ABSTRACT
PURPOSE: Adolescent and young adult (AYA) cancer patients, aged between 15 to 39 years old, suffer from long-term psychological distress, confronting low self-efficacy and various psychological problems. This study constructs a group online-based peer support intervention combined with offline activities to explore its impact on the psychological distress of AYA cancer patients. METHODS: A randomized, two-arm clinical trial was conducted in which 90 AYA cancer patients were recruited. The control group (N = 45) received conventional psychological care and treatment, and the experimental group (N = 45) received 8 weeks of an online peer support intervention. Outcome measures included psychological distress (Distress Thermometer, DT), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), perceived peer support (Cancer Peer Support Scales, CaPSS), and readiness for return to work (Readiness to Return-To-Work Scale, RRTW). RESULTS: Eight-week peer support intervention was effective in improving psychological distress, anxiety, and depressive symptoms in the experimental group with statistically significant differences (P < 0.05). Time affected psychological distress, anxiety, and depressive symptoms in AYA cancer patients (P < 0.05), and there was an interaction with intervention factors (P < 0.05). The intervention has a positive effect on relieving the psychological status of AYA cancer patients. For readiness for return to work, the experimental group was in the preparation for the action-behavioral stage immediately, 1 month and 3 months after the end of the intervention (P < 0.01), supporting AYA cancer patients who have not returned to work to maintain optimal return-to-work readiness. CONCLUSIONS: The group online-based peer support intervention is popular and has good scientificity, effectiveness, and practical significance for AYA cancer patients. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov. (ChiCTR2100053091, registered on 10 November 2021).
Subject(s)
Neoplasms , Peer Group , Psychological Distress , Social Support , Humans , Adolescent , Female , Male , Young Adult , Adult , Neoplasms/psychology , Neoplasms/therapy , Depression/therapy , Depression/etiology , Depression/psychology , Anxiety/etiology , Anxiety/therapy , Stress, Psychological/etiology , Stress, Psychological/therapy , Internet-Based InterventionABSTRACT
Image completion has made tremendous progress with convolutional neural networks (CNNs), because of their powerful texture modeling capacity. However, due to some inherent properties (e.g., local inductive prior, spatial-invariant kernels), CNNs do not perform well in understanding global structures or naturally support pluralistic completion. Recently, transformers demonstrate their power in modeling the long-term relationship and generating diverse results, but their computation complexity is quadratic to input length, thus hampering the application in processing high-resolution images. This paper brings the best of both worlds to pluralistic image completion: appearance prior reconstruction with transformer and texture replenishment with CNN. The former transformer recovers pluralistic coherent structures together with some coarse textures, while the latter CNN enhances the local texture details of coarse priors guided by the high-resolution masked images. To decode diversified outputs from transformers, auto-regressive sampling is the most common method, but with extremely low efficiency. We further overcome this issue by proposing a new decoding strategy, temperature annealing probabilistic sampling (TAPS), which firstly achieves more than 70× speedup of inference at most, meanwhile maintaining the high quality and diversity of the sampled global structures. Moreover, we find the full CNN architecture will lead to suboptimal solutions for guided upsampling. To render more realistic and coherent contents, we design a novel module, named texture-aware guided attention, to concurrently consider the procedures of texture copy and generation, meanwhile raising several important modifications to solve the boundary artifacts. Through dense experiments, we found the proposed method vastly outperforms state-of-the-art methods in terms of four aspects: 1) large performance boost on image fidelity even compared to deterministic completion methods; 2) better diversity and higher fidelity for pluralistic completion; 3) exceptional generalization ability on large masks and generic dataset, like ImageNet. 4) Much higher decoding efficiency over previous auto-regressive based methods.
ABSTRACT
Bladder cancer(BC) is one of the most prevalent cancers in the urinary tract, with high recurrence and fatality rates. Research indicates that go-ichi-ni-san complex subunit 1 (GINS1) crucially influences cancer progression by regulating DNA replication through cell cycle modulation. Thus, suppressing the active proliferation of cells in tumor tissues may require silencing GINS1. However, the consequences of GINS1 in bladder cancer aren't to be determined. In this paper, we examine the role and mechanism of GINS1 in the development of bladder cancer. GINS1 expression levels and prognostic relevance in bladder cancer were validated using Western blotting, immunohistochemistry, and Kaplan-Meier survival analysis. The influence of GINS1 on bladder cancer was investigated using a variety of approaches, including cell transfection, cell counts, transwell migrations, colony formation, and flow cytometry. Immunohistochemistry studies demonstrate that GINS1 expression is increased in bladder cancer tissues. GINS1 silencing resulted in an arrest of the cell cycle at the phase of G0/G1, which inhibited BC cell growth both in vitro and in vivo. GINS1 knockdown also hindered the AKT/mTOR pathway. Furthermore, increased GINS1 expression affects the cell cycle and stimulates the AKT/mTOR pathway, allowing BC to develop more quickly. Consequently, GINS1 occurs as a latent therapeutic target, particularly for individuals with BC.
