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1.
Cereb Cortex ; 34(1)2024 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-38044479

RESUMO

Accumulating evidence from functional magnetic resonance imaging studies supported brain dysfunction during emotional processing in bipolar disorder (BD) and major depressive disorder (MDD). However, child and adolescent BD and MDD could display different activation patterns, which have not been fully understood. This study aimed to investigate common and distinct activation patterns of pediatric BD (PBD) and MDD (p-MDD) during emotion processing using meta-analytic approaches. Literature search identified 25 studies, contrasting 252 PBD patients, and 253 healthy controls (HCs) as well as 311 p-MDD patients and 263 HCs. A total of nine meta-analyses were conducted pulling PBD and p-MDD experiments together and separately. The results revealed that PBD and p-MDD showed distinct patterns during negative processing. PBD patients exhibited activity changes in bilateral precuneus, left inferior parietal gyrus, left angular gyrus, and right posterior cingulate cortex while p-MDD patients showed functional disruptions in the left rectus, left triangular part of the inferior frontal gyrus, left orbital frontal cortex, left insula, and left putamen. In conclusion, the activity changes in PBD patients were mainly in regions correlated with emotion perception while the dysfunction among p-MDD patients was in the fronto-limbic circuit and reward-related regions in charge of emotion appraisal and regulation.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Adolescente , Criança , Humanos , Transtorno Bipolar/diagnóstico por imagem , Encéfalo , Emoções/fisiologia , Giro do Cíngulo , Imageamento por Ressonância Magnética/métodos , Córtex Pré-Frontal
2.
Proc Natl Acad Sci U S A ; 119(43): e2209218119, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36252031

RESUMO

Optical sensors, with great potential to convert invisible bioanalytical response into readable information, have been envisioned as a powerful platform for biological analysis and early diagnosis of diseases. However, the current extraction of sensing data is basically processed via a series of complicated and time-consuming calibrations between samples and reference, which inevitably introduce extra measurement errors and potentially annihilate small intrinsic responses. Here, we have proposed and experimentally demonstrated a calibration-free sensor for achieving high-precision biosensing detection, based on an optically controlled terahertz (THz) ultrafast metasurface. Photoexcitation of the silicon bridge enables the resonant frequency shifting from 1.385 to 0.825 THz and reaches the maximal phase variation up to 50° at 1.11 THz. The typical environmental measurement errors are completely eliminated in theory by normalizing the Fourier-transformed transmission spectra between ultrashort time delays of 37 ps, resulting in an extremely robust sensing device for monitoring the cancerous process of gastric cells. We believe that our calibration-free sensors with high precision and robust advantages can extend their implementation to study ultrafast biological dynamics and may inspire considerable innovations in the field of medical devices with nondestructive detection.


Assuntos
Neoplasias Gástricas , Humanos , Silício , Neoplasias Gástricas/diagnóstico
3.
Nano Lett ; 24(23): 6997-7003, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38721805

RESUMO

We report that constructed Au nanoclusters (NCs) can afford amazing white emission synergistically dictated by the Au(0)-dominated core-state fluorescence and Au(I)-governed surface-state phosphorescence, with record-high absolute quantum yields of 42.1% and 53.6% in the aqueous solution and powder state, respectively. Moreover, the dynamic color tuning is achieved in a wide warm-to-cold white-light range (with the correlated color temperature varied from 3426 to 24 973 K) by elaborately manipulating the ratio of Au(0) to Au(I) species and thus the electron transfer rate from staple motif to metal kernel. This study not only exemplifies the successful integration of multiple luminescent centers into metal NCs to accomplish efficient white-light emission but also inspires a feasible pathway toward customizing the optical properties of metal NCs by regulating electron transfer kinetics.

