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1.
Hum Cell ; 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662371

RESUMO

Oncofetal reprogramming of the tumor microenvironment is clinically relevant. This study used the non-negative matrix factorial (NMF) algorithm for single-cell RNA sequencing data of gastric cancer (GC) based on embryonic stem genes. Pseudotime analysis, cell-cell interaction analysis, and SCENIC analysis revealed that cancer-associated fibroblasts (CAFs), tumor-associated endothelial cells (TECs), and tumor-associated macrophages (TAMs) have different oncofetal reprogramming that affects cell function, enhances intercellular communication, and activates multiple transcription factors in these cells. Furthermore, based on the signatures of the newly defined oncofetal cell subtypes and expression profiles of large cohorts in GC patients, we determined that GJA1 + TEC-C2, IFITM1 + CAF-C3, PODXL + TEC-C1, SFRP2 + CAF-C2, and SRSF7 + CAF-C1 are crucial prognostic factors for GC patients and predictors of immune checkpoint blockade in GC. Cell subtypes were validated by immunohistochemical methods. Our novel, profound, and systematic analysis of the oncofetal reprogramming of GC may facilitate the development of improved drugs for treating GC.

2.
Curr Opin Microbiol ; 72: 102269, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36682279

RESUMO

Harnessing the power of beneficial microbes in the rhizosphere to improve crop performance is a key goal of sustainable agriculture. However, the precise management of rhizosphere microbes for crop growth and health remains challenging because we lack a comprehensive understanding of the plant-rhizomicrobiome relationship. In this review, we discuss the latest research progress on root colonisation by representative beneficial microbes (e.g. Bacillus spp. and Pseudomonas spp.). We also highlight the bidirectional chemical communication between microbes and plant roots for precise functional control of beneficial microbes in the rhizosphere, as well as advances in understanding how beneficial microbes overcome the immune system of plants. Finally, we propose future research objectives that will help us better understand the complex network of plant-microbe interactions.

3.
Small ; : e2207202, 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36683197

RESUMO

As an important multiferroic material, pure and low-dimensional phase-stable bismuth ferrite has wide applications. Herein, one-pot hydrothermal method was used to synthesize bismuth ferrite. Almost pure Bi2 Fe4 O9 , BiFeO3 , and their mixture were successfully obtained by controlling the KOH concentration in the hydrothermal solutions. The as-prepared Bi2 Fe4 O9 products were crystalline with Pbam space group, had nanosheet morphology, and tended to aggregate into nanofloret or random stacking. Each Bi2 Fe4 O9 nanosheet was a single crystal with (001) plane as its exposed surface. Single unit-cell layered Bi2 Fe4 O9 nanosheets had a uniform thickness of 1 nm. The surface energies of various (100), (010), and (001) planes were 3.6-4.0, 5.6-15.1, and 1.7-3.0 J m-2 , respectively, in the Bi2 Fe4 O9 crystal. The formation mechanism and structural model of the as-prepared single unit-cell layered Bi2 Fe4 O9 nanosheets have been given. The growth of Bi2 Fe4 O9 nanosheets was discussed. Thermal analysis showed that the Bi2 Fe4 O9 phase was stable up to 1260 K. The thermal expansion behavior of the Bi2 Fe4 O9 nanosheet was nonlinear. The thermal expansion coefficients of the ultrathin Bi2 Fe4 O9 nanosheets on the a-, b-, c-axes, and on the unit-cell volume V were determined, showing an anisotropic thermal expansion behavior. This study is helpful for the controllable synthesis of ultrathin Bi2 Fe4 O9 nanosheets.

