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1.
J Med Internet Res ; 26: e52490, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269753

RESUMO

BACKGROUND: The 2022 global outbreak of mpox has significantly impacted health facilities, and necessitated additional infection prevention and control measures and alterations to clinic processes. Early identification of suspected mpox cases will assist in mitigating these impacts. OBJECTIVE: We aimed to develop and evaluate an artificial intelligence (AI)-based tool to differentiate mpox lesion images from other skin lesions seen in a sexual health clinic. METHODS: We used a data set with 2200 images, that included mpox and non-mpox lesions images, collected from Melbourne Sexual Health Centre and web resources. We adopted deep learning approaches which involved 6 different deep learning architectures to train our AI models. We subsequently evaluated the performance of each model using a hold-out data set and an external validation data set to determine the optimal model for differentiating between mpox and non-mpox lesions. RESULTS: The DenseNet-121 model outperformed other models with an overall area under the receiver operating characteristic curve (AUC) of 0.928, an accuracy of 0.848, a precision of 0.942, a recall of 0.742, and an F1-score of 0.834. Implementation of a region of interest approach significantly improved the performance of all models, with the AUC for the DenseNet-121 model increasing to 0.982. This approach resulted in an increase in the correct classification of mpox images from 79% (55/70) to 94% (66/70). The effectiveness of this approach was further validated by a visual analysis with gradient-weighted class activation mapping, demonstrating a reduction in false detection within the background of lesion images. On the external validation data set, ResNet-18 and DenseNet-121 achieved the highest performance. ResNet-18 achieved an AUC of 0.990 and an accuracy of 0.947, and DenseNet-121 achieved an AUC of 0.982 and an accuracy of 0.926. CONCLUSIONS: Our study demonstrated it was possible to use an AI-based image recognition algorithm to accurately differentiate between mpox and common skin lesions. Our findings provide a foundation for future investigations aimed at refining the algorithm and establishing the place of such technology in a sexual health clinic.


Assuntos
Algoritmos , Inteligência Artificial , Saúde Sexual , Humanos , Masculino , Feminino , Dermatopatias/diagnóstico , Infecções Sexualmente Transmissíveis/diagnóstico , Diagnóstico Diferencial
2.
Langmuir ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39303101

RESUMO

All-solid-state lithium metal batteries (ASSLMBs) have been regarded as promising candidates to settle the safety issues of liquid electrolytes for rechargeable lithium batteries. However, the currently reported gel polymer electrolytes still have flammable liquid solvents, thus leading to the potential safety hazard. Here, solvent-free deep eutectic solid polymer electrolytes (SPEs) are designed and fabricated via an in situ polymerization, which are composed of a poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) electrospun membrane, succinonitrile (SN), poly(ethylene glycol) diacrylate (PEGDA200, Mn = 200 g mol-1), lithium bis(trifluoromethanesulfonyl)imide (LiTFSI), and lithium difluoro(oxalato)borate (LiDFOB). The deep eutectic solvent (DES) with SN/LiTFSI provides a superior room-temperature ionic conductivity, while the PEGDA200 precursor acts as cross-linking network to form SPEs under thermal initiation for free radical polymerization, and LiDFOB can form a stable solid electrolyte interface (SEI) layer. The PVDF-HFP electrospun membrane with a three-dimensional nanofibrous network structure for SN/PEGDA200/LiTFSI/LiDFOB SPEs exhibits a wide electrochemical stability window, high lithium-ion transference number, and good compatibility with the lithium metal anode. Furthermore, the obtained SPEs assembled with Li//LiMn0.6Fe0.4PO4, Li//LiFePO4, and Li//LiNi0.8Co0.1Mn0.1O2 asymmetric cells show excellent cycling performance and rate capability at a wide temperature. This strategy provides a promising path in designing high-energy-density ASSLMBs for practical application.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39133811

