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1.
J Hazard Mater ; 480: 135820, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39298960

RESUMO

Since December 2019, the COVID-19 pandemic has rapidly disseminated globally, posing significant threats to the world. The dining spaces are high-risk indoor environments for the transmission of SARS-CoV-2, posing challenges for intervention and control. This study, based on surveillance videos from two COVID-19 outbreak cases in restaurants, obtained real data on human behaviors of close contact and surface touch. A respiratory infectious disease transmission model was developed, incorporating four transmission routes: short-range airborne, long-range airborne, fomite and large droplet. The results indicate that diners and staff spent 21.9 %-28.7 % and 17.5 %-27.8 % of their time on speaking, respectively, while spending 85.9 %-90.7 % and 83.4 %-87.6 % of their time on surface touching. The primary transmission routes were short-range (contributing 5.8 %-70.9 %) and long-range airborne (contributing 28.4 %-93.0 %), with fomite and large droplet routes contributing less than 12.0 %. Staff-only mask wearing reduced infection risk by 12.8 %-31.8 %. It is recommended that mandatory mask wearing for staff is necessary, while diners should wear masks as much as possible, and that the equivalent ventilation rate of clean fresh air is suggested to 30.0 m3/ (h·person). This study provides a scientific support to make non-pharmaceutical interventions in dinning spaces.

2.
J Affect Disord ; 368: 599-606, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39303890

RESUMO

BACKGROUND: Although stressor exposure early in life was known risk factor for telomere length (TL) attrition, limited literature explored it across generations. Furthermore, the effects of resilience have rarely been examined. Here, we examined whether the effects of intergenerational parent-child separation on offspring 1-year TL attrition vary by the levels of resilience. METHOD: In a sample of 342 mother-child dyads living in rural China, the intergenerational continuation of parent-child separation was defined as the two generations both experiencing parent-child separation from both parents for >6 months a year early in life assessed by the parent-reported questionnaire, whereas intergenerational discontinuity refers to parent-child separation exposed in one generation only. TL was measured at baseline (from June to November 2021) and 1-year later with children's buccal mucosa swabs, with resilience polygenic risk scores (PRS) evaluated based on 4 single-nucleotide variations in 4 resilience-related genes (OXTR, FKBP5, NPY, and TNF-α). RESULTS: Among 342 mother-offspring dyads, 35 (10.2 %) experienced intergenerational continuation of parent-child separation, and 139 (40.6 %) were identified as discontinuous. Remarkably, a 0.12-point reduction in TL attrition was only associated with intergenerational continuation of parent-child separation (95 % CI: 0.04, 0.21, P < 0.01) but not discontinuity. Importantly, the association between intergenerational continuation of parent-child separation with accelerated TL attrition disappeared in offspring with high resilience PRS (ß = 0.07, 95%CI: -0.06, 0.21). CONCLUSION: Our findings highlight the importance of breaking the intergenerational cycle of parent-child separation and the moderating effects of resilience on TL attrition for children exposed to adversity.

3.
J Clin Pharmacol ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39297668

RESUMO

The accumulation of protoporphyrin IX in the liver caused by isoniazid and rifampicin through the disorder of heme biosynthesis was considered an important mechanism of anti-tuberculosis drug-induced liver injury (ATLI). Alanine synthase 1 (ALAS1) is a rate-limiting enzyme in the process of heme synthesis. This study aimed to investigate the association between ALAS1 gene polymorphism, serum ALAS1 level, and the risk of ATLI. This study was a case-control study including 58 ATLI cases and 192 controls. Four single nucleotide polymorphisms (SNPs) of the ALAS1 gene were selected for genotyping and serum ALAS1 concentrations were detected using ELISA kits. There was no significant difference in the genotype distribution of four SNPs between the ATLI cases and the controls under different genetic models. Patients carrying the GG genotype of SNP rs352163 in controls had higher baseline ALAS1 levels than those in ATLI cases (243.6 vs 290.2 ng/L, P = .034), and patients with baseline ALAS1 < 337.85 ng/L had a higher risk of ATLI than those with ALAS1 ≥ 337.85 ng/L (HR = 2.679, 95% CI: 1.360-5.278, P = .004). Our findings indicated that the serum ALAS1 concentrations in the ATLI cases were lower than those in the controls, and the lower baseline ALAS1 levels can be associated with higher ATLI risk.