4.
J Am Chem Soc ; 146(32): 22180-22192, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39087925

RESUMO

Metal nanoclusters (NCs) hold great promise for expressing multipeak emission based on their well-defined total structure with diverse luminescent centers. Herein, we report the surface motif-dictated triple phosphorescence of Au NCs with dynamic color turning. The deprotonation-triggered isomerization of terminal thiouracils can evolve into a mutual transformation among their hierarchical motifs, thus serving a multipeak-emission expression with good tailoring. More importantly, the underlying electron transfer is thoroughly identified by excluding the radiative and nonradiative energy transfer, where electrons flow from the first phosphorescent state to the last two ones. The findings shed light on finely tailing motifs at the molecular level to motivate studies on customizable luminescence characteristics of metal NCs.

5.
Anal Chem ; 96(19): 7577-7584, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38696338

RESUMO

Owing to the separation of field-effect transistor (FET) devices from sensing environments, extended-gate FET (EGFET) biosensor features high stability and low cost. Herein, a highly sensitive EGFET biosensor based on a GaN micropillar array and polycrystalline layer (GMP) was fabricated, which was prepared by using simple one-step low-temperature MOCVD growth. In order to improve the sensitivity and detection limit of EGFET biosensor, the surface area and the electrical conductivity of extended-gate electrode can be increased by the micropillar array and the polycrystalline layer, respectively. The designed GMP-EGFET biosensor was modified with l-cysteine and applied for Hg2+ detection with a low limit of detection (LOD) of 1 ng/L, a high sensitivity of -16.3 mV/lg(µg/L) and a wide linear range (1 ng/L-24.5 µg/L). In addition, the detection of Hg2+ in human urine was realized with an LOD of 10 ng/L, which was more than 30 times lower than that of reported sensors. To our knowledge, it is the first time that GMP was used as extended-gate of EGFET biosensor.


Assuntos
Técnicas Biossensoriais , Limite de Detecção , Mercúrio , Humanos , Mercúrio/urina , Mercúrio/análise , Transistores Eletrônicos , Gálio/química , Eletrodos
6.
J Virol ; 97(9): e0056923, 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37607059

RESUMO

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.

7.
J Transl Med ; 22(1): 93, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263056

RESUMO

BACKGROUND: Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare. Hypoxia and lipid metabolism-related gene acetyl-CoA synthetase 2 (ACSS2) is involved in tumor progression, but its role in pNENs is not revealed. This study showed that hypoxia can upregulate ACSS2, which plays an important role in the occurrence and development of pNENs through lipid metabolism reprogramming. However, the precise role and mechanisms of ACSS2 in pNENs remain unknown. METHODS: mRNA and protein levels of ACSS2 and 3-hydroxy-3-methylglutaryl-CoA synthase1 (HMGCS1) were detected using quantitative real-time PCR (qRT-PCR) and Western blotting (WB). The effects of ACSS2 and HMGCS1 on cell proliferation were examined using CCK-8, colony formation assay and EdU assay, and their effects on cell migration and invasion were examined using transwell assay. The interaction between ACSS2 and HMGCS1 was verified by Co-immunoprecipitation (Co-IP) experiments, and the functions of ACSS2 and HMGCS1 in vivo were determined by nude mouse xenografts. RESULTS: We demonstrated that hypoxia can upregulate ACSS2 while hypoxia also promoted the progression of pNENs. ACSS2 was significantly upregulated in pNENs, and overexpression of ACSS2 promoted the progression of pNENs and knockdown of ACSS2 and ACSS2 inhibitor (ACSS2i) treatment inhibited the progression of pNENs. ACSS2 regulated lipid reprogramming and the PI3K/AKT/mTOR pathway in pNENs, and ACSS2 regulated lipid metabolism reprogramming through the PI3K/AKT/mTOR pathway. Co-IP experiments indicated that HMGCS1 interacted with ACSS2 in pNENs. Overexpression of HMGCS1 can reverse the enhanced lipid metabolism reprogramming and tumor-promoting effects of knockdown of ACSS2. Moreover, overexpression of HMGCS1 reversed the inhibitory effect of knockdown of ACSS2 on the PI3K/AKT/mTOR pathway. CONCLUSION: Our study revealed that hypoxia can upregulate the lipid metabolism-related gene ACSS2, which plays a tumorigenic effect by regulating lipid metabolism through activating the PI3K/AKT/mTOR pathway. In addition, HMGCS1 can reverse the oncogenic effects of ACSS2, providing a new option for therapeutic strategy.


