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1.
Front Public Health ; 12: 1383308, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39040867

RESUMO

Background: With the increasing demand for joint replacement surgery in China, the government has successively issued the policies of national centralized procurement (NCP) and national volume-based procurement (NVBP) of artificial joints. The purpose of this study is to evaluate the impact of NCP and NVBP policies on hospitalization cost, rehospitalization and reoperation rate of total hip arthroplasty (THA). Methods: In total, 347 patients who underwent THA from January 2019 to September 2022 were retrospectively analyzed. According to the implementation of NCP and NVBP, patients were divided into three groups: control group (n = 147), NCP group (n = 130), and NVBP group (n = 70). Patient-level data on the total hospitalization costs, rehospitalization rate, THA reoperation rate and inpatient component costs were collected before and after the implementation of the policies and Consumer Price Index was used to standardize the cost. Results: After the implementation of NCP and NVBP, the total cost of hospitalization decreased by $817.41 and $3950.60 (p < 0.01), respectively. The implantation costs decreased from $5264.29 to $4185.53 and then rapidly to $1143.49 (p < 0.01), contributing to increased total cost savings. However, the cost of surgery and rehabilitation increased after NCP and NVBP implementation (p < 0.01). The proportion of implants decreased from 66.76 to 59.22% and then to 29.07%, whereas that of drugs increased from 7.98 to 10.11% and then to 12.06%. The proportion of operating expenses rose from 4.86 to 8.01% and then to 18.47%. Univariate linear regression analysis showed that hospital stay, NCP and NVBP were correlated with total hospitalization cost (p < 0.01). Multivariate analysis showed that hospital stay, NCP and NVBP were independent predictors of total hospitalization cost (p < 0.01). Conclusion: In this study, hospital stay, NCP, and NVBP were independent predictors of total inpatient costs. After the implementation of NVBP policy, the cost of implants and hospitalization has decreased significantly, and the technical labor value of medical staff has increased, but a multifaceted method is still needed to solve the problem of increasing costs of other consumables. Limitations of the study suggest the need for further and more comprehensive evaluation in the future.


Assuntos
Artroplastia de Quadril , Hospitalização , Humanos , Artroplastia de Quadril/economia , Artroplastia de Quadril/estatística & dados numéricos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , China , Idoso , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Custos Hospitalares/estatística & dados numéricos , Adulto , Reoperação/estatística & dados numéricos , Reoperação/economia , Readmissão do Paciente/estatística & dados numéricos , Readmissão do Paciente/economia
2.
Opt Lett ; 49(11): 3206-3209, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824364

RESUMO

In this work, we developed off-plane quartz-enhanced photoacoustic spectroscopy (OP-QEPAS). In the OP-QEPAS the light beam went neither through the prong spacing of the quartz tuning fork (QTF) nor in the QTF plane. The light beam is in parallel with the QTF with an optimal distance, resulting in low background noise. A radial-cavity (RC) resonator was coupled with the QTF to enhance the photoacoustic signal by the radial resonance mode. By offsetting both the QTF and the laser position from the central axis, we enhance the effect of the acoustic radial resonance and prevent the noise generated by direct laser irradiation of the QTF. Compared to IP-QEPAS based on a bare QTF, the developed OP-QEPAS with a RC resonator showed a >10× signal-to-noise ratio (SNR) enhancement. The OP-QEPAS system has great advantages in the use of light emitting devices (LEDs), long-wavelength laser sources such as mid-infrared quantum cascade lasers, and terahertz sources. When employing a LED as the excitation source, the noise level was suppressed by ∼2 orders of magnitude. Furthermore, the radial and longitudinal resonance modes can be combined to further improve the sensor performance.

