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1.
J Clin Oncol ; : JCO2302261, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950321

RESUMO

PURPOSE: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). PATIENTS AND METHODS: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT. RESULTS: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis (P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment. CONCLUSION: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

2.
MycoKeys ; 106: 201-224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962655

RESUMO

Four new fungi from Xizang in southwest China, Caloceraramaria, Ceraceomycesrhizomorphus, Leptosporomyceslinzhiensis, and Ramariaxizangensis are described and illustrated based on the morphological and molecular evidence. Caloceraramaria is characterized by the ramal and bright orange basidiomata, a monomitic hyphal system with simple septa generative hyphae, usually 4-septate basidiospores; Ceraceomycesrhizomorphus is characterized by the cream to yellowish basidiomata with rhizomorphs, cylindrical basidiospores; Leptosporomyceslinzhiensis is characterized by white with pink basidiomata, cylindrical to oblong ellipsoid basidiospores; Ramariaxizangensis is characterized by flesh pink basidiomata, branched dichotomously in 4-5 ranks, a monomitic hyphal system with clamped generative hyphae, ellipsoid to cylindrical and densely warted basidiospores.

3.
Chemistry ; : e202402264, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38981862

RESUMO

Modular synthesis can combine different functional module to flexibly regulate comprehensive properties and study the diversity of compounds. This study established a modular bicyclic synthesis strategy of combining polynitro energetic module with iodine-containing biocidal module. Compounds 1-6 with high iodine content (48.72-69.56%) and high thermal stability (Td: 172-304 ˚C) were synthesized and exhaustively identified. By modular synthesis, the detonation properties and gas-production of 3-6 improved greatly expanding their biocidal efficacy and maintained the iodine atomic utilization of iodine-containing module. Notably, 4,5-diiodo-3,4',5'-trinitro-1,3'-bipyrazole (5) and 3,5-diiodo-4,4',5'-trinitro-1,3'-bipyrazole (6) exhibit high detonation velocities (D: 5903 m s-1, 5769 m s-1, respectively) and highest gas production of 212.85 L mol-1 and 217.66 L mol-1 after decomposition. This study diversifies polyiodio-nitro compounds, and also inspire the implementation of similar synthesis strategies to provide family-level synthetic solutions to energetic biocidal materials.

4.
J Biopharm Stat ; : 1-10, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39001557

RESUMO

In this paper, we propose a new Bayesian adaptive design, score-goldilocks design, which has the same algorithmic idea as goldilocks design. The score-goldilocks design leads to a uniform formula for calculating the probability of trial success for different endpoint trials by using the normal approximation. The simulation results show that the score-goldilocks design is not only very similar to the goldilocks design in terms of operating characteristics such as type 1 error, power, average sample size, probability of stop for futility, and probability of early stop for success, but also greatly saves the calculation time and improves the operation efficiency.

5.
Nat Commun ; 15(1): 5987, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39013913

RESUMO

Ethylene regulates plant growth, development, and stress adaptation. However, the early signaling events following ethylene perception, particularly in the regulation of ethylene receptor/CTRs (CONSTITUTIVE TRIPLE RESPONSE) complex, remains less understood. Here, utilizing the rapid phospho-shift of rice OsCTR2 in response to ethylene as a sensitive readout for signal activation, we revealed that MHZ3, previously identified as a stabilizer of ETHYLENE INSENSITIVE 2 (OsEIN2), is crucial for maintaining OsCTR2 phosphorylation. Genetically, both functional MHZ3 and ethylene receptors prove essential for OsCTR2 phosphorylation. MHZ3 physically interacts with both subfamily I and II ethylene receptors, e.g., OsERS2 and OsETR2 respectively, stabilizing their association with OsCTR2 and thereby maintaining OsCTR2 activity. Ethylene treatment disrupts the interactions within the protein complex MHZ3/receptors/OsCTR2, reducing OsCTR2 phosphorylation and initiating downstream signaling. Our study unveils the dual role of MHZ3 in fine-tuning ethylene signaling activation, providing insights into the initial stages of the ethylene signaling cascade.


