H2S Donors and Their Use in Medicinal Chemistry.

Hydrogen sulfide (H2S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous H2S is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodulation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of H2S levels has a potential therapeutic value. Consequently, synthetic H2S-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available H2S donors; furthermore, herein we discuss their preparation, the H2S-releasing mechanisms, and their -biological applications.

Study of photocatalytic activity of green synthesized nickel oxide nanoparticles in the degradation of acid orange 7 dye under visible light.

Environmental pollution is one of the most important problems that human beings face. Today, nanotechnology has played an important role in green chemistry and the use of nanoparticles in the removal of environmental pollutants is one of the newest methods of removing pollutants in the world. So, in this study, Nickel oxide nanoparticles (NiO NPs) of this work were successfully synthesized via a green method by the usage of nickel nitrate hexahydrate as the source of metal and Biebersteinia multifida extract as the stabilizing agent throughout different annealing temperatures. The physicochemical properties of the obtained NiO NPs were characterized through the application of scanning electron microscopy (SEM), energy dispersive X-ray (EDX), powder X-ray diffraction (PXRD), ultraviolet visible (UV-vis), and Raman analysis. According to the results of SEM and PXRD, the prepared product contained a satisfying distribution and very fine cubic structure with minimal accumulation. The average crystal size of prepared nanoparticles was obtained 54-58 nm. The energy band gap of synthesized NiO NPs was calculated 3-3.7 using Tauc equation. The photocatalytic performance of NiO NPs was investigated under visible light through the decolourization reaction of acid orange 7 (AO7) dye in aqueous solution. Being composed at 300 °C of annealing temperature, these nanoparticles exhibited excellent adsorption and photocatalytic activity (90.2%) toward AO7 dye. Therefore, it can be indicated that the synthesized NiO NPs demonstrated an excellent dispersion in dye solution, as well as considerable photocatalytic activity.

Multiplexed non-invasive tumor imaging of glucose metabolism and receptor-ligand engagement using dark quencher FRET acceptor.

Rationale: Following an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imaging offers a unique method to robustly quantify receptor-ligand engagement in live intact animals, which is critical to assess the delivery efficacy of therapeutics. However, to date, non-invasive imaging approaches that can simultaneously measure cellular drug delivery efficacy and metabolic response are lacking. A major challenge for the implementation of concurrent optical and MFLI-FRET in vivo whole-body preclinical imaging is the spectral crowding and cross-contamination between fluorescent probes. Methods: We report on a strategy that relies on a dark quencher enabling simultaneous assessment of receptor-ligand engagement and tumor metabolism in intact live mice. Several optical imaging approaches, such as in vitro NIR FLI microscopy (FLIM) and in vivo wide-field MFLI, were used to validate a novel donor-dark quencher FRET pair. IRDye 800CW 2-deoxyglucose (2-DG) imaging was multiplexed with MFLI-FRET of NIR-labeled transferrin FRET pair (Tf-AF700/Tf-QC-1) to monitor tumor metabolism and probe uptake in breast tumor xenografts in intact live nude mice. Immunohistochemistry was used to validate in vivo imaging results. Results: First, we establish that IRDye QC-1 (QC-1) is an effective NIR dark acceptor for the FRET-induced quenching of donor Alexa Fluor 700 (AF700). Second, we report on simultaneous in vivo imaging of the metabolic probe 2-DG and MFLI-FRET imaging of Tf-AF700/Tf-QC-1 uptake in tumors. Such multiplexed imaging revealed an inverse relationship between 2-DG uptake and Tf intracellular delivery, suggesting that 2-DG signal may predict the efficacy of intracellular targeted delivery. Conclusions: Overall, our methodology enables for the first time simultaneous non-invasive monitoring of intracellular drug delivery and metabolic response in preclinical studies.

Optimizing the aryl-triazole of cjoc42 for enhanced gankyrin binding and anti-cancer activity.

Gankyrin is an oncoprotein overexpressed in numerous cancer types and appears to play a key role in regulating cell proliferation, cell growth, and cell migration. These roles are largely due to gankyrin's protein-protein interaction with the 26S proteasome. We previously published a study exploring the aryl sulfonate ester of cjoc42 in an effort to enhance gankyrin binding and inhibit cancer cell proliferation. In order to further improve the gankyrin binding ability of the cjoc42 scaffold, an extensive SAR for the aryl-triazole moiety of cjoc42 was developed. Our cjoc42 derivatives exhibited enhanced gankyrin binding, as well as enhanced antiproliferative activity against Hep3B, HepG2, A549, and MDA-MB-231 cancer cell lines.