4.
J Thorac Oncol ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36646210

RESUMO

INTRODUCTION: In CameL phase 3 study (ClinicalTrials.gov, NCT03134872), addition of camrelizumab to first-line chemotherapy significantly improved the progression-free survival in patients with stage IIIB-IV non-squamous NSCLC. Here, we present outcomes after a minimum follow-up of 43.9 months since last patient randomization. METHODS: Eligible patients were randomized 1:1 to 4-6 cycles of camrelizumab plus carboplatin and pemetrexed or chemotherapy alone every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only (n=205 and 207, respectively). Total camrelizumab exposure was up to 2 years. RESULTS: As of January 31, 2022, camrelizumab plus chemotherapy exhibited substantially improved overall survival over chemotherapy alone (median, 27.1 versus 19.8 mo; hazard ratio, 0.72 [95% CI, 0.57-0.92]). In the chemotherapy alone group, 95 (45.9%) patients crossed over to camrelizumab monotherapy. After adjustment for crossover, the survival benefit with camrelizumab plus chemotherapy was more pronounced (adjusted hazard ratio, 0.55 [95% CI, 0.42-0.71]). In camrelizumab plus chemotherapy group, 33 patients completed 2 years of camrelizumab. Objective response rate was 97.0%, with ongoing responses in 17 of the 32 responses (53.1%); and 93.9% (31/33) of patients were alive at data cutoff. Safety profiles were consistent with the previous report, and no obvious evidence of cumulative toxicity was found with long exposure to camrelizumab. CONCLUSIONS: Camrelizumab plus carboplatin and pemetrexed provides long-term survival benefit over chemotherapy, with manageable toxicity, as well as remarkable and durable response in patients receiving 2 years of camrelizumab, further supporting camrelizumab combination as first-line treatment for advanced non-squamous NSCLC.

5.
Eur J Cancer ; 178: 205-215, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36459768

RESUMO

BACKGROUND: Vorolanib is a highly potent tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor. This three-arm, randomised, registered study aimed to assess the combination of vorolanib and everolimus or vorolanib alone versus a control arm of everolimus as second-line treatment in patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with advanced or metastatic RCC who had received one prior VEGFR-TKI were randomised (1:1:1) to receive the combination of vorolanib and everolimus or either monotherapy. Patients with brain metastases were excluded. The primary end-point was progression-free survival (PFS) assessed by the independent review committee per Response Evaluation Criteria in Solid Tumours v1.1. RESULTS: Between 10th March 2017 and 30th May 2019, 399 patients (133 in each group) were enrolled. By the cutoff date (30th April 2020), a significant improvement in PFS was detected in the combination group compared with the everolimus group (10.0 versus 6.4 months; hazard ratio, 0.70; P = 0.0171). PFS was similar between the vorolanib group and the everolimus group (median: 6.4 versus 6.4 months; hazard ratio, 0.94; P = 0.6856). A significantly higher objective response rate was observed in the combination group than in the everolimus group (24.8% versus 8.3%; P = 0.0003), whereas there was no significant difference between the vorolanib group and the everolimus group (10.5% versus 8.3%; P = 0.5278). The overall survival data were immature. A total of 96 (72.2%), 52 (39.1%) and 71 (53.4%) grade 3 or higher treatment-related adverse events occurred in the combination group, vorolanib group and everolimus group, respectively. CONCLUSIONS: The addition of vorolanib to everolimus as 2nd-line treatment for patients with advanced or metastatic RCC who have experienced cancer progression after VEGFR-TKI therapy provided a better objective response rate and PFS than everolimus alone with a manageable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03095040; Chinadrugtrials, CTR20160987.

6.
Comput Struct Biotechnol J ; 20: 6543-6551, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467579

RESUMO

The world's population continues to increase and thus requires more food production to take place in nonarable land, such as saline soil; therefore, it is urgent to find solutions to enhance the salinity tolerance of crops. As the second genome of plants, the rhizosphere microbiome plays critical roles in plant fitness under stress conditions. Many beneficial microbes that help plants cope with salinity stress have been identified, highlighting their roles in mitigating salt stress-induced negative effects on plants. However, a comprehensive review of the microbial species that are able to confer plant salt tolerance and the underlying mechanisms is still lacking. In this review, we compared the representative fungal and bacterial taxa that demonstrate the ability to enhance plant growth in saline soil. We also reviewed the mechanisms by which rhizosphere microbes enhance plant salt stress tolerance, i.e., by re-establishing ion and osmotic homeostasis, preventing damage to plant cells, and resuming plant growth under salt stress. Finally, future research efforts to explore the rhizosphere microbiome for agricultural sustainability are proposed.