3.
Small ; : e2401214, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884200

RESUMO

Nowadays, capacitive deionization (CDI) has emerged as a prominent technology in the desalination field, typically utilizing porous carbons as electrodes. However, the precise significance of electrode properties and operational conditions in shaping desalination performance remains blurry, necessitating numerous time-consuming and resource-intensive CDI experiments. Machine learning (ML) presents an emerging solution, offering the prospect of predicting CDI performance with minimal investment in electrode material synthesis and testing. Herein, four ML models are used for predicting the CDI performance of porous carbons. Among them, the gradient boosting model delivers the best performance on test set with low root mean square error values of 2.13 mg g-1 and 0.073 mg g-1 min-1 for predicting desalination capacity and rate, respectively. Furthermore, SHapley Additive exPlanations is introduced to analyze the significance of electrode properties and operational conditions. It highlights that electrolyte concentration and specific surface area exert a substantially more influential role in determining desalination performance compared to other features. Ultimately, experimental validation employing metal-organic frameworks-derived porous carbons and biomass-derived porous carbons as CDI electrodes is conducted to affirm the prediction accuracy of ML models. This study pioneers ML techniques for predicting CDI performance, offering a compelling strategy for advancing CDI technology.

4.
Nature ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866052

RESUMO

Increasing planting density is a key strategy to enhance maize yields1-3. An ideotype for dense planting requires a 'smart canopy' with leaf angles at different canopy layers differentially optimized to maximize light interception and photosynthesis4-6, amongst other features. Here, we identified leaf angle architecture of smart canopy 1 (lac1), a natural mutant possessing upright upper leaves, less erect middle leaves and relatively flat lower leaves. lac1 has improved photosynthetic capacity and weakened shade-avoidance responses under dense planting. lac1 encodes a brassinosteroid C-22 hydroxylase that predominantly regulates upper leaf angle. Phytochrome A photoreceptors accumulate in shade and interact with the transcription factor RAVL1 to promote its degradation via the 26S proteasome, thereby attenuating RAVL1 activation of lac1 and reducing brassinosteroid levels. This ultimately decreases upper leaf angle in dense fields. Large-scale field trials demonstrate lac1 boosts maize yields under high densities. To quickly introduce lac1 into breeding germplasm, we transformed a haploid inducer and recovered homozygous lac1 edits from 20 diverse inbred lines. The tested doubled haploids uniformly acquired smart-canopy-like plant architecture. We provide an important target and an accelerated strategy for developing high-density-tolerant cultivars, with lac1 serving as a genetic chassis for further engineering of a smart canopy in maize.

5.
Acad Radiol ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38890032

RESUMO

RATIONALE AND OBJECTIVES: The aim of this study was to ascertain whether the utilization of multiple b-value diffusion-weighted habitat imaging, a technique that depicts tumor heterogeneity, could aid in identifying breast cancer patients who would derive substantial benefit from neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: This prospective study enrolled 143 women (II-III breast cancer), who underwent multi-b-value diffusion-weighted imaging (DWI) in 3-T magnetic resonance (MR) before NAC. The patient cohort was partitioned into a training set (consisting of 100 patients, of which 36 demonstrated a pathologic complete response [pCR]) and a test set (featuring 43 patients, 16 of whom exhibited pCR). Utilizing the training set, predictive models for pCR, were constructed using different parameters: whole-tumor radiomics (ModelWH), diffusion-weighted habitat-imaging (ModelHabitats), conventional MRI features (ModelCF), along with combined models ModelHabitats+CF. The performance of these models was assessed based on the area under the receiver operating characteristic curve (AUC) and calibration slope. RESULTS: In the prediction of pCR, ModelWH, ModelHabitats, ModelCF, and ModelHabitats+CF achieved AUCs of 0.733, 0.722, 0.705, and 0.756 respectively, within the training set. These scores corresponded to AUCs of 0.625, 0.801, 0.700, and 0.824 respectively in the test set. The DeLong test revealed no significant difference between ModelWH and ModelHabitats (P = 0.182), between ModelHabitats and ModelHabitats+CF (P = 0.113). CONCLUSION: The habitat model we developed, incorporating first-order features along with conventional MRI features, has demonstrated accurate predication of pCR prior to NAC. This model holds the potential to augment decision-making processes in personalized treatment strategies for breast cancer.

