Efficient EPID-based quality assurance of beam time delay for respiratory-gated radiotherapy with validation on Catalyst™ and AlignRT™ systems.

PURPOSE: To propose a straightforward and time-efficient quality assurance (QA) approach of beam time delay for respiratory-gated radiotherapy and validate the proposed method on typical respiratory gating systems, Catalyst™ and AlignRT™. METHODS: The QA apparatus was composed of a motion platform and a Winston-Lutz cube phantom (WL3) embedded with metal balls. The apparatus was first scanned in CT-Sim and two types of QA plans specific for beam on and beam off time delay, respectively, were designed. Static reference images and motion testing images of the WL3 cube were acquired with EPID. By comparing the position differences of the embedded metal balls in the motion and reference images, beam time delays were determined. The proposed approach was validated on three linacs with either Catalyst™ or AlignRT™ respiratory gating systems. To investigate the impact of energy and dose rate on beam time delay, a range of QA plans with Eclipse (V15.7) were devised with varying energy and dose rates. RESULTS: For all energies, the beam on time delays in AlignRT™ V6.3.226, AlignRT™ V7.1.1, and Catalyst™ were 92.13 ± $ \pm $ 5.79 ms, 123.11 ± $ \pm $ 6.44 ms, and 303.44 ± $ \pm $ 4.28 ms, respectively. The beam off time delays in AlignRT™ V6.3.226, AlignRT™ V7.1.1, and Catalyst™ were 121.87 ± $ \pm $ 1.34 ms, 119.33 ± $ \pm $ 0.75 ms, and 97.69 ± $ \pm $ 2.02 ms, respectively. Furthermore, the beam on delays decreased slightly as dose rates increased for all gating systems, whereas the beam off delays remained unaffected. CONCLUSIONS: The validation results demonstrate the proposed QA approach of beam time delay for respiratory-gated radiotherapy was both reproducible and time-efficient to practice for institutions to customize accordingly.

Determination of nitroimidazole antibiotics based on dispersive solid-phase extraction combined with capillary electrophoresis.

For a long time, the detection of nitroimidazole antibiotics (NIABs) has been a research focus in environmental analytical chemistry. In this work, a novel technique for the analysis of nitroimidazoles was established based on capillary electrophoresis (CE). UiO-66, synthesized using a solvothermal method, was utilized as an adsorbent in the dispersive solid-phase extraction (DSPE) of five different NIABs. The separation and detection of NIABs in environmental water samples were accomplished using the CE diode array detection method. The optimal extraction conditions were obtained after systematically studying the effects of adsorption time, the amount of extractant, and elution solvent on extraction efficiency. According to the results of the study, the limit of detections of the five NIABs were between 16 and 97 ng/mL, the relative standard deviations were between 0.32% and 0.55%, and the spike recoveries were between 87.43% and 104.8%. This study presents a novel technique for measuring NIABs in complex water samples.

Increased co-expression of MEST and BRCA1 is associated with worse prognosis and immune infiltration in ovarian cancer.

OBJECTIVE: The crosstalk between tumor microenvironment (TME) and cancer cells plays a critical role in the occurrence and development of ovarian cancer. Imprinted gene MEST is a tumor-promoting factor that modulates several carcinogenic signaling pathways. This study aimed to investigate the expression pattern of MEST and its association with immune cell infiltration. METHODS: The transcriptome data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database was utilized, and the expression and immune characteristics of MEST were verified by immunohistochemistry of ovarian cancer specimens. Kaplan-Meier Plotter was used to assess the prognostic value in patients with ovarian cancer. RESULTS: We found that high expression of MEST was associated with diminished immune cell infiltration and worse prognosis of ovarian cancer patients in independent cohorts. There was a positive correlation between MEST and BRCA1 expression. The MESThighBRCA1high ovarian cancer group was correlated with lower infiltration of CD4+ cells, CD57+ cells, CD68+ cells and MPO+ cells, had worse overall survival (OS) in TCGA (HR = 1.57, p = 0.0004) and GSE27651 (HR = 4.27, p = 0.0002) cohorts, and predicted poor progress free survival (PFS) in GSE9891 (HR = 1.76, p = 0.0098) and GSE15622 (HR = 4.80, p = 0.0121) cohorts. Moreover, the expression of PD-L1 predicted unfavorable OS (HR = 2.48, p = 0.0415) and PFS (HR = 2.36, p = 0.0215) in MESTlowBRCA1low ovarian cancer group in GSE9891 cohort. CONCLUSION: These findings suggest that the co-expression of MEST and BRCA1 may be an ideal combination for predicting the prognosis and response to immunotherapy in patients with ovarian cancer.

