ABSTRACT
BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the world, and its prognosis is closely related to many factors. In recent years, the incidence of vascular thrombosis in patients with GC has gradually attracted increasing attention, and studies have shown that it may have a significant impact on the survival rate and prognosis of patients. However, the specific mechanism underlying the association between vascular thrombosis and the prognosis of patients with GC remains unclear. AIM: To analyze the relationships between vascular cancer support and other clinicopathological factors and their influence on the prognosis of patients with GC. METHODS: This study retrospectively analyzed the clinicopathological data of 621 patients with GC and divided them into a positive group and a negative group according to the presence or absence of a vascular thrombus. The difference in the 5-year cumulative survival rate between the two groups was compared, and the relationships between vascular cancer thrombus and other clinicopathological factors and their influence on the prognosis of patients with GC were analyzed. RESULTS: Among 621 patients with GC, the incidence of vascular thrombi was 31.7% (197 patients). Binary logistic regression analysis revealed that the degree of tumor differentiation, depth of invasion, and extent of lymph node metastasis were independent influencing factors for the occurrence of vascular thrombi in GC patients (P < 0.01). The trend of the χ 2 test showed that the degree of differentiation, depth of invasion, and extent of lymph node metastasis were linearly correlated with the percentage of vascular thrombi in GC patients (P < 0.01), and the correlation between lymph node metastasis and vascular thrombi was more significant (r = 0.387). Univariate analysis revealed that the 5-year cumulative survival rate of the positive group was significantly lower than that of the negative group (46.7% vs 73.3%, P < 0.01). Multivariate analysis revealed that age, tumor diameter, TNM stage, and vascular thrombus were independent risk factors for the prognosis of GC patients (all P < 0.05). Further stratified analysis revealed that the 5-year cumulative survival rate of stage III GC patients in the thrombolase-positive group was significantly lower than that in the thrombolase-negative group (36.1% vs 51.4%; P < 0.05). CONCLUSION: Vascular cancer status is an independent risk factor affecting the prognosis of patients with GC. The combination of vascular cancer suppositories and TNM staging can better judge the prognosis of patients with GC and guide more reasonable treatment.
ABSTRACT
Molecular materials possessing switchable magneto-optical properties are of great interest due to their potential applications in spintronics and molecular devices. However, switching their photoluminescence (PL) and single-molecule magnet (SMM) behavior via light-induced structural changes still constitutes a formidable challenge. Here, a series of cubane structures were synthesized via self-assembly of 9-anthracene carboxylic acid (HAC) and rare-earth ions. All complexes exhibited obvious photochromic phenomena and complete PL quenching upon Xe lamp irradiation, which were realized via the synergistic effect of photogenerated radicals and [4 + 4] photocycloaddition of the AC components. The quenched PL showed the largest fluorescence intensity change (99.72%) in electron-transfer photochromic materials. A reversible decoloration process was realized via mechanical grinding, which is unexpectedly in the electron-transfer photochromic materials. Importantly, an SMM behavior of the Dy analog was observed after room-temperature irradiation due to the photocycloaddition of AC ligands and the photogenerated stable radicals changed the electrostatic ligand field and magnetic coupling. Moreover, based on the remarkably photochromic and photoluminescent properties of these compounds, 2 demos were applied to support their application in information anti-counterfeiting and inkless printing. This work, for the first time utilizing the simultaneous modulation of photocycloaddition and photogenerated radicals in one system, realizes complete PL quenching and light-induced SMM behavior, providing a dynamical switch for the construction of multifunctional polymorphic materials with optical response and optical storage devices.
ABSTRACT
To investigate the impacts of circ_0069094 on acute coronary syndrome. Real-time polymerase chain reaction was used to detect the expression levels of circ_0069094, and its diagnostic performance was evaluated using ROC curve. Spearman's method was performed for correlation analysis. The levels of SOD, MDA, vWF in ACS rat models were assessed by commercial kits. The activities of H/R cell models were detected by CCK-8, Transwell, flow cytometry. The GO and KEGG were performed to analyze the function of targeted genes of miR-484. The concentration of circ_0069094 was decreased in patients with ACS, ACS rat models and H/R HUVEC models. The dysfunction of SOD, MDA, vWF, LVIDs, LVDD, and LVEF in the ACS models was regulated by the increase of circ_0069094. The viability, migration, apoptosis of the H/R models were regulated by circ_0069094. MiR-484 was a ceRNA of circ_0069094 and mediated the function of circ_0069094.