6.
J Dairy Sci ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908696

RESUMO

Due to its beneficial effects on human health, Bifidobacterium is commonly added to milk powder. Accurate quantification of viable Bifidobacterium is essential for assessing the therapeutic efficacy of milk powder. In this study, we introduced a novel propidium monoazide (PMA) - antibiotic fluorescence in situ hybridization (AFISH) - flow cytometry (FCM) method to rapidly and accurately quantify viable Bifidobacterium cells in milk powder. Briefly, Bifidobacterium cells were treated with chloramphenicol (CM) to increase their rRNA content, followed by staining with RNA-binding oligonucleotide probes, based on the AFISH technique. Then, the DNA-binding dye PMA was used to differentiate between viable and non-viable cells. The PMA-AFISH-FCM method, including sample pretreatment, CM treatment, dual staining, and FCM analysis, required around 2 h and was found to be better than the current methods. This is the first study to implement FCM combined with PMA and oligonucleotide probe for detecting Bifidobacterium.

7.
Int J Biol Macromol ; 273(Pt 1): 133044, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38862059

RESUMO

Membrane separation technology has emerged as a powerful tool to separate organic dyes from industrial wastewater. However, continuously selective separation of organic dyes with similar molecular weight remains challenging. Herein, we presented a pH-triggered membrane composed of polydopamine-decorated tunicate-derived cellulose nanofibers (PDA@TCNFs) for selective separation of organic dyes. Such self-supporting membranes with nanoporous structure were fabricated by facile vacuum-assisted filtration of PDA@TCNF suspension. The incorporation of polydopamine not only enhanced the stability of the membranes, but also endowed membranes with excellent pH sensitivity, facilitating the continuously selective separation of organic dyes. These pH-triggered PDA@TCNF membranes could selectively separate Methyl Orange (MO) and Rhodamine B (RB) from the MO/RB mixed solution by switching the pH values. The continuously selective separation of the MO/RB mixed solution was demonstrated, where both MO and RB recovery ratios maintained at ∼99 % during 50 repeated cycles. This work provides a new strategy to develop a pH-triggered sustainable nanocellulose-based membrane for continuously selective separation of mixed dyes.


Assuntos
Celulose , Corantes , Indóis , Membranas Artificiais , Polímeros , Celulose/química , Indóis/química , Concentração de Íons de Hidrogênio , Polímeros/química , Corantes/química , Corantes/isolamento & purificação , Nanofibras/química , Rodaminas/química , Compostos Azo/química , Compostos Azo/isolamento & purificação
8.
Hum Pathol ; 149: 1-9, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38782102

RESUMO

There is no universally accepted method for evaluating lymph node metastasis (LNM) in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. Different protocols recommend evaluating the percentage of residual viable tumor (RVT%) and metastatic tumor size (MTS). Our aim was to determine the prognostic significance of RVT% and MTS, and identify the more effective parameter for pathological evaluating LNM. Two independent cohorts were collected (derivation, n = 84; external validation, n = 42). All patients exhibited metastatic cancer or treatment response in lymph nodes post-surgery. In the derivation cohort, we assessed the mean and largest values of MTS and RVT% in LNM, estimating their optimal cutoffs for event-free survival (EFS) using maximally selected rank statistics. Validation was subsequently conducted in the external validation cohort. The quality of prognostic factors was evaluated using the Area Under Curve (AUC). A positive association was identified between RVT% and MTS, but an absolute association could not be conclusively established. In the derivation cohort, neither the largest MTS (cutoff = 6 mm, p = 0.28), largest RVT% (cutoff = 75%, p = 0.23), nor mean RVT% (cutoff = 55%, p = 0.06) were associated with EFS. However, mean MTS (cutoff = 4.5 mm) in lymph nodes was statistically associated with EFS (p = 0.018), validated by the external cohort (p = 0.017). The prognostic value of MTS exceeded that of ypN staging in both cohorts, as evidenced by higher AUC values. The mean value of MTS can effectively serve as a parameter for the pathological evaluation of lymph nodes, with a threshold of 4.5 mm, closely linked to EFS. Its prognostic value outperforms that of ypN staging.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfonodos , Metástase Linfática , Terapia Neoadjuvante , Neoplasia Residual , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/imunologia , Masculino , Feminino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Idoso , Linfonodos/patologia , Adulto , Imunoterapia/métodos , Estudos Retrospectivos , Prognóstico , Quimioterapia Adjuvante , Resultado do Tratamento , Carga Tumoral
9.
Discov Oncol ; 15(1): 169, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753185