Assuntos
Metabolismo dos Lipídeos , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Reprogramação Metabólica , Serina-Treonina Quinases TOR , Lipídeos , Acetato-CoA Ligase , Hidroximetilglutaril-CoA Sintase
8.
Chemistry ; : e202402808, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39207820

RESUMO

The integration of polymers, supramolecular macrocycles and aggregation-induced emission (AIE) molecules provides numerous possibilities for constructing various functional supramolecular systems. Herein, we constructed supramolecular assembled systems based on discrete macrocyclic polymer hosts via the cooperation of hydra-headed macrocycles containing two or three pillar[5]arene units (defined as P2, P3), the block polymer F127 and AIE molecules (alkyl-cyano modified tetraphenylethene, alkyl-triazole-cyano modified 9,10-distyrylanthracene, defined as TPE-(CN)4 and DSA-(TACN)2). Compared with the binary assembly between hydra-headed hosts or F127 and AIE molecules, cascaded supramolecular assembly-induced emission enhancement (SAIEE) in aqueous solution was achieved in discrete macrocyclic polymer-based supramolecular assembled systems. Considering the cascaded SAIEE performance, we have successfully applied discrete macrocyclic polymer-based supramolecular assembled systems to bioimaging and constructed an artificial light-harvesting system (LHs) to explore more potential applications. The supramolecular assembly form of discrete macrocyclic polymers hosts and AIE molecules proposed in this work provides new inspiration for the construction and application of high-performance supramolecular luminescent systems.

9.
BMC Cancer ; 24(1): 422, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580944

RESUMO

BACKGROUND: As comprehensive surgical management for gastric cancer becomes increasingly specialized and standardized, the precise differentiation between ≤T1 and ≥T2 gastric cancer before endoscopic intervention holds paramount clinical significance. OBJECTIVE: To evaluate the diagnostic efficacy of contrast-enhanced gastric ultrasonography in differentiating ≤T1 and ≥T2 gastric cancer. METHODS: PubMed, Web of Science, and Medline were searched to collect studies published from January 1, 2000 to March 16, 2023 on the efficacy of either double contrast-enhanced gastric ultrasonography (D-CEGUS) or oral contrast-enhanced gastric ultrasonography (O-CEGUS) in determining T-stage in gastric cancer. The articles were selected according to specified inclusion and exclusion criteria, and the quality of the included literature was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 scale. Meta-analysis was performed using Stata 12 software with data from the 2 × 2 crosslinked tables in the included literature. RESULTS: In total, 11 papers with 1124 patients were included in the O-CEGUS analysis, which revealed a combined sensitivity of 0.822 (95% confidence interval [CI] = 0.753-0.875), combined specificity of 0.964 (95% CI = 0.925-0.983), and area under the summary receiver operating characteristic (sROC) curve (AUC) of 0.92 (95% CI = 0.89-0.94). In addition, five studies involving 536 patients were included in the D-CEGUS analysis, which gave a combined sensitivity of 0.733 (95% CI = 0.550-0.860), combined specificity of 0.982 (95% CI = 0.936-0.995), and AUC of 0.93 (95% CI = 0.91-0.95). According to the I2 and P values ​​of the forest plot, there was obvious heterogeneity in the combined specificities of the included papers. Therefore, the two studies with the lowest specificities were excluded from the O-CEGUS and D-CEGUS analyses, which eliminated the heterogeneity among the remaining literature. Consequently, the combined sensitivity and specificity of the remaining studies were 0.794 (95% CI = 0.710-0.859) and 0.976 (95% CI = 0.962-0.985), respectively, for the O-CEDUS studies and 0.765 (95% CI = 0.543-0.899) and 0.986 (95% CI = 0.967-0.994), respectively, for the D-CEGUS studies. The AUCs were 0.98 and 0.99 for O-CEGUS and D-CEGUS studies, respectively. CONCLUSION: Both O-CEGUS and D-CEGUS can differentiate ≤T1 gastric cancer from ≥T2 gastric cancer, thus assisting the formulation of clinical treatment strategies for patients with very early gastric cancer. Given its simplicity and cost-effectiveness, O-CEGUS is often favored as a staging method for gastric cancer prior to endoscopic intervention.


