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The Special Issue “Nanostructured Materials Based on Noble Metals for Advanced Biological Applications” highlights the recent progress in gold and silver nanomaterials preparation/synthesis as well as their innovative applications in advanced applications, such as in nanomedicine and nanosensors. It is nowadays generally accepted that nanostructured noble metals allow the production of highly competitive materials. In fact, a specific design and rather simple and reliable preparation techniques can be used to obtain optimized material uses and possibilities for their reusability. One expects amazing future developments for these nanotechnologies from research laboratories to key industrial areas. The Guest Editor and the MDPI staff are therefore pleased to offer this Special Issue to interested readers, including researchers, graduate and PhD students as well as postdoctoral researchers, but also to the entire community interested in the wide world of nanomaterials.
gold --- nanostructure --- EDTA tetrasodium salt --- photothermal therapy --- silver nanoparticles --- biomedical applications --- biological interactions --- biofunctional performances --- intrinsic anti-inflammatory activity --- antimicrobial efficiency --- localized surface plasmon resonance --- dip-coating --- capillary force --- exosome --- gold nanoparticles --- copper(I) complexes --- conjugates --- drug delivery --- anticancer compounds --- niosomes --- liposomes --- plasmonic materials --- nanocarriers --- Hg2+ sensors --- heavy metal sensing --- plasmonic sensors --- optical sensors --- ecosafety --- nanoparticles --- interactions --- protein corona --- nanomedicine --- biomolecules --- nanomaterials --- noble metal nanoparticles --- gold nanomaterials --- silver nanomaterials --- hybrid metal–polymer nanoparticles --- biotechnological applications --- nanomaterials for drug delivery --- nanomaterials for sensing
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The Special Issue “Nanostructured Materials Based on Noble Metals for Advanced Biological Applications” highlights the recent progress in gold and silver nanomaterials preparation/synthesis as well as their innovative applications in advanced applications, such as in nanomedicine and nanosensors. It is nowadays generally accepted that nanostructured noble metals allow the production of highly competitive materials. In fact, a specific design and rather simple and reliable preparation techniques can be used to obtain optimized material uses and possibilities for their reusability. One expects amazing future developments for these nanotechnologies from research laboratories to key industrial areas. The Guest Editor and the MDPI staff are therefore pleased to offer this Special Issue to interested readers, including researchers, graduate and PhD students as well as postdoctoral researchers, but also to the entire community interested in the wide world of nanomaterials.
Technology: general issues --- gold --- nanostructure --- EDTA tetrasodium salt --- photothermal therapy --- silver nanoparticles --- biomedical applications --- biological interactions --- biofunctional performances --- intrinsic anti-inflammatory activity --- antimicrobial efficiency --- localized surface plasmon resonance --- dip-coating --- capillary force --- exosome --- gold nanoparticles --- copper(I) complexes --- conjugates --- drug delivery --- anticancer compounds --- niosomes --- liposomes --- plasmonic materials --- nanocarriers --- Hg2+ sensors --- heavy metal sensing --- plasmonic sensors --- optical sensors --- ecosafety --- nanoparticles --- interactions --- protein corona --- nanomedicine --- biomolecules --- nanomaterials --- noble metal nanoparticles --- gold nanomaterials --- silver nanomaterials --- hybrid metal–polymer nanoparticles --- biotechnological applications --- nanomaterials for drug delivery --- nanomaterials for sensing
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The Special Issue “Nanostructured Materials Based on Noble Metals for Advanced Biological Applications” highlights the recent progress in gold and silver nanomaterials preparation/synthesis as well as their innovative applications in advanced applications, such as in nanomedicine and nanosensors. It is nowadays generally accepted that nanostructured noble metals allow the production of highly competitive materials. In fact, a specific design and rather simple and reliable preparation techniques can be used to obtain optimized material uses and possibilities for their reusability. One expects amazing future developments for these nanotechnologies from research laboratories to key industrial areas. The Guest Editor and the MDPI staff are therefore pleased to offer this Special Issue to interested readers, including researchers, graduate and PhD students as well as postdoctoral researchers, but also to the entire community interested in the wide world of nanomaterials.
