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Non-small cell lung cancer is recognized as the deadliest cancer across the globe. In some areas, it is more common in women than even breast and cervical cancer. Its rise, vaulted by smoking habits and increasing air pollution, has garnered much attention and resource in the medical field. The first lung cancer treatments were developed more than half a century ago. Unfortunately, many of the earlier chemotherapies often did more harm than good, especially when they were used to treat genetically unsuitable patients. With the introduction of personalized medicine, physicians are increasingly aware of when, how, and in whom, to use certain anti-cancer agents. Drugs such as tyrosine kinase inhibitors, anaplastic lymphoma kinase inhibitors, and monoclonal antibodies possess limited utility because they target specific oncogenic mutations, but other drugs that target mechanisms universal to all cancers do not. In this review, we discuss many of these non-oncogene-targeting anti-cancer agents including DNA replication inhibitors (i. e., alkylating agents and topoisomerase inhibitors) and cytoskeletal function inhibitors to highlight their application in the setting of personalized medicine as well as their limitations and resistance factors. This review discusses non-oncogene-targeting anti-cancer agents including DNA replication inhibitors and cytoskeletal function inhibitors to highlight their application in personalized medicine as well as their limitations and resistance factors. [Display omitted] [ABSTRACT FROM AUTHOR]

Recently, radioresistance has become a major obstacle in the radiotherapy of cervical cancer. To demonstrate enhanced radiosensitization against radioresistant cervical cancer, radioresistant cervical cancer cell line was developed and the mechanism of radioresistance was explored. Due to the overexpression of (death receptor 5, DR5) in cervical cancer, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-overexpressed cervical cancer cell membrane-camouflaged Cu 2−x Se nanomedicine (CCMT) was designed. Since the CCMT was encapsulated with TRAIL-modified cell membrane, it represented high target to cervical cancer cell and immune evasion. Furthermore, Cu 2−x Se had the ability to scavenge glutathione (GSH) and produce ·OH with excess H 2 O 2 in the tumor microenvironment. The presence of CCMT combined with radiation therapy could effectively increase the 1O 2 produced by X-rays. In vitro and in vivo studies elaborated that CCMT exhibited excellent radiosensitization properties to reverse radiotolerance by scavenging GSH and promoting DNA damage, apoptosis, mitochondrial membrane potential damage and metabolic disruption. Collectively, this study suggested that the development of TRAIL-overexpressed cell membrane-camouflaged Cu 2−x Se nanomedicine could advance future cervical cancer treatment and minimize the disadvantages associated with radiation treatment. [Display omitted] • DR5 overexpression enables CCMT with Cu 2−x Se/TRAIL-camouflaged membrane. • TRAIL-CCMT excels in targeting, immune evasion, and radiosensitization via GSH depletion and metabolic disruption. • CCMT proves superior against cervical cancer radioresistance. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer is a prevalent and rapidly-expanding challenge to modern medicine. While generalized medicine with traditional chemotherapy yielded comparatively poor response rates and treatment results, the cornerstone of personalized medicine using genetic profiling to direct treatment has exalted the successes seen in the field and raised the standard for patient treatment in lung and other cancers. Here, we discuss the current state and advances in the field of personalized medicine for lung cancer, reviewing several of the mutation-targeting strategies that are approved for clinical use and how they are guided by patient genetic information. These classes include inhibitors of tyrosine kinase (TKI), anaplastic lymphoma kinase (ALK), and monoclonal antibodies. Selecting from these treatment plans and determining the optimal dosage requires in-depth genetic guidance with consideration towards not only the underlying target genes but also other factors such as individual metabolic capability and presence of resistance-conferring mutations both directly on the target gene and along its cascade(s). Finally, we provide our viewpoints on the future of personalized medicine in lung cancer, including target-based drug combination, mutation-guided drug design and the necessity for data of population genetics, to provide rough guidance on treating patients who are unable to get genetic testing. [ABSTRACT FROM AUTHOR]