Biological treatment of non-biodegradable azo-dye enhanced by zero-valent iron (ZVI) pre-treatment.

Zero-valent iron (ZVI) pre-treatment in sequential strategy for removal of non-biodegradable azo-dye Orange II by activated-sludge was quantitatively examined. The decolorization and TOC (total organic carbon) removal of Orange II by ZVI pre-treatment were examined in the ranges of pH from 3 to 11 and ZVI dosage from 500 to 2000 mgL-1. While the decolorization was enhanced with decreasing pH and the optimal pH for decolorization was found at pH 3, the TOC removal rate at pH 3 remained at 22.2% and the maximum TOC removal rate of 78.2% was obtained at pH 4. The decolorization and TOC removal of Orange II were monotonously increased with increasing ZVI dosage. To quantify the ZVI pre-treatment, the contributions of redox degradation, complexation/precipitation and adsorption to TOC removal by ZVI were defined. Novel kinetic models for the ZVI pre-treatment and activated-sludge post-treatment were developed. The proposed kinetic models satisfactorily predicted the transitional behaviors of the ZVI pre-treatment and activated-sludge post-treatment and the contributions of redox degradation, complexation/precipitation and adsorption to TOC removal by the ZVI pre-treatment. The complete removal of non-biodegradable azo-dye Orange II of 300 mgL-1 was accomplished by 78.2% removal after 360 min ZVI pre-treatment with the ZVI dosage of 1000 mgL-1 at pH 4 and subsequently 21.8% removal after 480 min activated-sludge post-treatment. The ZVI pre-treatment integrated with activated-sludge post-treatment was proved to be an effective strategy for treating non-biodegradable pollutants.

Glutathione- and light-controlled generation of singlet oxygen for triggering drug release in mesoporous silica nanoparticles.

A combined stimulus-responsive photosensitiser and drug release system based on mesoporous silica nanoparticles was prepared. This nanoplatform encapsulated molecules of zinc(ii) phthalocyanine substituted with a glutathione-cleavable 2,4-dinitrobenzenesulfonate quencher and doxorubicin linked via a singlet-oxygen-cleavable 9,10-dialkoxyanthracene linker. In the presence of glutathione (in mM range) and upon irradiation (λ > 610 nm), the phthalocyanine units were activated by detaching from the quenching component to emit fluorescence and generate singlet oxygen. The latter subsequently cleaved the 9,10-dialkoxyanthracene linker to trigger the release of a doxorubicin derivative. The glutathione- and light-controlled activation and drug-release processes on this nanoplatform were demonstrated in phosphate buffered saline. The activation in fluorescence emission by intracellular thiols was also shown inside HepG2 human hepatocellular carcinoma cells. Upon irradiation, the nanosystem exhibited high cytotoxicity due to the photodynamic effect of the activated phthalocyanine units, but the cytotoxic effect of the released Dox moieties was not notable probably due to their reduced cytotoxicity as a result of the pendant substituent and the low drug loading in the nanoparticles.

Staining efficacy assessment of a differential routine and special stains for pathological stromal calcifications in maxillofacial lesions.

Head and neck connective tissue lesions may have diverse calcifications within the fibrous connective tissue stroma. The perplexity involved in the identification and determination of the nature or degree of calcification through routine hematoxylin and eosin (H&E) stains necessitates the usage of a specific, simple, and cost- and time-effective differential staining techniques. The aim of the present study was to develop criteria to distinguish bone formation from bone resorption using methylene blue-acid fuchsin (MB/AF) stain and the role of collagen fibers in the identification of stromal calcifications using polarizing microscopy with picrosirius red stain. Twenty cases with pathological diagnoses for various stromal calcifications in maxillofacial lesions were retrieved from the departmental archives. Decalcified formalin fixed paraffin embedded tissue sections were stained with hematoxylin and eosin, Masson's trichrome (MT), methylene blue-acid fuchsin (MB/AF), and picrosirius red. The stained sections were assessed to identify the calcifications found in the surrounding connective tissue stroma. It was observed that most cases showed maximum staining intensity with MB/AF stain as compared to the other staining methods. Moreover, the results suggested that contrast between calcification and stromal soft tissue was best distinguished with the MB/AF stain except in the case of dystrophic calcifications. Along with this, polarizing microscopy with picrosirius red enables better characterization of stromal components. Although the H&E stain and a connective tissue stain i.e. Masson's trichrome, are employed routinely in histopathology; the use of special stains such as MB-AF and picrosirius red facilitates the identification of calcifications from the stromal tissues.