Assuntos
Meios de Contraste , Estadiamento de Neoplasias , Neoplasias Gástricas , Ultrassonografia , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Humanos , Ultrassonografia/métodos , Sensibilidade e Especificidade , Curva ROC , Estômago/diagnóstico por imagem , Estômago/patologia
10.
BMC Cancer ; 24(1): 872, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030531

RESUMO

BACKGROUND: The aim of this study was to assess the risk factors for anastomotic stricture in esophageal cancer patients undergoing esophagectomy. Esophageal anastomotic stricture is the most common long-term complication for esophagectomy. The risk factors for esophageal anastomotic stricture still remain controversial. METHODS: MEDLINE, Cochrane Library, and EMBASE were searched to identify observational studies reporting the risk factors for esophageal anastomotic stricture after esophagectomy. A meta-analysis was conducted to investigate the impact of various risk factors on esophageal anastomotic stricture. The GRADE [Grading of Recommendations Assessment, Development and Evaluation] approach was used for quality assessment of evidence on outcome levels. RESULTS: This review included 14 studies evaluating 5987 patients.The meta-analysis found that anastomotic leakage (odds ratio [OR]: 2.75; 95% confidence interval[CI]:2.16-3.49), cardiovascular disease [OR:1.62; 95% CI: 1.22-2.16],diabete [OR: 1.62; 95% CI: 1.20-2.19] may be risk factors for esophageal anastomotic stricture.There were no association between neoadjuvant therapy [OR: 0.78; 95% CI:0.62-0.97], wide gastric conduit [OR:0.98; 95% CI: 0.37-2.56],mechanical anastomosis [OR: 0.84; 95% CI:0.47-1.48],colonic interposition[OR:0.20; 95% CI: 0.12-0.35],and transhiatal approach[OR:1.16; 95% CI:0.81-1.64],with the risk of esophageal anastomotic stricture. CONCLUSIONS: This meta-analysis provides some evidence that anastomotic leakage,cardiovascular disease and diabete may be associated with higher rates of esophageal anastomotic stricture.Knowledge about those risk factors may influence treatment and procedure-related decisions,and possibly reduce the anastomotic stricture rate.


Assuntos
Anastomose Cirúrgica , Neoplasias Esofágicas , Estenose Esofágica , Esofagectomia , Humanos , Esofagectomia/efeitos adversos , Fatores de Risco , Estenose Esofágica/etiologia , Estenose Esofágica/epidemiologia , Anastomose Cirúrgica/efeitos adversos , Neoplasias Esofágicas/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Razão de Chances
11.
FASEB J ; 37(8): e23090, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37428639

RESUMO

N6-methyladenosine modification, especially Wilms tumor 1-associated protein (WTAP), is reportedly associated with a variety of cancers, including colorectal cancer (CRC). Angiogenesis also plays an important role in the occurrence and development of CRC. However, only a few studies have reported the biological mechanisms underlying this connection. Therefore, tissue microarray and public database were used to explore WTAP levels in CRC. Then, WTAP was down-regulated and over-expressed, respectively. CCK8, EdU, colony formation, and transwell experiments were performed to study the role of WTAP in CRC. Combined RNA sequencing and m6A RNA immunoprecipitation (MeRIP) sequencing, we found downstream molecules VEGFA. Moreover, a tube formation assay was executed for tumor angiogenesis. Finally, a subcutaneous tumorigenesis assay in nude mice was used to examine the tumor-promoting effect of WTAP in vivo. In the present study, WTAP was significantly upregulated in CRC cells and patients with CRC. Moreover, higher WTAP expression was observed in the TCGA and CPATC databases in CRC tissues. WTAP over-expression exacerbates cell proliferation, migration, invasion, and angiogenesis. Conversely, WTAP knockdown inhibited the malignant biological behavior of CRC cells. Mechanistically, WTAP positively regulated VEGFA, as identified using RNA sequencing and MeRIP sequencing. Moreover, we identified YTHDC1 as a downstream effector of the YTHDC1-VEGFA axis in CRC. Furthermore, increased WTAP expression activated the MAPK signaling pathway, which led to enhanced angiogenesis. In conclusion, our study revealed that the WTAP/YTHDC1/VEGFA axis promotes CRC development, especially angiogenesis, suggesting that it may act as a potential biomarker of CRC.