7.
Cancer Commun (Lond) ; 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36336841

RESUMO

BACKGROUND: Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer (sqNSCLC) after failure of first-line chemotherapy are limited. This study (ORIENT-3) aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC. METHODS: ORIENT-3 was an open-label, multicenter, randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy. Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m2 of docetaxel intravenously every 3 weeks, stratified by the Eastern Cooperative Oncology Group performance status. The primary endpoint was overall survival (OS) in the full analysis set (FAS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. RESULTS: Between August 25, 2017, and November 7, 2018, 290 patients were randomized. For FAS, 10 patients from the docetaxel arm were excluded. The median OS was 11.79 (n = 145; 95% confidence interval [CI], 10.28-15.57) months with sintilimab versus 8.25 (n = 135; 95% CI, 6.47-9.82) months with docetaxel (hazard ratio [HR]: 0.74; 95% CI, 0.56-0.96; P = 0.025). Sintilimab treatment significantly prolonged PFS (median 4.30 vs. 2.79 months; HR: 0.52; 95% CI, 0.39-0.68; P < 0.001) and showed higher ORR (25.50% vs. 2.20%, P < 0.001) and DCR (65.50% vs. 37.80%, P < 0.001) than the docetaxel arm. The median DoR was 12.45 (95% CI, 4.86-25.33) months in the sintilimab arm and 4.14 (95% CI, 1.41-7.23) months in the docetaxel arm (P = 0.045). Treatment-related adverse events of grade ≥ 3 were reported in 26 (18.1%) patients in the sintilimab arm and 47 (36.2%) patients in the docetaxel arm. Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors, including OVOL2 (HR: 0.35; P < 0.001) and CTCF (HR: 3.50; P < 0.001),for sintilimab treatment. CONCLUSIONS: Compared with docetaxel, sintilimab significantly improved the OS, PFS, and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.

8.
Cancers (Basel) ; 14(21)2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36358598

RESUMO

Lung cancer is one of the most common malignant tumors in human beings. It is highly fatal, as its early symptoms are not obvious. In clinical medicine, physicians rely on the information provided by pathology tests as an important reference for the final diagnosis of many diseases. Therefore, pathology diagnosis is known as the gold standard for disease diagnosis. However, the complexity of the information contained in pathology images and the increase in the number of patients far outpace the number of pathologists, especially for the treatment of lung cancer in less developed countries. To address this problem, we propose a plug-and-play visual activation function (AF), CroReLU, based on a priori knowledge of pathology, which makes it possible to use deep learning models for precision medicine. To the best of our knowledge, this work is the first to optimize deep learning models for pathology image diagnosis from the perspective of AFs. By adopting a unique crossover window design for the activation layer of the neural network, CroReLU is equipped with the ability to model spatial information and capture histological morphological features of lung cancer such as papillary, micropapillary, and tubular alveoli. To test the effectiveness of this design, 776 lung cancer pathology images were collected as experimental data. When CroReLU was inserted into the SeNet network (SeNet_CroReLU), the diagnostic accuracy reached 98.33%, which was significantly better than that of common neural network models at this stage. The generalization ability of the proposed method was validated on the LC25000 dataset with completely different data distribution and recognition tasks in the face of practical clinical needs. The experimental results show that CroReLU has the ability to recognize inter- and intra-class differences in cancer pathology images, and that the recognition accuracy exceeds the extant research work on the complex design of network layers.