RESUMO

OBJECTIVES: The objective of this study was to evaluate the influence of marital status on overall survival (OS) and develop a nomogram for predicting 5-year OS in chondrosarcoma (CHS) patients. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify CHS patients diagnosed between 2010 and 2018. Survival rates were calculated using Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analyses. An independent cohort was used for external validation of the nomogram. Performance evaluation of the nomogram was conducted using Harrell's concordance index (C-index), calibration plot, and decision curve analysis (DCA). RESULTS: In the SEER cohort, Kaplan-Meier analysis showed significant differences in OS among CHS patients with different marital statuses (P < 0.001), with widowed patients having the lowest OS. In terms of gender, there were significant survival differences based on marital status in females (P < 0.001), but not in males (P = 0.067). The OS of married and single females is significantly higher than that of married (P < 0.001) and single male (P = 0.006), respectively. Kaplan-Meier curves showed no significant difference in OS between groups stratified by either gender or marital status in the external cohort. Univariate and multivariate analyses confirmed that age at diagnosis, gender, marital status, tumor size, histological type, tumor grade, SEER stage, and surgery were independent prognostic factors for OS. The nomogram demonstrated high internal and external validation C-indexes of 0.818 and 0.88, respectively. Calibration plots, DCA curve, and Kaplan-Meier curve (P < 0.001) confirmed the excellent performance and clinical utility of the nomogram. CONCLUSIONS: Marital status was an independent factor influencing OS in CHS patients, with widowed patients having the worst prognosis. The OS of both married and single females is significantly higher than that of their male counterparts. However, these findings require further validation in a large independent cohort. While the contribution of marital status on predicting OS appears modest, our nomogram accurately predicted 5-year OS and identified high-risk groups, providing a valuable tool for clinical decision-making.

10.
Br J Dev Psychol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747465

RESUMO

This study examined the development of social power perceptions among Chinese children aged 3-5 years (N = 105). After watching videos about various social power cues, such as resource possession, resource control, goal achievement, permission, giving orders, setting norms and popularity, the children were asked to identify the powerful agents (whom do you believe is the more powerful person?) in the videos and provide explanations (why do you think he (she) is a powerful person?). Three-year-olds can recognize powerful agents who can grant 'permission' to other agents. By the age of 4, children begin to associate 'popularity', 'resource possession' and 'goal achievement' with social power. Five-year olds demonstrated the ability to recognize agents who control resources as being more powerful. Analysis of the reasons the children provided for their judgements revealed that for almost every cue (except giving orders), more than 14% of the responses highlighted 'possession of material resources' as an indicator of power. For children aged 3-5 years, 'resource possession' cues may be their preferred basis for inferring and explaining power differences. These results would facilitate researchers to further unravel the mechanisms underlying the development of children's social power perceptions.

11.
Gen Comp Endocrinol ; 352: 114515, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38582177

RESUMO

Irisin, a myokine identified in 2012, has garnered research interest for its capacity to induce browning of adipocytes and improve metabolic parameters. As such, the potential therapeutic applications of this exercise-induced peptide continue to be explored. Though present across diverse animal species, sequence analysis has revealed subtle variation in the irisin protein. In this review, we consider the effects of irisin on disease states in light of its molecular evolution. We summarize current evidence for irisin's influence on pathologies and discuss how sequence changes may inform development of irisin-based therapies. Furthermore, we propose that the phylogenetic variations in irisin could potentially be leveraged as a molecular clock to elucidate evolutionary relationships.


Assuntos
Adipócitos , Fibronectinas , Animais , Fibronectinas/genética , Filogenia , Adipócitos/metabolismo , Evolução Molecular
12.
Sensors (Basel) ; 24(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38676060

RESUMO

Vibration monitoring is one of the most effective approaches for bearing fault diagnosis. Within this category of techniques, sparsity constraint-based regularization has received considerable attention for its capability to accurately extract repetitive transients from noisy vibration signals. The optimal solution of a sparse regularization problem is determined by the regularization term and the data fitting term in the cost function according to their weights, so a tradeoff between sparsity and data fidelity has to be made inevitably, which restricts conventional regularization methods from maintaining strong sparsity-promoting capability and high fitting accuracy at the same time. To address the limitation, a stepwise sparse regularization (SSR) method with an adaptive sparse dictionary is proposed. In this method, the bearing fault diagnosis is modeled as a multi-parameter optimization problem, including time indexes of the sparse dictionary and sparse coefficients. Firstly, sparsity-enhanced optimization is conducted by amplifying the regularization parameter, making the time indexes and the number of atoms adaptively converge to the moments when impulses occur and the number of impulses, respectively. Then, fidelity-enhanced optimization is carried out by removing the regularization term, thereby obtaining the high-precision reconstruction amplitudes. Simulations and experiments verify that the reconstruction accuracy of the SSR method outperforms other sparse regularization methods under most noise conditions, and thus the proposed method can provide more accurate results for bearing fault diagnosis.

