Prognostic value of semi-quantitative parameters of 18F-FDG PET/CT in newly diagnosed multiple myeloma patients.

OBJECTIVE: To investigate the prognostic value of fluroine-18 fluorodexyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) semi-quantitative parameter in newly diagnosed multiple myeloma (NDMM) and to design a new staging system including 18F-FDG PET/CT semi-quantitative parameters for NDMM. METHODS: A total of 38 NDMM patients who underwent 18F-FDG PET/CT examination in Yichang Central People's Hospital from February 2014 to April 2021 were collected. The relationship between the characteristics of 18F-FDG PET/CT (metabolic tumor volume of all lesions (aMTV), total lesion glycolysis of all lesions (aTLG), maximum standardized uptake values (SUVmax) of the lesion with largest MTV (mSUVmax), extramedullary disease (EMD), focal lesions (FLs)), the laboratory parameters, and prognostic parameters (progression-free survival (PFS) and overall survival (OS)) were analyzed retrospectively. SPSS 25.0 statistical software was used for statistical processing, Kaplan-Meier method was used for survival analysis, Log-rank method was used for univariate analysis, and Cox proportional risk model was used for multivariate analysis. RESULTS: Univariate analysis showed that aMTV ≥ 90.97cm3, aTLG ≥ 283.31 g, hemoglobin (Hb) < 100 g/L, focal lesions (FLs) ≥ 10, (percentage of circulating plasma cells (CPC%) ≥ 30%, creatinine (Cr) ≥ 177umol/L, lactic dehydrogenase (LDH) ≥ 250 g/L might be the adverse prognostic factors of PFS in patients with NDMM, all p < 0.05; aMTV ≥ 90.97 cm3, aTLG ≥ 283.31 g, Hb < 100 g/L, FLs ≥ 10, mSUVmax ≥ 5.8, the presence of extramedullary disease (EMD) and PCPs ≥ 30% may be adverse prognostic factors for OS in patients with NDMM, all p < 0.05. Multivariate regression analysis showed that aMTV ≥ 90.97 cm3 was an independent risk factor for PFS in NDMM patients, p < 0.05; aMTV ≥ 90.97 cm3, mSUVmax ≥ 5.8, and the presence of EMD were independent risk factors for OS in the NDMM patients, all p < 0.05. According to the multivariate analysis results of OS, the New stage (NS) was performed. The 3-year OS rates of stage I, stage II, and stage III in NDMM patients were 100.0, 53.5, and 32.1%, respectively, p = 0.000. CONCLUSION: aMTV can predict PFS and OS of NDMM patients better than other parameters. NS which combined with aMTV can predict OS of NDMM patients better and can provide an accurate and simple method for risk stratification of NDMM patients.

How Do Human-Driven Vehicles Avoid Pedestrians in Interactive Environments? A Naturalistic Driving Study.

One of the major challenges for autonomous vehicles (AVs) is how to drive in shared pedestrian environments. AVs cannot make their decisions and behaviour human-like or natural when they encounter pedestrians with different crossing intentions. The main reasons for this are the lack of natural driving data and the unclear rationale of the human-driven vehicle and pedestrian interaction. This paper aims to understand the underlying behaviour mechanisms using data of pedestrian-vehicle interactions from a naturalistic driving study (NDS). A naturalistic driving test platform was established to collect motion data of human-driven vehicles and pedestrians. A manual pedestrian intention judgment system was first developed to judge the pedestrian crossing intention at every moment in the interaction process. A total of 98 single pedestrian crossing events of interest were screened from 1274 pedestrian-vehicle interaction events under naturalistic driving conditions. Several performance metrics with quantitative data, including TTC, subjective judgment on pedestrian crossing intention (SJPCI), pedestrian position and crossing direction, and vehicle speed and deceleration were analyzed and applied to evaluate human-driven vehicles' yielding behaviour towards pedestrians. The results show how vehicles avoid pedestrians in different interaction scenarios, which are classified based on vehicle deceleration. The behaviour and intention results are needed by future AVs, to enable AVs to avoid pedestrians more naturally, safely, and smoothly.

Association between programmed cell death ligand 1 expression and thyroid cancer: A meta-analysis.

