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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124763, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38963944

ABSTRACT

Our work reveals for the first time that directly calcined bismuth nitrate derivatives (BNDs) possess significant photocatalytic activity towards rhodamine B (RhB). As the calcination temperature increased, the Bi(NO3)3·5H2O powder gradually ruptured and transformed into different bismuth nitrate products and their mixtures, finally into stable α-Bi2O3 at 500 °C. Among them, BNDs-100 could achieve 100 % photocatalytic degradation of 10 mg/L RhB solution under UV irradiation for 6 min. The ImageJ-led paper microzones (PMZs) method is introduced for the first time into the performance evaluation process of photocatalysts, which can achieve the green chemistry pathway and the rapid evaluation of different catalysts. The accuracy of the results of the PMZs method relative to the spectrophotometric method was up to 91.14 %, which has a better reliability and is suitable for qualitative analysis, and a certain ability when used for quantitative analysis. The results showed that the PMZs method was used to assess the photocatalytic degradation of rhodamine B by bismuth nitrate-derived materials at different calcination temperatures with well reliability, and the preparation of BNDs by direct calcination was a simple and effective strategy.

2.
Br J Ophthalmol ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38955480

ABSTRACT

AIM: To investigate the association of floor area ratio (FAR), an indicator of built environments, and myopia onset. METHODS: This prospective cohort study recruited 136 753 children aged 6-10 years from 108 schools in Shenzhen, China at baseline (2016-2017). Refractive power was measured with non-cycloplegic autorefraction over a 2-year follow-up period. FAR was objectively evaluated using geographical information system technology. Mixed-effects logistic regression models were constructed to examine the association of FAR with a 2-year cumulative incidence of myopia among individuals without baseline myopia; multiple linear regression model, with a 2-year cumulative incidence rate of myopia at each school. RESULTS: Of 101 624 non-myopic children (56.3% boys; mean (SE) age, 7.657±1.182 years) included in the study, 26 391 (26.0%) of them developed myopia after 2 years. In the individual-level analysis adjusting for demographic, socioeconomic and greenness factors, an IQR in FAR was associated with a decreased risk of 2-year myopia incidence (OR 0.898, 95% CI 0.866 to 0.932, p<0.001). Similar findings were observed in the analysis additionally adjusted for genetic and behavioural factors (OR 0.821, 95% CI 0.766 to 0.880, p<0.001). In the school-level, an IQR increase in FAR was found to be associated with a 2.0% reduction in the 2-year incidence rate of myopia (95% CI 1.3% to 2.6%, p<0.001). CONCLUSIONS: Exposure to higher FAR was associated with a decreased myopia incidence, providing insights into myopia prevention through school built environments in China.

3.
Angew Chem Int Ed Engl ; : e202410649, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965041

ABSTRACT

Cluster aggregation states are thermodynamically favored at the subnanoscale, for which an inverse growth from nanoparticles to clusters may be realized on subnanometer supports. Herein, we develop Au-polyoxometalate-layered double hydroxide (Au-POM-LDH) sub-1 nm nanosheets (Sub-APL) based on the above strategy, where sub-1 nm Au clusters with negative valence are generated by the in-situ disintegration of Au nanoparticles on POM-LDH supports. Sub-1 nm Au clusters with ultrahigh surface atom ratios exhibit remarkable efficiency for glutathione (GSH) depletion. The closely connected sub-1 nm Au with negative valence and POM hetero-units can promote the separation of hole-electrons, resulting in the enhanced reactive oxygen species (ROS) generation under ultrasound (US). Besides, the reversible redox of Mo in POM is able to deplete GSH and trigger chemodynamic therapy (CDT) simultaneously, further enhancing the oxidative stress. Consequently, the Sub-APL present 2-fold ROS generation under US and 7-fold GSH depletion compared to the discrete Au and POM-LDH mixture. Therefore, the serious imbalance of redox in the TME caused by the sharp increase of ROS and rapid decrease of GSH leads to death of tumor ultimately.

