154,523 results match your criteria radiosensitizing agents

Serum IgG level is a predicting factor for the response to neoadjuvant chemotherapy in patients with esophageal squamous cell carcinoma.

World J Surg Oncol 2021 Jul 19;19(1):217. Epub 2021 Jul 19.

Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya City, Aichi, 467-8602, Japan.

Background: Despite the established oncological benefits of neoadjuvant chemotherapy for esophageal squamous cell cancer, not all cases demonstrate benefit. Hence, predicting the response to chemotherapy before treatment is desirable. Some reports have shown that immune factors are related to the chemotherapy response. Read More

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Esomeprazole enhances the effect of ionizing radiation to improve tumor control.

Oncotarget 2021 Jul 6;12(14):1339-1353. Epub 2021 Jul 6.

Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas 77030, USA.

The resistance of cancer cells to radiation-based treatment is a major clinical challenge confounding standard of care in cancer. This problem is particularly notable in many solid tumors where cancer cells are only partially responsive to radiation therapy. Combination of radiation with radiosensitizers is able to enhance tumor cell killing. Read More

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Astonishing response to Cetuximab in metastatic nasopharyn- geal carcinoma: a case report.

Clin Ter 2021 Jul;172(4):260-263

Oncology - ASL Latina, District 1, University of Rome "Sapienza," Aprilia (LT), Italy.

Abstract: Nasopharyngeal carcinoma, one of the most common head and neck cancers in Southeast Asia, is uncommon in Western countries and it is frequently diagnosed in advanced stage. Chemotherapy given with radiation therapy, followed by more chemotherapy, is the standard of care of stage IV nasopharyngeal carcinoma but Cetuximab, an epidermal growth factor (EGFR) inhibitor, is now making its way in the treatment of locoregionally advanced nasopharyngeal carcinoma. We report a case of 58 years old patient with metastatic nasopharyngeal carcinoma with an astonishing response to Cetuximab. Read More

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Extracellular matrix protein-1 secretory isoform promotes ovarian cancer through increasing alternative mRNA splicing and stemness.

Nat Commun 2021 07 9;12(1):4230. Epub 2021 Jul 9.

Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXβ2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXβ2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. Read More

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[miR-483-5p aggravates cisplatin-induced premature ovarian insufficiency in rats by targeting FKBP4].

Nan Fang Yi Ke Da Xue Xue Bao 2021 Jun;41(6):801-810

Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Objective: To investigate the role of FKBP4 protein in cisplatin-induced premature ovarian insufficiency (POI).

Objective: We performed ITRAQ assay of the ovarian tissues from 4 mice with cisplatin-induced POI and 4 control mice, and identified FKBP4 as a significantly down-regulated protein in the oocytes and granulosa cells following cisplatin treatment. TargetScan software was used for target analysis of FKBP4, and qRT-PCR and Western blotting were used to verify the expression levels of miR-483-5p and FKBP4 in the mouse models. Read More

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Gold nanoparticles meet medical radionuclides.

Nucl Med Biol 2021 Jun 15;100-101:61-90. Epub 2021 Jun 15.

Radiobiology Research Unit, Interdisciplinary Biosciences, Institute for Environment, Health and Safety, Belgian Nuclear Research Centre (SCK CEN), Boeretang 200, 2400 Mol, Belgium.

Thanks to their unique optical and physicochemical properties, gold nanoparticles have gained increased interest as radiosensitizing, photothermal therapy and optical imaging agents to enhance the effectiveness of cancer detection and therapy. Furthermore, their ability to carry multiple medically relevant radionuclides broadens their use to nuclear medicine SPECT and PET imaging as well as targeted radionuclide therapy. In this review, we discuss the radiolabeling process of gold nanoparticles and their use in (multimodal) nuclear medicine imaging to better understand their specific distribution, uptake and retention in different in vivo cancer models. Read More

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Comparison of Chemotherapy-induced Nausea and Vomiting Between Gemcitabine Plus Nab-paclitaxel Combination Chemotherapy and Gemcitabine Monotherapy in Patients With Advanced Pancreatic Cancer.

Anticancer Res 2021 Jul;41(7):3643-3648

Department of Pharmacy, Gifu University Hospital, Gifu, Japan.

Background/aim: To clarify the risk of chemotherapy-induced nausea and vomiting (CINV) with GnP therapy, gemcitabine (GEM) plus nab-paclitaxel (nab-PTX), we compared CINV between GEM and GnP therapy.

