Inhibiting Delta-6 Desaturase Activity Suppresses Tumor Growth in Mice

Recent studies have shown that a tumor-supportive microenvironment is characterized by high levels of pro-inflammatory and pro-angiogenic eicosanoids derived from omega-6 (n−6) arachidonic acid (AA). Although the metabolic pathways (COX, LOX, and P450) that generate these n−6 AA eicosanoids have been targeted, the role of endogenous AA production in tumorigenesis remains unexplored. Delta-6 desaturase (D6D) is the rate-limiting enzyme responsible for the synthesis of n−6 AA and increased D6D activity can lead to enhanced n−6 AA production. Here, we show that D6D activity is upregulated during melanoma and lung tumor growth and that suppressing D6D activity, either by RNAi knockdown or a specific D6D inhibitor, dramatically reduces tumor growth. Accordingly, the content of AA and AA-derived tumor-promoting metabolites is significantly decreased. Angiogenesis and inflammatory status are also reduced. These results identify D6D as a key factor for tumor growth and as a potential target for cancer therapy and prevention

An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus.

A new SARS animal model was established by inoculating SARS coronavirus (SARS-CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5-60 after virus inoculation. All eight animals showed a transient fever 2-3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS-CoV-specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS-CoV RNA could be detected in pharyngeal swab samples using nested RT-PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS-CoV-related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS

Comparison of gemcitabine/carboplat in versus paclitaxel/cisplatin for the management of non small cell lung cancer

Purpose: To determine the comparative efficacy and toxicity of gemcitabine/carboplatin and paclitaxel/cisplatin in patients with completely resected stage IIa - IIIa non-small cell lung cancer (NSCLC). Methods: Sixty eligible NSCLC patients treated in Funan County People's Hospital were enrolled and assigned to two groups by randomization (n = 30 each). One group (CG group) received the combination of gemcitabine and carboplatin, while the second group (CP group) received a combination of cisplatin and paclitaxel. Efficacy was assessed based on 2-year progression-free survival, while adverse reactions were recorded to assess the toxicity of the chemotherapy treatments. Results: No marked difference was found in the 2-year relapse-free survival in the two groups with similar clinical baseline characteristics after follow-up (60 % in CG group vs. 56.67 % in CP group, p = 0.826). Specifically, no significant difference was found between the two groups with regard to incidence of local metastases, distant metastases, or brain tissue metastases within 2 years, and there were no treatment-related deaths. CG group was more likely to develop leukopenia (93.33 % vs. 63.33 % for CP group, p = 0.04), but no significant difference was observed for other adverse effects such as anemia, vomiting, and nausea. Conclusion: This study shows that adjuvant treatment using carboplatin and gemcitabine produces the same therapeutic efficacy as cisplatin and paclitaxel, but exhibits higher toxicity levels than the latter

Online Streaming Video Super-Resolution with Convolutional Look-Up Table

Online video streaming has fundamental limitations on the transmission bandwidth and computational capacity and super-resolution is a promising potential solution. However, applying existing video super-resolution methods to online streaming is non-trivial. Existing video codecs and streaming protocols (\eg, WebRTC) dynamically change the video quality both spatially and temporally, which leads to diverse and dynamic degradations. Furthermore, online streaming has a strict requirement for latency that most existing methods are less applicable. As a result, this paper focuses on the rarely exploited problem setting of online streaming video super resolution. To facilitate the research on this problem, a new benchmark dataset named LDV-WebRTC is constructed based on a real-world online streaming system. Leveraging the new benchmark dataset, we proposed a novel method specifically for online video streaming, which contains a convolution and Look-Up Table (LUT) hybrid model to achieve better performance-latency trade-off. To tackle the changing degradations, we propose a mixture-of-expert-LUT module, where a set of LUT specialized in different degradations are built and adaptively combined to handle different degradations. Experiments show our method achieves 720P video SR around 100 FPS, while significantly outperforms existing LUT-based methods and offers competitive performance compared to efficient CNN-based methods

Combined Multistate and Kohn-Sham Density Functional Theory Studies of the Elusive Mechanism of N-Dealkylation of N,N-Dimethylanilines Mediated by the Biomimetic Nonheme Oxidant FeIV(O)(N4Py)(ClO4)2