9.
Cancer Commun (Lond) ; 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36331328

RESUMO

BACKGROUND: Although programmed cell death 1 (PD-1) blockade plus chemotherapy can significantly prolong the progression-free survival (PFS) and overall survival (OS) in first-line settings in patients with driver-negative advanced non-small-cell lung cancer (NSCLC), the predictive biomarkers remain undetermined. Here, we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus chemotherapy. METHODS: Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy alone. Tumor immune microenvironmental markers, including PD-1 ligand (PD-L1), CD8, CD68, CD4 and forkhead box P3, were assessed using multiplex immunofluorescence (mIF) assays. Kaplan-Meier curves were used to determine treatment outcome differences according to their expression status. Mutational profiles were compared between tumors with distinct expression levels of these markers and their combinations. RESULTS: Responders had significantly higher CD8/PD-L1 (P = 0.015) or CD68/PD-L1 co-expression levels (P = 0.021) than non-responders in the camrelizumab plus chemotherapy group, while no difference was observed in the chemotherapy group. Patients with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS (P = 0.002, P = 0.024; respectively) and OS (P = 0.006, P = 0.026; respectively) than those with low co-expression in camrelizumab plus chemotherapy group. When comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification, significantly better PFS (P = 0.003) and OS (P = 0.032) were observed in high co-expression subgroups. The predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological features. Although the prevalence of TP53 or KRAS mutations was similar between patients with and without CD8/PD-L1 or CD68/PD-L1 co-expression, the positive groups had a significantly higher proportion of TP53/KRAS co-mutations than the negative groups (both 13.0% vs. 0.0%, P = 0.023). Notably, enriched PI3K (P = 0.012) and cell cycle pathway (P = 0.021) were found in the CD8/PD-L1 co-expression group. CONCLUSION: Tumor immune microenvironmental marker expression, especially CD8/PD-L1 or CD68/PD-L1 co-expression, was associated with the efficacy of PD-1 blockade plus chemotherapy as first-line treatment in patients with advanced NSCLC.

10.
ACS Nano ; 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36445074

RESUMO

Photon radiotherapy is a common tool in the armory against tumors, but it is limited by hypoxia-related radioresistance of tumors and radiotoxicity to normal tissues. Here, we constructed a spatiotemporally controlled synergistic therapy platform based on the heterostructured CuO@Graphdiyne (CuO@GDY) nanocatalyst for simultaneously addressing the two key problems above in radiotherapy. First, the in situ formed Z-scheme CuO@GDY heterojunction performs highly efficient and controlled photocatalytic O2 evolution upon near-infrared (NIR) laser stimulation for tumor hypoxia alleviation. Subsequently, the CuO@GDY nanocatalyst with X-ray-stimulated Cu+ active sites can accelerate Fenton-like catalysis of ·OH production by responding to endogenous H2O2 for the selective killing of tumor cells rather than normal cells. In this way, the sequential combination of NIR-triggered photocatalytic O2 production and X-ray-accelerated Fenton-like reaction can lead to a comprehensive radiosensitization. Overall, this synergism underscores a controllable and precise therapy modality for simultaneously unlocking the hypoxia and non-selectivity in radiotherapy.