A Glutathione Activatable Ion Channel Induces Apoptosis in Cancer Cells by Depleting Intracellular Glutathione Levels.

Cancer cells use elevated glutathione (GSH) levels as an inner line of defense to evade apoptosis and develop drug resistance. In this study, we describe a novel 2,4-nitrobenzenesulfonyl (DNS) protected 2-hydroxyisophthalamide system that exploits GSH for its activation into free 2-hydroxyisophthalamide forming supramolecular M+ /Cl- channels. Better permeation of the DNS protected compound into MCF-7 cells compared to the free 2-hydroxyisophthalamide and GSH-activatable ion transport resulted in higher cytotoxicity, which was associated with increased oxidative stress that further reduced the intracellular GSH levels and altered mitochondrial membrane permeability leading to the induction of the intrinsic apoptosis pathway. The GSH-activatable transport-mediated cell death was further validated in rat insulinoma cells (INS-1E); wherein the intracellular GSH levels showed a direct correlation to the resulting cytotoxicity. Lastly, the active compound was found to restrict the growth and proliferation of 3D spheroids of MCF-7 cells with efficiency similar to that of the anticancer drug doxorubicin.

Predicting Therapeutic Antibody Delivery into Human Head and Neck Cancers.

PURPOSE: The efficacy of antibody-based therapeutics depends on successful drug delivery into solid tumors; therefore, there is a clinical need to measure intratumoral antibody distribution. This study aims to develop and validate an imaging and computation platform to directly quantify and predict antibody delivery into human head and neck cancers in a clinical study. EXPERIMENTAL DESIGN: Twenty-four patients received systemic infusion of a near-infrared fluorescence-labeled therapeutic antibody followed by surgical tumor resection. A computational platform was developed to quantify the extent of heterogeneity of intratumoral antibody distribution. Both univariate and multivariate regression analyses were used to select the most predictive tumor biological factors for antibody delivery. Quantitative image features from the pretreatment MRI were extracted and correlated with fluorescence imaging of antibody delivery. RESULTS: This study not only confirmed heterogeneous intratumoral antibody distribution in-line with many preclinical reports, but also quantified the extent of interpatient, intertumor, and intratumor heterogeneity of antibody delivery. This study demonstrated the strong predictive value of tumor size for intratumoral antibody accumulation and its significant impact on antibody distribution in both primary tumor and lymph node metastasis. Furthermore, this study established the feasibility of using contrast-enhanced MRI to predict antibody delivery. CONCLUSIONS: This study provides a clinically translatable platform to measure antibody delivery into solid tumors and yields valuable insight into clinically relevant antibody tumor penetration, with implications in the selection of patients amenable to antibody therapy and the design of more effective dosing strategies.

MnCeOX with high efficiency and stability for activating persulfate to degrade AO7 and ofloxacin.

An efficient MnCeOx composite was successfully synthesized for activation of persulfate to degrade acid orange 7 (AO7) and ofloxacin. Pollutants degradation efficiencies with different catalytic systems were investigated. Results showed the performance of MnCeOx was better than MnOx, CeO2 and MnOx + CeO2. Thus, there was a clear synergistic effect (Se) between Mn and Ce in the composite, and the Se was 73.8% for AO7 and 39.6% for ofloxacin. In addition, AO7 removal fitted 1st order reaction while ofloxacin removal fitted 2nd order reaction in MnCeOx/persulfate system. Moreover, MnCeOx/persulfate system showed high efficiency in pH range of 5-9. Mechanism analysis showed that SO4- and OH on the surface of the catalyst were the main active species, and O2- also played an important role in pollutants degradation. Furthermore, MnCeOx showed high activity in actual water. Finally, the possible degradation pathway of ofloxacin was proposed according to the high performance liquid chromatography-mass spectrometry result. Overall, this study provides an efficient and stable catalyst to activate persulfate to degrade refractory pollutants.

The initiation of bud burst in grapevine features dynamic regulation of the apoplastic pore size.