4.
Am J Clin Exp Urol ; 12(4): 200-215, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39308594

RESUMO

Histopathology, which is the gold-standard for prostate cancer diagnosis, faces significant challenges. With prostate cancer ranking among the most common cancers in the United States and worldwide, pathologists experience an increased number for prostate biopsies. At the same time, precise pathological assessment and classification are necessary for risk stratification and treatment decisions in prostate cancer care, adding to the challenge to pathologists. Recent advancement in digital pathology makes artificial intelligence and learning tools adopted in histopathology feasible. In this review, we introduce the concept of AI and its various techniques in the field of histopathology. We summarize the clinical applications of AI pathology for prostate cancer, including pathological diagnosis, grading, prognosis evaluation, and treatment options. We also discuss how AI applications can be integrated into the routine pathology workflow. With these rapid advancements, it is evident that AI applications in prostate cancer go beyond the initial goal of being tools for diagnosis and grading. Instead, pathologists can provide additional information to improve long-term patient outcomes by assessing detailed histopathologic features at pixel level using digital pathology and AI. Our review not only provides a comprehensive summary of the existing research but also offers insights for future advancements.

5.
Am J Nucl Med Mol Imaging ; 14(4): 253-260, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39309419

RESUMO

PURPOSE: This study delves into the hemodynamic characteristics of Vertebrobasilar Artery Fenestration (VBAF) combined with Vertebrobasilar Dolichoectasia (VBD) using Magnetic Resonance Angiography (MRA). By summarizing the hemodynamic features and identifying high-risk populations, we aim to provide insights for clinical treatment. METHODS: Utilizing MRA images as a foundation, arterial three-dimensional geometric models were constructed. A total of 22 cases were categorized into control, S, L, U, and Spiral groups, and numerical simulation analysis of the vessels was conducted using computational fluid dynamics methods. RESULTS: Hemodynamic parameters of the VBAF combined with the VBD model were obtained, including blood flow velocity, oscillatory shear stress (OSI), wall shear stress (WSS), and aneurysm formation indicator (AFI). The V, OSI, and WSS indices of the L, U, and Spiral groups were significantly higher than those of the control group (P < 0.05). High-speed blood flow, elevated WSS, and increased OSI in these groups were concentrated at the fenestration site, with scattered distribution along the tortuous vertebral artery and basilar artery segments, accompanied by significant differences in the parameters of the bilateral vertebral arteries. CONCLUSION: This preliminary investigation identifies the L, U, and Spiral groups as high-risk populations. Abnormal hemodynamics may lead to a vicious cycle in vascular wall pathology, increasing the likelihood of adverse events such as cerebral infarction. Clinical attention should focus on individuals within these groups and their corresponding vascular regions.

6.
J Hazard Mater ; 479: 135717, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39241362

RESUMO

Chlorinated organophosphorus flame retardants (Cl-OPFRs) and microplastics (MPs) are emerging pollutants in landfills, but their synergistic behaviors and triggering risks were rarely focused on, impeding the resource utilization of landfill soils. This study systematically investigated the adsorption/desorption behaviors, bioaccessibility and human health risks of Cl-OPFRs in landfill soil particle-size fractions coexisted with MPs under simulated gastrointestinal conditions. The results showed that the adsorption capacity and bioaccessibility of Cl-OPFRs in humus soil were higher than that in subsoil. MPs promoted the adsorption of tris(1-chloro-2-methylethyl) phosphate (TCPP) and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) in landfill soils by up to 34.6 % and 34.1 % respectively, but inhibited the adsorption of tris(2-chloroethyl) phosphate (TCEP) by up to 43.6 %. The bioaccessibility of Cl-OPFRs in landfill soils was positively correlated with MPs addition ratio but negatively correlated with the KOW of Cl-OPFRs, soil organic matter and particle size. MPs addition increased the residual concentration of Cl-OPFRs and significantly increased the bioaccessibility of TCEP and TDCPP by up to 33.1 % in landfill soils, resulting in higher carcinogenic and noncarcinogenic risks. The study presents the first series of the combined behavior and effects of MPs and Cl-OPFRs in landfill soils, and provides a theoretical reference for landfill risk management.