Patients And Methods: Patients who had received an initial course of GEM and GnP therapy were enrolled. Primary endpoint was the incidence of nausea, and secondary endpoints were the incidence of vomiting and rescue. Read More

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Gemcitabine Plus Nanoparticle Albumin-bound Paclitaxel FOLFIRINOX for Recurrent Pancreatic Cancer After Resection.

Anticancer Res 2021 Jul;41(7):3573-3582

Department of Medical Oncology, Fukuoka Wajiro Hospital, Fukuoka, Japan.

Background/aim: The aim of the study was to evaluate gemcitabine plus nanoparticle albumin-bound paclitaxel (GnP) and FOLFIRINOX for recurrent pancreatic cancer (rPC) after resection.

Patients And Methods: Forty-four patients with rPC and 211 with de novo metastatic pancreatic cancer (mPC) who received GnP or FOLFIRINOX as first-line chemotherapy were retrospectively analyzed.

Results: On crude analysis, the median overall survival (OS) was significantly longer in the rPC group than in the mPC group (14. Read More

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Inhibition of AKT Enhances the Sensitivity of NSCLC Cells to Metformin.

Anticancer Res 2021 Jul;41(7):3481-3487

KIRAMS Radiation Biobank, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea

Background/aim: Metformin is an antidiabetic drug that has been reported to have antitumor activity in many cancer types. This study investigated the molecular mechanisms underlying the antitumor effect of metformin.

Materials And Methods: We investigated the molecular mechanism of the antitumor effect of metformin alone and in combination with AKT serine/threonine kinase (AKT) inhibition via cell viability and western blot analyses. Read More

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Cranberry Extract Is a Potent Radiosensitizer for Glioblastoma.

Anticancer Res 2021 Jul;41(7):3337-3341

Department of Surgery, University of Missouri School of Medicine, Columbia, MO, U.S.A.;

Background/aim: Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive type of primary brain tumor and a cornerstone in its treatment is radiotherapy (RT). However, RT for GBM is largely ineffective at clinically safe doses, thus, the study of radiosensitizers is of great significance.

Materials And Methods: With accumulating evidence for the anticancer effect of compounds from cranberry, this study was designed to investigate if cranberry extract (CE) sensitizes GBM to RT in the widely used human glioblastoma cell line U87. Read More

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Caco-2 in vitro model of human gastrointestinal tract for studying the absorption of titanium dioxide and silver nanoparticles from seafood.

Talanta 2021 Oct 11;233:122494. Epub 2021 May 11.

Trace Elements, Spectroscopy and Speciation Group (GETEE), Strategic Grouping in Materials (AEMAT), Department of Analytical Chemistry, Nutrition and Bromatology, Faculty of Chemistry, Universidade de Santiago de Compostela, Avenida Das Ciencias, S/n. E15782, Santiago de Compostela, Spain. Electronic address:

Titanium dioxide nanoparticles (TiO NPs) are widely used in industry as a white pigment (paints, paper industry and toothpastes), photocatalysts (environmental decontamination and photovoltaic cells), inorganic UV filter (sunscreens and personal care products) and as a food additive (E171) and antimicrobial food packaging material. Silver nanoparticles (Ag NPs) are used in photonics, microelectronics, catalysis and medicine due to their catalytic activity, magnetic and optical polarizability, electrical and thermal conductivities and enhanced Raman scattering. They also have antibacterial, antifungal and antiviral activities, as well as anti-inflammatory potential. Read More

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October 2021

A highly sensitive photoelectrochemical aptasensor based on BiVO nanoparticles-TiO nanotubes for detection of PCB72.

Talanta 2021 Oct 26;233:122551. Epub 2021 May 26.

Institute of Environmental Science, College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, Shanxi, 030006, PR China. Electronic address:

In this work, a simple and highly sensitive photoelectrochemical (PEC) aptasensor has been developed for detecting PCB72 based on TiO nanotubes (NTs) decorated with BiVO nanoparticles (NPs). The BiVO NPs-TiO NTs composites prepared through a simple hydrothermal method exhibit good visible-light adsorption ability, high PEC response and perfect photo-excited stability. The synthesized composites were explored as the photoactive sensing materials for development of a PEC sensing platform for the first time. Read More

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October 2021

Conjugation-regulating synthesis of high photosensitizing activity porphyrin-based covalent organic frameworks for photodynamic inactivation of bacteria.

Talanta 2021 Oct 24;233:122536. Epub 2021 May 24.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China; International Joint Laboratory on Food Safety, Jiangnan University, Wuxi, 214122, China; Institute of Analytical Food Safety, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, China; Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, Wuxi, 214122, China.