BACKGROUND: Programmed cell death ligand 1 (PD-L1), which is highly expressed in a variety of malignant tumors, is closely related to clinicopathological features and prognosis. However, there are few studies on the potential effects of PD-L1 on thyroid carcinoma, the incidence of which has shown an upward trend worldwide. This study aimed to explore the association between PD-L1 expression and clinicopathological features and prognosis of thyroid cancer. METHODS: An elaborate retrieval was performed using Medline, PubMed, Cochrane Library, EMBASE, Web of Science, WanFang databases, and China National Knowledge Infrastructure to determine the association between PD-L1 expression and disease-free survival (DFS), overall survival (OS), and clinicopathological features in patients with thyroid cancer. Study selection, data extraction, risk assessment, and data synthesis were performed independently by 2 reviewers. In this meta-analysis, RevMan 5.3 and Stata 15.1 were used for bias risk assessment and data synthesis. RESULTS: After a detailed search, 2546 cases reported in 13 articles were included in this meta-analysis. The outcomes revealed that high expression of PD-L1 in patients with thyroid cancer was associated with poor DFS (hazard ratio [HR] = 3.37, 95% confidence interval [CI] 2.54-4.48, P < .00001) and OS (HR = 2.52, 95% CI: 1.20-5.32, P = .01). High PD-L1 expression was associated with tumor size ≥2 cm, tumor recurrence, extrathyroidal extension, concurrent thyroiditis, unifocal tumor, and absence of psammoma body (P < .05). Subgroup analysis showed that positive expression of PD-L1 was related to poor prognosis for DFS of non-medullary thyroid carcinoma, and the overexpression of PD-L1 in differentiated thyroid carcinoma (DTC) was related to tumor recurrence, concurrent thyroiditis, extrathyroidal extension, unifocal DTC, late stage DTC, and BRAFV600E mutation in DTC. CONCLUSION: PD-L1 is a significant predictor of prognosis and malignancy of thyroid cancer (especially DTC), and PD-L1 inhibitors may be a promising therapeutic option for refractory thyroid cancer in the future.

Allicin ameliorates obesity comorbid depressive-like behaviors: involvement of the oxidative stress, mitochondrial function, autophagy, insulin resistance and NOX/Nrf2 imbalance in mice.

The increased prevalence of obesity has been a major medical and public health problem in the past decades. In obese status, insulin resistance and sustained oxidative stress damage might give rise to behavioral deficits. The anti-obesity and anti-oxidant effects of allicin have been previously reported in peripheral tissues. In the present study, the functions and mechanisms of allicin involved in the prevention of high-fat diet (HFD)-induced depressive-like behaviors were investigated to better understand the pharmacological activities of allicin. Obese mice (five weeks of age) were treated with allicin (50, 100, and 200 mg/kg) by gavage for 15 weeks and behavioral test (sucrose preference, open field, and tail suspension) were performed. Furthermore, markers of oxidative stress, mitochondrial function, autophagy, and insulin resistance were measured in the hippocampal tissue. Finally, the levels of NADPH oxidase (NOX2, NOX4) and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway were evaluated in the hippocampus. The body weight, metabolic disorders, and depressive-like behaviors in obese mice were ameliorated by allicin. The depressive-like behaviors presented in the obese mice were accompanied by remarkably excessive reactive oxygen species (ROS) production and oxidative stress, damaged mitochondrial function, imbalanced autophagy, and enhanced insulin resistance in the hippocampus. We found that allicin improved the above undesirable effects in the obese mice. Furthermore, allicin significantly decreased NOX2 and NOX4 levels and activated the Nrf2 pathway. Allicin attenuated depressive-like behaviors triggered by long-term HFD consumption by inhibiting ROS production and oxidative stress, improving mitochondrial function, regulating autophagy, and reducing insulin resistance in the hippocampus via optimization of NOX/Nrf2 imbalance.

Qing brick tea (QBT) aqueous extract protects monosodium glutamate-induced obese mice against metabolic syndrome and involves up-regulation Transcription Factor Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) antioxidant pathway.