Subject(s)
Cell Proliferation , Chromosomal Proteins, Non-Histone , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Humans , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Chromosomal Proteins, Non-Histone/metabolism , Chromosomal Proteins, Non-Histone/genetics , Cell Proliferation/genetics , Animals , Cell Line, Tumor , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins c-myc/genetics , Gene Expression Regulation, Neoplastic , Mice , Disease Progression , Mice, Nude , Male , Female , Prognosis , Mice, Inbred BALB C , DNA-Binding ProteinsABSTRACT
5-methylcytosine (m5C) is among the most common epigenetic modification in DNA and RNA molecules, and plays an important role in the animal development and disease pathogenesis. Interestingly, unlike other m5C DNA methyltransferases (DNMTs), DNMT2/TRDMT1 has the double-substrate specificity and adopts a DNMT-similar catalytic mechanism to methylate RNA. Moreover, it is widely involved in a variety of physiological regulatory processes, such as the gene expression, precise protein synthesis, immune response, and disease occurrence. Thus, comprehending the epigenetic mechanism and function of DNMT2/TRDMT1 will probably provide new strategies to treat some refractory diseases. Here, we discuss recent studies on the spatiotemporal expression pattern and post-translational modifications of DNMT2/TRDMT1, and summarize the research advances in substrate characteristics, catalytic recognition mechanism, DNMT2/TRDMT1-related genes or proteins, pharmacological application, and inhibitor development. This review will shed light on the pharmacological design by targeting DNMT2/TRDMT1 to treat parasitic, viral and oncologic diseases.
Subject(s)
DNA (Cytosine-5-)-Methyltransferases , Humans , Animals , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA (Cytosine-5-)-Methyltransferases/antagonists & inhibitors , DNA (Cytosine-5-)-Methyltransferases/genetics , Epigenesis, Genetic/drug effects , Protein Processing, Post-Translational/drug effects , DNA Methylation/drug effectsABSTRACT
Increased expression of CXCL10 and its receptor CXCR3 represents an inflammatory response in cells and tissues. Macrophage polarization and autophagy are major functions in inflammatory macrophages; however, the cellular functions of the CXCL10-CXCR3 axis in macrophages are not well understood. Here, we examined the role of CXCL10-CXCR3-axis-regulated autophagy in macrophage polarization. First, in non-inflammatory macrophages, whereas CXCL10 promotes M2 polarization and inhibits M1 polarization, CXCR3 antagonist AMG487 induces the opposite macrophage polarization. Next, CXCL10 promotes the expression of autophagy proteins (Atg5-Atg12 complex, p62, LC3-II, and LAMP1) and AMG487 inhibits their expression. Knockdown of LAMP1 by short interfering RNA switches the CXCL10-induced polarization from M2 to M1 in non-inflammatory macrophages. Furthermore, in inflammatory macrophages stimulated by poly(I:C), CXCL10 induces M1 polarization and AMG487 induces M2 polarization in association with a decrease in LAMP1. Finally, AMG487 alleviates lung injury after poly(I:C) treatment in mice. In conclusion, CXCL10-CXCR3 axis differentially directs macrophage polarization in inflammatory and non-inflammatory states, and autophagy protein LAMP1 acts as the switch controlling the direction of macrophage polarization by CXCL10-CXCR3.