ABSTRACT
The rapid development of the Internet of Things (IoT) has accelerated the advancement of indoor photovoltaics (IPVs) that directly power wireless IoT devices. The interest in lead-free perovskites for IPVs stems from their similar optoelectronic properties to high-performance lead halide perovskites, but without concerns about toxic lead leakage in indoor environments. However, currently prevalent lead-free perovskite IPVs, especially tin halide perovskites (THPs), still exhibit inferior performance, arising from their uncontrollable crystallization. Here, a novel adhesive bonding strategy is proposed for precisely regulating heterogeneous nucleation kinetics of THPs by introducing alkali metal fluorides. These ionic adhesives boost the work of adhesion at the buried interface between substrates and perovskite film, subsequently reducing the contact angle and energy barrier for heterogeneous nucleation, resulting in high-quality THP films. The resulting THP solar cells achieve an efficiency of 20.12% under indoor illumination at 1000 lux, exceeding all types of lead-free perovskite IPVs and successfully powering radio frequency identification-based sensors.
ABSTRACT
Gene regulatory networks (GRNs) are crucial for understanding organismal molecular mechanisms and processes. Construction of GRN in the epithelioma papulosum cyprini (EPC) cells of cyprinid fish by spring viremia of carp virus (SVCV) infection helps understand the immune regulatory mechanisms that enhance the survival capabilities of cyprinid fish. Although many computational methods have been used to infer GRNs, specialized approaches for predicting the GRN of EPC cells following SVCV infection are lacking. In addition, most existing methods focus primarily on gene expression features, neglecting the valuable network structural information in known GRNs. In this study, we propose a novel supervised deep neural network, named MEFFGRN (Matrix Enhancement- and Feature Fusion-based method for Gene Regulatory Network inference), to accurately predict the GRN of EPC cells following SVCV infection. MEFFGRN considers both gene expression data and network structure information of known GRN and introduces a matrix enhancement method to address the sparsity issue of known GRN, extracting richer network structure information. To optimize the benefits of CNN (Convolutional Neural Network) in image processing, gene expression and enhanced GRN data were transformed into histogram images for each gene pair respectively. Subsequently, these histograms were separately fed into CNNs for training to obtain the corresponding gene expression and network structural features. Furthermore, a feature fusion mechanism was introduced to comprehensively integrate the gene expression and network structural features. This integration considers the specificity of each feature and their interactive information, resulting in a more comprehensive and precise feature representation during the fusion process. Experimental results from both real-world and benchmark datasets demonstrate that MEFFGRN achieves competitive performance compared with state-of-the-art computational methods. Furthermore, study findings from SVCV-infected EPC cells suggest that MEFFGRN can predict novel gene regulatory relationships.
Subject(s)
Fish Diseases , Gene Regulatory Networks , Rhabdoviridae Infections , Rhabdoviridae , Animals , Rhabdoviridae/genetics , Fish Diseases/genetics , Fish Diseases/virology , Rhabdoviridae Infections/genetics , Rhabdoviridae Infections/virology , Carps/genetics , Carps/virology , Computational Biology/methods , Neural Networks, Computer , Cyprinidae/geneticsABSTRACT
Symbiotic nodules comprise two classes, indeterminate and determinate, defined by the presence/absence of apical meristem and developmental zonation. Why meristem and zonation are absent from determinate nodules remains unclear. Here, we define cell types in developing soybean nodules, highlighting the undifferentiated infection zones and differentiated nitrogen-fixation zones. Auxin governs infection zone maintenance. GRETCHEN HAGEN 3 (GH3) enzymes deactivate auxin by conjugation and promote cell differentiation. gh3 mutants increased undifferentiated cells and enlarged infection zones. The central symbiosis-transcription factor NIN2a activates GH3.1 to reduce auxin levels and facilitates cell differentiation. High auxin promotes NIN2a protein accumulation and enhances signaling, further deactivating auxin and depleting infection zones. Our findings shed light on the NIN2a-GH3-auxin module that drives soybean nodule cell differentiation. This study challenges our understanding of determinate nodule development and proposes that the regulation of nodule zonation offers valuable insights into broader mechanisms of cell differentiation across plant species.