11.
BMC Med ; 20(1): 408, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36280870

RESUMO

BACKGROUND: Dual inhibition of PD-1/PD-L1 and TGF-ß pathways is a rational therapeutic strategy for malignancies. SHR-1701 is a new bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused with the extracellular domain of TGF-ß receptor II. This first-in-human trial aimed to assess SHR-1701 in pretreated advanced solid tumors and find the population who could benefit from SHR-1701. METHODS: This was a dose-escalation, dose-expansion, and clinical-expansion phase 1 study. Dose escalation was initiated by accelerated titration (1 mg/kg q3w; intravenous infusion) and then switched to a 3+3 scheme (3, 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w), followed by dose expansion at 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w. The primary endpoints of the dose-escalation and dose-expansion parts were the maximum tolerated dose and recommended phase 2 dose. In the clinical-expansion part, selected tumors were enrolled to receive SHR-1701 at the recommended dose, with a primary endpoint of confirmed objective response rate (ORR). RESULTS: In total, 171 patients were enrolled (dose-escalation: n=17; dose-expansion, n=33; clinical-expansion, n=121). In the dose-escalation part, no dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. SHR-1701 showed a linear dose-exposure relationship and the highest ORR at 30 mg/kg every 3 weeks, without obviously aggravated toxicities across doses in the dose-escalation and dose-expansion parts. Combined, 30 mg/kg every 3 weeks was determined as the recommended phase 2 dose. In the clinical-expansion part, SHR-1701 showed the most favorable efficacy in the gastric cancer cohort, with an ORR of 20.0% (7/35; 95% CI, 8.4-36.9) and a 12-month overall survival rate of 54.5% (95% CI, 29.5-73.9). Grade ≥3 treatment-related adverse events occurred in 37 of 171 patients (22%), mainly including increased gamma-glutamyltransferase (4%), increased aspartate aminotransferase (3%), anemia (3%), hyponatremia (3%), and rash (2%). Generally, patients with PD-L1 CPS ≥1 or pSMAD2 histochemical score ≥235 had numerically higher ORR. CONCLUSIONS: SHR-1701 showed an acceptable safety profile and encouraging antitumor activity in pretreated advanced solid tumors, especially in gastric cancer, establishing the foundation for further exploration. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03710265.


Assuntos
Neoplasias Gástricas , Humanos , gama-Glutamiltransferase/uso terapêutico , Receptor de Morte Celular Programada 1 , Anticorpos Monoclonais/uso terapêutico , Aspartato Aminotransferases/uso terapêutico , Fator de Crescimento Transformador beta/uso terapêutico , Receptores de Fatores de Crescimento Transformadores beta/uso terapêutico
12.
Appl Opt ; 61(25): 7366-7372, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36256036

RESUMO

The design of a compact zoom lens requires a designer's most abundant and professional skills and experience, which increases the difficulty of zoom lens miniaturization. In this paper, an automatic optimal focal length search method for a catadioptric zoom lens is proposed. After 7 h of searching for the initial structure and further optimization, a 3× compact zoom lens based on a telecentric intermediate image is obtained, which is applicable for 1/4 inch (6.35 mm) CMOS, with a focal length range of -4.8∼-14mm and a F-number range of 2.7-8.0. The depth and total length are within 6 mm and 30 mm, separately. The proposed method helps to reduce researchers' difficulty in designing compact zoom lenses and can provide some reference for the development of the mobile zoom lens industry.

13.
Appl Opt ; 61(21): 6241-6248, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-36256238

RESUMO

In this paper, we propose a method to automatically generate design starting points for free-form three-mirror imaging systems with different folding configurations using deep neural networks. For a given range of system parameters, a large number of datasets are automatically generated using the double seed extended curve algorithm and coded optimization. Deep neural networks are then trained using a supervised learning approach and can be used to generate good design starting points directly. The feasibility of the method is verified by designing a free-form three-mirror system with three different folding configurations. This method can significantly reduce the design time and effort for free-form imaging systems, and can be extended to complex optical systems with more optical surfaces.

14.
Nanomaterials (Basel) ; 12(19)2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36234472

RESUMO

Bird pest control has become a major task for the operation and maintenance of distribution network lines. Epoxy resin that cures quickly at room temperature can be used to coat locations where birds frequently build their nests. However, epoxy resin has enormous internal stress and is brittle, so it is essential to toughen it. In this paper, for a room temperature curing system composed of polyurethane-modified epoxy resin and a polythiol curing agent, three kinds of particles, i.e., Al2O3, SiO2, and Mg(OH)2, were used to modify a polyurethane modified epoxy resin. Orthogonal experiments were designed to study the effects of different fillers on the comprehensive properties of polyurethane-modified epoxy resins. The experimental results showed that there were not only independent effects of different kinds if particles on the resin, but also synergistic effects of multiple particles. Nanoparticles can reduce the defects introduced by microparticles to a certain extent and improve the mechanical and electrical properties of the resin. The overall performance of the resin was optimized when the amounts of SiO2, Al2O3, and Mg(OH)2 were 1.7%, 2.5%, and 7%, respectively. The tensile strength of the resin was increased by 70%, the elongation at a break by 67.53%, and the breakdown strength by 20.31% compared with before the addition of filler. The microscopic morphology and thermal properties of the resin before and after the addition of filler were also studied. Adding fillers caused more cracks to absorb part of the energy when the resin matrix was stressed and increased the rigidity of the resin matrix and the resin's glass transition temperature (Tg) by 13.48 °C. Still, the temperature corresponding to the maximum rate of weight loss (Tmax) remained unchanged.

