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1.
Biomed Mater ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38574669

RESUMO

Recently, in vitro models of intestinal mucosa have become important tools for drug screening and studying the physiology and pathology of the intestine. These models enable the examination of cellular behavior in diseased states or in reaction to alterations in the microenvironment, potentially serving as alternatives to animal models. One of the major challenges in constructing physiologically relevant in vitro models of intestinal mucosa is the creation of three-dimensional (3D) microstructures that accurately mimic the integration of intestinal epithelium and vascularized stroma. Here, core-shell alginate (Alg) microspheres were generated to create the compartmentalized extracellular matrix (ECM) microenvironment needed to simulate the epithelial and vascularized stromal compartments of the intestinal mucosa. We demonstrated that NIH-3T3 and human umbilical vein endothelial cells (HUVECs) embedded in the core of the microspheres can proliferate and develop a vascular network, while human colorectal adenocarcinoma cells (Caco-2) can form an epithelial monolayer in the shell. Compared to Caco-2 monolayer encapsulated within the shell, the presence of the vascularized stroma enhances their proliferation and functionality. As such, our core-shell Alg microspheres provide a valuable method for generating in vitro models of vascularized intestinal mucosa with epithelial and vascularized stroma arranged in a spatially relevant manner and demonstrating near-physiological functionality.

2.
World J Gastroenterol ; 30(10): 1329-1345, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38596504

RESUMO

Postoperative pancreatic fistula (POPF) is a frequent complication after pancreatectomy, leading to increased morbidity and mortality. Optimizing prediction models for POPF has emerged as a critical focus in surgical research. Although over sixty models following pancreaticoduodenectomy, predominantly reliant on a variety of clinical, surgical, and radiological parameters, have been documented, their predictive accuracy remains suboptimal in external validation and across diverse populations. As models after distal pancreatectomy continue to be progressively reported, their external validation is eagerly anticipated. Conversely, POPF prediction after central pancreatectomy is in its nascent stage, warranting urgent need for further development and validation. The potential of machine learning and big data analytics offers promising prospects for enhancing the accuracy of prediction models by incorporating an extensive array of variables and optimizing algorithm performance. Moreover, there is potential for the development of personalized prediction models based on patient- or pancreas-specific factors and postoperative serum or drain fluid biomarkers to improve accuracy in identifying individuals at risk of POPF. In the future, prospective multicenter studies and the integration of novel imaging technologies, such as artificial intelligence-based radiomics, may further refine predictive models. Addressing these issues is anticipated to revolutionize risk stratification, clinical decision-making, and postoperative management in patients undergoing pancreatectomy.


Assuntos
Pancreatectomia , Fístula Pancreática , Humanos , Pancreatectomia/efeitos adversos , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiologia , Estudos Prospectivos , Inteligência Artificial , Fatores de Risco , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
3.
Comput Biol Chem ; 110: 108058, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38593480

RESUMO

Exploring the relationship between proteins and drugs plays a significant role in discovering new synthetic drugs. The Drug-Target Interaction (DTI) prediction is a fundamental task in the relationship between proteins and drugs. Unlike encoding proteins by amino acids, we use amino acid subsequence to encode proteins, which simulates the biological process of DTI better. For this research purpose, we proposed a novel deep learning framework based on Bidirectional Encoder Representation from Transformers (BERT), which integrates high-frequency subsequence embedding and transfer learning methods to complete the DTI prediction task. As the first key module, subsequence embedding allows to explore the functional interaction units from drug and protein sequences and then contribute to finding DTI modules. As the second key module, transfer learning promotes the model learn the common DTI features from protein and drug sequences in a large dataset. Overall, the BERT-based model can learn two kinds features through the multi-head self-attention mechanism: internal features of sequence and interaction features of both proteins and drugs, respectively. Compared with other methods, BERT-based methods enable more DTI-related features to be discovered by means of attention scores which associated with tokenized protein/drug subsequences. We conducted extensive experiments for the DTI prediction task on three different benchmark datasets. The experimental results show that the model achieves an average prediction metrics higher than most baseline methods. In order to verify the importance of transfer learning, we conducted an ablation study on datasets, and the results show the superiority of transfer learning. In addition, we test the scalability of the model on the dataset in unseen drugs and proteins, and the results of the experiments show that it is acceptable in scalability.