Subject(s)
Cell Differentiation , Gene Expression Regulation, Plant , Glycine max , Homeostasis , Indoleacetic Acids , Plant Proteins , Root Nodules, Plant , Signal Transduction , Symbiosis , Glycine max/metabolism , Glycine max/genetics , Glycine max/growth & development , Indoleacetic Acids/metabolism , Root Nodules, Plant/metabolism , Root Nodules, Plant/growth & development , Plant Proteins/metabolism , Plant Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Nitrogen FixationABSTRACT
As a derivative of the two-dimensional material family, two-dimensional Janus materials have garnered widespread attention in recent years. Consequently, in this work, we systematically investigated the stability, electronic properties, photocatalytic properties, optical properties, and carrier mobility of SPtAZ2 (A = Si and Ge; Z = N, P, and As) monolayers using first-principles calculations. In the equilibrium state, we identified four stable structures that exhibited the properties of indirect band gap semiconductors using the HSE06 hybrid functional. Through the exploration of the photocatalytic and optical properties of these four stable structures, we observed that SPtSiN2, SPtSiP2, and SPtGeAs2 monolayers possess favorable band edge positions, high solar-to-hydrogen efficiency (up to 30.74%), and light absorption efficiency, thus endowing these three structures with commendable photocatalytic and light absorption performance. We additionally calculated the carrier mobility of these three structures and identified significant differences in electron and hole mobilities in the same direction, facilitating the effective separation of electrons and holes. Finally, we explored the effects of biaxial strain on the electronic properties, photocatalysis, and light absorption of stable SPtAZ2 monolayers. Our research results not only expand the 2D Janus material family, but also successfully predict a type of photocatalyst capable of utilizing visible light for overall water splitting.
ABSTRACT
BACKGROUND: Icariin (ICA) inhibits inflammatory response in various diseases, but the mechanism underlying ICA treating airway inflammation in asthma needs further understood. We aimed to predict and validate the potential targets of ICA against asthma-associated airway inflammation using network pharmacology and experiments. METHODS: The ovalbumin-induced asthma-associated airway inflammation mice model was established. The effects of ICA were evaluated by behavioral, airway hyperresponsiveness, lung pathological changes, inflammatory cell and cytokines counts. Next, the corresponding targets of ICA were mined via the SEA, CTD, HERB, PharmMapper, Symmap database and the literature. Pubmed-Gene and GeneCards databases were used to screen asthma and airway inflammation-related targets. The overlapping targets were used to build an interaction network, analyze gene ontology and enrich pathways. Subsequently, flow cytometry, quantitative real-time PCR and western blotting were employed for validation. RESULTS: ICA alleviated the airway inflammation of asthma; 402 targets of ICA, 5136 targets of asthma and 4531 targets of airway inflammation were screened; 216 overlapping targets were matched and predicted ICA possesses the potential to modulate asthmatic airway inflammation by macrophage activation/polarization. Additionally, ICA decreased M1 but elevated M2. Potential targets that were disrupted by asthma inflammation were restored by ICA treatment. CONCLUSIONS: ICA alleviates airway inflammation in asthma by inhibiting the M1 polarization of alveolar macrophages, which is related to metabolic reprogramming. Jun, Jak2, Syk, Tnf, Aldh2, Aldh9a1, Nos1, Nos2 and Nos3 represent potential targets of therapeutic intervention. The present study enhances understanding of the anti-airway inflammation effects of ICA, especially in asthma.