The physiological constraints on bud burst in woody perennials, including vascular development and oxygenation, remain unresolved. Both light and tissue oxygen status have emerged as important cues for vascular development in other systems; however, grapevine buds have only a facultative light requirement, and data on the tissue oxygen status have been confounded by the spatial variability within the bud. Here, we analysed apoplastic development at early stages of grapevine bud burst and combined molecular modelling with histochemical techniques to determine the pore size of cell walls in grapevine buds. The data demonstrate that quiescent grapevine buds were impermeable to apoplastic dyes (acid fuchsin and eosin Y) until after bud burst was established. The molecular exclusion size was calculated to be 2.1 nm, which would exclude most macromolecules except simple sugars and phytohormones until after bud burst. We used micro-computed tomography to demonstrate that tissue oxygen partial pressure data correlated well with structural heterogeneity of the bud and differences in tissue density, confirming that the primary bud complex becomes rapidly and preferentially oxygenated during bud burst. Taken together, our results reveal that the apoplastic porosity is highly regulated during the early stages of bud burst, suggesting a role for vascular development in the initial, rapid oxygenation of the primary bud complex.

Hydrodynamics of up-flow hybrid anaerobic digestion reactors with built-in bioelectrochemical system.

Understanding the electrode configuration is vital for the successful application of bioelectrochemical system (BES) in recalcitrant wastewater treatment. Especially in those traditional anaerobic processes that integrate with BES to construct effective hybrid bioreactors. Hybrid bioreactors employed granular graphite as electrode material achieved 86.62 ±â€¯1.83% decolorization efficiency of azo dye acid orange 7 (AO7) at influent AO7 loading rate of 800 g/(m3∙d) and it was about 6% higher than that with carbon fiber brush electrodes. Such electrodes were positioned above the anaerobic sludge layer and higher efficiency (8%) than the reactors with electrodes placed beneath the sludge layer was observed. Tracer experiments and modeling of residence time distribution indicated that the fluid pattern in hybrid bioreactors was modified to plug flow pattern and had a better consummate mixing ability compared to the conventional anaerobic reactor. Simulation using computational fluid dynamics technique showcased favorable mass transfer near electrode modules. The hydrodynamics of simulation and experimental results were connected by simplifying electrode module as a porous media model. This study thus proved that hybrid bioreactors can effectively enhance wastewater treatment comprehensively through the analysis of decolorization performance and hydrodynamics.

Application of Membrane and Cell Wall Selective Fluorescent Dyes for Live-Cell Imaging of Filamentous Fungi.

The application of membrane and cell wall selective fluorescent dyes for live-cell imaging analyses of organelle dynamics in fungal cells started two decades ago and since then continues to contribute greatly to our understanding of the filamentous fungal lifestyle. This paper provides a practical guide for the utilization of the two membrane dyes FM 1-43 and FM 4-64 and the four cell wall stains Calcofluor White M2R, Solophenyl Flavine 7GFE 500, Pontamine Fast Scarlet 48 and Congo Red. The focus is on their low-dose application to ascertain artefact-free staining, their co-imaging properties, and their quantitative evaluation. The presented methods are applicable to all filamentous fungal samples that can be prepared in the described ways. The fundamental staining approaches can serve as starting points for adaptations to species that might require different cultivation conditions. First, biophysical and biochemical properties are reviewed as their understanding is essential for using these dyes as truly vital fluorescent stains. Secondly, step-by-step protocols are presented that detail the preparation of various fungal sample types for fluorescent live-cell imaging. Finally, example experiments illustrate different approaches to: (1) identify defects in the spatio-temporal organization of endocytosis in genetic mutants, (2) comparatively characterize shared and distinct co-localization of GFP-labeled target proteins in the endocytic pathway, (3) identify morphogenetic cell wall defects in a genetic mutant, and (4) monitor cell wall biogenesis in real time.

Potential Use of Probiotic Consortium Isolated from Kefir for Textile Azo Dye Decolorization.

Azo dyes are recalcitrant pollutants, which are toxic, carcinogenic, mutagenic and teratogenic, that constitute a significant burden to the environment. The decolorization and the mineralization efficiency of Remazol Brillant Orange 3R (RBO 3R) was studied using a probiotic consortium (Lactobacillus acidophilus and Lactobacillus plantarum). Biodegradation of RBO 3R (750 ppm) was investigated under shaking condition in Mineral Salt Medium (MSM) solution at pH 11.5 and temperature 25°C. The bio-decolorization process was further confirmed by FTIR and UV-Vis analysis. Under optimal conditions, the bacterial consortium was able to decolorize the dye completely (>99%) within 12 h. The color removal was 99.37% at 750 ppm. Muliplex PCR technique was used to detect the Lactobacillus genes. Using phytotoxicity, cytotoxicity, mutagenicity and biototoxicity endpoints, toxicological studies of RBO 3R before and after biodegradation were examined. A toxicity assay signaled that biodegradation led to detoxification of RBO 3R dye.