13.
Cancer Lett ; 590: 216869, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38593918

RESUMO

Lysine acetyltransferase 7 (KAT7), a histone acetyltransferase, has recently been identified as an oncoprotein and has been implicated in the development of various malignancies. However, its specific role in head and neck squamous carcinoma (HNSCC) has not been fully elucidated. Our study revealed that high expression of KAT7 in HNSCC patients is associated with poor survival prognosis and silencing KAT7 inhibits the Warburg effect, leading to reduced proliferation, invasion, and metastatic potential of HNSCC. Further investigation uncovered a link between the high expression of KAT7 in HNSCC and tumor-specific glycolytic metabolism. Notably, KAT7 positively regulates Lactate dehydrogenase A (LDHA), a key enzyme in metabolism, to promote lactate production and create a conducive environment for tumor proliferation and metastasis. Additionally, KAT7 enhances LDHA activity and upregulates LDHA protein expression by acetylating the lysine 118 site of LDHA. Treatment with WM3835, a KAT7 inhibitor, effectively suppressed the growth of subcutaneously implanted HNSCC cells in mice. In conclusion, our findings suggest that KAT7 exerts pro-cancer effects in HNSCC by acetylating LDHA and may serve as a potential therapeutic target. Inhibiting KAT7 or LDHA expression holds promise as a therapeutic strategy to suppress the growth and progression of HNSCC.


Assuntos
Proliferação de Células , Neoplasias de Cabeça e Pescoço , Histona Acetiltransferases , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Animais , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Acetilação , Linhagem Celular Tumoral , Histona Acetiltransferases/metabolismo , Histona Acetiltransferases/genética , Camundongos , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/genética , Lisina Acetiltransferases/metabolismo , Lisina Acetiltransferases/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Efeito Warburg em Oncologia , Masculino , Feminino , Movimento Celular , Ensaios Antitumorais Modelo de Xenoenxerto , Invasividade Neoplásica , Isoenzimas/metabolismo , Isoenzimas/genética
14.
Neural Netw ; 175: 106320, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38640696

RESUMO

The rhythm of bonafide speech is often difficult to replicate, which causes that the fundamental frequency (F0) of synthetic speech is significantly different from that of real speech. It is expected that the F0 feature contains the discriminative information for the fake speech detection (FSD) task. In this paper, we propose a novel F0 subband for FSD. In addition, to effectively model the F0 subband so as to improve the performance of FSD, the spatial reconstructed local attention Res2Net (SR-LA Res2Net) is proposed. Specifically, Res2Net is used as a backbone network to obtain multiscale information, and enhanced with a spatial reconstruction mechanism to avoid losing important information when the channel group is constantly superimposed. In addition, local attention is designed to make the model focus on the local information of the F0 subband. Experimental results on the ASVspoof 2019 LA dataset show that our proposed method obtains an equal error rate (EER) of 0.47% and a minimum tandem detection cost function (min t-DCF) of 0.0159, achieving the state-of-the-art performance among all of the single systems.


Assuntos
Redes Neurais de Computação , Humanos , Fala , Atenção/fisiologia , Algoritmos
15.
RSC Adv ; 14(18): 12650-12657, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38645530