Subject(s)
Asthma , Disease Models, Animal , Flavonoids , Macrophage Activation , Macrophages, Alveolar , Network Pharmacology , Animals , Asthma/drug therapy , Asthma/metabolism , Mice , Flavonoids/pharmacology , Flavonoids/therapeutic use , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/metabolism , Macrophages, Alveolar/immunology , Macrophage Activation/drug effects , Inflammation/drug therapy , Inflammation/metabolism , Cytokines/metabolism , Ovalbumin , Lung/pathology , Lung/drug effects , Lung/metabolism , FemaleABSTRACT
The prevalence of major bacterial infections has emerged as a significant menace to human health and life. Conventional treatment methods primarily rely on antibiotic therapy, but the overuse of these drugs has led to a decline in their efficacy. Moreover, bacteria have developed resistance towards antibiotics, giving rise to the emergence of superbugs. Consequently, there is an urgent need for novel antibacterial agents or alternative strategies to combat bacterial infections. Nanoantibiotics encompass a class of nano-antibacterial materials that possess inherent antimicrobial activity or can serve as carriers to enhance drug delivery efficiency and safety. In recent years, metal nanoclusters (M NCs) have gained prominence in the field of nanoantibiotics due to their ultra-small size (less than 3 nm) and distinctive electronic and optical properties, as well as their biosafety features. In this review, we discuss the recent progress of M NCs as a new generation of antibacterial agents. First, the main synthesis methods and characteristics of M NCs are presented. Then, we focus on reviewing various strategies for detecting and treating pathogenic bacterial infections using M NCs, summarizing the antibacterial effects of these nanoantibiotics on wound infections, biofilms, and oral infections. Finally, we propose a perspective on the remaining challenges and future developments of M NCs for bacterial infectious therapy.
Subject(s)
Anti-Bacterial Agents , Bacterial Infections , Metal Nanoparticles , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Bacterial Infections/microbiology , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Humans , Bacteria/drug effects , Biofilms/drug effects , AnimalsABSTRACT
BACKGROUND: Patients with lung adenocarcinoma (LUAD) have a low response rate to immune checkpoint blockade. It is highly important to explore the tumor immune escape mechanism of LUAD patients and expand the population of patients who may benefit from immunotherapy. METHODS: Based on 954 bulk RNA-seq data of LUAD patients and 15 single-cell RNA-seq data, the relationships between tumor immune dysfunction and exclusion (TIDE) scores and survival prognosis in each patient were calculated and evaluated, and the immune escape mechanism affecting the independent prognosis of LUAD patients was identified. Functional enrichment analysis explored the antitumour immune response and biological behavior of tumor cells among different LUAD groups. Single-cell annotation and pseudotemporal analysis were used to explore the target molecules and immune escape mechanisms of LUAD. RESULTS: Myeloid-derived suppressor cells (MDSCs) and IRF8 were identified as risk and protective factors for the independent prognosis of LUAD patients, respectively. In the tumor microenvironment of patients with high infiltration of MDSCs, the antitumor immune response is significantly suppressed, while tumor cell division, proliferation, and distant metastasis are significantly enhanced. Single-cell RNA-seq analysis revealed that IRF8 is an important regulator of MDSC differentiation in LUAD myeloid cells. In addition, IRF8 may regulate the differentiation of MDSCs through the IL6-JAK-STAT3 signalling pathway. CONCLUSIONS: IRF8 deficiency impairs the normal development of LUAD myeloid cells and induces their differentiation into MDSCs, thereby accelerating the immune escape of LUAD cells. IRF8-targeted activation to inhibit the formation of MDSCs may be a new target for immunotherapy in LUAD.