Decolorization of Acid Orange 7 by extreme-thermophilic mixed culture.

Although a large amount of textile wastewater is discharged at high temperatures, azo dye reduction under extreme-thermophilic conditions by mixed cultures has gained little attention. In this study, Acid Orange 7 (AO7) was used as the model azo dye to demonstrate the decolorization ability of an extreme-thermophilic mixed culture. The results showed that a decolorization efficiency of over 90% was achieved for AO7. The neutral red (NR, 0.1 mM) could promote AO7 decolorization, in which the group of Cell + NR offered the highest decolorization rate of 1.568 1/h and t1/2 was only 0.44 h, whereas after CuCl2 addition, the decolorization rate (0.141 1/h) was lower and t1/2 (4.92 h) was much longer. Thus, CuCl2 notably inhibited this process. Caldanaerobacter (64.0%) and Pseudomonas (25.4%) were the main enriched bacteria, which were not reported to have the ability for dye decolorization. Therefore, this study extends the application of extreme-thermophilic biotechnology.

The Stat3 inhibitor, S3I-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T+ Itpr3tf/J mouse model of autism.

Autism is a complex neurodevelopmental disorder with a high incidence rate. It is characterized by deficits in communication, a lack of social skills, cognitive inflexibility, and stereotypical behaviors. Autism has been gradually increasing in children over the past several years, without the existence of an effective treatment. BTBR T+ Itpr3tf/J (BTBR) mice serve as an accepted model to evaluate autistic-like behaviors as they display core behavioral symptoms displayed in autism. Previous findings showed that S3I-201, a selective Stat3 inhibitor, can be used to treat neuroinflammation disorders. Previously, we showed that S3I-201 treatment has therapeutic effects on autism-like behaviors, and Th1/Th17 and regulatory T cells in BTBR mice. The objective of the present study was to further explore the role of S3I-201 in BTBR mice, and this was performed by investigating the effects of S3I-201 treatment on lymphocyte activation markers (CD4+CD25+ and CD4+CD69+), chemokine receptors (CD4+CCR6+, CD4+CCR7+, CD4+CXCR4+, and CD4+CXCR5+), and proinflammatory cytokines (CD4+IL-6+ and CD4+TNF-α+) in the spleen cells of BTBR and C57BL/6 (C57) mice. The mRNA and protein expression levels of CD69, CCR6, CCR7, CXCR4, CXCR5, IL-1ß, IL-6, and TNF-α were examined in the brain tissues, and in BTBR mice, a significant decrease in CD25, CD69, CCR6, CCR7, CXCR4, CXCR5, IL-6, and TNF-α producing CD4+ T cells was observed. The present findings suggest that treatment with S3I-201 may be a therapeutic approach to improve immune abnormalities in a subgroup of autistic subjects.

Analysis of decolorization potential of Myrothecium roridum in the light of its secretome and toxicological studies.

To identify the enzymes potentially useful for the decolorization of azo dyes, the secretome of the ascomycetous fungus Myrothecium roridum IM6482 was studied by using a bottom-up proteomic approach. Among the identified proteins, the most promising for dye removal was laccase, which decolorized respectively, 66, 91, 79, and 80% of Acid Blue 113 (AB 113), Acid Red 27 (AR 27), Direct Blue 14 (DB 14), and Acid Orange 7 (AO 7). The degradation of dyes was enhanced at the wide range of pH from 4 to 8. The addition of redox mediators allowed eliminating AB 113 in concentrations up to 400 mg/L and decolorization of the simulated textile effluent. Microbial toxicity and phytotoxicity tests indicated that dyes are converted into low-toxicity metabolites. This is the first insight into the M. roridum secretome, its identification and its application for removal of select azo dyes. Obtained results extended knowledge concerning biodegradative potential of ascomycetous, ligninolytic fungi and will contribute to the improvement of dye removal by fungi.

Comparative study of persulfate oxidants promoted photocatalytic fuel cell performance: Simultaneous dye removal and electricity generation.