4.
Small ; : e2404595, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38966880

ABSTRACT

Integration of inherently incompatible elements into a single sublattice, resulting in the formation of monophasic metal oxide, holds great scientific promise; it unveils that the overlooked surface entropy in subnanometer materials can thermodynamically facilitate the formation of homogeneous single-phase structures. Here a facile approach is proposed for synthesizing multimetallic oxide subnanometer nanobelts (MMO-PMA SNBs) by harnessing the potential of phosphomolybdic acid (PMA) clusters to capture inorganic nuclei and inhibiting their subsequent growth in solvothermal reactions. Experimental and theoretical analyses show that PMA in MMO-PMA SNBs not only aids subnanometer structure formation but also induces in situ modifications to catalytic sites. The electron transfer from PMA, coupled with the loss of elemental identity of transition metals, leads to electron delocalization, jointly activating the reaction sites. The unique structure makes pentametallic oxide (PMO-PMA SNBs) achieve a current density of 10 mA cm-2 at a low potential of 1.34 V and remain stable for 24 h at 10 mA cm-2 on urea oxidation reaction (UOR). The exceptional UOR catalytic activity suggests a potential for utilizing multimetallic subnanometer nanostructures in energy conversion and environmental remediation.

5.
J Arrhythm ; 40(3): 455-462, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38939788

ABSTRACT

Objective: High-power ablation has been widely used in atrial fibrillation (AF). However, there were many studies observed the outcomes of the short-term follow-up. This study aims to the long-term results of high-power ablation guided by ablation index (AI) in patients with AF. Methods: Analysis of patients with AF, who first received high-power (40-50 W) ablation, to pulmonary vein isolation (PVI) in the Second Hospital of Shanxi Medical University from May 2020 to March 2022. All patients were managed perioperatively according to the routine treatment procedures. High-power ablation was conducted under the guidance of our conventional power AI and baseline data, first-pass PVI rate, ablation time, operative time, and long-term surgical success rate were analyzed. Results: A total of 83 patients with atrial fibrillation were enrolled in the study, with an average age of 61.62 ± 9.04 years, 47 male patients, and 49 paroxysmal atrial fibrillation. All patients achieved PVI, and the rate of first pass was 82%. The ablation time of the left atrial was 28.54 ± 9.11 min. There were no serious complications related to ablation, and only a small amount of pericardial effusion was found in 4 patients. During the follow-up period of 26.36 ± 6.11 months, 8 patients were lost to follow-up and the overall success rate was 84%, including 91% for paroxysmal AF and 71% for persistent AF. Conclusion: High-power ablation long-term results appear a high freedom atrial arrhythmia, but further expanded samples are needed for controlled studies.

6.
J Clin Invest ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38875287

ABSTRACT

It is unknown which post-transcriptional regulatory mechanisms are required for oncogenic competence. Here, we show that the LIN28 family of RNA-binding proteins (RBPs), which facilitate post-transcriptional RNA metabolism within ribonucleoprotein networks, are essential for the initiation of diverse oncotypes of hepatocellular carcinoma (HCC). In HCC models driven by NRASG12V/Tp53, CTNNB1/YAP/Tp53, or AKT/Tp53, mice without Lin28a and Lin28b were markedly impaired in cancer initiation. We biochemically defined an oncofetal regulon of 15 factors connected to Lin28 through direct mRNA and protein interactions. Interestingly, all were RBPs and only 1 of 15 is a Let-7 target. Polysome profiling and reporter assays showed that LIN28B directly increased the translation of 8 of these 15 RBPs. As expected, overexpression of LIN28B and IGFBP1-3 were able to genetically rescue cancer initiation. Using this platform to probe components downstream of LIN28, we found that 8 target RBPs were able to restore NRASG12V/Tp53 cancer formation in Lin28a/b deficient mice. Furthermore, these LIN28B targets promote cancer initiation through an increase in protein synthesis. LIN28B, central to an RNP regulon that increases translation of RBPs, is important for tumor initiation in the liver.