Assuntos
Adenosina , Neoplasias Colorretais , Animais , Camundongos , Bioensaio , Neoplasias Colorretais/genética , Metilação , Camundongos Nus , Humanos
12.
J Vasc Interv Radiol ; 35(8): 1194-1202.e2, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38723863

RESUMO

PURPOSE: To examine the relationship between hyperdense artery sign (HAS)/susceptibility vessel sign (SVS) and thrombus composition and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive patients with acute anterior circulation LVO (75 [63.1%] men; median age, 66 years) who underwent thrombectomy and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was assessed on unenhanced computed tomography (CT) and susceptibility-weighted imaging, respectively. Association of first-line thrombectomy techniques (stent retriever [SR] combined with contact aspiration [CA] vs CA alone) with outcomes was assessed according to HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS-negative, and 69 (67.0%) underwent first-line SR + CA. Higher relative densities of fibrin/platelets (0.56 vs 0.51; P < .001) and lower relative densities of erythrocytes (0.32 vs 0.42; P < .001) were observed in HAS/SVS-negative patients compared with HAS/SVS-positive patients. First-line SR + CA was associated with reduced odds of distal embolization (adjusted odds ratio, 0.18; 95% CI, 0.04-0.83; P = .027) and a more favorable 90-day functional outcome (adjusted odds ratio, 5.29; 95% CI, 1.06-26.34; P = .042) in HAS/SVS-negative patients and a longer recanalization time (53 vs 25 minutes; P = .025) and higher risk of subarachnoid hemorrhage (24.2% vs 0%; P = .044) in HAS/SVS-positive patients. CONCLUSIONS: Absence of HAS/SVS may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR + CA yielded superior functional outcomes than CA alone in patients with acute LVO without HAS/SVS.


Assuntos
Procedimentos Endovasculares , Stents , Trombectomia , Humanos , Masculino , Feminino , Trombectomia/efeitos adversos , Trombectomia/instrumentação , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Pessoa de Meia-Idade , Sucção , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/efeitos adversos , Valor Preditivo dos Testes , Fatores de Risco , Idoso de 80 Anos ou mais , Fatores de Tempo , Trombose Intracraniana/diagnóstico por imagem , Trombose Intracraniana/terapia , Trombose Intracraniana/fisiopatologia
13.
BMC Neurol ; 24(1): 313, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232681

RESUMO

BACKGROUND: There is still a lack of knowledge about the relationship between metabolic syndrome (MetS) and Parkinson's disease (PD). This study aimed to determine whether MetS increases PD risk. METHODS: To identify relevant clinical studies, databases such as PubMed, Embase, and the Cochrane Library were searched in depth from the inception of databases until March 31, 2024. The study evaluated the correlation between MetS and the likelihood of developing PD through the computation of aggregated relative risks (RR) and their respective 95% confidence intervals (CIs) utilizing selnRR and lnRR. RESULTS: Seven studies were included in our systematic review. The meta-analysis revealed that patients with MetS have a 0.3-fold increased risk of developing PD (p = 0.001). Furthermore, the analysis revealed a positive correlation between central obesity and the incidence of PD, with an RR of 1.19 (95% CI, 1.16-1.22; p = 0.001), as well as a greater risk of PD in patients with elevated blood pressure, with an RR of 1.13 (95% CI, 1.07-1.19; p = 0.001); elevated serum triglyceride levels, with an RR of 1.09 (95% CI, 1.02-1.15; p = 0.001); lower serum HDL cholesterol levels, with an RR of 1.21 (95% CI, 1.15-1.28; p = 0.001); and elevated plasma fasting glucose levels, with an RR of 1.18 (95% CI, 1.11-1.26; p = 0.001). CONCLUSION: MetS can contribute to the incidence of Parkinson's disease, with individual components of MetS demonstrating comparable effects.