Technology: general issues --- gold --- nanostructure --- EDTA tetrasodium salt --- photothermal therapy --- silver nanoparticles --- biomedical applications --- biological interactions --- biofunctional performances --- intrinsic anti-inflammatory activity --- antimicrobial efficiency --- localized surface plasmon resonance --- dip-coating --- capillary force --- exosome --- gold nanoparticles --- copper(I) complexes --- conjugates --- drug delivery --- anticancer compounds --- niosomes --- liposomes --- plasmonic materials --- nanocarriers --- Hg2+ sensors --- heavy metal sensing --- plasmonic sensors --- optical sensors --- ecosafety --- nanoparticles --- interactions --- protein corona --- nanomedicine --- biomolecules --- nanomaterials --- noble metal nanoparticles --- gold nanomaterials --- silver nanomaterials --- hybrid metal–polymer nanoparticles --- biotechnological applications --- nanomaterials for drug delivery --- nanomaterials for sensing
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The papers included in this Special Issue "Bioactive Molecules from Extreme Environments" provide an overview of the growing interest in species biodiversity, highlighting the importance of marine extreme environments as sources of a unique marine chemical diversity of molecules. It is worth noting that six articles in this Special Issue are focused on molecules and enzymes isolated from Antarctica. This means that there is a growing interest in this habitat, most probably due to being perceived as an important source of drug discovery. In fact, the unique environment and ecological pressures of marine polar regions might be the major drivers of a selection of unique biological communities that are able to biosynthesize new compounds with diverse biological activities. It is expected that, in the near future, more marine molecules from polar regions, as well as from other extreme habitats, will find their way into biomedical and biotechnological applications.
Medicine --- Latrunculia --- Antarctica --- deep-sea sponge --- molecular networking --- molecular docking --- discorhabdin --- Arctic/Antarctic environment --- biocatalysis --- cold-adaptation --- marine biotechnology --- deep sea --- extremophilic microorganisms --- extremozyme --- thermophilic enzyme --- psychrophilic enzyme --- halophilic enzyme --- piezophilic enzyme --- chitinase --- cold-adapted --- optimization --- antifungal --- Pseudomonas --- Deinococcus --- deinoxanthin --- carotenoid --- deep-sea --- extreme --- ecosystem --- fungi --- bioactive compounds --- secondary metabolites --- halophilic bacteria --- archaea and fungi --- biomolecules --- biomedicine --- antimicrobial compounds --- anticancer compounds --- green synthesis biomaterials --- silver nitrate --- antibiotics --- nanotechnology --- marine prokaryotes --- microbial diversity --- polyextremophiles --- deep hypersaline anoxic basins --- blue biotechnologies --- extremozymes --- limits of life --- Antarctic krill (Euphausia superba) --- genome survey --- mitochondrial genome --- whiteleg shrimp (Penaeus vannamei) --- antimicrobial peptide (AMP) --- antihypertensive peptide (AHTP) --- cypermethrin --- biosurfactants --- biodegradation capacities --- marine sediments --- Arctic/Antarctic --- deep hypersaline anoxic basin --- cold-adapted bacteria --- halophilic microorganisms --- marine natural product --- enzyme --- silver nanoparticle --- marine bioprospecting
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The papers included in this Special Issue "Bioactive Molecules from Extreme Environments" provide an overview of the growing interest in species biodiversity, highlighting the importance of marine extreme environments as sources of a unique marine chemical diversity of molecules. It is worth noting that six articles in this Special Issue are focused on molecules and enzymes isolated from Antarctica. This means that there is a growing interest in this habitat, most probably due to being perceived as an important source of drug discovery. In fact, the unique environment and ecological pressures of marine polar regions might be the major drivers of a selection of unique biological communities that are able to biosynthesize new compounds with diverse biological activities. It is expected that, in the near future, more marine molecules from polar regions, as well as from other extreme habitats, will find their way into biomedical and biotechnological applications.