Discovery of new small-molecule cyclin-dependent kinase 6 inhibitors through computational approaches.

Excessive cell proliferation due to cell cycle disorders is one of the hallmarks of breast cancer. Cyclin-dependent kinases (CDKs), which are involved in the transition of the cell cycle from G1 phase to S phase by combining CDKs with cyclin, are considered promising targets with broad therapeutic potential based on their critical role in cell cycle regulation. Pharmacological evidence has shown that abnormal cell cycle due to the overexpression of CDK6 is responsible for the hyperproliferation of cancer cells. Blocking CDK6 expression inhibits tumour survival and growth. Therefore, CDK6 can be regarded as a potential target for anticancer therapeutics. Thus, small molecules that can be considered CDK inhibitors have been developed into promising anticancer drugs. In this study, combined structure-based and ligand-based in silicon models were created to identify new chemical entities against CDK6 with the appropriate pharmacokinetic properties. The database used to screen drug-like compounds in this thesis was based on the best E-pharmacophore hypothesis and the best ligand-based drug hypothesis. As a result, 147 common compounds were identified by further molecular docking. Surprisingly, the in vitro evaluation results of 20 of those compounds showed that the two had good CDK6 inhibitory effects. The best compound was subjected to kinase panel screening, followed by molecular dynamic simulations. The 50-ns MD studies revealed the pivotal role of VAL101 in the binding of inhibitors to CDK6. Overall, the identification of two new chemical entities with CDK6 inhibitory activity demonstrated the feasibility and potential of the new method.

Combined Knockdown of D-dopachrome Tautomerase and Migration Inhibitory Factor Inhibits the Proliferation, Migration, and Invasion in Human Cervical Cancer.

OBJECTIVE: D-dopachrome tautomerase (D-DT) is a homologue of macrophage migration inhibitory factor (MIF) with similar functions. However, the possible biological roles of D-DT in cervical cancer remain unknown so far. METHODS: D-dopachrome tautomerase was assessed by immunohistochemistry in 83 cervical cancer and 31 normal cervix tissues. The stable knockdown of D-DT and MIF by lentivirus-delivered short hairpin RNA was established, and tumor growth was examined in vitro and in vivo. The effects of D-DT and MIF on the migration and invasion were further detected by wound healing assay and transwell assay. Western blot was used to explore the mechanism of D-DT and MIF in cervical cancer pathogenesis. RESULTS: We found that D-DT was significantly high in cervical cancer, which correlated with lymph node metastasis. The knockdown of D-DT and MIF, individually and additively, inhibited the proliferation, migration, and invasion in HeLa and SiHa cells and restrained the growth of xenograft tumor. The ablation of D-DT and MIF rescued the expression of E-cadherin and inhibited the expression of PCNA, cyclin D1, gankyrin, Sam68, and vimentin, as well as phospho-Akt and phospho-glycogen synthase kinase 3-ß. CONCLUSIONS: The inhibition of D-DT and MIF in combination may represent a potential therapeutic strategy for cervical cancer.

Clinical significance of Sam68 expression in endometrial carcinoma.