Assuntos
Síndrome Metabólica , Doença de Parkinson , Doença de Parkinson/epidemiologia , Doença de Parkinson/sangue , Humanos , Síndrome Metabólica/epidemiologia , Fatores de Risco
14.
Macromol Rapid Commun ; 45(14): e2400087, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38688322

RESUMO

The collapse or folding of an individual polymer chain into a nanoscale particle gives rise to single-chain nanoparticles (SCNPs), which share a soft nature with biological protein particles. The precise control of their properties, including morphology, internal structure, size, and deformability, are a long-standing and challenging pursuit. Herein, a new strategy based on amphiphilic alternating copolymers for producing SCNPs with ultrasmall size and uniform structure is presented. SCNPs are obtained by folding the designed alternating copolymer in N,N-dimethylformamide (DMF) and fixing it through a photocatalyzed cycloaddition reaction of anthracene units. Molecular dynamics simulation confirms the solvophilic outer corona and solvophobic inner core structure of SCNPs. Furthermore, by adjusting the length of PEG units, precise control over the mean size of SCNPs is achieved within the range of 2.8 to 3.9 nm. These findings highlight a new synthetic strategy that enables enhanced control over morphology and internal structure while achieving ultrasmall and uniform size for SCNPs.


Assuntos
Simulação de Dinâmica Molecular , Nanopartículas , Tamanho da Partícula , Polímeros , Nanopartículas/química , Polímeros/química , Tensoativos/química , Estrutura Molecular , Antracenos/química
15.
Phys Chem Chem Phys ; 26(7): 6180-6188, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38300128

RESUMO

The application of liquid crystal technology typically relies on the precise control of molecular orientation at a surface or interface. This control can be achieved through a combination of morphological and chemical methods. Consequently, variations in constrained boundary flexibility can result in a diverse range of phase behaviors. In this study, we delve into the self-assembly of liquid crystals within elastic spatial confinement by using the Gay-Berne model with the aid of molecular dynamics simulations. Our findings reveal that a spherical elastic shell promotes a more regular and orderly alignment of liquid crystals compared to a hard shell. Moreover, during the cooling process, the hard-shell confined system undergoes an isotropic-smectic phase transition. In contrast, the phase behavior within the spherical elastic shell closely mirrors the isotropic-nematic-smectic phase transition observed in bulk systems. This indicates that the orientational arrangement of liquid crystals and the deformations induced by a flexible interface engage in a competitive interplay during the self-assembly process. Importantly, we found that phase behavior could be manipulated by altering the flexibility of the confined boundaries. This insight offers a fresh perspective for the design of innovative materials, particularly in the realm of liquid crystal/polymer composites.

