention for OSR. In ODL, the spatial distribution of feature representation is optimized orientationally to increase the discriminability of decision boundaries for open set recognition. Then, a hierarchical spatial attention mechanism is proposed to assist ODL to capture the global distribution dependencies in the feature space based on spatial relationships. Moreover, a composite feature space is constructed to integrate the features from different layers and different mapping approaches, and it can well enrich the representation information. Finally, a decision-level fusion method is developed to combine the composite feature space and the naive feature space for producing a more comprehensive classification result. The effectiveness of ODL has been demonstrated on various benchmark datasets, and ODL achieves state-of-the-art performance.

16.
Epigenetics Chromatin ; 16(1): 32, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37568210

RESUMO

BACKGROUND: Cardiomyocyte growth and differentiation rely on precise gene expression regulation, with epigenetic modifications emerging as key players in this intricate process. Among these modifications, N6-methyladenosine (m6A) stands out as one of the most prevalent modifications on mRNA, exerting influence over mRNA metabolism and gene expression. However, the specific function of m6A in cardiomyocyte differentiation remains poorly understood. RESULTS: We investigated the relationship between m6A modification and cardiomyocyte differentiation by conducting a comprehensive profiling of m6A dynamics during the transition from pluripotent stem cells to cardiomyocytes. Our findings reveal that while the overall m6A modification level remains relatively stable, the m6A levels of individual genes undergo significant changes throughout cardiomyocyte differentiation. We discovered the correlation between alterations in chromatin accessibility and the binding capabilities of m6A writers, erasers, and readers. The changes in chromatin accessibility influence the recruitment and activity of m6A regulatory proteins, thereby impacting the levels of m6A modification on specific mRNA transcripts. CONCLUSION: Our data demonstrate that the coordinated dynamics of m6A modification and chromatin accessibility are prominent during the cardiomyocyte differentiation.


Assuntos
Cromatina , Miócitos Cardíacos , Miócitos Cardíacos/metabolismo , Diferenciação Celular , Regulação da Expressão Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
17.
Adv Sci (Weinh) ; 10(35): e2303799, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37890465

RESUMO

Cardiac development involves large-scale rearrangements of the proteome. How the developing cardiac cells maintain the integrity of the proteome during the rapid lineage transition remains unclear. Here it is shown that proteotoxic stress visualized by the misfolded and/or aggregated proteins appears during early cardiac differentiation of human pluripotent stem cells and is resolved by activation of the PERK branch of unfolded protein response (UPR). PERK depletion increases misfolded and/or aggregated protein accumulation, leading to pluripotency exit defect and impaired mesendoderm specification of human pluripotent stem cells. Mechanistically, it is found that PERK safeguards mesendoderm specification through its conserved downstream effector ATF4, which subsequently activates a novel transcriptional target WARS1, to cope with the differentiation-induced proteotoxic stress. The results indicate that protein quality control represents a previously unrecognized core component of the cardiogenic regulatory network. Broadly, these findings provide a framework for understanding how UPR is integrated into the developmental program by activating the PERK-ATF4-WARS1 axis.


Assuntos
Células-Tronco Pluripotentes , eIF-2 Quinase , Humanos , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo , Células-Tronco Pluripotentes/metabolismo , Proteoma/metabolismo , Proteostase , Resposta a Proteínas não Dobradas
18.
ACS Nano ; 17(6): 5421-5434, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36929948

RESUMO

Upon myocardial infarction (MI), activated cardiac fibroblasts (CFs) begin to remodel the myocardium, leading to cardiac fibrosis and even heart failure. No therapeutic approaches are currently available to prevent the development of MI-induced pathological fibrosis. Most pharmacological trials fail from poor local drug activity and side effects caused by systemic toxicity, largely due to the lack of a heart-targeted drug delivery system that is selective for activated CFs. Here, we developed a reduced glutathione (GSH)-responsive nanoparticle platform capable of targeted delivering of drugs to activated CFs within the infarct area of a post-MI heart. Compared with systemic drug administration, CF-targeted delivery of PF543, a sphingosine kinase 1 inhibitor identified in a high-throughput antifibrotic drug screening, had higher therapeutic efficacy and lower systemic toxicity in a MI mouse model. Our results provide a CF-targeted strategy to deliver therapeutic agents for pharmacological intervention of cardiac fibrosis.


Assuntos
Cisteína , Infarto do Miocárdio , Camundongos , Animais , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Miocárdio/patologia , Fibrose , Fibroblastos , Modelos Animais de Doenças
19.
Langmuir ; 28(25): 9244-9, 2012 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-22647237

RESUMO

Synthesis of silver nanoplates was studied in the modified polyol method, where the nucleation and seed stage occurred in a poly(ethylene glycol) (PEG)-water mixture solution, and the growth stage happened in the PEG environment. The morphological evolution of nanoplates was characterized using UV, SEM, and TEM. Interestingly, plane nanostructures with unusual jagged edges were finally formed in our modified polyol method. Using TEM, we observed the medium state of fusion between two nanoplates, resulting in generating unusual jagged edges. Therefore, a novel two-dimensional oriented attachment occurred in our modified polyol method, which involves smaller nanoplates as the building blocks. Further control experiments showed that the presence of water could break this kinetic preferred reactivity, leading to the formation of nanoparticles.

20.
Environ Sci Technol ; 46(11): 6127-33, 2012 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-22568856

RESUMO

Gravimetric analysis is the regulatory method for diesel particulate mass measurement. Because of issues such as adsorption/volatilization artifacts, it faces obstacles in measuring ultra low level emissions from modern diesel engines. Alternative methods of suspended particle mass measurement have been developed that show improvements in time resolution, sensitivity, and accuracy. Three size-resolved methods were considered here. Two methods rely on converting number size distributions obtained using a scanning mobility particle sizer (SMPS). Conversion techniques were based on effective density measurements and the Lall-Friedlander aggregate model. The third method employs the Universal Nanoparticle Analyzer (UNPA) to measure the aggregate size distribution from which mass is calculated. Results were compared with mass concentrations obtained using gravimetric analysis. The effective density conversion resulted in mass concentrations that were highly correlated (R(2) >0.99) with filter mass. The ratios to filter mass concentration were found to be 0.99 ± 0.04, 0.45 ± 0.03, and 0.45 ± 0.19 for the effective density conversion, the Lall-Friedlander conversion, and the UNPA, respectively, for a wide range of engine operating conditions. In addition, the diesel aerosol mass distributions measured by the online techniques are in agreement to within 15-20% with respect to the mass median diameter, while discrepancies were observed in the mass concentration.


Assuntos
Monitoramento Ambiental/métodos , Gasolina/análise , Sistemas On-Line , Material Particulado/análise , Adsorção , Artefatos , Catálise , Filtração , Microscopia Eletrônica de Transmissão , Peso Molecular , Tamanho da Partícula , Fuligem/análise
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