Radioresistance has been the main obstacle of cervical cancer radiotherapy. Hence, it's urgent need to develop effective radiosensitizers for improving the radiotherapeutic efficacy. MoSe 2 has been recognized as a promising therapeutic nanoplatform in radio/photo-mediated cancer therapy, due to its narrow bandgap and good photoelectric/photothermal conversion capabilities, while these physical properties and its biological performance can be various depending on its structure. Herein, radiosensitization nanosystems based on two common forms of MoSe 2 nanomaterial, 2D nanosheet (NS) and 3D nanoflower (NF), were developed, and their therapeutic efficacy and mechanisms in treating cervical cancer were contrastively analyzed. In vitro experiments on Hela and Siha cells demonstrated superior synergistic therapeutic efficacy of MoSe 2 NF-RGD over MoSe 2 NS-RGD. Further analysis revealed that compared to MoSe 2 NS-RGD, MoSe 2 NF-RGD efficiently targeted and accumulated in cancer cell mitochondria, leading to mitochondria-mediated apoptosis associated with p53 phosphorylation. Moreover, the metabolites of MoSe 2 NF-RGD including selenocystine (SeCys 2) and methylselenocysteine (MeSeCys 2) also contributed to its unique advantages in radiosensitized cancer-killing effect. Consistently, in vivo study confirmed higher therapeutic efficacies of MoSe 2 NF-RGD combined with X-ray against the primary tumor as well as distant tumor through boosting the infiltration of some specific immune cells including dendritic cells (DCs) and NK1.1 cells. Collectively, this work revealed the influence of material structure on the biological performance and radiotherapeutic efficacy of MoSe 2 -based nanosystems and the underlying mechanisms for these structure-dependent difference. Morphology-directed MoSe 2 nanosystems could regulate selenoproteins and promote DNA damage to enhance X-ray radiotherapy. The MoSe 2 nanoflower regulates TrxR2 expression through metabolism into SeCys 2 and MeSeCys 2 and induces ROS-mediated apoptosis and cell cycle arrest by triggering mitochondrial dysfunction. [Display omitted] • Nanoflower-shaped MoSe 2 can absorb more photon energy with stronger radiocatalytic ability. • MoSe 2 NF-RGD exerts superior synergistic radiotherapeutic efficacy. • Different morphology determines the mitochondrial accumulation of MoSe 2 nanosystems. • Metabolism into SeCys 2 and MeSeCys 2 contributes to stronger radiosensitization of MoSe 2 NF-RGD. • MoSe 2 NF-RGD exhibits stronger antitumor efficacy through boosting immune response. [ABSTRACT FROM AUTHOR]

In this paper, a rapid and sensitive multiplex flow-through immunoaffinity chromatography test (FTIACT) was developed for the on-site screening of 14 sulfonamide and 13 quinolone residues in milk. The developed FTIACT method combines the purification, preconcentration and immunochemical detection of multiple antibiotics on the sepharose gel test layers. The use of liposome-encapsulated quantum dots (LQDs) with the FTIACT method exhibited the best results, with limits of detection (LODs) of 1 and 0.5 ng/mL for the sulfonamides (SAs) and quinolones (QNs), respectively, through qualitative analysis (visual detection by the naked eye). In order to achieve low detection limit, the color intensity of the images were converted into relative optical density values to enable a quantitative evaluation. Quantitative analysis of the samples enabled the detection of SAs (0.13 ng/mL) and QNs (0.062 ng/mL) in spiked milk samples. The FTIACT described in this work shows promise as a multiplex immunoassay for the qualitative and quantitative screening of multiple chemical residues in milk. [ABSTRACT FROM AUTHOR]

Highlights: [•] The efficacy and safety of LNG-IUSs use in women with symptomatic uterine leiomyoma. [•] LNG-IUSs could decrease uterine volume and endometrial thickness. [•] LNG-IUSs could reduce menstrual blood loss. [•] LNG-IUS expulsion was related to leiomyoma size. [•] LNG-IUSs have no adverse effects on the ovarian function except for ovarian cysts. [Copyright &y& Elsevier]

