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Advanced cervical cancer (aCC) is associated with a poor prognosis. This study aimed to develop and validate a deep learning-based risk stratification model to predict overall survival in aCC patients using pre-treatment CT images. A total of 396 patients with aCC were retrospectively enrolled and randomly allocated into training ( n  = 198) and validation ( n  = 198) cohorts. A deep learning model integrating a Vision Transformer (ViT) for feature extraction and a Recurrent Neural Network (RNN) for sequence modeling was developed to generate a prognostic radiomic signature (Rad-score) from baseline CT scans. The Rad-score was incorporated into a Cox proportional hazards model alongside clinical variables to construct an integrative nomogram. The model’s performance was evaluated using the concordance index (C-index), time-dependent receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). Multivariate Cox regression identified the Rad-score as a strong independent prognostic factor (Hazard Ratio [HR] = 4.06, 95% confidence interval [CI]: 2.46–6.70, p  < 0.001). The integrative nomogram achieved C-indexes of 0.784 (95% CI: 0.733–0.835) and 0.726 (95% CI: 0.677–0.785) in the training and validation cohorts, respectively. Calibration and DCA curves indicated good clinical utility. Kaplan-Meier analysis confirmed that the model-based risk stratification significantly discriminated between high- and low-risk patients ( p  < 0.001). The proposed deep learning-based nomogram offers a non-invasive and reproducible tool for predicting survival in aCC patients. It shows potential for assisting clinicians in making personalized treatment decisions and warrants further validation in prospective, multi-center studies before widespread clinical application.

Background This study aimed to evaluate alterations in macular microstructure and blood flow density in patients with transfusion-dependent β-thalassemia (TDT) using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA), and to explore their associations with markers of iron metabolism. Methods A cross-sectional study was conducted involving 31 TDT patients (61 eyes) and 31 age- and sex-matched healthy controls (61 eyes) at the Affiliated Hospital of Guangdong Medical University from October 2022 to December 2023. Data collected included basic information, medical history, best-corrected visual acuity, ocular biometry, fundus photography, and OCT/OCTA imaging. Parameters assessed comprised the thickness and blood flow density of individual macular layers, as well as choroidal stromal area, choroidal luminal area, and choroidal vascular index (CVI). Pearson correlation analysis was employed to examine relationships among macular parameters, serum ferritin (SF) levels, duration of iron chelation therapy (ICT), and other variables. Results Compared to healthy controls, TDT patients exhibited significant thinning of the central macular area ganglion cell layer, retinal nerve fiber layer, and ganglion cell complex (mGCC), accompanied by increased blood flow density in the deep vascular complex, nerve fiber layer vascular plexus, and deep capillary plexus (all P  < 0.05). The choroidal stromal area was reduced ( P  = 0.037), whereas CVI was elevated ( P  = 0.034). Pearson correlation analysis revealed a positive correlation between central mGCC thickness and the duration of ICT ( r  = 0.280, P <  0.05),and a significant positive correlation between CVI with SF levels ( r  = 0.426, P  < 0.01). Stepwise linear regression analysis identified the duration of ICT ( β  = 0.306, P  = 0.011) as a significant independent factor influencing central mGCC thickness. Similarly, SF levels significantly influenced CVI ( β  = 0.469, P  < 0.001). Additionally, 62.30% of TDT patients’ eyes presented with tilted optic discs, 34.43% showed tessellated fundus, and 6.56% had pseudoxanthoma elasticum. Conclusions TDT patients exhibit both macular neuroretinal thinning and increased microvascular blood flow density. CVI and central mGCC thickness may serve as potential biomarkers for monitoring iron-related ocular pathology and therapeutic efficacy. Future longitudinal studies are warranted to validate their predictive value and establish causality. Regular ocular screening is warranted in this population.