RESUMO

Tin oxide used in electron transport layer (ETL) exhibits key role in transmitting electrons and blocking holes in perovskite solar cells (PSCs) device. However, crystal tin oxide nanoparticles (NPs) become necessary to form SnO2 film by method of spin-coating, resulting in possible surface defect and cracks among SnO2 NPs, corresponding to unsatisfied performance PSCs. Herein, an amorphous tin oxide thin film is creatively in situ grew onto Fluorine-doped Tin Oxide (FTO) substrate as ETL. The designed solar cell device with structure of FTO/SnO2/MAPbI3/Sprio-OMeTAD/Ag owns a champion photoelectric conversion efficiency (PCE) up to 17.64%, 76.20% of filling coefficient (FF), and 1.09 V of open-circuit voltage (Voc), in comparing with 16.43%, 64.35% and 1.05 V for control group (crystal tin oxide as ETL), respectively. Besides, the champion device keeps 83.33% of initial PCE under nitrogen (N2) condition for one month, in comparison with 76.09% for control group. This work provides a viable strategy for facile preparing amorphous tin oxide film based ETL in perovskite solar cells.

16.
Opt Express ; 32(7): 12609-12619, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571079

RESUMO

Virtual image lenses play essential roles in various optical devices and applications, including vision correction, photography, and scientific instruments. Here, we introduce an approach for creating virtual image Luneburg lenses (LL) on graphene. Remarkably, the graphene plasmonic lens (GPL) exhibits electrically tunable virtual focusing capabilities. The design principle of the tunability is based on the nonlinear relationship between surface plasmon polariton (SPP) wave mode index and chemical potential of graphene. By controlling the gate voltage of graphene, we can achieve continuous tuning of virtual focus. A ray-tracing technique is employed to determine the required gate voltages for various virtual focal lengths. The proposed GPL facilitates adjustable virtual focusing, promising advancements in highly adaptive and transformative nanophotonic devices.

17.
RSC Adv ; 14(17): 11659-11667, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38605895

RESUMO

Fluorination is one of the most effective ways to manipulate molecular packing, optical bandgap and molecular energy levels in organic semiconductor materials. In this work, different number of fluorine atoms was introduced into the acceptor moiety 2,2'-dithiophene linked 2,1,3-benzothiadiazole, utilizing the alkylthiophene modified dithieno[2,3-d:2',3'-d']benzo[1,2-b:4,5-b] (DTBDT) as the donor unit, three polymers: PDTBDT-0F-BTs, PDTBDT-2F-BTs and PDTBDT-6F-FBTs were synthesized. With the number of fluorine atoms in each repeat unit of polymers varying from 0 to 2 and then up to 6, PDTBDT-0F-BTs, PDTBDT-2F-BTs and PDTBDT-6F-FBTs exhibited gradually downshifted energy levels and improved dielectric constants (εr) from 3.4 to 4.3 to 5.8, further successively increased charge transport mobilities. As a result, the power conversion efficiency (PCE) of the bulk heterojunction organic photovoltaic devices (BHJ-OPV) from the blend films of aforementioned polymers paired with PC71BM were gradually increased from 1.69 for PDTBDT-0F-BTs to 1.89 for PDTBDT-2F-BTs and then to 5.28 for PDTBDT-6F-FBTs. The results show that the continuous insertion of fluorine atoms into the repeating units of the benzothiadiazole conjugated polymer leads to the deepening of HOMO energy level, the increase of εr and the increase of charge mobility, which improve the efficiency of charge transfer and electron collection, thus improving the photovoltaic performance of BHJ-OPV.