Assuntos
Etilenos , Regulação da Expressão Gênica de Plantas , Oryza , Proteínas de Plantas , Receptores de Superfície Celular , Transdução de Sinais , Oryza/metabolismo , Oryza/genética , Etilenos/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fosforilação , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética , Plantas Geneticamente Modificadas , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética
6.
Environ Res ; 260: 119630, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019137

RESUMO

Although many studies have discussed the impact of Europe's air quality, very limited research focused on the detailed phenomenology of ambient trace elements (TEs) in PM10 in urban atmosphere. This study compiled long-term (2013-2022) measurements of speciation of ambient urban PM10 from 55 sites of 7 countries (Switzerland, Spain, France, Greece, Italy, Portugal, UK), aiming to elucidate the phenomenology of 20 TEs in PM10 in urban Europe. The monitoring sites comprised urban background (UB, n = 26), traffic (TR, n = 10), industrial (IN, n = 5), suburban background (SUB, n = 7), and rural background (RB, n = 7) types. The sampling campaigns were conducted using standardized protocols to ensure data comparability. In each country, PM10 samples were collected over a fixed period using high-volume air samplers. The analysis encompassed the spatio-temporal distribution of TEs, and relationships between TEs at each site. Results indicated an annual average for the sum of 20 TEs of 90 ± 65 ng/m3, with TR and IN sites exhibiting the highest concentrations (130 ± 66 and 131 ± 80 ng/m3, respectively). Seasonal variability in TEs concentrations, influenced by emission sources and meteorology, revealed significant differences (p < 0.05) across all monitoring sites. Estimation of TE concentrations highlighted distinct ratios between non-carcinogenic and carcinogenic metals, with Zn (40 ± 49 ng/m3), Ti (21 ± 29 ng/m3), and Cu (23 ± 35 ng/m3) dominating non-carcinogenic TEs, while Cr (5 ± 7 ng/m3), and Ni (2 ± 6 ng/m3) were prominent among carcinogenic ones. Correlations between TEs across diverse locations and seasons varied, in agreement with differences in emission sources and meteorological conditions. This study provides valuable insights into TEs in pan-European urban atmosphere, contributing to a comprehensive dataset for future environmental protection policies.

7.
Org Lett ; 26(26): 5488-5492, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38900414

RESUMO

Exploiting novel fused cyclic frameworks through simple and efficient methods has provided a blueprint for developing advanced explosives. In this study, six new [5,6,5]-tricyclic fused energetic compounds (I-VI) were synthesized through an intramolecular cyclization strategy involving a C-NH2 directed cyclization reaction. The work not only boosts the development of fused cyclic energetic compounds but also highlights their potential applications as secondary or heat-resistant explosives.

8.
J Nanobiotechnology ; 22(1): 375, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926721

RESUMO

As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu2+, 3,3'-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O2 production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer.


Assuntos
Carcinoma Hepatocelular , Cobre , Neoplasias Hepáticas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Cobre/química , Cobre/farmacologia , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Fotoquimioterapia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/química , Porfirinas/química , Porfirinas/farmacologia , Clorofilídeos , Glutationa/metabolismo , Nanopartículas/química , Catálise , Nanopartículas Metálicas/química , Liberação Controlada de Fármacos , Camundongos Nus , Antineoplásicos/farmacologia , Antineoplásicos/química
9.
World Neurosurg ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38871287

RESUMO

OBJECTIVE: Hydrocephalus, a major complication in tuberculous meningitis (TBM) patients, often necessitates treatment via ventriculoperitoneal shunt (VPS). However, post-VPS, some patients develop a complication called contralateral isolated lateral ventricle (CILV), leading to persistent hydrocephalus symptoms. This study aims to evaluate cerebrospinal fluid (CSF) parameters in predicting CILV occurrence post-VPS in adult TBM patients. METHODS: A retrospective analysis was conducted, focusing on the relationship between preoperative CSF parameters and the development of CILV in 40 adult TBM patients who underwent VPS. The study compared CSF parameters from lumbar puncture after admission with those from ventricular CSF post-external ventricular drainage tube insertion. RESULTS: CILV was observed in 6 of the 40 patients following VPS. Statistical analysis showed no significant difference between the CSF parameters obtained via lumbar and ventricular punctures. Notably, the mean CSF glucose level in patients with CILV was significantly lower (1.92 mmol/L) compared to the non-CILV group (3.03 mmol/L). Conversely, the median adenosine deaminase (ADA) level in the CILV group was higher (5.69 U/L) compared to the non-CILV group (3.18 U/L). The optimal cutoff values for CSF glucose and ADA levels were 1.90 mmol/L and 4.80 U/L, respectively, with a sensitivity of 66.67% and 83.33% and a specificity of 88.24% and 79.41%. CONCLUSIONS: The study identified elevated ADA levels and decreased glucose levels in CSF as potential risk factors for CILV development in adult TBM patients post-VPS. These findings suggest the necessity for more tailored surgical approaches, in patients with altered CSF parameters to mitigate the risk of CILV.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38944196