Subject(s)
Acetamides , Autophagy , Chemokine CXCL10 , Inflammation , Macrophages , Mice, Inbred C57BL , Pyrimidinones , Receptors, CXCR3 , Animals , Receptors, CXCR3/metabolism , Receptors, CXCR3/genetics , Chemokine CXCL10/metabolism , Chemokine CXCL10/genetics , Macrophages/immunology , Macrophages/metabolism , Mice , Autophagy/immunology , Inflammation/immunology , Inflammation/metabolism , Poly I-C/pharmacology , Lysosomal Membrane Proteins/metabolism , Lysosomal Membrane Proteins/genetics , Male , Signal Transduction , Humans , Macrophage ActivationABSTRACT
Text-driven 3D scene generation is widely applicable to video gaming, film industry, and metaverse applications that have a large demand for 3D scenes. However, existing text-to-3D generation methods are limited to producing 3D objects with simple geometries and dreamlike styles that lack realism. In this work, we present Text2NeRF, which is able to generate a wide range of 3D scenes with complicated geometric structures and high-fidelity textures purely from a text prompt. To this end, we adopt NeRF as the 3D representation and leverage a pre-trained text-to-image diffusion model to constrain the 3D reconstruction of the NeRF to reflect the scene description. Specifically, we employ the diffusion model to infer the text-related image as the content prior and use a monocular depth estimation method to offer the geometric prior. Both content and geometric priors are utilized to update the NeRF model. To guarantee textured and geometric consistency between different views, we introduce a progressive scene inpainting and updating strategy for novel view synthesis of the scene. Our method requires no additional training data but only a natural language description of the scene as the input. Extensive experiments demonstrate that our Text2NeRF outperforms existing methods in producing photo-realistic, multi-view consistent, and diverse 3D scenes from a variety of natural language prompts. Our code and model will be available upon acceptance.
ABSTRACT
PURPOSE: To evaluate the diagnostic accuracy of single and multiple fluorescence in situ hybridization (FISH) tests for upper urinary tract cancer (UTUC), we analyzed the diagnostic efficacy of FISH in patients with UTUC and the difference between it and the Tumor Node Metastasis (TNM) stage and grade of the tumor. MATERIALS AND METHODS: Patients treated for UTUC at our institution between 2011 and 2021 who had not been previously diagnosed with UTUC were included. Patients were divided into single, two, and multiple (three times or four times) FISH groups based on the number of FISH tests performed on different samples from the same patient, and the diagnostic efficiency of single, two, and multiple FISH tests for muscle-invasive tumors and highgrade tumors were assessed. RESULTS: We included a total of 207 patients with UTUC, and when compared to single FISH, the sensitivity of multiple and double FISH for the diagnosis of UTUC increased from 62% to 76% and 78%, respectively. It went from 67% to 78% and 80% for muscle-invasive UTUC (> = pT2) and from 71% to 79% and 81% for the highest- grade UTUC. CONCLUSION: Multiple FISH improves the diagnostic efficacy of UTUC and helps to differentiate aggressive tumors.
Subject(s)
Carcinoma, Transitional Cell , Kidney Neoplasms , Ureteral Neoplasms , Urinary Bladder Neoplasms , Urinary Tract , Urologic Neoplasms , Humans , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/pathology , Urinary Bladder Neoplasms/pathology , In Situ Hybridization, Fluorescence , Kidney Neoplasms/diagnosis , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Ureteral Neoplasms/diagnosis , Ureteral Neoplasms/pathology , Urologic Neoplasms/diagnosisABSTRACT
Bisphenol A (BPA) and its structural analogs (bisphenol S (BPS) and bisphenol F (BPF)) are widely consumed endocrine disrupting chemicals that may contribute to the etiology of obesity. To date, few studies have directly investigated the sex-related associations between bisphenols and body fat distribution in adults. In this study, we included 2669 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to evaluate and compare sex-specific differences of the associations of BPA, BPS, and BPF with body fat distribution. We found that there were significant positive correlations between BPS and body fat indices (STFAT [adjustedß=1.94, 95% CI: (0.24, 3.64)], TAF [0.18 (0.04, 0.32)], SAT [0.15 (0.03, 0.27)], android fat mass [0.20 (0.004, 0.40)], BMI [1.63 (0.61, 2.65)], and WC [3.19 (0.64, 5.73)] in the highest quartiles of BPS), but not in BPA and BPF. Stratified analyses suggested that the significant associations of BPS with body fat indices were stronger in women than men (STFAT [adjustedß=3.75, 95% CI: (1.04, 6.45) vs. adjustedß=-0.06, 95% CI: (-2.23, 2.11), P for interaction < 0.001], TAF [ 0.32 (0.09, 0.54) vs. 0.01 (-0.17, 0.19), P for interaction < 0.001], SAT [0.27 (0.09, 0.45) vs. 0.01 (-0.14, 0.16), P for interaction < 0.001], android fat mass [0.41 (0.12, 0.71) vs. -0.02 (-0.28, 0.24), P for interaction < 0.001], gynoid fat mass [0.56 (0.11, 1.01) vs. -0.05 (-0.41, 0.31), P for interaction = 0.002], BMI [2.76 (1.08, 4.44) vs. 0.47 (-0.80, 1.74), P for interaction < 0.001], and WC [5.51 (1.44, 9.58) vs. 0.61 (-2.67, 3.88), P for interaction < 0.001]), and positive associations between BPS with fat distribution were also observed in non-smoking women. Our study indicated that in women, higher concentration of urinary BPS was associated with increased body fat accumulation, except for visceral adipose tissue mass. These findings emphasize the role of environmental BPS exposure in the increasing fat deposits, and confirm the need for more prospective cohort studies on a sex-specific manner.