7.
Science ; 384(6701): eadj4301, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38870309

ABSTRACT

Mitochondria are critical for proper organ function and mechanisms to promote mitochondrial health during regeneration would benefit tissue homeostasis. We report that during liver regeneration, proliferation is suppressed in electron transport chain (ETC)-dysfunctional hepatocytes due to an inability to generate acetyl-CoA from peripheral fatty acids through mitochondrial ß-oxidation. Alternative modes for acetyl-CoA production from pyruvate or acetate are suppressed in the setting of ETC dysfunction. This metabolic inflexibility forces a dependence on ETC-functional mitochondria and restoring acetyl-CoA production from pyruvate is sufficient to allow ETC-dysfunctional hepatocytes to proliferate. We propose that metabolic inflexibility within hepatocytes can be advantageous by limiting the expansion of ETC-dysfunctional cells.


Subject(s)
Acetyl Coenzyme A , Hepatocytes , Liver Regeneration , Mitochondria, Liver , Pyruvic Acid , Animals , Hepatocytes/metabolism , Acetyl Coenzyme A/metabolism , Mice , Pyruvic Acid/metabolism , Mitochondria, Liver/metabolism , Oxidation-Reduction , Cell Proliferation , Fatty Acids/metabolism , Liver/metabolism , Electron Transport , Mice, Inbred C57BL , Mitochondria/metabolism , Male
8.
iScience ; 27(6): 110029, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38883844

ABSTRACT

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), unfortunately encounters resistance in most patients, leading to disease progression. Traditional approaches to counteract this resistance, particularly those targeting the RAF-MEK-ERK pathway, often face clinical feasibility limitations. Magnetic hyperthermia (MH), unlike conventional thermal therapies, emerges as a promising alternative. It uniquely combines magnetothermal effects with an increase in reactive oxygen species (ROS). This study found the potential of intracellular MH enhanced the efficacy of sorafenib, increased cellular sensitivity to sorafenib, and reversed sorafenib resistance by inhibiting the RAF-MEK-ERK pathway in an ROS-dependent manner in a sorafenib-resistant HCC cell. Further, in a sorafenib-resistant HCC mouse model, MH significantly sensitized tumors to sorafenib therapy, resulting in inhibited tumor growth and improved survival rates. This presents a promising strategy to overcome sorafenib resistance in HCC, potentially enhancing therapeutic outcomes for patients with this challenging condition.

9.
Biochim Biophys Acta Mol Basis Dis ; : 167318, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38909849

ABSTRACT

Myocardial ischemia-reperfusion (I/R) injury is a prevalent cause of myocardial injury, involving a series of interconnected pathophysiological processes. However, there is currently no clinical therapy for effectively mitigating myocardial I/R injury. Here, we show that p85α protein levels increase in response to I/R injury through a comprehensive analysis of cardiac proteomics, and confirm this in the I/R-injured murine heart and failing human myocardium. Genetic inhibition of p85α in mice activates the Akt-GSK3ß/Bcl-x(L) signaling pathway and ameliorates I/R-induced cardiac dysfunction, apoptosis, inflammation, and mitochondrial dysfunction. p85α silencing in cardiomyocytes alleviates hypoxia-reoxygenation (H/R) injury through activating the Akt-GSK3ß/Bcl-x(L) signaling pathway, while its overexpression exacerbates the damage. Mechanistically, the interaction between MG53 and p85α triggers the ubiquitination and degradation of p85α, consequently enhancing Akt phosphorylation and ultimately having cardioprotective effects. Collectively, our findings reveal that substantial reduction of p85α and subsequently activated Akt signaling have a protective effect against cardiac I/R injury, representing an important therapeutic strategy for mitigating myocardial damage.