Background The aim of this study was to evaluate the effectiveness and safety of different treatment strategies for endogenic caesarean scar pregnancy (CSP) patients. Methods According to Vial’s standard, we defined endogenic-type CSP as (1) the gestational sac growing towards the uterine cavity and (2) a greater than 0.3 cm thickness of myometrial tissue at the caesarean scar. A total of 447 endogenic CSP patients out of 527 patients from 4 medical centres in China were enrolled in this study. A total of 120 patients were treated with methotrexate (MTX) followed by surgery, 106 received ultrasound-guided curettage directly and 221 received curettage combined with hysteroscopy. The clinical information and clinical outcomes of these patients were reviewed. Successful treatment was defined as (1) no additional treatment needed, (2) no retained mass of conception and (3) serum β subunit of human chorionic gonadotropin (β-hCG) level returning to a normal level within 4 weeks. The success rate was analysed based on these factors. Result Among 447 patients, no significant difference was observed in baseline characteristics between groups except for foetal heartbeat. The success rate was significantly different ( p <0.001) among the three groups. The highest success rate of 95.9% was noted in the hysteroscopy group, and the lowest success rate of 84.0% was noted in the curettage group. In addition, the MTX group reported the longest hospital stay and highest expenses, but the curettage group showed the shortest and lowest expenses, respectively. Nevertheless, no difference in blood loss was observed between the groups. Conclusion The combination of curettage and hysteroscopy represents the most effective strategy. Pretreatment with MTX did not result in better clinical outcomes. Ultrasound-guided curettage directly should not be considered a first-line treatment choice for endogenic CSP patients.

Sasa argenteostriata (Regel) E.G. Camus is a gramineous plant with the potential for phytoremediation. In this study, we aimed to determine its tolerance to zinc stress and combined lead–zinc stress and the effect of zinc on its absorption and accumulation characteristics of lead. The results showed that S. argenteostriata had good tolerance to zinc stress, and S. argenteostriata was not significantly damaged when the zinc stress concentration was 600 mg/L. Under both zinc stress and combined lead–zinc stress, the root was the main organ that accumulated heavy metals in S. argenteostriata. The presence of zinc promoted the absorption of lead by the root of S. argenteostriata, and the lead content in the root under PZ1, PZ2, PZ3 and PZ4 treatments was 2.15, 4.31, 4.47 and 6.01 times that of PZ0 on the 20 days. In the combined lead–zinc stress treatments, the toxicity of heavy metals to S. argenteostriata was mainly caused by lead. Under high concentrations of combined lead–zinc stress (PZ4), the proportion of zinc in the leaf of S. argenteostriata on the 20 days increased, which was used as a tolerance strategy to alleviate the toxicity of lead.

Naturally occurring fluorescent proteins (FPs) are the most widely used tools for tracking cellular proteins and sensing cellular events. Here, we chemically evolved the self-labeling SNAP-tag into a palette of SNAP-tag mimics of fluorescent proteins (SmFPs) that possess bright, rapidly inducible fluorescence ranging from cyan to infrared. SmFPs are integral chemical-genetic entities based on the same fluorogenic principle as FPs, i.e., induction of fluorescence of non-emitting molecular rotors by conformational locking. We demonstrate the usefulness of these SmFPs in real-time tracking of protein expression, degradation, binding interactions, trafficking, and assembly, and show that these optimally designed SmFPs outperform FPs like GFP in many important ways. We further show that the fluorescence of circularly permuted SmFPs is sensitive to the conformational changes of their fusion partners, and that these fusion partners can be used for the development of single SmFP-based genetically encoded calcium sensors for live cell imaging.

Human pancreatic ductal adenocarcinoma (PDAC) is characterized by early systemic dissemination. Although RhoC has been implicated in cancer cell migration, the relevant underlying molecular mechanisms remain unknown. RhoC has been implicated in the enhancement of cancer cell migration and invasion, with actions which are distinct from RhoA (84% homology), and are possibly attributed to the divergent C-terminus domain. Here, we confirm that RhoC significantly enhances the migratory and invasive properties of pancreatic carcinoma cells. In addition, we show that RhoC over-expression decreases cancer cell adhesion and, in turn, accelerates cellular body movement and focal adhesion turnover, especially, on fibronectin-coated surfaces. Whilst RhoC over-expression did not alter integrin expression patterns, we show that it enhanced integrin α5β1 internalization and re-cycling (trafficking), an effect that was dependent specifically on the C-terminus (180-193 amino acids) of RhoC protein. We also report that RhoC and integrin α5β1 co-localize within the peri-nuclear region of pancreatic tumor cells, and by masking the CAAX motif at the C-terminal of RhoC protein, we were able to abolish this interaction in vitro and in vivo. Co-localization of integrin α5β1 and RhoC was demonstrable in invading cancer cells in 3D-organotypic cultures, and further mimicked in vivo analyses of, spontaneous human, (two distinct sources: operated patients and rapid autopsy programme) and transgenic murine (LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre), pancreatic cancers. In both cases, co-localization of integrin α5β1 and RhoC correlated with poor differentiation status and metastatic potential. We propose that RhoC facilitates tumor cell invasion and promotes subsequent metastasis, in part, by enhancing integrin α5β1 trafficking. Thus, RhoC may serve as a biomarker and a therapeutic target.