7.
Clin Pharmacol Ther ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39295563

RESUMO

T-cell-engaging bispecific antibodies (TCEs) that target tumor antigens and T cells have shown great promise in treating cancer, particularly in hematological indications. The clinical development of TCEs often involves a lengthy first-in-human (FIH) trial with many dose-escalation cohorts leading up to an early proof of concept (POC), enabling either a no-go decision or dose selection for further clinical development. Multiple factors related to the target, product, disease, and patient population influence the efficacy and safety of TCEs. The intricate mechanism of action limits the translatability of preclinical models to the clinic, thereby posing challenges to streamline clinical development. In addition, unlike traditional chemotherapy, the top dose and recommended phase II doses (RP2Ds) for TCEs in the clinic are often not guided by the maximum tolerated dose (MTD), but rather based on the integrated dose-response assessment of the benefit/risk profile. These uncertainties pose complex challenges for translational and clinical pharmacologists (PK/PD scientists), as well as clinicians, to design an efficient clinical study that guides development. To that end, experts in the field, under the umbrella of the American Association of Pharmaceutical Scientists, have reviewed learnings from published literature and currently marketed products to share perspectives on the FIH and clinical pharmacology strategies to support early clinical development of TCEs.

8.
Emerg Microbes Infect ; 13(1): 2400546, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39221898

RESUMO

The vast majority of data obtained from sequence analysis of influenza A viruses (IAVs) have revealed that nonstructural 1 (NS1) proteins from H1N1 swine, H3N8 equine, H3N2 avian and the correspondent subtypes from dogs have a conserved four C-terminal amino acid motif when independent cross-species transmission occurs between these species. To test the influence of the C-terminal amino acid motifs of NS1 protein on the replication and virulence of IAVs, we systematically generated 7 recombinants, which carried naturally truncated NS1 proteins, and their last four C-terminal residues were replaced with PEQK and SEQK (for H1N1), EPEV and KPEI (for H3N8) and ESEV and ESEI (for H3N2) IAVs. Another recombinant was generated by removing the C-terminal residues by reverse genetics. Remarkably, the ESEI and KPEI motifs circulating in canines largely contributed efficient replication in cultured cells and these had enhanced virulence. In contrast, the avian ESEV motif was only responsible for high pathogenicity in mice. We examined the effects of these motifs upon interferon (IFN) induction. The 7 mutant viruses replicated in vitro in an IFN-independent manner, and the canine SEQK motif was able to induced higher levels of IFN-ß in human cell lines. These findings shed further new light on the role of the four C-terminal residues in replication and virulence of IAVs and suggest that these motifs can modulate viral replication in a species-specific manner.


Assuntos
Motivos de Aminoácidos , Vírus da Influenza A Subtipo H1N1 , Infecções por Orthomyxoviridae , Proteínas não Estruturais Virais , Replicação Viral , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/química , Animais , Cães , Virulência , Camundongos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H1N1/fisiologia , Infecções por Orthomyxoviridae/virologia , Humanos , Células Madin Darby de Rim Canino , Camundongos Endogâmicos BALB C , Doenças do Cão/virologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/patogenicidade , Vírus da Influenza A Subtipo H3N2/fisiologia , Vírus da Influenza A Subtipo H3N8/genética , Vírus da Influenza A Subtipo H3N8/patogenicidade , Feminino
9.
J Mech Behav Biomed Mater ; 160: 106742, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39284273