RESUMO

BACKGROUND: Oral immunotherapy (OIT) has emerged as the most popular therapy for food allergy. However, data on the long-term adherence and efficacy of this approach are sparse. OBJECTIVE: We aimed to assess the long-term adherence rates to OIT protocol and the associated risk of allergic reactions. METHODS: Patients who completed milk OIT and reached a maintenance dose of 200 mL of milk were surveyed biannually on their dairy consumption and occurrence of allergic reactions. A survival analysis was performed to evaluate the association between the risk of reaction and the adherence to OIT maintenance protocol. RESULTS: The cohort consisted of 50 patients. Only 56% of the cohort adhered to the protocol, which consisted of ingesting a minimum of 200 mL of milk at least 3 times per week. Adherent patients had a significantly reduced risk of allergic reactions as well as a reduced incidence of anaphylaxis, health care/emergency room visits, and epinephrine/antihistamine administration. CONCLUSIONS: The findings demonstrate the importance of consistent maintenance dose consumption in the management of food allergies, with regular milk consumption contributing to the maintenance of unresponsiveness and decreased risk of allergic symptoms.

11.
Environ Geochem Health ; 46(7): 243, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850467

RESUMO

Soil contamination by petroleum, including crude oil from various sources, is increasingly becoming a pressing global environmental concern, necessitating the exploration of innovative and sustainable remediation strategies. The present field-scale study developed a simple, cost-effective microbial remediation process for treating petroleum-contaminated soil. The soil treatment involves adding microbial activators to stimulate indigenous petroleum-degrading microorganisms, thereby enhancing the total petroleum hydrocarbons (TPH) degradation rate. The formulated microbial activator provided a growth-enhancing complex of nitrogen and phosphorus, trace elements, growth factors, biosurfactants, and soil pH regulators. The field trials, involving two 500 m3 soil samples with the initial TPH content of 5.01% and 2.15%, were reduced to 0.41% and 0.02% in 50 days, respectively, reaching the national standard for cultivated land category II. The treatment period was notably shorter than the commonly used composting and bioaugmentation methods (typically from 8 to 12 weeks). The results indicated that the activator could stimulate the functional microorganisms in the soil and reduce the phytotoxicity of the contaminated soil. After 40 days of treatment, the germination rate of rye seeds increased from 20 to 90%, indicating that the microbial activator could be effectively used for rapid on-site remediation of oil-contaminated soils.


Assuntos
Biodegradação Ambiental , Petróleo , Microbiologia do Solo , Poluentes do Solo , Poluentes do Solo/metabolismo , Projetos Piloto , Hidrocarbonetos/metabolismo , Poluição por Petróleo , Solo/química , Recuperação e Remediação Ambiental/métodos , Germinação/efeitos dos fármacos , Bactérias/metabolismo , Nitrogênio/metabolismo
12.
Front Public Health ; 12: 1370282, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38841678

