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.

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.

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.

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.

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.

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.

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.

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.

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.

Determination of pyrethroids in water samples by dispersive solid-phase extraction coupled with high-performance liquid chromatography.

A metal-organic framework UiO-66 was prepared and used as a sorbent for dispersive solid-phase extraction combined with high-performance liquid chromatography (DSPE-HPLC) for extracting and determining four pyrethroids in water samples for the first time. The as-synthesized material was confirmed by Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and N2 adsorption-desorption analysis. In addition, several important parameters affecting DSPE efficiency, including sorbent dosage, extraction time, salt concentration, pH, elution solvent, elution volume, and elution time, were optimized. Under the optimum conditions, the UiO-66 based on the DSPE-HPLC method displayed a wide linear range (10-1000 ng/ml), low limits of detection (2.8-3.5 ng/ml), and good precision (relative standard deviations [RSDs] < 3%) for the four pyrethroids. The recoveries at different spiked levels ranged from 89.3% to 107.7%. In addition, UiO-66 featured good reusability and reproducibility. The results demonstrated that π-π stacking interactions, hydrophobic interactions, and van der Waals forces between UiO-66 and the four pyrethroids played a crucial role in the adsorption process. Meanwhile, the maximum extraction capability could be obtained within 5 min. Thus, the DSPE coupled with the UiO-66 sorbent can be successfully used in the analysis of four pyrethroids in environmental water samples. PRACTITIONER POINTS: Simultaneous determination of four pyrethroids using the developed UiO-66-based DSPE-HPLC method in water samples. The developed method had a short enrichment time, broad linear ranges, a low detection limit, and high enrichment factor. It is showed that π-π stacking interaction, hydrophobic interaction, and van der Waals forces were the main mechanism.

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.

pH-Activatable Organic Nanoparticles for Efficient Low-Temperature Photothermal Therapy of Ocular Bacterial Infection.

Low-temperature photothermal therapy (PTT) systems constructed by integrating organic photothermal agents with other bactericidal components that initiate bacterial apoptosis at low hyperthermia possess a promising prospect. However, these multicomponent low-temperature PTT nanoplatforms have drawbacks in terms of the tedious construction process, suboptimal synergy effect of diverse antibacterial therapies, and high laser dose needed, compromising their biosafety in ocular bacterial infection treatment. Herein, a mild PTT nanotherapeutic platform is formulated via the self-assembly of a pH-responsive phenothiazinium dye. These organic nanoparticles with photothermal conversion efficiency up to 84.5% necessitate only an ultralow light dose of 36 J/cm2 to achieve efficient low-temperature photothermal bacterial inhibition at pH 5.5 under 650 nm laser irradiation. In addition, this intelligent mild photothermal nanoplatform undergoes negative to positive charge reversion in acid biofilms, exhibiting good penetration and highly efficient elimination of drug-resistant E. coli biofilms under photoirradiation. Further in vivo animal tests demonstrated efficient bacterial elimination and inflammatory mitigation as well as superior biocompatibility and biosafety of the photothermal nanoparticles in ocular bacterial infection treatment. Overall, this efficient single-component mild PTT system featuring simple construction processes holds great potential for wide application and clinical transformation.

The efficacy and safety of Longmu Tang granule for the treatment of atopic dermatitis: study protocol for a single-centred, double-blinded, randomised, placebo-controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing skin disease that has long-term physical and mental health impacts on children with this condition. Current treatments mainly include anti-inflammatory, antibacterial, and anti-allergic interventions, systemic therapy, and recently emerging target-focused agents. However, these treatments have limited effectiveness and unwanted side effects. The use of traditional Chinese medicine (TCM) in the treatment of AD has a long history, with promising efficacies, low toxicity, and improvements in the quality of life of patients with AD. Longmu Tang granule, a TCM, has been used to effectively treat AD since 2008 through doctors' prescriptions. To scientifically evaluate the clinical efficacy and safety of Longmu Tang granule, we proposed to launch a single-centred, double-blinded, randomised, placebo-controlled trial. METHODS: In this single-centred, double-blinded, randomised, placebo-controlled clinical trial conducted at Xiyuan Hospital of China Academy of Chinese Medical Sciences, a total of 60 participants will be randomly assigned (1:1) to receive the Longmu Tang granule or placebo granule for 8 weeks. The primary outcome will be evaluated using the index of Scoring Atopic Dermatitis. The secondary outcomes will be evaluated using the Children's Dermatology Life Quality Index and the number cancellation test. The mechanistic evidence will be the serum levels of inflammatory cytokines, including immunoglobulin E, tumour necrosis factor-α, interleukin-1, and interleukin-6. DISCUSSION: The results of this trial will provide evidence of the efficacy and safety of the Longmu Tang granule and prove its anti-inflammatory action in patients with AD. TRIAL REGISTRATION: Chinese Clinical Trial Registry Chictr.org ID: ChiCTR2100041591 . Registered on 1 January 2021.

Cyanobacteria-based self-oxygenated photodynamic therapy for anaerobic infection treatment and tissue repair.

