First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient.</p> <p>Purpose</p> <p>To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC), a study of single agent treatment with gefitinib in Chinese patients was conducted.</p> <p>Methods</p> <p>45 patients with advanced NSCLC were treated with gefitinib (250 mg daily) until the disease progression or intolerable toxicity.</p> <p>Results</p> <p>Among the 45 patients, 15 patients achieved partial response (PR), 17 patients experienced stable disease (SD), and 13 patients developed progression disease (PD). None of the patients achieved complete response (CR). The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively). The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively). In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively).</p> <p>Conclusions</p> <p>Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.</p

Regression of mouse-derived renal cancer by adoptive transfer of tumor-reactive RNAi-induced TGF-beta-insensitive CD8+ T cells

Transforming growth factor beta (TGF-beta) is a potent immunosuppressant. The present study was conducted to develop a treatment strategy through adoptive transfer of tumor-reactive RNAi-induced TGF-beta-insensitive CD8+ T cells. BALB/c mice were primed with irradiated Renca cells. CD8+ T cells were isolated from the spleen of primed animals, expanded ex vivo and were rendered TGF-beta-insensitive by infecting with a retrovirus containing shRNA to mouse TGF-beta type II receptor gene (MSCV-shRNA-T). Control CD8+ T cells consist of those infected with retroviruses containing shRNA to non specific gene (MSCV-shRNA-N) and naive CD8+ T cells. The effect of all groups of CD8+ T cells on Renca cells were analyzed by semi-quantitative RT-PCR, Western-blot, in vitro and in vivo assay. MSCVshRNA-T group of CD8+ T cells were resistant to the antiproliferative effect of exogenous TGF-beta, while control groups were not. Results of Western blot showed the Smad pathway was disrupted in MSCV-shRNA-T group, which confirmed the blockade of the signal transduction pathway. In vitro cytotoxic assay revealed that these tumor-reactive, TGF-beta-insensitive CD8+ T cells killed Renca cells specifically and strongly. Adoptive transfer of these MSCV-shRNA-T CD8+ T cells to BALB/c tumorbearing mice showed strong tumor-specific cytotoxic T lymphocyte responses and antitumor immunity against Renca renal cancer. Based on these results, we predict that adoptive transfer of tumor-reactive RNAi-induced TGF-beta-insensitive CD8+ T cells may be effective to renal cancer therapy.Keywords: Transforming growth factor beta, adoptive transfer, RNA interference, renal cancer, renca cells, immunotherapyAfrican Journal of Biotechnology Vol. 9(33), pp. 5274-5283, 16 August, 201

Adherence to a planetary health diet, environmental impacts, and mortality in Chinese adults

mportance Although the EAT-Lancet Commission has recently proposed a planetary health diet (PHD) to promote human and environmental health, little is known about how PHD affects environment and mortality risk among an Asian population. Objective To investigate whether a PHD score is associated with environmental impacts and mortality outcomes in a Chinese cohort living in Singapore. Design, Setting, and Participants This cohort study used data from the Singapore Chinese Health Study. Eligible participants were without known cardiovascular disease and cancer at baseline; they were recruited between 1993 and 1998 and followed up using record linkage data until 2020. Data were analyzed from September 2022 to April 2023. Exposures PHD score was calculated based on the reference consumption of 14 dietary components in PHD and individual energy intake assessed using a validated food frequency questionnaire in this cohort. Main Outcomes and Measures Diet-related environmental impacts were estimated using a food frequency questionnaire. Mortality outcomes (all-cause, cardiovascular disease, cancer, and respiratory disease) were identified via linkage with a nationwide registry. Results A total of 57 078 participants were included in this study (mean [SD] age, 56.1 (7.9) years; 31 958 women [56.0%]). During a median (IQR) follow-up of 23.4 (18.7-26.2) years, 22 599 deaths occurred. Comparing the highest and lowest quintiles, higher PHD scores were associated with lower greenhouse gas emissions (β = −0.13 kg CO2 equivalent; 95% CI, −0.14 to −0.12 kg CO2 equivalent), but with higher total water footprint (β = 0.12 m3; 95% CI, 0.11-0.13 m3) and land use (β = 0.29 m2; 95% CI, 0.28-0.31 m2). In the adjusted multivariable model, compared with the lowest quintile, participants in the highest quintile of PHD score had lower risk of all-cause mortality (hazard ratio [HR], 0.85; 95% CI, 0.81-0.89), cardiovascular disease mortality (HR, 0.79; 95% CI, 0.73-0.85), cancer mortality (HR, 0.93; 95% CI, 0.86-1.00), and respiratory disease mortality (HR, 0.81; 95% CI, 0.74-0.89). Conclusions and Relevance In this study of Singapore Chinese adults, higher adherence to PHD was associated with reduced risk of chronic disease mortality. However, environmental impacts were uncertain, as higher adherence was associated with lower greenhouse gas emissions but higher total water footprint and land use