Subject(s)
Benzhydryl Compounds , Body Fat Distribution , Phenols , Sulfones , Male , Adult , Humans , Female , Nutrition Surveys , Prospective StudiesABSTRACT
Endothelial cell (EC) barrier dysfunction and increased adhesion of immune inflammatory cells to ECs crucially contribute to acute lung injury (ALI). Angiotensin-converting enzyme 2 (ACE2) is an essential regulator of the renin-angiotensin system (RAS) and exerts characteristic vasodilatory and anti-inflammatory effects. SARS-COV-2 infects the lungs by binding to ACE2, which can lead to dysregulation of ACE2 expression, further leading to ALI with predominantly vascular inflammation and eventually to more severe acute respiratory distress syndrome (ARDS). Therefore, restoration of ACE2 expression represents a valuable therapeutic approach for SARS-COV-2-related ALI/ARDS. In this study, we used polyinosinic-polycytidylic acid (Poly(I:C)), a double-stranded RNA analog, to construct a mouse ALI model that mimics virus infection. After Poly(I:C) exposure, ACE2 was downregulated in mouse lung tissues and in cultured ECs. Treatment with DIZE, an ACE2-activating compound, upregulated ACE2 expression and relieved ALI in mice. DIZE also improved barrier function and reduced the number of THP-1 monocytes adhering to cultured ECs. Focal adhesion kinase (FAK) and phosphorylated FAK (p-FAK) levels were increased in lung tissues of ALI mice as well as in Poly(I:C)-treated ECs in vitro. Both DIZE and the FAK inhibitor PF562271 decreased FAK/p-FAK expression in both ALI models, attenuating ALI severity in vivo and increasing barrier function and reducing monocyte adhesion in cultured ECs. Furthermore, in vivo experiments using ANG 1-7 and the MAS inhibitor A779 corroborated that DIZE-mediated ACE2 activation stimulated the activity of the ANG 1-7/MAS axis, which inhibited FAK/p-FAK expression in the mouse lung. These findings provide further evidence that activation of ACE2 in ECs may be a valuable therapeutic strategy for ALI.
Subject(s)
Acute Lung Injury , Indoles , Pyridines , Respiratory Distress Syndrome , Sulfonamides , Animals , Mice , Acute Lung Injury/drug therapy , Angiotensin-Converting Enzyme 2/metabolism , Endothelial Cells/metabolism , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Focal Adhesion Protein-Tyrosine Kinases/therapeutic use , Lung/metabolism , Peptidyl-Dipeptidase A/metabolism , Respiratory Distress Syndrome/metabolismABSTRACT
Background: Solitary fibrous tumors (SFTs) manifest in various anatomical locations but are seldom encountered in the prostate. Despite their rare occurrence in this region, SFTs demonstrate a marked propensity for recurrence. This study elucidates a case of recurrent prostate SFT, previously misdiagnosed, and delineates the salient features and diagnostic criteria pertaining for SFTs. Methods: Through a meticulous analysis of the patients antecedent medical records and corroborative diagnostic evaluations, we hypothesized that the presenting pathology was indicative of a prostate SFT. In order to substantiate this supposition, we re-examined archival pathological specimens from the patient. The ensuing pathological assessment validated our conjecture. To address the recurrence, we conducted an open surgical procedure to excise the tumor. Subsequent postoperative pathological evaluations further corroborated the diagnosis of prostate SFT. Results: Upon re-evaluation of the patients earlier pathological specimens, we discerned that what had been previously classified as a seminal vesicle tumor was, in fact, a prostate SFT. During the surgical intervention, it was observed that the prostatic tumor had invaded the bladder, yet there was no seminal vesicle involvement. The tumor dimensions were approximately 7 × 5 × 4 cm, and the margin between the tumor and the surgical resection edge was less than 0.1 cm. The postoperative histological analysis confirmed the diagnosis of recurrent prostate SFT, substantiating our designation of the patients condition as such. A year-long follow-up revealed no conspicuous signs of tumor recurrence. Conclusions: Therapeutic intervention for prostate SFT is predominantly surgical. However, given the tumors marked predisposition for recurrence, the specific mechanisms underlying its etiology and pathogenesis remain enigmatic (AU)