Latrunculia --- Antarctica --- deep-sea sponge --- molecular networking --- molecular docking --- discorhabdin --- Arctic/Antarctic environment --- biocatalysis --- cold-adaptation --- marine biotechnology --- deep sea --- extremophilic microorganisms --- extremozyme --- thermophilic enzyme --- psychrophilic enzyme --- halophilic enzyme --- piezophilic enzyme --- chitinase --- cold-adapted --- optimization --- antifungal --- Pseudomonas --- Deinococcus --- deinoxanthin --- carotenoid --- deep-sea --- extreme --- ecosystem --- fungi --- bioactive compounds --- secondary metabolites --- halophilic bacteria --- archaea and fungi --- biomolecules --- biomedicine --- antimicrobial compounds --- anticancer compounds --- green synthesis biomaterials --- silver nitrate --- antibiotics --- nanotechnology --- marine prokaryotes --- microbial diversity --- polyextremophiles --- deep hypersaline anoxic basins --- blue biotechnologies --- extremozymes --- limits of life --- Antarctic krill (Euphausia superba) --- genome survey --- mitochondrial genome --- whiteleg shrimp (Penaeus vannamei) --- antimicrobial peptide (AMP) --- antihypertensive peptide (AHTP) --- cypermethrin --- biosurfactants --- biodegradation capacities --- marine sediments --- Arctic/Antarctic --- deep hypersaline anoxic basin --- cold-adapted bacteria --- halophilic microorganisms --- marine natural product --- enzyme --- silver nanoparticle --- marine bioprospecting
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The papers included in this Special Issue "Bioactive Molecules from Extreme Environments" provide an overview of the growing interest in species biodiversity, highlighting the importance of marine extreme environments as sources of a unique marine chemical diversity of molecules. It is worth noting that six articles in this Special Issue are focused on molecules and enzymes isolated from Antarctica. This means that there is a growing interest in this habitat, most probably due to being perceived as an important source of drug discovery. In fact, the unique environment and ecological pressures of marine polar regions might be the major drivers of a selection of unique biological communities that are able to biosynthesize new compounds with diverse biological activities. It is expected that, in the near future, more marine molecules from polar regions, as well as from other extreme habitats, will find their way into biomedical and biotechnological applications.
Medicine --- Latrunculia --- Antarctica --- deep-sea sponge --- molecular networking --- molecular docking --- discorhabdin --- Arctic/Antarctic environment --- biocatalysis --- cold-adaptation --- marine biotechnology --- deep sea --- extremophilic microorganisms --- extremozyme --- thermophilic enzyme --- psychrophilic enzyme --- halophilic enzyme --- piezophilic enzyme --- chitinase --- cold-adapted --- optimization --- antifungal --- Pseudomonas --- Deinococcus --- deinoxanthin --- carotenoid --- deep-sea --- extreme --- ecosystem --- fungi --- bioactive compounds --- secondary metabolites --- halophilic bacteria --- archaea and fungi --- biomolecules --- biomedicine --- antimicrobial compounds --- anticancer compounds --- green synthesis biomaterials --- silver nitrate --- antibiotics --- nanotechnology --- marine prokaryotes --- microbial diversity --- polyextremophiles --- deep hypersaline anoxic basins --- blue biotechnologies --- extremozymes --- limits of life --- Antarctic krill (Euphausia superba) --- genome survey --- mitochondrial genome --- whiteleg shrimp (Penaeus vannamei) --- antimicrobial peptide (AMP) --- antihypertensive peptide (AHTP) --- cypermethrin --- biosurfactants --- biodegradation capacities --- marine sediments --- Arctic/Antarctic --- deep hypersaline anoxic basin --- cold-adapted bacteria --- halophilic microorganisms --- marine natural product --- enzyme --- silver nanoparticle --- marine bioprospecting
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This book is a printed edition of the Special Issue entitled “Anticancer Agents: Design, Synthesis and Evaluation” that was published in Molecules. Two review articles and thirty research papers are included in the Special Issue. Three second-generation androgen receptor antagonists that have been approved by the U.S. FDA for the treatment of prostate cancer have been reviewed. Identification of mimics of protein partners as protein-protein interaction inhibitors via virtual screening has been summarized and discussed. Anticancer agents targeting various protein targets, including IGF-1R, Src, protein kinase, aromatase, HDAC, PARP, Toll-Like receptor, c-Met, PI3Kdelta, topoisomerase II, p53, and indoleamine 2,3-dioxygenase, have been explored. The analogs of three well-known tubulin-interacting natural products, paclitaxel, zampanolide, and colchicine, have been designed, synthesized, and evaluated. Several anticancer agents representing diverse chemical scaffolds were assessed in different kinds of cancer cell models. The capability of some anticancer agents to overcome the resistance to currently available drugs was also studied. In addition to looking into the in vitro ability of the anticancer agents to inhibit cancer cell proliferation, apoptosis, and cell cycle, in vivo antitumor efficacy in animal models and DFT were also investigated in some papers.