Ca1_xLixAl1_xSi1+xN3：Eu2+ solid solutions as broadband,color-tunable and thermally robust red phosphors for superior color rendition white light-emitting diodes

日前，我院解荣军教授及其合作者在半导体照明用稀土掺杂氮化物发光材料研究上取得突破性进展。稀土发光材料是半导体照明技术中最为关键的核心材料之一，决定了半导体照明器件的发光效率、显色指数、色温和可靠性等重要性能。解荣军教授及其合作者在长期研究氮化物发光材料及半导体照明器件的工作基础上，巧妙地通过发光材料的晶体结构局域调控和能带工程设计，研究和开发了具有宽谱发射、光谱可控的高可靠性氮化物固溶体红色发光材料，成功解决了半导体照明技术中的重要科学问题和关键技术难题。该论文的第一作者为中国计量大学光学与电子技术学院的王乐副教授，解荣军和王乐为共同通讯作者，厦门大学为第一通讯单位。合作单位还有日本国立材料研究所、重庆邮电大学和台湾大学。由于文章具有创新性和重要性，被选为当期封面文章。【Abstract】Color rendition, luminous efficacy and reliability are three key technical parameters for white light-emitting diodes (wLEDs) that are dominantly determined by down-conversion phosphors. However, there is usually an inevitable trade-off between color rendition and luminescence efficacy because the spectrum of red phosphor (that is, spectral broadness and position) cannot satisfy them simultaneously. In this work, we report a very promising red phosphor that can minimize the aforementioned trade-off via structure and band-gap engineering, achieved by introducing isostructural LiSi2N3 into CaAlSiN3:Eu2+. The solid solution phosphors show both substantial spectra broadening (88→117 nm) and blueshift (652→642 nm), along with a significant improvement in thermal quenching (only a 6% reduction at 150 °C), which are strongly associated with electronic and crystal structure evolutions. The broadband and robust red phosphor thus enables fabrication of super-high color rendering wLEDs (Ra=95 and R9=96) concurrently with the maintenance of a high-luminous efficacy (101 lm W−1), validating its superiority in high-performance solid state lightings over currently used red phosphors.We are grateful for the financial support from the JSPS KAKENHI (No. 23560811), the National Natural Science Foundation of China (Nos. 51272259, 61575182, 5157223 and 51561135015), the Natural Science Foundation of Zhejiang Province (No. Y16F050012) and the Taiwan Science and Technology Authority (No. ‘MOST’ 104-2113-M-002-012-MY3 and No. 104-2119-M-002-027-MY3)

Aluminate red phosphor in light-emitting diodes : theoretical calculations, charge varieties and high-pressure luminescence analysis