Preparation of porphyrin-based covalent organic frameworks (Por-COFs) with high photosensitizing activity for photodynamic inactivation of bacteria is of great challenge, but significant for economy and human health. Herein, we show a conjugation-regulating strategy to design and synthesize Por-COFs with high photosensitizing activity for the photodynamic inactivation of bacteria. Terephthalaldehyde (Da), 2,5-Dihydroxyterephthalaldehyde (Dha), and 2,5-Diethoxyterephthalaldehyde (Deta) with different conjugation degrees are selected to condense with 5,10,15,20-Tetrakis(4-aminophenyl)porphyrin (Tph) to synthesize COF-366, DhaTph, and JNU-2, respectively. Read More

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October 2021

Development of efficient SALDI substrate based on Au-TiO nanohybrids for environmental and forensic detection of dyes and NSAIDs.

Talanta 2021 Oct 18;233:122530. Epub 2021 May 18.

Kuwait University, Faculty of Science, Department of Chemistry, P.O. Box: 5969, 13060, Kuwait. Electronic address:

Herein, a matrix-free approach is presented for comprehensive environmental and forensic analysis of dyes and nonsteroidal anti-inflammatory drugs (NSAIDs) using Au-TiO nanohybrids coupled with surface-assisted pulsed laser desorption ionization-mass spectrometry (SALDI-MS). The Au-TiO nanohybrids was prepared and characterized using inductively coupled plasma-optical emission spectrometry (ICP-OES), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), surface area measurements, ultraviolet-visible (UV-vis) spectroscopy, transmission electron microscopy (TEM), and scanning electron microscopy-energy dispersive spectrometry (SEM-EDS). Initially, the optimal Au content was assessed using the survival yield (SY) method, confirming that 7. Read More

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October 2021

Nanoengineering of a newly designed chlorin e6 derivative for amplified photodynamic therapy regulating lactate metabolism.

Nanoscale 2021 Jul;13(27):11953-11962

Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.

Chlorin e6 (Ce6) is a widely utilized photosensitizer in photodynamic therapy (PDT) against tumor growth, but its hydrophobic feature and the hypoxia in the tumor microenvironment greatly compromise its therapeutic efficacy. To address the issues, here we designed a new Ce6 derivative (TCe6) by coupling Ce6 with amphiphilic d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), endowing Ce6 with an excellent amphiphilic feature. In particular, the overall reactive oxygen species (ROS) generation by TCe6 was significantly enhanced because TPGS could interact with mitochondrial complex II to induce extra ROS production, amplifying the total ROS production under PDT. Read More

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Interdigitated Electrode Biosensor Based on Plasma-Deposited TiO Nanoparticles for Detecting DNA.

Biosensors (Basel) 2021 Jun 29;11(7). Epub 2021 Jun 29.

Department of Chemistry and Research Institute of Basic Sciences, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.

Bioelectrodes mediated by metal oxide nanoparticles have facilitated the development of new sensors in medical diagnosis. High-purity TiO nanoparticles (NPs) were synthesized through thermal plasma and deposited directly on an interdigitated electrode. The surface of the TiO-deposited electrode was activated with (3-aminopropyl) triethoxysilane (APTES) followed by fixing the single-stranded probe deoxyribonucleic acid (DNA) to fabricate the DNA biosensor. Read More

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Photosensitizing Antivirals.

Molecules 2021 Jun 29;26(13). Epub 2021 Jun 29.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia.

Antiviral action of various photosensitizers is already summarized in several comprehensive reviews, and various mechanisms have been proposed for it. However, a critical consideration of the matter of the area is complicated, since the exact mechanisms are very difficult to explore and clarify, and most publications are of an empirical and "phenomenological" nature, reporting a dependence of the antiviral action on illumination, or a correlation of activity with the photophysical properties of the substances. Of particular interest is substance-assisted photogeneration of highly reactive singlet oxygen (O). Read More

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Generation of Fluorescent Bacteria with the Genes Coding for Lumazine Protein and Riboflavin Biosynthesis.

Sensors (Basel) 2021 Jun 30;21(13). Epub 2021 Jun 30.

Department of Biochemistry, Chungnam National University, Daejeon 34134, Korea.