10.
Natl Health Stat Report ; (205): 1-11, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38912919

ABSTRACT

Objectives-This report examines changes in telemedicine use among U.S. adults between 2021 and 2022 by selected sociodemographic and geographic characteristics. Methods-Data from the 2021 and 2022 National Health Interview Survey were used to assess changes between these 2 years in the percentage of adults who used telemedicine in the previous 12 months, by sex, age, race and Hispanic origin, family income, education, region of residence, urbanization level, and health insurance coverage. Results-Overall, the percentage of adults who used telemedicine in the past 12 months decreased from 37.0% in 2021 to 30.1% in 2022. This pattern was observed across several sociodemographic and geographic characteristics, such as sex, family income, education, region, and urbanization level. Women, adults with a college degree or higher, and adults living in more urban areas were all more likely to use telemedicine in 2022. In 2021 and 2022, uninsured adults ages 18-64 were less likely to use telemedicine compared with those who had private or public insurance, while adults age 65 and older who had Medicare only were less likely to use telemedicine compared with those with other types of insurance. However, for both age groups, telemedicine use decreased from 2021 to 2022 for all insurance types except public coverage for adults ages 18-64. Summary-National Health Interview Survey data may be used to monitor national trends and understand patterns of telemedicine use by sociodemographic and geographic characteristics as the transition forward from the global COVID-19 pandemic continues.


Subject(s)
Telemedicine , Humans , Telemedicine/statistics & numerical data , Telemedicine/trends , United States , Adult , Middle Aged , Female , Male , Young Adult , Adolescent , Aged , Insurance Coverage/statistics & numerical data , COVID-19/epidemiology , Insurance, Health/statistics & numerical data , Socioeconomic Factors , Health Surveys , Sociodemographic Factors
11.
Front Bioeng Biotechnol ; 12: 1358670, 2024.
Article in English | MEDLINE | ID: mdl-38832133

ABSTRACT

To enhance physical capabilities of workers who regularly perform physically demanding tasks involving heavy lifting and awkward postures, various tools and occupational exoskeletons can be used. Most of the studies aiming to explore the efficiency of these tools and exoskeletons have been performed in confined and controlled laboratory spaces, which do not represent the real-world work environment. This study aimed to compare the outcome of biomechanical assessment of using a back support exoskeleton and assistive tools (Lever and Jake) in the procedure of a high demanding manual material handling task versus the results found by performing the same task in a laboratory. Ten able-bodied participants and ten able-bodied utility workers performed the same manhole removal task in-lab and in-field, respectively, with the aid of an exoskeleton and Lever and Jake tools. Muscle activity and Rapid Entire Body Assessment (REBA) scores were recorded using surface electromyography and inertial measurement units, respectively and compared between in-lab and in-field trials. The field experiments indicated significant differences (p < 0.05) in normalized muscle activity across most muscles when compared to laboratory data. These results revealed how muscle activity is affected by the controlled lab setting compared to real-world field conditions. However, REBA scores indicate similar ergonomic implications regardless of the utilization of exoskeletons or tools. These findings underscore that real-world field assessments are crucial for evaluating ergonomic risks and effects of occupational exoskeletons and tools to account for environmental factors and workers' skills in ergonomic evaluations of this nature.

12.
Opt Express ; 32(9): 16212-16234, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38859255

ABSTRACT

In this paper, we investigate the theoretical models and potential applications of spatial diffractive neural network (SDNN) structures, with a particular focus on mode manipulation. Our research introduces a novel diffractive transmission simulation method that employs matrix multiplication, alongside a parameter optimization algorithm based on neural network gradient descent. This approach facilitates a comprehensive understanding of the light field manipulation capabilities inherent to SDNNs. We extend our investigation to parameter optimization for SDNNs of various scales. We achieve the demultiplexing of 5, 11 and 100 orthogonal orbital angular momentum (OAM) modes using neural networks with 4, 10 and 50 layers, respectively. Notably, the optimized 100 OAM mode demultiplexer shows an average loss of 0.52 dB, a maximum loss of 0.62 dB, and a maximum crosstalk of -28.24 dB. Further exploring the potential of SDNNs, we optimize a 10-layer structure for mode conversion applications. This optimization enables conversions from Hermite-Gaussian (HG) to Laguerre-Gaussian (LG) modes, as well as from HG to OAM modes, showing the versatility of SDNNs in mode manipulation. We propose an innovative assembly of SDNNs on a glass substrate integrated with photonic devices. A 10-layer diffractive neural network, with a size of 49 mm × 7 mm × 7 mm, effectively demultiplexes 11 orthogonal OAM modes with minimal loss and crosstalk. Similarly, a 20-layer diffractive neural network, with a size of 67 mm × 7 mm × 7 mm, serves as a highly efficient 25-channel OAM to HG mode converter, showing the potential of SDNNs in advanced optical communications.