15.
Comput Intell Neurosci ; 2022: 2551137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211002

RESUMO

Big data has the traits such as "the curse of dimensionality," high storage cost, and heavy computation burden. Self-representation-based feature extraction methods cannot effectively deal with the image-level structural noise in the data, so how to character a better relationship of reconstruction representation is very important. Recently, sparse representation with smoothed matrix multivariate elliptical distribution (SMED) using structural information to handle low-rank error images caused by illumination or occlusion has been proposed. Based on SMED, we present a new method named SMEDP for feature extraction. SMEDP firstly utilizes SMED to automatically construct an adjacency graph and then obtains an optimal projection matrix by maximizing the ratio of the local scatter matrix and the total scatter matrix in the PCA subspace. Experiments on the COIL-20 object database, ORL face database, and CMU PIE face database prove that SMEDP works well and can achieve considerable visual and recognition performance than the relevant methods.


Assuntos
Algoritmos , Reconhecimento Automatizado de Padrão , Bases de Dados Factuais , Iluminação , Reconhecimento Automatizado de Padrão/métodos , Reconhecimento Psicológico
16.
Aging (Albany NY) ; 14(19): 7986-8000, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-36227138

RESUMO

BACKGROUND: Lung cancer is the most frequent cancer globally with a high number of cancer-related deaths. The 4-and-a-half LIM domain protein 2 (FHL2) is an oncogenic gene, which promotes the proliferation, invasion, and metastasis of cancer cells. In this study, we aimed to demonstrate that lung cancer patients with high FHL2 expression have worse overall survival (OS) and relapse-free survival (RFS). METHODS: TCGA was used to study FHL2 mRNA expression. Nomograms were used to predict the relationship between FHL2 expression levels and survival. The qRT-PCR was used to detect the FHL2 expression in lung cancer cells. In vitro experiments including CCK-8 assay, wound healing, and Transwell assay were performed. RESULTS: This study comprised RNA-Seq gene expression data and clinical features for 1018 lung cancer patients. FHL2 was found to be overexpressed in lung cancer tissues. FHL2 demonstrated moderate diagnostic ability for lung cancer (AUC = 0.857). Kaplan-Meier curves and Cox regression analysis revealed the higher FHL2 expression with the poorer OS and RFS (P < 0.001). The nomogram results indicated that FHL2 could be used to predict the survival of lung cancer patients. GSEA analysis results show that high expression of FHL2 is related to glycolysis and unfolded protein reflection. FHL2 was highly expressed in lung cancer cells and related to their proliferation, migration, and invasion ability. CONCLUSIONS: The high expression level of FHL2 in lung cancer can be used as an independent predictor of prognosis in clinical practice.


Assuntos
Neoplasias Pulmonares , Fatores de Transcrição , Humanos , Proteínas com Homeodomínio LIM/genética , Proteínas com Homeodomínio LIM/metabolismo , Prognóstico , RNA Mensageiro/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Sincalida , Recidiva Local de Neoplasia , Neoplasias Pulmonares/genética
17.
J Clin Oncol ; : JCO2200727, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36206498

RESUMO

PURPOSE: The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients (N = 465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety. RESULTS: At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS 8.4 v 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P < .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P = .0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P = .026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values ≤ .001). CONCLUSION: Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.