Photodynamic therapy (PDT) is an important technique to deal with drug-resistant bacterial infections in the post-antibiotic era. However, the hypoxic environment in intractable infections such as refractory keratitis and periodontitis, makes PDT more difficult. In this work, spontaneous oxygen-producing cyanobacteria were used as the carrier of photosensitizer (Ce6), and ultrasmall Cu5.4O nanoparticles (Cu5.4O USNPs) with catalase activity for infection and inflammation elimination and rapid tissue repair (CeCycn-Cu5.4O). The loading of Ce6 and Cu5.4O USNPs onto cyanobacteria surface were confirmed by transmission electron microscopy, nano particle size analyzer, scanning electron microscopy. In vitro sterilization and biofilm removal experiments demonstrated that the restriction of hypoxic environment to PDT was significantly alleviated due to the oxygen production of cyanobacteria. Under laser irradiation, the close transfer of energy photons to oxygen produced by cyanobacteria reduced more than 90% of Ce6 dosages (660 nm, 200 mW/cm2, 2 min). It is worth mentioning that both rapid sterilization through PDT and long-term oxidized free radicals elimination were achieved by adjusting the ratio of Ce6 and Cu5.4O USNPs. Both periodontitis and refractory keratitis animal models proved the excellent self-oxygenation enhanced antibacterial property and promotion of tissue repair.

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.

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.

Potential Role of SWI/SNF Complex Subunit Actin-Like Protein 6A in Cervical Cancer.

SWI/SNF complex subunit Actin-like protein 6A (ACTL6A) has been regarded as an oncogene, regulating the proliferation, migration and invasion of cancer cells. However, the expression pattern and biological role of ACTL6A in cervical cancer have not been reported. In this study, the mRNA expression and protein level of ACTL6A in cervical cancer samples were determined by public database and immunohistochemical (IHC) analysis. The effects of ACTL6A on cervical cancer cells were investigated via MTT, colony-formation assay, tumor xenografts and flow cytometry. Gene set enrichment analysis (GSEA) was used to explore the potential mechanism of ACTL6A in regulating tumorigenesis of cervical cancer. The results revealed that ACTL6A was markedly upregulated in cervical cancer tissues. Silencing ACTL6A expression resulted in decreased cervical cancer cell proliferation, colony formation and tumorigenesis in vitro and in vivo. Furthermore, we demonstrated that knockdown of ACTL6A induced cell cycle arrest at G1 phase, ACTL6A-mediated proliferation and cell cycle progression were c-Myc dependent. Our study provides the role of ACTL6A in cervical oncogenesis and reveals a potential target for therapeutic intervention in this cancer type.

Genome-Wide Identification and Co-Expression Analysis of ARF and IAA Family Genes in Euscaphis konishii: Potential Regulators of Triterpenoids and Anthocyanin Biosynthesis.

Euscaphis konishii is an evergreen plant that is widely planted as an industrial crop in Southern China. It produces red fruits with abundant secondary metabolites, giving E. konishii high medicinal and ornamental value. Auxin signaling mediated by members of the AUXIN RESPONSE FACTOR (ARF) and auxin/indole-3-acetic acid (Aux/IAA) protein families plays important roles during plant growth and development. Aux/IAA and ARF genes have been described in many plants but have not yet been described in E. konishii. In this study, we identified 34 EkIAA and 29 EkARF proteins encoded by the E. konishii genome through database searching using HMMER. We also performed a bioinformatic characterization of EkIAA and EkARF genes, including their phylogenetic relationships, gene structures, chromosomal distribution, and cis-element analysis, as well as conserved motifs in the proteins. Our results suggest that EkIAA and EkARF genes have been relatively conserved over evolutionary history. Furthermore, we conducted expression and co-expression analyses of EkIAA and EkARF genes in leaves, branches, and fruits, which identified a subset of seven EkARF genes as potential regulators of triterpenoids and anthocyanin biosynthesis. RT-qPCR, yeast one-hybrid, and transient expression analyses showed that EkARF5.1 can directly interact with auxin response elements and regulate downstream gene expression. Our results may pave the way to elucidating the function of EkIAA and EkARF gene families in E. konishii, laying a foundation for further research on high-yielding industrial products and E. konishii breeding.

Clinicopathological and immunological characterization of RNA m6 A methylation regulators in ovarian cancer.

BACKGROUND: N6 -methyladenosine (m6 A) modification is one of the critical gene regulatory mechanisms implicated in cancer biology. However, the roles of m6 A regulators in ovarian cancer are still poorly understood. METHODS: We integrated multiple databases including Gene Expression Omnibus (GEO), ROC Plotter, Kaplan-Meier Plotter, and Tumor Immune Estimation Resource (TIMER) to explore clinicopathological significance of m6 A regulators in ovarian cancer. RESULTS: We showed that alterations in the expression of m6 A regulators were related to the malignancy and poor prognosis of ovarian cancer. We found decreased YTHDC1 and increased RBM15 expressions were associated with ovarian cancer cell metastases and HNRNPC was a predictor of paclitaxel resistance. Moreover, dysregulated m6 A regulators were enriched in the activation of cancer-related pathways. Our results further demonstrated that the level of immune cell infiltration and the expression of various immune gene markers were closely associated with the expressions of specific m6 A regulators (RBM15B, ZC3H13, YTHDF1, and IGF2BP1). CONCLUSIONS: Our study establishes a new prognostic profile of ovarian cancer patients based on m6 A regulators, and highlights the potential roles of m6 A regulators in ovarian cancer development.

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.