RESUMO

CONTEXT: ß-cell dedifferentiation ratio is increased in type 2 diabetes; but its direct link to in vivo ß-cell function in human remains unclear. OBJECTIVE: The present study was designed to investigate whether ß-cell dedifferentiation in situ was closely associated with ß-cell function in vivo and to identify targets crucial for ß-cell dedifferentiation/function in human. METHODS: We acquired HOMA-ß values, calculated the number of hormone-negative endocrine cells and evaluated important markers and novel candidates for ß-cell dedifferentiation/function on paraneoplastic pancreatic tissues from 13 patients with benign pancreatic cystic neoplasm (PCN) or intrapancreatic accessory spleen. RESULTS: Both ß-cell dedifferentiation ratio and dedifferentiation marker (Aldh1a3) were inversely related with in vivo ß-cell function (HOMA-ß) and in situ ß-cell functional markers Glut2 and Ucn3 in human. Moreover, the islets from HOMA-ßlow subjects were manifested as 1) increased ß-cell dedifferentiation ratio, 2) enriched dedifferentiation maker Aldh1a3, and 3) lower expression of Glut2 and Ucn3, compared to those from HOMA-ßhigh subjects. We found that basic leucine zipper transcription factor 2 (Bach2) expression was significantly induced in islets from HOMA-ßlow patients and was positively correlated with the ratio of ß-cell dedifferentiation in human. CONCLUSIONS: Our findings emphasize the contribution of ß-cell dedifferentiation to ß-cell dysfunction in human. The Bach2 induction in ß-cells with higher frequency of dedifferentiation observed in HOMA-ßlow subjects reinforce its distinctive role as a pharmaceutical target of ß-cell dedifferentiation for the treatment of human diabetes.

4.
Zhongguo Gu Shang ; 37(7): 670-5, 2024 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-39104067

RESUMO

OBJECTIVE: To investigate the clinical effect of anterior cervical discectomy and fusion (ACDF) in the treatment of cervical spondylosis of vertebral artery type(CSA). METHODS: The clinical data of 42 patients with CSA from January 2020 to January 2022 were retrospectively analyzed. There were 25 males and 17 females, aged from 30 to 74 years old with an average of (53.9±11.0) years old. There were 18 cases with single-segment lesions, 17 cases with two-segment lesions, and 7 cases with three-segment lesions. The American Academy of Otolaryngology-Head and Neck Surgery's Hearing and Balance Committee score (CHE), the Neck Disability Index (NDI) and the cervical curvature Cobb angle were recorded before surgery and after surgery at 6 months. RESULTS: All 42 ACDF patients were followed up for 6 to 30 months with an average of (14.0±5.2) months. The operative time ranged from 95 to 220 min with an average of (160.38±36.77) min, the intraoperative blood loss ranged from 30 to 85 ml with an average of (53.60±18.98) ml. Tow patients had mild postoperative dysphagia, which improved with symptomatic treatment such as nebulized inhalation. CHE score decreased from (4.05±0.96) preoperatively to (2.40±0.70) at 6 months postoperatively (t=12.97, P<0.05). The number of improved vertigo at 6 months postoperatively was 38, with an improvement rate of 90.5%. NDI score was reduced from (34.43±8.04) preoperatively to (20.76±3.91) at 6 months postoperatively (t=11.83, P<0.05). The cervical curvature Cobb angle improved from (8.04±6.70)° preoperatively to (12.42±5.23)° at 6 months postoperatively (t=-15.96, P<0.05). CONCLUSION: The ACDF procedure has outstanding clinical efficacy in treating CSA. The operation can rapidly relieve patients' episodic vertigo symptoms by relieving bony compression and reconstructing cervical curvature. However, it is necessary to strictly grasp the indications for surgery and clarify the causes of vertigo in patients, and ACDF surgery is recommended for CSA patients for whom conservative treatment is ineffective.