RESUMO

Spider silk is a type of natural protein fiber with excellent toughness and tensile strength. The mechanical properties of chimeric silk have been improved by integrating the spider silk protein gene into the silkworm (Bombyx mori) genome, but this strategy requires a long time to produce genetically modified silkworms. In this study, to rapidly produce chimeric silkworms/spider silk with improved toughness and tensile strength, recombinant Autographa californica multiple nucleopolyhedrovirus (AcMNPV), AcMNPV-FHP-MaSp-G, harboring a full-length Trichonephila clavipes major ampullate spidroin G (MaSp-G) gene driven by the silkworm fibroin heavy chain (Fib-H) promoter, was constructed, in which the signal peptide sequence of the MaSp-G gene was replaced by the signal peptide sequence of the Fib-H gene. Western blot and LC-MS/MS results showed that MaSp-G was successfully expressed in the posterior silk gland of silkworm larvae infected with AcMNPV-FHP-MaSp-G and secreted into the cocoon. Mechanical property tests revealed that the average maximum breaking stress and the average maximum elastic strain of chimeric silkworms/spider silk were 497.867 MPa and 14.824%, respectively, which were 36.53% and 23.55% greater than those of silk produced by normal silkworms. Fourier transform infrared (FTIR) spectroscopy revealed that the proportions of ß-sheets, α-helices, and ß-turns in the chimeric silk increased by 18.22%, 16.92%, and 18.72%, respectively. These results indicate that the mechanical properties of the chimeric silk produced by silkworms infected with AcMNPV-FHP-MaSp-G were significantly improved, which provides a new method for rapid production of chimeric silk in a genetically modified/genome-edited silkworm-independent manner.

10.
Mycoses ; 67(9): e13785, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39245647

RESUMO

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal⁃Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.


Assuntos
Antifúngicos , Consenso , Farmacorresistência Fúngica , Tinha , Humanos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Arthrodermataceae/efeitos dos fármacos , China , Tinha/tratamento farmacológico , Tinha/microbiologia , Tinha/diagnóstico , Trichophyton/efeitos dos fármacos , Trichophyton/isolamento & purificação
11.
Int J Mol Sci ; 25(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39273103

RESUMO

Understanding the mechanisms that regulate plant root growth under soil drying is an important challenge in root biology. We observed that moderate soil drying promotes wheat root growth. To understand whether metabolic and hormonic changes are involved in this regulation, we performed transcriptome sequencing on wheat roots under well-watered and moderate soil drying conditions. The genes upregulated in wheat roots under soil drying were mainly involved in starch and sucrose metabolism and benzoxazinoid biosynthesis. Various plant hormone-related genes were differentially expressed during soil drying. Quantification of the plant hormones under these conditions showed that the concentrations of abscisic acid (ABA), cis-zeatin (CZ), and indole-3-acetic acid (IAA) significantly increased during soil drying, whereas the concentrations of salicylic (SA), jasmonic (JA), and glycosylated salicylic (SAG) acids significantly decreased. Correlation analysis of total root length and phytohormones indicated that CZ, ABA, and IAA are positively associated with wheat root length. These results suggest that changes in metabolic pathways and plant hormones caused by moderate soil drying help wheat roots grow into deeper soil layers.


Assuntos
Regulação da Expressão Gênica de Plantas , Reguladores de Crescimento de Plantas , Raízes de Plantas , Solo , Transcriptoma , Triticum , Triticum/metabolismo , Triticum/crescimento & desenvolvimento , Triticum/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Reguladores de Crescimento de Plantas/metabolismo , Solo/química , Ácidos Indolacéticos/metabolismo , Ácido Abscísico/metabolismo , Perfilação da Expressão Gênica/métodos , Dessecação
13.
Cardiovasc Res ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39288197