16.
Acta Pharmacol Sin ; 45(7): 1477-1491, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38538716

RESUMO

Refractory wounds are a severe complication of diabetes mellitus that often leads to amputation because of the lack of effective treatments and therapeutic targets. The pathogenesis of refractory wounds is complex, involving many types of cells. Rho-associated protein kinase-1 (ROCK1) phosphorylates a series of substrates that trigger downstream signaling pathways, affecting multiple cellular processes, including cell migration, communication, and proliferation. The present study investigated the role of ROCK1 in diabetic wound healing and molecular mechanisms. Our results showed that ROCK1 expression significantly increased in wound granulation tissues in diabetic patients, streptozotocin (STZ)-induced diabetic mice, and db/db diabetic mice. Wound healing and blood perfusion were dose-dependently improved by the ROCK1 inhibitor fasudil in diabetic mice. In endothelial cells, fasudil and ROCK1 siRNA significantly elevated the phosphorylation of adenosine monophosphate-activated protein kinase at Thr172 (pThr172-AMPKα), the activity of endothelial nitric oxide synthase (eNOS), and suppressed the levels of mitochondrial reactive oxygen species (mtROS) and nitrotyrosine formation. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that ROCK1 inhibited pThr172-AMPKα by binding to receptor-interacting serine/threonine kinase 4 (RIPK4). These results suggest that fasudil accelerated wound repair and improved angiogenesis at least partially through the ROCK1/RIPK4/AMPK pathway. Fasudil may be a potential treatment for refractory wounds in diabetic patients.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina , Diabetes Mellitus Experimental , Transdução de Sinais , Cicatrização , Quinases Associadas a rho , Animais , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Cicatrização/efeitos dos fármacos , Humanos , Diabetes Mellitus Experimental/metabolismo , Masculino , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/uso terapêutico , Camundongos , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por AMP/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Células Endoteliais da Veia Umbilical Humana , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Feminino
17.
Compr Psychiatry ; 133: 152487, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38714144

RESUMO

BACKGROUND: The incidence of non-suicidal self-injury (NSSI) has been on the rise in recent years. Studies have shown that people with NSSI have difficulties in emotion regulation and cognitive control. In addition, some studies have investigated the cognitive emotion regulation of people with NSSI which found that they have difficulties in cognitive emotion regulation, but there was a lack of research on cognitive emotion regulation strategies and related neural mechanisms. METHODS: This study included 117 people with NSSI (age = 19.47 ± 5.13, male = 17) and 84 non-NSSI participants (age = 19.86 ± 4.14, male = 16). People with NSSI met the DSM-5 diagnostic criteria, and non-NSSI participants had no mental or physical disorders. The study collected all participants' data of Cognitive Emotion Regulation Questionnaire (CERQ) and functional magnetic resonance imaging (fMRI) to explore the differences in psychological performance and brain between two groups. Afterwards, Machine learning was used to select the found differential brain regions to obtain the highest correlation regions with NSSI. Then, Allen's Human Brain Atlas database was used to compare with the information on the abnormal brain regions of people with NSSI to find the genetic information related to NSSI. In addition, gene enrichment analysis was carried out to find the related pathways and specific cells that may have differences. RESULTS: The differences between NSSI participants and non-NSSI participants were as follows: positive refocusing (t = -4.74, p < 0.01); refocusing on plans (t = -4.11, p < 0.01); positive reappraisal (t = -9.22, p < 0.01); self-blame (t = 6.30, p < 0.01); rumination (t = 3.64, p < 0.01); catastrophizing (t = 9.10, p < 0.01), and blaming others (t = 2.52, p < 0.01), the precentral gyrus (t = 6.04, pFDR < 0.05) and the rolandic operculum (t = -4.57, pFDR < 0.05). Rolandic operculum activity was negatively correlated with blaming others (r = -0.20, p < 0.05). Epigenetic results showed that excitatory neurons (p < 0.01) and inhibitory neurons (p < 0.01) were significant differences in two pathways, "trans-synaptic signaling" (p < -log108) and "modulation of chemical synaptic transmission" (p < -log108) in both cells. CONCLUSIONS: People with NSSI are more inclined to adopt non-adaptive cognitive emotion regulation strategies. Rolandic operculum is also abnormally active. Abnormal changes in the rolandic operculum of them are associated with non-adaptive cognitive emotion regulation strategies. Changes in the excitatory and inhibitory neurons provide hints to explore the abnormalities of the neurological mechanisms at the cellular level of them. Trial registration number NCT04094623.