Medicine --- benzofurans --- chemical synthesis --- cytotoxic properties --- HeLa --- MOLT-4 --- K562 --- anticancer --- anti-neuroinflammation --- coumarin --- dihydroartemisinin --- flavonoids --- allene --- E-stereoselective --- regioselective --- anti-cancer activity --- cyanopyridone --- substituted pyridine --- pyridotriazine --- pyrazolopyridine --- thioxotriazopyridine --- anticancer activity --- HepG2 --- antitumor activity --- computational docking --- MDM2-p53 interaction --- xanthones --- yeast-based assays --- estrone derivatives --- hydrazine --- N-substituted pyrazoline --- anti-ovarian cancer --- topoisomerase II inhibitor --- kinase inhibitor --- antiproliferative agent --- urea --- synthesis --- antiproliferative activity --- apoptosis --- indoleamine 2,3-dioxygenase --- inhibitor --- anti-tumor --- immune modulation --- tryptophan metabolism --- taxoids --- βIII-tubulin --- P-glycoprotein --- drug resistance --- thiopene --- thienopyrimidinone --- thiazolidinone --- breast cancer --- benzofuran–pyrazole --- nanoparticles --- cytotoxic activity --- PARP-1 inhibition --- 3,6-dibromocarbazole --- 5-bromoindole --- carbazole --- actin --- migration --- Thienopyrimidine --- Pyrazole --- PI3Kα inhibitor --- quinazolin-4(3H)-one --- quinazolin-4(3H)-thione --- Schiff base --- antioxidant activity --- DFT study --- ortho-quinones --- beta-lapachone --- tanshione IIA --- PI3Ks --- PI3Kδ inhibitors --- 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide --- anticancer agents --- protein–protein interactions --- virtual screening --- mimetics --- drug discovery --- bivalency --- polyvalency --- antitumor --- cell cycle --- ovarian cancer --- P-MAPA --- IL-12 --- TLR signaling --- inflammation --- chemoresistance --- 4-(pyridin-4-yloxy)benzamide --- 1,2,3-triazole --- c-Met --- natural product --- anticancer agent --- zampanolide --- Talazoparib --- PARP inhibitor --- prodrug --- o-nitro-benzyl --- photoactivatable protecting groups --- salinomycin --- overcoming drug resistance --- tumor specificity --- synergy --- 5-fluorouracil --- gemcitabine --- amides/esters --- colchicine analogs --- thiocolchicine --- colchiceine --- antimitotic agents --- hydrates --- dihydropyranoindole --- HDAC inhibitors --- neuroblastoma --- aromatase --- MCF-7 --- NIH3T3 --- benzimidazole --- triazolothiadiazine --- docking --- ADME --- organosilicon compounds --- SILA-409 (Alis-409) --- SILA-421 (Alis-421) --- multidrug resistance (MDR) reversal --- ABCB1 (P-glycoprotein) --- colon cancer --- colchicine amide --- colchicine sulfonamide --- tubulin inhibitors --- docking studies --- crystal structure --- PROTACs --- protein degradation --- IGF-1R --- Src --- protein kinase --- phenylpyrazolopyrimidine --- enzyme inhibition --- molecular simulation --- androgen receptor --- prostate cancer --- enzalutamide --- apalutamide --- darolutamide --- triple-negative breast cancer --- cytotoxicity --- chrysin analogues --- flavonoid --- anticancer compounds
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This book is a printed edition of the Special Issue entitled “Anticancer Agents: Design, Synthesis and Evaluation” that was published in Molecules. Two review articles and thirty research papers are included in the Special Issue. Three second-generation androgen receptor antagonists that have been approved by the U.S. FDA for the treatment of prostate cancer have been reviewed. Identification of mimics of protein partners as protein-protein interaction inhibitors via virtual screening has been summarized and discussed. Anticancer agents targeting various protein targets, including IGF-1R, Src, protein kinase, aromatase, HDAC, PARP, Toll-Like receptor, c-Met, PI3Kdelta, topoisomerase II, p53, and indoleamine 2,3-dioxygenase, have been explored. The analogs of three well-known tubulin-interacting natural products, paclitaxel, zampanolide, and colchicine, have been designed, synthesized, and evaluated. Several anticancer agents representing diverse chemical scaffolds were assessed in different kinds of cancer cell models. The capability of some anticancer agents to overcome the resistance to currently available drugs was also studied. In addition to looking into the in vitro ability of the anticancer agents to inhibit cancer cell proliferation, apoptosis, and cell cycle, in vivo antitumor efficacy in animal models and DFT were also investigated in some papers.