Assuntos
Vértebras Cervicais , Discotomia , Fusão Vertebral , Espondilose , Artéria Vertebral , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Discotomia/métodos , Fusão Vertebral/métodos , Espondilose/cirurgia , Idoso , Adulto , Vértebras Cervicais/cirurgia , Artéria Vertebral/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
5.
J Hazard Mater ; 477: 135392, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39094314

RESUMO

Iron (Fe) oxides have a strong adsorption affinity for Cd and organic carbon (SOC). However, under alternate wet-dry (IF) condition,the influences of Fe oxides on the speciation and disrtribution of Cd and SOC in soil aggregates are unkown. In the present study, soils untreated (S), removed (S-Fe) or added (S+Fe) Fe oxide soils were blended with cadmium chloride solution and cultivated for 56 days under different moisture management practices. Compared with the S-Fe soil, the IF treatment increased the contents of Fe oxide-bound SOC (Fe-OC) and Fe/Mn oxide-bound Cd (Fe/Mn-Cd) by 18.5-29.8-fold and 1.45-2.45-fold, repectively, in the S and S+Fe soils, corresponding to a 36 %-42 % increase in the recalcitrant C pool (RCP) and a 53 %-87 % decrease in the exchangeable Cd content. These results could be attributed to soil particle aggregation and Fe redistribution. Fe addition promoted the transfer of Cd/SOC accumulated in microaggregates to macroaggregates and increased the variable negative charge content in macroaggregates and the adsorption capacity of macroaggregates for Cd/SOC. More Cd/SOC accumulated in macroaggregates in Fe oxide-bound form, which reduced the risk of Cd migration and Cd availability and increased the physical protection of SOC. Therefore, Fe oxide has great potential to simultaneously reduce carbon emissions and cadmium toxicity in paddy soil.

6.
AIDS Behav ; 28(9): 3128-3138, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39066859

RESUMO

Men who have sex with men (MSM) is a high-risk population for HIV and sexually transmitted infections (STIs). Pre-exposure prophylaxis (PrEP) is effective in HIV prevention. This study aims to examine the differences in sexual behaviors, STI prevalence and HIV/STI testing across subgroups of MSM with various PrEP use. Data were collected via a cross-sectional survey in an MSM community in Xi'an, Shaanxi, from 2022.01 to 2022.09. Participants were categorized as 'PrEP-naïve and unwilling to use', 'PrEP-naïve but willing to use', and 'current or former PrEP users'. Shannon index was used to assess sexual act diversity and multivariate logistic regression analyzed factors associated with PrEP use. Of the 1,131 MSM participants, 23.52% were PrEP-naïve and unwilling, 64.98% were PrEP-naïve but willing, and 11.49% were current or former PrEP users. The PrEP-naïve but willing group had the highest recent STI testing rates at 73.06% and showed greater sexual act diversity (Shannon index 1.61). This group also had the highest syphilis rates (7.49% vs. 6.47% and2.54%, p < 0.01). Younger age (18-30: OR = 0.39 (0.18-0.85); 31-40: OR = 0.43 (0.20-0.96)) and lower education (high school/vocational: OR = 0.15 (0.04-0.58); associate degree: OR = 0.21 (0.06-0.71)) were factors that negatively influenced PrEP use. Current or former PrEP users had the highest oropharyngeal gonorrhea (14.39% vs. 9.68% and 5.80%, p < 0.01) and overall gonorrhea rates (20.86% vs. 17.17% and 8.37%, p < 0.001). 'PrEP-naïve but willing' participants consistently demonstrated high-risk sexual behavior, increased STI testing, and more diverse sexual acts, whereas PrEP users had the highest STI prevalence.


Assuntos
Infecções por HIV , Homossexualidade Masculina , Profilaxia Pré-Exposição , Comportamento Sexual , Infecções Sexualmente Transmissíveis , Humanos , Masculino , Estudos Transversais , Homossexualidade Masculina/estatística & dados numéricos , Homossexualidade Masculina/psicologia , Adulto , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Profilaxia Pré-Exposição/estatística & dados numéricos , Comportamento Sexual/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , China/epidemiologia , Prevalência , Adulto Jovem , Pessoa de Meia-Idade , Parceiros Sexuais , Adolescente , Minorias Sexuais e de Gênero/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Assunção de Riscos , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde , População do Leste Asiático
7.
Int J Chron Obstruct Pulmon Dis ; 19: 1197-1206, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38831891