4.
Small ; : e2400661, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38597688

RESUMO

Renewable energy-driven conversion of CO2 to value-added fuels and chemicals via electrochemical CO2 reduction reaction (CO2RR) technology is regarded as a promising strategy with substantial environmental and economic benefits to achieve carbon neutrality. Because of its sluggish kinetics and complex reaction paths, developing robust catalytic materials with exceptional selectivity to the targeted products is one of the core issues, especially for extensively concerned Cu-based materials. Manipulating Cu species by anionic coordination is identified as an effective way to improve electrocatalytic performance, in terms of modulating active sites and regulating structural reconstruction. This review elaborates on recent discoveries and progress of Cu-based CO2RR catalytic materials enhanced by anionic coordination control, regarding reaction paths, functional mechanisms, and roles of different non-metallic anions in catalysis. Finally, the review concludes with some personal insights and provides challenges and perspectives on the utilization of this strategy to build desirable electrocatalysts.

5.
Comput Med Imaging Graph ; 115: 102379, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38608333

RESUMO

Deep learning (DL) has demonstrated its innate capacity to independently learn hierarchical features from complex and multi-dimensional data. A common understanding is that its performance scales up with the amount of training data. However, the data must also exhibit variety to enable improved learning. In medical imaging data, semantic redundancy, which is the presence of similar or repetitive information, can occur due to the presence of multiple images that have highly similar presentations for the disease of interest. Also, the common use of augmentation methods to generate variety in DL training could limit performance when indiscriminately applied to such data. We hypothesize that semantic redundancy would therefore tend to lower performance and limit generalizability to unseen data and question its impact on classifier performance even with large data. We propose an entropy-based sample scoring approach to identify and remove semantically redundant training data and demonstrate using the publicly available NIH chest X-ray dataset that the model trained on the resulting informative subset of training data significantly outperforms the model trained on the full training set, during both internal (recall: 0.7164 vs 0.6597, p<0.05) and external testing (recall: 0.3185 vs 0.2589, p<0.05). Our findings emphasize the importance of information-oriented training sample selection as opposed to the conventional practice of using all available training data.

6.
World J Gastrointest Oncol ; 16(3): 614-629, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38577449

RESUMO

Solid pseudopapillary tumor of the pancreas (SPTP) is a rare neoplasm predominantly observed in young females. Pathologically, CTNNB1 mutations, ß-catenin nuclear accumulation, and subsequent Wnt-signaling pathway activation are the leading molecular features. Accurate preoperative diagnosis often relies on imaging techniques and endoscopic biopsies. Surgical resection remains the mainstay treatment. Risk models, such as the Fudan Prognostic Index, show promise as predictive tools for assessing the prognosis of SPTP. Establishing three types of metachronous liver metastasis can be beneficial in tailoring individualized treatment and follow-up strategies. Despite advancements, challenges persist in understanding its etiology, establishing standardized treatments for unresectable or metastatic diseases, and developing a widely recognized grading system. This comprehensive review aims to elucidate the enigma by consolidating current knowledge on the epidemiology, clinical presentation, pathology, molecular characteristics, diagnostic methods, treatment options, and prognostic factors.