Sam68 (Src-associated in mitosis of 68 kDa) is a substrate for tyrosine kinase c-Src during mitosis. The nuclear protein level has been found to be associated with progression and prognosis in various human malignant tumors. The aim of this study is to investigate the clinical value of Sam68 in endometrial carcinoma (EC). Sam68 expression was confirmed by real-time PCR, Western blot, and immunofluorescent assay in primary normal endometrial epithelial cells, endometrial carcinoma cell lines, as well as seven pairs of EC and matched adjacent noncancerous endometrial tissues. Moreover, the protein level of Sam68 was evaluated by immunohistochemistry in a cohort of surgical specimens derived from 131 patients including primary endometrial carcinoma (n = 95), endometrial atypical hyperplasia (precancerous lesions, n = 26), and normal endometria (n = 10). In endometrial cancer cell lines, RNA interfering approach was employed to downregulate Sam68 expression to determine its role in proliferation. Clinicopathological relevance and prognostic associations were examined by statistical analyses. Compared with normal endometrial and endometrial atypical hyperplasia tissues, Sam68 significantly elevated in endometrial cancer samples (P < 0.01), which was negative or low in 37 cases (38.9 %) and high in 58 cases (61.1 %). The high expression of Sam68 was associated with histological grade (P < 0.001), FIGO stage (P = 0.039), and myometrial invasion (P = 0.002). Kaplan-Meier analysis demonstrated that overexpression of Sam68 correlated with shorter overall survival. It is confirmed by univariate and multivariate analysis (P < 0.001 and P = 0.048, respectively). Additionally, we found that Sam68 was highly expressed at both the transcriptional and translational levels in endometrial cancer cell lines (Ishikawa, HEC-1B, AN3CA, KLE, and RL95-2) and siRNA knockdown of Sam68 remarkably inhibited cellular proliferation in in vitro models. Sam68 may be useful prognostic marker for EC, and it plays an important role in promoting the cellular proliferation. Further investigation of Sam68 as a potential therapeutic target for EC patients could be of interest.

Downregulation of microRNA-145 is associated with aggressive progression and poor prognosis in human cervical cancer.

MicroRNAs (miRNAs) play important roles in the processes of tumor initiation and progression. However, miR-145 expression in cervical cancer has been rarely investigated. The aim of this study was to investigate the clinical significance and prognostic value of miR-145 expression in cervical cancer. MiR-145 expression in 114 pairs of human cervical cancer and adjacent normal tissues was detected by real-time quantitative RT-PCR assay. The results showed that miR-145 expression was significantly downregulated in cervical cancer tissues when compared with corresponding adjacent normal tissues (P < 0.001). It was also significantly lower in the cancerous tissues of patients with advanced International Federation of Gynecology and Obstetrics (FIGO) stage cervical cancer than those with early FIGO stage (P = 0.006). In addition, miR-145 was expressed at significantly lower levels in lymph node metastasis-positive patients than in lymph node metastasis-negative patients (P = 0.037). Moreover, poorly differentiated tumors expressed lower miR-145 than well or moderately differentiated tumors (P = 0.012). Patients with vascular invasion or human papillomavirus (HPV) infection also had lower miR-145 expression levels than those without (P = 0.016 and P = 0.025, respectively). Furthermore, Kaplan-Meier analysis showed that cervical cancer patients with low miR-145 expression had shorter overall survival time than those with high miR-145 expression (P < 0.001). When analyzed with a multivariate Cox regression model, miR-145 was identified as an independent prognostic factor for overall survival. Taken together, our results suggest that downregulation of miR-145 in cervical cancer is associated with aggressive progression and poor prognosis and that miR-145 may serve as a prognostic marker.

The expression of GLTSCR2 in cervical intra-epithelial lesion and cancer.