RESUMO

Introduction: The burden of colorectal cancer (CRC) plays a pivotal role in the global cancer epidemic. Our study reported the incidence trends in CRC and the associated effects of age, period, and birth cohort in 204 countries and territories over the past 30 years. Methods: The incidence data of CRC were extracted from the Global Burden of Disease Study (GBD) 2019. We performed the age-period-cohort (APC) model to estimate the overall annual percentage change (net drift) in the incidence rate, the annual percentage change by age group (local drift), and the relative risk (period and cohort effects) of the period and cohort in CRC during 1990-2019. This approach allows examining and distinguishing age, period, and cohort effects in incidence and potentially distinguishing colorectal cancer gaps in prevention and screening. Results: In 2019, the incidence of CRC was 2.17 (95% UI 2.00-2.34) million, of which China, the United States of America, and Japan had the highest incidence population, accounting for 45.9% of the global population. The age-standardized incidence rate (ASIR) was 26.7 (95% UI 28.9-24.6) per 100,000 people, of which 30 countries had an incidence rate greater than 40.0 per 100,000 people. From 1990 to 2019, the middle SDI region had the largest increase in incidence rate, with a net drift of 2.33% (95% CI 2.2-2.46%, p < 0.001). Globally, the incidence population was concentrated in the age group of 50-69 years, and the age group of 30-34 years had the largest increase in incidence rate (local drift 1.19% (95% CI 1.01-1.37%)). At the same time, the sex and age distributions of CRC incidence had significant heterogeneity across regions and countries. In the past 30 years, the incidence rate in 31 countries has been well controlled (net drift <0), and most of them were concentrated in high-and high-middle-SDI regions, such as Australia, Czechia, and Belgium, and the relative risk of incidence generally improved over time and consecutive young birth cohorts. CRC incidence showed an unfavorable trend (net drift ≥1%) in 89 countries, of which 27 countries were more significant (net drift >2%), mostly concentrated in the middle SDI region, such as China, Mexico, and Brazil, and the risk of period and birth cohort was unfavorable. Conclusion: Globally, the incidence of CRC has shown an overall upward trend over the past 30 years, with the exception of some countries with higher SDI values. Significant age-period-cohort differences were observed in the risk of incidence in CRC worldwide. Effective prevention and control policies need to take into account the age-period-cohort effect characteristics of different regions.


Assuntos
Neoplasias Colorretais , Carga Global da Doença , Humanos , Neoplasias Colorretais/epidemiologia , Incidência , Pessoa de Meia-Idade , Masculino , Idoso , Feminino , Adulto , Estudos de Coortes , Saúde Global/estatística & dados numéricos , Idoso de 80 Anos ou mais , Fatores Etários , Adulto Jovem
13.
Carbohydr Polym ; 339: 122260, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823924

RESUMO

A deep eutectic solvent (DES) formulated with tetramethylammonium hydroxide pentahydrate /urea (TMAH·5H2O/Urea) was designed for the first time to dissolve cellulose at room temperature. The optimized system, characterized by a 1:3 M ratio, demonstrates the capability to dissolve approximately 7.5 wt% cellulose, boasting a high degree of polymerization (DP = 526). Notably, both the pure DES and 4.0 wt% cellulose/TMAH·5H2O/Urea mixtures manifests low viscosity, establishing its potential as an effective spinning aid in fiber manufacturing. The structural analyses shows that the cellulose crystal type shifts from type I to type II form, accompanied by a reduction in both crystallinity and DP. A pivotal aspect of this research involves determining Kamlet-Taft parameters for TMAH·5H2O/Urea-DES with different molar ratios. The results reveal these solvate DESs exhibit the high hydrogen bond basicity, which enables them to easily form hydrogen bonds with hydroxyl groups of cellulose and demonstrate good cellulose solubility. In conclusion, this solvent system presents notable advantages, including straightforward synthesis procedures, low viscosity, and well cellulose solubility, paving the way for new approaches and techniques in cellulose utilization.