18.
Acta Biomater ; 179: 256-271, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38484831

RESUMO

In rheumatoid arthritis (RA), macrophages infiltrate joints, while fibroblast-like synovial cells proliferate abnormally, forming a barrier against drug delivery, which hinders effective drug delivery to joint focus. Here we firstly designed a pH-responsive size-adjustable nanoparticle, composed by methotrexate (MTX)-human serum albumin (HSA) complex coating with pH-responsive liposome (Lipo/MTX-HSA) for delivering drugs specifically to inflamed joints in acidic environments. We showed in vitro that the nanoparticles can induce mitochondrial dysfunction, promote apoptosis of fibroblast-like synoviocytes and macrophages, further reduce the secretion of inflammatory factors (TNF-α, IL-1ß, MMP-9), and regulate the inflammatory microenvironment. We also demonstrated similar effects in a rat model of arthritis, in which Lipo/MTX-HSA accumulated in arthritic joints, and at low pH, liposome phospholipid bilayer cleavage released small-sized MTX-HSA, which effectively reduced the number of fibroblast-synoviocytes and macrophages in joints, alleviated joint inflammation, and repaired bone erosion. These findings suggest that microenvironment-responsive size-adjustable nanoparticles show promise as a treatment against rheumatoid arthritis. STATEMENT OF SIGNIFICANCE: Abnormal proliferation of fibroblast synoviocytes poses a physical barrier to effective nanoparticle delivery. We designed size-adjustable nano-delivery systems by preparing liposomes with cholesterol hemisuccinate (CHEM), which were subsequently loaded with small-sized albumin nanoparticles encapsulating the cytotoxic drug MTX (MTX-HSA), termed Lipo/MTX-HSA. Upon tail vein injection, Lipo/MTX-HSA could be aggregated at the site of inflammation via the ELVIS effect in the inflamed joint microenvironment. Specifically, intracellular acidic pH-triggered dissociation of liposomes promoted the release of MTX-HSA, which was further targeted to fibroblasts or across fibroblasts to macrophages to exert anti-inflammatory effects. The results showed that liposomes with adjustable particle size achieved efficient drug delivery, penetration and retention in joint sites; the strategy exerted significant anti-inflammatory effects in the treatment of rheumatoid arthritis by inducing mitochondrial dysfunction to promote apoptosis in fibrosynoviocytes and macrophages.


Assuntos
Apoptose , Artrite Reumatoide , Fibroblastos , Lipossomos , Macrófagos , Metotrexato , Lipossomos/química , Artrite Reumatoide/patologia , Artrite Reumatoide/tratamento farmacológico , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fibroblastos/metabolismo , Animais , Concentração de Íons de Hidrogênio , Metotrexato/farmacologia , Metotrexato/química , Apoptose/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Humanos , Ratos , Ratos Sprague-Dawley , Camundongos , Tamanho da Partícula , Masculino , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/patologia , Sinoviócitos/metabolismo , Células RAW 264.7 , Albumina Sérica Humana/química , Albumina Sérica Humana/farmacologia , Nanopartículas/química
19.
Org Biomol Chem ; 22(12): 2380-2383, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38436087

RESUMO

A nickel-catalyzed acylation of vinylpyridines with CO at atmospheric pressure is reported, allowing for an expedient approach to synthesize ß-acyl pyridine derivatives with high regio- and chemoselectivity. The electron-withdrawing property of pyridine plays pivotal roles in activating the alkenyl group, thereby facilitating this carbonylative process. In addition to vinylpyridines, other alkenylheterocycles such as thiazole and quinoline were also suitable for this method.

20.
Ann Diagn Pathol ; 69: 152268, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38301396

RESUMO

BACKGROUND: Major pathological response (MPR) is proposed as a surrogate endpoint for survival in non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. However, the criteria for estimating MPR differ between the recommendations of the International Association for the Study of Lung Cancer (IASLC) and the immune-related pathologic response criterion (irPRC). IASLC's criteria focus solely on evaluating the primary tumor, while irPRC's criteria encompass both the primary tumor and lymph node metastasis. Our objective is to compare the prognostic value of different criteria for estimating MPR. METHODS: We conducted a retrospective study on a cohort of 235 patients with NSCLC after neoadjuvant chemoimmunotherapy. The survival endpoint was event-free survival (EFS). The MPR status of each patient was evaluated using both IASLC's criteria and irPRC's criteria. The prognostic value was compared using the Area Under Curve (AUC). RESULTS: The MPR rates were 63.4 % (149/235) and 57.4 % (135/235) according to IASLC's and irPRC's criteria, respectively. Inconsistent cases, characterized by MPR status according to IASLC's criteria but non-MPR status according to irPRC's criteria, constituted 6.0 % (14/235) of the overall cohort and 15.2 % (14/92) of patients with pretreatment N positive disease. Interestingly, all inconsistent patients showed no recurrence during the study period. Although both MPR statuses according to IASLC (p = 0.00039) and irPRC (p = 0.0094) were associated with improved EFS, IASLC's criteria (AUC = 0.65) were superior to irPRC's criteria (AUC = 0.62) with a higher AUC value. CONCLUSION: IASLC's criteria for estimating MPR were superior to irPRC's criteria in predicting EFS for NSCLC after neoadjuvant chemoimmunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Terapia Neoadjuvante , Estudos Retrospectivos , Imunoterapia
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