Dysregulation of TCONS_00006091 contributes to the elevated risk of oral squamous cell carcinoma by upregulating SNAI1, IRS and HMGA2.

In this study, we aimed to study the role of TCONS_00006091 in the pathogenesis of oral squamous cellular carcinoma (OSCC) transformed from oral lichen planus (OLP). This study recruited 108 OSCC patients which transformed from OLP as the OSCC group and 102 OLP patients with no sign of OSCC as the Control group. ROC curves were plotted to measure the diagnostic values of TCONS_00006091, miR-153, miR-370 and let-7g, and the changes in gene expressions were measured by RT-qPCR. Sequence analysis and luciferase assays were performed to analyze the molecular relationships among these genes. Cell proliferation and apoptosis were observed via MTT and FCM. TCONS_00006091 exhibited a better diagnosis value for OSCC transformed from OLP. OSCC group showed increased TCONS_00006091 expression and decreased expressions of miR-153, miR-370 and let-7g. The levels of SNAI1, IRS and HMGA2 was all significantly increased in OSCC patients. And TCONS_00006091 was found to sponge miR-153, miR-370 and let-7g, while these miRNAs were respectively found to targe SNAI1, IRS and HMGA2. The elevated TCONS_00006091 suppressed the expressions of miR-153, miR-370 and let-7g, leading to the increased expression of SNAI1, IRS and HMGA2. Also, promoted cell proliferation and suppressed apoptosis were observed upon the over-expression of TCONS_00006091. This study demonstrated that the expressions of miR-153, miR-370 and let-7g were down-regulated by the highly expressed TCONS_00006091 in OSCC patients, which accordingly up-regulated the expressions of SNAI1, IRS and HMGA2, resulting in the promoted cell proliferation and suppressed cell apoptosis.

Direct Fuzzy Adaptive Regulation for High-Order Delayed Systems: A Lyapunov-Razumikhin Function Method.

A slow time-delay assumption restricts the application of control approaches for numerous systems which are constantly affected by multiple uncertainties, including parameters, control coefficients, and the asymmetric dead-zone input. This work presents a new adaptive method for a class of high-order nonlinear delayed systems by removing the so-called slow time-delay assumption and multiple uncertainties. Remarkably, with a novel Lyapunov-Razumikhin (L-R) function and a direct fuzzy adaptive regulation scheme, a memoryless adaptive feedback controller is skillfully constructed to guarantee that the output tracks the given reference signal while keeping the boundedness of all closed-system signals. Finally, the presented scheme is applied to control a single-link robot system.

miR-19a may function as a biomarker of oral squamous cell carcinoma (OSCC) by regulating the signaling pathway of miR-19a/GRK6/GPCRs/PKC in a Chinese population.

BACKGROUND: In this study, we aimed to investigate the potential of miR-19a as a biomarker of OSCC and its underlying molecular mechanisms. METHODS: We collected serum and saliva samples from 66 OSCC patients and 66 healthy control subjects. Real-time PCR analysis, bioinformatic analysis and luciferase assays were performed to establish a potential signaling pathway of miR-19a/GRK6/GPCRs/PKC. Flowcytometry and Transwell assays were performed to observe the changes in cell apoptosis, metastasis and invasion. RESULTS: We found that miR-19a, GPR39 mRNA and PKC mRNA were upregulated while GRK6 mRNA was downregulated in the serum and saliva samples collected from OSCC patients. Moreover, in silico analysis confirmed a potential binding site of miR-19a on the 3'UTR of GRK6 mRNA, and the subsequent luciferase assays confirmed the molecular binding between GRK6 and miR-19a. We further identified that the over-expression of miR-19a could regulate the signaling between GRK6, GPR39 and PKC via the signaling pathway of miR-19a/GRK6/GPR39/PKC, which accordingly resulted in suppressed cell apoptosis and promoted cell migration and invasion. CONCLUSION: Collectively, the findings of our study propose that miR-19a is a crucial mediator in the advancement of OSCC, offering a potential avenue for the development of innovative therapeutic interventions aimed at regulating GRK6 and its downstream signaling pathways.