RESUMO

Background: Malnutrition adversely affects prognosis in various medical conditions, but its implications in older adults with Chronic Obstructive Pulmonary Disease (COPD) in the ICU are underexplored. The geriatric nutritional risk index (GNRI) is a novel tool for assessing malnutrition risk. This study investigates the association between GNRI and 90-day mortality in this population. Methods: We selected older adults with COPD admitted to the ICU from Medical Information Mart for Intensive Care (MIMIC)-IV 2.2 database. A total of 666 patients were categorized into four groups based on their GNRI score: normal nutrition (>98), mild malnutrition (92-98), moderate malnutrition (82-91), and severe malnutrition (≤81) groups. We employed a restricted cubic spline (RCS) analysis to assess the presence of a curved relationship between them and to investigate any potential threshold saturation effect. Results: In multivariate Cox regression analyses, compared with individuals had normal nutrition (GNRI in Q4 >98), the adjusted HR values for GNRI in Q3 (92-98), Q2 (82-91), and Q1 (≤81) were 1.81 (95% CI: 1.27-2.58, p=0.001), 1.23 (95% CI: 0.84-1.79, p=0.296), 2.27 (95% CI: 1.57-3.29, p<0.001), respectively. The relationship between GNRI and 90-day mortality demonstrates an L-shaped curve (p=0.016), with an approximate inflection point at 101.5. Conclusion: These findings imply that GNRI is a useful prognostic tool in older adults with COPD in the ICU. An L-shaped relationship was observed between GNRI and 90-day mortality in these patients.


Assuntos
Avaliação Geriátrica , Desnutrição , Avaliação Nutricional , Estado Nutricional , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Masculino , Feminino , Estudos Retrospectivos , Fatores de Risco , Desnutrição/mortalidade , Desnutrição/diagnóstico , Medição de Risco , Avaliação Geriátrica/métodos , Fatores de Tempo , Idoso de 80 Anos ou mais , Prognóstico , Fatores Etários , Bases de Dados Factuais , Unidades de Terapia Intensiva/estatística & dados numéricos
8.
Carcinogenesis ; 45(8): 527-542, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-38902892

RESUMO

Currently, cancer is the second leading cause of death worldwide, and potential targeted drugs and molecular pathways for cancer development and progression have been a hot research topic worldwide. In recent years, the importance of the kinase superfamily in diseases has been well demonstrated by studies on various molecular mechanisms of kinases and the successful application of their inhibitors in diseases. Pseudokinases are members of the kinase superfamily, which have been increasingly documented to play a crucial role in cancers year after year. As a member of pseudokinases, tribbles homolog 3 (TRIB3) also exerts diverse functions in different cancers through different interacting proteins and molecular pathways, especially in tumor immunity, stemness, drug resistance, metabolism, and autophagy. In addition, peptide drugs targeting TRIB3 have high specificity in preclinical studies, which shows great promise for TRIB3 application in diseases including cancers. In this review, we dissect diverse functions played by TRIB3 in different cancers, describing the underlying mechanisms in detail. Notably, inhibitors and agonists currently available for TRIB3 are discussed, indicating the potential for TRIB3 as a therapeutic target.


Assuntos
Proteínas de Ciclo Celular , Neoplasias , Proteínas Serina-Treonina Quinases , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Animais , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Terapia de Alvo Molecular/métodos , Autofagia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos
9.
Cell Death Discov ; 10(1): 251, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789412

RESUMO

Damage to the ribosome or an imbalance in protein biosynthesis can lead to some human diseases, such as diabetic retinopathy (DR) and other eye diseases. Here, we reported that the kri1l gene was responsible for retinal development. The kri1l gene encodes an essential component of the rRNA small subunit processome. The retinal structure was disrupted in kri1l mutants, which resulted in small eyes. The boundaries of each layer of cells in the retina were blurred, and each layer of cells was narrowed and decreased. The photoreceptor cells and Müller glia cells almost disappeared in kri1l mutants. The lack of photoreceptor cells caused a fear of light response. The development of the retina started without abnormalities, and the abnormalities began two days after fertilization. In the kri1l mutant, retinal cell differentiation was defective, resulting in the disappearance of cone cells and Müller cells. The proliferation of retinal cells was increased, while apoptosis was also enhanced in kri1l mutants. γ-H2AX upregulation indicated the accumulation of DNA damage, which resulted in cell cycle arrest and apoptosis. The kri1l mutation reduced the expression of some opsin genes and key retinal genes, which are also essential for retinal development.