14.
Heart Lung Circ ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38925995

RESUMO

AIM: Admission systolic blood pressure is a significant predictor of in-hospital mortality in patients with acute type A aortic dissection (ATAAD). While previous studies have focussed on recording the highest blood pressure value from both arms, this study aimed to evaluate the associations between blood pressure in bilateral arms and in-hospital mortality. METHODS: Data were analysed from 262 patients with ATAAD treated at a single centre. The relationship between bilateral arm blood pressure upon admission and in-hospital mortality was assessed in a logistic regression model. To comprehensively evaluate potential non-linear relationships, the association between admission bilateral systolic blood pressure (SBP) and the risk of in-hospital mortality was analysed using restricted cubic splines on a continuous scale. RESULTS: Mean age was 53.6±12.5 years and 194 (74.0%) were male. Baseline and operative data showed that ages, body mass index, smoking, left-arm SBP, left-arm diastolic blood pressure (DBP), right-arm SBP, right-arm DBP, syncope, cerebral/cardiac ischaemia, retrograde brain perfusion, Bentall procedure, coronary artery bypass grafting, and aortic valve replacement significantly differed among the left-arm SBP tertiles. In-hospital mortality was 17.6% (46 of 262). Restricted cubic splines demonstrated that the relationship between presenting left-arm SBP and in-hospital mortality followed a U-shaped curve, whereas non-linearity was not detected in the right arm. CONCLUSION: This study found a U-shaped association between admission left-arm SBP and in-hospital mortality in ATAAD surgery patients, whereas a non-linearity relationship was not detected for right-arm SBP. Low left-arm SBP independently correlated with increased in-hospital mortality, underscoring the significance of bilateral blood pressure differences in ATAAD prognosis.

16.
An Sist Sanit Navar ; 47(2)2024 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-38817086

RESUMO

BACKGROUND: This study aimed to assess the effectiveness of high-risk human papillomavirus (HR-HPV) primary testing for cervical cancer screening in China's rural areas. METHODS: Women aged 21-64 years were recruited. Cervical cytology was diagnosed following the Bethesda 2001 classification system, HPV infection (HR-HPV, HPV-16, HPV-18, and other 12 genotypes) identified by Cobas-4800, and colposcopy and biopsy performed when required. Primary outcomes were defined as the cumulative incidence of cervical intraepithelial neoplasia grade 2/3/higher (CIN2/3+) and its relative risk at baseline and at the 36-month follow-up. RESULTS: The study included 9,218 women; mean age was 45.15 years (SD: 8.74); 81% completed the follow-up. The most frequent type of cytological lesions (12.4% ) were ASCUS (8.4%) and LSIL (2.2%). HR-HPV infection (16.3%) was more prevalent in HPV-16 than in HPV-18 (3 vs 1.5%); a positive relationship with the severity of the lesions, from 29.8% in ASCUS to 89.6% in HSIL was found. At baseline, 3.5% of the patients underwent colposcopy; 20% had a positive diagnosis. At the 36-month follow-up, the cumulative incidences of CIN2+ and CIN3+ were higher in women with HR-HPV infection (16.9 vs 0.5% and 8.2 vs 0.2%). The relative risk of CIN2/3+ was lower in HR-HPV-negative women compared to those with a negative cytology at baseline (0.4; 95%CI: 0.3-0.4). CONCLUSIONS: High-risk HPV-based screening may significantly reduce the risk of CIN2/3+ compared with cytology testing. This may be a new resource for public health demands in China's rural areas.


Assuntos
Detecção Precoce de Câncer , Genótipo , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Adulto , Pessoa de Meia-Idade , China/epidemiologia , Detecção Precoce de Câncer/métodos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Adulto Jovem , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologia , Estudos de Coortes , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Saúde da População Rural , Colposcopia , População Rural , Papillomavirus Humano
17.
Angew Chem Int Ed Engl ; 63(29): e202404142, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38715431

RESUMO

Fluorescent imaging and biosensing in the near-infrared-II (NIR-II) window holds great promise for non-invasive, radiation-free, and rapid-response clinical diagnosis. However, it's still challenging to develop bright NIR-II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR-II aggregation-induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR-II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6-fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal-to-background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal-to-noise ratio 1.9-fold higher than the TEH counterpart in detecting low-concentration antigens. This work highlights the potential for developing bright NIR-II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research.


Assuntos
Corantes Fluorescentes , Raios Infravermelhos , Imagem Óptica , Eletricidade Estática , Corantes Fluorescentes/química , Humanos , Nanopartículas/química , Tiofenos/química , Animais , Camundongos , Estrutura Molecular
18.
Angew Chem Int Ed Engl ; 63(30): e202401683, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38719735

RESUMO

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency. Benefiting from the favorable host matrix and the luminescence-protective effect of core-shell engineering, NaGdF4 : 15 %Eu@NaLuF4 nanoparticle scintillators with tailored structures emerged as the top candidates. Living imaging experiments based on optimal LnNP scintillators validated the feasibility of laser-free continuous RL activated by clinical radiopharmaceuticals for tumor multiplex visualization. This research provides unprecedented insights into the rational design of LnNP scintillators, which would enable efficient energy conversion from Cerenkov luminescence, γ-radiation, and ß-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics.