18.
iScience ; 25(11): 105294, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36300004

RESUMO

Root colonization by beneficial rhizobacteria determines their plant beneficial effects. The messenger c-di-GMP is involved in the bacterial transition process between motility and biofilm, which are crucial to the colonization ability of the rhizobacteria. In this study, we identified three GGDEF domain-containing proteins (YdaK, YhcK, and YtrP) and two EAL domain-containing proteins (YuxH and YkuI) in beneficial rhizobacterium Bacillus velezensis SQR9. We found that deficiency of ytrP or ykuI in SQR9 led to impaired biofilm formation, while deficiency of yuxH led to weakened motility. Further investigation showed that YtrP, YuxH, and YkuI all contributed to the root colonization of SQR9 on cucumber root. Further bioinformatics analysis showed that YtrP and YuxH are conserved in plant beneficial Bacillus group, while they do not occur in animal pathogenic Bacillus. This research will be useful for enhancing the beneficial function of Bacillus spp. in agricultural application.

19.
Brain Imaging Behav ; 16(6): 2735-2743, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36307619

RESUMO

Psychological resilience is characterized as the ability to recover from stress, which is essential for sleep quality. However, the neurological underpinnings of psychological resilience and the neural substrates of the links between psychological resilience and sleep quality in healthy brains remain not well understood. To address these issues, we adopted the method of resting-state functional connectivity (rs-FC) analysis in 144 young college students. The functional connectivity analysis indicated that psychological resilience was associated with the middle frontal gryus (MFG) functional connectivity, which mainly involved the right middle cingulum gyrus (rMCG), the right precentral gyrus (rPreCG), the left postcentral gyrus (lPoCG), and the left thalamus. Furthermore, mediation analysis suggested that psychological resilience played a mediating role in the relationship between MFG functional connectivity and sleep quality. Overall, the current study offered further evidence for the neurological underpinnings of psychological resilience and provided new insights into the relationship between psychological resilience and sleep quality from a neural basis perspective.


Assuntos
Resiliência Psicológica , Humanos , Imageamento por Ressonância Magnética/métodos , Qualidade do Sono , Encéfalo , Mapeamento Encefálico/métodos
20.
J Thorac Oncol ; 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36184068

RESUMO

INTRODUCTION: The phase 3 RATIONALE-303 trial (NCT03358875) investigated the efficacy and safety of tislelizumab versus docetaxel in pretreated patients with advanced NSCLC. Here, we report the efficacy and safety results and describe the exploratory biomarker analyses. METHODS: A total of 805 patients aged more than or equal to 18 years with locally advanced or metastatic squamous or nonsquamous NSCLC were randomized 2:1 to intravenous tislelizumab 200 mg or docetaxel 75 mg/m2 every 3 weeks. Coprimary end points were overall survival (OS) in the intent-to-treat (ITT) and programmed death-ligand 1 (PD-L1) tumor cell expression greater than or equal to 25% populations. The exploratory biomarker analyses included PD-L1 expression, tumor mutation burden, and gene expression profile. RESULTS: At the prespecified interim analysis (August 10, 2020), the co-primary end point of OS in the ITT population was met, with a statistically significant and clinically meaningful improvement in OS with tislelizumab versus docetaxel (median 17.2 versus 11.9 mo, respectively; hazard ratio [HR] = 0.64, p < 0.0001). At the final analysis (July 15, 2021), the other co-primary end point of OS in the PD-L1 tumor cell greater than or equal to 25% population was further met (median 19.3 versus 11.5 mo, respectively; HR = 0.53, p < 0.0001), and OS continued to improve in the ITT population (median 16.9 versus 11.9 mo, respectively, HR = 0.66). Exploratory biomarker analyses revealed the potential association of NOTCH1-4 mutations with improved tislelizumab efficacy for both OS and progression-free survival, whereas tissue tumor mutation burden correlated with progression-free survival benefit, but not OS benefit. No new safety signals were identified. CONCLUSIONS: Tislelizumab was found to have a significantly improved and long-term clinical benefit in OS versus docetaxel in pretreated patients with advanced NSCLC, regardless of PD-L1 expression.

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