Abstract: Fumonisin B1 (FB1) is a mycotoxin, mainly produced by Fusarium fungi and present in food and feed. It causes harmful effects on human and animal health. Therefore, it is necessary to develop sensitive and reliable screening methods. In this study, a highly sensitive monoclonal antibody (MAb) against FB1, clone 2D7, was produced, and the 50% inhibition concentration (IC50) of the MAb was 2.2 ng/mL in buffer. The MAb showed high cross-reactivity with fumonisin B2 (FB2), and negligible cross-reactivity with other mycotoxins. A sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) based on this MAb was developed for the determination of FB1 in maize. In spiked samples (100, 200 and 500 μg/kg), the average recoveries ranged from 78 ± 11 to 107 ± 4%, and the coefficient of variation ranged from 3 to 15%. The limit of detection of the icELISA was 5.4 μg/kg. This method was compared to liquid chromatography tandem mass spectrometry (LC–MS/MS) using naturally contaminated samples, and the correlation coefficient was above 0.82. These results show the reliability of the icELISA method for the determination of FB1 in maize. [Copyright &y& Elsevier]

Abstract: A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the detection of 1-amino-hydantoin (AHD) is described. AHD, the marker residue for nitrofurantoin, is a tissue bound toxic metabolite. To monitor the illegal use of nitrofurantoin, a monoclonal antibody-based ELISA method was developed to detect AHD residue in animal tissues. The highly specific antibody against AHD was prepared by monoclonal antibody technology. The antibody exhibited negligible cross reactivity with other nitrofurans, their metabolites and derivatives, and 50% inhibitory concentration was 0.68 μg/L. The limit of detection in four kinds of animal tissues were all below 0.2 μg/kg and recoveries ranged from 75% to 116.7% for fortified samples at levels of 0.2–5 μg/kg with coefficient of variation values below 15%. Analysis of natural contaminated samples by the ELISA method gave similar results to those of the liquid chromatography-tandem mass spectrometry method. These results indicate the ELISA method is suitable for the detection of AHD residue in animal tissues. [Copyright &y& Elsevier]

Abstract: Here, we present a case in which the result of a maternity test was obscured due to two false indirect exclusions that occurred in two out of 15 genetic loci through the use of the AmpFlSTR Identifiler PCR Amplification kit (Applied Biosystems, Foster City, CA). The Identifiler kit failed to amplify allele 11 of the D5S818 system on the child and failed to capture the existence of allele 13 on the FGA system on both mother and child. The situation was remedied through use of the PowerPlex 16 PCR Amplification Kit (Promega, Madison, WI) which used different primers with a different allele range than that of the Identifiler kit. Maternity was confirmed through sequencing and it was found that the failure of the Identifiler kit to amplify allele 11 on the D5S818 system was the result of an incompatibility to the primer-binding site due to a mutation that changed a guanine (G) into a thymine (T) 55 base pairs (bp) downstream of the repeat. The inability of the Identifiler kit to pick up allele 13 of the FGA system was due to the out-of-range location of the allele. Indirect exclusions can be misleading if they are not fully investigated since allele range as well as primer-binding affinity are two confounders that must be addressed to ensure accuracy of the test results. [Copyright &y& Elsevier]

Online ride-hailing as an innovative travel mode becomes increasingly popular in cities around the world. To improve the efficiency of dispatching system of ride-hailing, many ride-hailing demand prediction models based on deep learning architecture have been proposed to reduce the gross travel distance between drivers and passengers. However, in most of these prediction models, only the error metrics are used for performance evaluation. There is scarce evidence on how much the demand prediction model reduces the unnecessary travel distance in reality. In this study, a multi-scenario-based method is proposed to evaluate technical potentials of the ride-hailing demand prediction model in ride-hailing dispatching system simulation. The ride-hailing dispatching is simulated in three scenarios: traditional dispatching system, prediction model-based dispatching system, and perfect prediction model-based dispatching system. One-month data of Didi Express service provided by Didi Chuxing GAIA Initiative in Chengdu is employed to support the simulation. Two terms, empty distance and relative performance, are introduced as the criteria of prediction model performance measurement. Simulation results reveal that the total empty distance reduced 1,164 km per day by using the prediction model compared with the traditional dispatching system. The relative performance is only 58.9% compared with the perfect prediction model-based dispatching system. [ABSTRACT FROM AUTHOR]