19.
J Med Virol ; 96(6): e29716, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38818787

RESUMO

Accumulating evidence has demonstrated that high-risk human papillomaviruses (HR-HPVs) are involved in the etiology of a subset of oropharyngeal squamous cell carcinoma (OPSCC). In this regard, the International Agency for Research on Cancer (IARC) has recommended direct molecular HPV testing. So far, there is no agreement on the most appropriate method for HPV detection on OPSCC formalin-fixed paraffin-embedded (FFPE) materials. In this study, we aimed to evaluate the performance of the high-sensitive SureX HPV assay in OPSCC FFPE tissues compared with LiPA-25 and p16ink4a immunostaining. A retrospective series of FFPE primary OPSCC cases were diagnosed between 2008 and 2019 and provided by the Henan Cancer Hospital, China. The level of agreement of two assays was determined using Cohen's Kappa (κ) statistics. A total of 230 FFPE OPSCC samples from tumor resections (n = 160) and diagnostic biopsies (n = 70) were detected. Sixty-six (28.7%) and 70 (30.4%) samples were identified as HPV-DNA-positive by LiPA-25 and SureX, respectively, of which HPV16 was largely the most common type (95.5% vs 94.3%). We found a perfect concordance between LiPA-25 and SureX for HPV-DNA status (κ = 0.906, 95% CI: 0.875-0.937) and for HPV16 (κ = 0.925, 95% CI: 0.897-0.953). In addition, SureX and p16ink4a immunostaining had a perfect concordance (κ = 0.917, 95% CI: 0.888-0.946). Moreover, the HPV-driven fraction, based on double positivity for HPV-DNA and p16ink4a, was similar between SureX (63 of 230, 27.4%) and LiPA-25 (60 of 230, 26.1%). Similar results were found in samples from resections and biopsies. SureX and LiPA-25 are comparable. SureX could be used for routine HPV-DNA detection and genotyping on archival OPSCC FFPE tissues.


Assuntos
DNA Viral , Genótipo , Proteínas Oncogênicas Virais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Inclusão em Parafina , Humanos , Neoplasias Orofaríngeas/virologia , Estudos Retrospectivos , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Pessoa de Meia-Idade , Masculino , Feminino , Proteínas Oncogênicas Virais/genética , Idoso , DNA Viral/genética , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Papillomaviridae/classificação , Reação em Cadeia da Polimerase/métodos , Técnicas de Genotipagem/métodos , China , Adulto , Formaldeído , Papillomavirus Humano
20.
Sensors (Basel) ; 24(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38793855

RESUMO

Recently, due to physical aging, diseases, accidents, and other factors, the population with lower limb disabilities has been increasing, and there is consequently a growing demand for wheelchair products. Modern product design tends to be more intelligent and multi-functional than in the past, with the popularization of intelligent concepts. This supports the design of a new, fully functional, intelligent wheelchair that can assist people with lower limb disabilities in their day-to-day life. Based on the UCD (user-centered design) concept, this study focused on the needs of people with lower limb disabilities. Accordingly, the demand for different functions of intelligent wheelchair products was studied through a questionnaire survey, interview survey, literature review, expert consultation, etc., and the function and appearance of the intelligent wheelchair were then defined. A brain-machine interface system was developed for controlling the motion of the intelligent wheelchair, catering to the needs of disabled individuals. Furthermore, ergonomics theory was used as a guide to determine the size of the intelligent wheelchair seat, and eventually, a new intelligent wheelchair with the features of climbing stairs, posture adjustment, seat elevation, easy interaction, etc., was developed. This paper provides a reference for the design upgrade of the subsequently developed intelligent wheelchair products.


Assuntos
Interfaces Cérebro-Computador , Estudos de Viabilidade , Cadeiras de Rodas , Humanos , Pessoas com Deficiência , Desenho de Equipamento , Ergonomia/métodos , Design Centrado no Usuário , Inquéritos e Questionários
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