Subject(s)
Adenocarcinoma of Lung , Interferon Regulatory Factors , Lung Neoplasms , Myeloid-Derived Suppressor Cells , Tumor Microenvironment , Humans , Myeloid-Derived Suppressor Cells/immunology , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Interferon Regulatory Factors/metabolism , Interferon Regulatory Factors/genetics , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Tumor Microenvironment/immunology , Prognosis , Female , Gene Expression Regulation, Neoplastic , Signal Transduction , Male , Tumor Escape , Immune Evasion , Single-Cell Analysis , Cell DifferentiationABSTRACT
Introduction: Blastocystis is one of the most critical intestinal protozoans in various hosts, including humans and mice. To determine the status of Blastocystis infection in wild rodents in China. Methods: A total of 344 faecal samples were collected from seven wild rodent species from three provinces, and the small subunit ribosomal RNA (SSU rRNA) genes of Blastocystis were amplified to determine their prevalence and subtypes. Results: Of the 344 samples, 54 (15.70%) were detected as Blastocystis-positive. The prevalence of Blastocystis was 26.14% (40/153), 7.95% (7/88), and 6.80% (7/103) in wild rodents from Hunan Province, Yunnan Province, and Guangxi Province, respectively. The prevalence of Blastocystis in different wild rodent species varied from 0.00% (0/13) in Mus musculus to 40.00% (2/5) in Rattus rattus sladeni. The prevalence of Blastocystis in samples from the lake beach area (27.40%, 40/146) was significantly higher than in those from the mountain (6.80%, 7/103) and field regions (7.37%, 7/95). The prevalence in different seasons was 26.14% in summer (40/153), 7.95% in autumn (7/88), and 6.80% in winter (7/103). Moreover, a total of two Blastocystis subtypes were identified in the investigated wild rodents, including ST4 and ST5. Discussion: The present study discovered the existence of Blastocystis infection in Rattus favipectus, Microtus fortis, Apodemus agrarius, Bandicota indica, Rattus rattus sladeni, and Rattus losea, expanding the host range of this parasite. The findings also demonstrate that wild rodents may be an important potential infection source for Blastocystis infection in humans and other animals.
ABSTRACT
In the current antiretroviral landscape, continuous efforts are still needed to search for novel chemotypes of human immunodeficiency virus type 1 (HIV-1) inhibitors with improved drug resistance profiles and favorable drug-like properties. Herein, we report the design, synthesis, biological characterization, and druggability evaluation of a class of non-nucleoside reverse transcriptase inhibitors. Guided by the available crystallographic information, a series of novel indolylarylsulfone derivatives were rationally discovered via the substituent decorating strategy to fully explore the chemical space of the entrance channel. Among them, compound 11h bearing the cyano-substituted benzyl moiety proved to be the most effective inhibitor against HIV-1 wild-type and mutant strains (EC50 = 0.0039-0.338 µM), being far more potent than or comparable to etravirine and doravirine. Besides, 11h did not exhibit cytotoxicity at the maximum test concentration. Meanwhile, the binding target of 11h was further confirmed to be reverse transcriptase (IC50 = 0.055 µM). Preliminary structure-activity relationship were discussed to guide further optimization work. Molecular docking and dynamics simulation studies were investigated in detail to rationalize the biological evaluation results. Further drug-likeness assessment indicated that 11h possessed excellent physicochemical properties. Moreover, no apparent hERG blockade liability and cytochrome P450 inhibition were observed for 11h. Notably, 11h was characterized by favorable in vitro metabolic stability with moderate clearance rates and long half-lives in human plasma and liver microsomes. Overall, 11h holds great promise as an ideal Anti-HIV-1 lead compound due to its potent antiviral efficacy, low toxicity, and favorable drug-like profiles.
Subject(s)
Anti-HIV Agents , Drug Design , HIV-1 , Molecular Docking Simulation , Reverse Transcriptase Inhibitors , Sulfones , HIV-1/drug effects , Humans , Anti-HIV Agents/pharmacology , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/chemistry , Structure-Activity Relationship , Sulfones/pharmacology , Sulfones/chemical synthesis , Sulfones/chemistry , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/chemical synthesis , Reverse Transcriptase Inhibitors/chemistry , HIV Reverse Transcriptase/antagonists & inhibitors , HIV Reverse Transcriptase/metabolismABSTRACT
OBJECTIVE: To investigate the efficacy of 125I seed brachytherapy for non-central pelvic recurrence of cervical cancer after external beam radiotherapy, and to analyze the clinical influential factors. METHODS: Between June 2015 and April 2022, 32 patients with 41 lesions were treated with 125I seed brachytherapy. The seeds were implanted under the guidance of CT and/or 3D-printed template images at a median dose of 100 Gy (range, 80-120 Gy), and the local control rate (LCR) and survival rates were calculated. We used multivariate logistic regression to identify prognosis predictors, and receiver operating characteristic (ROC) curve analysis to determine the optimal cut-off values. RESULTS: The median follow-up was 48.52 months (range, 4-86 months), and the 6-, 12-, and 24-month LCR was 88.0%, 63.2%, and 42.1%, respectively. The 1- and 2-year survival rates were 36% and 33%, respectively, and the median survival time was 13.26 months. No significant adverse events occurred. Multivariate regression analysis showed that tumor diameter, tumor stage, and LCR were independent factors influencing survival. ROC curve analysis showed that the area under the curve for tumor diameter and D90 were 0.765 and 0.542, respectively, with cut-off values of 5.3 cm and 108.5 Gy. CONCLUSIONS: The present findings indicate that 125I seed brachytherapy is feasible for treating non-central pelvic recurrence of cervical cancer after external beam radiotherapy. Further, tumor diameter < 5.3 cm and immediate postoperative D90 > 108.5 Gy were associated with better efficacy.