7.
Pestic Biochem Physiol ; 200: 105814, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582586

RESUMO

To explore active natural products against tobacco powdery mildew caused by Golovinomyces cichoracearum, an extract from the fermentation of endophytic Aspergillus fumigatus 0338 was investigated. The mechanisms of action for active compounds were also studied in detail. As a result, 14 indole alkaloid derivatives were isolated, with seven being newly discovered (1-7) and the remaining seven previously described (8-14). Notably, compounds 1-3 are rare linearly fused 6/6/5 tricyclic prenylated indole alkaloids, with asperversiamide J being the only known natural product of this kind. The isopentenyl substitutions at the 5-position in compounds 4 and 5 are also rare, with only compounds 1-(5-prenyl-1H-indol-3-yl)-propan-2-one (8) and 1-(6-methoxy-5-prenyl-1H-indol3-yl)-propan-2-one currently available. In addition, compounds 6 and 7 are new framework indole alkaloid derivatives bearing a 6-methyl-1,7-dihydro-2H-azepin-2-one ring. The purified compounds were evaluated for their activity against G. cichoracearum, and the results revealed that compounds 7 and 9 demonstrated obvious anti-G. cichoracearum activities with an inhibition rate of 82.6% and 85.2%, respectively, at a concentration of 250 µg/mL, these rates were better than that of the positive control agent, carbendazim (78.6%). The protective and curative effects of compounds 7 and 9 were also better than that of positive control, at the same concentration. Moreover, the mechanistic study showed that treatment with compound 9 significantly increased the structural tightness of tobacco leaves and directly affect the conidiospores of G. cichoracearum, thereby enhancing resistance. Compounds 7 and 9 could also induce systemic acquired resistance (SAR), directly regulating the expression of defense enzymes, defense genes, and plant semaphorins, which may further contribute to increased plant resistance. Based on the activity experiments and molecular dockings, the indole core structure may be the foundation of these compounds' anti-G. cichoracearum activity. Among them, the indole derivative parent structures of compounds 6, 7, and 9 exhibit strong effects. Moreover, the methoxy substitution in compound 7 can enhance their activity. By isolating and structurally identifying the above indole alkaloids, new candidates for anti-powdery mildew chemical screening were discovered, which could enhance the utilization of N. tabacum-derived fungi in pesticide development.


Assuntos
Alcaloides , Aspergillus fumigatus , Neopreno , Tabaco , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/química , Alcaloides/farmacologia
8.
MedComm (2020) ; 5(4): e528, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38606362

RESUMO

Lipid metabolic reprogramming is closely related to tumor progression with the mechanism not fully elucidated. Here, we report the immune-regulated role of lanosterol synthase (LSS), an essential enzyme in cholesterol synthesis. Database analysis and clinical sample experiments suggest that LSS was lowly expressed in colon and breast cancer tissues, which indicates poor prognosis. The biological activity of tumor cell lines and tumor progression in NOD scid gamma (NSG) mice were not affected after LSS knockdown, whereas LSS deficiency obviously aggravated tumor burden in fully immunized mice. Flow cytometry analysis showed that LSS knockdown significantly promoted the formation of tumor immunosuppressive microenvironment, characterized by the increase in M2 macrophages and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), as well as the decrease in anti-tumoral T lymphocytes. With the inhibition of myeloid infiltration or loss function of T lymphocytes, the propulsive effect of LSS knockdown on tumor progression disappeared. Mechanistically, LSS knockdown increased programmed death ligand 1 (PDL1) protein stability by 2,3-oxidosqualene (OS) binding to PDL1 protein. Anti-PDL1 therapy abolished LSS deficiency-induced immunosuppressive microenvironment and cancer progression. In conclusion, our results show that LSS deficiency promotes tumor progression by establishing an OS-PDL1 axis-dependent immunosuppressive microenvironment, indicative of LSS or OS as a potential hallmark of response to immune checkpoint blockade.

9.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1113-1121, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621918

RESUMO

This study systematically collected, analyzed, and evaluated randomized controlled trial(RCT) in the treatment of diabetic foot ulcer(DFU). The aim as provide references for future studies and to enhance the application of clinical evidence. The RCT of DFU treated with Chinese Patent Medicine was obtained and analyzed using the AI-Clinical Evidence Database of Chinese Patent Medicine(AICED-CPM). The analysis was supplemented with data from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science. A total of 275 RCTs meeting the requirements were retrieved, with only 7 of them having a sample size of 200 or more. These trials involved 66 different Chinese patent medicine including 25 oral medications, 24 Chinese herbal injections, and 17 external drugs. Among the 33 different intervention/control designs identified, the most common design was Chinese patent medicine + conventional treatment vs conventional treatment(86 cases, 31.27%). Out of the 275 articles included in the literature, 50 did not provide information on the specific course of treatment(18.18%). A total of 10 counting indicators(with a frequency of 426) and 36 measuring indicators(with a frequency of 962) were utilized. The methodological quality of the RCT for the treatment of DFU with Chinese patent medicine was found to be low, with deficiencies in blind methods, other bias factors, study registration, and sample size estimation. There were noticeable shortcomings in the reporting of allocation hiding and implementation bias(blind method application). More studies should prioritize trial registration, program design, and strict quality control during implementation to provide valuable data for clinical practice and serve as a reference for future investigations.