10.
Int J Biol Macromol ; 271(Pt 1): 132565, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38782327

RESUMO

There is a growing demand for the development of epoxy resin modified with biomaterials, aiming to achieve high toughness. Herein, chitosan crosslinked epoxy resin (CE) was synthesized by diisocyanate as a bridge. With 4,4'-diamino-diphenylmethane (DDM) as the curing agent, thanks to the unique cross-linking structure of the CE resin and the presence of carbamate groups, the cured CE/DDM exhibited superior properties compared to commercially available epoxy resin (E51). The tensile strength of the cured CE-3/DDM reached 90.17 MPa, the elongation at break was 11.2 %, and the critical stress intensity factor (KIC) measured 1.78 MPa m1/2. These values were 21.4 %, 151.6 %, and 81.6 % higher than those of the cured E51/DDM, respectively. It is worth noting that the addition of biomass material chitosan did not reduce the thermal stability of the resin. Additionally, the CE coatings on the metal substrate exhibited exceptional corrosion resistance, as evidenced by higher impedance values in electrochemical impedance spectroscopy (EIS) and polarization voltages in the Tafel curve compared to those of the E51 coating. This study opens up a novel approach to modifying epoxy resin with biomass materials with high toughness and corrosion resistance, without sacrificing other performance.


Assuntos
Quitosana , Reagentes de Ligações Cruzadas , Resinas Epóxi , Resinas Epóxi/química , Quitosana/química , Corrosão , Reagentes de Ligações Cruzadas/química , Teste de Materiais , Resistência à Tração , Fenômenos Mecânicos
11.
Nanoscale ; 16(25): 12013-12020, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38805240

RESUMO

Magnetic skyrmions are potential candidates for neuromorphic computing because of their inherent topological stability, low drive current density and nanoscale size. However, an artificial neuron device based on current-driven skyrmion motion cannot satisfy the requirement of energy efficiency and integration density due to hundreds of millions of interconnected neurons and synapses present in the deep networks. Here, we present a compact and energy efficient skyrmion-based artificial neuron consisting of ferromagnetic/heavy metal/ferroelectric layers which uses strain-mediated voltage manipulation of skyrmion states to mimic the Integrate-and-Fire (IF) function of biological neurons. By implementation of a spiking neural network (SNN) based on the proposed skyrmionic neuronal devices, it can achieve a high accuracy of 95.08% on a modified National Institute of Standards and Technology (MNIST) handwritten digit dataset, as well as a low power consumption of ∼46.8 fJ per epoch per neuron. The present work suggests a novel way to realize energy-efficient and high-density neuromorphic computing.

12.
Diabetes Obes Metab ; 26(7): 2890-2904, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38686512

RESUMO

AIM: This study investigated the depot- and sex-specific associations of adiposity indicators with incident multimorbidity and comorbidity pairs. MATERIALS AND METHODS: We selected 382 678 adults without multimorbidity (≥2 chronic diseases) at baseline from the UK Biobank. General obesity, abdominal obesity and body fat percentage indices were measured. RESULTS: Cox proportional hazard regression analyses of general obesity indices revealed that for every one-unit increase in body mass index, the risk of incident multimorbidity increased by 5.2% (95% confidence interval 5.0%-5.4%). A dose-response relationship was observed between general obesity degrees and incident multimorbidity. The analysis of abdominal obesity indices showed that for every 0.1 increment in waist-to-height ratio and waist-to-hip ratio, the risk of incident multimorbidity increased by 42.0% (37.9%-46.2%) and 27.9% (25.7%-30.0%), respectively. Central obesity, as defined by waist circumference, contributed to a 23.2% increased risk of incident multimorbidity. Hip circumference and hip-to-height ratio had protective effects on multimorbidity onset. Consistent findings were observed for males and females. Body fat percentage elevated 3% (0.2%-5.9%) and 5.3% (1.1%-9.7%) risks of incident multimorbidity in all adults and females, respectively. Arm fat percentages elevated 5.3% (0.8%-9.9%) and 19.4% (11.0%-28.5%) risks of incident multimorbidity in all adults and males, respectively. The general obesity indices, waist circumference, waist-to-height ratio, waist-to-hip ratio and central obesity increased the onset of comorbidity pairs, whereas hip circumference and hip-to-height ratio decreased the onset of comorbidity pairs. These adiposity indicators mainly affect diabetes mellitus-related comorbidity onset in males and hypertensive-related comorbidity onset in females. CONCLUSIONS: Adiposity indicators are predictors of multimorbidity and comorbidity pairs and represent a promising approach for intervention.