Chemoresistance including intrinsic and acquired anticancer drug resistance continues to be a primary hindrance towards curative cancer treatment. Therefore, deciphering the underlying molecular mechanisms is of paramount importance required towards the overcoming of chemoresistance. Cumulative evidence revealed that long non-coding RNAs (lncRNAs) play a pivotal role in conferring anticancer drug resistance upon a broad spectrum of cancers. Hence, numerous lncRNAs are recognized as novel biomarkers and therapeutic targets in the diagnosis and treatment of malignancies, which urges us to comprehensively delineate the critical functions of lncRNAs in chemoresistance. In this respect, we herein succinctly elucidate the molecular mechanisms by which lncRNAs modulate their downstream targets to mediate cancer chemoresistance. Therefore, the current review may provide a significant basis for the future conquering of chemoresistance via targeting lncRNAs in cancer therapeutics. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel aggregation-induced emission luminogens encoded microspheres were synthesized. • An anti-microcystin-LR antibody conjugated Sepharose gel column was prepared. • A fast and sensitive immunoaffinity chromatographic method was developed for microcystin-LR. Despite decades of efforts, we are faced with the daunting task of on-site ultratrace environmental toxins detecting, especially the microcystins caused by water bloom. In this work, a novel fluorescent microsphere-based flow-through immunoaffinity chromatographic assay has been designed for detecting ultratrace microcystin-LR in water and aquatic products. The aggregation-induced emission luminogens were encapsulated into fluorescent microspheres to ensure microcystin-LR quantitation with a whole analytical time of less than 30 min. Furthermore, the colorimetric images were captured and quantitatively analyzed, which offered a limit of detection at 0.217 pg/mL and a limit of quantitation at 0.362 pg/mL in water and aquatic muscle samples. The developed immunoassays provide average recovery ranging from 79.1 % to 95.7 %, with relative standard deviations less than 13.4 %. Thus, the validated flow-through immunoaffinity chromatographic assay is an easy-to-use alternative for on-site screening of microcystin-LR in water and aquatic samples at picogram levels. [ABSTRACT FROM AUTHOR]

In this study, new clindamycin (CLIN) artificial antigens were prepared and used to produce broad-specificity monoclonal antibodies. Based on the as-produced mAbs, a heterologous ELISA was developed to detect CLIN and lincomycin (LIN) residues in edible animal tissues. The IC 50 values of the developed assay were 0.3 ng/mL (CLIN) and 1.2 ng/mL (LIN) in buffer, respectively. The detection limits were estimated to be 1.8 μg/kg (CLIN) and 6.8 μg/kg (LIN) in bovine, chicken, porcine and fish muscles. In the spike and recovery tests, the mean recovery rate ranged from 76% to 112% at different spiked levels, and the intra −/inter-assay coefficients of variation were in the range of 7.1% to 13.2%. This method was verified using LC − MS/MS with a correlation coefficient > 0.97. The developed ELISA is therefore well suited for simultaneous determination of CLIN and LIN residues in bovine, chicken, porcine and fish muscles. [ABSTRACT FROM AUTHOR]