Flexible Hollow Human Serum Albumin-Catalase Nanocapsules with High Accumulation and Uptake Ability for Enhanced Photodynamic Therapy.

Introduction: Photodynamic therapy (PDT) has attracted increasing attention for tumor treatment because of its minimal invasiveness and specific spatiotemporal selectivity. However, insufficient tumor accumulation and low cellular uptake of photosensitizers limit its therapeutic efficacy. Methods: In this study, flexible hollow human serum albumin/catalase nanocapsules (HSA/CATs) were created using a core-assisted protein-coating method and combined with the photosensitizer chlorin e6 (HSA/CAT@Ce6) for PDT. Results and Discussion: Transmission electron microscopy (TEM) images demonstrate that HSA/CAT nanocapsules are flexible, with a uniform diameter (310 nm) and a well-defined hollow structure. Thanks to their flexibility, HSA/CAT@Ce6 nanocapsules show a higher cellular uptake than rigid nanoparticles. The nanocapsules effectively generate reactive oxygen species (ROS) in 4T1 cells because of their high cellular uptake and catalytic capacity, remarkably enhancing their in vitro PDT efficacy. In addition, the in vivo tumor accumulation of HSA/CAT@Ce6 nanocapsules is significantly larger than that of rigid nanoparticles and Ce6, meaning they are highly effective in tumor cell ablation. This demonstrates that our flexible nanoplatform holds great promise for enhancing PDT of tumor.

Flexible human serum albumin nanocapsules to enhance drug delivery and cellular uptake for photodynamic/chemo cancer therapy.

As a non-invasive cancer treatment, photodynamic therapy (PDT) has great applications in superficial tumors because of its high selectivity and low cumulative toxicity. However, the poor tumor-targeting ability and short blood circulation time of conventional photosensitizers (PSs) limit the efficacy of PDT to some extent. In this study, we synthesized flexible hollow human serum albumin (HHSA) and loaded photosensitizer Chlorin e6 (Ce6) and the chemotherapeutic drug Doxorubicin (DOX) for synergistic cancer therapy. HHSA can enhance drug delivery and cellular uptake through targeting gp60 and SPARC receptors and unique flexible hollow structures. The TEM images show that HHSA possesses distinct flexible hollow structures, as well as good monodispersity and deformability. After loading Ce6 and DOX, HHSA@Ce6-DOX displays better therapeutic effects than HHSA@DOX on the growth of 4T1 breast cancers without irradiation. Remarkably, it has a significantly higher therapeutic effect (relative cell activity: 45% vs. 74%) than HHSA@Ce6 under 660 nm irradiation. Furthermore, the excellent biocompatibility of HHSA@Ce6-DOX has been proved both in vitro and in vivo, indicating that it has a promising future in synergistic tumor treatments.

Effects of bisphenol A on antioxidation and nitrogen assimilation of maize seedlings roots.

Bisphenol A (BPA) is becoming a potential environmental toxicity factor. However, BPA's effect and function mechanism on maize roots remain unknown. Here, we investigated characters of root growth of maize seedlings exposed to BPA for 8 d and without BPA for 3 d, and a series of indicators on reactive oxygen homeostasis and nitrogen assimilation were measured. High-dose BPA(15 and 50 mg·L-1) suppressed the root growth and caused increased contents of O2ˑ-, H2O2 and MDA in maize seedling roots. The disturbed ROS homeostasis resulted from the change of antioxidant enzymes, including the increase of APX, GPX, and CAT, and decrease of SOD and POD, and a decrease of antioxidant substance GSH. Meanwhile, High-dose BPA caused a decrease in the soluble protein content, nitrate reductase (NR), glutamate dehydrogenase (GDH), and glutamine oxoglutarate aminotransferase (GOGAT) under the BPA processing phase and recovery period. The low-dose BPA（1.5 and 5 mg·L-1）significantly promoted root growth of maize seedlings and maintained the ROS homeostasis through antioxidant enzyme APX and GPX eliminating redundant ROS. Our results showed that BPA could cause a dual effect on the root growth of maize seedlings, that is, promotion of low-dose and inhibition of high-dose, through ROS homeostasis and nitrogen assimilation in Zea mays.