Assuntos
Adiposidade , Multimorbidade , Obesidade , Relação Cintura-Quadril , Humanos , Masculino , Feminino , Reino Unido/epidemiologia , Pessoa de Meia-Idade , Adulto , Obesidade/epidemiologia , Idoso , Bancos de Espécimes Biológicos , Estudos de Coortes , Obesidade Abdominal/epidemiologia , Índice de Massa Corporal , Fatores Sexuais , Circunferência da Cintura , Razão Cintura-Estatura , Incidência , Fatores de Risco , Biobanco do Reino Unido
13.
Adv Mater ; 36(27): e2314175, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38635920

RESUMO

Sorption-based atmospheric water harvesting (SAWH) is a promising technology to alleviate freshwater scarcity. Recently, hygroscopic salt-hydrogel composites (HSHCs) have emerged as attractive candidates with their high water uptake, versatile designability, and scale-up fabrication. However, achieving high-performance SAWH applications for HSHCs has been challenging because of their sluggish kinetics, attributed to their limited mass transport properties. Herein, a universal network engineering of hydrogels using a cryogelation method is presented, significantly improving the SAWH kinetics of HSHCs. As a result of the entangled mesh confinements formed during cryogelation, a stable macroporous topology is attained and maintained within the obtained entangled-mesh hydrogels (EMHs), leading to significantly enhanced mass transport properties compared to conventional dense hydrogels (CDHs). With it, corresponding hygroscopic EMHs (HEMHs) simultaneously exhibit faster moisture sorption and solar-driven water desorption. Consequently, a rapid-cycling HEMHs-based harvester delivers a practical freshwater production of 2.85 Lwater kgsorbents -1 day-1 via continuous eight sorption/desorption cycles, outperforming other state-of-the-art hydrogel-based sorbents. Significantly, the generalizability of this strategy is validated by extending it to other hydrogels used in HSHCs. Overall, this work offers a new approach to efficiently address long-standing challenges of sluggish kinetics in current HSHCs, promoting them toward the next-generation SAWH applications.

14.
Cancer Lett ; 585: 216647, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38301911

RESUMO

The Notch signaling pathway plays pivotal roles in cell proliferation, stemness and invasion of non-small cell lung cancer (NSCLC). The human Notch family consists of four receptors, namely Notch1, Notch2, Notch3, and Notch4. These receptors are transmembrane proteins that play crucial roles in various cellular processes. Notch1 mostly acts as a pro-carcinogenic factor in NSCLC but sometimes acts as a suppressor. Notch2 has been demonstrated to inhibit the growth and progression of NSCLC, whereas Notch3 facilitates these biological behaviors of NSCLC. The role of Notch4 in NSCLC has not been fully elucidated, but it is evident that Notch4 promotes tumor progression. At present, drugs targeting the Notch pathway are being explored for NSCLC therapy, a majority of which are already in the stage of preclinical research and clinical trials, with bright prospects in the clinical treatment of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptor Notch1/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Receptores Notch/metabolismo , Receptor Notch2/metabolismo , Receptor Notch3 , Transdução de Sinais
15.
Cell Rep ; 43(2): 113703, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38265933

RESUMO

Pancreas development is tightly controlled by multilayer mechanisms. Despite years of effort, large gaps remain in understanding how histone modifications coordinate pancreas development. SETD2, a predominant histone methyltransferase of H3K36me3, plays a key role in embryonic stem cell differentiation, whose role in organogenesis remains elusive. Here, by combination of cleavage under targets and tagmentation (CUT&Tag), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and bulk RNA sequencing, we show a dramatic increase in the H3K36me3 level from the secondary transition phase and decipher the related transcriptional alteration. Using single-cell RNA sequencing, we define that pancreatic deletion of Setd2 results in abnormalities in both exocrine and endocrine lineages: hyperproliferative tip progenitor cells lead to abnormal differentiation; Ngn3+ endocrine progenitors decline due to the downregulation of Nkx2.2, leading to insufficient endocrine development. Thus, these data identify SETD2 as a crucial player in embryonic pancreas development, providing a clue to understanding the dysregulation of histone modifications in pancreatic disorders.