benzofurans --- chemical synthesis --- cytotoxic properties --- HeLa --- MOLT-4 --- K562 --- anticancer --- anti-neuroinflammation --- coumarin --- dihydroartemisinin --- flavonoids --- allene --- E-stereoselective --- regioselective --- anti-cancer activity --- cyanopyridone --- substituted pyridine --- pyridotriazine --- pyrazolopyridine --- thioxotriazopyridine --- anticancer activity --- HepG2 --- antitumor activity --- computational docking --- MDM2-p53 interaction --- xanthones --- yeast-based assays --- estrone derivatives --- hydrazine --- N-substituted pyrazoline --- anti-ovarian cancer --- topoisomerase II inhibitor --- kinase inhibitor --- antiproliferative agent --- urea --- synthesis --- antiproliferative activity --- apoptosis --- indoleamine 2,3-dioxygenase --- inhibitor --- anti-tumor --- immune modulation --- tryptophan metabolism --- taxoids --- βIII-tubulin --- P-glycoprotein --- drug resistance --- thiopene --- thienopyrimidinone --- thiazolidinone --- breast cancer --- benzofuran–pyrazole --- nanoparticles --- cytotoxic activity --- PARP-1 inhibition --- 3,6-dibromocarbazole --- 5-bromoindole --- carbazole --- actin --- migration --- Thienopyrimidine --- Pyrazole --- PI3Kα inhibitor --- quinazolin-4(3H)-one --- quinazolin-4(3H)-thione --- Schiff base --- antioxidant activity --- DFT study --- ortho-quinones --- beta-lapachone --- tanshione IIA --- PI3Ks --- PI3Kδ inhibitors --- 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide --- anticancer agents --- protein–protein interactions --- virtual screening --- mimetics --- drug discovery --- bivalency --- polyvalency --- antitumor --- cell cycle --- ovarian cancer --- P-MAPA --- IL-12 --- TLR signaling --- inflammation --- chemoresistance --- 4-(pyridin-4-yloxy)benzamide --- 1,2,3-triazole --- c-Met --- natural product --- anticancer agent --- zampanolide --- Talazoparib --- PARP inhibitor --- prodrug --- o-nitro-benzyl --- photoactivatable protecting groups --- salinomycin --- overcoming drug resistance --- tumor specificity --- synergy --- 5-fluorouracil --- gemcitabine --- amides/esters --- colchicine analogs --- thiocolchicine --- colchiceine --- antimitotic agents --- hydrates --- dihydropyranoindole --- HDAC inhibitors --- neuroblastoma --- aromatase --- MCF-7 --- NIH3T3 --- benzimidazole --- triazolothiadiazine --- docking --- ADME --- organosilicon compounds --- SILA-409 (Alis-409) --- SILA-421 (Alis-421) --- multidrug resistance (MDR) reversal --- ABCB1 (P-glycoprotein) --- colon cancer --- colchicine amide --- colchicine sulfonamide --- tubulin inhibitors --- docking studies --- crystal structure --- PROTACs --- protein degradation --- IGF-1R --- Src --- protein kinase --- phenylpyrazolopyrimidine --- enzyme inhibition --- molecular simulation --- androgen receptor --- prostate cancer --- enzalutamide --- apalutamide --- darolutamide --- triple-negative breast cancer --- cytotoxicity --- chrysin analogues --- flavonoid --- anticancer compounds
Choose an application
This book is a printed edition of the Special Issue entitled “Anticancer Agents: Design, Synthesis and Evaluation” that was published in Molecules. Two review articles and thirty research papers are included in the Special Issue. Three second-generation androgen receptor antagonists that have been approved by the U.S. FDA for the treatment of prostate cancer have been reviewed. Identification of mimics of protein partners as protein-protein interaction inhibitors via virtual screening has been summarized and discussed. Anticancer agents targeting various protein targets, including IGF-1R, Src, protein kinase, aromatase, HDAC, PARP, Toll-Like receptor, c-Met, PI3Kdelta, topoisomerase II, p53, and indoleamine 2,3-dioxygenase, have been explored. The analogs of three well-known tubulin-interacting natural products, paclitaxel, zampanolide, and colchicine, have been designed, synthesized, and evaluated. Several anticancer agents representing diverse chemical scaffolds were assessed in different kinds of cancer cell models. The capability of some anticancer agents to overcome the resistance to currently available drugs was also studied. In addition to looking into the in vitro ability of the anticancer agents to inhibit cancer cell proliferation, apoptosis, and cell cycle, in vivo antitumor efficacy in animal models and DFT were also investigated in some papers.