Introducing peroxymonosulfate (PMS) and peroxydisulfate (PDS) into the photocatalytic fuel cell (PFC) system were investigated by comparing the Reactive Brilliant Blue (KN-R) degradation and synchronous electricity production. The two persulfates (PS) themselves are strong oxidant, and could be activated and as electron sacrificial agent in the PFCs, facilitating the photoelectrocatalysis and expanding redox to the entire cell space. Hence, the two established PFC/PS systems manifested prominent cell performances, enhancing the KN-R decomposition and electric power production relative to the virgin PFC. Thereinto, the KN-R removal rate of PFC/PMS was faster than that of PFC/PDS, but an opposite trend appeared in the electricity generation. Besides, the cell performances of the two cooperative systems were evaluated at different operation conditions, including PS dosage, solution pH, and irradiation strength. Moreover, the dye elimination principle was explored by radicals scavenging experiment, and the consequence revealed that hydroxyl radical (HO•), sulfate radical (SO4•-) and singlet oxygen were chief active species in the PFC/PMS, and HO•, SO4•- and superoxide anion played the key roles in the PFC/PDS. Furthermore, the calculated economic indicator demonstrated that the economy of the two synergistic processes were greater than that of UV/PS and solo PFC, and the PFC/PDS was more cost-effective than PFC/PMS.

Molecular dynamics simulations of the interaction of Mouse and Torpedo acetylcholinesterase with covalent inhibitors explain their differential reactivity: Implications for drug design.

Although the three-dimensional structures of mouse and Torpedo californica acetylcholinesterase are very similar, their responses to the covalent sulfonylating agents benzenesulfonyl fluoride and phenylmethylsulfonyl fluoride are qualitatively different. Both agents inhibit the mouse enzyme effectively by covalent modification of its active-site serine. In contrast, whereas the Torpedo enzyme is effectively inhibited by benzenesulfonyl fluoride, it is almost completely resistant to phenylmethylsulfonyl fluoride. A bottleneck midway down the active-site gorge in both enzymes restricts access of ligands to the active site at the bottom of the gorge. Molecular dynamics simulations revealed that the mouse enzyme is substantially more flexible than the Torpedo enzyme, suggesting that enhanced 'breathing motions' of the mouse enzyme relative to the Torpedo enzyme may explain why phenylmethylsulfonyl fluoride can reach the active site in mouse acetylcholinesterase, but not in the Torpedo enzyme. Accordingly, we performed docking of the two sulfonylating agents to the two enzymes, followed by molecular dynamics simulations. Whereas benzenesulfonyl fluoride closely approaches the active-site serine in both mouse and Torpedo acetylcholinesterase in such simulations, phenylmethylsulfonyl fluoride is able to approach the active-site serine of mouse acetylcholinesterase, but remains trapped above the bottleneck in the Torpedo enzyme. Our studies demonstrate that reliance on docking tools in drug design can produce misleading information. Docking studies should, therefore, also be complemented by molecular dynamics simulations in selection of lead compounds. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:CHEMBIOINT:2.

Self-assembled CeVO4/Ag nanohybrid as photoconversion agents with enhanced solar-driven photocatalysis and NIR-responsive photothermal/photodynamic synergistic therapy performance.

The plasmonic cerium vanadate (CeVO4) semiconductor and plasmonic silver (Ag) metal exhibit a localized surface plasmon resonance (LSPR) effect in the visible (Vis)-light region; however, weak absorption in the near-infrared (NIR) region restricts their environmental remediation and biomedical application. Herein, CeVO4/Ag nanohybrids with self-assembled heterostructure and improved Vis/NIR light absorption were synthesized from CeVO4 nanosheets and AgNO3 solution, which could serve as potential solar-driven catalytic agents and near-infrared (NIR) light responsive anticancer agents. Oleic acid-stabilized CeVO4 nanosheets were modified with the HS-PEG1000-OH by the thiol-ene click reaction and presented self-assembly morphology in aqueous solution due to hydrophobic-hydrophobic interactions. Sulfhydryl (-SH) groups provided stable sites for Ag+ ions on the surface of CeVO4, and Ag+ ions could be directly reduced by Ce3+ ions to form CeVO4/Ag heterojunction nanocrystals (NCs). Due to the higher absorption in the Vis/NIR light region than CeVO4 nanosheets, CeVO4/Ag NCs led to the improved solar light responsive photocatalytic degradation of organic dyes. Upon the exposure of these NCs to an 808 nm laser, CeVO4/Ag NCs show high photothermal conversion efficiency, ROS generation ability and photoacoustic (PA) signal for implementing PA imaging-guided photothermal/photodynamic synergistic cancer therapy with better tumor inhibition effect.