BACKGROUND: GLTSCR2 was originally identified as a candidate tumor suppressor in several types of cancers. The present study was to investigate the expression pattern of GLTSCR2 in different cervical lesion tissues, appraise its potential role in cervical cancerogenesis. METHODS: 225 histologically confirmed samples representing a wide range of cervical disease processes were studied in this study using immunohistochemistry (IHC). RESULTS: Compared with normal cervix and low-grade cervical intra-epithelial neoplasia (CIN I), cervical cancer and high-grade cervical intra-epithelial neoplasia (CIN II-III) tissues had lower expression scores of IHC staining of GLTSCR2. The positive staining signals of GLTSCR2 in CIN were decreased according to the grades of the intra-epithelial lesions. The IHC scores of GLTSCR2 in cervical cancer tissues were significantly lower than that in adjacent normal tissues. Different from previous report, we also found that GLTSCR2 was expressed in both nucleus and cytoplasm of cervical tissues, and the cytoplasmic expression of GLTSCR2 was observed in almost all tissues. CONCLUSIONS: We demonstrated the GLTSCR2 expression decreased with the rise of the grade of cervical lesions. GLTSCR2 may play an important role in carcinogenesis of cervical cancer.

MicroRNA-222 promotes the proliferation and migration of cervical cancer cells.

PURPOSE: This study aimed to investigate the role of small non-coding RNA-222 (microRNA-222; miR-222) in the development of cervical cancer (CC). METHODS: Normal and CC specimens were obtained from 18 patients. HeLa and SiHa cells were grown in Dulbecco's modified Eagle's medium. RT-PCR, Western blot, migration assay, flow cytometry and immunofluorescence microscopy were used for analyses. RESULTS: When compared with normal cervical tissues, miR-222 was upregulated in human CC, and the extent of up-regulation was associated with the extent and depth of CC invasion. Expression of miR-222 was inversely related to the expression of phosphatase and tensin homolog (PTEN) and p27. The reduced the expression of PTEN and p27 by miR-222 in HeLa cells and SiHa cells was associated with increased proliferation and migration of CC cells. The expression of proteins (E-cadherin and paxillin) related to the proliferation and migration was also elevated. CONCLUSION: MiR-222 plays an important role in the tumorigenesis of CC, possibly by specifically down-regulating p27Kip1 and PTEN. Our findings suggest that miR-222 may serve as a new therapeutic target in CC.

Levonorgestrel-releasing intrauterine system versus medical therapy for menorrhagia: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to compare the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) with conventional medical treatment in reducing heavy menstrual bleeding. MATERIAL AND METHODS: Relevant studies were identified by a search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and clinical trials registries (from inception to April 2014). Randomized controlled trials comparing the LNG-IUS with conventional medical treatment (mefenamic acid, tranexamic acid, norethindrone, medroxyprogesterone acetate injection, or combined oral contraceptive pills) in patients with menorrhagia were included. RESULTS: Eight randomized controlled trials that included 1170 women (LNG-IUS, n=562; conventional medical treatment, n=608) met inclusion criteria. The LNG-IUS was superior to conventional medical treatment in reducing menstrual blood loss (as measured by the alkaline hematin method or estimated by pictorial bleeding assessment chart scores). More women were satisfied with the LNG-IUS than with the use of conventional medical treatment (odds ratio [OR] 5.19, 95% confidence interval [CI] 2.73-9.86). Compared with conventional medical treatment, the LNG-IUS was associated with a lower rate of discontinuation (14.6% vs. 28.9%, OR 0.39, 95% CI 0.20-0.74) and fewer treatment failures (9.2% vs. 31.0%, OR 0.18, 95% CI 0.10-0.34). Furthermore, quality of life assessment favored LNG-IUS over conventional medical treatment, although use of various measurements limited our ability to pool the data for more powerful evidence. Serious adverse events were statistically comparable between treatments. CONCLUSIONS: The LNG-IUS was the more effective first choice for management of menorrhagia compared with conventional medical treatment. Long-term, randomized trials are required to further investigate patient-based outcomes and evaluate the cost-effectiveness of the LNG-IUS and other medical treatments.