A sensitive and specific monoclonal antibody against clindamycin (CLIN) was produced and used to develop an immuno-affinity test column (IATC) assay for on-site screening of CLIN residues in milk. The qualitative limit of detection of the IATC assay, estimated as 1.0 μg L −1 by visual detection, was sufficient to measure maximum residue levels for lincosamide antibiotics in milk. The quantitative IATC assay resulted in a lower detection limit (0.11 μg L −1 ) by evaluating the colour intensity of the test layers, which was approximately 9 times greater sensitivity than visual detection. During the spike and recovery test, the average recoveries ranged from 76% to 114% at different spiked levels, and the intra-/interday coefficients of variation were in the range 9.6–16.7%. The detection time was shortened to 20 min, whereas the sensitivity was comparable with a traditional ELISA. The IATC assay shows promise for on-site screening of CLIN residues in milk. [ABSTRACT FROM AUTHOR]

Objective: To conduct a meta-analysis of the studies assessing the effects of mifepristone on the uterus, uterine leiomyoma, and leiomyoma-related symptoms in premenopausal women. Design: Meta-analysis. Setting: Centers for reproductive care. Patient(s): Premenopausal women who suffered from leiomyoma. Intervention(s): We identified all of the studies published before December 2012 that compared the status of patients with leiomyoma before and after treatment with mifepristone. Main Outcome Measure(s): Leiomyoma-related symptoms, uterine or leiomyoma volume, changes in endometrial thickness. Result(s): A meta-analytic technique was used to study 11 randomized controlled trials involving 780 women with symptomatic uterine leiomyomas. The subjects received 2.5–25 mg/d of mifepristone for 3–6 months. Mifepristone could effectively reduce uterine and leiomyoma volume and alleviate leiomyoma symptoms, including hypermenorrhea, the mean menstrual blood loss, pelvic pain, pelvic pressure, anemia, and dysmenorrhea. There was no significant difference in the rate of atypical endometrial hyperplasia between the mifepristone treatment group and the placebo group. Conclusion(s): Mifepristone significantly reduced uterine and leiomyoma volume and alleviated leiomyoma-related symptoms. We recommend 2.5 mg of mifepristone administered daily for 3 or 6 months as the optimum clinical treatment for leiomyoma. There is insufficient evidence that mifepristone treatment led to atypical endometrial hyperplasia. [Copyright &y& Elsevier]

[Display omitted] • We synthesized carbon dots with quantum yields reaching 97.1%. • An inner filter effect immunosensor was setup for aflatoxin M 1 residue analysis. • Our immunosensor detection limit was 0.0186 ng/mL for aflatoxin M 1 in milk. • This immunosensor format is flexible for other chemical residue analysis. Here, a facile hydrothermal method was used to synthesize highly photoluminescent N -doped carbon dots, and the quantum yields reached 97.1%. Then, a label-free immunosensor based on the inner filter effect of carbon dots was developed for ultrasensitive detection of aflatoxin M 1 residues in milk. The detection limit was 0.0186 ng/mL (equivalents to 18.10 ng/kg), which satisfied the most stringent maximum tolerable limit value of 25 ng/kg. Besides, the immunosensor showed a good linear relationship from 0.003 ng/mL to 0.81 ng/mL, and the average recoveries ranged from 79.6% to 112.5% for spiked milk samples, with relative standard deviations ranging from 6.7% to 13.3%. Compared with other immunoassays, the inner filter effect-based immunosensor incorporating fluorescent detection into conventional enzymatic cascade amplification systems and could be a reliable on-site screening method for aflatoxin M 1 residue analysis. [ABSTRACT FROM AUTHOR]