The oxidative C-H bond activation mediated by heme and nonheme enzymes and related biomimetics is one of the most interesting processes in bioinorganic and oxidative chemistry. However, the mechanisms of these reactions are still elusive and controversy due to the involvement of highly reactive metal-oxo intermediates with multiple spin states, despite extensive experimental efforts, especially for the N-dealkylation of N,N-dialkyalinines. In this work, we employed multistate density functional theory (MSDFT) and the Kohn-Sham DFT to investigate the mechanism of N-demethylation of N,N-dimethyalinines oxidized by the reaction intermediate FeIV(O)(N4Py)(ClO4)2. The Kohn-Sham DFT study demonstrated that the reaction proceeds via a rate-limiting hydrogen atom transfer (HAT) step and a subsequent barrier-free oxygen rebound step to form the carbinol product. The MSDFT investigation on the first C-H activation further showed that this step is an initial hydrogen atom abstraction that is highly correlated between CEPT and HAT, i.e., both CEPT and HAT processes make significant contributions to the mechanism before reaching the diabatic crossing point, then the valence bond character of the adiabatic ground state is switched to the CEPT product configuration. The findings from this work may be applicable to other hydrogen abstraction process

Development and validation of prognostic nomogram for lung cancer patients below the age of 45 years

This study aimed to establish a nomogram for the prognostic prediction of patients with early-onset lung cancer (EOLC) in both overall survival (OS) and cancer-specific survival (CSS). EOLC patients diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and further divided into training and validation sets randomly. The prognostic nomogram for predicting 3-, 5- and 10-years OS and CSS was established based on the relative clinical variables determined by the multivariate Cox analysis results. Furthermore, the predictive performance of nomogram was assessed by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve. A total of 1,822 EOLC patients were selected and randomized into a training cohort (1,275, 70%) and a validation cohort (547, 30%). The nomograms were established based on the statistical results of Cox analysis. In training set, the C-indexes for OS and CSS prediction were 0.797 (95% confidence interval [CI]: 0.773-0.818) and 0.794 (95%CI:0.771-0.816). Significant agreement in the calibration curves was noticed in the nomogram models. The results of ROC and DCA indicated nomograms possessed better predict performance compared with TNM-stage and SEER-stage. And the area under the curve (AUC) of the nomogram for OS and CSS prediction in ROC analysis were 0.766 (95%CI:0.745-0.787) and 0.782 (95%CI:0.760-0.804) respectively. The prognostic nomogram provided an accurate prediction of 3-, 5-, and 10-year OS and CSS of EOLC patients which contributed clinicians to optimize individualized treatment plans.&nbsp

Clinical efficacy and safety of adjunctive treatment of chronic ischemic heart failure with Qishen Yiqi dropping pills: a systematic review and meta-analysis

ObjectivesOur study was to evaluate the effect of Qishen Yiqi Dropping Pills(QSYQ) on the prognosis of chronic ischemic heart failure(CIHF) and its safety.MethodsDatabases including CNKI, Wanfang, VIP, CBM, PubMed, Web of Science, The Cochrane Library and EMbase were searched from their inception to April 2023 to screen relevant randomized controlled trials (RCTs). Primary indicators included readmission rates, rates of major adverse cardiovascular events (MACE), and all-cause mortality rates. The quality of the literature was assessed according to the Cochrane Reviewers' Handbook 5.0 and the Modified Jadad Scale (with a score of 4–7 rated as high quality). Meta-analysis was performed using the meta-package created by R software version 4.2.3, continuous data were compared using SMDs, and dichotomous and ordered data were compared using ORs; and the I2 test was used to assess the heterogeneity.ResultsFifty-nine studies out of 1,745 publications were finally included, totalling 6,248 patients. Most studies were poorly designed and had some publication bias, with only 26 high-quality papers (Jadad score ≥4). Meta-analysis showed that the combined application of QSYQ was able to reduce the readmission rate [OR = 0.42, 95% CI (0.33, 0.53), P < 0.001], all-cause mortality rate [OR = 0.43, 95% CI (0.27, 0.68), P < 0.001], and the incidence of MACE [OR = 0.42, 95% CI (0.31, 0.56), P < 0.001]. Also, the treatment method can improve clinical effectiveness [OR = 2.25, 95% CI (1.97, 2.58), P < 0.001], increase 6-min walking distance (6MWD) [SMD = 1.87, 95% CI (1.33, 2.41), P < 0.0001] and left ventricular ejection fraction (LVEF) [SMD = 1.08, 95% CI (0.83, 1.33), P < 0.0001], and decrease the Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores [SMD = −2.03, 95% CI (−3.0, −1.07), P < 0.0001], BNP levels [SMD = −2.07, 95% CI (−2.81, −1.33), P < 0.0001] and NT-ProBNP levels [SMD = −2.77, 95% CI (−4.90, −0.63), P < 0.05]. A total of 21 studies (n = 2,742) evaluated their adverse effects, of which 13 studies reported no adverse effects and 8 studies reported minor adverse effects.ConclusionOur results suggest that the combined application of QSYQ can further improve patients' cardiac function and exercise tolerance, improve their quality of life, and ultimately improve patients' prognosis with a favorable safety profile. Nonetheless, limited by the quality and high heterogeneity of the literature, we must be conservative and cautious about the present results.Systematic Review RegistrationPROSPERO (CRD42023449251)