CD44 expression is predictive of poor prognosis in pharyngolaryngeal cancer: systematic review and meta-analysis.

Pharyngolaryngeal cancer is one of the most common head and neck cancer worldwide, and the early diagnosis and prognosis prediction are still difficult because of lacking in reliable cell markers. Although the expression of CD44 has been reported to correlate with poor prognosis of pharyngolaryngeal cancer in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and clinicopathological features and prognosis in pharyngolaryngeal cancer. A search of PubMed, ISI Web of Science and China National Knowledge Infrastructure databases (up to June 2013) was performed. Nineteen studies with 1,405 patients met the inclusion criteria. The expression of pan-CD44, including all variant isoforms, was detected in 58.0% (14.1-79.2%) specimens, while CD44-v6 (variant isoform 6 of CD44) was expressed in 54.8% (12-79.2%). In pooled analysis, CD44 expression was significantly associated with larger tumor size (T category, RR (relative risk) = 1.21, 95% CI: 1.01-1.46), lymph nodes metastasis (N category, RR = 1.94, 95% CI: 1.38-2.73) and poor prognosis [3-year overall survival (OS): RR = 0.70, 95% CI: 0.53-0.91; 5-year OS: RR = 0.66, 95% CI: 0.66-0.94]. In the stratified analysis of CD44 isoforms, high expression of CD44-v6 was related with a poor 5-year OS rate (RR = 0.53, 95% CI: 0.37-077). We propose that CD44 expression is associated with tumor size, lymph node metastasis, and poor prognosis in pharyngolaryngeal cancer patients.

CA125-Associated Activated Partial Thromboplastin Time and Thrombin Time Decrease in Patients with Adenomyosis.

Objective: Adenomyosis patients are in a hypercoagulable state, and studies have shown that carbohydrate antigen125 (CA125) may relate to the hypercoagulability and thrombosis of patients with adenomyosis, but there is still a lack of clarity regarding the changes in CA125-related coagulation indicators. This study was to explore the changes and influencing factors of CA125-related coagulation parameters in patients with adenomyosis. Methods: Retrospective observational study conducted on 200 patients with adenomyosis (AM group), 240 patients with uterine leiomyoma (LM group) and 81 patients with cervical intraepithelial neoplasia (CIN)-III (control group), of which the coagulation parameters were detected by clinical blood sample collection and statistical method analysis and informed consent was obtained. Results: The level of CA125 in the AM group was significantly higher than that in the LM group and control group. However, thrombin time (TT) shortened in the AM group when compared with the LM and control group. Activated partial thromboplastin time (APTT) in the AM group was shorter than in the control group. Multivariate logistic regression analysis found that adenomyosis was associated with CA125 level (OR=323.860, 95% CI 90.424-1159.924, P<0.001), APTT (OR=1.295, 95% CI 1.050-1.598, P=0.016), TT (OR=0.642, 95% CI 0.439-0.938, P=0.022), menorrhagia (OR=7.363, 95% CI 2.544-21.315, P<0.001), dysmenorrhea (OR=22.590, 95% CI 8.185-62.347, P<0.001). Correlation analysis revealed that APTT (r= -0.207) and TT (r = -0.174) were negatively correlated with the level of CA125. Conclusion: The shortening of CA125-related APTT and TT indicates that it is meaningful to detect coagulation parameters of patients with elevated CA125 levels early, dysmenorrhea and menorrhagia, and maybe further discover the hypercoagulability and prevent the occurrence of thrombus in adenomyosis.

Spatial mapping of corneal biomechanical properties using wave-based optical coherence elastography.