Assuntos
Diabetes Mellitus , Pé Diabético , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Diabetes Mellitus/tratamento farmacológico , Pé Diabético/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos sem Prescrição/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
PM R ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656703

RESUMO

OBJECTIVE: Navigating obstacles involves adjusting walking patterns, particularly when stepping over them. This task may be particularly challenging for people with Parkinson disease (PD) for several reasons. This review aims to compare the spatiotemporal gait parameters of people with and without PD while stepping over obstacles. LITERATURE SURVEY: A systematic literature search was conducted in six databases (PubMed, Scopus, Web of Science, EBSCO, Embase, and SciELO) from inception to September 2023. METHODOLOGY: Studies were selected that evaluated gait parameters of people with and without PD while walking over obstacles. Two independent researchers evaluated the eligibility and extracted gait parameters during obstacle crossing. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Heterogeneity was assessed using I2-tests. Random effects models were determined for effect sizes as standardized mean differences (SMD). SYNTHESIS: Twenty-five studies were included in the review and 17 in the meta-analysis. Most of the studies (58%) showed a low risk of bias. People with PD exhibit a shorter step when landing after crossing an obstacle (SMD = -0.50 [-0.69 to -0.31]). Compared to people without PD, people with PD also widen their support base (SMD = 0.27 [0.07-0.47]) and reduce gait velocity (SMD = -0.60 [-0.80 to -0.39]) when crossing the obstacle. CONCLUSIONS: People with PD adopt a more conservative motor behavior during obstacle crossing than those without PD, with a shorter step length when landing after crossing an obstacle, greater step width and lower crossing speed.

11.
J Org Chem ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651598

RESUMO

Polycyclic energetic materials make up a distinctive class of conjugated structures that consist of two or more rings. In this work, 1,3-bis(3,5-dinitro-1H-pyrazol-4-yl)-4,6-dinitrobenzene (BDPD) was synthesized and investigated in detail as a polycyclic heat-resistant energetic molecule that can be deprotonated by bases to obtain its anionic (3-5) salts. All compounds were thoroughly characterized by 1H and 13C NMR, infrared spectroscopy, high-resolution mass spectrometry, and elemental analysis. The structural features of BDPD and its salts were investigated by single-crystal X-ray diffraction and analyzed by different kinds of computing software, like Multiwfn, Gaussian 09W, and so on. In addition, their thermal decomposition temperatures were evaluated by differential scanning calorimetry to be 319.8-329.0 °C, revealing that they possessed high thermal stabilities. The results of impact sensitivity and friction sensitivity analysis confirm that these energetic compounds were insensitive. The detonation properties of neutral compound BDPD and all its nonmetallic salts were calculated by the EXPLO5 v6.05.04 program. The results revealed that their detonation performances were higher than those of the widely used heat-resistant explosive 2,2',4,4',6,6'-hexanitrostilbene (HNS). Combining the above results, it is reasonable to suggest that these compounds have the potential to be heat-resistant energetic materials.

12.
Biol Direct ; 19(1): 29, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654312

RESUMO

BACKGROUND: Oocyte quality is critical for the mammalian reproduction due to its necessity on fertilization and early development. During aging, the declined oocytes showing with organelle dysfunction and oxidative stress lead to infertility. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase which is important for energy homeostasis for metabolism. Little is known about the potential relationship between AMPK with oocyte aging. RESULTS: In present study we reported that AMPK was related with low quality of oocytes under post ovulatory aging and the potential mechanism. We showed the altered AMPK level during aging and inhibition of AMPK activity induced mouse oocyte maturation defect. Further analysis indicated that similar with its upstream regulator PKD1, AMPK could reduce ROS level to avoid oxidative stress in oocytes, and this might be due to its regulation on mitochondria function, since loss of AMPK activity induced abnormal distribution, reduced ATP production and mtDNA copy number of mitochondria. Besides, we also found that the ER and Golgi apparatus distribution was aberrant after AMPK inhibition, and enhanced lysosome function was also observed. CONCLUSIONS: Taken together, these data indicated that AMPK is important for the organelle function to reduce oxidative stress during oocyte meiotic maturation.