Medicine --- benzofurans --- chemical synthesis --- cytotoxic properties --- HeLa --- MOLT-4 --- K562 --- anticancer --- anti-neuroinflammation --- coumarin --- dihydroartemisinin --- flavonoids --- allene --- E-stereoselective --- regioselective --- anti-cancer activity --- cyanopyridone --- substituted pyridine --- pyridotriazine --- pyrazolopyridine --- thioxotriazopyridine --- anticancer activity --- HepG2 --- antitumor activity --- computational docking --- MDM2-p53 interaction --- xanthones --- yeast-based assays --- estrone derivatives --- hydrazine --- N-substituted pyrazoline --- anti-ovarian cancer --- topoisomerase II inhibitor --- kinase inhibitor --- antiproliferative agent --- urea --- synthesis --- antiproliferative activity --- apoptosis --- indoleamine 2,3-dioxygenase --- inhibitor --- anti-tumor --- immune modulation --- tryptophan metabolism --- taxoids --- βIII-tubulin --- P-glycoprotein --- drug resistance --- thiopene --- thienopyrimidinone --- thiazolidinone --- breast cancer --- benzofuran–pyrazole --- nanoparticles --- cytotoxic activity --- PARP-1 inhibition --- 3,6-dibromocarbazole --- 5-bromoindole --- carbazole --- actin --- migration --- Thienopyrimidine --- Pyrazole --- PI3Kα inhibitor --- quinazolin-4(3H)-one --- quinazolin-4(3H)-thione --- Schiff base --- antioxidant activity --- DFT study --- ortho-quinones --- beta-lapachone --- tanshione IIA --- PI3Ks --- PI3Kδ inhibitors --- 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide --- anticancer agents --- protein–protein interactions --- virtual screening --- mimetics --- drug discovery --- bivalency --- polyvalency --- antitumor --- cell cycle --- ovarian cancer --- P-MAPA --- IL-12 --- TLR signaling --- inflammation --- chemoresistance --- 4-(pyridin-4-yloxy)benzamide --- 1,2,3-triazole --- c-Met --- natural product --- anticancer agent --- zampanolide --- Talazoparib --- PARP inhibitor --- prodrug --- o-nitro-benzyl --- photoactivatable protecting groups --- salinomycin --- overcoming drug resistance --- tumor specificity --- synergy --- 5-fluorouracil --- gemcitabine --- amides/esters --- colchicine analogs --- thiocolchicine --- colchiceine --- antimitotic agents --- hydrates --- dihydropyranoindole --- HDAC inhibitors --- neuroblastoma --- aromatase --- MCF-7 --- NIH3T3 --- benzimidazole --- triazolothiadiazine --- docking --- ADME --- organosilicon compounds --- SILA-409 (Alis-409) --- SILA-421 (Alis-421) --- multidrug resistance (MDR) reversal --- ABCB1 (P-glycoprotein) --- colon cancer --- colchicine amide --- colchicine sulfonamide --- tubulin inhibitors --- docking studies --- crystal structure --- PROTACs --- protein degradation --- IGF-1R --- Src --- protein kinase --- phenylpyrazolopyrimidine --- enzyme inhibition --- molecular simulation --- androgen receptor --- prostate cancer --- enzalutamide --- apalutamide --- darolutamide --- triple-negative breast cancer --- cytotoxicity --- chrysin analogues --- flavonoid --- anticancer compounds
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