BACKGROUND: Qing brick tea (QBT), traditional and popular beverage for Chinese people, is an important post-fermentation dark tea. Our present study was performed to investigate the ameliorative effects of QBT aqueous extract on metabolic syndrome (Mets) in monosodium glutamate-induced obese mice and the potential mechanisms. METHOD: Monosodium glutamate-induced obese mice were used to evaluate the anti-Mets effects of QBT. Content levels of malonaldehyde (MDA), reactive oxygen species (ROS) and protein carbonylation, antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR) in the skeletal muscle were assessed by commercial kits, respectively. Western blot and Q-PCR were used to detect the expressions of Transcription Factor Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) signaling pathway and downstream antioxidant factors. In addition, activity of AKT signaling and expression of glucose transporter type 4 (GLUT4) in the skeletal muscle were investigated by western blot. RESULT: QBT treatment limited gain of body weight, waistline and LEE index, improved insulin resistance and glucose intolerance, reduced lipid level in MSG mice. Content levels of MDA, ROS and protein carbonylation in skeletal muscle of QBT group were significantly improved compared to those of MSG mice. The antioxidant enzyme activities of SOD, GPx, CAT, and GR were increased in skeletal muscle of MSG mice intervened with QBT. After 20-week QBT treatment, Nrf2 signaling pathway and downstream antioxidant factors were both increased in the skeletal muscle. In addition, QBT treatment improved insulin signaling by preferentially augmenting AKT signaling, as well as increased the protein expression of GLUT4 in the skeletal muscle. CONCLUSION: Our results showed that QBT intake was effective in protecting monosodium glutamate-induced obese mice against metabolic syndrome and involved in the Nrf2 signaling pathway in the skeletal muscle.

Enrichment of provitamin A content in wheat (Triticum aestivum L.) by introduction of the bacterial carotenoid biosynthetic genes CrtB and CrtI.

Carotenoid content is a primary determinant of wheat nutritional value and affects its end-use quality. Wheat grains contain very low carotenoid levels and trace amounts of provitamin A content. In order to enrich the carotenoid content in wheat grains, the bacterial phytoene synthase gene (CrtB) and carotene desaturase gene (CrtI) were transformed into the common wheat cultivar Bobwhite. Expression of CrtB or CrtI alone slightly increased the carotenoid content in the grains of transgenic wheat, while co-expression of both genes resulted in a darker red/yellow grain phenotype, accompanied by a total carotenoid content increase of approximately 8-fold achieving 4.76 µg g(-1) of seed dry weight, a ß-carotene increase of 65-fold to 3.21 µg g(-1) of seed dry weight, and a provitamin A content (sum of α-carotene, ß-carotene, and ß-cryptoxanthin) increase of 76-fold to 3.82 µg g(-1) of seed dry weight. The high provitamin A content in the transgenic wheat was stably inherited over four generations. Quantitative PCR analysis revealed that enhancement of provitamin A content in transgenic wheat was also a result of the highly coordinated regulation of endogenous carotenoid biosynthetic genes, suggesting a metabolic feedback regulation in the wheat carotenoid biosynthetic pathway. These transgenic wheat lines are not only valuable for breeding wheat varieties with nutritional benefits for human health but also for understanding the mechanism regulating carotenoid biosynthesis in wheat endosperm.

Sesamin induces cell cycle arrest and apoptosis through the inhibition of signal transducer and activator of transcription 3 signalling in human hepatocellular carcinoma cell line HepG2.

Sesamin, one of the most abundant lignans in sesame seeds, has been shown to exhibit various pharmacological effects. The aim of this study was to elucidate whether sesamin promotes cell cycle arrest and induces apoptosis in HepG2 cells and further to explore the underlying molecular mechanisms. Here, we found that sesamin inhibited HepG2 cell growth by inducing G2/M phase arrest and apoptosis. Furthermore, sesamin suppressed the constitutive and interleukin (IL)-6-induced signal transducer and activator of transcription 3 (STAT3) signalling pathway in HepG2 cells, leading to regulate the downstream genes, including p53, p21, cyclin proteins and the Bcl-2 protein family. Our studies showed that STAT3 signalling played a key role in sesamin-induced G2/M phase arrest and apoptosis in HepG2 cells. These findings provided a molecular basis for understanding of the effects of sesamin in hepatocellular carcinoma tumour cell proliferation. Therefore, sesamin may thus be a potential chemotherapy drug for liver cancer.

Atmospheric pressure room temperature plasma jets facilitate oxidative and nitrative stress and lead to endoplasmic reticulum stress dependent apoptosis in HepG2 cells.

Atmospheric pressure room temperature plasma jets (APRTP-Js) that can emit a mixture of different active species have recently found entry in various medical applications. Apoptosis is a key event in APRTP-Js-induced cellular toxicity, but the exact biological mechanisms underlying remain elusive. Here, we explored the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in APRTP-Js-induced apoptosis using in vitro model of HepG2 cells. We found that APRTP-Js facilitated the accumulation of ROS and RNS in cells, which resulted in the compromised cellular antioxidant defense system, as evidenced by the inactivation of cellular antioxidants including glutathione (GSH), superoxide dismutase (SOD) and catalase. Nitrotyrosine and protein carbonyl content analysis indicated that APRTP-Js treatment caused nitrative and oxidative injury of cells. Meanwhile, intracellular calcium homeostasis was disturbed along with the alteration in the expressions of GRP78, CHOP and pro-caspase12. These effects accumulated and eventually culminated into the cellular dysfunction and endoplasmic reticulum stress (ER stress)-mediated apoptosis. The apoptosis could be markedly attenuated by N-acetylcysteine (NAC, a free radical scavenger), which confirmed the involvement of oxidative and nitrative stress in the process leading to HepG2 cell apoptosis by APRTP-Js treatment.