Assuntos
Proteínas Quinases Ativadas por AMP , Oócitos , Estresse Oxidativo , Oócitos/metabolismo , Animais , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Feminino , Mitocôndrias/metabolismo , Organelas/metabolismo , Senescência Celular , Espécies Reativas de Oxigênio/metabolismo
13.
Virol Sin ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38452856

RESUMO

Hand, foot, and mouth disease (HFMD) is a common pediatric illness mainly caused by enteroviruses, which are important human pathogens. Currently, there are no available antiviral agents for the therapy of enterovirus infection. In this study, an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed. Using this screening system, we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors. Fangchinoline (FAN), a bis-benzylisoquinoline alkaloid, exhibits potential inhibitory effects against various enteroviruses that cause HFMD, such as EV-A71, CV-A10, CV-B3 and CV-A16. Further investigations revealed that FAN targets the early stage of the enterovirus life cycle. Through the selection of FAN-resistant EV-A71 viruses, we demonstrated that the VP1 protein could be a potential target of FAN, as two mutations in VP1 (E145G and V258I) resulted in viral resistance to FAN. Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

14.
J Thorac Dis ; 16(2): 1097-1107, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38505065

RESUMO

Background: Vasopressors and inotropes are crucial in managing cardiogenic shock (CS) as they enhance microcirculation in patients. Numerous studies have demonstrated the adverse outcomes associated with excessive use of vasoactive drugs and the vasoactive drug scoring system has emerged as a valuable prognostic tool, particularly in pediatric patients. This study aimed to examine the prognostic significance of the Vasoactive Inotropic Score (VIS) in adult patients with CS receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. Methods: This retrospective multi-center study involved 2,453 adult patients who underwent VA-ECMO in China between 2015 and 2021. Among them, 1,742 adult patients with CS following VA-ECMO were finally included. The maximum VIS (VISmax) was determined by considering the highest doses of vasoactive and inotropic drugs administered within the first 6 hours before ECMO initiation. Based on the VISmax, patients were classified into two groups: 0-20 and >20. The primary outcome of this study was in-hospital mortality. Results: A total of 1,146 patients were included in the high VISmax group, while 596 patients were assigned to the low VISmax group. Overall, 882 (50.6%) patients experienced in-hospital mortality, with significantly higher rates observed among those with higher VISmax scores (41.4% for VIS ≤20 versus 68.3% for VIS >20; P<0.001). Similar trends were observed for 30-day mortality (40.7% for VIS ≤20 versus 64.9% for VIS >20; P<0.001). Multivariable regression analysis demonstrated that a VIS score exceeding 20 independently predicted in-hospital mortality [odds ratio (OR) 2.64; 95% confidence interval (CI): 2.10-3.33; P<0.001]. The receiver operating characteristic (ROC) analysis revealed that VIS had an area under the curve (AUC) of 0.65 (95% CI: 0.63-0.68; P<0.001) as a predictor of in-hospital mortality, with an optimal cutoff value of 20.1. Moreover, the VIS exhibited good predictive ability for in-hospital mortality in patients with acute myocarditis (AUC 0.70; 95% CI: 0.63-0.78; P<0.001). Conclusions: Firstly, higher maximum level of VIS within the first 6 hours before ECMO initiation independently predicted poorer clinical outcomes in patients supported with ECMO for CS. Secondly, VIS exceeding 20 was significantly associated with increased risks of in-hospital mortality and 30-day mortality. Thirdly, when categorized by the cause of CS, a high VIS exhibited good predictive ability in patients with acute myocardial infarction, heart failure, and acute myocarditis.