Assuntos
Cromatina , Pâncreas , Animais , Camundongos , Diferenciação Celular , Histona-Lisina N-Metiltransferase/genética , Organogênese/genética
16.
Graefes Arch Clin Exp Ophthalmol ; 262(3): 847-855, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37672101

RESUMO

OBJECTIVE: To study the effect of astigmatism correction, rotational stability, and related factors of two different haptic type toric intraocular lenses. METHODS: A prospective, randomized, controlled trial. Cataract patients with preoperative corneal astigmatism of > 1 D were randomly implanted with C-loop haptic toric IOL (AcrySof-toric IOL) (group A) or plate-haptic toric IOL (AT TORBI 709 M IOL) (group B). The residual astigmatism, intraocular lens rotation, and visual quality were determined and compared between the two groups at 3 months after surgery. RESULTS: Seventy-nine eyes were included in this study, including 40 eyes in the group A and 39 eyes in the group B. No significant difference in preoperative visual acuity, intraocular pressure, and ophthalmic biological parameters was found between the two groups. There was no significant difference in residual astigmatism between the two groups at 3 months after surgery (P > 0.05). The rotation degree in the group A was 3.85 ± 2.92°, the rotation degree in the group B was 2.33 ± 2.31°, and a significant difference in intraocular lens rotation was identified between the two groups (P < 0.05). Upon exploring the rotation-related factors of the two different haptic type toric intraocular lenses, the rotation after implanting C-loop haptic toric IOL was positively correlated with axial length (Pearson r = 0.522, P = 0.01) and corneal white-to-white distance (Pearson correlation analysis r = 0.356, P = 0.024). CONCLUSIONS: The two different haptic type toric intraocular lenses effectively corrected regular corneal astigmatism and provided a good rotational stability after surgery. But the stability of plate-haptic toric IOL was better than that of C-loop haptic toric IOL. The rotational stability of C-loop haptic toric IOL was often related to axial length and corneal white-to-white distance.


Assuntos
Astigmatismo , Doenças da Córnea , Lentes Intraoculares , Humanos , Astigmatismo/cirurgia , Tecnologia Háptica , Estudos Prospectivos , Córnea
17.
Diabetes ; 73(2): 237-249, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37963393

RESUMO

The important role of m6A RNA modification in ß-cell function has been established; however, how it regulates pancreatic development and endocrine differentiation remains unknown. Here, we generated transgenic mice lacking RNA methyltransferase-like 3 (Mettl3) specifically in Pdx1+ pancreatic progenitor cells and found the mice with the mutation developed hyperglycemia and hypoinsulinemia at age 2 weeks, along with an atrophic pancreas, reduced islet mass, and abnormal increase in ductal formation. At embryonic day 15.5, Mettl3 deletion had caused a significant loss of Ngn3+ endocrine progenitor cells, which was accompanied by increased Sox9+ ductal precursor cells. We identified histone deacetylase 1 (Hdac1) as the critical direct m6A target in bipotent progenitors, the degeneration of which caused abnormal activation of the Wnt/Notch signaling pathway and blocked endocrine differentiation. This transformation could be manipulated in embryonic pancreatic culture in vitro through regulation of the Mettl3-Hdac1-Wnt/Notch signaling axis. Our finding that Mettl3 determines endocrine lineage by modulating Hdac1 activity during the transition of bipotent progenitors might help in the development of targeted endocrine cell protocols for diabetes treatment.