13.
Talanta ; 277: 126364, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38861763

ABSTRACT

Acute myocardial infarction (AMI) is a life-threatening disease with a short course and a high mortality rate. However, it is still a great challenge to achieve the on-site diagnosis of this disease within minutes, meaning there is an urgent need to develop an efficient technology for realizing the rapid diagnosis and early warning of AMI in clinical emergencies. In this study, an ultrasensitive electrochemical aptasensor based on an extended-gate ion-sensitive field-effect transistor (EGISFET) was designed to achieve the quantitative assay of cardiac troponin I (cTnI), which is a highly sensitive and specific biomarker of AMI, within only 5 min. The EGISFET exhibits extremely high detection sensitivity due to its separated structure with a large sensing area and the surface-modified Prussian blue-gold nanoparticles (PB-AuNPs) composite, which serves as a signal magnifier and DNA loading platform for good electrocatalytic ability with a large specific area. Additionally, a target-induced strand-release strategy is proposed to shorten the recognition time of cTnI using a particular DNA strand. Under optimal conditions, the as-prepared aptasensor exhibits a wide linear range of 1-1000 pg/mL, an ultralow detection limit of 0.3 pg/mL, and reliable detection results in real serum samples. It is highly anticipated that this EGISFET-based aptasensor will have broad applications in the early warning and rapid diagnosis of AMI and other acute diseases in emergency treatment.

14.
Water Res ; 260: 121951, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38896884

ABSTRACT

Land use plays a critical role in managing water quality in a watershed, as it governs the import and distribution of nutrients. In addition to the land use, some rivers in Southwest China are encountering a new environmental stressor of damming, which is being driven by the national strategy of hydropower development. However, the coupling effect of land use and dams on nutrients remains poorly understood, challenging the effective management of riverine water quality. Therefore, this study examined the nutrients in the Nu, Yarlung Tsangpo (YT), and Lancang (LC) Rivers, which have no dam, 1 dam, and 11 dams, respectively, during different regulatory periods (spring and fall) to identify variations in nutrient control patterns influenced by land use and dams. The findings suggested that an increase in hydropower development contributed to a notable shift in nutrient patterns from land use regulation towards dam regulation and coupling effects. Land use dominated the nutrient variations of the Nu (27.4 %-32.8 %) and low hydropower development YT (25.2 %-30.9 %) Rivers during both seasons, but the primary contributors to the nutrient variations of the high hydropower development LC River were dams (17.9 %-41.6 %) and coupling effects (16.5 %-29.0 %). Dams transform nutrient levels and compositions through internal reservoir cycling, decoupling land use and nutrients. Partial least-squares structural equation model analysis further suggested that the coupling effects of the LC River were seasonal-specific, which was primarily attributed to hydrological variations that affected their interactions. During spring, the reservoir underwent a drainage mode characterized by high-level nutrients in the bottom water. Combined with the import of riverine nutrients, it exacerbated the increase of nutrients (synergistic effect). In contrast, the reservoir transitioned into a storage mode where it intercepted nutrients from the upstream and watershed during the fall, leading to a reduction in the previously observed increasing trend and an increase in nutrient variability (antagonism effect).