Lumazine protein is a member of the riboflavin synthase superfamily and the intense fluorescence is caused by non-covalently bound to 6,7-dimethyl 8-ribityllumazine. The pRFN4 plasmid, which contains the riboflavin synthesis genes from , was originally designed for overproduction of the fluorescent ligand of 6,7-dimethyl 8-ribityllumazine. To provide the basis for a biosensor based on the gene from bioluminescent bacteria of , the gene coding for N-terminal domain half of the lumazine protein extending to amino acid 112 (N-LumP) and the gene for whole lumazine protein (W-LumP) from were introduced by polymerase chain reaction (PCR) and ligated into pRFN4 vector, to construct the recombinant plasmids of N-P-pRFN4 and W-P-pRFN4 as well as their modified plasmids by insertion of the promoter. Read More

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Furanocoumarins from with Amebicide Activity.

Molecules 2021 Jun 16;26(12). Epub 2021 Jun 16.

Departamento de Ciencias Básicas, Universidad de Monterrey, Av. Ignacio Morones Prieto 4500 Pte., San Pedro Garza García C.P. 66238, Nuevo León, Mexico.

(protozoan; family Endomoebidae) is the cause of amoebiasis, a disease related to high morbidity and mortality. Nowadays, this illness is considered a significant public health issue in developing countries. In addition, parasite resistance to conventional medicinal treatment has increased in recent years. Read More

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Dispersion of Natural Airborne TiO Fibres in Excavation Activity as a Potential Environmental and Human Health Risk.

Int J Environ Res Public Health 2021 06 18;18(12). Epub 2021 Jun 18.

Department of Earth, Environment and Life Sciences, University of Genoa, 16132 Genoa, Italy.

Titanium is the ninth most abundant element, approximately 0.7% of the Earth crust. It is used worldwide in large quantities for various applications. Read More

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Photosensitizer-Functionalized Nanocomposites for Light-Activated Cancer Theranostics.

Int J Mol Sci 2021 Jun 22;22(13). Epub 2021 Jun 22.

Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan.

Photosensitizers (PSs) have received significant attention recently in cancer treatment due to its theranostic capability for imaging and phototherapy. These PSs are highly responsive to light source of a suitable wavelength for image-guided cancer therapy from generated singlet oxygen and/or thermal heat. Various organic dye PSs show tremendous attenuation of tumor cells during cancer treatment. Read More

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Combined Gemcitabine and Immune-Checkpoint Inhibition Conquers Anti-PD-L1 Resistance in Low-Immunogenic Mismatch Repair-Deficient Tumors.

Int J Mol Sci 2021 Jun 1;22(11). Epub 2021 Jun 1.

Department of Medicine, Clinic III-Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, University of Rostock, 18057 Rostock, Germany.

Tumors arising in the context of Lynch Syndrome or constitutional mismatch repair deficiency are hypermutated and have a good response towards immune-checkpoint inhibitors (ICIs), including α-PD-L1 antibodies. However, in most cases, resistance mechanisms evolve. To improve outcomes and prevent resistance development, combination approaches are warranted. Read More

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Electrochemotherapy with Bleomycin Enhances Radiosensitivity of Uveal Melanomas: First In Vitro Results in 3D Cultures of Primary Uveal Melanoma Cell Lines.

Cancers (Basel) 2021 Jun 21;13(12). Epub 2021 Jun 21.

Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Hufeland Str. 55, 45147 Essen, Germany.

Electrochemotherapy (ECT) is emerging as a complementary treatment modality for local tumor control in various cancer entities. Irradiation is an established therapeutic option for oncologic patients, which is commonly combined with chemotherapy due to its insufficient targeting ability. The efficiency of radiotherapy for tumors can be enhanced with different radiosensitizers. Read More

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Photocatalytic Activity of Fibrous Ti/Ce Oxides Obtained by Hydrothermal Impregnation of Short Flax Fibers.

Molecules 2021 Jun 3;26(11). Epub 2021 Jun 3.

Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.

Fibrous Ti/Ce oxide photocatalysts were prepared for the first time by a biomimetic solution process using short flax fibers (flax straw processing waste) as a biotemplate. Titanium polyhydroxy complex solutions with 3% and 5% cerium were used as precursors. Flax fibers were impregnated in an autoclave under hydrothermal conditions. Read More

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Resveratrol Modulation of Apoptosis and Cell Cycle Response to Cisplatin in Head and Neck Cancer Cell Lines.

Int J Mol Sci 2021 Jun 12;22(12). Epub 2021 Jun 12.

Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, 030304 Bucharest, Romania.