Fluorescent RNAs (FRs), aptamers that bind and activate fluorescent dyes, have been used to image abundant cellular RNA species. However, limitations such as low brightness and limited availability of dye/aptamer combinations with different spectral characteristics have limited use of these tools in live mammalian cells and in vivo. Here, we develop Peppers, a series of monomeric, bright and stable FRs with a broad range of emission maxima spanning from cyan to red. Peppers allow simple and robust imaging of diverse RNA species in live cells with minimal perturbation of the target RNA’s transcription, localization and translation. Quantification of the levels of proteins and their messenger RNAs in single cells suggests that translation is governed by normal enzyme kinetics but with marked heterogeneity. We further show that Peppers can be used for imaging genomic loci with CRISPR display, for real-time tracking of protein–RNA tethering, and for super-resolution imaging. We believe these FRs will be useful tools for live imaging of cellular RNAs.

Objective Peripheral systemic inflammatory, nutritional, and coagulation biomarkers have prognostic and predictive value in various malignancies. We evaluated the prognostic and predictive roles of systemic inflammatory, nutritional, and coagulation biomarkers in the circulating blood of patients with advanced cervical cancer. Methods A retrospective study of 795 patients with cervical cancer who received concurrent chemoradiation therapy was performed. Overall survival was evaluated by the Kaplan–Meier estimator. Univariate and multivariate Cox regression models were used to determine prognostic factors associated with overall survival. Results The median follow-up time was 76 months. In the univariate analysis, overall survival showed positive prognostic value in patients with a platelet-to-lymphocyte ratio (PLR) <164.29 (P = 0.010), and a plasma fibrinogen (FIB) level <4 g/L(P = 0.012). In the multivariate analysis, the PLR (P = 0.036), and FIB level (P = 0.047) maintained their significance for overall survival. Therefore, the PLR and FIB levels are independent prognostic factors in patients with advanced cervical cancer. Conclusions Systemic inflammatory and coagulation biomarkers could help to understand survival differences in the clinical treatment of advanced cervical cancer. The PLR and FIB levels are independent prognostic factors of poor survival in patients with advanced cervical cancer.

Approximately 90% of malignant ovarian tumours are epithelial and thought to arise from a single cell layer, the ovarian surface epithelium. In culture, human normal ovarian surface epithelial (OSE) cells have a very limited lifespan before they senesce, rarely progressing beyond 10 population doublings. This has restricted the use of normal OSE cells for studying the biology of ovarian surface epithelium and identifying molecular events that contribute to malignant transformation. We have investigated the conditions for culturing human, normal OSE cells in vitro using modified media. Culturing normal OSE cells in a modified medium (NOSE-CM) supplemented with epidermal growth factor, hydrocortisone, insulin and bovine pituitary extract led to significant improvements in the seeding and cloning efficiencies, overall cell growth and lifespan compared to culturing in a basic, nonsupplemented medium (BM) and previously used media (F-12 K medium and William's medium E). Cells cultured in NOSE-CM underwent, on an average, 19.0 population doublings (95% CI 16.3–21.7); cells cultured in BM underwent 0.43–3.52 population doublings over a similar time period. Growth curves established for different lines indicated that OSE cells continued to grow beyond passage 11 and up to passage 18 in NOSE-CM, but never beyond passage 7 when cultured in BM. It is likely that establishing optimal conditions for the growth of OSE cells in vitro will enable studies of the biological and genetic mechanisms of transformation in epithelial ovarian cancers.

Sasa argenteostriata (Regel) E.G. Camus is a gramineous plant with the potential for phytoremediation. In this study, we aimed to determine its tolerance to zinc stress and combined lead–zinc stress and the effect of zinc on its absorption and accumulation characteristics of lead. The results showed that S. argenteostriata had good tolerance to zinc stress, and S. argenteostriata was not significantly damaged when the zinc stress concentration was 600 mg/L. Under both zinc stress and combined lead–zinc stress, the root was the main organ that accumulated heavy metals in S. argenteostriata. The presence of zinc promoted the absorption of lead by the root of S. argenteostriata, and the lead content in the root under PZ1, PZ2, PZ3 and PZ4 treatments was 2.15, 4.31, 4.47 and 6.01 times that of PZ0 on the 20 days. In the combined lead–zinc stress treatments, the toxicity of heavy metals to S. argenteostriata was mainly caused by lead. Under high concentrations of combined lead–zinc stress (PZ4), the proportion of zinc in the leaf of S. argenteostriata on the 20 days increased, which was used as a tolerance strategy to alleviate the toxicity of lead.