15.
ACS Appl Mater Interfaces ; 16(24): 30671-30684, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38843203

ABSTRACT

Indoleamine 2,3-dioxygenase (IDO), highly expressed in hepatocellular carcinoma (HCC), plays a pivotal role in creating an immune-suppressive tumor microenvironment. Inhibiting IDO activity has emerged as a promising immunotherapeutic strategy; however, the delivery of IDO inhibitors to the tumor site is constrained, limiting their therapeutic efficacy. In this study, we developed a magnetic vortex nanodelivery system for the targeted delivery of the IDO inhibitor NLG919, integrated with magnetic hyperthermia therapy to reverse the immune-suppressive microenvironment of liver cancer and inhibit tumor growth. This system comprises thermoresponsive polyethylenimine-coated ferrimagnetic vortex-domain iron oxide nanorings (PI-FVIOs) loaded with NLG919 (NLG919/PI-FVIOs). Under thermal effects, NLG919 can be precisely released from the delivery system, counteracting IDO-mediated immune suppression and synergizing with NLG919/PI-FVIOs-mediated magnetothermodynamic (MTD) therapy-induced immunogenic cell death (ICD), resulting in effective HCC suppression. In vivo studies demonstrate that this combination therapy significantly inhibits tumor growth and metastasis by enhancing the accumulation of cytotoxic T lymphocytes and suppressing regulatory T cells within the tumor. Overall, our findings reveal that NLG919/PI-FVIOs can induce a potent antitumor immune response by disrupting the IDO pathway and activating the ICD, offering a promising therapeutic avenue for HCC treatment.


Subject(s)
Indoleamine-Pyrrole 2,3,-Dioxygenase , Liver Neoplasms , Tumor Microenvironment , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Animals , Tumor Microenvironment/drug effects , Mice , Humans , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Hyperthermia, Induced , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Mice, Inbred BALB C , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Imidazoles , Isoindoles
16.
Int J Phytoremediation ; : 1-8, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38825962

ABSTRACT

The effects of rootstocks tomato (Solanum lycopersicum L.), eggplant (Solanum melongena L.), and nightshade (Solanum nigrum L.) grafting on the growth and selenium (Se) accumulation of Cyphomandra betacea Sendt. seedlings were studied to identify the most suitable rootstock for increasing Se uptake of fruit trees grown in Se-contaminated soil. The rootstocks of tomato, eggplant, and nightshade grafting increased the scion biomass of C. betacea seedlings by 146.1%, 23.2%, and 94.5%, respectively, compared with the un-grafted seedlings. Moreover, tomato, eggplant, and nightshade rootstocks grafting increased the photosynthesis, superoxide dismutase activity, and peroxidase activity, while reducing the catalase activity and soluble protein content of C. betacea seedlings. Although all three rootstocks grafting decreased Se contents in rootstock roots and stems, only nightshade rootstock grafting increased Se content in the scions of C. betacea seedlings. Notably, root biomass, catalase activity, soluble protein content, rootstock root Se content, and rootstock stem Se content were closely related to the scion Se content. These findings suggest that only grafting onto nightshade rootstock significantly enhances Se uptake in C. betacea, whereas tomato and eggplant rootstocks grafting have no effect on Se uptake.


This study shows that under selenium (Se)-contaminated soil conditions, tomato, eggplant, and nightshade rootstocks can promote the growth of C. betacea seedlings and improve their stress resistance. The nightshade rootstock stands out for its ability to promote Se uptake in C. betacea seedlings, suggesting its suitability as a promising rootstock to enhance both growth and Se uptake in C. betacea.

17.
Hum Pathol ; 149: 1-9, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38782102

ABSTRACT

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.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Lymph Nodes , Lymphatic Metastasis , Neoadjuvant Therapy , Neoplasm, Residual , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/immunology , Male , Female , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lung Neoplasms/mortality , Middle Aged , Aged , Lymph Nodes/pathology , Adult , Immunotherapy/methods , Retrospective Studies , Prognosis , Chemotherapy, Adjuvant , Treatment Outcome , Tumor Burden
18.
J Chem Theory Comput ; 20(11): 4469-4480, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38816696