Assuntos
Regulação Emocional , Imageamento por Ressonância Magnética , Comportamento Autodestrutivo , Humanos , Comportamento Autodestrutivo/psicologia , Comportamento Autodestrutivo/fisiopatologia , Masculino , Feminino , Regulação Emocional/fisiologia , Adulto , Adulto Jovem , Adolescente , Cognição/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Inquéritos e Questionários
18.
BMC Med Imaging ; 24(1): 228, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39210250

RESUMO

BACKGROUND: The presence of lateral lymph node metastases (LNM) in paediatric patients with papillary thyroid cancer (PTC) is an independent risk factor for recurrence. We aimed to identify risk factors and establish a prediction model for lateral LNM before surgery in children and adolescents with PTC. METHODS: We developed a prediction model based on data obtained from 63 minors with PTC between January 2014 and June 2023. We collected and analysed clinical factors, ultrasound (US) features of the primary tumour, and pathology records of the patients. Multivariate logistic regression analysis was used to determine independent predictors and build a prediction model. We evaluated the predictive performance of risk factors and the prediction model using the area under the receiver operating characteristic (ROC) curve. We assessed the clinical usefulness of the predicting model using decision curve analysis. RESULTS: Among the minors with PTC, 21 had lateral LNM (33.3%). Logistic regression revealed that independent risk factors for lateral LNM were multifocality, tumour size, sex, and age. The area under the ROC curve for multifocality, tumour size, sex, and age was 0.62 (p = 0.049), 0.61 (p = 0.023), 0.66 (p = 0.003), and 0.58 (p = 0.013), respectively. Compared to a single risk factor, the combined predictors had a significantly higher area under the ROC curve (0.842), with a sensitivity and specificity of 71.4% and 81.0%, respectively (cutoff value = 0.524). Decision curve analysis showed that the prediction model was clinically useful, with threshold probabilities between 2% and 99%. CONCLUSIONS: The independent risk factors for lateral LNM in paediatric PTC patients were multifocality and tumour size on US imaging, as well as sex and age. Our model outperformed US imaging and clinical features alone in predicting the status of lateral LNM.


Assuntos
Metástase Linfática , Curva ROC , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Ultrassonografia , Humanos , Feminino , Criança , Masculino , Adolescente , Metástase Linfática/diagnóstico por imagem , Estudos Retrospectivos , Ultrassonografia/métodos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Fatores de Risco , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Modelos Logísticos , Pré-Escolar , Fatores Etários
19.
BMC Med Imaging ; 24(1): 78, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570748

RESUMO

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.


Assuntos
Hiperuricemia , Ratos , Animais , Hiperuricemia/diagnóstico por imagem , Rim/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Fibrose
20.
Int J Urol ; 31(5): 536-543, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38291596

RESUMO

OBJECTIVES: To explore the relationship between Fuhrman grade of renal cell carcinoma (RCC) and the DDD score. METHODS: We reviewed the records of 527 nonmetastatic RCC patients. Demographic, clinical, and pathologic characteristics were reviewed. Binary logistic regression was used to explore the independent risk factors for high-grade RCC (HGRCC). RESULTS: Sex, BMI (Body Mass Index), RNS, and DDD score were significantly correlated with HGRCC. Based on these independent risk factors, we constructed two predictive models integrating the RNS and DDD scores with sex and BMI to predict tumor grade. The calibration curves of the predictive model showed good agreement between the observations and predictions. The concordance indexes (C-indexes) of the predictive models were 0.768 (95% CI, 0.713-0.824), and 0.809 (95% CI, 0.759-0.859). Receiver operating characteristic (ROC) curves were performed to compare the predictive power of the nomograms, and the prediction model including the DDD score had better prognostic ability (p = 0.01). CONCLUSIONS: This study found that RNS, DDD score, BMI, and sex were independent predictors of HGRCC. We developed effective nomograms integrating the above risk factors to predict HGRCC. Of note, the nomogram including the DDD score achieves better prediction ability for HGRCC.


Assuntos
Índice de Massa Corporal , Carcinoma de Células Renais , Neoplasias Renais , Gradação de Tumores , Nomogramas , Humanos , Carcinoma de Células Renais/patologia , Masculino , Feminino , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Fatores de Risco , Adulto , Prognóstico , Curva ROC , Fatores Sexuais , Idoso de 80 Anos ou mais , Modelos Logísticos
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