Quantifying the mechanical properties of the cornea can provide valuable insights into the occurrence and progression of keratoconus, as well as the effectiveness of corneal crosslinking surgery. This study presents a non-contact and non-invasive wave-based optical coherence elastography system that utilizes air-pulse stimulation to create a two-dimensional map of corneal elasticity. Homogeneous and dual concentration phantoms were measured with the sampling of 25 × 25 points over a 6.6 × 6.6 mm2 area, to verify the measurement capability for elastic mapping and the spatial resolution (0.91 mm). The velocity of elastic waves distribution of porcine corneas before and after corneal crosslinking surgery were further mapped, showing a significant change in biomechanics in crosslinked region. This system features non-invasiveness and high resolution, holding great potential for application in ophthalmic clinics.

A water transfer printing method for contact lenses surface 2D MXene modification to resist bacterial infection and inflammation.

Contact lenses (CLs) are prone to adhesion and invasion by pollutants and pathogenic bacteria, leading to infection and inflammatory diseases. However, the functionalization of CL (biological functions such as anti-fouling, antibacterial, and anti-inflammatory) and maintaining its transparency still face great challenges. In this work, as a member of the MXenes family, vanadium carbide (V2C) is modified onto CL via a water transfer printing method after the formation of a tightly arranged uniform film at the water surface under the action of the Marangoni effect. The coating interface is stable owing to the electrostatic forces. The V2C-modified CL (V2C@CL) maintains optical clarity while providing good biocompatibility, strong antioxidant properties, and anti-inflammatory activities. In vitro antibacterial experiments indicate that V2C@CL shows excellent performance in bacterial anti-adhesion, sterilization, and anti-biofilm formation. Last, V2C@CL displays notable advantages of bacteria elimination and inflammation removal in infectious keratitis treatment.

Determination of trace bisphenols in milk based on Fe3O4@NH2-MIL-88(Fe)@TpPa magnetic solid-phase extraction coupled with HPLC.

Herein, a covalent organic framework (COF) was grown on a magnetic metal-organic framework (MOF) by a solvothermal method for the efficient extraction of bisphenols (BPs). The magnetic solid-phase extraction (MSPE) of four bisphenols (bisphenol A, bisphenol B, bisphenol AF and bisphenol C) was carried out without adjusting the pH and salt concentration. When 30 mg Fe3O4@NH2-MIL-88(Fe)@TpPa was used to adsorb for 25 min, 6 mL methanol was used to elute for 20 min, and the extract was detected by high-performance liquid chromatography (HPLC). The proposed method has a low detection limit of 0.011-0.036 ng mL-1, a wide linear range of 0.05-100 ng mL-1, and a correlation coefficient (R2) of 0.9980-0.9998. The intra-day and inter-day precisions are 0.74-2.54% and 1.68-3.72%, respectively. Bisphenol A was determined by applying the proposed method to the determination of actual milk samples. The standard addition experiment showed that the relative recovery of the four bisphenols was 85.70-119.7%. Pseudosecond-order, first-order, Langmuir and Freundlich models were applied to explore the adsorption characteristics of Fe3O4@NH2-MIL-88(Fe)@TpPa. In general, the established Fe3O4@NH2-MIL-88(Fe)@TpPa-MSPE-HPLC-UV method exhibits attractive sensitivity, simple manipulation, and excellent reusability, and it has excellent prospects for the detection of trace BPs in complex milk matrices.

High-dimensional automated radiation therapy treatment planning via Bayesian optimization.