15.
J Cell Biol ; 223(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38526325

RESUMO

N6, 2'-O-dimethyladenosine (m6Am) is a widespread RNA modification catalyzed by the methyltransferase PCIF1 (phosphorylated CTD interacting factor 1). Despite its prevalence, the biological functions of m6Am in RNA remain largely elusive. Here, we report a critical role of PCIF1-dependent m6Am RNA modification in ciliogenesis in RPE-1 cells. Our findings demonstrate that PCIF1 acts as a negative regulator of ciliation through its m6Am methyltransferase activity. A quantitative proteomic analysis identifies BICD2 as a downstream target of PCIF1, with PCIF1 depletion resulting in a significant increase in BICD2 levels. BICD2 depletion leads to a significant reduction in ciliation. Crucially, the ciliary phenotype in PCIF1-depleted cells is reversed upon BICD2 knockdown. Further investigations reveal that PCIF1 regulates BICD2 protein levels through its m6Am catalytic activity, which reduces the stability and translation efficiency of BICD2 mRNA. Single-base resolution LC-MS analysis identifies the m6Am site on BICD2 mRNA modified by PCIF1. These findings establish the essential involvement of PCIF1-dependent m6Am modification in ciliogenesis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , 60705 , Proteínas Associadas aos Microtúbulos , Proteínas Nucleares , Proteômica , Metiltransferases/genética , RNA , RNA Mensageiro/genética , Humanos , Linhagem Celular , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo
16.
Cell Death Dis ; 15(3): 235, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531846

RESUMO

Ubiquitin-specific protease 3 (USP3) plays an important role in the progression of various tumors. However, the role of USP3 in osteosarcoma (OS) remains poorly understood. The aim of this study was to explore the biological function of USP3 in OS and the underlying molecular mechanism. We found that OS had higher USP3 expression compared with that of normal bone tissue, and high expression of USP3 was associated with poor prognosis in patients with OS. Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion. Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation. Notably, the truncation mutant USP3-F2 (159-520) interacted with EPHA2, and amino acid 203 was found to play an important role in this process. And knockdown of EPHA2 expression reversed the pro-tumour effects of USP3-upregulating. Thus, our study indicates the USP3/EPHA2 axis may be a novel potential target for OS treatment.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , Proliferação de Células , Osteossarcoma/patologia , Neoplasias Ósseas/patologia , Movimento Celular , Proteases Específicas de Ubiquitina/metabolismo
17.
Nat Commun ; 15(1): 2654, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531972

RESUMO

The Myoviridae cyanophage A-1(L) specifically infects the model cyanobacteria Anabaena sp. PCC 7120. Following our recent report on the capsid structure of A-1(L), here we present the high-resolution cryo-EM structure of its intact tail machine including the neck, tail and attached fibers. Besides the dodecameric portal, the neck contains a canonical hexamer connected to a unique pentadecamer that anchors five extended bead-chain-like neck fibers. The 1045-Å-long contractile tail is composed of a helical bundle of tape measure proteins surrounded by a layer of tube proteins and a layer of sheath proteins, ended with a five-component baseplate. The six long and six short tail fibers are folded back pairwise, each with one end anchoring to the baseplate and the distal end pointing to the capsid. Structural analysis combined with biochemical assays further enable us to identify the dual hydrolytic activities of the baseplate hub, in addition to two host receptor binding domains in the tail fibers. Moreover, the structure of the intact A-1(L) also helps us to reannotate its genome. These findings will facilitate the application of A-1(L) as a chassis cyanophage in synthetic biology.


Assuntos
Anabaena , Myoviridae , Proteínas do Capsídeo/química , Capsídeo
18.
Spinal Cord ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38555388