RESUMO

AIMS: ß3-AR (ß3-adrenergic receptor) is essential for cardiovascular homeostasis through regulating adipose tissue function. Perivascular adipose tissue (PVAT) has been implicated in the pathogenesis of aortic dissection and aneurysm (AD/AA). Here, we aim to investigate ß3-AR activation-mediated PVAT function in AD/AA. METHODS AND RESULTS: Aortas from patients with thoracic aortic dissection (TAD) were collected to detect ß3-AR expression in PVAT. ApoE-/- and ß-aminopropionitrile monofumarate (BAPN)-treated C57BL/6 mice were induced with Angiotensin II (AngII) to simulate AD/AA, and subsequently received either placebo or mirabegron, a ß3-AR agonist. The results demonstrated an up-regulation of ß3-AR in PVAT of TAD patients and AD/AA mice. Moreover, activation of ß3-AR by mirabegron significantly prevented AngII-induced AD/AA formation in mice. RNA-sequencing analysis of adipocytes from PVAT revealed a notable increase of the lymphangiogenic factor VEGF-C in mirabegron-treated mice. Consistently, enhanced lymphangiogenesis was found in PVAT with mirabegron treatment. Mechanistically, the number of CD4+/CD8+ T cells and CD11c+ cells was reduced in PVAT but increased in adjacent draining lymph nodes (LNs) of mirabegron-treated mice, indicating the improved draining and clearance of inflammatory cells in PVAT by lymphangiogenesis. Importantly, adipocyte-specific VEGF-C knockdown by the adeno-associated virus system restrained lymphangiogenesis and exacerbated inflammatory cell infiltration in PVAT, which ultimately abolished the protection of mirabegron on AD/AA. In addition, the conditional medium derived from mirabegron-treated adipocytes activated the proliferation and tube formation of lymphatic endothelial cells (LECs), which was abrogated by the silencing of VEGF-C in adipocytes. CONCLUSIONS: Our findings illustrated the therapeutic potential of ß3-AR activation by mirabegron on AD/AA, which promoted lymphangiogenesis by increasing adipocyte-derived VEGF-C and, therefore, ameliorated PVAT inflammation.

14.
Plant Dis ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39295135

RESUMO

Phytoplasmas are minute phytopathogenic bacteria that induce excessive vegetative growth, known as witches'-broom (WB), in many infected plant species during the later stages of infection. The WB structure is characterized by densely clustered little (small) leaves, which are frequently accompanied by chlorosis (yellowing). The mechanisms behind the formation of little leaves within WB structures (LL-WB) are poorly understood. To address this gap, the LL-WB formation was extensively studied using sweet cherry virescence (SCV) phytoplasma-infected sweet cherry plants. Based on morphological examinations, signs of premature leaf senescence were observed in LL-WB samples, including reduced leaf size, chlorosis, and alterations in shape. Subsequent physiological analyses indicated decreased sucrose and glucose levels and changes in hormone concentrations in LL-WB samples. Additionally, the transcriptomic analysis revealed impaired ribosome biogenesis and DNA replication. As an essential process in protein production, the compromised ribosome biogenesis and the inhibited DNA replication led to cell cycle arrest, thus affecting leaf morphogenesis and further plant development. Moreover, the expression of marker genes involved in premature leaf senescence was significantly altered. These results indicate a complicated interplay between the development of leaves, premature leaf senescence, and the pathogen-induced stress responses in SCV phytoplasma-infected sweet cherry trees. The results of this study provide insight into understanding the underlying molecular mechanisms driving the formation of little leaves and interactions between plants and pathogens. The findings might help control phytoplasma diseases in sweet cherry cultivation.

16.
Chemosphere ; 364: 143163, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39181456

RESUMO

Incineration is an effective method for reducing and safely treating municipal solid waste. However, microplastics (MPs) inevitably remain in the bottom ash, potentially introducing new pollution risks during subsequent treatment processes. This study conducted an analysis of the accumulation and release potential of MPs in bottom ash samples collected from 4 municipal solid waste incineration plants in Zhejiang, China. The results showed that the abundance of MPs ranged from 20 to 118 items g-1. Remarkably, MPs were found to accumulate predominantly in smaller bottom ash particles below 4.75 mm accounted for up to 70% of the total MPs. Most MPs in the bottom ash were under 100 µm in size, with a majority exceeding 50% being less than 50 µm, typically manifesting as shafts and fibers. In scenarios of secondary crushing, the abundance of MPs increased gradually with the degree of bottom ash crushing. When bottom ash was crushed to a particle size of less than 0.6 mm, the abundance of MPs reached up to 87-901 items g-1, which is 5-10 times higher than the original bottom ash. It is estimated that the annual release of MPs may reach up to 4.05 × 1016 particles. Re-incinerating thoroughly crushed bottom ash at 600 °C successfully decomposed the MPs. Mechanical stress can significantly increase the risk of MPs releasing in bottom ash. This risk can be eliminated by using secondary incineration to achieve complete MPs decomposition.