In head and neck cancers, the effectiveness of cisplatin (CisPt) treatment is limited by its toxicity, especially when higher doses are necessary, and the possible occurrence of cisplatin resistance. This study evaluated the effects of resveratrol (RSV) on the expression of different genes involved in the response of human tumor cells (FaDu, PE/CA-PJ49) to cisplatin therapy. Our results revealed that RSV induced apoptosis amplification in both FaDu and PE/CA-PJ49 cells and modulated the expression of specific genes differently than in normal HaCaT cells. Read More

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Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles.

Int J Mol Sci 2021 Jun 15;22(12). Epub 2021 Jun 15.

ARC Centre of Excellence in Nanoscale Biophotonics, The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.

Radiodynamic therapy (RDT) is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of high-energy X-rays. This enables greater tissue penetration to allow non-invasive treatment of large, deep-seated tumors. We report here the design and testing of a drug delivery system for RDT that is intended to enhance intra- or peri-nuclear localization of the photosensitizer, leading to DNA damage and resulting clonogenic cell kill. Read More

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A Supramolecular Photosensitizer System Based on Nano-Cu/ZIF-8 Capped with Water-Soluble Pillar[6]arene and Methylene Blue Host-Guest Complexations.

Molecules 2021 Jun 25;26(13). Epub 2021 Jun 25.

Key Laboratory of Natural Products & Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Yangling 712100, China.

Photodynamic therapy (PDT) as a safe, non-invasive modality for cancer therapy, in which the low oxygen and high glutathione in the tumor microenvironment reduces therapeutic efficiency. In order to overcome these problems, we prepared a supramolecular photosensitive system of O-Cu/[email protected]@WP6-MB (OCZWM), which was loaded with oxygen to increase the oxygen concentration in the tumor microenvironment, and the Cu in the system reacted with glutathione (GSH) to reduce the GSH concentration to generate Cu. It is worth noting that the generated Cu can produce the Fenton reaction, thus realizing the combination therapy of PDT and chemodynamic therapy (CDT) to achieve the purpose of significantly improving the anti-cancer efficiency. Read More

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The Influence of Nd and Sm on the Structure and Properties of Sol-Gel-Derived TiO Powders.

Molecules 2021 Jun 23;26(13). Epub 2021 Jun 23.

Department Biotechnology, Faculty of Chemical and Systems Engineering, University of Chemical Technology and Metallurgy, Kl. Ohridski Blvd, 8, 1756 Sofia, Bulgaria.

TiO nanopowders modified by Nd and Sm were prepared using the sol-gel technique. It was found by XRD analysis that the samples containing Sm are amorphous up to 300 °C, while those with Nd preserve a mixed organic-inorganic amorphous structure at higher temperatures (400 °C). The TiO (rutile) was not detected up to 700 °C in the presence of both modified oxides. Read More

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Development of Antimicrobial Laser-Induced Photodynamic Therapy Based on Ethylcellulose/Chitosan Nanocomposite with 5,10,15,20-Tetrakis(-Hydroxyphenyl)porphyrin.

Molecules 2021 Jun 10;26(12). Epub 2021 Jun 10.

Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, Trinity College Dublin, The University of Dublin, St. James's Hospital, Dublin 8, Ireland.

The development of new antimicrobial strategies that act more efficiently than traditional antibiotics is becoming a necessity to combat multidrug-resistant pathogens. Here we report the efficacy of laser-light-irradiated 5,10,15,20-tetrakis(-hydroxyphenyl)porphyrin (THPP) loaded onto an ethylcellulose (EC)/chitosan (Chs) nanocomposite in eradicating multi-drug resistant , , and Surface loading of the ethylcelllose/chitosan composite with THPP was carried out and the resulting nanocomposite was fully characterized. The results indicate that the prepared nanocomposite incorporates THPP inside, and that the composite acquired an overall positive charge. Read More

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New Oxaliplatin-Pyrophosphato Analogs with Improved In Vitro Cytotoxicity.

Molecules 2021 Jun 4;26(11). Epub 2021 Jun 4.

Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy.

Two new Pt(II)-pyrophosphato complexes containing the carrier ligands -1,3-diaminocyclohexane (-1,3-DACH) and -1,2-diamine-4-cyclohexene (1,2-DACHEX), variants of the 1,2-diaminocyclohexane ligand present in the clinically used Pt-drug oxaliplatin, have been synthesized with the aim of developing new potential antitumor drugs with high bone tropism. The complexes are more stable at physiological pH than in acid conditions, with Na[Pt(pyrophosphato)(-1,3-DACH)] () slightly more stable than [Pt(dihydrogenpyrophosphato)(1,2-DACHEX)] (). The greater reactivity at acidic pH ensures a greater efficacy at the tumor site. Read More

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