Assuntos
Adenina/análogos & derivados , Pâncreas , Via de Sinalização Wnt , Camundongos , Animais , Pâncreas/metabolismo , Camundongos Transgênicos , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo
18.
Materials (Basel) ; 16(15)2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37570174

RESUMO

The water retention curve (WRC) of a geosynthetic clay liner (GCL) is influenced by the presence of exchangeable cations in the leachate during changes in water content in a landfill construction. This research aims to investigate the impact of salinity on the WRC of GCL. To measure the WRC of GCL under different sodium chloride (NaCl) concentrations on the drying path, a chilled-mirror dew-point device capable of controlling the GCL's volume was employed. Additionally, the dry state microstructure of the GCL was examined using electron microscopy. The test outcomes indicate that GCL hydrated with higher salinity has greater suction at the same water content during drying. This influence can be attributed to changes in salinity and the precipitation of NaCl crystals within the bentonite when water evaporates, which in turn affects the bentonite's microstructure and leads to increased matric suction. By introducing the Fredlund and Xing model and parameter relationship, it is possible to predict the WRC of GCL under salinity effects after measuring the WRC under different salinity conditions on the drying path.

19.
Phys Rev Lett ; 130(25): 256701, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37418721

RESUMO

The interaction between acoustic wave and magnetization in ferromagnetic thin films has attracted great attention due to its interesting physics and potential applications. However, up to now, the magneto-acoustic interaction has mainly been studied on the basis of magnetostriction. In this Letter, we develop a phase field model of magneto-acoustic interaction based on the Einstein-de Haas effect, and predict the acoustic wave during the ultrafast core reversal of magnetic vortex in a ferromagnetic disk. Because of the Einstein-de Haas effect, the ultrafast change of magnetization at the vortex core leads to a large mechanical angular momentum, which induces a body couple at the vortex core and excites a high-frequency acoustic wave. Moreover, the displacement amplitude of the acoustic wave is highly dependent on the gyromagnetic ratio. The smaller the gyromagnetic ratio is, the larger the displacement amplitude is. The present work not only provides a new mechanism for dynamic magnetoelastic coupling but also sheds new insights on the magneto-acoustic interaction.


Assuntos
Acústica , Som , Física , Movimento (Física) , Aminas , Fenômenos Magnéticos
20.
Sci Rep ; 13(1): 11354, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443369

RESUMO

There are various internal fixation methods in treating lumbosacral spinal tuberculosis. The study compared the stability and stress distribution in surrounding tissues/implants, such as discs, endplates and screw-rod internal fixation system, etc. when applying three different lumbar internal fixation methods to treat lumbosacral spinal tuberculosis. A finite element model was constructed and validated. The spinal stability was restored using three methods: a titanium cage with lateral double screw-rod fixation (group 1), autologous bone with posterior double screw-rod fixation (group 2), and a titanium cage with posterior double screw-rod fixation (group 3). For comparison, group 4 represented the intact L3-S1 spine. Finally, a load was applied, and the ranges of motion and Von Mises stresses in the cortical endplates, screw-rod internal fixation system and cortical bone around the screws in the different groups were recorded and analyzed. All six ranges of motion (flexion, extension, left/right lateral bending, left/right rotation) of the surgical segment were substantially lower in groups 1 (0.53° ~ 1.41°), 2 (0.68° ~ 1.54°) and 3 (0.55° ~ 0.64°) than in group 4 (4.48° ~ 10.12°). The maximum stress in the screw-rod internal fixation system was clearly higher in group 2 than in groups 1 and 3 under flexion, left/right lateral bending, and left/right rotation. However, in extension, group 1 had the highest maximum stress in the screw-rod internal fixation system. Group 2 had the lowest peak stresses in the cortical endplates in all directions. The peak stresses in the cortical bone around the screws were higher in group 1 and group 2 than in group 3 in all directions. Thus, titanium cage with posterior double screw-rod fixation has more advantages in immediate reconstruction of lumbosacral spinal stability and prevention of screw loosening.


Assuntos
Fusão Vertebral , Tuberculose da Coluna Vertebral , Humanos , Análise de Elementos Finitos , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Tuberculose da Coluna Vertebral/cirurgia , Titânio , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Rotação , Fenômenos Biomecânicos , Fusão Vertebral/métodos , Amplitude de Movimento Articular
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