The on-road braking emission has been proved by former studies to account for a considerable part of on-road transportation. To improve cleaner air in urban area, the spatio-temporal analysis on emission performance of on-road braking is necessary as a guideline for decision-making. In this paper, we propose a framework for analysis on the particle matter emission of on-road vehicle braking events on an urban scale. We used massive vehicle trajectories in Tokyo area with short time interval as the database for analysis. From the result, we found that within the in the study area, the average driving distance during braking takes up about 20.60% of total driving distance. The average quantity of PM10 emission from braking for each driving trajectory is 14.09 mg and the one from exhaust emission is 35.36 mg. The emission from braking can averagely occupy 39.85% of exhaust emission. What's more, in our finding, the braking emission from heavy duty vehicle is 2.33 times of light duty vehicle. From the spatial distribution of PM10 braking emission, we found that braking emission usually happened in the city center and popular crowded areas due to the large traffic volume, as well as the main trunk roads of capital expressway or highway. We also found a different spatial pattern between the light duty vehicle and heavy-duty vehicle. In temporal change, we found that rapid peaks during the rush hour on weekday and contrastive stabilization on weekend. We believe our finding can provide a clearer pattern and understanding on the emission behavior of on-road vehicle braking. Image 1 • Proposing a framework to for analysis on the particle matter emission of on-road vehicle braking events on an urban scale. • Proposing a method to detect and mine emission from braking behaviors from GPS trajectory data of vehicle travelling. • Over twenty million historical GPS points of individual vehicle in Tokyo area are employed for analysis. • We found that emission from braking can occupy 39.85% of exhaust emission and HDV emits 2.33 times of LDV. [ABSTRACT FROM AUTHOR]

Low tumor mutational burden and absence of T cells within the tumor sites are typical characteristics of "cold immune tumors" that paralyzes the immune system. The strategy of reversing "cold tumors" to "hot tumors" infiltrated high degree of T cells in order to activate anti-tumor immunity has attracted lots of attentions. Herein, immunogenic core–shell Au@Se NPs is fabricated by gold-selenium coordination bond to realize nanoparticles-mediated local photothermal-triggered immunotherapy. As expected, incorporation of gold nanostars (AuNSs) with improved photothermal stability and conversion efficiency promotes the disintegration and transformation of selenium nanoparticles (SeNPs), thus leading to enhanced cancer cells apoptosis by producing higher hyperthermia. Moreover, the results of in vivo experiments demonstrate that the synergy between SeNPs-mediated chemotherapy and AuNSs-induced photothermal therapy not only generated a localized antitumor-immune response with excellent cancer killing effect under the presence of tumor-associated antigens, but also effectively reprogrammed the tumor associated macrophages (TAMs) from M2 to M1 phenotype with tumoricidal activity to devour distant tumors. Without a doubt, this study not only provides a potent strategy to reverse the immunosuppressive tumor microenvironment, but also offers a new insight for potential clinical application in tumor immunotherapy. The present study provides demonstration of rational design of immunogenic nanotherapeutics Au@Se NPs for PTT-triggered immunotherapy involving reprogramming immunosuppression and activating systemic antitumor responses, which offers a new insight for potential clinical application in tumor immunotherapy. Image 1 [ABSTRACT FROM AUTHOR]

In recent years, Internet-supported non-dock bicycle-sharing service had emerged and gradually become warmly applauded by the public. In the non-dock bicycle-sharing system planning, the definition of coverage area and the division of sub service areas are highly essential and fundamental, which get little attention in the existing studies. In this paper, we propose a market-oriented methodology for non-dock bicycle-sharing system planning. Firstly, the potential demand of bicycle-sharing use is identified using mobile phone data. Then, a link network is constructed to represent the spatial distribution of potential demand. The algorithm of community detection is applied to the link network to discover the densely connected nodes in the area and define the division of sub service areas. Finally, the potential patterns of bicycle-sharing use, the spatial distribution of the potential demand, and the potential emission reduction are analysed based on the resulting division of sub service areas. The proposed method is tested using a data set of approximately 34 million GPS trajectories obtained in Tokyo. The area of Tokyo is subdivided into 21 sub service areas. Suggestions for bicycle management, infrastructure development, and the bicycle-sharing system planning are given regarding sub service areas with different properties. The potential emission reduction for the introduction of bicycle-sharing system is calculated in the area of Tokyo. Image 1 • A data set of 34 million trajectories is adopted to develop an integrated method. • A method of sub-area division for the bicycle-sharing system is proposed. • Travel pattern of potential bicycle-sharing behavior is described and analyzed. • Potential emission reduction of promoting bicycle-sharing is analyzed. [ABSTRACT FROM AUTHOR]