Assuntos
Cinza de Carvão , Incineração , Microplásticos , Resíduos Sólidos , Resíduos Sólidos/análise , Microplásticos/análise , China , Cinza de Carvão/química , Eliminação de Resíduos/métodos , Tamanho da Partícula , Monitoramento Ambiental
17.
Front Plant Sci ; 15: 1451897, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39166250

RESUMO

Plant spotted leaf (spl) mutants are useful to reveal the regulatory mechanisms of immune responses. Thus, in crop plants, their agronomic traits, especially the grain quality are usually ignored. Here, we characterized a rice spl mutant named spl-A (spotted leaf mutant from A814) that shows autoimmunity, broad-spectrum disease resistance and growth deterioration including decreased rice quality. A single nucleotide mutation of C1144T, which leads to change of the 382nd proline to serine, in the gene encoding the ATPases associated with diverse cellular activities (AAA)-type ATPase LRD6-6 is responsible for the phenotype of the spl-A mutant. Mechanistically, this mutation impairs LRD6-6 ATPase activity and disrupts its interaction with endosomal sorting complex required for transport (ESCRT)-III subunits OsSNF7.1/7.2/7.3. And thus, leading to compromise of multivesicular bodies (MVBs)-mediated vesicle trafficking and accumulation of ubiquitinated proteins in both leaves and seeds of spl-A. Therefore, the immune response of spl-A is activated, and the growth and grain quality are deteriorated. Our study identifies a new amino acid residue that important for LRD6-6 and provides new insight into our understanding of how MVBs-mediated vesicle trafficking regulates plant immunity and growth, including grain quality in rice.

18.
PLoS One ; 19(8): e0306711, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39163387

RESUMO

BACKGROUND: There is ongoing uncertainty about the effectiveness of various adjuvant treatments for low-grade gliomas (LGGs). Machine learning (ML) models that predict individual treatment effects (ITE) and provide treatment recommendations could help tailor treatments to each patient's needs. OBJECTIVE: We sought to discern the individual suitability of radiotherapy (RT) or chemoradiotherapy (CRT) in LGG patients using ML models. METHODS: Ten ML models, trained to infer ITE in 4,042 LGG patients, were assessed. We compared patients who followed treatment recommendations provided by the models with those who did not. To mitigate the risk of treatment selection bias, we employed inverse probability treatment weighting (IPTW). RESULTS: The Balanced Survival Lasso-Network (BSL) model showed the most significant protective effect among all the models we tested (hazard ratio (HR): 0.52, 95% CI, 0.41-0.64; IPTW-adjusted HR: 0.58, 95% CI, 0.45-0.74; the difference in restricted mean survival time (DRMST): 9.11, 95% CI, 6.19-12.03; IPTW-adjusted DRMST: 9.17, 95% CI, 6.30-11.83). CRT presented a protective effect in the 'recommend for CRT' group (IPTW-adjusted HR: 0.60, 95% CI, 0.39-0.93) yet presented an adverse effect in the 'recommend for RT' group (IPTW-adjusted HR: 1.64, 95% CI, 1.19-2.25). Moreover, the models predict that younger patients and patients with overlapping lesions or tumors crossing the midline are better suited for CRT (HR: 0.62, 95% CI, 0.42-0.91; IPTW-adjusted HR: 0.59, 95% CI, 0.36-0.97). CONCLUSION: Our findings underscore the potential of the BSL model in guiding the choice of adjuvant treatment for LGGs patients, potentially improving survival time. This study emphasizes the importance of ML in customizing patient care, understanding the nuances of treatment selection, and advancing personalized medicine.