Subject(s)
Brachytherapy , Iodine Radioisotopes , Neoplasm Recurrence, Local , Uterine Cervical Neoplasms , Humans , Brachytherapy/methods , Female , Uterine Cervical Neoplasms/radiotherapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/mortality , Iodine Radioisotopes/therapeutic use , Middle Aged , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/pathology , Aged , Adult , Survival Rate , Retrospective Studies , Pelvic Neoplasms/radiotherapy , Pelvic Neoplasms/pathology , Pelvic Neoplasms/mortality , Prognosis , Radiotherapy Dosage , Follow-Up Studies , Aged, 80 and overABSTRACT
Inferring gene regulatory network (GRN) is one of the important challenges in systems biology, and many outstanding computational methods have been proposed; however there remains some challenges especially in real datasets. In this study, we propose Directed Graph Convolutional neural network-based method for GRN inference (DGCGRN). To better understand and process the directed graph structure data of GRN, a directed graph convolutional neural network is conducted which retains the structural information of the directed graph while also making full use of neighbor node features. The local augmentation strategy is adopted in graph neural network to solve the problem of poor prediction accuracy caused by a large number of low-degree nodes in GRN. In addition, for real data such as E.coli, sequence features are obtained by extracting hidden features using Bi-GRU and calculating the statistical physicochemical characteristics of gene sequence. At the training stage, a dynamic update strategy is used to convert the obtained edge prediction scores into edge weights to guide the subsequent training process of the model. The results on synthetic benchmark datasets and real datasets show that the prediction performance of DGCGRN is significantly better than existing models. Furthermore, the case studies on bladder uroepithelial carcinoma and lung cancer cells also illustrate the performance of the proposed model.
Subject(s)
Computational Biology , Gene Regulatory Networks , Neural Networks, Computer , Humans , Computational Biology/methods , Algorithms , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Escherichia coli/geneticsABSTRACT
BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Hepatectomy , Humans , Cholangiocarcinoma/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Male , Female , Middle Aged , Prognosis , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Aged , ROC Curve , Retrospective Studies , Kaplan-Meier Estimate , Adult , Risk FactorsABSTRACT
BACKGROUND: Micropapillary (MP) and solid(S) pattern adenocarcinoma are highly malignant subtypes of lung adenocarcinoma. In today's era of increasingly conservative surgery for small lung cancer, effective preoperative identification of these subtypes is greatly important for surgical planning and long term survival of patients. METHODS: For this retrospective study, the presence of MP and/or S was evaluated in 2167 consecutive patients who underwent surgical resection for clinical stage IA1-2 lung adenocarcinoma. MP and/or S pattern-positive patients and negative-pattern patients were matched at a ratio of 1:3. The Lasso regression model was used for data dimension reduction and imaging signature building. Multivariate logistic regression was used to establish the predictive model, presented as an imaging nomogram. The performance of the nomogram was assessed based on calibration, identification, and clinical usefulness, and internal and external validation of the model was conducted. RESULTS: The proportion of solid components (PSC), Sphericity, entropy, Shape, bronchial honeycomb, nodule shape, sex, and smoking were independent factors in the prediction model of MP and/or S lung adenocarcinoma. The model showed good discrimination with an area under the ROC curve of 0.85. DCA demonstrated that the model could achieve good benefits for patients. RCS analysis suggested a significant increase in the proportion of MP and/or S from 11% to 48% when the PSC value was 68%. CONCLUSION: Small MP and/or S adenocarcinoma can be effectively identified preoperatively by their typical 3D and 2D imaging features.