ABSTRACT

Protein-protein interactions are the basis of many protein functions, and understanding the contact and conformational changes of protein-protein interactions is crucial for linking the protein structure to biological function. Although difficult to detect experimentally, molecular dynamics (MD) simulations are widely used to study the conformational ensembles and dynamics of protein-protein complexes, but there are significant limitations in sampling efficiency and computational costs. In this study, a generative neural network was trained on protein-protein complex conformations obtained from molecular simulations to directly generate novel conformations with physical realism. We demonstrated the use of a deep learning model based on the transformer architecture to explore the conformational ensembles of protein-protein complexes through MD simulations. The results showed that the learned latent space can be used to generate unsampled conformations of protein-protein complexes for obtaining new conformations complementing pre-existing ones, which can be used as an exploratory tool for the analysis and enhancement of molecular simulations of protein-protein complexes.


Subject(s)
Molecular Dynamics Simulation , Protein Conformation , Proteins , Proteins/chemistry , Neural Networks, Computer , Protein Binding
19.
Plant Physiol Biochem ; 212: 108767, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38797009

ABSTRACT

Salt stress is a critical limiting factor for fruit yield and quality of apples. Brassinosteroids (BRs) play an important role in response to abiotic stresses. In the present study, application of 2,4- Epicastasterone on seedlings of Malus 'M9T337' and Malus domestica 'Gala3' alleviated the physiological effects, such as growth inhibition and leaf yellowing, induced by salt stress. Further analysis revealed that treatment with NaCl induced expression of genes involved in BR biosynthesis in 'M9T337' and 'Gala3'. Among which, the expression of BR biosynthetic gene MdBR6OX2 showed a three-fold upregulation upon salt treatment, suggesting its potential role in response to salt stress in apple. MdBR6OX2, belonging to the CYP450 family, contains a signal peptide region and a P450 domain. Expression patterns analysis showed that the expression of MdBR6OX2 can be significantly induced by different abiotic stresses. Overexpressing MdBR6OX2 enhanced the tolerance of apple callis to salt stress, and the contents of endogenous BR-related compounds, such as Typhastero (TY), Castasterone (CS) and Brassinolide (BL) were significantly increased in transgenic calli compared with that of wild-type. Extopic expression of MdBR6OX2 enhanced tolerance to salt stress in Arabidopsis. Genes associated with salt stress were significantly up-regulated, and the contents of BR-related compounds were significantly elevated under salt stress. Our data revealed that BR-biosynthetic gene MdBR6OX2 positively regulates salt stress tolerance in both apple calli and Arabidopsis.


Subject(s)
Arabidopsis , Brassinosteroids , Gene Expression Regulation, Plant , Malus , Plant Proteins , Salt Tolerance , Malus/genetics , Malus/metabolism , Malus/drug effects , Brassinosteroids/metabolism , Brassinosteroids/biosynthesis , Brassinosteroids/pharmacology , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/drug effects , Salt Tolerance/genetics , Gene Expression Regulation, Plant/drug effects , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified , Salt Stress/genetics , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism
20.
Ultrasonics ; 141: 107334, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38733864

ABSTRACT

Grain size is one of the key microstructural factors affecting the mechanical properties of polycrystalline metal materials. In this study, a novel method for grain size evaluation using ultrasonic coda waves is proposed. Different from conventional bulk wave methods that require a point-by-point scanning of the structure, the proposed method allows for a rapid evaluation of the average grain size of the whole part from a single inspection location using one-pass testing data. A piecewise energy attenuation function dealing with different attenuation mechanisms is proposed to obtain the effective attenuation coefficient of coda waves. A power-law model is constructed to correlate the effective attenuation coefficient with the average grain size. Ultrasonic testing on nickel-based superalloy plate specimens with different average grain sizes is performed for model calibration and method verification. The applicability and robustness of the proposed method are further validated using a realistic turbine disk specimen with an irregular shape and non-uniform grain sizes. Results show that the proposed method yields a reliable and accurate estimation of the average grain size with a maximum relative error less than 20 %.

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