A wheat WRKY transcription factor TaWRKY10 confers tolerance to multiple abiotic stresses in transgenic tobacco.

WRKY transcription factors are reported to be involved in defense regulation, stress response and plant growth and development. However, the precise role of WRKY transcription factors in abiotic stress tolerance is not completely understood, especially in crops. In this study, we identified and cloned 10 WRKY genes from genome of wheat (Triticum aestivum L.). TaWRKY10, a gene induced by multiple stresses, was selected for further investigation. TaWRKY10 was upregulated by treatment with polyethylene glycol, NaCl, cold and H2O2. Result of Southern blot indicates that the wheat genome contains three copies of TaWRKY10. The TaWRKY10 protein is localized in the nucleus and functions as a transcriptional activator. Overexpression of TaWRKY10 in tobacco (Nicotiana tabacum L.) resulted in enhanced drought and salt stress tolerance, mainly demonstrated by the transgenic plants exhibiting of increased germination rate, root length, survival rate, and relative water content under these stress conditions. Further investigation showed that transgenic plants also retained higher proline and soluble sugar contents, and lower reactive oxygen species and malonaldehyde contents. Moreover, overexpression of the TaWRKY10 regulated the expression of a series of stress related genes. Taken together, our results indicate that TaWRKY10 functions as a positive factor under drought and salt stresses by regulating the osmotic balance, ROS scavenging and transcription of stress related genes.

Anti-tumor effect of germacrone on human hepatoma cell lines through inducing G2/M cell cycle arrest and promoting apoptosis.

Germacrone is one of the main bioactive components in the traditional Chinese medicine Rhizoma curcuma. In this study, the anti-proliferative effect of germacrone on the human hepatoma cell lines and the molecular mechanism underlying the cytotoxicity of germacrone were investigated. Treatment of human hepatoma cell lines HepG2 and Bel7402 with germacrone resulted in cell cycle arrest and apoptosis in a dose-dependent manner as measured by MTT assay, flow cytometric and fluorescent microscopy analysis, while much lower effect on normal human liver cell L02 was observed. Flow cytometric analysis revealed that germacrone induced G2/M arrest in the cell cycle progression that was associated with an obvious decrease in the protein expression of cyclin B1 and its activating partner CDK1 with concomitant inductions of p21. Hoechst 33258 and Annexin V/PI staining results showed that the total cell number in apoptosis associated with a dose-dependent up-regulation of Bax and down-regulation of Bcl-2/Bcl-xl was increased. In the meantime, the up-regulation of p53 and reactive oxygen species increase were observed, which suggested that germacrone might be a new potent chemopreventive drug candidate for liver cancer via regulating the expression of proteins related to G2/M cell cycle and apoptosis, and p53 and oxidative damage may play important roles in the inhibition of human hepatoma cells growth by germacrone.

Sesamin induces melanogenesis by microphthalmia-associated transcription factor and tyrosinase up-regulation via cAMP signaling pathway.

In this study, we confirmed that sesamin, an active lignan isolated from sesame seed and oil, is a novel skin-tanning compound. The melanin content and tyrosinase activity were increased by sesamin in a dose-dependent manner in B16 melanoma cells. The mRNA and protein levels of tyrosinase were also enhanced after the treatment with sesamin. Western blot analysis revealed that sesamin induced and sustained up-regulation of microphthalmia-associated transcription factor (MITF). Sesamin could activate cAMP response element (CRE) binding protein (CREB), but it had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) or Akt. Moreover, sesamin activated protein kinase A (PKA) via a cAMP-dependent pathway. Consistent with these results, sesamin-mediated increase of melanin synthesis was reduced significantly by H-89, a PKA inhibitor, but not by SB203580, a p38 MAPK inhibitor or by LY294002, a phosphatidylinositol-3-kinase (PI3K) inhibitor. Sesamin-mediated phosphorylation of CREB and induction of MITF and tyrosinase expression were also inhibited by H-89. These findings indicated that sesamin could stimulate melanogenesis in B16 cells via the up-regulation of MITF and tyrosinase, which was, in turn, due to the activation of cAMP signaling.