PURPOSE: Radiation therapy treatment planning can be viewed as an iterative hyperparameter tuning process to balance conflicting clinical goals. In this work, we investigated the performance of modern Bayesian optimization (BO) methods on automated treatment planning problems in high-dimensional settings. METHODS: Twenty locally advanced rectal cancer patients treated with intensity-modulated radiation therapy (IMRT) were retrospectively selected as test cases. The adjustable planning parameters included both dose objectives and their corresponding weights. We implemented an automated treatment planning framework and tested the performance of two BO methods on the treatment planning task: one standard BO method (Gaussian Process with Expected Improvement [GPEI]) and one BO method dedicated to high-dimensional problems (Sparse Axis Aligned Subspace BO [SAAS-BO]). Another derivative-free method (Nelder-Mead simplex search) and the random tuning method were also included as baselines. The four automated methods' plan quality and planning efficiency were compared with the clinical plans regarding target coverage and organs at risk (OAR) sparing. The predictive models in both BO methods were compared to analyze the different search patterns of the two BO methods. RESULTS: For the target structures, the SAAS-BO plans achieved comparable hot spot control ( p = 0.43 $p=0.43$ ) and homogeneity ( p = 0.96 $p=0.96$ ) with the clinical plans, significantly better than the GPEI and Nelder-Mead plans ( p < 0.05 $p < 0.05$ ). Both SAAS-BO and GPEI plans significantly outperformed the clinical plans in conformity and dose spillage ( p < 0.05 $p < 0.05$ ). Compared with the clinical plans, the treatment plans generated by the four automated methods all made reductions in evaluated dosimetric indices for the femoral head and the bladder. The Nelder-Mead plans achieved similar plan quality scores compared with the BO plans, but exhibited poorer control in the target hot spot and dose spillage. The analysis of the underlying predictive models has shown that both BO methods have identified similar sensitive planning parameters. CONCLUSIONS: This work implemented a BO-based hyperparameter tuning framework for automated treatment planning. Both tested BO methods were able to produce high-quality treatment plans and reduce the workload of treatment planners. The model analysis also confirmed the intrinsic low dimensionality of the tested treatment planning problems.

The predictive value of prognosis and therapeutic response for STAT family in pancreatic cancer.

Background: Signal transducers and activators of transcription (STAT) proteins, well-known cytoplasmic transcription factors, were found to be abnormally expressed in various cancers and play essential parts in the initiation, progression and therapy resistance of cancer. Nevertheless, the functions of different STATs in pancreatic cancer (PC) and their relationship to the prognosis and immune infiltration as well as drug efficacy in PC patients have not been systematically elucidated. Methods: Expression, prognosis, genetic alterations and pathway enrichment analyses of the STAT family were investigated via Oncomine, GEPIA, Kaplan Meier-plotter, cBioPortal, Metascape and GSEA. Analysis of tumor immune microenvironment was conducted by ESTIMATE and TIMER. "pRRophetic" packages were used for analysis of chemotherapeutic response. Finally, the diagnostic and prognostic value of key STATs were further validated through public datasets and immunohistochemistry. Results: In this study, only STAT1 mRNA level was significantly increased in tumor tissues and highly expressed in PC cell lines via multiple datasets. PC patients with higher STAT1/4/6 expression had a worse overall survival (OS) and progression-free survival (PFS), while higher STAT5B expression was correlated with better prognosis in the TCGA cohort. The STATs-associated genes were enriched in pathways about the remodeling of tumor immune microenvironment. The STATs levels were significantly correlated with immune infiltration, except STAT6. The STAT1 was identified as a potential biomarker and its diagnostic and prognostic value were further validated at mRNA and protein levels. GSEA showed that STAT1 may be involved in the progression and immune regulations of PC. Moreover, STAT1 expression was significantly related to the level of immune checkpoint, and predicted immunotherapy and chemotherapy responses. Conclusion: STAT family members were comprehensively analyzed and STAT1 was identified as an effective biomarker for predicting the survival and therapeutic response, which could be beneficial to develop better treatment strategies.

A Novel "Inside-Out" Intraocular Nanomedicine Delivery Mode for Nanomaterials' Biological Effect Enhanced Choroidal Neovascularization Occlusion and Microenvironment Regulation.