Assuntos
Neoplasias Encefálicas , Quimiorradioterapia , Glioma , Aprendizado de Máquina , Humanos , Glioma/terapia , Glioma/radioterapia , Glioma/patologia , Glioma/mortalidade , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Quimiorradioterapia/métodos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Gradação de Tumores , Idoso , Resultado do Tratamento
19.
Arch Biochem Biophys ; 760: 110130, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39173700

RESUMO

Lung adenocarcinoma (LUAC) as the most common lung cancer, and its incidence is increasing. Complement factor B (CFB) is an important factor in the alternative complement pathway. CFB has been reported to be involved in the progression of many cancers, including in pancreatic cancer, cutaneous squamous cell carcinoma, and nasopharyngeal carcinoma, but the function and molecular mechanism of CFB in LUAC remains unclear. The present study aimed to explore the role of CFB in LUAC malignant progression. In our previous study, we found that CFB was downregulated expression in LUAC clinical samples. Here, we firstly detected the cell function in vitro. Cell proliferation and migration were increased, while cell apoptosis and cell cycle arrest were suppressed after CFB knockdown. Overexpression of CFB repressed the malignant progression of LUAC in vitro. Besides, in vivo experiments revealed that upregulation of CFB inhibited tumor growth and Ki67 expression. Additionally, our data indicated that CFB negatively regulated Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, upregulation of CFB inhibited the progression of LUAC was reversed by Ras/MAPK pathway activators (ML-098 or C16-PAF). Our study uncovered that CFB acts as a tumor suppressor repressed tumorigenesis of LUAC through inhibiting the Ras/MAPK pathway, suggesting that CFB may be a potential biomarker and therapeutic target for LUAC.


Assuntos
Adenocarcinoma de Pulmão , Proliferação de Células , Fator B do Complemento , Regulação para Baixo , Neoplasias Pulmonares , Sistema de Sinalização das MAP Quinases , Humanos , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Animais , Fator B do Complemento/metabolismo , Fator B do Complemento/genética , Proteínas ras/metabolismo , Camundongos Nus , Progressão da Doença , Camundongos , Linhagem Celular Tumoral , Apoptose , Movimento Celular , Camundongos Endogâmicos BALB C , Regulação Neoplásica da Expressão Gênica , Masculino , Feminino
20.
Int J Biol Macromol ; 278(Pt 2): 134713, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39154686

RESUMO

The exploration of environmentally friendly slow-release fertilizer (SRF) based on natural bio-polymers is of great importance in the development of modern agriculture and horticulture. Herein, a novel starch carbamate (SC) modified sodium alginate (SA) hydrogel (SC/SAH) was prepared utilizing as-synthesized SC and natural SA through the cationic ions crosslinking method and ultimately the corresponding slow-release fertilizer (SC/SAH-SRF) was successfully developed by immersing the dried SC/SAH matrix into saturated urea solution. Due to the low gelation temperature and high viscosity of the synthesized SC, the formed SC/SAH exhibits significantly enhanced properties including excellent water absorbency up to 8.02 g/g with considerable repeatability, abundant pore structure and high hydrophilicity compared with the neat SAH and natural starch based hydrogel (NS/SAH). Accordingly, the SC/SAH leads to higher urea loading amount âˆ¼ 1.28 g/g. Importantly, the resultant SC/SAH-SRF also shows superior slow-release performance, yielding a cumulative urea release of only 61.6 % within 10 h and almost completely release >16 h in water, what's more, only 58.5 % of the urea releases within 25 days and exceeding 50 days for complete release in soil column assays. The slow-release of urea from SC/SAH-SRF well complies for the first-order kinetics and accomplishes via a non-Fickian diffusion process. Moreover, the pot experiment demonstrates that the SC/SAH-SRF has higher growth promotion role for the maize seedlings than those of others. Consequently, this work provides a novel strategy for preparing environmentally friendly SRF by blending modified starch and hydrogel.


Assuntos
Alginatos , Carbamatos , Preparações de Ação Retardada , Fertilizantes , Hidrogéis , Amido , Alginatos/química , Amido/química , Hidrogéis/química , Carbamatos/química , Preparações de Ação Retardada/química , Zea mays/química , Água/química , Ureia/química , Viscosidade
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