RESUMO

STUDY DESIGN: Retrospective study. OBJECTIVES: To investigate the risk factors of tracheostomy and decannulation after cervical spinal cord injury (CSCI) and their epidemiological changes over the past 8 years in Beijing Bo'ai Hospital, China Rehabilitation Research Center (CRRC), China. SETTING: Beijing Bo'ai Hospital, CRRC. METHODS: We reviewed 8 years of patient data (2013.1.1 to 2020.12.31) at CRRC, focusing on those hospitalized and diagnosed with CSCI. We analyzed changes in demographic and clinical data's trends. Logistic regression analysis was used to determine factors impacting tracheostomy and decannulation. RESULTS: Finally, 1641 CSCI patients met the inclusion criteria. Over the past 8 years, the proportion of tracheostomized patients with CSCI was 16.3%, and the proportion of successfully decannulated of tracheostomized patients with TCSCI was 77.9%. We found that Traumatic (OR = 1.8, 95% CI = 1.06, 3.22; p = 0.046), Motor level of injury (C5-C8) (OR = 0.32, 95% CI = -1.91,-0.34; p = 0.005), AIS = A/B/C (OR = 22.7/11.1/4.2, 95% CI = 12.16,42.26/5.74,21.56/2.23,7.89; p < 0.001/p < 0.001/p < 0.001), age > 56 (OR = 1.6, 95% CI = 1.04, 2.32; p = 0.031) were the risk factors for tracheostomy. By analyzing the risk factors of decannulation failure in tracheostomized patients with TCSCI through multivariable logistic regression, statistically significant differences were found in age > 45 (OR = 4.1, 95% CI = 1.44, 11.81; p = 0.008), complete injury (OR = 2.7, 95% CI = 1.26, 5.95; p = 0.011), facet dislocation (OR = 2.8, 95% CI = 1.13,7.07; p = 0.027). CONCLUSIONS: Recent years have witnessed shifts in the epidemiological characteristics of CSCI. Identifying the factors influencing tracheostomy and decannulation in CSCI can aid in improving patient prognosis.

19.
Anal Chem ; 96(12): 4835-4844, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38488022

RESUMO

The rapid proliferation of new psychoactive substances (NPS) poses significant challenges to conventional mass-spectrometry-based identification methods due to the absence of reference spectra for these emerging substances. This paper introduces PS2MS, an AI-powered predictive system designed specifically to address the limitations of identifying the emergence of unidentified novel illicit drugs. PS2MS builds a synthetic NPS database by enumerating feasible derivatives of known substances and uses deep learning to generate mass spectra and chemical fingerprints. When the mass spectrum of an analyte does not match any known reference, PS2MS simultaneously examines the chemical fingerprint and mass spectrum against the putative NPS database using integrated metrics to deduce possible identities. Experimental results affirm the effectiveness of PS2MS in identifying cathinone derivatives within real evidence specimens, signifying its potential for practical use in identifying emerging drugs of abuse for researchers and forensic experts.


Assuntos
Aprendizado Profundo , Drogas Ilícitas , Cromatografia Líquida/métodos , Psicotrópicos/análise , Espectrometria de Massas/métodos , Drogas Ilícitas/análise , Detecção do Abuso de Substâncias/métodos
20.
Foods ; 13(6)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38540841

RESUMO

Effects of different ionic strengths (0.2, 0.4, and 0.6 mol/L) and different hydrodynamic cavitation (HC) treatment times (0, 1, 2, 3, and 4 min) on the conformation and gel properties of tilapia myofibrillar proteins (TMP) were investigated. The results showed that the solubility of TMP was significantly enhanced (p < 0.05) with the increase in NaCl concentration, and the gel characteristics were significantly improved. After HC treatment of TMP, the average particle size was significantly reduced (p < 0.05) and solubility was significantly enhanced (p < 0.05) with the increase in treatment time, the internal hydrophobic groups and reactive sulfhydryl groups were exposed. The intrinsic fluorescence spectra showed the unfolding of the spatial tertiary structure of proteins, and the circular dichroism spectroscopy showed the significant reduction in the content of α-helix in the secondary structure of the proteins (p < 0.05). In addition, the WHC and gel strength of the TMP heat-induced gels were enhanced, which improved the microstructure of the gels, and scanning electron microscopy showed that the gel network of the TMP gels became denser and more homogeneous. Dynamic rheology results showed that HC treatment resulted in a significant increase in the final G' and G" values of TMP. In conclusion, HC treatment was able to improve the physicochemical structure and gel properties of TMP at different ionic strengths. This study presents a novel processing technique for the quality maintenance aspect of salt-reduced surimi gel products.

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