Photodynamic therapy (PDT) is commonly used in choroidal neovascularization (CNV) treatment due to the superior light transmittance of the eye. However, PDT often leads to surrounding tissue damage and further microenvironmental deterioration, including exacerbated hypoxia, inflammation, and secondary neovascularization. In this work, Pt nanoparticles (NPs) and Au NPs decorated zeolitic imidazolate framework-8 nanoplatform is developed to load indocyanine green for precise PDT and microenvironment amelioration, which can penetrate the internal limiting membrane through Müller cells endocytosis and target to CNV by surface-grafted cyclo(Arg-Gly-Asp-d-Phe-Lys) after intravitreal injection. The excessive H2 O2 in the CNV microenvironment is catalyzed by catalase-like Pt NPs for hypoxia relief and enhanced PDT occlusion of neovascular. Meanwhile, Au NPs show significant anti-inflammatory and anti-angiogenesis properties in regulating macrophages and blocking vascular endothelial growth factor (VEGF). Compared with verteporfin treatment, the mRNA expressions of hypoxia-inducible factor-1α and VEGF in the nanoplatform group are downregulated by 90.2% and 81.7%, respectively. Therefore, the nanoplatform realizes a comprehensive CNV treatment effect based on the high drug loading capacity and biosafety. The CNV treatment mode developed in this work provides a valuable reference for treating other diseases with similar physiological barriers that limit drug delivery and similar microenvironment.

Selective and sensitive detection of tartrazine in beverages by sulfur quantum dots with high fluorescence quantum yield.

In this work, sulfur quantum dots (TPA-SQDs) protected by terephthalic acid as a stabilizer were synthesized using a one-pot method. When excited at 310 nm, the synthesized TPA-SQDs solution emitted strong blue fluorescence at 428 nm, and the absolute quantum yield was as high as 85.99%. The proposed SQDs can be used as a fluorescent probe to specifically quench tartrazine (TZ), showing a good linear relationship (R2 = 0.996) at TZ concentrations of 0.1-20 µM, with a detection limit of 39 nM. By analysing the fluorescence lifetime, UV-Vis absorption spectrum and zeta potential of the assay system, it can be speculated that the fluorescence quenching mechanism of TZ on TPA-SQDs is the inner filter effect (IFE). The proposed method was applied to the detection of TZ in vitamin water and orange juice, and the results were consistent with the determination results by high-performance liquid chromatography. The recoveries and relative standard deviations were 93.2-102.6% and 1.34-2.88%, respectively, which provided an alternative method for the determination of TZ in beverages or other food samples.

In situ assessment of lens elasticity with noncontact optical coherence elastography.

Lens biomechanics has great potential for application in clinical diagnostics and treatment monitoring of presbyopia and cataracts. However, current approaches to lens elastography do not meet the desired safety or sensitivity for clinical application. In this regard, we propose a noncontact optical coherence elastography (OCE) method to facilitate quantitative in situ imaging of lens elasticity. Elastic waves induced by air-pulse stimulation on the limbus propagate to the lens and are then imaged using custom-built swept-source optical coherence tomography to obtain the elastic wave velocity and Young's modulus. The proposed OCE method was first validated by comparing the results of in situ and in vitro measurements of porcine lenses. The results demonstrate that the Young's modulus measured in situ was highly consistent with that measured in vitro and had an intraclass correlation coefficient of 0.988. We further investigated the elastic changes induced by cold storage and microwave heating. During 36-hour cold storage, the mean Young's modulus gradually increased (from 5.62 ± 1.24 kPa to 11.40 ± 2.68 kPa, P < 0.0001, n = 9) along with the formation of nuclear opacities. 15-second microwave heating caused a greater increase in the mean Young's modulus (from 6.86 ± 1.21 kPa to 25.96 ± 8.64 kPa, P < 0.0025, n = 6) without apparent cataract formation. Accordingly, this study reports the first air-pulse OCE measurements of in situ lenses, which quantified the loss of lens elasticity during simulated cataract development with good repeatability and sensitivity, thus enhancing the potential for adoption of lens biomechanics in the clinic.