The impact of age and body mass index on a bra sizing system formed by anthropometric measurements of Sichuan Chinese females.

Existing bra sizing systems are based only on bust and underbust girths, which do not guarantee an accurate fit or comfort for consumers. This study presents a comprehensive investigation of the impact of age and body mass index (BMI) on bra sizing systems, and the distributions of band and cup sizes based on anthropometric measurement data. The first four principal components were extracted by principal component analysis, and the factor loadings of age and BMI were found to be significant determinants of bra size along with 12 other variables. Furthermore, chi-square analysis revealed that bra size allocations were significantly influenced by age and BMI. Thus, we propose that age and BMI should be considered as auxiliary criteria for the bra sizing system. Taken together, these findings will be of value to designers and bra manufacturers in developing well-fitting bras for their target consumers, and to consumers for selecting well-fitting bras with confidence. Practitioner Summary: This study contributes to an understanding of how bra sizing systems are affected by age and BMI. This understanding is valuable to bra designers, manufacturers, and retailers, as it will enable the adjustment of bra sizes for different target markets and in turn improve consumer confidence in selecting proper fitting and comfortable bras.

MiR-181d functions as a potential tumor suppressor in oral squamous cell carcinoma by targeting K-ras.

Oral squamous cell carcinoma (OSCC) is one of the most frequent carcinomas all over the world, and the mechanism of its progression remains poorly understood. MicroRNAs have been found to play pivotal roles in many cancers including OSCC. However, the detailed roles of miRNAs in OSCC remain to be fully elucidated. In this study, we aimed to investigate the role of miR-181d in the progression of OSCC and to further elucidate its possible regulatory mechanism. Differentially expressed miRNAs between OSCC tissues and adjacent normal tissues were identified by microarray and validated using quantitative reverse transcription PCR (qRT-PCR). Moreover, the effects of miR-181d on the cell viability and apoptosis were investigated. In addition, a direct target of miR-181a, K-ras was assessed by the luciferase reporter assay and western blot. K-ras was overexpressed to evaluate its reverse effect on miR-181d mediated tumor suppression in OSCC. A panel of 54 differentially expressed miRNAs was identified by microRNA array. Among them, miR-181d was showed to be significantly downregulated. We also found that miR-181d lowly expressed in 20 pairs of OSCC tissues and four cell lines compared with that in adjacent normal tissues and human normal oral keratinocyte cells. In vitro assays showed that upregulation of miR-181d markedly decreased cell viability and increased OSCC cell apoptosis. Furthermore, we demonstrated that K-ras was a target of miR-181d and there was a negative correlation between miR-181d and K-ras expression in OSCC tissues. Importantly, overexpression of K-ras reversed the inhibitory effects of miR-181d mimics on OSCC cells. miR-181d functions as an OSCC suppressor by targeting K-ras oncogene. Thus, miR-181d may serve as a novel therapeutic target for treating OSCC.

Anti-diabetes constituents in leaves of Smallanthus sonchifolius.

The inhibitory effect of smallanthaditerpenic acids A, B, C and D previously isolated from leaves of Smallanthus sonchifolius (yacon) on alpha-glucosidase were examined and their IC50 were determined to be 0.48 mg/mL, 0.59 mg/mL, 1.00 mg/mL, and 1.17 mg/mL respectively. In addition, a rapid, reliable RP-HPLC method for the analysis of chlorogenic acid, caffeic acid, and smallanthaditerpenic acids A and C in yacon leaves was established, and the variation in their contents in leaves from plants cultivated in different places and collected at different times of the year were compared. The established analytical method for determining smallanthaditerpenic acids A and C, chlorogenic acid and caffeic acid presented good results and could be used as a method for the quality control of S. sonchifolius leaves.