ABSTRACT
The high intensity of diverse human activities in urban-rural areas leads to complex soil Pb accumulation processes and high spatiotemporal heterogeneity, making it difficult to reveal the spatiotemporal characteristics of soil Pb accumulation in these areas. This study used a typical urban-rural area in a large city in Central China as the study area, constructed a soil Pb accumulation model, and established a spatiotemporal simulation method for soil Pb accumulation processes combining this model and land use classification and simulation results. Using this method, we simulated the soil Pb content in the study area from 2013 to 2040 and elucidated the future spatiotemporal variation characteristics of soil Pb content. The results showed that the average soil Pb content in the study area in 2013 was approximately 1.77 times the background value of the Pb content in the surface soil of the province where the city is located, indicating significant soil Pb pollution. The soil Pb content was predicted to continue increasing from 2013 to 2040, with relatively low increases (0.53-2.25 mg·kg-1) in the western, northern, and southern parts of the study area, accounting for 25.46 % of the total area, and relatively high increases (3.98-5.70 mg·kg-1) in the eastern part, accounting for 17.14 % of the total area. The increase in the area of forest land and the decrease in the area of water bodies and grassland in the eastern part of the study area led to a substantial rise in soil Pb content in this region; in addition, the spatial distribution of soil Pb content was highly correlated with the distribution of important factories and transportation facilities. This study overcomes the limitations of previous research that treated land use as unchanging and to a certain extent reflects the impact of regional land use changes on the heavy metal accumulation process. It provides a method for simulating the soil Pb accumulation process in urban-rural areas and a basis for controlling soil Pb pollution in the city's urban-rural areas.
ABSTRACT
While it is well known that plants interpret UV-B as an environmental cue and a potential stressor influencing their growth and development, the specific effects of UV-B-induced oxidative stress on the dynamics of membrane lipids and proteins remain underexplored. Here, we demonstrate that UV-B exposure notably increases the formation of ordered lipid domains on the plasma membrane (PM) and significantly alters the behavior of the Glycine max nodule autoregulation receptor kinase (GmNARK) protein in Arabidopsis leaves. The GmNARK protein was located on the PM and accumulated as small particles in the cytoplasm. We found that UV-B irradiation interrupted the lateral diffusion of GmNARK proteins on the PM. Furthermore, UV-B light decreases the efficiency of surface molecule internalization by clathrin-mediated endocytosis (CME). In brief, UV-B irradiation increased the proportion of the ordered lipid phase and disrupted clathrin-dependent endocytosis; thus, the endocytic trafficking and lateral mobility of GmNARK protein on the plasma membrane are crucial for nodule formation tuning. Our results revealed a novel role of low-intensity UV-B stress in altering the organization of the plasma membrane and the dynamics of membrane-associated proteins.
ABSTRACT
PURPOSE: Gastric cancer is the most common malignancy worldwide and is the third leading cause of cancer-related deaths, urgently requiring an early and non-invasive diagnosis. Circulating extracellular vesicles may emerge as promising biomarkers for the rapid diagnosis in a non-invasive manner. METHODS: Using high-throughput small RNA sequencing, we profiled the small RNA population of serum-derived extracellular vesicles from healthy controls and gastric cancer patients. Differentially expressed microRNAs (miRNAs) were randomly selected and validated by reverse transcription-quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miRNAs for gastric cancer. RESULTS: In this study, 193 differentially expressed miRNAs were identified, of which 152 were upregulated and 41 were signiï¬cantly downregulated. Among the differently expressed miRNA, the expression levels of miR-21-5p, miR-26a-5p, and miR-27a-3p were significantly elevated in serum-derived extracellular vesicles of gastric cancer patients. The miR-21-5p and miR-27a-3p were closely correlated with the tumor size. Moreover, the expression levels of serum miR-21-5p and miR-26a-5p were signiï¬cantly decreased in gastric cancer patients after surgery. CONCLUSIONS: The present study discovered the potential of serum miR-21-5p and miR-26a-5p as promising candidates for the diagnostic and prognostic markers of gastric cancer.