This work was supported by the Ministry of Science and Technology of Taiwan (Contract Nos. MOST 104-2113-M- 002-012-MY3 and MOST 104-2923-M-002-007-MY3). This research was also supported by National Centre for Re- search and Development, Poland (Grant No. PL- TW2/8/2015).Searching for a non-rare earth-based oxide red-emitting phosphor is crucial for phosphor-converted light- emitting diodes (LEDs). In this study, we optimized a blue and UV-light excited Sr4Al14O25:Mn phosphor exhibiting red emission peaked at ~653 nm, which was successfully synthesized by solid-state reaction. The crystal structure, micromorphology, and luminescent properties of Sr4Al14O25:Mn phosphors were characterized by X-ray Rietveld refinement, high-resolution transmission electron microscopy, and photoluminescence spectra. The band gap and electronic structure of Sr4Al14O25 were analyzed by density functional theory calculation using the hybrid exchange- correlation functional. The crystal field environment effect of Al sites from introducing activator Mn ions was investigated with the aid of Raman 27Al nuclear magnetic resonance spectra and electron spin resonance. The pressure dependent on the luminescent properties and decay time of this compound were presented. The tricolor display spectrum by combining blue InGaN chips, commercial β-SiAlON:Eu2+ green phosphor, and Sr4Al14O25:Mn red phosphor were evaluated for commercial applications: using the present Sr4Al14O25:Mn red phosphor converted LED as backlighting source.PostprintPeer reviewe

Current status of xenotransplantation research and the strategies for preventing xenograft rejection

Transplantation is often the last resort for end-stage organ failures, e.g., kidney, liver, heart, lung, and pancreas. The shortage of donor organs is the main limiting factor for successful transplantation in humans. Except living donations, other alternatives are needed, e.g., xenotransplantation of pig organs. However, immune rejection remains the major challenge to overcome in xenotransplantation. There are three different xenogeneic types of rejections, based on the responses and mechanisms involved. It includes hyperacute rejection (HAR), delayed xenograft rejection (DXR) and chronic rejection. DXR, sometimes involves acute humoral xenograft rejection (AHR) and cellular xenograft rejection (CXR), which cannot be strictly distinguished from each other in pathological process. In this review, we comprehensively discussed the mechanism of these immunological rejections and summarized the strategies for preventing them, such as generation of gene knock out donors by different genome editing tools and the use of immunosuppressive regimens. We also addressed organ-specific barriers and challenges needed to pave the way for clinical xenotransplantation. Taken together, this information will benefit the current immunological research in the field of xenotransplantation

Plasma microRNA Profiles as a Potential Biomarker in Differentiating Adult-Onset Still's Disease From Sepsis

Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by cytokine storm. However, a diagnostic test for AOSD in clinical use is yet to be validated. The aim of our study was to identify non-invasive biomarkers with high specificity and sensitivity to diagnosis of AOSD. MicroRNA (miRNA) profiles in PBMC from new-onset AOSD patients without any treatment and healthy controls (HCs) were analyzed by miRNA deep sequencing. Plasma samples from 100 AOSD patients and 60 HCs were used to validated the expression levels of miRNA by qRT-PCR. The correlations between expression levels of miRNAs and clinical manifestations were analyzed using advanced statistical models. We found that plasma samples from AOSD patients showed a distinct miRNA expression profile. Five miRNAs (miR-142-5p, miR-101-3p, miR-29a-3p, miR-29c-3p, and miR-141-3p) were significantly upregulated in plasma of AOSD patients compared with HCs both in training and validation sets. We discovered a panel including 3 miRNAs (miR-142-5p, miR-101-3p, and miR-29a-3p) that can predict the probability of AOSD with an area under the receiver operating characteristic (ROC) curve of 0.8250 in training and validation sets. Moreover, the expression levels of 5 miRNAs were significantly higher in active AOSD patients compared with those in inactive patients. In addition, elevated level of miR-101-3p was found in AOSD patients with fever, sore throat and arthralgia symptoms; the miR-101-3p was also positively correlated with the levels of IL-6 and TNF-α in serum. Furthermore, five miRNAs (miR-142-5p, miR-101-3p, miR-29c-3p, miR-29a-3p, and miR-141-3p) expressed in plasma were significantly higher in AOSD patients than in sepsis patients (P &lt; 0.05). The AUC value of 4-miRNA panel (miR-142-5p, miR-101-3p, miR-29c-3p, and miR-141-3p) for AOSD diagnosis from sepsis was 0.8448, revealing the potentially diagnostic value to distinguish AOSD patients from sepsis patients. Our results have identified a specific plasma miRNA signature that may serve as a potential non-invasive biomarker for diagnosis of AOSD and monitoring disease activity

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe